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    2020-07-04


    Conflict of interest
    The authors declare no potential conflicts of interest.
    Funding
    Appendix A. Supplementary data
    References
    Farnsworth, W.E., 1973. Human prostatic dehydroepiandrosterone sulfate sulfatase.
    Klein, H., Bressel, M., Kastendieck, H., Voigt, K.D., 1988a. Quantitative assessment of endogenous testicular and adrenal sex steroids and of steroid metabolizing Nocodazole in untreated human prostatic cancerous tissue. J. Steroid Biochem. 30, 119–130. Klein, H., Bressel, M., Kastendieck, H., Voigt, K.D., 1988b. Androgens, adrenal androgen precursors, and their metabolism in untreated primary tumors and lymph node me-tastases of human prostatic cancer. Am. J. Clin. Oncol. 11 (Suppl. 2), S30–S36.
    Klein, H., Molwitz, T., Bartsch, W., 1989. Steroid sulfate sulfatase in human benign prostatic hyperplasia: characterization and quantification of the enzyme in epithe-lium and stroma. J. Steroid Biochem. 33, 195–200.
    McNamara, K.M., Nakamura, Y., Miki, Y., Sasano, H., 2013. Phase two steroid metabolism and its roles in breast and prostate cancer patients. Front Endocrinol (Lausanne) 4,
    Mostaghel, E.A., 2013. Steroid hormone synthetic pathways in prostate cancer. Transl.
    88 THE PRACTICE OF EMERGENCY MEDICINE/ORIGINAL RESEARCH
    Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center
    Imad El Majzoub, MD; Aiham Qdaisat, MD; Kyaw Z. Thein, MD; Myint A. Win, MD; Myat M. Han, MD; Kalen Jacobson, MD; Patrick S. Chaftari, MD; Michael Prejean, RN; Cielito Reyes-Gibby, PhD; Sai-Ching J. Yeung, MD, PhD*
    *Corresponding Author. E-mail: [email protected]
    Study objective: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs).
    Methods: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death.
    Results: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival.
    Conclusion: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added. [Ann Emerg Med. 2019;73:79-87.]
    Please see page 80 for the Editor’s Capsule Summary of this article.
    Readers: click on the link to go directly to a survey in which you can provide feedback to Annals on this particular article.
    A podcast for this article is available at www.annemergmed.com.
    Copyright © 2018 by the American College of Emergency Physicians.
    INTRODUCTION
    Background
    Cancer immunotherapy is rapidly evolving and is transforming cancer care.1 Active research is investigating the development of and emerging results from immune checkpoint therapies, including the most effective treatment duration, the safety and effectiveness of immune checkpoint therapy in selected patient populations, the sequence of therapy in relation to chemotherapy or radiotherapy or targeted therapy, and appropriate combinations of immune checkpoint therapy agents.2-8
    Cytotoxic T-lymphocyte–associated protein 4 (CTLA4) and programmed cell death protein-1 signaling are involved in the mechanisms by which cancer cells escape surveillance by the immune system, and are the 2 earliest drug targets for
    immune checkpoint therapy (Figure 1).9 The first immune checkpoint therapy to be approved by the Food and Drug
    Administration (FDA) was ipilimumab, which is an antibody against CTLA4.10 This was followed by the