Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature.

BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457). METHODS: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2. RESULTS: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved. CONCLUSION: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.

Genotype-phenotype associations in microtia: a systematic review.

BACKGROUND: Microtia is a congenital ear malformation that can occur as isolated microtia or as part of a syndrome. The etiology is currently poorly understood, although there is strong evidence that genetics has a role in the occurrence of microtia. This systematic review aimed to determine the genes involved and the abnormalities in microtia patients' head and neck regions. METHODS: We used seven search engines to search all known literature on the genetic and phenotypic variables associated with the development or outcome of microtia. The identified publications were screened and selected based on inclusion and exclusion criteria and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 papers in this systematic review with phenotypic data in microtia involving 1459 patients and 30 articles containing genetic data involved in microtia. RESULT: The most common accompanying phenotype of all microtia patients was external ear canal atresia, while the most common head and neck abnormalities were the auricular, mental, and oral regions. The most common syndrome found was craniofacial microsomia syndrome. In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%). CONCLUSIONS: Our systematic review shows some genes involved in the microtia development, including TCOF1, SIX2, HSPA9, GSC exon 2, FANCB, HOXA2, GSC exon 3, MARS1, and CDT1 genes. We also reveal a genotype-phenotype association in microtia. In addition, further studies with more complete and comprehensive data are needed, including patients with complete data on syndromes, phenotypes, and genotypes.

[The research of the contralateral ear hearing thresholds and the hearing prognosis in unilateral Meniere's disease].

Objective:This study analyzed the pure tone audiometry results of the affected ear and the contralateral ear of unilateral Meniere's disease to investigate the correlation of the hearing threshold of the contralateral ear and the hearing prognosis of unilateral Meniere's disease. Methods:In this study, the follow-up data of 135 patients with unilateral Meniere's disease in Beijing Tongren Hospital were used to analyze the pure tone audiometry results of the affected and contralateral ears at the first visit and 1 year later. Results:①At the first visit, there was no statistically significant difference between the mean hearing thresholds of the affected ear in the normal hearing group and the high-frequency hearing loss group of the contralateral ear（P>0.05）. ②The range of improvement of hearing thresholds in the affected ear was greater in the contralateral ear normal hearing group than in the contralateral ear high-frequency hearing loss group. In the normal hearing group of the contralateral ear, the hearing thresholds of the affected ear at 0.25 kHz（P<0.01）, 0.50 kHz（P<0.01）, 1.00 kHz（P<0.01）, and 2.00 kHz（P<0.05） were significantly improved; and in the high-frequency hearing loss group of the contralateral ear, the hearing thresholds at 0.25 kHz（P<0.01） hearing thresholds improved significantly, and there was no significant difference between the rest of the frequencies before and after treatment（P>0.05）. A consistent pattern was observed in both higher and lower age groups. ③After 1 year of follow-up, the low and mid-frequency hearing of the affected ear improved. 0.25 kHz（P<0.01）, 0.50 kHz（P<0.01）, 1.00 kHz（P<0.01） hearing thresholds improved significantly; 8.00 kHz hearing thresholds decreased slightly（P<0.05）. Conclusion:After standardized treatment, the results of 1-year follow-up suggested that the low-frequency hearing of MD patients could be improved, but the high-frequency hearing was slightly decreased. The hearing prognosis of the affected ear with normal hearing threshold of the contralateral ear may be better.

Dental disease in companion rabbits under UK primary veterinary care: Frequency and risk factors.

BACKGROUND: Some prior evidence has suggested that lop-eared rabbits and those with brachycephalic skull conformations have a higher dental disease risk. This retrospective cohort study reports the frequency and conformational risk factors for primary-care veterinary diagnosis with dental disease in companion rabbits in the UK. METHODS: Anonymised VetCompass clinical records were manually reviewed to confirm dental disease cases. Risk factor analysis used multivariable binary logistic regression modelling. RESULTS: From 161,979 rabbits under primary veterinary care in 2019, the 1-year period prevalence of overall dental disease was 15.36% (95% confidence interval [CI]: 14.78-15.96). The prevalence of dental disease affecting incisors was 3.14% (95% CI: 2.87-3.44), and for cheek teeth it was 13.72% (95% CI: 13.17-14.29). Neither lop-eared conformation nor brachycephalic skull conformation was significantly associated with increased odds of dental disease. Dental disease odds increased as age increased and decreased as bodyweight increased. LIMITATIONS: This study retrospectively accessed clinical records, so breed names may sometimes be imprecise. CONCLUSION: The high overall prevalence of dental disease represents a major welfare concern for all companion rabbits, regardless of conformation. This information can be used to encourage regular routine dental assessment of rabbits of all conformations to promote earlier diagnosis, paying particular attention to older rabbits and those with low bodyweight.

Outcomes and device use in children with bone-conduction hearing devices in South Africa.

BACKGROUND:  Bone-conduction hearing devices (BCHD) can provide hearing solutions in settings where middle ear pathology is rife. OBJECTIVES:  Describe functional hearing outcomes and device use of children fitted with BCHD. METHOD:  Retrospective review of 79 children fitted with BCHD between January 2017 and May 2022. Outcomes included device use and subjective reports measured with the Parents' Evaluation of Aural/Oral Performance of Children (PEACH) and the Teachers' Evaluation of Aural/Oral Performance of Children (TEACH). Analysis of variance established association between mean data logging and type and degree of hearing loss. Thematic analyses were done for qualitative outcomes. RESULTS:  Average usage was 7.0 h/day (5.4 SD; range 0.1-24). PEACH ratings indicated 93.3% of children wore their BCHD 'always' or 'often', with 80% displaying Typical auditory performance at 1-month follow-up. TEACH ratings indicated 84.2% of children wore their BCHD 'always' or 'often', with 78.9% showing typical auditory behaviour. Increased usage was noted for conductive, mixed, moderate and severe hearing losses. There was a mean delay of 17.2 months (23.4 SD; range 0-90) between age of diagnosis and fitting. Thematic analyses identified two main themes: advantages and barriers to BCDH use. CONCLUSION:  Average device use fell short of the internationally recommended 10 h/day. Higher BCHD use was associated with higher functional listening performance scores. Long waiting times for medical or surgical intervention for conductive hearing losses can delay BCHD fitting.Contribution: Limited information is available to examine outcomes in children fitted with BCHD.

Brain Wearables: Validation Toolkit for Ear-Level EEG Sensors.

EEG-enabled earbuds represent a promising frontier in brain activity monitoring beyond traditional laboratory testing. Their discrete form factor and proximity to the brain make them the ideal candidate for the first generation of discrete non-invasive brain-computer interfaces (BCIs). However, this new technology will require comprehensive characterization before we see widespread consumer and health-related usage. To address this need, we developed a validation toolkit that aims to facilitate and expand the assessment of ear-EEG devices. The first component of this toolkit is a desktop application ("EaR-P Lab") that controls several EEG validation paradigms. This application uses the Lab Streaming Layer (LSL) protocol, making it compatible with most current EEG systems. The second element of the toolkit introduces an adaptation of the phantom evaluation concept to the domain of ear-EEGs. Specifically, it utilizes 3D scans of the test subjects' ears to simulate typical EEG activity around and inside the ear, allowing for controlled assessment of different ear-EEG form factors and sensor configurations. Each of the EEG paradigms were validated using wet-electrode ear-EEG recordings and benchmarked against scalp-EEG measurements. The ear-EEG phantom was successful in acquiring performance metrics for hardware characterization, revealing differences in performance based on electrode location. This information was leveraged to optimize the electrode reference configuration, resulting in increased auditory steady-state response (ASSR) power. Through this work, an ear-EEG evaluation toolkit is made available with the intention to facilitate the systematic assessment of novel ear-EEG devices from hardware to neural signal acquisition.

[A sampling survey of intraoperative facial nerve monitoring in China].

Objective: This study aims to investigate the current application and the level of knowledge of intraoperative facial nerve monitoring among medical staff in China. Methods: A comprehensive online questionnaire was conducted among medical professionals across different regions in China from October 2022 to February 2023. The survey exclusively targeted departments specializing in otolaryngology, head and neck surgery, neurosurgery, and oral and maxillofacial surgery. The questionnaire covered various aspects including general information, intraoperative facial nerve monitoring practices, training history, indications for monitoring, parameters used during monitoring procedures, as well as factors influencing its implementation. Results: A total of 417 participants from 31 provincial, municipal, and autonomous regions were included. Intraoperative facial nerve monitoring was found to be implemented in 227 (54.4%,227/417) repondents of 53 institutions (24.9%, 53/213). The top three indications for implementing this technique were acoustic neuroma, parotid gland surgery, and modified middle ear surgery (mastoidectomy). Herein 81.1%(184/227) medical staff involved in intraoperative facial nerve monitoring had received relevant training, 57.3%(130/227)-92.1%(209/227) reported a lack of clear description regarding recording thresholds, stimulation currents/frequencies/wave widths. Conclusion: The majority of the institutions surveyed have not yet adopted intraoperative facial nerve monitoring. Furthermore, significant gaps concerning the procedure exist. It is imperative to establish standards or guidelines to promote its better development and application.

Grounded language acquisition through the eyes and ears of a single child.

Starting around 6 to 9 months of age, children begin acquiring their first words, linking spoken words to their visual counterparts. How much of this knowledge is learnable from sensory input with relatively generic learning mechanisms, and how much requires stronger inductive biases? Using longitudinal head-mounted camera recordings from one child aged 6 to 25 months, we trained a relatively generic neural network on 61 hours of correlated visual-linguistic data streams, learning feature-based representations and cross-modal associations. Our model acquires many word-referent mappings present in the child's everyday experience, enables zero-shot generalization to new visual referents, and aligns its visual and linguistic conceptual systems. These results show how critical aspects of grounded word meaning are learnable through joint representation and associative learning from one child's input.

The Right-Ear Advantage in Static and Dynamic Cocktail-Party Situations.

When presenting two competing speech stimuli, one to each ear, a right-ear advantage (REA) can often be observed, reflected in better speech recognition compared to the left ear. Considering the left-hemispheric dominance for language, the REA has been explained by superior contralateral pathways (structural models) and language-induced shifts of attention to the right (attentional models). There is some evidence that the REA becomes more pronounced, as cognitive load increases. Hence, it is interesting to investigate the REA in static (constant target talker) and dynamic (target changing pseudo-randomly) cocktail-party situations, as the latter is associated with a higher cognitive load than the former. Furthermore, previous research suggests an increasing REA, when listening becomes more perceptually challenging. The present study examined the REA by using virtual acoustics to simulate static and dynamic cocktail-party situations, with three spatially separated talkers uttering concurrent matrix sentences. Sentences were presented at low sound pressure levels or processed with a noise vocoder to increase perceptual load. Sixteen young normal-hearing adults participated in the study. The REA was assessed by means of word recognition scores and a detailed error analysis. Word recognition revealed a greater REA for the dynamic than for the static situations, compatible with the view that an increase in cognitive load results in a heightened REA. Also, the REA depended on the type of perceptual load, as indicated by a higher REA associated with vocoded compared to low-level stimuli. The results of the error analysis support both structural and attentional models of the REA.

Proton-FLASH: effects of ultra-high dose rate irradiation on an in-vivo mouse ear model.

FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-ß1, TNF-α, IL1α, and IL1ß were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.

Experiences of Percutaneous Endoscopic Approach for the Mastoid Lesions: A Novel Minimally Invasive Ear Surgery.

OBJECTIVES: We developed a novel keyhole surgery, named "percutaneous endoscopic ear surgery" (PEES), with the aim of further reducing the invasiveness of otologic surgery. We reported the cases we encountered and retrospectively analyzed the invasiveness of PEES. METHODS: We analyzed the ears of eight patients who underwent PEES for mastoid lesions that could not be manipulated with transcanal endoscopic ear surgery (TEES) at our hospital between July 2021 and November 2022. We performed PEES alone in three patients, including one case of type A (preauricular incision) and two cases of type B (retroauricular incision). The last five patients underwent combined endoscopic ear surgery, which is simultaneous PEES and TEES. In these cases, one patient underwent type A PEES, and four patients underwent type B PEES. RESULTS: PEES was performed in all patients without converting to conventional microscopic mastoidectomy. The mean length of skin incisions was 19.1 ± 4.5 mm, which was smaller than that in conventional mastoidectomy. In all cases, the average length of the major axis of the keyhole was <10 mm, indicating that sufficient minimally invasive surgery was achieved. The average depth from the keyhole to the deepest site was 21.6 ± 8.9 mm. There was no change in the mean hearing level before and after the surgery. CONCLUSION: PEES is a minimally invasive procedure for manipulating lesions in the mastoid. In addition, the combination of PEES and TEES is an ideal, minimally invasive procedure that can be used to treat all regions of the temporal bone.

Hearing loss and history of otolaryngological conditions in adults with microdeletion 22q11.2.

Previous studies have shown that the 22q11.2 microdeletion, associated with 22q11.2 deletion syndrome (22q11.2DS), conveys an increased risk of chronic otitis media, and hearing loss at young age. This study reports on hearing loss and history of otolaryngological conditions in adults with 22q11.2DS. We conducted a retrospective study of 60 adults with 22q11.2DS (41.7% male) at median age 25 (range 16-74) years who had visited an otolaryngologist and audiologist for routine assessment at a 22q11.2 expert center. Demographic, genetic, audiometric, and otolaryngological data were systematically extracted from the medical files. Regression analysis was used to evaluate the effect of age, sex, full-scale intelligence quotient, and history of chronic otitis media on the severity of hearing loss. Hearing loss, mostly high-frequency sensorineural, was found in 78.3% of adults. Higher age and history of chronic otitis media were associated with more severe hearing loss. Otolaryngological conditions with possible treatment implications included chronic otitis media (56.7%), globus pharyngeus (18.3%), balance problems (16.7%), and obstructive sleep apnea (8.3%). The results suggest that  in 22q11.2DS, high-frequency hearing loss appears to be common from a young adult age, and often unrecognized. Therefore, we recommend periodic audiometric screening in all adults, including high-frequency ranges.

Question Mark Ear: An Unusual Anomaly and a Novel Surgical Technique for Reconstruction.

The question mark ear is a rare abnormality characterized by a cleft between the helix and the earlobe, resulting in a protrusion of the upper part of the ear. The severity of this ear malformation can range from a minor notch in the helix to a complete separation of the helix and the earlobe. In this study, we present a case of a patient with a moderately severe right-sided unilateral question mark deformity. To address this issue, we utilized a novel technique that involves a combination of a Y-V flap with double opposing Z-plasty. Our clinical study demonstrates that using this technique for reconstructing the deformity yields excellent results in terms of the helical rim and fold contour, utilizing solely the local tissues.

Laterality and otorhinolaryngology: a review.

BACKGROUND: Laterality of paired organs involves the function of the eyes, ears, hands and feet. Whilst most people have a right-handed preference, about 10 per cent are left-handed. Similarly, the right eye is usually preferred to the left. Medicine is both taught and practised for those with right hand and eye preference, and left-handed medical students and doctors must negotiate the right-handed world. OBJECTIVE: This brief review looks at society's attitudes, medical training and the practice of otolaryngology in the UK towards laterality and handedness. METHOD: Literature review. RESULTS: Studies suggest that left-handers are more versatile and so are more ambidextrous. Conversely, this may result in problems when a right-hander tries to undertake a procedure with the non-dominant hand. CONCLUSION: Cultures and attitudes are changing towards those who are left-handed. Left-handed surgeons may encounter difficulties in the clinical environment throughout their training.

Long-term results and quality of life after vibrant soundbridge implantation (VSBs) in children and adults with aural atresia.

PURPOSE: The aim of this study was to evaluate the long-term effectiveness and acceptance of the active middle ear implant system Vibrant Soundbridge (VSB®, MED-EL, Austria) in patients with aural atresia or aplasia (children and adults). METHODS: Data from 51 patients (mean age 13.9 ± 11.3 years), 42 (79.2%) children and adolescents, and 11 (20.8%) adults) who received a VSB implant between 2009 and 2019 at the Department of Otolaryngology at LMU Clinic Großhadern, Munich were included in the study. Pure-tone audiometry, speech recognition in a quiet environment and in a noisy environment were performed preoperatively, during the first fitting of the audio processor, after 1-3 years, after 3-5 years, and after 5 years (if possible). The follow-up period ranged from 11 to 157 months with a mean of 58.6 months (4.8 years). Furthermore, the benefit of the VSB was evaluated by self-assessment questionnaires (Speech, Spatial, and Qualities of Hearing Scale, respectively, for parents). RESULTS: Significant improvements were observed in hearing and speech comprehension immediately after the initial fitting of the VSB system (mean hearing gain 38.4 ± 9.4 dB HL) and at follow-up intervals (1-3, 3-5 and after 5 years) for children and adults (p < 0.01). The values remained stable over the long-term, indicating a sustained functional gain from the VSB (mean hearing gain 38.9 ± 9.2 dB HL). The results of the self-assessments affirm the positive influence on hearing and speech comprehension with the VSB. With the VSB, there was an improvement of 41.3 ± 13.7% in the Freiburg monosyllable test. CONCLUSION: These results (a stable hearing gain over the long term, a good tolerance of the implant and an improvement in quality of life) affirm the recommendation for using the active middle ear implant VSB as early as permitted for aural atresia and aplasia patients. This study represents the audiometric results with the (to date) largest collective of aural atresia patients and with a long follow-up period.

Hearing rehabilitation in children with malformed ears: The endoscopic-assisted approach for cochlear implantation.

BACKGROUND: Cochlear implantation (CI) in children with malformed ears can be challenging through the standard surgical technique. Several alternative approaches have been described. The endoscopic-assisted approach can be chosen as an effective and safe surgical technique, overcoming the drawbacks of the traditional approach. MATERIAL: We further describe a combined technique based on a limited mastoidectomy with no posterior tympanotomy and an endoscopic transmeatal approach to the round window (RW): the electrode is driven from the mastoid to the middle ear through the attic. RESULTS: The concomitant endoscopic assistance allows for improved surgical vision, reducing the risk of major complications. The main advantages of this technique are related to better visualization of the RW for safe insertion of the electrode; avoidance of damage to the facial nerve (FN), due to direct visualization, and sparing the posterior tympanotomy; avoidance of subtotal petrosectomy, if not necessary. CONCLUSION: The purpose of this article, supported with a video file, is to describe step by step this endoscopic-assisted procedure in a patient with middle ear malformation.

Comparison of Transcutaneous and Percutaneous Implantable Hearing Devices for the Management of Congenital Aural Atresia: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare audiometric outcomes, complications, and revisions required for percutaneous (pBCD) versus transcutaneous (tBCD) implantable bone-conduction devices for the treatment of hearing loss associated with congenital aural atresia (CAA).Databases Reviewed.PubMed, Scopus, CINAHL. METHODS: A systematic review was performed searching for English language articles from inception to December 14, 2022. Studies reporting audiometric outcomes or complications for either pBCDs or tBCDs for the treatment of CAA were selected for inclusion. A meta-analysis of single means and meta-analysis of proportions with comparison (Δ) of weighted proportions was conducted. RESULTS: A total of 56 articles with 756 patients were selected for inclusion. One hundred ninety patients were implanted with pBCDs, whereas the remaining 566 were implanted with tBCDs. Mean pure-tone audiometry improvement in the pBCD group (39.1 ± 1.1 dB) was significantly higher than in the tBCD group (34.6 ± 1.6 dB; Δ4.5 dB; 95% confidence interval, 4.2-4.7 dB; p < 0.0001). The average improvement in speech reception threshold was 38.6 ± 2.5 dB in the percutaneous group as compared with 32.7 ± 1.6 dB in the transcutaneous group (Δ5.9 dB [5.3-6.5 dB], p < 0.0001). Overall complication rates for patients implanted with pBCDs and tBCDs were 29.0% (15.7-44.4%) and 9.4% (6.5%-13.0%), respectively (Δ19.6% [12.0-27.7%], p < 0.0001). CONCLUSIONS: Patients with CAA implanted with pBCDs had significantly better audiometric outcomes than those implanted with tBCDs. However, complication rates were significantly higher among the pBCD group.