Cochlear Aqueduct Post-Natal Growth: A Computed Tomography Study.

The cochlear aqueduct (CA) is a bony canal located at the base of the scala tympani of the cochlea. It connects the inner ear perilymph fluid to the cerebrospinal fluid of the posterior cerebral fossa. Its function is not well understood, as it seems to be patent in only a fraction of adult patients. Indirect observations argue in favor of the CA being more patent in children. To study the CA morphology in children, we performed a retrospective single-center study of 85 high-resolution temporal bone computed tomography (hrCT) scans of children with a mean age of 3.23 ± 3.07 years (13 days of life up to 18 years), and compared them with a group of 22 adult hrCT (mean age of 24.01 ± 3.58 years). The CA morphology measurements included its total length, its funnel (wider intracranial portion) length and width and its type (indicating its radiological patency), according to a previously published classification. The dimensions of the CA were significantly smaller in children compared with adults for the axial length (10.37 ± 2.58 versus 14.63 ± 2.40 mm, respectively, p < 0,001) and the funnel length (3.94 ± 1.59 versus 6.01 ± 1.77 mm, respectively, p < 0,001). The funnel width tended to be smaller but the difference was not significant: 3.49 ± 1,33 versus 3.89 ± 1.07 mm, p = 0,22. The repartition of types of CA was also statistically different. The CA appeared to be more identifiable in the children population. Type 1 (CA visible along its entire course) accounted for 42% (36/85) of children and only 5% (1/22) of adults, type 2 (visible in the medial two thirds) for 30% (25/85) versus 31% (7/22), type 3 (not visible completely along the medial two thirds) for 27% (23/85) versus 50% (11/22). Finally, type 4 (undetectable) was found in only 1% (1/85) of children and 14% (3/22) of adults (p < 0,001). Our study showed significant postnatal growth of the length of the CA, which was more rapid before the age of 2, and slowed after 6 years of age. Its width increased less, with children older than 2 years presenting a similar width to adults. The CA was more identifiable in hrCT in children, arguing for a more permeable tract. The number of completely ossified CA was significantly lower in the children population. These findings highlight the differences between the CA morphology in adults and children and raise the question of differences in function. Moreover, these differences may impact the pharmacodynamics of drugs or vectors delivered into the pediatric inner ear. Further studies are required, both on the anatomy of temporal bones and on the function of the CA in children.

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.

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.

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.

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.

Locoregional Control and Survival in Children, Adolescents, and Young Adults With Localized Head and Neck Alveolar Rhabdomyosarcoma-The French Experience.

INTRODUCTION: The head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to lymph nodes (LNs). The aim was to report locoregional control, event-free survival (EFS), and overall survival (OS), according to clinical and pathological features, LN staging, and treatment modalities. METHODS: The study included all patients prospectively enrolled in EpSSG RMS 2005 study under 21 years of age with localized HN ARMS and diagnosed between 2005 and 2016 in France. Medical data including imaging, surgical report, and radiation therapy planes were analyzed. RESULTS: Forty-eight patients (median age 6 years; range 4 months-21 years), corresponding to 30 parameningeal and 18 non-parameningeal ARMS, were included. There were 33 boys (69%). Tumor locations included the following: orbit (n = 7) among which four cases had bone erosion, paranasal sinuses and nasal cavity (n = 16), deep facial spaces (n = 10), nasolabial fold (n = 8), and other non-parameningeal HN sites (n = 7). A fusion transcript of PAX3-FOXO1 or PAX7-FOXO1 was expressed in 33 of the 45 cases (73%) with molecular analysis. At diagnosis, 10 patients had primary resection of the primary tumor (PRPT) (none with microscopic complete resection) and 9 had LN staging. After induction chemotherapy, 26 patients (54%) had secondary resection of the primary tumor (SRPT) and 13 patients (27%) had cervical LN dissection. A total of 43 patients (90%) were treated with radiation therapy.With a median follow-up of 7 years (range 2-13 years), 5-year OS and EFS were 78% (95% CI, 63-88%) and 66% (95% CI, 51-78%), respectively. We observed 16 events (10 deaths): 4 local, 4 regional, 1 local and regional, and 7 metastatic. In univariate analysis, OS was only superior for patients under 10 years of age (p = 0.002), while FOXO1-negative ARMS, SRPT for parameningeal ARMS, and LN surgery were associated with significantly better EFS. CONCLUSION: Our study confirms a better outcome for fusion-negative ARMS and ARMS in children under 10 years. Moreover, LN surgery and SRPT of parameningeal tumor may improve EFS of ARMS. Larger studies are needed to confirm our findings.

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.

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.

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.

rAAV-Mediated Cochlear Gene Therapy: Prospects and Challenges for Clinical Application.

Over the last decade, pioneering molecular gene therapy for inner-ear disorders have achieved experimental hearing improvements after a single local or systemic injection of adeno-associated, virus-derived vectors (rAAV for recombinant AAV) encoding an extra copy of a normal gene, or ribozymes used to modify a genome. These results hold promise for treating congenital or later-onset hearing loss resulting from monogenic disorders with gene therapy approaches in patients. In this review, we summarize the current state of rAAV-mediated inner-ear gene therapies including the choice of vectors and delivery routes, and discuss the prospects and obstacles for the future development of efficient clinical rAAV-mediated cochlear gene medicine therapy.

Fourth branchial anomalies: Predictive factors of therapeutic success.

PURPOSE: The purpose of this work was to determine the epidemiology and the predictive factors of success of the surgical management of fourth branchial anomalies. METHODS: This is a multicentric retrospective review from 1998 to 2016 of patients who presented with an endoscopically-confirmed fourth branchial pouch anomaly. Data were analyzed according to sex, age, clinical features, number of recurrences, treatment modalities (endoscopic and/or cervicotomy), post-operative complications and follow-up. RESULTS: Fifty-two children have been included. The average age at diagnosis was 4.5 years. Among them, 73.1% were female, 11.4% were neonatal forms; 94.2% of lesions were left-sided; 75% of patients presented a cervical abscess as first symptom, and 7.7% of children presented with dyspnea. Average time between first symptoms and management was 9.5 months. Management was endoscopic in 73.1% of patients (laser in 84.2%, coagulation in 15.8%) with about a third of recurrence after one procedure. Overall success of endoscopic procedures reached 84.2%. A cervical open surgery was performed in 26.9% as first line treatment. Overall success of cervicotomy reached 85.7%. No complications of endoscopic surgery have been identified. There were 35.7% complications of cervicotomy (2 recurrent nerve palsy, 2 keloid scars, 1 pharyngostoma). An association was proved between recurrences and initial abscess (OR = 2.44), and with age between 3 and 5 (OR = 4). CONCLUSION: Endoscopic treatments appear to be effective in first line approach in the management of fourth branchial anomalies, offering an excellent efficiency with rare complications. We identified two risk factors of recurrence: age between 3 and 5 years old and history of cervical abscesses. LEVEL OF EVIDENCE: IV.

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.

Benefit of Preoperative Temporal Bone CT for Atraumatic Cochlear Implantation.

HYPOTHESIS: Evaluate the benefit of preoperative surgical planning using computed tomography (CT) for atraumatic cochlear implantation. BACKGROUND: The surgical technique has a direct impact on hearing and structure preservation. Much interest has been given to depth of electrode insertion. We focused on electrode diameter depending on exposure of round window membrane (RWM) as calculated on preoperative CT. METHODS: Measurements were calculated radiologically and anatomically on 10 temporal bones. Results were compared with CT scans of a control population. Thereafter, preoperative CT scan measurements were applied to seven additional temporal bones that underwent cochlear implantation with the insertion of two electrodes of different diameters (14 implantations) to validate radiological analysis. RESULTS: RWM size was 1.5 ±â€Š0.2 mm on CT and 1.2 ±â€Š0.2 mm during dissection; posterosuperior bony overhang of round window niche was 1.1 ±â€Š0.1 mm on CT and 1.3 ±â€Š0.2 mm during dissection. There was no statistically significant difference between radiological and anatomical measurements and between radiological measurements of cadaveric temporal bones and control population (p > 0.05 for both). Also, preoperative surgical planning was reliable in the seven temporal bones implanted with two electrode types (accuracy 93%, sensitivity 85.7%, specificity 100%) yielding no damage to intracochlear structures. CONCLUSION: Difficulties to access RWM could be predicted on preoperative CT of temporal bones and control population, which correlated well with anatomical dissections and surgical findings during cochlear implantation. According to CT planning, electrode insertion through RWM was feasible in most patients, with or without drilling posterosuperior bony overhang of round window niche. Promontory cochleostomy could be recommended when electrode apical diameter exceeded maximal RWM exposure. There was no case of intracochlear trauma on microdissections.

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.

Geometric and mechanical evaluation of 3D-printing materials for skull base anatomical education and endoscopic surgery simulation - A first step to create reliable customized simulators.

INTRODUCTION: Endoscopic skull base surgery allows minimal invasive therapy through the nostrils to treat infectious or tumorous diseases. Surgical and anatomical education in this field is limited by the lack of validated training models in terms of geometric and mechanical accuracy. We choose to evaluate several consumer-grade materials to create a patient-specific 3D-printed skull base model for anatomical learning and surgical training. METHODS: Four 3D-printed consumer-grade materials were compared to human cadaver bone: calcium sulfate hemihydrate (named Multicolor), polyamide, resin and polycarbonate. We compared the geometric accuracy, forces required to break thin walls of materials and forces required during drilling. RESULTS: All materials had an acceptable global geometric accuracy (from 0.083mm to 0.203mm of global error). Local accuracy was better in polycarbonate (0.09mm) and polyamide (0.15mm) than in Multicolor (0.90mm) and resin (0.86mm). Resin and polyamide thin walls were not broken at 200N. Forces needed to break Multicolor thin walls were 1.6-3.5 times higher than in bone. For polycarbonate, forces applied were 1.6-2.5 times higher. Polycarbonate had a mode of fracture similar to the cadaver bone. Forces applied on materials during drilling followed a normal distribution except for the polyamide which was melted. Energy spent during drilling was respectively 1.6 and 2.6 times higher on bone than on PC and Multicolor. CONCLUSION: Polycarbonate is a good substitute of human cadaver bone for skull base surgery simulation. Thanks to short lead times and reasonable production costs, patient-specific 3D printed models can be used in clinical practice for pre-operative training, improving patient safety.

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.

Cone-beam computed tomography in children with cochlear implants: The effect of electrode array position on ECAP.

OBJECTIVES: To assess the feasibility of using cone-beam computed tomography (CBCT) in young children with cochlear implants (CIs) and study the effect of intracochlear position on electrophysiological and behavioral measurements. METHODS: A total of 40 children with either unilateral or bilateral cochlear implants were prospectively included in the study. Electrode placement and insertion angles were studied in 55 Cochlear® implants (16 straight arrays and 39 perimodiolar arrays), using either CBCT or X-ray imaging. CBCT or X-ray imaging were scheduled when the children were leaving the recovery room. We recorded intraoperative and postoperative neural response telemetry threshold (T-NRT) values, intraoperative and postoperative electrode impedance values, as well as behavioral T (threshold) and C (comfort) levels on electrodes 1, 5, 10, 15 and 20. RESULTS: CBCT imaging was feasible without any sedation in 24 children (60%). Accidental scala vestibuli insertion was observed in 3 out of 24 implants as assessed by CBCT. The mean insertion angle was 339.7°±35.8°. The use of a perimodiolar array led to higher angles of insertion, lower postoperative T-NRT, as well as decreased behavioral T and C levels. We found no significant effect of either electrode array position or angle of insertion on electrophysiological data. CONCLUSION: CBCT appears to be a reliable tool for anatomical assessment of young children with CIs. Intracochlear position had no significant effect on the electrically evoked compound action potential (ECAP) threshold. Our CBCT protocol must be improved to increase the rate of successful investigations.

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.