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The prevalence of UHL is estimated 1 per 1000 children at birth, increasing with age; appoximately 10% of children born with UHL eventually develop bilateral hearing loss. Although genetic causes are predominant for bilateral hearing loss, this seems not true for UHL. Some syndromic causes can be associated with UHL, for example Waardenburg or BOR syndrome. Although families with sensorineural HL have been reported, only a few genetic mutations have been identified as being possibly associated with UHL. Other important causes include congenital CMV infection, meningitis and trauma, but in a high percentage of UHL the cause still remains uknown. A very important point is that the incidence of temporal bone anomalies in congenital UHL is high compared with congenital bilateral HL. Large Vestibular Acqueduct and cochlear nerve aplasya/hypoplasia are increasingly identified using high resolution CT and MRI. Malformations of the inner ear with unilateral hearing loss can be associated with an increased risk of developing bacterial meningitis in the pediatric population. Matherial and Methods: We reviewed imaging findings of pediatric subjects with sensorineural or mixed UHL consecutively diagnosed between 2013 and 2017 in our Audiology and ENT department. Results: The likelihood of identifing a malformation depends on the severity of UHL. LVA and IAC stenosis with cochlear nerve hypo/aplasia are the most frequent anomalies. More severe losses are associated with a greater percentage of anatomical abnormalities. Conclusions: All children with unilateral sensorineural hearing loss should undergo radiologic examination with CT and MRI. In these cases, genetic counseling and prognosis are influenced by imaging results. Finally, because of the risk of ipsi- and contralateral progression also in normal temporal bone imaging group, long-term audiological surveillance is needed. [ABSTRACT FROM AUTHOR]

Children with congenital unilateral hearing loss (CUHL), although they can hear and learn through the normal hearing side, cannot benefit from binaural advantages and may encounter difficulties in accessing relevant acoustic information in adverse listening environments. Literature has shown that children with CUHL also experience greater difficulties than their normal hearing peers in a variety of domains. Nevertheless, individual performance is highly variable, with some children showing developmental delay and other seemingly demonstrating normal performance and development. Similarly, while recent neuroimaging research information shows effects of CUHL on auditory but also non-auditory brain regions, little is known about specific consequences on clinical neuropsychological domains. In order to highlight if CUHL affects cognitive disabilities that go beyond auditory system, particularly those connected with Executive Attention, we evaluated 15 children affected by CUHL (age 8-11yrs) with average scores on general cognitive abilities compared to control group (15 children). The assessment battery included tests examining several abilities (Executive attention, visuo-spatial short term memory, visual and motor search, complex visual constructive skills, word and non-word reading), following the rationale that Executive Attention is the basis of several complex abilities. The clinical sample shows significant differences with the control group. We found impairments that go beyond auditory problems and our results support the information derived from functional neuroimaging studies, showing effects of CUHL on auditory but also on non-auditory brain regions and suggesting that CUHL can represent the source of a functional connectivity alteration. Even though CUHL represents a modality specific deficit, it may well involve complex neuropsychological development and multi-modal processing. [ABSTRACT FROM AUTHOR]

A 4 years old boy developed a progressive hearing loss (HL) starting 3 weeks after Neisseria Meningitidis type B meningitis leading to a severe and profound degree on both ears. For the prospective risk of cochlear ossification, bilateral cochlear implantation (CI) was performed with optimal auditory-speech perception outcome achievement. Unaided hearing threshold began to show fluctuations and improvement up to a moderate HL on the left ear, starting 4 months after meningitis and continuing for years post CI surgery. In order to explore the residual cochlear function, an exclusively acoustic amplification was fitted on the improved left side 5 years post implantation. Audiological testing showed very satisfactory discrimination outcomes with acoustic amplification demonstrate that a good cochlear function has been preserved in this case. A certain degree of hearing recovery may be expected after meningitis related deafness. Moreover, this case example encourages surgeons and CI technology researchers to intensely explore techniques, therapies and technological solutions that can facilitate the preservation of inner ear structure and the still existing cochlear function during and after CI surgery in order to leave open the opportunities of new strategies adoption. [ABSTRACT FROM AUTHOR]

Acute myocarditis leading to severe heart failure in paediatric patients is an uncommon but potentially life-threatening condition. The prompt implant of mechanical circulatory devices such as veno-arterial extra-corporeal membrane oxygenation remains the best treatment option to restore an adequate perfusion and improve patient survival in case of refractory cardiogenic shock cases. While few reports describe the in-hospital course of this dramatic disease, with an in-hospital mortality under veno-arterial extra-corporeal membrane oxygenation support around 30%, our study aims to analyse both short- and long-term outcomes after extra-corporeal membrane oxygenation implant.

Objective: To investigate which factors influence the adherence to hearing aid (HA) use in elderly patients with moderate-to-severe hearing loss., Methods: This observational, prospective, single-centre study enrolled patients with moderate-to-severe hearing loss. They were evaluated before and 1 year after having either one or two HAs fitted., Results: A total of 86 patients were enrolled in the study and of these 69.8% (60 of 86; USER group) continued to use their HA at 1 year after fitting; six patients had not continued their use (NON-USERS). The USER group was younger than the NON-USER group, but the difference was not significant. The USER group had a significantly better unaided auditory threshold at baseline than the NON-USER group. HA use resulted in improvements in speech audiometry and auditory threshold. There was also a maintenance of cognitive function in the USER group., Conclusion: Use of HA for 1 year resulted in improved auditory performance and an absence of a deterioration of cognitive function. Trial registration: This research was retrospectively registered under no. NCT04333043 at ClinicalTrials.gov (http://www.clinicaltrials.gov/) on the 26 March 2020. This research has been registered with the Ethics Committee of the Area Vasta Emilia Nord under number 104, date of approval 17/07/2017., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Background : Baraitser-Winter Syndrome (BRWS) is a rare autosomal dominant condition associated with hearing loss (HL). In the literature, two types of this condition are reported, Baraitser-Winter type 1 (BRWS1) and type 2 (BRWS2) produced by specific pathogenetic variants of two different genes, ACTB for BRWS1 and ACTG1 for BRWS2. In addition to syndromic BRWS2, some pathogenic variants in ACTG1 are associated also to another pathologic entity, the "Autosomal dominant non-syndromic hearing loss 20/26". In these syndromes, typical craniofacial features, sensory impairment (vision and hearing) and intellectual disabilities are frequently present. Heart anomalies, renal and gastrointestinal involvement and seizure are also common. Wide inter- and intra-familial variety in the phenotypic spectrum is reported. Some phenotypic aspects of these syndromes are not yet fully described, such as the degree and progression of HL, and better knowledge of them could be useful for correct follow-up and treatment. Methods and Results : In this study, we report two cases of children with HL and diagnosis of BRWS and a review of the current literature on HL in these syndromes.

Background: It is known that subjects with a cochlear implant (CI) need to exert more listening effort to achieve adequate speech recognition compared to normal hearing subjects. One tool for assessing listening effort is pupillometry. The aim of this study is to evaluate the effectiveness of adaptive directional microphones in reducing listening effort for CI recipients., Methods: We evaluated listening in noise and listening effort degree (by pupillometry) in eight bimodal subjects with three types of CI microphones and in three sound configurations., Results: We found a correlation only between sound configurations and listening in noise score ( p -value 0.0095). The evaluation of the microphone types shows worse scores in listening in noise with Opti Omni (+3.15 dB SNR) microphone than with Split Dir (+1.89 dB SNR) and Speech Omni (+1.43 dB SNR). No correlation was found between microphones and sound configurations and within the pupillometric data., Conclusions: Different types of microphones have different effects on the listening of CI patients. The difference in the orientation of the sound source is a factor that has an impact on the listening effort results. However, the pupillometry measurements do not significantly correlate with the different microphone types.

There are several pathologies that can change the anatomy of the otic capsule and that can distort the bone density of the bony structures of the inner ear, but otosclerosis is one of the most frequent. Similar behavior has been shown in patients affected by osteogenesis imperfecta (OI), a genetic disorder due to a mutation in the genes coding for type I (pro) collagen. In particular, we note that otosclerosis and OI can lead to bone resorption creating pericochlear cavitations in contact with the internal auditory canal (IAC). In this regard, we have collected five cases presenting this characteristic; their audiological data and clinical history were analyzed. This feature can be defined as a potential cause of a third-window effect, because it causes an energy loss during the transmission of sound waves from the oval window (OW) away from the basilar membrane.

Mitral valve replacement in infants is challenging and there are limited alternative valves available. Since the Boston group published their first report on alternative valves for mitral valve replacement in infants, there has been a growth in the literature on the topic, mostly based on the use of a stented bovine jugular vein graft (Melody® valve). The challenges of the Melody valve are firstly in its length of 28 mm unexpanded, which has the potential to cause left ventricular outflow tract obstruction, and secondly, the valve needs mechanical dilatation, which is laborious. A modified No-React® Injectable Biopulmonic™ Prosthesis (Bio Integral Surgical, Inc., Mississauga, ON, Canada) which is shorter (19 mm) and simpler in that it is self-expanding was implanted in a 14-month-old child to replace her mitral valve. The operation was successful and the short-term function of the prosthesis is good., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Early bilateral cochlear implants (CIs) may enhance attention to speech, and reduce cognitive load in noisy environments. However, it is sometimes difficult to measure speech perception and listening effort, especially in very young children. Behavioral measures cannot always be obtained in young/uncooperative children, whereas objective measures are either difficult to assess or do not reliably correlate with behavioral measures. Recent studies have thus explored pupillometry as a possible objective measure. Here, pupillometry is introduced to assess attention to speech and music in noise in very young children with bilateral CIs (N = 14, age: 17-47 months), and in the age-matched group of normally-hearing (NH) children (N = 14, age: 22-48 months). The results show that the response to speech was affected by the presence of background noise only in children with CIs, but not NH children. Conversely, the presence of background noise altered pupil response to music only in in NH children. We conclude that whereas speech and music may receive comparable attention in comparable listening conditions, in young children with CIs, controlling for background noise affects attention to speech and speech processing more than in NH children. Potential implementations of the results for rehabilitation procedures are discussed.

COVID-19 infection can cause a wide spectrum of symptoms. The audio-vestibular system can also be involved, but there is still debate about this so findings need to be considered carefully. Furthermore, mother to fetus intrauterine transmission of COVID-19 infection in pregnant women is controversial. Few studies are available about the audio-vestibular symptomatology of newborns with intrauterine COVID19 exposure., Objectives: This study investigates the possible correlation between the COVID19 gestational infection and hearing impairment onset in newborns. The involvement of hearing in COVID19 is verified so the timing and methodology of audiological evaluation of children can be planned., Methods: Children were subject to newborn hearing screening and audiological evaluation. Newborn hearing screening is carried out prior to hospital discharge using the Automatic Transient Evoked Otoacoustic Emissions test. Audiological evaluation is performed within the child age of 4 months by using maternal, pregnancy, and perinatal case history, COVID19 case history, otoscopy, acoustic immittance test, Distortion Product Otoacoustic Emissions test, and the Auditory Brainstem Response test., Results: 63 children were included in the study. 82.5% of these children were subjects of the newborn hearing screening program. The remaining 11 newborns were not subjected to hearing screening due to isolation measures and their audiological evaluation was carried out directly. Only one of 52 screened neonates showed a bilateral REFER test result but hearing threshold was normal at audiological evaluation. Audiological evaluation showed normal bilateral ABR thresholds in 59/63 children. Four children (6.3% of the total) had ABR threshold alterations but two showed normal threshold at ABR retest performed within 1 month of the first. The other two infants showed monolateral ABR alterations but one of these had a concomitant middle ear effusion. In conclusion, only one child (1.6% of the sample) had an altered ABR. This child had shown one positive SARS-CoV-2 swab in the absence of risk factors for hearing loss., Conclusion: This study finds no evidence that maternal COVID19 infection is a risk factor in the development of congenital hearing loss in newborns., (Copyright © 2022 Elsevier Inc. All rights reserved.)

(1) Background: Schwannomas of the vestibulocochlear nerve are benign, slow-growing tumors, arising from the Schwann cells. When they originate from neural elements within the vestibule or cochlea, they are defined as intralabyrinthine schwannomas (ILSs). Cochlear implant (CI) has been reported as a feasible solution for hearing restoration in these patients. (2) Methods: Two patients with single-sided deafness (SSD) due to sudden sensorineural hearing loss and ipsilateral tinnitus were the cases. MRI detected an ILS. CI was positioned using a standard round window approach without tumor removal. (3) Results: The hearing threshold was 35 dB in one case and 30 dB in the other 6 mo after activation. Speech audiometry with bisillables in quiet was 21% and 27% at 65 dB, and the tinnitus was completely resolved or reduced. In the localization test, a 25.9° error azimuth was obtained with CI on, compared to 43.2° without CI. The data log reported a daily use of 11 h and 14 h. In order to not decrease the CI's performance, we decided not to perform tumor exeresis, but only CI surgery to restore functional binaural hearing. (4) Conclusions: These are the sixth and seventh cases in the literature of CI in patients with ILS without any tumor treatment and the first with SSD. Cochlear implant without tumor removal can be a feasible option for restoring binaural hearing without worsening the CI's performance.

Very early bilateral implantation is thought to significantly reduce the attentional effort required to acquire spoken language, and consequently offer a profound improvement in quality of life. Despite the early intervention, however, auditory and communicative outcomes in children with cochlear implants remain poorer than in hearing children. The distorted auditory input via the cochlear implants requires more auditory attention resulting in increased listening effort and fatigue. Listening effort and fatigue may critically affect attention to speech, and in turn language processing, which may help to explain the variation in language and communication abilities. However, measuring attention to speech and listening effort is demanding in infants and very young children. Three objective techniques for measuring listening effort are presented in this paper that may address the challenges of testing very young and/or uncooperative children with cochlear implants: pupillometry, electroencephalography, and functional near-infrared spectroscopy. We review the studies of listening effort that used these techniques in paediatric populations with hearing loss, and discuss potential benefits of the systematic evaluation of listening effort in these populations.

Background: Every year, around 15 million children, in developing countries, die or develop life-long disabilities because of congenital cardiac diseases. In this report we measure the effect of a pediatric cardiac surgery humanitarian project on the health of the individual and on the potential influence this has on the countries economy and its growing health services. Methods: We collected and analyzed data from the Italian NGO, Mission Bambini's database, including all congenital cardiac missions undertaken in Cambodia between 2012 and 2019. DALY's (Disability Adjusted Life Years) saved by the humanitarian mission were estimated and used to reflect on the impact this had on the populations economy. Progression in the local medical teams skills emulated the advancements made in the health sector of the region. Results: Between 2012 and 2019, 128 patients underwent a congenital cardiac operation at Angkor Hospital for Children at Siem Reap, Cambodia. The median age was 6 years. The majority of the pathologies included VSD, TOF, ASD. The mean Aristotle's Complexity Score was 6. Post-operative mortality was 0.8% (1/128). The cost-effectiveness analysis identified 5.360 DALY's saved by surgery. The competency of the local team was progressive with them being able to handle more complex cases on subsequent missions. Conclusion: In developing Countries, performing congenital cardiac surgery cases can be carried out successfully with improvement in both the economy and the health system of the country by increasing the years and the quality of life of the working population and developing the expertise of the regional team., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Marianeschi, Uricchio, Cerri, Ghiselli, Carro, Albano and Viola.)

A new non-invasive adhesive bone conduction hearing device (ABCD) has been proposed as an alternative solution for reversible bilateral conductive hearing loss in recurrent or long-lasting forms of otitis media with effusion (OME) in children that cannot undergo surgical treatment. Our aim was to assess the effectiveness of ABCD in children with OME. Twelve normal-hearing Italian-speaking volunteers, in whom a conductive hearing loss was simulated, participated in the study. The free-field average hearing threshold was determined and, to evaluate binaural hearing skills, loudness summation and the squelch effect were assessed. Five conditions were tested: (1) unaided without earplugs, (2) unaided with bilateral earplugs, (3) aided right ear with bilateral earplugs, (4) aided left ear with bilateral earplugs, and (5) bilateral aid with bilateral earplugs. Post-hoc analysis showed a significant statistical difference between plugged, unplugged, and each aided condition. The main results were a better loudness summation and a substantial improvement of the squelch effect in the bilaterally aided. Our results suggest that ABCD is a valid treatment for patients with conductive hearing loss that cannot undergo bone conduction implant surgery. It is also important to consider bilateral aids in order to deal with situations in which binaural hearing is fundamental.

Background: Prevalence of hearing loss increases with age. Its estimated prevalence is 40-50 % in people over 75 years of age. Recent studies agree that declinein hearing threshold contribute to deterioration in sociality, sensitivity, cognition, and quality of life for elderly subjects. The aim of the study presented in this paper is to verify whether or not rehabilitation using first time applied Hearing Aids (HA) in a cohort of old people with hearing impairment improves both speech perception in a noisy environment over time and the overall health-related quality of life., Methods: The monocentric, prospective, repeated measurements, single-subject, clinical observational study is to recruit 100 older adults, first-time HA recipients (≥ 65 years).The evaluation protocol is designed to analyze changes in specific measurement tools a year after the first HA usage in comparison with the evaluation before HA fitting. Evaluations will consist of multiparametric details collected through self-report questionnaires completed by the recipients and a series of commonly used audiometric measures and geriatric assessment tools. The primary indicator of changes in speech perception in noise to be used is the Italian version of Oldenburg Satz (OLSA) test whereas the indicator of changes in overall quality of life will be the Assessment of Quality of Life (AQoL) and Hearing Handicap Inventory for the Elderly (HHIE) questionnaires. The Montreal Cognitive Assessment (MoCA) will help in screening the cognitive state of the subjects., Discussion: The protocol is designed to make use of measurement tools that have already been applied to the hearing-impaired population in order to compare the effects of HA rehabilitation in the older adults immediately before first HA usage (Pre) and after 1 year of experience (Post). This broad approach will lead to a greater understanding of how useful hearing influences the quality of life in older individuals, and therefore improves potentials for healthy aging. The data is to be analyzed by using an intrasubject endpoint comparison. Outcomes will be described and analyzed in detail., Trial Registration: This research was retrospectively registered underno. NCT04333043at ClinicalTrials.gov (http://www.clinicaltrials.gov/) on the 26 March 2020. This research has been registered with the Ethics Committee of the Area Vasta Emilia Nord under number 104, date of approval 17/07/2017.

Objectives: Chronic pulmonary valve (PV) regurgitation is a common late sequela after repair of congenital heart diseases like tetralogy of Fallot or pulmonary stenosis, leading to right ventricular dilatation and failure and increased late morbidity and mortality. Timely reoperation may lead to a complete right ventricular recovery. An injectable PV allows pulmonary valve replacement, with or without cardiopulmonary bypass, under direct observation, thereby minimizing the impact of surgery on cardiac function. The aim of this study was to evaluate the feasibility and mid- to long-term clinical outcomes with this device., Methods: From April 2007 to October 2019, a total of 85 symptomatic patients with severe pulmonary regurgitation or pulmonary stenosis underwent pulmonary valve replacement with an injectable stented pulmonary prosthesis. Data were collected from the international proctoring registry. Mean patient age was 26.7 years. The underlying diagnosis was repaired tetralogy of Fallot in 69.4% patients; moderate or severe pulmonary regurgitation was present in 72.9%. All patients had echocardiographic scans before the operation and during the follow-up period. A total of 54.1% patients also had preoperative/postoperative cardiac magnetic resonance imaging (MRI) or catheterization; 25.9% had off-pump implants. In 53% patients, pulmonary valve replacement was associated with the repair of other cardiac defects., Results: Minor postoperative complications were observed in 10.8% patients. The overall mortality rate was 2.3%; mortality after valve replacement was linked to a severe cardiac insufficiency and it was not related to a prosthesis failure; 1 prosthesis was explanted from 1 patient because of endocarditis, and 6% of patients developed PV stenosis; minor complications occurred in 4.8%. The mean follow-up period was 4.8 years (2 months-12.7 years); 42% of the patients were followed for more than 5 years. Follow-up echocardiography and cardiac MRI showed a significant reduction in RV size and low gradients across the PV., Conclusions: An injectable PV may be implanted without cardiopulmonary bypass and in a hybrid operating theatre with minimal surgical impact. The bioprosthesis, available up to large sizes, has a low profile, laminar flow and no risk of coronary artery compression. Incidence of endocarditis is rare. The lack of a suture ring permits the implant of a relatively larger prosthesis, thereby avoiding a right ventricular outflow tract obstruction. This device permits future percutaneous valve-in-valve procedures, if needed. Results concerning durability are encouraging, and mid- to long-term haemodynamic performance is excellent., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Hearing loss (HL), one of the most common congenital disorder, affects about one child in 1000. Among the genetic forms of HL, ∼30% of the cases are associated with other signs or symptoms, leading to Syndromic Hearing Loss (SHL) with about 700 different forms described so far. In this report, we refer the clinical and molecular data of 38 Italian SHL unrelated patients, and their relatives, affected by the most common syndromes associated with HL (i.e., Usher, Pendred, Charge, Waardenburg, Alport, Stickler, Branchiootorenal and Microdeletions syndromes). Patients have been analysed using next-generation sequencing (NGS) and High Density (HD)-SNP array technologies. Data analysis led to the identification of nine novel and 27 known causative mutations in 12 genes and two microdeletions in chromosomes 1 and 10, respectively. In particular, as regards to Usher syndrome, that affects 32% of our patients, we were able to reach a molecular diagnosis in 83% of the cases and to identify in Northern Eastern Italy a very common USH2A gene mutation (39%) (c.11864G > A, p.(Trp3955*) which can be defined "Central-Eastern European allele." As regards to Alport syndrome, we were able to potentially reclassify a pathogenic allele in the COL4A3 gene, previously associated only with benign familial hematuria. In all the other cases, the genomic analysis allowed us to confirm the role of known causative genes and to identify several novel and known alleles. Overall, our results highlight the effectiveness of combining an accurate clinical characterization with the use of genomic technologies (NGS and SNP arrays) for the molecular diagnosis of SHL, with a clear positive impact in the management and treatment of all the patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Permanent hearing impairment is the most common sensory disorder in newborns. The Universal Newborn Hearing Screening (UNHS) is widely adopted as a cost-effective procedure to achieve early identification and treatment of congenital hearing impairment, with the final goal of an improved linguistic and cognitive outcome for hearing impaired children. The Italian Ministry of Health has recently comprised UNHS in the Essential Level of Health Assistance. Nevertheless, programs still vary both across and within Italian Regions in terms of coverage, testing, referral and tracking protocols. In Friuli-Venezia Giulia region the program for the early identification of newborn and childhood hearing impairment is operative since 2012. In order to minimize the lost to follow-up cases, UNHS and childhood hearing surveillance activities have been organized in close collaboration among birth centres, paediatric audiology services, territorial Family Paediatricians and the sole regional centre for paediatric hearing loss management., Material and Methods: We performed a five years' retrospective analysis of the UNHS experience in Friuli-Venezia Giulia comparing the UNHS activity of year 2013 and year 2017. The focus of the study concerns the "missing" cases. Three different typologies of "miss" cases ("documentation-miss", "access-miss" and "pathway-miss") have been defined in correspondence with main reasons for their occurrence., Results: Births in Friuli-Venezia Giulia were 9465 and 8432, respectively in 2013 and 2017. International quality indicators improved with a gain of efficiency in 5 years' experience. However, "missing" cases were 486 in 2013 and 321 in 2017, mainly due to the lack of an efficient documentation system., Conclusion: UNHS programs have proven to be valuable and cost-effective in Friuli-Venezia Giulia and other Italian regions. New resources and efforts are required to achieve a complete standardization and informatisation of the UNHS data to avoid documentation gaps. A possible strategy would point to the opportunity to unify data management systems for all the ongoing newborn screening programs (metabolic, hearing and visual), linking the integrated IT system with the regional repository of current datasets., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hereditary hearing loss (HHL) is a common disorder characterized by a huge genetic heterogeneity. The definition of a correct molecular diagnosis is essential for proper genetic counseling, recurrence risk estimation, and therapeutic options. From 20 to 40% of patients carry mutations in GJB2 gene, thus, in more than half of cases it is necessary to look for causative variants in the other genes so far identified (~100). In this light, the use of next-generation sequencing technologies has proved to be the best solution for mutational screening, even though it is not always conclusive. Here we describe a combined approach, based on targeted re-sequencing (TRS) of 96 HHL genes followed by high-density SNP arrays, aimed at the identification of the molecular causes of non-syndromic HHL (NSHL). This strategy has been applied to study 103 Italian unrelated cases, negative for mutations in GJB2 , and led to the characterization of 31% of them (i.e., 37% of familial and 26.3% of sporadic cases). In particular, TRS revealed TECTA and ACTG1 genes as major players in the Italian population. Furthermore, two de novo missense variants in ACTG 1 have been identified and investigated through protein modeling and molecular dynamics simulations, confirming their likely pathogenic effect. Among the selected patients analyzed by SNP arrays (negative to TRS, or with a single variant in a recessive gene) a molecular diagnosis was reached in ~36% of cases, highlighting the importance to look for large insertions/deletions. Moreover, copy number variants analysis led to the identification of the first case of uniparental disomy involving LOXHD1 gene. Overall, taking into account the contribution of GJB2 , plus the results from TRS and SNP arrays, it was possible to reach a molecular diagnosis in ~51% of NSHL cases. These data proved the usefulness of a combined approach for the analysis of NSHL and for the definition of the epidemiological picture of HHL in the Italian population.

Bacterial meningitis may cause inner ear fibrosis and progressive cochlear ossification with irreversible profound hearing loss (HL). Recognition of potential ossification is essential for effective management. We present a clinical case of a 4 year old boy who developed a progressive HL starting 3 weeks after meningitis. For the prospective risk of cochlear ossification, bilateral cochlear implantation (CI) was performed. Unexpectedly, unaided hearing threshold began to show improvement on the left ear, starting 4 months after meningitis and continuing for years post CI surgery. In order to explore the residual cochlear function, a trial of exclusively acoustic amplification was performed on the improved left side 5 years post implantation, providing good results. A certain degree of hearing recovery may be expected after meningitis related deafness. This case encourages surgeons to always adopt atraumatic surgical techniques that can enable the preservation of cochlear structure and residual function after CI surgery.