Hemangiol in infantile haemangioma: A paediatric post-marketing surveillance drug study.

AIM: Infantile haemangioma (IH) is the most common benign tumour in children. Since 2014, propranolol has become the first-choice therapy and currently Hemangiol is the only approved drug for complicated haemangioma. This post-marketing study reports the use of Hemangiol for IH in paediatric practice. METHOD AND RESULTS: From January 2014 to November 2018, 94 children (median age 4 [0; 21] months; 75% female) treated with Hemangiol for proliferative IH were enrolled in the study. The systematic paediatric cardiology consultation never contraindicated beta-blockers. Two Hemangiol initiation protocols were used: a conventional ambulatory 3-week titration phase protocol (n = 76, 80.9%), and a rapid initiation protocol with a 48-hour dose escalation in conventional hospitalization for severe proliferative or ulcerated IH (n = 18, 19.1%). In both protocols, the haemodynamic tolerance was good. The mean maintenance dose of Hemangiol was 2.7 ± 0.8 mg/kg/day, with a median treatment duration of 7 [1.5; 19] months. Adverse events (AEs) have been found in 25 (26,6%) patients, including 8 (8.5%) patients with serious AEs (uncontrolled bronchial hyperreactivity, n = 5; serious hypoglycaemia, n = 3). Some patients had one or more AEs, a total of 24 nonserious AEs was reported in 19 patients (sleep disturbances, n = 9; respiratory disorders, n = 5; digestive disorders, n = 6). No cardiac adverse event was reported. CONCLUSION: This post-marketing surveillance drug study supports the good tolerance of Hemangiol in children with IH. A rapid initiation protocol is of interest when treatment is urgent. The pretherapeutic paediatric cardiology consultation should not be systematic but only indicated for specific patients. CLINICALTRIALS.GOV: NCT04105517.

Cochlear Implantation and Other Treatments in Single-Sided Deafness and Asymmetric Hearing Loss: Results of a National Multicenter Study Including a Randomized Controlled Trial.

INTRODUCTION: Cochlear implantation is a recent approach proposed to treat single-sided deafness (SSD) and asymmetric hearing loss (AHL). Several cohort studies showed its effectiveness on tinnitus and variable results on binaural hearing. The main objective of this study is to assess the outcomes of cochlear implantation and other treatment options in SSD/AHL on quality of life. METHODS: This prospective multicenter study was conducted in 7 tertiary university hospitals and included an observational cohort study of SSD/AHL adult patients treated using contralateral routing of the signal (CROS) hearing aids or bone-anchored hearing systems (BAHSs) or who declined all treatments, and a randomized controlled trial in subjects treated by cochlear implantation, after failure of CROS and BAHS trials. In total, 155 subjects with SSD or AHL, with or without associated tinnitus, were enrolled. After 2 consecutive trials with CROS hearing aids and BAHSs on headband, all subjects chose any of the 4 treatment options (abstention, CROS, BAHS, or cochlear implant [CI]). The subjects who opted for a CI were randomized between 2 arms (CI vs. initial observation). Six months after the treatment choice, quality of life was assessed using both generic (EuroQoL-5D, EQ-5D) and auditory-specific quality-of-life indices (Nijmegen Cochlear implant Questionnaire [NCIQ] and Visual Analogue Scale [VAS] for tinnitus severity). Performances for speech-in-noise recognition and localization were measured as secondary outcomes. RESULTS: CROS was chosen by 75 subjects, while 51 opted for cochlear implantation, 18 for BAHSs, and 11 for abstention. Six months after treatment, both EQ-5D VAS and auditory-specific quality-of-life indices were significantly better in the "CI" arm versus "observation" arm. The mean effect of the CI was particularly significant in subjects with associated severe tinnitus (mean improvement of 20.7 points ± 19.7 on EQ-5D VAS, 20.4 ± 12.4 on NCIQ, and 51.4 ± 35.4 on tinnitus). No significant effect of the CI was found on binaural hearing results. Before/after comparisons showed that the CROS and BAHS also improved significantly NCIQ scores (for CROS: +7.7, 95% confidence interval [95% CI] = [4.5; 10.8]; for the BAHS: +14.3, 95% CI = [7.9; 20.7]). CONCLUSION: Cochlear implantation leads to significant improvements in quality of life in SSD and AHL patients, particularly in subjects with associated severe tinnitus, who are thereby the best candidates to an extension of CI indications.

Treatment choice in single-sided deafness and asymmetric hearing loss. A prospective, multicentre cohort study on 155 patients.

OBJECTIVES: To describe the treatment choice in a cohort of subjects with single-sided deafness (SSD) and asymmetric hearing loss (AHL). To assess the reliability of the treatment trials. DESIGN: In this national, multicentre, prospective study, the choice of subjects was made after two consecutive trials of Contralateral Routing Of the Signal (CROS) hearing aids and a Bone Conduction Device (BCD) on a headband. Subjects could proceed with one of these two options, opt for cochlear implantation or decline all treatments. SETTING: Seven tertiary university hospitals. PARTICIPANTS: One hundred fifty-five subjects with SSD or AHL fulfilling the candidacy criteria for cochlear implantation, with or without associated tinnitus. MAIN OUTCOME MEASURES: After the two trials, the number of subjects choosing each option was described. Repeated assessments of both generic and auditory-specific quality of life were conducted, as well as hearing assessments (speech recognition in noise and horizontal localization). RESULTS: CROS was chosen by 75 subjects, followed by cochlear implantation (n = 51), BCD (n = 18) and abstention (n = 11). Patients who opted for cochlear implantation had a poorer quality of life (P = .03). The improvement of quality of life indices after each trial was significantly associated with the final treatment choice (P = .008 for generic indices, P = .002 for auditory-specific indices). The follow-up showed that this improvement had been overestimated in the CROS group, with a long-term retention rate of 52.5%. CONCLUSIONS: More than one third of SSD/AHL subjects are unsatisfied after CROS and BCD trials. Repeated quality of life assessments help counselling the patient for his/her treatment choice.

Isolated neonatal bilateral vocal cord paralysis revealing a unilateral medullary defect: a case report.

BACKGROUND: Congenital bilateral vocal cord paralysis is a rare occurrence. Approximately half the cases are associated with a major comorbidity, usually neurological, neuromuscular or malformative. CASE PRESENTATION: In a male newborn, respiratory distress syndrome and stridor were observed immediately following birth. The cause was bilateral vocal cord paralysis in the adducted position. Neuroradiological investigation revealed a unilateral discontinuity between the upper pons and the right medulla oblongata. Hypoplasia of the right posterior hemiarches of C1-C2 and the right exo-occipital bone was observed, as was a small clivus. MR angiography showed the absence of the distal right vertebral artery, with hypoplasia and parietal irregularities of the proximal segments. Respiratory autonomy was not obtained despite endoscopic laser cordotomy, corticosteroid therapy and nasal continuous positive airway pressure. The infant died at the age of 4 weeks after treatment was limited to comfort care. CONCLUSIONS: A medullary lesion is an exceptional cause of congenital bilateral vocal cord paralysis. The strictly unilateral neurological and vascular defect and the absence of associated intracranial or extracranial malformation make this clinical case unique and suggest a disruptive mechanism. This case also highlights the help provided by advanced neuroimaging techniques, i.e. fibre tracking using diffusion tensor imaging, in the decision-making process.

Evaluation of otoscopy simulation as a training tool for real-time remote otoscopy.

OBJECTIVE: Teleotoscopy requires the assistance of telehealth facilitators; but their training requirements remain to be determined. We evaluated the use of an otoscopy simulator to train facilitators to remote otoscopies sent via the Internet using a teleaudiology platform. DESIGN: Neurotologists experts were asked to identify images using the otoscopy simulator and to perform an identification task of significant anatomical landmarks. The experts were asked to repeat those tasks remotely, with the help of facilitators who either received basic training, or no training prior to the experiment. STUDY SAMPLE: Three experts, three trained facilitators and three untrained facilitators participated in this study. RESULTS: The use of an otoscopy simulator in addition to remote otoscopy yielded a good inter- and intrarater agreement (κ between 0.81-1, and 0.80-0.87, respectively). The accuracy of diagnosis was high on-site (11.7% error) and remotely (0% error). The time required for landmark identification task was not increased when performed remotely with a trained facilitator versus on-site otoscopy (9.3 versus 9.2 s/landmark). Conversely, the lack of training of facilitators increased significantly this time (15.6 s/landmark, p < 0.001). CONCLUSION: An otoscopic simulator coupled to teleaudiology software can be used to efficiently train both experts and facilitators to perform remote otoscopy.

A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis).

OBJECTIVES: Inflammasomes are multiprotein complexes that sense pathogens and trigger biological mechanisms to control infection. Nucleotide-binding oligomerisation domain-like receptor (NLR) containing a PYRIN domain 1 (NLRP1), NLRP3 and NLRC4 plays a key role in this innate immune system by directly assembling in inflammasomes and regulating inflammation. Mutations in NLRP3 and NLRC4 are linked to hereditary autoinflammatory diseases, whereas polymorphisms in NLRP1 are associated with autoimmune disorders such as vitiligo and rheumatoid arthritis. Whether human NLRP1 mutation is associated with autoinflammation remains to be determined. METHODS: To search for novel genes involved in systemic juvenile idiopathic arthritis, we performed homozygosity mapping and exome sequencing to identify causative genes. Immunoassays were performed with blood samples from patients. RESULTS: We identified a novel disease in three patients from two unrelated families presenting diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Molecular screening revealed a non-synonymous homozygous mutation in NLRP1 (c.2176C>T; p.Arg726Trp) in two cousins born of related parents originating from Algeria and a de novo heterozygous mutation (c.3641C>G, p.Pro1214Arg) in a girl of Dutch origin. The three patients showed elevated systemic levels of caspase-1 and interleukin 18, which suggested involvement of NLRP1 inflammasome. CONCLUSIONS: We demonstrate the responsibility of human NLRP1 in a novel autoinflammatory disorder that we propose to call NAIAD for NLRP1-associated autoinflammation with arthritis and dyskeratosis. This disease could be a novel autoimmuno-inflammatory disease combining autoinflammatory and autoimmune features. Our data, combined with that in the literature, highlight the pleomorphic role of NLRP1 in inflammation and immunity. TRIAL REGISTRATION NUMBER: NCT02067962; Results.

Five-Year Hearing Outcomes in Bilateral Simultaneously Cochlear-Implanted Adult Patients.

OBJECTIVE: To report the speech performance and sound localization in adult patients 5 years after bilateral simultaneous cochlear implantation and to evaluate the change in speech scores between 1 and 5 years. DESIGN: In this prospective multicenter study, 26 patients were evaluated 5 years after implantation using long straight electrode arrays (MED-EL Combi 40+, standard electrode array, 31 mm). Speech perception was measured using disyllabic words in quiet and noise, with the speech coming from the front and a cocktail party background noise coming from 5 loudspeakers. Speech localization measurements were performed in noise under the same test conditions. These results were compared to those obtained at 1 year reported in a previous study. RESULTS: Five years after implantation, an improvement in speech performance scores compared to 1 year after implantation was found for the poorer ear both in quiet and in noise (+12.1 ± 2.6%, p < 0.001). The lower the speech score of the poorer ear at 1 year, the greater the improvement at 5 years, both in quiet (r = -0.62) and at a signal-to-noise ratio of +15 dB (r = -0.58). The sound localization on the horizontal plane in noise provided by bilateral implantation was better than the unilateral one and remained stable after the results observed at 1 year. CONCLUSION: In adult patients simultaneously and bilaterally implanted, the poorest speech scores improved between 1 and 5 years after implantation. These findings are an additional element to recommend bilateral implantation in adult patients. The use of both cochlear implants and speech training sessions for patients with poor performance should continue in the period after 1 year following implantation, since the speech scores will improve over time.

Effects of electrode array length on frequency-place mismatch and speech perception with cochlear implants.

Frequency-place mismatch often occurs after cochlear implantation, yet its effect on speech perception outcome remains unclear. In this article, we propose a method, based on cochlea imaging, to determine the cochlear place-frequency map. We evaluated the effect of frequency-place mismatch on speech perception outcome in subjects implanted with 3 different lengths of electrode arrays. A deeper insertion was responsible for a larger frequency-place mismatch and a decreased and delayed speech perception improvement by comparison with a shallower insertion, for which a similar but slighter effect was noticed. Our results support the notion that selecting an electrode array length adapted to each individual's cochlear anatomy may reduce frequency-place mismatch and thus improve speech perception outcome.

Neonatal respiratory distress syndrome revealing a cervical bronchogenic cyst: a case report.

BACKGROUND: Bronchogenic cyst is a congenital malformation, rarely located in the cervical region and almost never involved in a neonate with acute respiratory distress in the delivery room. CASE PRESENTATION: A female newborn with respiratory distress syndrome caused by a large left cervical mass. Intubation was difficult due to tracheal deviation. Magnetic resonance imaging confirmed a left cervical cyst displacing the trachea and esophagus laterally. Surgical excision was performed via a cervical approach on the 5th day, and pathological examination revealed a bronchogenic cyst. The patient's course was complicated by left vocal cord paralysis and necrotic lesions in the glottic and subglottic regions; she required a tracheostomy on the 13th day. Inflammatory stenosis in the subglottic region required balloon dilation once, 20 days later. Proximal esophageal stenosis induced transient upper airway obstruction with salivary stasis. Decannulation was performed at 2 months and the patient was discharged 10 days later. CONCLUSION: A bronchogenic cyst can exceptionally obstruct the airways in the neonatal period. Surgical excision is necessary, but postoperative complications may occur if the cyst is in close contact with the trachea and esophagus, including necrotic and stenotic lesions of the upper aerodigestive tract. In those situations, tracheostomy may be necessary for mechanical ventilation weaning and the initiation of oral feeding.

Refining the audiological assessment in children using narrow-band CE-Chirp-evoked auditory steady state responses.

OBJECTIVE: To demonstrate the feasibility and reliability of simultaneous binaural recording of auditory steady-state responses (ASSR) in young children using narrow-band CE-Chirps as stimuli. DESIGN: Prospective cohort study comparing ASSR thresholds to four frequency stimuli (0.5, 1, 2, and 4 kHz), with click-evoked auditory brainstem responses (ABR) and behavioral response audiometry. STUDY SAMPLE: Thirty-two young children (mean age 7.4 ± 5.2 months) referred for auditory assessment were evaluated. RESULTS: The mean duration for ABR recordings was 13.3 ± 7.2 min versus 22.9 ± 15.8 min for ASSR (p < 0.01). ASSR (means of 2 and 4 kHz thresholds) were highly correlated with ABR thresholds (R2 = 0.935, p < 0.001), though significantly different (3 ± 10.7 dB, p = 0.02). ASSR (means of 0.5, 1, 2, and 4 kHz thresholds) were highly correlated with mean behavioral response audiometry thresholds (R2 = 0.968, p < 0.001). ASSRs were highly and significantly correlated with behavioral response audiometry at 0.5, 1, 2, and 4 kHz (R2 = 0.845, 0.907, 0.929, and 0.859 respectively, p < 0.001). 87.5% and 90.7% ASSR thresholds were within a ± 10 dB range around their corresponding ABR and mean behavioral response audiometry thresholds. CONCLUSIONS: Narrow-band CE-Chirps allow a fast and reliable assessment of auditory thresholds in children, especially in the low-frequency range, by comparison with other stimuli.

Predictive factors of cochlear implant outcomes in the elderly.

OBJECTIVE: To analyze predictive factors of cochlear implant outcomes and postoperative complications in the elderly. STUDY DESIGN: Prospective, longitudinal study performed in 10 tertiary referral centers. METHODS: Ninety-four patients aged 65-85 years with a profound, postlingual hearing loss were evaluated before implantation, at time of activation, and 6 and 12 months after cochlear implantation. Speech perception and lipreading were measured using disyllabic word recognition in quiet and noise, and lipreading using disyllabic words and sentences. The influence of preoperative factors on speech perception in quiet and noise at 12 months was tested in a multivariate analysis. Complications, presence of tinnitus and of vestibular symptoms were collected at each evaluation. RESULTS: The effect of age was observed only in difficult noisy conditions at SNR 0 dB. Lipreading ability for words and sentences was negatively correlated with speech perception in quiet and noise. Better speech perception scores were observed in patients with shorter duration of hearing deprivation, persistence of residual hearing for the low frequencies, the use of a hearing aid before implantation, the absence of cardiovascular risk factors, and in those with implantation in the right ear. General and surgical complications were very rare, and the percentage of vestibular symptoms remained stable over time. CONCLUSION: This study demonstrates that cochlear implantation in the elderly is a well-tolerated procedure and an effective method to improve communication ability. Advanced age has a low effect on cochlear implant outcome. Analyses of predictive factors in this population provide a convincing argument to recommend treatment with cochlear implantation as early as possible in elderly patients with confirmed diagnosis of a severe-to-profound hearing loss and with only limited benefit from hearing aid use in one ear.

Value of the video head impulse test in assessing vestibular deficits following vestibular neuritis.

To evaluate the performance of the video head impulse test (VHIT) in assessing vestibular deficit in vestibular neuritis. Test validation study was conducted in Tertiary referral center. Twenty-nine patients, referred for vestibular neuritis between October 2009 and March 2012, were included. We recorded age, gender, values of caloric deficit (caloric testing), and deficits in semicircular function (VHIT) at initial presentation and at the follow-up visit (1-3 months). Multivariate linear regression analysis was performed to determine variables associated with values of caloric testing at the follow-up visit. Diagnostic values of VHIT were compared with caloric testing data using the receiver-operating characteristic (ROC) curve and subsequent statistical analysis. At the follow-up visit, complete recovery occurred in 31% of cases according to caloric evaluation, and VHIT normalized in 51.8%. Multivariate regression showed that a higher caloric deficit at the follow-up visit was associated with elevated age (p = 0.012) and high caloric deficit at initial presentation (p = 0.042). A lower caloric deficit was associated with normal VHIT results at the follow-up visit (p < 0.001). The ROC curve showed that specificity and sensitivity of VHIT were 100% when the caloric deficit was respectively lower than 40% or higher than 62.5%. At the caloric testing value of 30%, specificity was 100%, sensitivity 68.84%, positive predictive value 100% and negative predictive value 62.5%. VHIT is a fast, convenient and specific test to detect vestibular deficits in vestibular neuritis. However, VHIT lacks sensitivity by comparison with caloric testing, especially for moderate vestibular lesions.

The transtympanic promontory stimulation test in patients with auditory deprivation: correlations with electrical dynamics of cochlear implant and speech perception.

Transtympanic promontory stimulation test (TPST) has been suggested to be a useful tool in predicting postoperative outcomes in patients at risk of poor auditory neuron functioning, especially after a long auditory deprivation. However, only sparse data are available on this topic. This study aimed at showing correlations between the auditory nerve dynamic range, evaluated by TPST, the electrical dynamic range of the cochlear implant and speech perception outcome. We evaluated 65 patients with postlingual hearing loss and no residual hearing, implanted with a Nucleus CI24 cochlear implant device for at least 2 years and with a minimum of 17 active electrodes. Using the TPST, we measured the threshold for auditory perception (T-level) and the maximum acceptable level of stimulation (M-level) at stimulation frequencies of 50, 100 and 200 Hz. General linear regression was performed to correlate 1/speech perception, evaluated using the PBK test 1 year after surgery, and 2/cochlear implant electrical dynamic range, with the age at time of implantation, the duration of auditory deprivation, the etiology of the deafness, the duration of cochlear implant use and auditory nerve dynamic range. Postoperative speech perception outcome correlated with etiology, duration of auditory deprivation and implant use, and TPST at 100 and 200 Hz. The dynamic range of the cochlear implant map correlated with duration of auditory deprivation, speech perception outcome at 6 months and TPST at 100 and 200 Hz. TPST test can be used to predict functional outcome after cochlear implant surgery in difficult cases.

Quantification of Female Chimeric Cells in the Tonsils of Male Children and Their Determinants.

The factors influencing mother-to-child cell trafficking and persistence over children's lives have yet to be established. The quantification of maternal microchimerism was previously reported through HLA-based approaches, which introduced bias regarding the tolerogenic environment. We aimed to identify cells of maternal origin irrespective of the HLA repertoire and to ascertain the determinants of microchimeric cells. This case-control study enrolled 40 male infants attending pediatric surgery from January 2022 to October 2022. Female cells were quantified in infants' tonsil tissue by using cytogenetic fluorescent in situ hybridization (FISH) coupled with optimized automated microscopy. Out of the 40 infants, half (47.4%) had been breastfed for more than one month, a quarter for less a month, and 10 children (26.3%) were never breastfed. XX cells were observed in male tonsils in two-thirds of participants at a median density of 5 cells per 100,000 cells. In univariate analyses, child age was negatively associated with a high female cell density. In exploratory multivariate analyses, previous breastfeeding is a likely determinant of the persistence of these cells in the host, as well as the rank among siblings. Part of the benefit of breastmilk for child health may therefore be driven by breastfeeding-related microchimerism.

Genetic Evaluation of Prelingual Hearing Impairment: Recommendations of an European Network for Genetic Hearing Impairment.

The cause of childhood hearing impairment (excluding infectious pathology of the middle ear) can be extrinsic (embryofoetopathy, meningitis, trauma, drug ototoxicity, noise trauma, etc [...].

Audiological Outcomes and Associated Factors after Pediatric Cochlear Reimplantation.

Cochlear implants are the most common and successful sensory neuroprosthetic devices. However, reimplantation can be required for medical reasons, device failure, or technological upgrading. Resolving the problem driving the intervention and offering stable or better audiological results are the main challenges. We aimed to analyze the success rate of this intervention and to identify factors influencing speech perception recovery after reimplantation in the pediatric population. We retrospectively collected the causes and the outcomes of 67 consecutive reimplantations in one cochlear implant center over 30 years. Reimplantation resolved the cause without recurrence for 94% of patients. The etiology of deafness, time since implantation, indication of reimplantation, sex, and age did not influence word discrimination test scores in silence, 3 years after surgery. However, adherence to a speech rehabilitation program was statistically associated with gain in perception scores: +8.9% [-2.2; +31.0%] versus -19.0% [-47.5; -7.6%] if no or suboptimal rehabilitation was followed (p = 0.0037). Cochlear reimplantation in children is efficient and is associated with predictable improvement in speech perception, 3 years after intervention. However, good adherence to speech rehabilitation program is necessary and should be discussed with the patient and parents, especially for the indication of reimplantation for technological upgrading.

Effect of surgical technique on electrode impedance after cochlear implantation.

OBJECTIVES: We compare the evolution of electrode impedance values (IVs) following either conventional cochlear implantation or implantation by the soft surgery (SS) technique. METHODS: We performed a retrospective chart review of 20 consecutive adult patients who underwent implantation with the Nucleus CA 24 device between 2004 and 2007. Five patients with preoperative residual hearing at the frequencies 256, 512, and 1,024 Hz underwent implantation by an SS cochlear implantation technique (SS group), and the 15 other patients underwent a conventional implantation technique (conventional cochleostomy [CC] group). The active electrodes were classified as distal (17 to 22), middle (10 to 16), or proximal (3 to 9) according to their position in relation to the tip of the electrode array. Their IVs were collected at 1, 3, 12, 24, and 36 months after implantation. Changes in auditory thresholds at 3 and 24 months were reported for patients in the SS group. RESULTS: The postoperative IVs of both the CC and SS groups decreased significantly between 1 and 3 months after implantation (p < 0.05) and then remained stable. The IVs after 12 months were significantly lower (p < 0.05) in the SS group than in the CC group. CONCLUSIONS: Patients who underwent the SS technique displayed lower long-term electrode IVs than did their counterparts in the CC group. If electrode IVs are indeed an indirect representation of cochlear fibrosis, the use of the SS technique in lieu of the CC technique could reduce fibrotic development.

Feasibility of Cochlea High-frequency Ultrasound and Microcomputed Tomography Registration for Cochlear Computer-assisted Surgery: A Testbed.

INTRODUCTION: There remains no standard imaging method that allows computer-assisted surgery of the cochlea in real time. However, recent evidence suggests that high-frequency ultrasound (HFUS) could permit real-time visualization of cochlear architecture. Registration with an imaging modality that suffers neither attenuation nor conical deformation could reveal useful anatomical landmarks to surgeons. Our study aimed to address the feasibility of an automated three-dimensional (3D) HFUS/microCT registration, and to evaluate the identification of cochlear structures using 2D/3D HFUS and microCT. METHODS: MicroCT, and 2D/3D 40 MHz US in B-mode were performed on ex vivo guinea pig cochlea. An automatic rigid registration algorithm was applied to segmented 3D images. This automatic registration was then compared to a reference method using manual annotated landmarks placed by two senior otologists. Inter- and intrarater reliabilities were evaluated using intraclass correlation coefficient (ICC) and the mean registration error was calculated. RESULTS: 3D HFUS/microCT automatic registration was successful. Excellent levels of concordance were achieved with regards intra-rater reliability for both raters with micro-CT and US images (ICC ranging from 0.98 to 1, p < 0.001) and with regards inter-rater reliability (ICC ranging from 0.99 to 1, p < 0.001). The mean HFUS/microCT automated RE for both observers was 0.17 ±â€Š0.03 mm [0.10-0.25]. Identification of the basilar membrane, modiolus, scala tympani, and scala vestibuli was possible with 2D/3D HFUS and micro-CT. CONCLUSIONS: HFUS/microCT image registration is feasible. 2D/3D HFUS and microCT allow the visualization of cochlear structures. Many potential clinical applications are conceivable.

A Single Cisterna Magna Injection of AAV Leads to Binaural Transduction in Mice.

Viral-mediated gene augmentation, silencing, or editing offers tremendous promise for the treatment of inherited and acquired deafness. Inner-ear gene therapies often require a safe, clinically useable and effective route of administration to target both ears, while avoiding damage to the delicate structures of the inner ear. Here, we examined the possibility of using a cisterna magna injection as a new cochlear local route for initiating binaural transduction by different serotypes of the adeno-associated virus (AAV2/8, AAV2/9, AAV2/Anc80L65). The results were compared with those following canalostomy injection, one of the existing standard inner ear local delivery routes. Our results demonstrated that a single injection of AAVs enables high-efficiency binaural transduction of almost all inner hair cells with a basal-apical pattern and of large numbers of spiral ganglion neurons of the basal portion of the cochlea, without affecting auditory function and cochlear structures. Taken together, these results reveal the potential for using a cisterna magna injection as a local route for binaural gene therapy applications, but extensive testing will be required before translation beyond mouse models.

When Familial Hearing Loss Means Genetic Heterogeneity: A Model Case Report.

We describe a family with both hearing loss (HL) and thrombocytopenia, caused by pathogenic variants in three genes. The proband was a child with neonatal thrombocytopenia, childhood-onset HL, hyper-laxity and severe myopia. The child's mother (and some of her relatives) presented with moderate thrombocytopenia and adulthood-onset HL. The child's father (and some of his relatives) presented with adult-onset HL. An HL panel analysis, completed by whole exome sequencing, was performed in this complex family. We identified three pathogenic variants in three different genes: MYH9, MYO7A and ACTG1. The thrombocytopenia in the child and her mother is explained by the MYH9 variant. The post-lingual HL in the paternal branch is explained by the MYO7A variant, absent in the proband, while the congenital HL of the child is explained by a de novo ACTG1 variant. This family, in which HL segregates, illustrates that multiple genetic conditions coexist in individuals and make patient care more complex than expected.