Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma.

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

Microscopic vs Endoscopic Ear Surgery for Congenital Ossicular Anomaly.

OBJECTIVE: To compare surgical outcomes of transcanal endoscopic ear surgery (TEES) for congenital ossicular anomalies with those of conventional microscopic surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral academic center. SUBJECTS AND METHODS: From March 2012 to November 2018, 42 consecutive ears in 40 patients with congenital ossicular anomaly who underwent ossiculoplasty or stapes surgery using either ear endoscopes (TEES group) or an operating microscope (microscopic group) were included. Postoperative audiometric results, operation time, switch of approach, and complications were compared between the 2 groups. RESULTS: Twenty-four ears (66.1%) were in the microscopic group and 18 ears (33.9%) were in the TEES group. The mean (SD) preoperative air-bone gap was 31.8 (10.0) dB in the microscopic group and 35.2 (11.1) dB in the TEES group. The mean (SD) postoperative air-bone gap was 7.4 (6.5) dB in the microscopic group and 5.6 (5.0) dB in the TEES group. The differences in the preoperative and postoperative air-bone gaps between the 2 groups were not statistically significant (P = .316 and P = .412, respectively). Average operation time in the TEES group was 24.6 minutes shorter than that in the microscopic group, which was statistically significant (P = .019). None of patients in the TEES group did require a switch of approach. There was no significant difference in complication incidence between the 2 groups. CONCLUSIONS: TEES for congenital ossicular anomaly has comparable audiometric results and complication rates to conventional microscopic surgery. TEES appears to have the advantages of shorter operation times.

Prognostic value of psychological state in cochlear implantation.

CONCLUSION: Perioperative Minnesota Multiphasic Personality Inventory (MMPI) scores may be beneficial for predicting prognosis of cochlear implantation (CI). A positive attitude for social interaction in particular correlates with a better speech outcome. Proper perioperative psychological management may, therefore, assist in the auditory rehabilitation of CI patients. OBJECTIVE: To determine the perioperative psychological state of CI patients and its relationship with patient prognosis after CI. METHODS: This study prospectively enrolled 29 patients who underwent CI from 2005-2013. The MMPI was administered to assess psychosocial and emotional issues surrounding CI and the Korean version of the Central Institute of Deafness (K-CID) score was used to measure speech perception. RESULTS: CI resulted in a significant improvement on the MMPI Paranoia scale (p = 0.02). Patients with abnormal pre-operative and post-operative MMPI scores also had an earlier onset of deafness, longer duration of deafness, and lower K-CID scores than patients with normal MMPI scores (all p < 0.05). The post-CI K-CID score had a significant negative correlation with the pre-operative MMPI Schizophrenia score (p < 0.01) and significant negative correlations with the post-operative MMPI Paranoia (p = 0.02), Psychasthenia (p = 0.02), Schizophrenia (p = 0.04), Hypomania (p = 0.02) and Social Introversion (p = 0.03) scores.

Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss.

Identification of causative genes for hereditary nonsyndromic hearing loss (NSHL) is important to decide treatment modalities and to counsel the patients. Due to the genetic heterogeneity in sensorineural genetic disorders, the high-throughput method can be adapted for the efficient diagnosis. To this end, we designed a new diagnostic pipeline to screen all the reported candidate genes for NSHL. For validation of the diagnostic pipeline, we focused upon familial NSHL cases that are most likely to be genetic, rather than to be infectious or environmental. Among the 32 familial NSHL cases, we were able to make a molecular genetic diagnosis from 12 probands (37.5%) in the first stage by their clinical features, characteristic inheritance pattern and further candidate gene sequencing of GJB2, SLC26A4, POU3F4 or mitochondrial DNA. Next we applied targeted resequencing on 80 NSHL genes in the remaining 20 probands. Each proband carried 4.8 variants that were not synonymous and had the occurring frequency of less than three among the 20 probands. These variants were then filtered out with the inheritance pattern of the family, allele frequency in normal hearing 80 control subjects, clinical features. Finally NSHL-causing candidate mutations were identified in 13(65%) of the 20 probands of multiplex families, bringing the total solve rate (or detection rate) in our familial cases to be 78.1% (25/32) Damaging mutations discovered by the targeted resequencing were distributed in nine genes such as WFS1, COCH, EYA4, MYO6, GJB3, COL11A2, OTOF, STRC and MYO3A, most of which were private. Despite the advent of whole genome and whole exome sequencing, we propose targeted resequencing and filtering strategy as a screening and diagnostic tool at least for familial NSHL to find mutations based upon its efficacy and cost-effectiveness.