Cyclodextrins are simple yet powerful molecules widely used in medicinal formulations and industry for their ability to stabilize and solubilize guest compounds. However, recent evidence shows that 2-hydroxypropyl-β-cyclodextrin (HPβCD) causes severe hearing loss in mice, selectively killing outer hair cells (OHC) within 1 week of subcutaneous drug treatment. In the current study, the impact of HPβCD on auditory physiology and pathology was explored further as a function of time and route of administration. When administered subcutaneously or directly into cerebrospinal fluid, single injections of HPβCD caused up to 60 dB threshold shifts and widespread OHC loss in a dose-dependent manner. Combined dosing caused no greater deficit, suggesting a common mode of action. After drug treatment, OHC loss progressed over time, beginning in the base and extending toward the apex, creating a sharp transition between normal and damaged regions of the cochlea. Administration into cerebrospinal fluid caused rapid ototoxicity when compared to subcutaneous delivery. Despite the devastating effect on the cochlea, HPβCD was relatively safe to other peripheral and central organ systems; specifically, it had no notable nephrotoxicity in contrast to other ototoxic compounds like aminoglycosides and platinum-based drugs. As cyclodextrins find expanding medicinal applications, caution should be exercised as these drugs possess a unique, poorly understood, ototoxic mechanism.

Objectives (1) Compare efficacy of primary medical therapy vs primary surgical intervention in patients with esophageal foreign bodies (EFBs). (2) Investigate variables that may predict successful outcomes in patients treated for EFBs. Study Design Case series with chart review. Setting Single-institution academic tertiary care medical center. Subjects and Methods Adult patients (older than 18 years) seen at the University of Michigan Emergency Department (ED) over an 8-year period with the diagnosis of EFBs (January 1, 2003, to December 31, 2011; N = 250). Decision was made by ED physicians whether to treat patients with first-line medical therapy vs surgical intervention. Pertinent clinical and demographic data were extracted from medical records and summarized by descriptive statistics. Results First-line treatment with surgical intervention (flexible or rigid esophagoscopy with foreign body removal) was much more likely to lead to resolution of symptoms than medical therapy (glucagon alone or in combination with other medical therapy) (98% vs 28%, P < .0001). When delivered within 12 hours of symptom onset, medical therapy was more likely to be successful (34% resolution vs 12% resolution, P < .01). There was no difference in complication rates for primary medical therapy vs surgical intervention (8% vs 8%). Conclusions Patients with EFBs are a commonly encountered consultation for both otolaryngologists and gastroenterologists. In these patients, first-line surgical intervention is superior to medical therapy and should not be avoided for a trial of medical therapy or concern for higher morbidity. Implementation of these findings has the ability to positively affect treatment patterns, outcomes, and patient quality of life.

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