The Effect of Postoperative Naloxone in Certain Otolaryngologic Surgeries.

OBJECTIVE: To evaluate the association of postoperative naloxone with the development of new substance use disorder (SUD), overdose, and death within 6 months of otolaryngologic surgery. STUDY DESIGN: Retrospective cohort database study on TriNetX. METHODS: Adult patients who underwent tonsil surgery (noncancerous), thyroid/parathyroid, septorhinoplasty, otology/neurotology, sinus/anterior skull base, and head and neck cancer surgeries between January 2003 and April 2023. Patients were excluded if they had an instance of SUD or overdose recorded in their charts prior to surgery, or had undergone another surgery within that 6-month time frame. We hypothesized that patients prescribed naloxone postoperatively would have decreased odds for experiencing new SUD, overdose, and/or death within 6 months of surgery compared to patients who did not receive naloxone. P < .01 was considered statistically significant. RESULTS: There were 2,305,655 patients in this study. The average age was 36.7 ± 19.5 years old, with 46% female patients. Before matching, cohorts showed equivocal odds for developing new SUD, increased odds for overdose, and mixed odds for dying. After matching for demographic variables and comorbidities such as other substance use, opioid use for other pathologies, and psychiatric conditions, these effects diminished (P > .01). CONCLUSION: Our results suggest that postoperative naloxone may not significantly affect development of new SUD and incident overdose and death in certain otolaryngologic surgeries after controlling for prior SUD and psychiatric conditions. Clinicians should be aware of these comorbidities when considering their postoperative pain management protocol, which may or may not include naloxone.

Cognitive and language outcomes for pediatric hearing loss with otologic surgery.

OBJECTIVES: To test the hypothesis that surgical otologic intervention for any type of pediatric hearing loss decreases the odds for incident adverse cognitive and linguistic developmental outcomes. STUDY DESIGN: Retrospective cohort database study. METHODS: Electronic medical record data from the TriNetX Research Network were queried for children with congenital, sensorineural, conductive, and mixed hearing loss (HL) between ages 0 and 5 years. Patients were further stratified by presence (HL + surgery) or absence (HL-surgery) of surgical intervention at any point following diagnosis, including cochlear implantation, tympanoplasty with or without mastoidectomy, and tympanostomy. Primary outcomes were defined as odds for new adverse cognitive or linguistic outcomes at any point given HL treatment status [odds ratio with 95% confidence interval, (OR; 95%CI, p-value)]. Cohorts were balanced using propensity-score matching (PSM) based on US census-defined demographics and clinically relevant congenital conditions. RESULTS: Of 457,636 total patients included in the study, 118,576 underwent surgery (HL + surgery cohort) and 339,060 did not (HL-surgery). In matched cohorts, surgical otologic intervention significantly decreased the odds of developing cognitive disorders including scholastic, motor, psychological developmental disorders, and pervasive developmental delays (p < 0.01). CONCLUSIONS: Surgical interventions for treatment of pediatric HL including cochlear implantation, tympanoplasty with or without mastoidectomy, and tympanostomy should be considered as they may prevent delays in development.

Evaluation of Subjective Tinnitus Severity and Distortion Product Otoacoustic Emissions and Extended High-Frequency Audiometry.

OBJECTIVE: Tinnitus is a multifactorial phenomenon with quality-of-life detriments for those affected by it. We aim to establish a relationship between subjective tinnitus severity with objective audiometric data in the extended high frequency (EHF) from 9 to 16 khz and with distortion product otoacoustic emissions (DPOAE). We hypothesize that severe subjective tinnitus as measured by the Tinnitus Handicap Inventory (THI) does not correlate with increased hearing thresholds in the EHF range. STUDY DESIGN: Prospective. SETTING: Single Tertiary Care Center. METHODS: Patients identified with tinnitus and normal hearing thresholds within standard frequency range (250-8000 Hz) were consented for participation. Those with underlying otologic disease, trauma, radiotherapy, or ototoxic drug use were excluded. The THI questionnaire was given to eligible patients and audiometric test results were collected. THI scores were categorized by severity groups. An n = 20 to 30 was determined to have an effect size of 0.7 with a significance level of P = .05. RESULTS: THI and audiometric data were collected for 38 patients and categorized into mild (n = 18, 47.4%), moderate (n = 8, 21.1%), slight (n = 7, 18.4%), and severe (n = 5, 13.2%) tinnitus severity groups. Mean THI score was 32.3 ± 19.6 with a statistically significant difference in scores by assigned THI severity group (P < .01). There were no significant differences or linear relationship among hearing thresholds in EHF range or DPOAE stratified by subjective tinnitus group (P = .49, r2 = 0.10) CONCLUSION: Subjective tinnitus severity is not predictive of audiometric outcomes. This finding can be used as a counseling tool to help tinnitus patients manage symptoms, expectations, and overall treatment outcomes.

Conductive Hearing Loss Associates With Dementia, and Middle Ear Reconstruction Mitigates This Association: A Multinational Database Study.

OBJECTIVE: To test the hypothesis that conductive hearing loss (CHL) is associated with dementia, and that middle ear reconstruction (MER) associates with improved outcomes for these measures in a multinational electronic health records database. STUDY DESIGN: Retrospective cohort study with propensity-score matching (PSM). SETTING: TriNetX is a research database representing about 110 million patients from the United States, Taiwan, Brazil, and India. PATIENTS: Subjects older than 50 years with no HL and any CHL (ICD-10: H90.0-2). Subjects of any age with and without any MER (CPT: 1010174). MAIN OUTCOME MEASURES: Odds ratios (ORs) and hazard ratios with 95% confidence intervals (95% CIs) for incident dementia (ICD-10: F01, F03, G30). RESULTS: Of 103,609 patients older than 50 years experiencing any CHL, 2.74% developed dementia compared with 1.22% of 38,216,019 patients with no HL (OR, 95% CI: 2.29, 2.20-2.37). Of patients experiencing CHL, there were 39,850 who received MER. The average age was 31.3 years, with 51% female patients. A total of 343,876 control patients with CHL were identified; 39,900 patients remained in each cohort after 1:1 PSM for HL- and dementia-related risk factors. Matched risk for developing dementia among MER recipients was 0.33% compared with 0.58% in controls (OR: 0.58, 0.46-0.72). CONCLUSIONS: CHL increases the odds for dementia, and MER improves the odds for incident dementia. This study represents the first population study on the topic of CHL, MER, and dementia.

Association of Smoke and Nicotine Product Consumption With Sensorineural Hearing Loss: A Population-Level Analysis.

OBJECTIVE: To test the hypothesis that use of cigarettes or other products with either cigarette-like smoke profile or high nicotine content by young populations increases the odds of developing sensorineural hearing loss (SNHL). STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX US Collaborative Network (2003-2022). PATIENTS: Approximately 3.6 million patients at least 18 years old. INTERVENTION: None. MAIN OUTCOME MEASURES: The primary outcome of interest was diagnosis of SNHL, defined using medical billing codes ( International Classification of Diseases, Tenth Revision , Current Procedural Terminology , etc.). Cohort inclusion criteria included electronic health record entry after 2003, age 18 to 54 or 55+ years at index, and status of cigarette, noncigarette nicotine, or cannabis use. Covariates were controlled via 1:1 propensity score matching for SNHL-related conditions, including diabetes mellitus and ischemic diseases. Odds for developing SNHL were calculated against control subjects aged 18 to 54 years who have no record of nicotine/cannabis use. RESULTS: Odds for developing SNHL are higher for people 18 to 54 years old who use any nicotine product (odds ratio [95% confidence interval], 5.91 [5.71-6.13]), cigarettes only (4.00 [3.69-4.33]), chewing tobacco only (9.04 [7.09-11.63]), or cannabis only (3.99 [3.60-4.44]) compared with control. People 55+ years old who use no products also showed increased odds for SNHL (4.73 [4.63-4.85]). CONCLUSIONS: Both nicotine and smoke exposure seem to be strongly associated with increased odds for developing SNHL, with chewing tobacco having the strongest association.

A Comparison of Outcomes Using Combined Intra- and Extradural versus Extradural-Only Repair of Tegmen Defects.

Objective Tegmen tympani or tegmen mastoideum defects involve dehiscence of the temporal bone that can be a source of cerebrospinal fluid (CSF) otorrhea. Herein, we compare a combined intra-/extradural repair strategy with an extradural-only repair as it pertains to surgical and clinical outcomes. Design A retrospective review from our institution was performed of patients with tegmen defects requiring surgical intervention. Participants Patients with tegmen defects who underwent surgery (combined transmastoid and middle fossa craniotomy) for repair of tegmen defects between 2010 and 2020 were inclined in this study. Results A total of 60 patients with 40 intra-/extradural (mean follow-up time: 1,060 ± 1,103 days) and 20 extradural-only (mean follow-up time: 519 ± 369 days) repairs were identified. No major differences in demographic factors or presenting symptoms were identified between the two cohorts. There was no difference in hospital length of stay between the two patient cohorts (mean: 4.15 vs. 4.35 days, p = 0.8). In the extradural-only repair technique, synthetic bone cement was more frequently used (100 vs. 7.5%, p < 0.01), whereas in the combined intra-/extradural repair, synthetic dural substitute was used more often (80 vs. 35%, p < 0.01), with similar successful surgical outcomes achieved. Despite disparities in the techniques and materials used for repair, there were no differences in complication rates (wound infection, seizures, and ossicular fixation), 30-day readmission rates, or persistent CSF leak between the two treatment cohorts. Conclusion The results of this study suggest no difference in clinical outcomes between combined intra-/extradural versus extradural-only repair of tegmen defects. A simplified extradural-only repair strategy can be effective, and may reduce the morbidity of intradural reconstruction (seizures, stroke, and intraparenchymal hemorrhage).

Cost-effectiveness of Inpatient Tympanostomy Prophylaxis.

OBJECTIVE: Tympanostomy is the most common pediatric ambulatory surgery. Post-tympanostomy otorrhea is a prevalent complication leading to high costs to patients for treatment. The cost-effectiveness of intraoperative prophylaxis for both patient and institution has not been examined. STUDY DESIGN: An analytical observational study of data collected from the literature and purchasing records. METHODS: A break-even analysis was performed to determine the required absolute risk reduction (ARR) and final infection rate in post-tympanostomy otorrhea to make intraoperative prophylaxis using ofloxacin and ciprofloxacin dexamethasone otic version cost effective with the following outpatient treatments: ofloxacin, ciprofloxacin-dexamethasone ophthalmic version, and ciprofloxacin-dexamethasone otic version. Absolute risk reduction is a statistic used to express the difference in risk between a treatment and control. The conservative initial infection rate used was 10%. RESULTS: Ofloxacin intraoperative prophylaxis was not cost effective when prescribing ofloxacin outpatient treatment with an ARR of 0.20. Ofloxacin intraoperative prophylaxis was cost-effective with an ARR of 0.08 for ciprofloxacin-dexamethasone ophthalmic version outpatient treatment. Ofloxacin intraoperative prophylaxis was cost-effective for ciprofloxacin-dexamethasone otic version outpatient treatment with an ARR of 0.01.Ciprofloxacin-dexamethasone intraoperative prophylaxis was not cost-effective when prescribing ofloxacin outpatient treatment with an ARR of 1.52. Ciprofloxacin-dexamethasone intraoperative prophylaxis was not cost-effective when prescribing ciprofloxacin-dexamethasone ophthalmic version outpatient treatment with an ARR of 0.60. Ciprofloxacin-dexamethasone intraoperative prophylaxis was cost effective when prescribing ciprofloxacin-dexamethasone otic version outpatient treatment with an ARR of 0.09. CONCLUSION: Intraoperative prophylaxis can be cost effective for preventing post-tympanostomy otorrhea. Physicians can use this economic model to determine the cost-effectiveness of these interventions for their patients and institutions.

cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression.

cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in quiescent cells but dramatically reducing it in cycling cells. The latter is due to a rapid and dramatic loss of mitotic histone H3 phosphorylation caused by a disruption in G2 progression, as evidenced by the inhibition of mitotic entry and decreased activity of the CyclinB/Cdk1 kinase. The inhibition of G2 progression induced through cAMP signaling is dependent on expression of the catalytic subunit of PKA and is highly sensitive to intracellular cAMP concentration. The mechanism by which G2 progression is inhibited is independent of both DNA damage and MAP kinase signaling. Our results suggest that cAMP signaling activates a G2 checkpoint by a unique mechanism and provide new insight into normal cellular regulation of G2 progression.

Volumetric MRI analysis pre- and post-Transoral robotic surgery for obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: To quantitatively measure volumetric changes in upper airway soft tissue structures using magnetic resonance imaging (MRI) pre- and post transoral robotic surgery for obstructive sleep apnea (OSA-TORS). STUDY DESIGN: Prospective, nonrandomized, institutional board-approved study. METHODS: Apneics undergoing OSA-TORS, which included bilateral posterior hemiglossectomy with limited pharyngectomy and uvulopalatopharyngoplasty, had upper airway MRIs pre- and postoperatively. Changes (percent and absolute values) in upper airway and surrounding soft tissue volumes were calculated. We assessed whether there were significant volumetric changes and if changes correlated with apnea-hypopnea index (AHI) changes. RESULTS: Nineteen MRIs and 18 polysomnograms were analyzed pre- and postoperation. Total airway volume increased by 19.4% (P = 0.030). Soft palate and tongue volumes decreased by 18.3% (P = 0.002) and 5.8% (P = 0.013), respectively. Retropalatal and total lateral wall volumes decreased by 49.8% (P = 0.0001) and 17.9% (P = 0.008), respectively. Changes in other structures were not significant. Eleven patients had surgical success, with a mean AHI decrease of 52.9; six were nonsuccesses with a mean AHI decrease of 4.5 (P =0.006). Decreased retropalatal lateral wall volume correlated with decreased AHI. CONCLUSION: Airway, tongue, soft palate, and lateral wall volumes change significantly after OSA-TORS. Changes in the volume of the lateral walls correlated with changes in AHI. Volumetric upper airway MRI may be a helpful tool to better understand reasons for surgical success. LEVEL OF EVIDENCE: 4.

cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines.

The phosphorylation of histone H3 is known to play a role in regulation of transcription as well as preparation of chromosomes for mitosis. Various signaling cascades induce H3 phosphorylation, particularly at genes activated by these pathways. In this study, we show that signaling can also have the opposite effect. Activators of cAMP signaling induce a rapid and potent loss of H3 phosphorylation. This effect is not mediated through a cAMP metabolite since a membrane-permeable form of AMP had no effect on H3 phosphorylation and a phosphodiesterase-resistant cAMP analog efficiently reduced it. cAMP is also the likely regulator of H3 phosphorylation under physiological conditions since only supra-pharmacological doses of cGMP induce the loss of H3 phosphorylation. The loss of phosphorylation is specific for histone H3 since we do not observe drastic losses in total phosphorylation of other histones. In addition, other H3 modifications are unaffected with the exception of lysine 9 methylation, which is elevated. Analysis of cell growth and cell cycle shows that cAMP signaling inhibits cell growth and arrests cells at both G1 and G2/M. Similar effects of cAMP signaling on H3 phosphorylation are observed in a variety of mammary adenocarcinoma-derived cell lines. In syngeneic human breast-derived cell lines, one diploid and non-transformed, the other derived from a ductal carcinoma, the loss of H3 phosphorylation is significantly more sensitive to cAMP concentration in the transformed cell line.