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OBJECTIVE: The aim of this study was to determine the incidence of cochlear fibrosis after vestibular schwannoma (VS) resection via middle cranial fossa (MCF) approach. DESIGN: A retrospective case review was conducted. SETTING: The review was conducted in a tertiary care academic medical center. PARTICIPANTS: Patients who (1) underwent resection of VS via MCF approach between 2013 and 2018, (2) had complete pre- and post-audiometric testing, and (3) had clinical follow-up with magnetic resonance imaging (MRI) for at least 1 year after surgery were included. MAIN OUTCOME MEASURE(S): The main outcome of this study was cochlear fibrosis as assessed by MRI 1 year after surgery. RESULTS: Fifty-one patients underwent VS resection via MCF technique during the study period. Of 31 patients with AAO-HNS class A or B preoperative hearing ability, 18 (58.0%) maintained class A, B, or C hearing postoperatively. Of 16 patients who lost hearing and had MRI 1 year after surgery, 11 (61.1%) had MRI evidence of fibrosis in at least some portion of the labyrinth and 4 (22.2%) showed evidence of cochlear fibrosis. Of 16 patients with preserved hearing and MRI 1 year after surgery, 4 (25%) had fibrosis in some portion of the labyrinth, with no fibrosis in the cochlea. CONCLUSIONS: In patients who lose hearing during VS resection with the MCF approach, there is usually MRI evidence of fibrosis in the labyrinth 1 year after surgery. However, there is also, but less commonly, fibrosis involving the cochlea. It is unclear if this will affect the ability to insert a cochlear implant electrode array.
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Fossa Craniana Média , Neuroma Acústico , Cóclea/cirurgia , Fossa Craniana Média/cirurgia , Fibrose , Humanos , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression. Mutations of the NF2 gene are strongly associated with NF2 diagnosis, leading to benign proliferative conditions such as vestibular schwannomas and meningiomas. Unfortunately, even though these tumors are benign, they are associated with significant morbidity and the potential for early mortality. In this review, we aim to encompass meningiomas and vestibular schwannomas as they pertain to NF2 by assessing molecular genetics, common tumor types, and tumor pathogenesis.
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Neoplasias Encefálicas/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Neurofibromatose 2/patologia , Neuroma Acústico/patologia , Animais , Apoptose/genética , Neoplasias Encefálicas/genética , Proliferação de Células/genética , Humanos , Neoplasias Meníngeas/genética , Meningioma/genética , Mutação/genética , Neurofibromatose 2/genética , Neuroma Acústico/genéticaRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is a multifaceted disease with a significant genetic component. The importance of taste receptor signaling has recently been highlighted in CRS; single nucleotide polymorphisms (SNPs) of bitter tastant-responsive G-protein-coupled receptors have been linked with CRS and with altered innate immune responses to multiple bacterially derived signals. OBJECTIVE: To determine in CRS the frequency of six SNPs in genes with known bitter tastant signaling function. METHODS: Genomic DNA was isolated from 74 CRS volunteers in West Virginia, and allele frequency was determined and compared with demographically matched data from the 1,000 Genomes database. RESULTS: For two SNPs in a gene recently associated with bitterant signaling regulation, RGS21, there were no associations with CRS (although the frequency of the minor allele of RGS21, rs7528947, was seen to increase with increasing Lund-Mackay CT staging score). Two TAS2R bitter taste receptor gene variants (TAS2R19 rs10772420 and TAS2R38 rs713598), identified in prior CRS genetics studies, were found to have similar associations in this study. CONCLUSION: Unique to our study is the establishment of an association between CRS in this patient population and GNB3 SNP rs5443, a variation in an established G protein component downstream of bitterant receptor signal transduction.
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Proteínas Heterotriméricas de Ligação ao GTP/genética , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas G/genética , Rinite/diagnóstico , Rinite/genética , Sinusite/diagnóstico , Sinusite/genética , Adulto , Idoso , Alelos , Doença Crônica , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Rinite/imunologia , Fatores de Risco , Sinusite/imunologiaRESUMO
Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.
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Neoplasias Encefálicas/enzimologia , Glioma/enzimologia , Isocitrato Desidrogenase/genética , Mutação , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas em Tandem/instrumentação , Biópsia , Neoplasias Encefálicas/patologia , Estudos de Coortes , Glioma/patologia , Humanos , Período IntraoperatórioRESUMO
We have developed and tested two linked but separable structured inquiry exercises using a set of Drosophila melanogaster GAL4 enhancer trap strains for an upper-level undergraduate laboratory methods course at Bucknell University. In the first, students learn to perform inverse PCR to identify the genomic location of the GAL4 insertion, using FlyBase to identify flanking sequences and the primary literature to synthesize current knowledge regarding the nearest gene. In the second, we cross each GAL4 strain to a UAS-CD8-GFP reporter strain, and students perform whole mount CNS dissection, immunohistochemistry, confocal imaging, and analysis of developmental expression patterns. We have found these exercises to be very effective in teaching the uses and limitations of PCR and antibody-based techniques as well as critical reading of the primary literature and scientific writing. Students appreciate the opportunity to apply what they learn by generating novel data of use to the wider research community.
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Currículo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Elementos Facilitadores Genéticos , Laboratórios , Aprendizagem , Fatores de Transcrição/genética , Universidades , Animais , Sequência de Bases , Encéfalo/metabolismo , Regulação da Expressão Gênica , Genes de Insetos , Dados de Sequência Molecular , Corpos Pedunculados/metabolismo , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: Placement of an active transcutaneous bone-conduction implant (BCI) requires drilling of a precise bone bed to accommodate the device and allow for fixation points to make appropriate contact with bone, which can be difficult even when lifts are used. We describe a subtemporalis muscle middle cranial fossa bone-island craniotomy technique that simplifies the procedure and obviates the need for lifts in securing the device. STUDY DESIGN: Prospective case series. SETTING: Tertiary academic medical center. PATIENTS: Seventeen patients underwent surgery for placement of 18 transcutaneous BCIs, 14 for conductive or mixed hearing loss, and 4 for single-sided deafness. INTERVENTIONS: Surgical placement of a transcutaneous BCI with a bone-island craniotomy technique. MAIN OUTCOME MEASURES: Functional gain in air-conduction thresholds, aided air-bone gap, frequency of need for lifts, and minor and major complications. RESULTS: For the conductive or mixed hearing loss cohort, with the transcutaneous BCI in place, there was a highly statistically significant mean functional gain of 35.4 dB hearing level (HL) (range, 16.7-50.25 dB HL; standard deviation, 12.4 dB HL) compared with the unaided condition (p < 0.0001; 95% confidence interval, 36.6-51.6 dB HL). Lifts were not needed in any case. There was one minor complication requiring a second procedure in a patient who had previously received radiation and no major complications. There was no device loss or failure. CONCLUSIONS: A subtemporalis muscle middle cranial fossa bone-island craniotomy technique eliminates the need for lifts and is a safe and effective method for placement of a transcutaneous BCI.
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Auxiliares de Audição , Perda Auditiva Condutiva-Neurossensorial Mista , Percepção da Fala , Humanos , Perda Auditiva Condutiva-Neurossensorial Mista/cirurgia , Condução Óssea/fisiologia , Fossa Craniana Média/cirurgia , Músculos , Perda Auditiva Condutiva/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: To characterize the viability and volume of autologous free fat grafts over time, determine clinical/patient factors that may affect free fat graft survival and assess the clinical impact of free fat graft survival on patient outcomes in the translabyrinthine approach for lateral skull base tumor resection. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary neurotologic referral center. PATIENTS: Forty-two adult patients who underwent translabyrinthine craniotomy for resection of a lateral skull base tumor with the mastoid defect filled by autologous abdominal fat graft and subsequently underwent more than one postoperative magnetic resonance imaging (MRI) scans of the brain. INTERVENTIONS: Mastoid obliteration with abdominal fat after craniotomy, postoperative MRI. MAIN OUTCOME MEASURES: Rate of fat graft volume loss, fraction retention of original fat graft volume, initial fat graft volume, time to steady-state fat graft retention, rate of postoperative cerebrospinal fluid (CSF) leak, and/or pseudomeningocele formation. RESULTS: Patients were followed postoperatively with MRI for a mean of 31.6 months with a mean of 3.2 postoperative MRIs per patient. Initial graft size was a mean of 18.7 cm3 with a steady-state fat graft retention of 35.5%. Steady-state graft retention (<5% loss per year) was achieved at a mean of 24.96 months postoperatively. No significant association was found in multivariate regression analysis of clinical factors impact on fat graft retention and CSF leak/pseudomeningocele formation. CONCLUSIONS: In the use of autologous abdominal free fat graft for filling mastoid defects after translabyrinthine craniotomy, there is a logarithmic decline in fat graft volume over time, reaching steady state in 2 years. Rates of CSF leak or pseudomeningocele formation were not significantly affected by initial volume of the fat graft, rate of fat graft resorption, nor the fraction of original fat graft volume at steady state. In addition, no analyzed clinical factors significantly influenced fat graft retention over time.
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Neoplasias da Base do Crânio , Adulto , Humanos , Estudos Retrospectivos , Vazamento de Líquido Cefalorraquidiano , Encéfalo , Imageamento por Ressonância MagnéticaRESUMO
Vestibular nerve section (VNS) is a surgical intervention with hearing preservation used for the treatment of Menière's disease after conservative medical therapy has failed (1,2). With the recent rise in less invasive treatments such as intratympanic gentamicin, VNS has been performed less frequently (3). The middle cranial fossa (MCF) approach for VNS is an uncommon approach due to its technical difficulty. However, it can provide the best distinction of internal auditory canal contents compared with retrosigmoid and retrolabyrinthine approaches. Several advancements in the MCF approach have been described, including the use of intraoperative facial nerve monitoring with electromyography, early removal of the temporal lobe retractor, and the use of an ultrasonic bone aspirator for internal auditory canal decompression (4-6). We demonstrate a case study with a step-by-step approach to successfully sectioning the superior and inferior vestibular nerves while utilizing these advancements and avoiding facial and cochlear nerve injury via the MCF (7). SDC video link: http://links.lww.com/MAO/B409.
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Orelha Interna , Doença de Meniere , Fossa Craniana Média/cirurgia , Orelha Interna/cirurgia , Humanos , Doença de Meniere/cirurgia , Procedimentos Neurocirúrgicos , Nervo VestibularRESUMO
Lipid peroxidation-derived aldehydes, such as acrolein, the most reactive aldehyde, have emerged as key culprits in sustaining post-spinal cord injury (SCI) secondary pathologies leading to functional loss. Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2 (ALDH2), a key oxidoreductase and powerful endogenous anti-aldehyde machinery, is likely important for protecting neurons from aldehydes-mediated degeneration. Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator (Alda-1), we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2. Over an acute 2 day period post injury, we found that ALDH2 expression was significantly lowered post-SCI, but not so in rats given Alda-1. This lower enzymatic expression may be linked to heightened acrolein-ALDH2 adduction, which was revealed in co-immunoprecipitation experiments. We have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord, and reduced cyst pathology. In addition, Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days post-SCI. Finally, ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein exposure. It is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI victims. All animal work was approved by Purdue Animal Care and Use Committee (approval No. 1111000095) on January 1, 2021.
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OBJECTIVE: Examine the effects of a multi-disciplinary skull base conference (MDSBC) on the management of patients seen for skull base pathology in a neurotology clinic. METHODS: Retrospective case review of patients who were seen in a neurotology clinic at a tertiary academic medical center for pathology of the lateral skull base and were discussed at an MDSBC between July 2019 and February 2020. Patient characteristics, nature of the skull base pathology, and pre- and post-MDSBC plan of care was categorized. RESULTS: A total of 82 patients with pathology of the lateral skull base were discussed at a MDSBC during an 8-month study period. About 54 (65.9%) had a mass in the internal auditory canal and/or cerebellopontine angle while 28 (34.1%) had other pathology of the lateral skull base. Forty-nine (59.8%) were new patients and 33 (40.2%) were established. The management plan changed in 11 (13.4%, 7.4-22.6 95% CI) patients as a result of the skull base conference discussion. The planned management changed from some form of treatment to observation in 4 patients, and changed from observation to some form of treatment in 4 patients. For 3 patients who underwent surgery, the planned approach was altered. CONCLUSIONS: For a significant proportion of patients with pathology of the lateral skull base, the management plan changed as a result of discussion at an MDSBC. Although participants of a MDSBC would agree of its importance, it is unclear how an MDSBC affects patient outcomes.
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Tomada de Decisão Clínica , Neuroma Acústico/diagnóstico , Neuroma Acústico/cirurgia , Equipe de Assistência ao Paciente/organização & administração , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/cirurgia , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: Examine the effect of preoperative bone conduction pattern on outcomes of stapedotomy/stapedectomy. STUDY DESIGN: Retrospective case series. SETTING: Tertiary-care academic medical center. PATIENTS: Patients who underwent stapedotomy or stapedectomy from 2013 to 2019. INTERVENTIONS: Primary small-fenestra stapedotomy or partial stapedectomy. MAIN OUTCOME MEASURES: Association between preoperative bone conduction patterns and hearing after stapes surgery. RESULTS: Complete audiometric data were available for 137 patients who had surgery. The mean preoperative air-bone gap (ABG) was 26.8âdBHL. The ABG was closed to less than 20 and 10âdBHL in 88.7 and 65.2% of patients, respectively. A notch at 2000âHz was present in 32.1% of operated ears and was rarely found at other frequencies. There was no statistically significant association between the presence of a notch and hearing outcomes. The slope of the bone conduction line had no association with hearing outcomes, though an increased bone conduction PTA compared with the contralateral ear was associated with ABG closure less than 10âdBHL and overclosure (odds ratio: 2.14, pâ=â0.027 and odds ratio: 2.20, pâ=â0.04). CONCLUSION: In properly selected otosclerosis patients, depressions in bone conduction other than near 2000âHz are rare and hearing outcomes are generally favorable regardless of the preoperative bone conduction pattern. Despite the association with otosclerosis, the presence of a notch at 2000âHz is not associated with better hearing outcomes with surgery.
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Otosclerose , Cirurgia do Estribo , Condução Óssea , Audição , Humanos , Otosclerose/complicações , Otosclerose/cirurgia , Estudos Retrospectivos , Estribo , Resultado do TratamentoRESUMO
A focused history, otoscopic and tuning fork examination and formal hearing testing are the diagnostic pillars for the workup of hearing loss and tinnitus. The causes of hearing loss and tinnitus are varied and range from relatively common age-related hearing loss to rare tumors of the brain and skull base. In this chapter, the authors explain the diagnostic workup of hearing loss and tinnitus, review the pathophysiology of the most common causes, and describe the treatments available.
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Perda Auditiva/fisiopatologia , Zumbido/fisiopatologia , Audiometria , Implantes Cocleares , Auxiliares de Audição , Perda Auditiva/diagnóstico , Perda Auditiva/etiologia , Perda Auditiva/terapia , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/fisiopatologia , Perda Auditiva Condutiva/terapia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Neurossensorial/terapia , Testes Auditivos , Humanos , Atenção Primária à Saúde , Índice de Gravidade de Doença , Zumbido/diagnóstico , Zumbido/etiologia , Zumbido/terapiaRESUMO
Vertigo is defined as the illusion of internal or external motion. The evaluation of a patient with vertigo in the primary care setting should not necessarily focus on providing a specific diagnosis. Rather, the physician should aim to localize the lesion. This practice streamlines the workup of patients. This article provides detailed information regarding appropriate organ system-based clinical history and the clinical workup of vertigo. Additional signs and symptoms that can facilitate appropriate referral and treatment are highlighted. Although disorder-specific treatments exist the mainstay of therapy for vertigo-induced pathology is physical therapy.
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Vertigem/patologia , Diagnóstico Diferencial , Humanos , Exame Físico , Modalidades de Fisioterapia , Atenção Primária à Saúde , Vertigem/diagnóstico , Vertigem/etiologia , Vertigem/terapiaRESUMO
OBJECTIVE: Traditionally, auditory brainstem implants (ABIs) have been placed via the translabyrinthine or retrosigmoid approaches. In select patients, a modified extended middle cranial fossa (xMCF) approach with tentorial ligation may be advantageous for vestibular schwannoma (VS) resection and auditory rehabilitation. This manuscript describes the application of this modification of the MCF approach for simultaneous VS resection and ABI placement. PATIENTS: Patients with neurofibromatosis type 2, profound bilateral sensorineural hearing loss, single functioning sigmoid/jugular venous system, and giant (>4âcm) VS. INTERVENTIONS: Simultaneous VS resection and ABI placement via a modified xMCF approach with tentorial ligation. MAIN OUTCOME MEASURES: Extent of tumor removal and brainstem decompression, access to lateral recess of the fourth ventricle, functional hearing improvement, surgical complications. RESULTS: Two patients met indications and underwent surgery. There were no immediate or delayed surgical complications. Both had subtotal tumor removal with significant decompression of the brainstem and ABI placement. One patient achieved voice and environmental sound awareness at 35 to 55 dbHL across frequencies. The second patient presented with failure to thrive and multiple lower cranial neuropathies in addition to the above-listed indications. She was hospitalized multiple times after surgery due to failure to thrive and recurrent aspiration pneumonia. Her device was never activated, and she expired 1 year after surgery. CONCLUSIONS: The xMCF with tentorial ligation is an additional approach for tumor resection and ABI placement in selected patients with neurofibromatosis type 2. Future studies will further define when this approach is most applicable as well as the challenges and pitfalls.
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Implantes Auditivos de Tronco Encefálico , Neurofibromatose 2 , Tronco Encefálico , Fossa Craniana Média/cirurgia , Feminino , Perda Auditiva Bilateral , Humanos , Neurofibromatose 2/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: Treatment of ruptured cerebral aneurysms by endovascular coiling is associated with a better neurologic outcome when compared with neurosurgical clipping but has a higher risk for target aneurysm rebleeding after treatment. We hypothesize that aggressive retreatment of coiled aneurysms will lead to fewer recurrent hemorrhages as compared with historical values of 2.3%-3.0%. METHODS: All first-time Guglielmi detachable coil-embolized cerebral aneurysms were retrospectively reviewed at a single institution from 2004 to 2015. Aneurysm retreatment after first-time embolization was recorded as well as time to retreatment. Retreatment at our institution is routinely performed for incomplete coiling with etiologies including incomplete initial coiling, coil compaction, and aneurysmal dilatation. Aneurysm rerupture was treated with additional coiling. Kaplan-Meier survival analysis was performed to evaluate embolization durability. RESULTS: There were 214 aneurysms that met inclusion criteria. Mean (standard deviation) follow-up was 2.74 (2.24) years. Aneurysms that were patent or recanalized were retreated. Mean (standard deviation) time to retreatment was 9 (9) months. Overall, 46 (21.5%) aneurysms required retreatment. Retreatment was performed for coil compaction/remnant growth, recanalization, persistent remnant, and rebleed. Two (0.9%) patients had recurrent aneurysm hemorrhage and both were treated with additional coil embolization. There were no new long-term neurologic deficits caused by aneurysm retreatment. CONCLUSIONS: Aggressive retreatment of previously ruptured, coiled cerebral aneurysms for persistent aneurysm patency reduces the recurrent hemorrhage risk to that historically seen in neurosurgically clipped aneurysms with minimal additional morbidity. This study validates a large body of literature demonstrating the significance of post-treatment aneurysm remnants and their association with recurrent hemorrhage.
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Aneurisma Roto/cirurgia , Aneurisma Intracraniano/cirurgia , Procedimentos de Cirurgia Plástica , Retratamento , Adulto , Idoso , Prótese Vascular/efeitos adversos , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/efeitos adversos , Recidiva , Retratamento/efeitos adversosRESUMO
BACKGROUND: Traditional paradigms of care recommend close audiology follow-up and regular speech perception outcomes assessment indefinitely for cochlear implant (CI) recipients after device activation. However, there is scant published data on actual compliance with this paradigm in clinical practice. METHODS: A multi-center cochlear implant database was queried to identify follow-up rates after cochlear implantation. Follow-up rates where speech perception outcomes assessment occurred at 1-, 3-, 6-, 12-, 18-, and 24-months post-activation were determined by tabulating observed follow-up divided by expected follow-up (O/E ratio) expressed as a percentage. To determine all-cause audiology follow-up rates (with or without testing speech perception outcomes assessment), the database patients from two participating centers (one private practice and one academic center) were similarly analyzed using electronic health record (EHR) data to calculate O/E rates where audiology follow-up occurred for any reason. RESULTS: O/E follow-up rates where speech perception outcomes assessment occurred was 42, 40, 31, 29, 5, and 22% for 1-, 3-, 6-, 12-, 18-, and 24-months post-activation, respectively (nâ=â2,554). All-cause audiology follow-up rates (with or without speech perception outcomes assessment) using EHR-confirmed data from two individual centers were 97, 94, 81, 66, 41, and 35% at 1-, 3-, 6-, 12-, 18-, and 24-months post-activation visits, respectively (nâ=â118). CONCLUSIONS: Compliance with audiology follow-up and speech perception outcomes assessment is generally low and decreases significantly as time post-activation increases. Future paradigms of care for CI should be designed recognizing the significant attrition that occurs with CI follow-up.
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Audiologia , Implante Coclear , Implantes Cocleares , Percepção da Fala , Seguimentos , HumanosRESUMO
Clinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T cell dysfunction such as exhaustion in GBM patients. However, reversing T cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8+ T cells with downregulated CD28 coreceptors, low CD27 expression, increased CD57 expression, and telomere shortening are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in Ag-induced proliferation. In the context of GBM, presence and/or function of these CD8+CD28- T cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8+ T cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8+CD28- T cells in both the blood and tumor-infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8+CD28- T cells represent a distinct population compared with exhausted T cells. Comparative transcriptomic and pathway analysis of CD8+CD28- T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population.
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Envelhecimento/imunologia , Neoplasias Encefálicas/tratamento farmacológico , Linfócitos T CD8-Positivos/imunologia , Glioblastoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Antígenos CD28/análise , Antígenos CD28/imunologia , Antígenos CD28/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Senescência Celular/imunologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Glioblastoma/sangue , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunofenotipagem , Ativação Linfocitária , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Adulto JovemRESUMO
OBJECTIVE: Report the details of an unusual case of initially unilateral intradural spontaneous otogenic pneumocephalus in which the patient developed contralateral pneumocephalus after surgical repair of temporal bone and dural defects on the initial side. Discuss the lessons learned concerning management and pathophysiology of this rare case. PATIENT: A 73-year-old male presenting with bilateral retro-orbital pain and headache was found to have unilateral intradural pneumocephalus in the temporal lobe with an adjacent defect in the temporal bone. INTERVENTION: Surgical repair of the initial defect in the temporal bone and dura via a middle cranial fossa approach with obliteration of the mastoid cavity. RESULTS: The patient's symptoms and degree of pneumocephalus on first affected side decreased initially after surgery. Two weeks after surgery he developed worsening pneumocephalus on the contralateral side in the temporal and frontal lobes with weakness and mild somnolence. This side was repaired via a similar technique without mastoid obliteration. Two weeks after surgery the patient recovered to normal level of consciousness with mild residual weakness. CONCLUSIONS: Spontaneous otogenic intradural pneumocephalus is an extremely rare but serious condition related to defects in the temporal bone and dura. The precise mechanism by which this occurs is poorly understood. This unusual case where there were bilateral defects presenting with spontaneous otogenic pneumocephalus in sequence illustrates that it represents a rare sequelae of processes which thin the skull base. These processes should be addressed in addition to acute management of the defect and intracranial air.
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Pneumocefalia , Idoso , Fossa Craniana Média , Humanos , Masculino , Pneumocefalia/diagnóstico por imagem , Pneumocefalia/etiologia , Pneumocefalia/cirurgia , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia , Lobo TemporalRESUMO
OBJECTIVE: Determine if changes in middle ear absorbance measured with wide-band tympanometry (WBT) occur following hearing-preservation cochlear implantation (CI). Such measures may provide insight into the mechanisms of acoustic hearing loss postimplantation. STUDY DESIGN: Clinical capsule report. SETTING: Tertiary academic referral center. DESIGN: WBT absorbance was measured bilaterally during pre- and postoperative clinical office visits in five unilaterally-implanted cochlear implant recipients. Pre- and postoperative WBT measures were compared within each subject in the implanted and contralateral, unimplanted ears. RESULTS: In general, WBT absorbance measurements show a broad spectral pattern including two or three distinct peaks measured over a frequency range of 226 to 8000âHz. Grand average and linear mixed model comparisons between the pre- and postoperative WBT patterns show significantly reduced (pâ<â0.05) low-frequency absorbance in the implanted ears in the frequency region over 0.6 to 1.1âkHz, but not in the unimplanted ears. The maximum effect occurred at 1âkHz with absorbance decreasing from â¼0.8 to â¼0.5 after implantation. The limited data are consistent with expected relationships between WBT absorbance and air- and bone-conduction thresholds, assuming an increased air-bone gap reflects conductive hearing loss. CONCLUSION: Cochlear implantation can result in reduction of low-frequency acoustic absorbance as measured by WBT. WBT may be a useful and sensitive tool for monitoring the mechanical status of the middle and inner ears following cochlear implantation.
Assuntos
Implante Coclear , Implantes Cocleares , Perda Auditiva , Testes de Impedância Acústica , Audição , Perda Auditiva/cirurgia , HumanosRESUMO
OBJECTIVE: Compare outcomes for patients who were seen via telemedicine visits after otology/neurotology surgical procedures with those who were seen in traditional office visits. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care academic medical center. PATIENTS: Inclusion criteria were patients who underwent otologic/neurotologic surgery and were seen in at least one telemedicine visit for postoperative care. INTERVENTION (S): Telemedicine visit for postoperative care. MAIN OUTCOME MEASURE (S): Comparison of the number of patient calls, unplanned visits, and delayed complications between telemedicine patients and controls matched for age, procedure, and American Society of Anesthesiologists (ASA) status. RESULTS: Eighteen patients were seen in telemedicine visits postoperatively after the following otologic/neurotologic surgical procedures: cochlear implant surgery (10), vestibular schwannoma resection (4), combined middle fossa and transmastoid cerebrospinal fluid (CSF) leak repair (2), middle fossa repair of superior canal dehiscence (1), and stapedectomy (1). All telehealth visits were for the second postoperative visit. The mean number of patient calls after surgery was 2.3 for the telemedicine group and 1.9 for matched controls which was not a statistically significant difference (pâ=â0.466). Both groups each had two patients who went to the emergency room, with one in each group being admitted. There was one delayed complication in the control group. CONCLUSION: Our preliminary experience suggests telemedicine may be used safely in caring for patients after otologic/neurotologic surgery, though it may be associated with more patient phone calls. Further study and experience, including assessing patient satisfaction, will clarify the future role of telemedicine in otology and neurotology.