Xiaoting Cheng

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .

More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.

Due to limited spectral resolution, cochlear implants (CIs) do not convey pitch information very well. Pitch cues are important for perception of music and tonal language; it is possible that music training may improve performance in both listening tasks. In this study, we investigated music training outcomes in terms of perception of music, lexical tones, and sentences in 22 young (4.8 to 9.3 years old), prelingually deaf Mandarin-speaking CI users. Music perception was measured using a melodic contour identification (MCI) task. Speech perception was measured for lexical tones and sentences presented in quiet. Subjects received 8 weeks of MCI training using pitch ranges not used for testing. Music and speech perception were measured at 2, 4, and 8 weeks after training was begun; follow-up measures were made 4 weeks after training was stopped. Mean baseline performance was 33.2%, 76.9%, and 45.8% correct for MCI, lexical tone recognition, and sentence recognition, respectively. After 8 weeks of MCI training, mean performance significantly improved by 22.9, 14.4, and 14.5 percentage points for MCI, lexical tone recognition, and sentence recognition, respectively ( p < .05 in all cases). Four weeks after training was stopped, there was no significant change in posttraining music and speech performance. The results suggest that music training can significantly improve pediatric Mandarin-speaking CI users' music and speech perception.

Patients with single-sided deafness (SSD) often experience poor sound localization, reduced speech understanding in noise, reduced quality of life, and tinnitus. The present study aims to evaluate effects of tinnitus and duration of deafness on sound localization and speech recognition in noise by SSD subjects. Sound localization and speech recognition in noise were measured in 26 SSD and 10 normal-hearing (NH) subjects. Speech was always presented directly in front of the listener. Noise was presented to the deaf ear, in front of the listener, or to the better hearing ear. Tinnitus severity was measured using visual analog scale and Tinnitus Handicap Inventory. Relative to NH subjects, SSD subjects had significant deficits in sound localization and speech recognition in all listening conditions ( p < .001). For SSD subjects, speech recognition in noise was correlated with mean hearing thresholds in the better hearing ear ( p < .001) but not in the deaf ear. SSD subjects with tinnitus performed poorer in sound localization and speech recognition in noise than those without tinnitus. Shorter duration of deafness was associated with greater tinnitus and sound localization difficulty. Tinnitus visual analog scale and Tinnitus Handicap Inventory were highly correlated; the degree of tinnitus was negatively correlated with sound localization and speech recognition in noise. Those experiencing noticeable tinnitus may benefit more from cochlear implantation than those without; subjective tinnitus reduction may be correlated with improved sound localization and speech recognition in noise. Subjects with longer duration of deafness demonstrated better sound localization, suggesting long-term compensation for loss of binaural cues.