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Newborn (Clarksville, Md.) 2023Congenital cytomegalovirus (cCMV) infection is the most common fetal viral infection and contributes to about 25% of childhood hearing loss by the age of 4 years. It is...
Congenital cytomegalovirus (cCMV) infection is the most common fetal viral infection and contributes to about 25% of childhood hearing loss by the age of 4 years. It is the leading nongenetic cause of sensorineural hearing loss (SNHL). Infants born to seroimmune mothers are not completely protected from SNHL, although the severity of their hearing loss may be milder than that seen in those whose mothers had a primary infection. Both direct cytopathic effects and localized inflammatory responses contribute to the pathogenesis of cytomegalovirus (CMV)-induced hearing loss. Hearing loss may be delayed onset, progressive or fluctuating in nature, and therefore, a significant proportion will be missed by universal newborn hearing screening (NHS) and warrants close monitoring of hearing function at least until 5-6 years of age. A multidisciplinary approach is required for the management of hearing loss. These children may need assistive hearing devices or cochlear implantation depending on the severity of their hearing loss. In addition, early intervention services such as speech or occupational therapy could help better communication, language, and social skill outcomes. Preventive measures to decrease intrauterine CMV transmission that have been evaluated include personal protective measures, passive immunoprophylaxis and valacyclovir treatment during pregnancy in mothers with primary CMV infection. Several vaccine candidates are currently in testing and one candidate vaccine in phase 3 trials. Until a CMV vaccine becomes available, behavioral and educational interventions may be the most effective strategy to prevent maternal CMV infection.
PubMed: 38348106
DOI: 10.5005/jp-journals-11002-0081 -
Advanced Science (Weinheim,... Mar 2024Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is...
Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.
Topics: Humans; Animals; Mice; Dependovirus; Hearing Loss, Sensorineural; Hearing; Deafness; Genetic Therapy
PubMed: 38189623
DOI: 10.1002/advs.202306788 -
International Archives of... Oct 2023Ménière disease (MD) affects the inner ear, comprising the cochlea and semicircular canals. Symptoms include severe incapacitating vertigo, nausea, vomit, aural...
Ménière disease (MD) affects the inner ear, comprising the cochlea and semicircular canals. Symptoms include severe incapacitating vertigo, nausea, vomit, aural fullness, and sensorineural hearing loss - in which speech discrimination and intelligibility are impaired and can be quantified with speech audiometry. To investigate the influence of the stimuli presentation level in speech audiometry and the quality of life in adults with and without a diagnosis of MD. Two groups were formed with nine individuals each - one with and the other without MD. The Speech Recognition Percentage Index was researched with stimuli presented above the self-reported comfort level or 5 dB below the discomfort level. Dizziness Handicap and Tinnitus Handicap Inventories were administered to individuals with tinnitus and vertigo complaints. Speech recognition was better in the study group with higher presentation levels, as 75% of the sample improved their performance. The presence of vertigo significantly impacted the quality of life of individuals in the study group. Speech recognition improves with higher presentation levels. Also, MD impacts the quality of life, especially regarding limitations caused by vertigo.
PubMed: 37876685
DOI: 10.1055/s-0043-1767677 -
Allergology International : Official... Oct 2023Eosinophilic otitis media (EOM) is a refractory condition associated with eosinophilic chronic rhinosinusitis and bronchial asthma. EOM is characterized by type-2...
BACKGROUND
Eosinophilic otitis media (EOM) is a refractory condition associated with eosinophilic chronic rhinosinusitis and bronchial asthma. EOM is characterized by type-2 inflammation and is refractory to various treatments. We investigated the efficacy of dupilumab, interleukin-4 receptor alpha antagonist, for patients with EOM complicated by eosinophilic chronic rhinosinusitis (ECRS).
METHODS
Between April 2017 and April 2022, we treated 124 patients with dupilumab for refractory CRS or bronchial asthma. Of these, 14 had EOM concurrently, and 10 of them who had been treated for >6 months were included in our study. We retrospectively evaluated the efficacy of dupilumab by the amount of systemic corticosteroid used, the frequency of exacerbations, severity score of EOM, computed tomography (CT) score of temporal bones, and pure tone audiometry. We also enrolled 8 EOM patients without dupilumab treatment as a control group.
RESULTS
Dupilumab significantly improved the amount of systemic corticosteroid used and the frequency of exacerbation and compared with before dupilumab was used (p = 0.01 and <0.01, respectively). All patients could be weaned from systemic-corticosteroid therapy by 54 weeks of dupilumab use. The severity score of EOM and CT score for temporal bones were significantly lower than before the treatment (p = 0.01 and 0.01, respectively). Compared to the control group, the systemic corticosteroid used and severity scores were improved in the dupilumab group (p = 0.02 and < 0.01, respectively).
CONCLUSIONS
Dupilumab could be used to wean patients from systemic corticosteroids with the improvement of severity score in EOM associated with ECRS and bronchial asthma.
Topics: Humans; Retrospective Studies; Otitis Media; Asthma; Chronic Disease; Sinusitis; Adrenal Cortex Hormones
PubMed: 37061391
DOI: 10.1016/j.alit.2023.03.007