International Consensus Statements on Intraoperative Testing for Cochlear Implantation Surgery.

OBJECTIVES: A wide variety of intraoperative tests are available in cochlear implantation. However, no consensus exists on which tests constitute the minimum necessary battery. We assembled an international panel of clinical experts to develop, refine, and vote upon a set of core consensus statements. DESIGN: A literature review was used to identify intraoperative tests currently used in the field and draft a set of provisional statements. For statement evaluation and refinement, we used a modified Delphi consensus panel structure. Multiple interactive rounds of voting, evaluation, and feedback were conducted to achieve convergence. RESULTS: Twenty-nine provisional statements were included in the original draft. In the first voting round, consensus was reached on 15 statements. Of the 14 statements that did not reach consensus, 12 were revised based on feedback provided by the expert practitioners, and 2 were eliminated. In the second voting round, 10 of the 12 revised statements reached a consensus. The two statements which did not achieve consensus were further revised and subjected to a third voting round. However, both statements failed to achieve consensus in the third round. In addition, during the final revision, one more statement was decided to be deleted due to overlap with another modified statement. CONCLUSIONS: A final core set of 24 consensus statements was generated, covering wide areas of intraoperative testing during CI surgery. These statements may provide utility as evidence-based guidelines to improve quality and achieve uniformity of surgical practice.

Characterization of otologic symptoms appearing after COVID-19 vaccination.

OBJECTIVES: Anecdotal reports of sudden sensorineural hearing loss (SSNHL) following COVID-19 vaccination have emerged in the otolaryngology community. Studies have demonstrated no association between COVID-19 vaccination and SSNHL. We aim to characterize the spectrum of otologic symptoms following COVID-19 vaccination. METHODS: A cross-sectional study of patients seen in the otology clinic at an academic center was performed. Patients completed a questionnaire on the development of new otologic symptoms within 4 weeks of COVID-19 vaccination. Diagnostic and audiometric data was collected retrospectively for patients reporting otologic symptoms. RESULTS: Between May and July 2021, 500 patients were screened. Median age was 56.6 years old, with 59.4 % female and 40.2 % male. 420 patients (84.0 %) were vaccinated, with 58.4 % receiving Pfizer, 29.1 % receiving Moderna, and 3.8 % receiving Johnson & Johnson. 61 patients (14.5 %) reported one or more otologic symptoms within 4 weeks of vaccination, including 21 (5.0 %) with hearing loss, 26 (6.2 %) with tinnitus, 33 (7.9 %) with dizziness, and 19 (4.5 %) with vertigo. Of the 16 patients (3.2 %) reporting tinnitus with no associated hearing loss, 8 were diagnosed with subjective tinnitus and 4 were diagnosed with temporomandibular joint syndrome. Of the 18 patients reporting hearing loss, 11 had exacerbations of underlying pathologies (e.g. Meniere's disease, presbycusis) and 7 were newly diagnosed with SSNHL (1.4 %). CONCLUSIONS: Patients reporting otologic symptoms following COVID-19 vaccination received various diagnoses of uncertain etiology. The incidence of SSNHL in these patients is comparable to the general otology patient population. Additional studies are required to determine the incidence of specific diagnoses following vaccination.

Hearing Rehabilitative Treatment for Older Adults With Comorbid Hearing Loss and Depression: Effects on Depressive Symptoms and Executive Function.

OBJECTIVES: Recent research has revealed important neural and psychiatric consequences of hearing loss (HL) in older adults. This pilot study examined the neural effects of HL and the impact of hearing aids on neuropsychiatric outcomes in major depressive disorder (MDD). DESIGN: Twelve-week, double-blind, randomized controlled trial. PARTICIPANTS/INTERVENTION: N = 25 (≥60 years) with MDD and moderate-profound HL were randomized to receive hearing aids (100% gain targets) or sham hearing aids (flat 30 dB HL) in addition to psychiatric treatment-as-usual. MEASUREMENTS: Depressive symptoms (Hamilton Rating Scale for Depression [HRSD]), executive functioning (NIH Toolbox Flanker), integrity of auditory brain areas (structural MRI, diffusion tensor imaging). RESULTS: At baseline, worse speech discrimination was associated with auditory cortical thinning (Left anterior transverse temporal gyrus: r = 0.755, p = 0.012) and lower integrity of the superior longitudinal fasciculus (FA: Left r = 0.772, p = 0.025, Right r = 0.782, p = 0.022). After 12-weeks, hearing aids were effective at improving hearing functioning (Hearing Handicap for the Elderly: active -12.47 versus sham -4.19, t = -2.64, df = 18, p = 0.016) and immediate memory (active +14.9 versus sham +5.7, t = 2.28, df = 16, p = 0.037). Moderate improvement was observed for hearing aids on executive functioning but did not reach statistical significance (Flanker: active +4.8 versus sham -2.4, t = 1.95, df = 15, p = 0.071). No significant effect on depression was found (HRSD: active -5.50 versus sham -7.32, t = 0.75, df = 19, p = 0.46). CONCLUSIONS: HL can affect brain regions important for auditory and cognitive processing, and hearing remediation may have beneficial effects on executive functioning in MDD. Future studies may evaluate whether impairment in cognitive control consequent to HL may be an important risk mechanism for MDD.

A precision medicine tool to understand who responds best to hearing aids in late-life depression.

OBJECTIVES: Accumulating evidence suggests that hearing loss (HL) treatment may benefit depressive symptoms among older adults with Major Depressive Disorder (MDD), but the specific individual characteristics of those who stand to improve most are unknown. METHODS: N = 37 patients ≥60 years with HL and MDD received either active or sham hearing aids in this 12-week double-blind randomized controlled trial. A combined moderator approach was utilized in the analysis in order to examine multiple different pretreatment individual characteristics to determine the specific qualities that predicted the best depressive symptom response to hearing aids. Pretreatment characteristics included: Hearing Handicap Inventory for the Elderly (HHIE-S), pure tone average (PTA), speech reception threshold (SRT), Short Physical Performance Battery (SPPB), cognition (Repeatable Battery for the Assessment of Neuropsychological Status). RESULTS: The analysis revealed a combined moderator, predicting greater improvement with active versus sham hearing aids, that had a larger effect size than any individual moderator (combined effect size [ES] = 0.49 [95% CI: 0.36, 0.76]). Individuals with worse hearing-related disability (HHIE-S: individual ES = -0.16), speech recognition (SRT: individual ES = -0.14), physical performance (SPPB: individual ES = 0.41), and language functioning (individual ES = 0.19) but with relatively less severe audiometric thresholds (PTA: individual ES = 0.17) experienced greater depressive symptom improvement with active hearing aids. CONCLUSIONS: Older adults with relatively worse HL-related, physical, and cognitive functioning may stand to benefit most from hearing aids. Given the large number of older adults experiencing HL and MDD, a non-invasive and scalable means of targeting those most likely to respond to interventions would be valuable.

Modelling and treating GRIN2A developmental and epileptic encephalopathy in mice.

NMDA receptors play crucial roles in excitatory synaptic transmission. Rare variants in GRIN2A encoding the GluN2A subunit are associated with a spectrum of disorders, ranging from mild speech and language delay to intractable neurodevelopmental disorders, including but not limited to developmental and epileptic encephalopathy. A de novo missense variant, p.Ser644Gly, was identified in a child with this disorder, and Grin2a knock-in mice were generated to model and extend understanding of this intractable childhood disease. Homozygous and heterozygous mutant mice exhibited altered hippocampal morphology at 2 weeks of age, and all homozygotes exhibited lethal tonic-clonic seizures by mid-third week. Heterozygous adults displayed susceptibility to induced generalized seizures, hyperactivity, repetitive and reduced anxiety behaviours, plus several unexpected features, including significant resistance to electrically-induced limbic seizures and to pentylenetetrazole induced tonic-clonic seizures. Multielectrode recordings of neuronal networks revealed hyperexcitability and altered bursting and synchronicity. In heterologous cells, mutant receptors had enhanced NMDA receptor agonist potency and slow deactivation following rapid removal of glutamate, as occurs at synapses. NMDA receptor-mediated synaptic currents in heterozygous hippocampal slices also showed a prolonged deactivation time course. Standard anti-epileptic drug monotherapy was ineffective in the patient. Introduction of NMDA receptor antagonists was correlated with a decrease in seizure burden. Chronic treatment of homozygous mouse pups with NMDA receptor antagonists significantly delayed the onset of lethal seizures but did not prevent them. These studies illustrate the power of using multiple experimental modalities to model and test therapies for severe neurodevelopmental disorders, while revealing significant biological complexities associated with GRIN2A developmental and epileptic encephalopathy.

Subclinical Hearing Loss is Associated With Depressive Symptoms.

OBJECTIVE: To assess whether the relationship between hearing and depressive symptoms is present among older adults classified as normal hearing (≤25 dB). DESIGN: Cross-sectional epidemiologic study (Hispanic Community Health Study). SETTING: US multicentered. PARTICIPANTS: Adults ≥50 years old (n = 5,499) with normal hearing or hearing loss (HL). MEASUREMENTS: The primary exposure was hearing, defined continuously by the 4-frequency pure-tone average threshold (dB) on audiometry. Hearing was additionally categorized into normal hearing (≤25 dB) and HL (>25 dB). The main outcome was depressive symptoms, measured with the Center for Epidemiologic Studies Depression Scale-10 (CESD-10). Depressive symptoms were defined both continuously and binarily (where CESD-10 ≥10 was categorized as clinically significant depressive symptoms). Multivariable linear, logistic, and generalized additive modeling (GAM) regressions were performed. RESULTS: Among those with normal hearing, the CESD-10 score increased by 1.04 points (95% confidence interval [CI]: 0.70, 1.37) for every 10 dB decrease in hearing, adjusting for age, gender, education, cardiovascular disease, and hearing aid use. Among those with HL, the CESD-10 score increased by 0.62 points (95% CI: 0.23, 1.01) for every 10 dB decrease in hearing, adjusting for the same confounders. Similar findings were noted when the outcome was clinically significant depressive symptoms (adjusted odds ratio: 1.28 [1.14, 1.44] in normal hearing versus 1.26 [1.11, 1.44] in HL). In certain sensitivity analyses, the relationship between hearing and depressive symptoms was significantly stronger among those with normal hearing than in those with HL. CONCLUSION: The relationship between hearing and clinically significant depressive symptoms is present among older adults with normal hearing (<25 dB). We introduce the term subclinical HL as imperfect hearing that is classically defined as normal (1-25 dB). The relationship between hearing and late life depressive symptoms may be more sensitive than previously recognized.

A pilot randomized controlled trial of hearing aids to improve mood and cognition in older adults.

OBJECTIVES: Age-related hearing loss (ARHL) is a prevalent condition associated with increased risk for depression and cognitive decline. This 12-week prospective, double-blind pilot randomized controlled trial (RCT) of hearing aids (HAs) for depressed older adults with ARHL evaluated the feasibility of a novel research design. METHODS/DESIGN: N = 13 individuals aged ≥60 years with Major Depressive Disorder or Persistent Depressive Disorder and at least mild hearing loss (pure tone average ≥ 30 dB) were randomized to receive full- (active) vs low-amplification (sham) HAs added to psychiatric treatment as usual. Duration of HA use in hours/day, adverse events frequency, attrition rate, and maintenance of the study blinding were the primary outcome measures. RESULTS: Compliance with HAs was excellent (>9 hours/day for both groups) and rates of adverse events and drop-outs did not differ between groups. Preliminary data demonstrated differential improvement for active vs sham HAs on hearing functioning (Hearing Handicap Inventory for the Elderly [nonparametric effect size (np-ES) = 0.62]), depressive symptoms (Inventory for Depressive Symptomatology [np-ES = 0.31]), cognition (Repeatable Battery for the Assessment of Neuropsychological Status Immediate Memory [np-ES = 0.25]), and general functioning (World Health Organization Disability Assessment Schedule [np-ES = 0.53]). Significantly greater than 50% of both groups correctly guessed their treatment assignment, indicating incomplete concealment of treatment allocation. CONCLUSIONS: This pilot RCT for ARHL and late-life depression was feasible to execute and showed clinical promise, but improved methods of blinding the experimental treatments are needed. Larger studies should investigate whether hearing remediation may be an effective preventative and/or therapeutic strategy for late-life depression and cognitive decline.

Lack of an association of BDNF Val66Met polymorphism and plasma BDNF with hippocampal volume and memory.

Brain-derived neurotrophic factor (BDNF) has been shown to be important for neuronal survival and synaptic plasticity in the hippocampus in nonhuman animals. The Val66Met polymorphism in the BDNF gene, involving a valine (Val) to methionine (Met) substitution at codon 66, has been associated with lower BDNF secretion in vitro. However, there have been mixed results regarding associations between either circulating BDNF or the BDNF Val66Met polymorphism with hippocampal volume and memory in humans. The current study examined the association of BDNF genotype and plasma BDNF with hippocampal volume and memory in two large independent cohorts of middle-aged and older adults (both cognitively normal and early-stage dementia). Sample sizes ranged from 123 to 649. Measures of the BDNF genotype, plasma BDNF, MRI-based hippocampal volume, and memory performance were obtained from the Knight Alzheimer Disease Research Center (ADRC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). There were no significant differences between BDNF Met+ and Met- groups on either hippocampal volume or memory in either cohort. In addition, plasma BDNF was not significantly associated with either hippocampal volume or memory in either cohort. Neither age, cognitive status, nor gender moderated any of the relationships. Overall, current findings suggest that BDNF genotype and plasma BDNF may not be robust predictors for variance in hippocampal volume and memory in middle age and older adult cohorts.

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina.

Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide.

Facial nerve paralysis after pre-operative embolization of a paraganglioma.

Vascular tumors pose a challenging problem in treatment, as surgical planning can be extensive. Often times, pre-operative embolization is required to minimize blood loss during surgery. With the advent of new biochemical compounds, embolization modalities have evolved over the past decade. Although rare, side effects and complications of embolic materials have been cited sporadically in the literature. We present an interesting case of a patient afflicted with facial paralysis and other cranial neuropathies following embolization of a paraganglioma, along with the appropriate imaging that confirms the etiology of her paralysis.

Expanding Global Surgery Education in Brazil: Perspectives after the 35th Brazilian Surgical Congress.

The 35th Brazilian Congress of Surgery marked a turning point for surgical education in the country. For the first time, the Brazilian College of Surgeons included Global Surgery on the main congressional agenda, providing a unique opportunity to rethink how surgical skills are taught from a public health perspective. This discussion prompts us to consider why and how Global Surgery education should be expanded in Brazil. Although Brazilian researchers and institutions have contributed to the fields expansion since 2015, Global Surgery education initiatives are still incipient in our country. Relying on successful strategies can be a starting point to promote the area among national surgical practitioners. In this editorial, we discuss potential strategies to expand Global Surgery education opportunities and propose a series of recommendations at the national level.

Impact of Transcranial Direct Current Stimulation in Pain, Fatigue, and Health Quality of Life of Patients with Idiopathic Inflammatory Myopathies: A Randomized, Double-Blind, Sham-Controlled Crossover Clinical Trial.

Objectives: To assess the effectiveness of transcranial direct current stimulation (tDCS) for pain, fatigue, physical function, and health-related quality of life in patients with idiopathic inflammatory myopathy (IIM). Methods: This randomized, double-blind, sham-controlled, crossover clinical trial enrolled IIM patients with fatigue and pain who received tDCS (20 min, 2 mA) or sham stimulation for 10 daily sessions. Electrodes were placed according to the 10/20 EEG system. Both the groups underwent aerobic exercise training during the intervention period. The patients were evaluated for disease perception, pain, and fatigue using uni-multidimensional questionnaires and physical tests in the periods before and after the first and second interventions and after 12 weeks of follow-up. Results: After the tDCS intervention, a reduction in the general score of multidimensional pain of 32.0 (1.5-38.0) vs. 0.0 (0.0-13.4) with effect size (ES) of -0.78 was noted, and after sham intervention, a reduction of 26.0 (0.0-37.0) vs. 5.0 (0.0-19.2) with ES of -0.54 (P = 0.047) was also noted. Similar results were evidenced with fatigue (22.5 (15.4-33.2) vs. 5.5 (0.0-14.6) with ES of -0.82) and sham intervention (21.0 (15.8-29.5) vs. 4.0 (4.0-17.5) with ES of -0.80 (P = 0.012)). There were no differences in the domains of the fatigue and pain questionnaires. Adherence was observed in 88.8% of the patients without adverse events. Conclusion: The association of tDCS with aerobic training promoted additional effects in relation to the group subjected to placebo stimulation on general pain and fatigue scores, as well as on pain intensity, without changes in the subdomains of the pain and fatigue questionnaire. This trial is registered with NCT04678635.

Clinical Practice Guideline: Age-Related Hearing Loss.

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

Clinical Practice Guideline: Age-Related Hearing Loss Executive Summary.

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

Skull Base Osteomyelitis: Historical Perspective, Diagnosis and Management Update.

SBO is a life-threatening disease that requires a high index of suspicion based on these patients complex underlying medical co-morbidities and clinician's acumen. Once a diagnosis is made, is it critical to communicate and work closely with other multidisciplinary teams (neuroradiology for appropriate choice of imaging study and interpretation; infectious disease for appropriate medical treatment and duration; internist to properly manage their underlying medical co-morbidities). Despite advances in imaging, the diagnosis is first made based on clinical judgment, appropriate culture, and tissue biopsy.

Thinking Beyond the Temporal Bone Lab: A Systematic Process for Expanding Surgical Simulation in Otolaryngology Training.

The COVID-19 pandemic led to a temporary lapse in the development of otolaryngology trainee operative skills due to the cancellation of elective procedures and redeployment of trainees and attendings to COVID-19 units. Although transient, this disruption provided an opportunity for otolaryngology programs to develop contingency plans and formalize nascent simulation training curricula. Integration of formal simulation training alongside current didactic and surgical education may offset lost exposure during surgically lean times while providing the framework and resources for enhanced baseline training. Here, we provide an up-to-date overview of surgical simulation models in otolaryngology and identify easily implementable, low-cost, low fidelity models for junior trainees. By taking advantage of rapid advancements in technology and a paradigm shift to a more hands-on approach in medical education, formal simulation training may prove to be a beneficial tool at all stages of residency training, allowing for expanded peer-mentored skill development and providing a safe haven during unforeseen disruptions in surgical case volume.

Myosin Mutations and Sudden Sensorineural Hearing Loss: Results of Whole Exome Sequencing.

OBJECTIVE: Idiopathic sudden sensorineural hearing loss (ISSNHL) affects 66,000 patients per year in the United States. Genetic mutations have been associated with progressive hearing loss; however, genetic mutations associated with ISSNHL have not been identified. METHODS: A prospective cohort study of adults older than 18 years presenting with ISSNHL at a tertiary academic medical center. Whole exome sequencing (WES) was conducted using Genome Analysis Toolkit best practices. An automated diagnostic screen employing a variety of models for pathogenicity was conducted across all genes with no specific targets. Candidate pathogenic variants were reviewed by a team of geneticists and clinicians. Variants were crossed-referenced with 92 known hearing loss associated genes. RESULTS: Twenty-nine patients with SSNHL were screened using WES. The average age of patients was 53 ± 17.1 years, and most patients were White (62%) and men (55%). The mean pure tone average was 64.8 ± 31.3 dB for the affected ear. Using a 0.1% allele frequency screen, 12 (41%) cases had a mutation in any of the nine selected myosin genes. When we restrict to singletons (allele frequency = 0%), 21% (n = 6) of cases have qualifying variants, whereas only 3.8% (n = 481) of 12,577 healthy controls carry qualifying variants (p < 0.01). Most mutations (80%) were missense mutations. Of the novel mutations, one was a frameshift mutation, and two were a stop-gained function. Three were missense mutations. CONCLUSION: Myosin mutations may be associated with ISSNHL. However, larger population screening is needed to confirm the association of myosin mutation with ISSNHL and steroid responsiveness.

Notes From the Field: Diverse Partner Perspectives Improve the Usability and Equity Focus of Implementation Guides.

Context: School-based asthma programs (SBAPs) have improved health and educational disparities among youth with asthma. Design: To support scaling out effective SBAPs, our school partners identified a need for online implementation guides that are "always available," to meet the needs of school nurses' demanding schedules. School nurses play a key role in the adoption and implementation of SBAPs, so it is important to ensure the implementation guide would be highly usable and acceptable to them. Objective: Accordingly, our research team collaborated with human-centered design experts to identify the "user journeys" of school nurses and co-created our online implementation guide as a public-facing website with input from local and national school nurse partners. Main Results: In this perspectives article, our school nurse implementation partners and human-centered design experts reflect on challenges overcome in this process of developing a tailored implementation guide to school nurses and offer lessons from the field to others seeking to co-create implementation guides with community partners.

Characterization of extrastriatal D2 in vivo specific binding of [¹8F](N-methyl)benperidol using PET.

PET imaging studies of the role of the dopamine D2 receptor family in movement and neuropsychiatric disorders are limited by the use of radioligands that have near-equal affinities for D2 and D3 receptor subtypes and are susceptible to competition with endogenous dopamine. By contrast, the radioligand [¹8F]N-methylbenperidol ([¹8F]NMB) has high selectivity and affinity for the D2 receptor subtype (D2R) and is not sensitive to endogenous dopamine. Although [¹8F]NMB has high binding levels in striatum, its utility for measuring D2R in extrastriatal regions is unknown. A composite MR-PET image was constructed across 14 healthy adult participants representing average NMB uptake 60 to 120 min after [¹8F]NMB injection. Regional peak radioactivity was identified using a peak-finding algorithm. FreeSurfer and manual tracing identified a priori regions of interest (ROI) on each individual's MR image and tissue activity curves were extracted from coregistered PET images. [¹8F]NMB binding potentials (BP(ND) s) were calculated using the Logan graphical method with cerebellum as reference region. In eight unique participants, extrastriatal BP(ND) estimates were compared between Logan graphical methods and a three-compartment kinetic tracer model. Radioactivity and BP(ND) levels were highest in striatum, lower in extrastriatal subcortical regions, and lowest in cortical regions relative to cerebellum. Age negatively correlated with striatal BP(ND) s. BP(ND) estimates for extrastriatal ROIs were highly correlated across kinetic and graphical methods. Our findings indicate that PET with [¹8F]NMB measures specific binding in extrastriatal regions, making it a viable radioligand to study extrastriatal D2R levels in healthy and diseased states.

High prevalence of fatigue in patients with Takayasu arteritis: a case-control study in a Brazilian centre.

Objectives: Several studies have shown not only a high prevalence of fatigue but also a reduction in health-related quality of life (HRQoL) in patients with rheumatic diseases. Owing to insufficient research in this area, we aimed to assess the prevalence of fatigue and its contribution to impairment of HRQoL in patients with Takayasu arteritis (TAK). Methods: This single-centre case-control study included 53 TAK patients who were matched by age, BMI and sex with 100 healthy individuals. Aside from the patients' general data, the following information was collected: disease activity, level of activities of daily living (HAQ), physical activity levels and chronic fatigue. Results: The TAK patients and healthy individuals were comparable in terms of current age, BMI and sex distribution. The median disease duration of TAK was 13.0 (7.0-20.0) years, and 11 (20.8%) patients had active disease. Compared with healthy individuals, patients with TAK had a higher prevalence of fatigue and lower HAQ score, physical activity level and intensity, and physical and psychosocial domains of the modified fatigue impact scale (P < 0.01). Moreover, TAK patients had increased fatigue rates compared with the healthy individuals (fatigue severity scale: odds ratio = 2.6; 95% CI = 1.2, 5.4; modified fatigue impact scale: odds ratio = 2.6; 95% CI = 1.2, 5.5). Fatigue was positively correlated with worsening HAQ, CRP levels, daily prednisone dose and disease activity, and negatively correlated with disease duration. Conclusion: TAK patients have a higher prevalence of fatigue, which affects different aspects of the disease, including physical function. Thus, fatigue-focused treatments should also be considered in clinical practice. Trial registration: The Brazilian Clinical Trials Registry (ReBEC), https://ensaiosclinicos.gov.br/, RBR-9n4z2hh.