Adverse Events and Subsequent Management Associated With Eustachian Tube Balloon Dilation.

Objective: Eustachian tube balloon dilation is a minimally invasive technique used to improve persistent Eustachian tube dysfunction. Currently, the US Food and Drug Administration (FDA) has approved the use of balloon dilation devices produced by three manufacturers, but little is known about associated adverse events and subsequent management. Study Design: Case series. Setting: FDA Manufacturer and User Facility Device Experience (MAUDE) database. Methods: Reports submitted to the FDA using the MAUDE database searched from January 2000 to July 2022 were analyzed for adverse events and management. Results: A total of 13 adverse events were found in the database. Subcutaneous emphysema (n = 8) was the most common event. Other less frequent events included patulous Eustachian tube (n = 2), vascular dissection (n = 1), nasopharyngeal mucocele (n = 1), and tinnitus (n = 1). A majority of patients who experienced subcutaneous emphysema received antibiotics (n = 5) and were admitted to the hospital (n = 4). The patient with a carotid dissection 7 days postprocedure presented with a stroke and fully recovered after stent placement. There was limited preprocedure information in the MAUDE database. There were 2 patients who did not fully recover after a complication. Three patients underwent corrective surgical interventions. No one company had more associated adverse events reported. Conclusion: Subcutaneous emphysema is the most common adverse event after Eustachian tube dilation. Further studies exploring potential balloon dilation adverse events to allow for better patient counseling are warranted.

Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice.

The prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/-), and Foxo3 knock-out (Foxo3-/-) mice to better understand FOXO3's role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3-/- OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3's absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3-/- mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise-exposed Foxo3-/- mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

Integrated measurement of intracellular proteins and transcripts in single cells.

Biological function arises from the interplay of proteins, transcripts, and metabolites. An ongoing revolution in miniaturization technologies has created tools to analyze any one of these species in single cells, thus resolving the heterogeneity of tissues previously invisible to bulk measurements. An emerging frontier is single cell multi-omics, which is the measurement of multiple classes of analytes from single cells. Here, we combine bead-based transcriptomics with microchip-based proteomics to measure intracellular proteins and transcripts from single cells and defined small numbers of cells. The transcripts and proteins are independently measured by sequencing and fluorescent immunoassays respectively, to preserve their optimal measurement modes, and linked by encoding the physical address locations of the cells into digital sequencing space using spatially patterned DNA barcodes. We resolve cell-type-specific protein and transcript signatures and present a path forward to scaling the platform to high-throughput.