Natural History of Untreated Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: Although corticosteroids and other treatments for idiopathic sudden sensorineural hearing loss (ISSNHL) have been described, understanding its prognosis without intervention provides valuable information for patient management. The objective of this study is to provide a comprehensive, quantitative statistical analysis of the natural history of untreated idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY TYPE AND DESIGN: A systematic review and meta-analyses. METHODS: Two independent searches of PubMed, Scopus, Web of Science, and Cochrane Library databases up to June 30, 2022, were performed. Adults with idiopathic sudden sensorineural hearing loss who received placebo or were untreated and had audiometric outcome measures in all study types were reviewed. These data indicative of the natural history of ISSNHL were analyzed, as were study characteristics related to risk of bias. Heterogeneity as assessed via I2 and random effects analyses were performed. RESULTS: Six studies meeting the inclusion criteria yielded 319 untreated patients whose natural history could be assessed. Heterogeneity among studies was moderate, with a variety of reported outcomes. A hearing improvement of at least 30 dB HL was observed in 36% (95% CI 0.28-0.44) of untreated patients, and of at least 10 dB HL was observed in 70% (95% CI 0.57-0.82) of untreated patients at 3 months. The mean hearing gain among untreated patients was 24.0 dB HL (95% CI 2.65-45.37) at 2-3 months. CONCLUSIONS: The observed natural history of ISSNHL suggests that patients can regain some hearing without active treatment. In the absence of future studies collecting prospective natural history data from untreated or placebo-treated ISSNHL patients, the data presented here provide the best available historical control data for reconsideration of results in past ISSNHL studies, as well as a roadmap for design and interpretation of future ISSNHL treatment clinical trials. Furthermore, knowing there is a statistically significant mean hearing gain of 24.0 dB HL in the untreated/placebo group provides an ethical basis for future placebo study of ISSNHL. The current status on ISSNHL management calls for a multi-institutional, randomized, double-blind placebo-controlled trial with validated outcome measures to provide science-based treatment guidance. Laryngoscope, 2024.

Perioperative analgesia for patients undergoing otologic surgery: An evidence-based review.

OBJECTIVES/HYPOTHESIS: Opioid misuse and diversion is a major concern, with a negative impact on both the individual and society. The objective of this study was to perform an evidence-based systematic review of the efficacy of perioperative analgesic regimens following otologic surgery. METHODS: Embase, Cochrane Library, and PubMed/MEDLINE databases (January 1, 1947 to June 30, 2018) were searched for studies investigating pain management in otologic surgeries. All studies were assessed for quality and bias using the Cochrane bias tool. Patient demographics, type of surgery, medication class, dose, administration characteristics, pain scores, and adverse events were reported. RESULTS: Twenty-three studies encompassing 1,842 patients met inclusion criteria. In 21.4% of studies, an overall reduction in pain scores was reported when the treatment group included more than one analgesic. Nausea and vomiting were the most common adverse events across all medication types (10.2%), with local anesthetic patients experiencing these side effects most frequently (38.0%). Perioperative acetaminophen was reported to have the fewest adverse drug reactions overall (6.1%), but did not reduce pain scores as much as other modalities, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesics. CONCLUSIONS: There is evidence that combination analgesics, such as acetaminophen plus codeine, provide superior pain relief to monotherapy analgesics in the perioperative pain management of otologic surgeries. NSAIDs, α-agonists, and nerve blocks may also be viable single-therapy options. Further prospective randomized controlled trials into perioperative analgesia for patients undergoing otologic surgery may be helpful in establishing a definitive consensus. Laryngoscope, 130:190-199, 2020.

Activation of CHK1 in Supporting Cells Indirectly Promotes Hair Cell Survival.

The sensory hair cells of the inner ear are exquisitely sensitive to ototoxic insults. Loss of hair cells after exposure to ototoxic agents causes hearing loss. Chemotherapeutic agents such as cisplatin causes hair cell loss. Cisplatin forms DNA mono-adducts as well as intra- and inter-strand DNA crosslinks. DNA cisplatin adducts are repaired through the DNA damage response. The decision between cell survival and cell death following DNA damage rests on factors that are involved in determining damage tolerance, cell survival and apoptosis. Cisplatin damage on hair cells has been the main focus of many ototoxic studies, yet the effect of cisplatin on supporting cells has been largely ignored. In this study, the effects of DNA damage response in cochlear supporting cells were interrogated. Supporting cells play a major role in the development, maintenance and oto-protection of hair cells. Loss of supporting cells may indirectly affect hair cell survival or maintenance. Activation of the Phosphoinositide 3-Kinase (PI3K) signaling was previously shown to promote hair cell survival. To test whether activating PI3K signaling promotes supporting cell survival after cisplatin damage, cochlear explants from the neural subset (NS) Cre Pten conditional knockout mice were employed. Deletion of Phosphatase and Tensin Homolog (PTEN) activates PI3K signaling in multiple cell types within the cochlea. Supporting cells lacking PTEN showed increased cell survival after cisplatin damage. Supporting cells lacking PTEN also showed increased phosphorylation of Checkpoint Kinase 1 (CHK1) levels after cisplatin damage. Nearest neighbor analysis showed increased numbers of supporting cells with activated PI3K signaling in close proximity to surviving hair cells in cisplatin damaged cochleae. We propose that increased PI3K signaling promotes supporting cell survival through phosphorylation of CHK1 and increased survival of supporting cells indirectly increases hair cell survival after cisplatin damage.