SUMMARYWe have demonstrated previously that histone deacetylase (HDAC6) expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) New Zealand Black (NZB)/White F 1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for 5 weeks. As the mice aged, we determined autoantibody production and cytokine levels by enzyme-linked immunosorbent assay (ELISA) and renal function by measuring proteinuria. At the termination of the study, we performed a comprehensive analysis on B cells, T cells and innate immune cells using flow cytometry and examined renal tissue for immune-mediated pathogenesis using immunohistochemistry and immunofluorescence. Our results showed a reduced germinal centre B cell response, decreased T follicular helper cells and diminished interferon (IFN)-g production from T helper cells in splenic tissue. Additionally, we found the IFN-a-producing ability of plasmacytoid dendritic cells was decreased along with immunoglobulin isotype switching and the generation of pathogenic autoantibodies. Renal tissue showed decreased immunoglobulin deposition and reduced inflammation as judged by glomerular and interstitial inflammation. Taken together, these studies show selective HDAC6 inhibition decreased several parameters of disease pathogenesis in lupusprone mice. The decrease was due in part to inhibition of B cell development and response.

Smoking tobacco products is the leading cause of preventable death worldwide. Coordinated efforts have successfully reduced tobacco cigarette smoking in the United States; however, electronic cigarettes (e-cigarette) and other electronic nicotine delivery systems (ENDS) recently have replaced traditional cigarettes for many users. While the clinical risks associated with longterm ENDS use remain unclear, advancements in preclinical rodent models will enhance our understanding of their overall health effects. This review examines the peripheral and central effects of ENDS-mediated exposure to nicotine and other drugs of abuse in rodents and evaluates current techniques for implementing ENDS in preclinical research.

Objective This study sought to validate alternative pain management strategies that can reduce reliance on opioids for postoperative pain management in otology. Study Design Prospective cohort study. Setting Single tertiary‐care facility. Methods Adult patients who underwent outpatient otologic surgery from September 2021 to July 2022 were randomized into treatment cohorts. The opioid monotherapy cohort received a standard opioid prescription. The multimodal analgesia cohort received the same opioid prescription, prescriptions for acetaminophen and naproxen, and additional pain management education with a flyer on discharge. All patients completed a questionnaire 1 week after surgery to evaluate opioid usage and pain scores. Results Eighty‐six patients completed the study. The opioid monotherapy cohort (n = 42) and multimodal analgesia cohort (n = 44) were prescribed an average of 42.1 ± 20.4 morphine milligram equivalents (MME) and 38.4 ± 5.7 MME, respectively (p = 0.373). Four patients (9.52%) in the opioid monotherapy cohort required opioid refills compared to 1 patient (2.27%) in the multimodal analgesia cohort (p = 0.156). Multivariate analysis demonstrated that the multimodal analgesia cohort consumed significantly fewer opioids on average than the opioid monotherapy cohort (11.9 ± 15.9 MME vs 22.8 ± 28.0 MME, respectively). There were no significant differences in postoperative rehospitalizations (p = 0.317) or Emergency Department visits (p = 0.150). Pain scores on the day of surgery, postoperative day (POD) 1, POD3, and POD7 were not significantly different between cohorts (p = 0.395, 0.896, 0.844, 0.765, respectively). Conclusion The addition of patient education, acetaminophen, and naproxen to postoperative opioid prescriptions significantly reduced opioid consumption without affecting pain scores, refill rates, or complication rates after otologic surgery.

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