COVID-19 has brought up the use of the old remedy convalescent serum. What is it? Did it work? This series walks us through the history of the serum, how it was discovered, how it was first used, and how it inspired the field of immunology. Intro :11 In this episode :15 A quick tale :20 Outline of these three episodes 2:51 Quick definitions 3:50 How it all began 7:16 A solo paper on diphtheria 12:57 A trial of children 17:07 Giving fluids from a horse 21:57 What happened with tetanus? 25:12 Switching gears to our understanding of antibodies 27:09 The next target: snakes 29:17 The plague 32:00 Summary of Part 1, what’s next 39:05 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Butler T. Clin Microbiol Infect. 2014;20:202-209. Crum FS. Am J Public Health. 1917;7:445. Eibl MM. Immunol Allergy Clin North Am. 2008;28:737-764, viii. Graham BS, Abrosino DM. Curr Opin HIV AIDS. 2015;10:129-134. Grundbacher FJ. Immunol Today. 1992;13:188-190. Hawgood BJ. Toxicon. 1999;37:1241-1258. Kantha SS. Keio J Med. 1991;40:35-39. Kaufmann SHE. mBio. 2017;8:e00117-17. Klass, Perri. “An Apocryphal Christmas Miracle.” The New York Times, The New York Times, 23 Dec. 2019, www.nytimes.com/2019/12/23/well/family/diphtheria-antitoxin-Christmas-miracle.html. Lindenmann J. Scand J Immunol. 1984;19:281-285. Meyer KF, et al. Ann N Y Acad Sci. 1952;55:1228-1274. Ramon G. Bull Soc Centr Med Vet. 1925;101:227-234. von Behring, Emil. Geschichte der Diphtherie (mit besonderer Berücksichtigung der Immunitätslehre). Leipzig, Germany, Thieme, 1893. von Behring E. Ueber das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren. German Medical Weekly; 1890.

With COVID-19 and the question of whether glucocorticoids could be beneficial, this episode digs into the data on the use of glucocorticoids in the setting of infections, from pneumonia and septic arthritis, to meningitis and septic shock. Intro :11 In this episode :25 The first published case series of patients with serious infection 6:45 Otolaryngologic infections 7:43 Pneumonia, malaria and flu 8:26 Cortisone in strep throat 9:22 Major severe infections 11:26 A review article 12:12 Specific organ systems 13:25 Dexamethasone for bacterial meningitis 25:28 Septic shock 26:19 Dearth of data on glucocorticoids for influenza 32:10 Summary and take-home 35:19 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Annane D, et al. JAMA. 2002;288:862-871. Annane D, et al. N Engl J Med. 2018;378:809-818. Bennett IL, et al. JAMA. 1963;183:462-465. Blum CA, et al. Lancet. 2015;385:1511-1518. de Gans J, van de Beek D. N Engl J Med. 2002;347:1549-1556. Dellinger RP, et al. Crit Care Med. 2013;41:580-637. Fogel I, et al. Pediatrics. 2015;136:e776. Hahn EO, et al. J Clin Invest. 1951;30:274-281. Hartman FA, Merle Scott WJ. Proc Soc Exp Biol and Med. 1931;28:478-479. Hinshaw LB, et al. J Surg Res. 1980;28:151-170. Nedel WL, et al. World J Crit Care Med. 2016;5:89-95. Odio CM, et al. Pediatr Infect Dis J. 2003;22:883-888. Perla D, Marmorston J. Endocrinology. 1940;27:368-374. Stern A, et al. Cochrane Database Syst Rev. 2017;12:doi:10.1002/14651858.CD007720.pub3 Venkatesh B, et al. N Engl J Med. 2018;378:797-808. Wenner WF, Cone AJ. Arch Otolaryngol. 1934;20:178-187. Whitehead KW, Smith C. Proc Soc Expert Biol and Med. 1932;29:672-673. Wysenbeek AJ, et al. Ann Rheum Dis. 1998;57:687–690.  Zhou Y, et al. Sci Rep. 2020;10:https://doi.org/10.1038/s41598-020-59732-7.

This episode delves into the history of Whipple’s disease — from its initial description, to the lengthy process of proving it’s an infectious disease. Intro :11 In this episode :12 The initial case report 1:35 How I fit into the history of Whipple’s 4:46 Back to the case report 6:56 Bodies in the intestines 10:12 More about George Hoyt Whipple 10:50 Whipple may not have been the first to identify this condition 14:19 First treatment with antibiotics 15:55 Personality change after antibiotics 19:12 Whipple’s disease intestines have positive staining 20:20 Using the electron microscope in Whipple’s disease 21:18 Summary and take-home 25:19 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Bayless, TM. Adv intern Med. 1970;16:171-189. Black-Schaffer B. Proc Soc Exp Biol Med. 1949;72:225-227. Fenollar F, et al. N Engl J Med. 2007;356:55‐66. Hendrix JP, et al. Arch Intern Med (Chic).1950;85:91-131. Morgan AD. Gut. 1961;2:370-372. Paulley JW. Gastroenterology. 1952;​22:128-133.​ Raoult D, et al. N Engl J Med. 2000;342:620-625. Relman DA, et al. N Engl J Med. 1992;327:293-301. ​ Whipple GH. Bull Johns Hopkins Hosp. 1907;18:382-391.

This episode dives into the rare Whipple’s disease, focusing on the articular manifestations of this infectious masquerader and when a rheumatologist should consider it in the differential. Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Intro :20 In this episode :28 Background on the organism 5:25 An important point when making the diagnosis 7:48 Who gets infected? 8:55 What is Whipple’s disease? 11:48 This disease is fatal 15:53 A look at the joints 16:28 What happens when you give these patients immunosuppression? 26:36 How to diagnose 28:38 Summary so far 31:00 Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Other organ manifestations of Whipple’s disease 32:08 Summary and take-home 44:36 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Bousbia S, et al. Emerg Infect Dis. 2010;16:258-63. Chan RY, et al. Ophthalmology. 2001;108:2225-2231. Dobbins 3rd WO, et al. Arthritis Rheum. 1987;30:102-105. Durand DV, et al. Medicine (Baltimore). 1997;76:170-84. Fenollar F, et al. BMC Infect Dis. 2011;11:171. Feurle GE, et al. Eur J Clin Invest. 1979;9:385-389. Geissdörfer W, et al. J Clin Microbiol. 2012;50:216-22. Guérin A, et al. Elife. 2018;7:e32340. Heffner DK. Lancet. 2007;370:738-9; author reply 739. Keita AK, et al. PLoS Negl Trop Dis. 2011;5:e1403. Lagier JC, et al. Medicine (Baltimore). 2010;89:337-345. Lozupone C, et al. Am J Respir Crit Care Med. 2013;187:1110-7. McAllister Jr. HA, Fenoglio Jr. JJ. Circulation. 1975;52:152-6. O’Duffy JD, et al. Arthritis Rheum. 1999;42:812-817. Puéchal X. Joint Bone Spine. 2016;83:631-635. Puéchal X, et al. Arthritis Rheum. 2002;46:1130-1132. Puéchal X, et al. Arthritis Rheum. 2007;56:1713-1718. Raheja AA, et al. Clin Imaging. 2010;34:143-147. Ramos JM, et al. J Med Case Rep. 2015;9:165. Raoult D, et al. Emerg Infect Dis. 2010;16:776-82. Schöniger-Hekele M, et al. Appl Environ Microbiol. 2007;73:2033-2035. Stein A, et al. Am J Respir Crit Care Med. 2013;188:1036-7. Additional resource: Neurosigns.org’s video on oculomasticatory myorhythmia can be viewed at: https://www.youtube.com/watch?v=Zwb5bt749Jo

This episode explores the history of cryoglobulinemic vasculitis, from the first person who froze a tube of blood and noticed something strange happened, to the discovery of hepatitis C. We also throw in how the lab test for cryoglobulins is performed and some of the data we have on therapy. Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Intro :20 In this episode :45 How is this test done? 1:30 What is the first description of cryoglobulins? 4:15 The first time “cryoglobulins” is used 10:26 Hepatitis C is discovered and linked to cryoglobulinemia 16:28 What do we know about the pathophysiology? 19:38 Why does HCV do this? 22:12 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. What’s in the blood as a result of immune complex? 24:52 What do we know about autoimmune diseases and the prevalence of cryoglobulins? 26:03 What about treatment? 28:25 Summary of this three-part series 36:16 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Brouet JC, et al. Am J Med. 1974;57:775-788. Cacoub P, et al. Clin Gastroenterol Hepatol. 2019;17:518-526. De Vita S, et al. Arthritis Rheum. 2012;64:843-853. Fuentes A, et al. Curr Rheumatol Rep. 2019;21:doi:10.1007/s11926-019-0859-0. Lerner AB, Watson CJ. Am J Med Sci. 1947;214:410-415. Lospalluto J, et al. Am J Med. 1962;32:142-147. Meltzer M, Franklin EC. Am J Med. 1966;40:828-836. Pascual M, et al. J Infect Dis. 1990;162:569-570. Ragab G, Hussein MA. J Adv Res. 2017;8:99-111. Tzioufas AG, et al. Arthritis Rheum. 1986;29:1098-1104. Wintrobe MM, Buell, MV. Bull. Johns Hopkins Hosp. 1933;52:156-165.

In Part 2, I sit down with nephrologist Ali Mehdi, MD, and neurologist Ghulam Abbas Kharal, MD, MPH, to discuss their different specialty perspectives on working up patients with suspected cryoglobulinemic vasculitis. Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Intro :20 Introduction of Ali Mehdi, MD :45 Interview with Dr. Mehdi 2:02 Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Introduction of Ghulam Abbas Kharal, MD, MPH 25:01 Interview with Dr. Kharal 26:37 To hear more of my interview with Abbas, keep listening 44:47 Thank you, Dr. Kharal 53:07 Ghulam Abbas Kharal, MD, MPH, is a Partners Neurology Resident at Massachusetts General Hospital, Brigham & Women's Hospital, Harvard School of Medicine. Ghulam Abbas Kharal, MD, MPH, is a staff neurologist at Cleveland Clinic. Kharal did his training in a combined program at Massachusetts General Hospital and Brigham & Women's Hospital, Harvard School of Medicine. Ali Mehdi, MD, is a Nephrology Fellow at the Cleveland Clinic. Mehdi did his Internal medicine residency and chief year at the Cleveland Clinic. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum

Try your hand at this medical mystery, which is followed by some didactics on a fascinating disease which will hopefully make sense of this inscrutable title. Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Intro :22 What to expect in each episode :30 The case: A 75-year-old man with Sjogren’s and MALT lymphoma presents with recurrent cerebral infarcts of multiple territories 1:10 Rheumatology is consulted 6:11 Decreased sensation in toes occurs between strokes 7:14 What’s going on with this patient? 8:36 What additional labs can we perform? 9:36 We spin the urine 11:10 What kind of vasculitis are Sjogren’s and lymphoma associated with? 12:22 C3 and C4 had already been performed 13:00 An overall picture of this patient 13:54 What about the strokes? 14:19 Should we do more imaging? 15:57 At this point we can make a clinical decision 16:33 Why make a decision so quickly vs. waiting for biopsy? 18:18 Two things you must check before moving forward with a cryoglobulinemic vasculitis 19:46 Spoiler alert: The patient is doing really well 20:16 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. What is cryoglobulinemic vasculitis? 21:00 What are these immunoglobulins? There are three types of cryoglobulins 22:55 Usually driven by another identifiable disease 25:18 What is making these immunoglobulins? 26:49 We don’t know why these immunoglobulins behave this way 27:18 How do you explain the kidneys? 28:28 What’s occurring at the tissue level? 29:35 How does type 1 present? 30:50 Type 2 and type 3 31:12 What other organ systems are involved? 33:11 I hope you enjoyed this patient presentation 36:00 What we’ll discuss in episodes 2 and 3 36:05 Thanks for listening 38:03 **Coming soon from Healio, Unmasking COVID-19, a podcast hosted by Gitanjali Pai, MD, infectious disease physician at Memorial Hospital and Physicians’ Clinic in Stilwell, Oklahoma. In this timely new show, Dr. Pai will explore COVID-19’s impact on vulnerable patient populations by answering questions from experts in various medical fields, including oncology, endocrinology and rheumatology. To submit your question for Dr. Pai, email covid19podcast@healio.com.** We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO @CCalabreseDO Disclosure: Brown reports no relevant financial disclosures. References: Fuentes A, et al. Current Rheumatology Reports. 2019;21:60. Silva F, et al. J Autoimmun. 2019;105:102313.

In this episode, Leonard H. Calabrese, DO, is joined by his colleague and daughter Cassandra Calabrese, DO, as they discuss specifics of irAEs, including unusual toxicities, rheumatic conditions associated with checkpoint inhibitors and the rheumatologist’s role in this new area of medicine. Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Intro :22 Recap of Part 1 :40 An interview with Cassandra Calabrese, DO 2:02 The number of patients with irAEs will grow 2:22 How many people actually experience irAEs? 3:40 Any examples of unusual toxicities? 5:49 What’s the timeline? 6:51 Have you seen patients with delayed onset? 8:10 Most of our patients have had one irAE or another beforehand 9:04 Who’s the captain of this ship? 10:15 What about inflammatory arthritis? 10:55 What about polymyalgia rheumatica? 13:48 Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com What about sicca, is it Sjogren’s? 16:22 Can you tell us about myositis in this context? 18:38 An overview of the guidelines 21:47 Check out our article in March Current Opinions in Rheumatology 24:12 What about patients with preexisting autoimmunity? 24:33 Are you worried about blunting tumor response? 27:10 Are there any biomarkers to predict this? 28:30 How have you been working with oncologists to manage/educate? 29:42 What about meetings? 31:04 Rheumatologists have a special place in this new area of medicine 31:45 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO @CCalabreseDO Disclosure: Brown and Cassandra Calabrese report no relevant financial disclosures. Leonard Calabrese reports serving as an investigator and a consultant to Horizon Pharmaceuticals. Cassandra Calabrese, DO, is associate staff member in the department of rheumatic and immunologic disease and department of infectious disease at the Cleveland Clinic. Leonard H. Calabrese, DO, is chief medical editor of Healio Rheumatology and director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

Checkpoint inhibitors have changed the field of oncology, as well as our understanding of autoimmunity. This episode, hosted by Leonard H. Calabrese, DO, walks us through the history of checkpoint inhibitors — from Dr. William Coley’s use of infections in cancer to the development of PD-1 inhibitors. Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Intro :20 In this episode with Dr. Calabrese 3:07 Book recommendations 4:28 Harnessing the power of the immune system to fight cancer 5:33 William Coley and a patient 6:30 The search for Fred Stein 11:40 Coley designs an experiment 13:09 A different strain of streptococcus 16:16 The beginning of cancer therapy and immunotherapy 19:18 Where do we go from there? 20:49 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. What about tumor immunology? 21:55 The breakthrough 24:01 What do immunology and checkpoints have to do with it? 26:47 What happens when the danger signal cannot be dispatched? 34:02 Why do we, as rheumatologists, care about this? 36:04 CHAI and LATTE 38:49 Check out some papers on immunopathogenesis of irAEs 40:56 Checkpoint inhibitors for autoimmune diseases; RA and GCA 41:41 Come back for part 2 43:00 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO Disclosures: Brown reports no relevant financial disclosures. Calabrese reports serving as an investigator and a consultant to Horizon Pharmaceuticals. Leonard H. Calabrese, DO, is chief medical editor of Healio Rheumatology and director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

Join Peter Grayson, MD, MSc, and I as we discuss a range of topics, including imaging in large-vessel vasculitis, doctors going into research, Twitter, rock ‘n’ roll and Disney World. Intro :10 A bit about Peter Grayson :55 Come see me in Phoenix in February 3:35 The interview 4:07 How did you make it to the NIH? 4:27 Why do you think MDs aren’t going into research these days 6:45 Social media and major meetings 9:43 Tell us about the NIH rock ‘n’ roll band 11:10 What imaging modalities are most used for large-vessel vasculitis? 13:32 What is PET scan? 14:23 Do you think PET scanning is the best imaging modality? 15:29 What are the limitations to PET? 17:48 Does vessel size affect PET scanning? 20:01 Are these machines available in most hospitals? 21:12 Grayson’s secret sauce 22:27 How do glucocorticoids affect imaging? 23:19 Are you ever using PET as follow-up? 25:07 Do you have hope for any specific targets for Takayasu’s arteritis? 27:12 What drives the surgical intervention process for these patients? 28:23 Collateral artery formation 30:30 Where do you think Takayasu’s will be in 10 years? 31:35 Thank you, Dr. Grayson 33:36 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum Disclosures: Brown and Grayson report no relevant financial disclosures. Peter Grayson, MD, MSc, is head of the Vasculitis Translational Research Program at National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and associate director of the NIAMS Fellowship Program, Systemic Autoimmunity Branch.