Academic Outcomes with Hearing Amplification Devices in Children with Unilateral Hearing Loss: A Systematic Review and Narrative Synthesis.

BACKGROUND: Many studies have shown increased academic problems in children with unilateral hearing loss (UHL). However, whether hearing devices can ameliorate the educational difficulties associated with UHL is not well studied. Therefore, the objective of the current systematic review was to answer the question: do nonsurgical amplification devices, bone-anchored hearing aids, and/or cochlear implants improve academic outcomes in school-aged children and adolescents with UHL? METHODS: Embase, MEDLINE, Scopus, CINAHL, APA PsycInfo, ClinicalTrials.gov, and Cochrane databases were searched from inception to December 21, 2022. Published, peer-reviewed studies comparing academic outcomes in patients with UHL aged ≥5 and ≤19 years with and without hearing devices (nonsurgical amplification devices, bone-anchored hearing aids, or cochlear implants) were included. Results of studies were qualitatively synthesized, and the risk of bias was evaluated with the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool. RESULTS: A total of 5,644 non-duplicate publications were identified by the search, and four studies were included for synthesis, every one of which was investigating nonsurgical amplification. One small, single-arm study demonstrated significant improvement in subjective classroom listening difficulties after a 3- to 4-month trial with a behind-the-ear hearing aid. The other three studies of nonsurgical amplification devices showed no benefit across multiple academic outcomes with FM systems and conventional and CROS-style hearing aids. DISCUSSION: The small sample sizes, heterogeneous and/or ill-defined study samples, and overall low quality of the available literature ultimately make it hard to draw definitive conclusions regarding nonsurgical amplification devices' effectiveness in improving academic outcomes in children with UHL. No articles were identified that studied cochlear implants or bone-anchored hearing aids. Further studies with high-quality study design, large sample sizes, and long-term follow-up are needed to answer this clinically important question.

Evolving microbial patterns of acute mastoiditis in pediatric patients undergoing mastoidectomy.

OBJECTIVE: To investigate the microbial patterns and clinical outcomes of pediatric patients undergoing mastoidectomy for acute coalescent mastoiditis and to identify factors associated with poor outcomes and/or prolonged treatment. STUDY DESIGN: Monocentric retrospective cohort study. SETTING: Tertiary referral pediatric hospital in Indiana. METHODS: By cross-referencing database data from the Pediatric Health Information System (PHIS) querying for all inpatient stays (patients younger than eighteen) with a diagnostic code of mastoiditis between January 1st, 2010 and August 31, 2019, and the electronic health record (Cerner) for Riley Hospital for Children, 46 patients with mastoidectomy were included. A two-tailed T-test was used to evaluate continuous parametric data. Statistical significance was determined as P < 0.05. For continuous variables, data was analyzed using continuous logistic regression. A criteria of p > 0.1 was used for inclusion in the multivariate regression. RESULTS: Inclusion criteria was met by 46 patients. From 2010 to 2019, S. pyogenes and S. pneumoniae were the most common bacteria, each isolated in 11 of 42 bacterial isolates (26.2%). There was no growth in 35.4% (17/48) of intra-operative wound cultures. On univariate analysis, patients with negative cultures had longer length of hospital stay (LOS) (7.7 days [6.5] vs. 4.3 [2.8]; p = 0.018) as well as higher rates of PICC (peripherally inserted central catheter) placement (53.3% vs. 19.4%; p = 0.021). There was a statistically significant difference in terms of gender (p = 0.021), with 15 males and 16 females in the positive culture cohort and 13 males and 2 females in the negative culture cohort. On multivariate analysis, which included gender, PICC placement, both intracranial and extracranial complications, duration of antibiotics, and LOS, female gender was the only significant predictor of positive culture status (p = 0.039). CONCLUSION: S. pyogenes and S. pneumoniae were the predominant etiologic agents in acute coalescent mastoiditis between 2010 and 2019, and negative wound cultures were associated with worse clinical outcomes.

Generating high-fidelity cochlear organoids from human pluripotent stem cells.

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.

Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids.

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.

Verbal Working Memory Error Patterns and Speech-Language Outcomes in Youth With Cochlear Implants.

PURPOSE: Verbal working memory (VWM) delays are commonly found in prelingually deaf youth with cochlear implants (CIs), albeit with considerable interindividual variability. However, little is known about the neurocognitive information-processing mechanisms underlying these delays and how these mechanisms relate to spoken language outcomes. The goal of this study was to use error analysis of the letter-number sequencing (LNS) task to test the hypothesis that VWM delays in CI users are due, in part, to fragile, underspecified phonological representations in short-term memory. METHOD: Fifty-one CI users aged 7-22 years and 53 normal hearing (NH) peers completed a battery of speech, language, and neurocognitive tests. LNS raw scores and error profiles were compared between samples, and a hierarchical regression model was used to test for associations with measures of speech, language, and hearing. RESULTS: Youth with CIs scored lower on the LNS test than NH peers and committed a significantly higher number of errors involving phonological confusions (recalling an incorrect letter/digit in place of a phonologically similar one). More phonological errors were associated with poorer performance on measures of nonword repetition and following spoken directions but not with hearing quality. CONCLUSIONS: Study findings support the hypothesis that poorer VWM in deaf children with CIs is due, in part, to fragile, underspecified phonological representations in short-term/working memory, which underlie spoken language delays. Programs aimed at strengthening phonological representations may improve VWM and spoken language outcomes in CI users.

A single center retrospective clinical evaluation of anterior cervical discectomy and fusion comparing allograft spacers to silicon nitride cages.

BACKGROUND: Iliac crest autograft or allograft spacers have been traditionally utilized in anterior cervical discectomy and fusion (ACDF) to provide vertebral stabilization and enhanced osteogenesis. However, abiotic cages have largely replaced these allogenic sources due to host-site morbidities and disease transmission risks, respectively. Although devices made of polyetheretherketone (PEEK) or titanium-alloys (Ti) have gained wide popularity, they lack osteoinductive or conductive capabilities. In contrast, silicon nitride (Si3N4) is a relatively new implant material that also provides structural stability and yet purportedly offers osteopromotive and antimicrobial behavior. This study compared radiographic outcomes at ≥12 months of follow-up for osseous integration, fusion rate, time to fusion, and subsidence in ACDF patients with differing intervertebral spacers. METHODS: Fifty-eight ACDF patients (108 segments) implanted with Si3N4 cages were compared to thirty-four similar ACDF patients (61 segments) implanted with fibular allograft spacers. Lateral radiographs (normal, flexion, and extension) were obtained at 3, 6, 12, and 24 months to assess osseous integration, the presence of bridging bone, the absence of peri-implant radiolucencies, subsidence, and fusion using both interspinous distance (ISD) and Cobb angle methods. RESULTS: In patients with ≥12 months of follow-up, fusion for the allograft spacers and Si3N4 cages was 86.84% and 96.83%, respectively (ISD method, P=0.10), and 67.65% and 84.13%, respectively (Cobb angle method P=0.07), while osseointegration was 76.32% and 93.65%, respectively (P=0.02). The time to fusion significantly favored the Si3N4 cages (4.08 vs. 8.64 months (ISD method, P=0.01), and 6.76 vs. 11.74 months (Cobb angle method, P=0.04). The assessed time for full osseointegration was 7.83 and 19.24 months for Si3N4 and allograft, respectively (P=0.00). Average subsidence at 1-year follow-up was 0.51 and 2.71 mm for the Si3N4 and allograft cohorts, respectively (P=0.00). CONCLUSIONS: In comparison to fibular allograft spacers, Si3N4 cages showed earlier osseointegration and fusion, higher fusion rates, and less subsidence.

Competitive tuning: Competition's role in setting the frequency-dependence of Ca2+-dependent proteins.

A number of neurological disorders arise from perturbations in biochemical signaling and protein complex formation within neurons. Normally, proteins form networks that when activated produce persistent changes in a synapse's molecular composition. In hippocampal neurons, calcium ion (Ca2+) flux through N-methyl-D-aspartate (NMDA) receptors activates Ca2+/calmodulin signal transduction networks that either increase or decrease the strength of the neuronal synapse, phenomena known as long-term potentiation (LTP) or long-term depression (LTD), respectively. The calcium-sensor calmodulin (CaM) acts as a common activator of the networks responsible for both LTP and LTD. This is possible, in part, because CaM binding proteins are "tuned" to different Ca2+ flux signals by their unique binding and activation dynamics. Computational modeling is used to describe the binding and activation dynamics of Ca2+/CaM signal transduction and can be used to guide focused experimental studies. Although CaM binds over 100 proteins, practical limitations cause many models to include only one or two CaM-activated proteins. In this work, we view Ca2+/CaM as a limiting resource in the signal transduction pathway owing to its low abundance relative to its binding partners. With this view, we investigate the effect of competitive binding on the dynamics of CaM binding partner activation. Using an explicit model of Ca2+, CaM, and seven highly-expressed hippocampal CaM binding proteins, we find that competition for CaM binding serves as a tuning mechanism: the presence of competitors shifts and sharpens the Ca2+ frequency-dependence of CaM binding proteins. Notably, we find that simulated competition may be sufficient to recreate the in vivo frequency dependence of the CaM-dependent phosphatase calcineurin. Additionally, competition alone (without feedback mechanisms or spatial parameters) could replicate counter-intuitive experimental observations of decreased activation of Ca2+/CaM-dependent protein kinase II in knockout models of neurogranin. We conclude that competitive tuning could be an important dynamic process underlying synaptic plasticity.