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Hearing Disorders: HELP
Articles by Alessandro Martini
Based on 44 articles published since 2010
(Why 44 articles?)
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Between 2010 and 2020, A. Martini wrote the following 44 articles about Hearing Disorders.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Editorial. 2014

Martini, Alessandro. · ·Audiol Neurootol · Pubmed #25733357.

ABSTRACT: -- No abstract --

2 Review Epidemiologic, Imaging, Audiologic, Clinical, Surgical, and Prognostic Issues in Common Cavity Deformity: A Narrative Review. 2019

Brotto, Davide / Avato, Irene / Lovo, Elisa / Muraro, Eva / Bovo, Roberto / Trevisi, Patrizia / Martini, Alessandro / Manara, Renzo. ·ENT Unit, Neurosciences Department, Università degli Studi di Padova, Padova, Italy. · Department of Otorhinolaryngology, PhD in Experimental Medicine, University of Pavia, Pavia, Italy. · Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy. · Department of Neuroradiology, University of Salerno, Salerno, Italy. ·JAMA Otolaryngol Head Neck Surg · Pubmed #30419122.

ABSTRACT: Importance: Common cavity deformity is a rare congenital inner ear malformation associated with profound hearing loss and attributed to an early developmental arrest of the cochlear-vestibular structures. This narrative review highlights the need to identify reliable indicators of hearing rehabilitation outcome. Observations: Despite its relatively simple definition, common cavity deformity varies widely in morphologic features, presence of cochlear nerve fibers and remnants of Corti organ, and outcome after cochlear or brainstem implant. Conclusions and Relevance: Cochlear implant has been shown to be a valid option for common cavity deformity, but its outcome remains variable and poor. Identification of specific neuroradiologic, audiologic, and neurophysiologic prognostic features; tailoring of the surgical approach; and standardization of outcome measures are needed to optimize the management of common cavity deformity and hearing rehabilitation after implant.

3 Review Regenerative medicine in hearing recovery. 2017

Simoni, Edi / Orsini, Giulia / Chicca, Milvia / Bettini, Simone / Franceschini, Valeria / Martini, Alessandro / Astolfi, Laura. ·Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy. · Auromet srl, Pisa, Italy. · Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. · Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy. · Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy; Foundation Onlus Staminali e Vita, Padua, Italy. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy; Foundation Onlus Staminali e Vita, Padua, Italy. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy; Foundation Onlus Staminali e Vita, Padua, Italy. Electronic address: laura.astolfi@unipd.it. ·Cytotherapy · Pubmed #28532627.

ABSTRACT: Hearing loss, or deafness, affects 360 million people worldwide of which about 32 million are children. Deafness is irreversible when it involves sensory hair cell death because the regenerative ability of these cells is lost in mammals after embryo development. The therapeutic strategies for deafness include hearing aids and/or implantable devices. However, not all patients are eligible or truly benefit from these medical devices. Regenerative medicine based on stem cell application could play a role in both improvement of extant medical devices and in vivo recovery of auditory function by regeneration of inner ear cells and neurons. A review of recent literature on the subject indicates that two promising approaches to renewal and differentiation of cochlear tissues are transplantation of stem cells and in situ administration of growth factors. Rather than directly regenerating dead cells, these procedures apparently induce, through various pathways, differentiation of resident cochlear cells. More studies on the possible adverse effects of transplanted cells and the recovery of tonotopic sensorineural activity or required. To date, no reliable clinical results have been obtained in the field of cochlear regeneration.

4 Review Combined Surgical Approach to Giant Cholesteatoma: A Case Report and Literature Review. 2016

Cazzador, Diego / Favaretto, Niccolò / Zanoletti, Elisabetta / Martini, Alessandro. ·Department of Neurosciences, Otolaryngology Section, University of Padova, Italy gkmcaz@hotmail.it. · Department of Neurosciences, Otolaryngology Section, University of Padova, Italy. ·Ann Otol Rhinol Laryngol · Pubmed #27117903.

ABSTRACT: OBJECTIVES: Cholesteatomas can grow to a remarkable size before clinically making their presence felt. Managing giant cholesteatomas and their complications can become a challenge for the otological surgeon. METHODS: We describe a case of a giant congenital cholesteatoma of the mastoid in an adult. The lesion extended to the sigmoid sinus, jugular bulb, carotid canal, occipital condyle, and the lateral portion of the first cervical vertebra. Surgical excision was performed using a combined microscopic and endoscopic surgical approach. RESULTS: Our combined surgical technique enabled a more accurate removal of the cholesteatoma than a microscopic approach alone, with no surgical complications or damage to the structures affected by the disease. CONCLUSIONS: Using endoscopic instruments to manage giant cholesteatomas can help to avoid complications and improve surgical radicality.

5 Review Aging, cognitive load, dementia and hearing loss. 2014

Martini, Alessandro / Castiglione, Alessandro / Bovo, Roberto / Vallesi, Antonino / Gabelli, Carlo. ·Department of Neurosciences, Otolaryngology and Otosurgery, University of Padova, Padova, Italy. ·Audiol Neurootol · Pubmed #25733358.

ABSTRACT: Sensorineural systems play a crucial role in the diagnosis, treatment and management of several neurological disorders. The function of the eye and ear represents a unique window for testing various conditions in cognitive decline or dementia. Touch and smell have also been found to be strongly involved in neurodegenerative conditions, and their decline has been significantly associated with the progression of the disease; hence, the idea that restoring sensory function in cognitively impaired adults might enable a significant improvement in their cognitive status, reducing the worldwide incidence and prevalence of dementia. Not all sensorineural 'windows' can benefit equally from the same procedures; however, hearing and vision can certainly gain the most from dependable therapeutic and other diagnostic options. The ear, including the vestibular system, deserves an honored place among the sensory organs in this context due mainly to the sophisticated electrical devices available that have amply demonstrated their effectiveness in treating hearing loss. Restoring an individual's hearing can reduce the cognitive 'load', i.e. the neural activity needed to understand/recognize the spoken word - an activity that becomes more demanding if the brain is obliged to recruit different neural populations to achieve the same performance, as happens in older adults with sensory impairments. The sensory interfaces may also facilitate the early diagnosis of conditions characterized by a lengthy preclinical phase, as well as enabling noninvasive, follow-up procedures to assess the outcome of rehabilitation measures and distinguish physiological brain aging from neurodegenerative disorders. The present study is a brief literature review on the issues and prospects relating to the unique relationship between hearing and cognitive decline, with a general introduction to the main topics before focusing on rehabilitation training with hearing aids and cochlear implants to combat cognitive decline.

6 Review Hearing loss and cognitive decline in older adults: questions and answers. 2014

Bernabei, Roberto / Bonuccelli, Ubaldo / Maggi, Stefania / Marengoni, Alessandra / Martini, Alessandro / Memo, Maurizio / Pecorelli, Sergio / Peracino, Andrea P / Quaranta, Nicola / Stella, Roberto / Lin, Frank R / Anonymous2740808. ·Department of Geriatrics, Neuroscience and Orthopaedics, Catholic University of the Sacred Heart, Rome, Italy. ·Aging Clin Exp Res · Pubmed #25281432.

ABSTRACT: The association between hearing impairment, the diagnosis of dementia, and the role of sensory therapy has been proposed for some time, but further research is needed. Current understanding of this association requires the commitment of those experts who can integrate experience and research from several fields to be able to understand the link from hearing to dementia. A workshop whose panelists included experts from many areas, ranging from ear, nose and throat (ENT) to dementia's specialists, was promoted and organized by the Giovanni Lorenzini Medical Science Foundation (Milan, Italy; Houston, TX, USA) to increase the awareness of the relationship between hearing loss and dementia, and included questions and comments following a presentation from the clinical researcher, Frank Lin, who has been evaluating the relationship between hearing loss and cognitive decline since 2009.

7 Review [Cochlear implant in children: rational, indications and cost/efficacy]. 2013

Martini, A / Bovo, R / Trevisi, P / Forli, F / Berrettini, S. ·Dipartimento di Neuroscienze e Organi di Senso, Università di Padova, Padova, Italia. alessandromartini@unipd.it ·Minerva Pediatr · Pubmed #23685383.

ABSTRACT: A cochlear implant (CI) is a partially implanted electronic device that can help to provide a sense of sound and support speech to severely to profoundly hearing impaired patients. It is constituted by an external portion, that usually sits behind the ear and an internal portion surgically placed under the skin. The external components include a microphone connected to a speech processor that selects and arranges sounds pucked up by the microphone. This is connected to a transmitter coil, worn on the side of the head, which transmits data to an internal receiver coil placed under the skin. The received data are delivered to an array of electrodes that are surgically implanted within the cochlea. The primary neural targets of the electrodes are the spiral ganglion cells which innervate fibers of the auditory nerve. When the electrodes are activated by the signal, they send a current along the auditory nerve and auditory pathways to the auditory cortex. Children and adults who are profoundly or severely hearing impaired can be fitted with cochlear implants. According to the Food and Drug Administration, approximately 188,000 people worldwide have received implants. In Italy it is extimated that there are about 6-7000 implanted patients, with an average of 700 CI surgeries per year. Cochlear implantation, followed by intensive postimplantation speech therapy, can help young children to acquire speech, language, and social skills. Early implantation provides exposure to sounds that can be helpful during the critical period when children learn speech and language skills. In 2000, the Food and Drug Administration lowered the age of eligibility to 12 months for one type of CI. With regard to the results after cochlear implantation in relation to early implantation, better linguistic results are reported in children implanted before 12 months of life, even if no sufficient data exist regarding the relation between this advantage and the duration of implant use and how long this advantage persists in the subsequent years. With regard to cochlear implantation in children older than 12 months the studies show better hearing and linguistic results in children implanted at earlier ages. A sensitive period under 24-36 months has been identified over which cochlear implantation is reported to be less effective in terms of improvement in speech and hearing results. With regard to clinical effectiveness of bilateral cochlear implantation, greater benefits from bilateral implants compared to monolateral ones when assessing hearing in quiet and in noise and in sound localization abilities are reported to be present in both case of simultaneous or sequential bilateral implantation. However, with regard to the delay between the surgeries in sequential bilateral implantation, although benefit is reported to be present even after very long delays, on average long delays between surgeries seems to negatively affect the outcome with the second implant. With regard to benefits after cochlear implantation in children with multiple disabilities, benefits in terms of speech perception and communication as well as in quality of the daily life are reported even if benefits are slower and lower in comparison to those generally attained by implanted children without additional disabilities. Regarding the costs/efficacy ratio, the CI is expensive, in particular because of the cost of the high technological device, long life support, but even if healthcare costs are high, the savings in terms of indirect costs and quality of life are important. The CI, in fact, has a positive impact in terms of quality of life.

8 Review [Permanent childhood hearing impairment: universal newborn hearing screening, PCHI management]. 2013

Martini, A / Marchisio, P / Bubbico, L / Trevisi, P / Perletti, L. ·Dipartimento di Neuroscienze e Organi di Senso, Università di Padova, Padova, Italia. ·Minerva Pediatr · Pubmed #23612271.

ABSTRACT: The most recent advances in technology and scientific knowledge have allowed better outcomes in permanent childhood hearing impairment (PCHI) than in the past period. The Universal Newborn Hearing Screening with OtoAcoustic Emissions provides an early identification/habilitation program for hearing impaired children, giving them immediate access to intervention when needed. The aim of this paper was to treat the organization and management of health care procedures for PCHI in Italy, which are not well coordinated with respect to other European Countries. Pediatrician and neonatologists appear to be especially engaged in these aspects.

9 Review Endocochlear inflammation in cochlear implant users: case report and literature review. 2013

Benatti, Alice / Castiglione, Alessandro / Trevisi, Patrizia / Bovo, Roberto / Rosignoli, Monica / Manara, Renzo / Martini, Alessandro. ·Operative Unit of Otolaryngology and Otosurgery, Padua University, Via Giustiniani, 2, Padua, Italy. alicebenatti@gmail.com ·Int J Pediatr Otorhinolaryngol · Pubmed #23578804.

ABSTRACT: OBJECTIVES: Cochlear implantation is a relatively safe procedure with a low complication rate. The overall rate of complications among cochlear implant patients ranges from 6% to 20%. Major complications are those that are life-threatening or require surgery, whereas minor complications are those that can be medically treated. Nonetheless, certain complications, even if highly rare, may require specific investigations and treatments. Among these rare complications are those with endocochlear involvement, such as cochleitis or labyrinthitis, with fibrosis or ossification that could lead to explantation. The aims of the present study were to report a particular case of post-operative cochleitis and to review the rate of complications after cochlear implantation, emphasising those conditions with proven endocochlear involvement. METHODS: We refer to the case of an eight-year-old Italian boy affected by the sudden onset of headache, ipsilateral otalgia and facial paresis, who presented to our clinic for inexplicable worsening of the performance of his implant and his residual hearing, six years after surgery. A complete investigation including (clinical history, routine, autoimmune and serological blood tests, electrophysiological measurements from the cochlear implant and neuroimaging) was performed and is herein described. Additionally, a comprehensive review of the literature was conducted using internet search engines; 274 papers were selected, 88 of which were best suited to our purposes. RESULTS: In our case, the progression of the symptoms and the performance decrement required explantation, followed by a complete recovery. Reviewing the literature revealed only three reports concerning cases of proven endocochlear phlogosis that required revision surgery. Wound swelling/infection and vertigo remain the two most common complications of cochlear implantation. Failure of the device is the third most frequent complication (10.06% of all complications and 1.53% of cochlear implantations). Other rare conditions (such as granulating labyrinthitis with cochlear fibrosis, ossification and erosion, silicone allergy and the formation of a biofilm around the internal device) are possible and unpredictable. Although rare (approximately 1%), such cases may require explantation. CONCLUSIONS: Despite efforts by both surgeons and manufacturers, device-related and surgical complications still occur. These and other rare conditions demand specific management, and their frequency may be underestimated. Further studies are needed to assess more realistic rates of complications and devise more efficient strategies for early diagnosis and treatment.

10 Review How to motivate newborn hearing screening in the absence of a national programme: a collaboration between parents and professionals. 2012

Cutler, Jodi / Lenzi, Giovanni / Berrettini, Stefano / Martini, Alessandro / Martinelli, Stefano. ·Global Coalition of Parents of Children who are Deaf and Hard of Hearing, Italy. jodi.cutler@alice.it ·J Matern Fetal Neonatal Med · Pubmed #22958038.

ABSTRACT: The establishment of the Italian Pediatric Federation Newborn Hearing Screening Network and the Italian Society of Neonatology Infant Hearing Study Group is the result of an international collaboration between Parents and Medical Professionals in order to promote an effective model in developing Early Hearing Detection Intervention Programs that recognize the role of parents as partners in the process. Among other factors, one important component frequently underestimated in most early intervention programs, both in the USA and other countries, involves the role of parental involvement within the Early Hearing Detection Intervention (EHDI) process. When a parent receives the news of their child's hearing loss, reactions may include, but are not limited to denial, grief, guilt, shame, fear and impotency. A parent may begin to ask certain questions: How do we know if the professionals in our children's lives are capable, educated, trained, up to date in their chosen fields of expertise? Do they respect our children and us as parents? Do they understand the needs of children who are deaf or hard of hearing? A life-long health professional - parental collaboration begins at the moment of the diagnosis of that child. When analyzing the habilitation process of a deaf child, the relationship between health professionals and the crucial role of parents in raising that child is a 50-50 shared responsibility. An objective of EHDI programs must be to empower parents by providing support from the beginning of the process. Distributing informative literature regarding the newborn hearing screening process and providing parents with access to resources such as parental support groups upon diagnosis equips parents with the tools necessary to immediately begin advocating for their children. The Italian Federation Pediatric Audiology Network was created by combining the parental perspective and medical protocols in order to establish the roots for stronger EHDI programs.

11 Review Environmental and genetic factors in age-related hearing impairment. 2011

Bovo, Roberto / Ciorba, Andrea / Martini, Alessandro. ·Department of Audiology, University of Ferrara, Ferrara, Italy. roberto.bovo@unife.it ·Aging Clin Exp Res · Pubmed #21499014.

ABSTRACT: Age-related hearing impairment (ARHI), or presbycusis, is a complex disease with multifactorial etiology. It is the most prevalent sensory impairment in the elderly, and may have detrimental effects on their quality of life and psychological well-being. The aim of this paper is to give an overview of the current data on ARHI, focusing mainly on environmental agents and genetic predisposition in animal models and in humans. With improvement of our understanding of ARHI, treatment other than with amplification will be hopefully possible in the long term.

12 Article Cochlear implant outcomes in the elderly: a uni- and multivariate analyses of prognostic factors. 2019

Favaretto, Niccolò / Marioni, Gino / Brotto, Davide / Sorrentino, Flavia / Gheller, Flavia / Castiglione, Alessandro / Montino, Silvia / Giacomelli, Luciano / Trevisi, Patrizia / Martini, Alessandro / Bovo, Roberto. ·Department of Neuroscience DNS, Otolaryngology Section, Padova University, Via Giustiniani 2, 35128, Padova, Italy. niccolo.favaretto.87@gmail.com. · Department of Neuroscience DNS, Otolaryngology Section, Padova University, Via Giustiniani 2, 35128, Padova, Italy. · Department of Medicine DIMED, Padova University, Padova, Italy. ·Eur Arch Otorhinolaryngol · Pubmed #31463602.

ABSTRACT: PURPOSE: To assess preoperative features that could predict the audiological outcome after cochlear implantation in the elderly, in terms of pure tone audiometry, speech audiometry, and speech perception performance. METHODS: All available records of patients with cochlear implants aged 65 or more at the time of their implantation at our Institution were reviewed (50 patients, mean age 70.76 ± 4.03 years), recording preoperative clinical features. Pure tone audiometry, speech audiometry, and speech perception performance 1 year after cochlear implant activation and fitting were used as outcome measures. RESULTS: No statistically significant association emerged between clinical features and pure tone audiometry. On univariate analysis, progressive sensorineural hearing loss of unknown origin was associated with a better outcome in terms of speech audiometry and speech perception performance (p = 0.035 and p = 0.033, respectively). On multivariate analysis, progressive sensorineural hearing loss retained its independent prognostic significance in terms of speech perception performance (p = 0.042). The discriminatory power of a two-variable panel (age and etiology of hearing loss) featured an AUC (ROC) of 0.738 (an acceptable discriminatory power according to the Hosmer-Lemeshow scale). CONCLUSIONS: A progressive sensorineural hearing loss of unknown origin was associated with a better outcome in terms of speech perception in the elderly in our case study. Further features that can predict audiological outcome achievable with cochlear implants in the elderly are desirable to perform adequate counselling and rehabilitation programs.

13 Article Surgery of the lateral skull base: a 50-year endeavour. 2019

Zanoletti, E / Mazzoni, A / Martini, A / Abbritti, R V / Albertini, R / Alexandre, E / Baro, V / Bartolini, S / Bernardeschi, D / Bivona, R / Bonali, M / Borghesi, I / Borsetto, D / Bovo, R / Breun, M / Calbucci, F / Carlson, M L / Caruso, A / Cayé-Thomasen, P / Cazzador, D / Champagne, P-O / Colangeli, R / Conte, G / D'Avella, D / Danesi, G / Deantonio, L / Denaro, L / Di Berardino, F / Draghi, R / Ebner, F H / Favaretto, N / Ferri, G / Fioravanti, A / Froelich, S / Giannuzzi, A / Girasoli, L / Grossardt, B R / Guidi, M / Hagen, R / Hanakita, S / Hardy, D G / Iglesias, V C / Jefferies, S / Jia, H / Kalamarides, M / Kanaan, I N / Krengli, M / Landi, A / Lauda, L / Lepera, D / Lieber, S / Lloyd, S L K / Lovato, A / Maccarrone, F / Macfarlane, R / Magnan, J / Magnoni, L / Marchioni, D / Marinelli, J P / Marioni, G / Mastronardi, V / Matthies, C / Moffat, D A / Munari, S / Nardone, M / Pareschi, R / Pavone, C / Piccirillo, E / Piras, G / Presutti, L / Restivo, G / Reznitsky, M / Roca, E / Russo, A / Sanna, M / Sartori, L / Scheich, M / Shehata-Dieler, W / Soloperto, D / Sorrentino, F / Sterkers, O / Taibah, A / Tatagiba, M / Tealdo, G / Vlad, D / Wu, H / Zanetti, D. ·Department of Neuroscience DNS, Otolaryngology Section, Padova University, Padova, Italy. · Department of Neurosurgery, Lariboisière Hospital, University of Paris Diderot, Paris, France. · Gruppo Otologico, Piacenza-Rome, Italy. · Academic Neurosurgery, Department of Neuroscience DNS, University of Padova Medical School, Padova, Italy. · Neurosurgery, Bellaria Hospital, Bologna, Italy. · AP-HP, Groupe Hôspital-Universitaire Pitié-Salpêtrière, Neuro-Sensory Surgical Department and NF2 Rare Disease Centre, Paris, France. · Sorbonne Université, Paris, France. · ENT and Skull-Base Surgery Department, Department of Neurosciences, Ospedale Papa Giovanni XXIII, Bergamo, Italy. · Otolaryngology-Head and Neck Surgery Department, University Hospital of Modena, Italy. · Neurosurgery, Maria Cecilia Hospital, Cotignola (RA), Italy. · Department of Neurosurgery, Julius Maximilians University Hospital Würzburg, Bavaria, Germany. · Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA. · Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA. · The Department of Otorhinolaryngology, Head & Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Department of Neuroscience DNS, Section of Human Anatomy, Padova University, Padova, Italy. · Department of Neuroradiology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy. · Department of Radiation Oncology, University Hospital Maggiore della Carità, Novara, Italy. · Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. · Unit of Audiology, Department of Clinical Sciences and Community Health, University of Milano, Italy. · Department of Surgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy. · Department of Neurosurgery, Eberhard Karls University Tübingen, Germany. · Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. · Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, "Julius-Maximilians" University Hospital of Würzburg, Bavaria, Germany. · Department of Neurosurgery, Cambridge University Hospital, Cambridge, UK. · Oncology Department, Cambridge University Hospital, Cambridge, UK. · Department of Otolaryngology Head and Neck Surgery, Shanghai Ninh People's Hospital, Shanghai Jiatong University School of Medicine, China. · Department of Neurosciences, King Faisal Specialist Hospital & Research Center, Alfaisal University, College of Medicine, Riyadh, KSA. · ENT & Skull-Base Department, Ospedale Nuovo di Legnano, Legnano (MI), Italy. · Department of Neuro-Otology and Skull-Base Surgery Manchester Royal Infirmary, Manchester, UK. · Department of Neuroscience DNS, Audiology Unit, Padova University, Treviso, Italy. · University Aix-Marseille, France. · Otolaryngology-Head and Neck Surgery Department, University Hospital of Verona, Italy. · Mayo Clinic School of Medicine, Rochester, MN, USA. · Department of Neuro-otology and Skull Base Surgery, Cambridge University Hospital, Cambridge, UK. · ENT Department, Treviglio (BG), Italy. ·Acta Otorhinolaryngol Ital · Pubmed #31130732.

ABSTRACT: -- No abstract --

14 Article The Father of the Electrical Stimulation of the Ear. 2019

Marchese-Ragona, Rosario / Pendolino, Alfonso Luca / Mudry, Albert / Martini, Alessandro. ·Department of Neurosciences, Otolaryngology Section, University of Padova, Padova, Italy. · Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California. ·Otol Neurotol · Pubmed #30741901.

ABSTRACT: : The Italian physicist Count Alessandro Volta, inventor of the electric battery, is considered the first scientist to have stimulated the ear with electricity, and the results of his experiments were presented in June 1800, at a meeting held by the Royal Society of London. Just recently, Mudry reported an electrical stimulation of the ear performed in 1748 by Benjamin Wilson (1721-1788), a British painter and scientist. After a thorough review of the literature available from the 18th century, we found that the first electrical stimulation of the ear was done in 1747, by a scientist in Bologna, Giuseppe Veratti.

15 Article Surgical timing for bilateral simultaneous cochlear implants: When is best? 2018

Franchella, Sebastiano / Bovo, Roberto / Bandolin, Luigia / Gheller, Flavia / Montino, Silvia / Borsetto, Daniele / Ghiselli, Sara / Martini, Alessandro. ·Department of Neurosciences, Otolaryngology Section, University of Padua, Padua, Italy. Electronic address: sebastiano.franchella@studenti.unipd.it. · Department of Neurosciences, Otolaryngology Section, University of Padua, Padua, Italy. ·Int J Pediatr Otorhinolaryngol · Pubmed #29728185.

ABSTRACT: INTRODUCTION: Hearing loss is considered the most common congenital disease and the prevalence of neonatal deafness can be estimated between 1 and 2 cases per 1000 live births. Infant deafness must be diagnosed as early as possible and an effective therapeutic intervention needs to be carried out in order to avoid the serious consequences of hearing deprivation during the evolutionary period: alterations in the development of central auditory pathways and lack of language acquisition. The cochlear implant (CI) has proved to be the best instrument to solve the problem of auditory deprivation. In particular, the bilateral CI gives the patient access to binaural hearing which results in benefits in terms of sound localisation and discrimination. The optimal age of application of the CI is a widely discussed topic in the scientific community and the current guidelines indicate a period between 12 and 24 months of age, even though the supporters of the application before 12 months of age are nowadays increasing. MATERIALS AND METHODS: The study is observational, retrospective, monocentric. 49 paediatric patients (<18 years) with simultaneous bilateral CIs were included. The audiometric threshold and speech tests were carried out during the follow-up 3, 6 and 12 months after the CIs activation and when the patient reached 2 years of age. RESULTS: The statistical analysis showed that undergoing bilateral implantation surgery before 2 years of age allows a satisfactory audiometric performance, while there are no particular benefits in performing the surgery before 1 year of age. As far as the speech outcome is concerned, the statistical analysis didn't show significant correlation between the earlier age of implantation and better speech performance if the operation is carried out before 2.5 years of age. CONCLUSIONS: The results of the study indicate that the optimal age to perform the simultaneous bilateral CIs surgery is between 12 and 24 months, without demonstrating any particular benefit in carrying out the procedure before 1 year of age. This may be clinically relevant in terms of avoiding the risks of diagnostic mistakes and reducing the related surgical risk in children under 1 year of age.

16 Article Microsurgical Decompression of the Cochlear Nerve to Treat Disabling Tinnitus via an Endoscope-Assisted Retrosigmoid Approach: The Padua Experience. 2018

Di Stadio, Arianna / Colangeli, Roberta / Dipietro, Laura / Martini, Alessandro / Parrino, Daniela / Nardello, Ennio / D'Avella, Domenico / Zanoletti, Elisabetta. ·San Camillo Hospital IRCCS, Neurology Department, Venice, Italy. Electronic address: ariannadistadio@hotmail.com. · Department of Neurosciences DNS, Otolaryngology Section, Padova University, Padova, Italy. · Highland Instruments, Cambridge, Massachusetts, USA. · Neurosurgery Department, Neurosciences Department, University Hospital of Padova, Padova, Italy. ·World Neurosurg · Pubmed #29486316.

ABSTRACT: BACKGROUND: The use of surgical cochlear nerve decompression is controversial. This study aimed at investigating the safety and validity of microsurgical decompression via an endoscope-assisted retrosigmoid approach to treat tinnitus in patients with neurovascular compression of the cochlear nerve. CASE DESCRIPTION: Three patients with disabling tinnitus resulting from a loop in the internal auditory canal were evaluated with magnetic resonance imaging and tests of pure tone auditory, tinnitus, and auditory brain response (ABR) to identify the features of the cochlear nerve involvement. We observed a loop with a caliber greater than 0.8 mm in all patients. Patients were treated via an endoscope-assisted retrosigmoid microsurgical decompression. After surgery, none of the patients reported short-term or long-term complications. After surgery, tinnitus resolved immediately in 2 patients, whereas in the other patient symptoms persisted although they improved; in all patients, hearing was preserved and ABR improved. CONCLUSION: Microsurgical decompression via endoscope-assisted retrosigmoid approach is a promising, safe, and valid procedure for treating tinnitus caused by cochlear nerve compression. This procedure should be considered in patients with disabling tinnitus who have altered ABR and a loop that has a caliber greater than 0.8 mm and is in contact with the cochlear nerve.

17 Article Retrolabyrinthine Meatotomy as Part of Retrosigmoid Approach to Expose the Whole Internal Auditory Canal: Rationale, Technique, and Outcome in Hearing Preservation Surgery for Vestibular Schwannoma. 2018

Mazzoni, Antonio / Zanoletti, Elisabetta / Denaro, Luca / Martini, Alessandro / Avella, Domenico d'. ·Otolaryngology Department, Neurosciences Department, University Hospital of Padova, Padova, Italy. · Neurosurgery Department, Neurosciences Department, University Hospital of Padova, Padova, Italy. ·Oper Neurosurg (Hagerstown) · Pubmed #29253291.

ABSTRACT: BACKGROUND: Vestibular schwannoma extending to the fundus of the internal auditory canal is currently considered an unfavorable condition for hearing preservation surgery via a retrosigmoid approach because the lateral end of the canal is hard to view directly during microsurgery. OBJECTIVE: To present an improved retrolabyrinthine meatotomy (RLM) technique that enables the full length of the cochlear and facial nerves to be inspected up to their orifices on the fundus. Long-term results are briefly reported. METHODS: A consecutive series of 100 cases with various degrees of fundus involvement underwent surgery via a retrosigmoid approach and RLM. The follow-up ranged from 4 to 14 yr. Outcomes on hearing and facial nerve function were recorded, and preoperative MRI findings of the tumor on the fundus were correlated with the surgical findings and the long-term radicality of the tumor resection. RESULTS: Residual tumor on the fundus was identified in 3 cases, all belonging to the group with tumors adhering to the fundus. The functional results were in line with the best reported outcomes of this surgery. CONCLUSION: RLM via a retrosigmoid approach seemed adequate for the purposes of hearing preservation surgery and enabled the full course of the facial and cochlear nerves through the internal auditory canal to be exposed to direct view. Tumors adhering to the vestibular quadrant of the fundus were more difficult to remove, and there were a few cases of local residual tumor.

18 Article Human mesenchymal stromal cell therapy for damaged cochlea repair in nod-scid mice deafened with kanamycin. 2018

Bettini, Simone / Franceschini, Valeria / Astolfi, Laura / Simoni, Edi / Mazzanti, Benedetta / Martini, Alessandro / Revoltella, Roberto P. ·Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy. · Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy; Foundation Onlus 'Staminali e Vita', Padua, Italy. Electronic address: valeria.franceschini@unibo.it. · Foundation Onlus 'Staminali e Vita', Padua, Italy; Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy. · Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy. · Foundation Onlus 'Staminali e Vita', Padua, Italy; Institute for Chemical, Physical Processes, Centro Nazionale delle Ricerche (C.N.R.), Pisa, Italy. ·Cytotherapy · Pubmed #29246648.

ABSTRACT: BACKGROUND: Kanamycin, mainly used in the treatment of drug-resistant-tuberculosis, is known to cause irreversible hearing loss. Using the xeno-transplant model, we compared both in vitro and in vivo characteristics of human mesenchymal stromal cells (MSCs) derived from adult tissues, bone marrow (BM-MSCs) and adipose tissue (ADSCs). These tissues were selected for their availability, in vitro multipotency and regenerative potential in vivo in kanamycin-deafened nod-scid mice. METHODS: MSCs were isolated from informed donors and expanded ex vivo. We evaluated their proliferation capacity in vitro using the hexosaminidase assay, the phenotypic profile using flow-cytometry of a panel of surface antigens, the osteogenic potential using alkaline phosphatase activity and the adipogenic potential using oil-red-O staining. MSCs were intravenously injected in deafened mice and cochleae, liver, spleen and kidney were sampled 7 and 30 days after transplantation. The dissected organs were analyzed using lectin histochemistry, immunohistochemistry, polymerase chain reaction (PCR) and dual color fluorescence in situ hybridization (DC-FISH). RESULTS: MSCs showed similar in vitro characteristics, but ADSCs appeared to be more efficient after prolonged expansion. Both cell types engrafted in the cochlea of damaged mice, inducing regeneration of the damaged sensory structures. Several hybrid cells were detected in engrafted tissues. DISCUSSION: BM-MSCs and ADSCs showed in vitro characteristics suitable for tissue regeneration and fused with resident cells in engrafted tissues. The data suggest that paracrine effect is the prevalent mechanism inducing tissue recovery. Overall, BM-MSCs and ADSCs appear to be valuable tools in regenerative medicine for hearing loss recovery.

19 Article Aging, Cognitive Decline and Hearing Loss: Effects of Auditory Rehabilitation and Training with Hearing Aids and Cochlear Implants on Cognitive Function and Depression among Older Adults. 2016

Castiglione, Alessandro / Benatti, Alice / Velardita, Carmelita / Favaro, Diego / Padoan, Elisa / Severi, Daniele / Pagliaro, Michela / Bovo, Roberto / Vallesi, Antonino / Gabelli, Carlo / Martini, Alessandro. ·Department of Neurosciences and Complex Operative Unit of Otolaryngology, University Hospital of Padua, Padua, Italy. ·Audiol Neurootol · Pubmed #27806352.

ABSTRACT: A growing interest in cognitive effects associated with speech and hearing processes is spreading throughout the scientific community essentially guided by evidence that central and peripheral hearing loss is associated with cognitive decline. For the present research, 125 participants older than 65 years of age (105 with hearing impairment and 20 with normal hearing) were enrolled, divided into 6 groups according to their degree of hearing loss and assessed to determine the effects of the treatment applied. Patients in our research program routinely undergo an extensive audiological and cognitive evaluation protocol providing results from the Digit Span test, Stroop color-word test, Montreal Cognitive Assessment and Geriatric Depression Scale, before and after rehabilitation. Data analysis was performed for a cross-sectional and longitudinal study of the outcomes for the different treatment groups. Each group demonstrated improvement after auditory rehabilitation or training on short- and long-term memory tasks, level of depression and cognitive status scores. Auditory rehabilitation by cochlear implants or hearing aids is effective also among older adults (median age of 74 years) with different degrees of hearing loss, and enables positive improvements in terms of social isolation, depression and cognitive performance.

20 Article Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats. 2016

Astolfi, Laura / Simoni, Edi / Valente, Filippo / Ghiselli, Sara / Hatzopoulos, Stavros / Chicca, Milvia / Martini, Alessandro. ·Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy. · Foundation Onlus 'Staminali e Vita', Padua, Italy. · ENT surgery - Department of Neurosciences, University of Padua, Padua, Italy. · Clinic of ENT, University of Ferrara, Ferrara, Italy. · Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. ·PLoS One · Pubmed #27632426.

ABSTRACT: Cisplatin (Cpt) is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter). The Cpt was administered intraperitoneally in a single dose (14 mg/kg) or in three daily doses (4.6 mg/kg/day) to rats orally treated or untreated with Acu-Qter for 5 days. The auditory function was assessed by measuring auditory brainstem responses from 2 to 32 kHz at day 0 and 5 days after treatment. Similar hearing threshold and body weight alterations were observed in both Cpt administration protocols, but mortality reduced to zero when Cpt was administered in three daily doses. The Acu-Qter treatment was able to prevent and completely neutralize ototoxicity in rats treated with three daily Cpt doses, supporting the synergic protective effects of coenzyme Q terclatrate and Acuval 400® against Cpt-induced oxidative stress. The administration protocol involving three Cpt doses is more similar to common human chemotherapy protocols, therefore it appears more useful for long-term preclinical studies on ototoxicity prevention.

21 Article Outcomes of long-term audiological rehabilitation in charge syndrome. 2016

Trevisi, P / Ciorba, A / Aimoni, C / Bovo, R / Martini, A. ·Audiology Department, Padua University Hospital, Italy; · Audiology Department, Ferrara University Hospital, Italy. ·Acta Otorhinolaryngol Ital · Pubmed #27214832.

ABSTRACT: The aim of this paper is to assess the long-term audiological features and outcomes of hearing rehabilitation in a large group of individuals with CHARGE Syndrome. The study has been conducted retrospectively, on a paediatric patient database, at the Audiology Department of the University Hospitals of Ferrara and Padua. The study sample included 31 children presenting with different degrees of hearing impairment associated with CHARGE syndrome. Hearing was assessed using auditory brainstem responses (ABRs) and/or electrocochleography, or conditioned audiometry (visual reinforcement audiometry [VRA] or play audiometry). Auditory-perceptual outcomes in terms of communication skills and expressive language were also recorded. The effects of hearing rehabilitation (with hearing aids or cochlear implants) in this group of children and language outcomes after rehabilitation were monitored during long-term follow-up. The outcomes of rehabilitation measures differed in relation to the heterogeneous and often severe disabilities associated with CHARGE syndrome, e.g. developmental delay, intellectual delay, visual impairment, thin 8(th) nerve with retrocochlear auditory dysfunction (as described in cases of auditory neuropathy/dyssynchrony). Oral expressive language was severely impaired in most cases, even after lengthy follow-up, suggesting the need for alternative augmentative communication modes. The early identification of sensorineural hearing loss, and carefully planned rehabilitation treatments, can be of some benefit in children with CHARGE syndrome.

22 Article Cochlear implant and inflammation reaction: Safety study of a new steroid-eluting electrode. 2016

Astolfi, L / Simoni, E / Giarbini, N / Giordano, P / Pannella, M / Hatzopoulos, S / Martini, A. ·Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Via G. Orus, 2/B, 35129, Padua, Italy. Electronic address: laura.astolfi@unipd.it. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Via G. Orus, 2/B, 35129, Padua, Italy. Electronic address: edi.simoni@unipd.it. · ENT - Head and Neck Surgery Department, F. Tappeiner Hospital, Via Rossini 5, 39012, Merano, BZ, Italy. Electronic address: nadia.giarbini@asbmeran-o.it. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Via G. Orus, 2/B, 35129, Padua, Italy. Electronic address: grdptr@unife.it. · Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, 91120, Jerusalem, Israel. Electronic address: micaela.pannella@gmail.com. · ENT & Audiology Department, University Hospital of Ferrara, Via Aldo Moro 8, 44124, Cona, Ferrara, Italy. Electronic address: sdh1@unife.it. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Via G. Orus, 2/B, 35129, Padua, Italy; ENT Surgery - Department of Neurosciences, University of Padua, Via Giustiniani 2, 35129, Padua, Italy. Electronic address: alessandromartini@unipd.it. ·Hear Res · Pubmed #27109196.

ABSTRACT: Dexamethasone is a common anti-inflammatory agent added to cochlear implants to reduce hearing loss due to electrode insertion trauma. We evaluated the safety of eluting silicone rods containing 10% dexamethasone in a Guinea pig model. Animals were implanted with a dexamethasone eluting silicone electrode (DER) or with a non-eluting electrode (NER). The control group only underwent a cochleostomy (CS). Prior to implantation and during the two weeks following implantation, the hearing status of the animals was assessed by means of Compound Action Potentials (CAPs) with an electrode placed near the round window. Two weeks after implantation, the mean click threshold shifts were 1 dB ± 10 dB in the DER group, 10 dB ± 10 dB in the NER group and -4 dB ± 10 dB in the control group. After two weeks the bullae of each animal were extracted to verify the presence of macrophages, the percent of tissue growth in the scala tympani and the tissue sealing around cochleostomy. Silicone electrodes samples were also explanted and examined for bacterial infection. Neither bacterial infection nor enhanced number of macrophages were observed. A limited, but not significant, tissue growth was found in the scala tympani between the experimental and the control group. The data suggest that, in the Guinea pig model, the use of DER is apparently safe as an anti-inflammatory slow-release additive to the cochlear implant.

23 Article Cochlear Implant Outcomes and Genetic Mutations in Children with Ear and Brain Anomalies. 2015

Busi, Micol / Rosignoli, Monica / Castiglione, Alessandro / Minazzi, Federica / Trevisi, Patrizia / Aimoni, Claudia / Calzolari, Ferdinando / Granieri, Enrico / Martini, Alessandro. ·Department of Medical & Surgical Disciplines of Communication and Behavior, University Hospital of Ferrara, Via Fossato di Mortara 64/A, 44121 Ferrara, Italy. · ENT & Audiology Department, University Hospital of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy. · Department of Neurosciences, Complex Operative Unit of Otorhinolaryngology and Otosurgery, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy. · Neuroradiology Service, University Hospital of Udine, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy. · Neurological Clinic, University Hospital of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy. ·Biomed Res Int · Pubmed #26236732.

ABSTRACT: BACKGROUND: Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. METHODS: The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations) on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. RESULTS: Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years). Among these, 143 patients (64 females and 79 males) presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children) ranged from 9 months and 16 years (average = 4.4; median = 3.0). CONCLUSIONS: Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities, even if central nervous system anomalies represent a negative prognostic factor that is made worse by the concomitant presence of cochlear malformations. Common cavity and stenosis of the internal auditory canal (less than 2 mm) are negative prognostic factors even if brain lesions are absent.

24 Article Sensorineural hearing loss and ischemic injury: Development of animal models to assess vascular and oxidative effects. 2015

Olivetto, E / Simoni, E / Guaran, V / Astolfi, L / Martini, A. ·Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, 35129 Padua, Italy. Electronic address: elena.olivetto@unipd.it. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, 35129 Padua, Italy. Electronic address: edi.simoni@unipd.it. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, 35129 Padua, Italy. Electronic address: valeria.guaran@unipd.it. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, 35129 Padua, Italy. Electronic address: laura.astolfi@unipd.it. · Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, 35129 Padua, Italy; ENT Surgery, Department of Neurosciences, University of Padua, 35129 Padua, Italy. Electronic address: alessandromartini@unipd.it. ·Hear Res · Pubmed #25987500.

ABSTRACT: Hearing loss may be genetic, associated with aging or exposure to noise or ototoxic substances. Its aetiology can be attributed to vascular injury, trauma, tumours, infections or autoimmune response. All these factors could be related to alterations in cochlear microcirculation resulting in hypoxia, which in turn may damage cochlear hair cells and neurons, leading to deafness. Hypoxia could underlie the aetiology of deafness, but very few data about it are presently available. The aim of this work is to develop animal models of hypoxia and ischemia suitable for study of cochlear vascular damage, characterizing them by electrophysiology and gene/protein expression analyses. The effects of hypoxia in infarction were mimicked in rat by partial permanent occlusion of the left coronary artery, and those of ischemia in thrombosis by complete temporary carotid occlusion. In our models both hypoxia and ischemia caused a small but significant hearing loss, localized at the cochlear apex. A slight induction of the coagulation cascade and of oxidative stress pathways was detected as cell survival mechanism, and cell damages were found on the cuticular plate of outer hair cells only after carotid ischemia. Based on these data, the two developed models appear suitable for in vivo studies of cochlear vascular damage.

25 Article Is very early hearing assessment always reliable in selecting patients for cochlear implants? A case series study. 2015

Bovo, R / Trevisi, P / Ghiselli, S / Benatti, A / Martini, A. ·ENT Clinic, Padova University Hospital, Italy. Electronic address: roberto.bovo@sanita.padova.it. · ENT Clinic, Padova University Hospital, Italy. ·Int J Pediatr Otorhinolaryngol · Pubmed #25799382.

ABSTRACT: INTRODUCTION: This study concerns a case series of 23 infants with a diagnosis of severe-to-profound hearing loss at 3 months old, who significantly improved (even reaching a normal auditory threshold) within their first year of life. METHODS: All infants were routinely followed up with audiological tests every 2 months after being fitted with hearing aids as necessary. A reliable consistency between the various test findings (DPOAE, ABR, behavioral responses, CAEP and ECoG) clearly emerged in most cases during the follow-up, albeit at different times after birth. RESULTS: The series of infants included 7 cases of severe prematurity, 6 of cerebral or complex syndromic malformations, 5 healthy infants, 2 with asymptomatic congenital CMV infection, and 1 case each of hyperbilirubinemia, hypoxia, and sepsis. All term-born infants showed a significant improvement over their initial hearing threshold by 6 months of age, while in most of those born prematurely the first signs of threshold amelioration occurred beyond 70 weeks of gestational age, and even beyond 85 weeks in one case. CONCLUSIONS: Cochlear implantation (CI) should only be considered after a period of auditory stimulation and follow-up with electrophysiological and behavioral tests, and an accurate analysis of their correlation. In our opinion, CI can be performed after a period of 8 months in all term-born infants with persistent severe-to-profound hearing loss without risk of diagnostic error, whereas the follow-up for severely preterm infants should extend to at least 80 weeks of gestational age.

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