Healio Rheuminations

• The Tumultuous Tale of Th17-and the IL23/IL17 immune axis

  In this episode, we dive into a two-part story of intrigue starting from a paradigm shift in understanding of T cell biology because of a mouse model of post-measles encephalopathy, to the eventual recognition of the IL-23/17 immune axis. •    Intro 0:01 •    In this episode 0:12  •    Interleukin-17 (IL-17) is a relatively recent discovery 1:34 •    The beginning of TH-17 2:20 •    Looking at autoimmune encephalopathy: A story of measles 03:30 •    1790’s woman with post measles inflammatory process in the brain 10:26 •    What is causing post-infection encephalitis? 12:00 •    Acute disseminated encephalomyelitis 12:30 •    How did we find out the immune system was behind this - The rabies vaccine 13:09 •    Similarity between the rabies vaccine and infections like measles 16:04 •    T-cell lymphocytes 17:12 •    The forgotten thymus 18:00 •    What’s the function of T-cells? 19:35 •    How do you tell T-cells apart? 21:14 •    The Human Leukocyte Differentiation Antigens Party 24:05 •    The godfather of T-cells 24:45 •    The TH-1 and TH-2 axis 27:30 •    Experimental Autoimmune Encephalomyelitis model screwed everything up 29:16 •    Interferon gamma 32:32 •    What’s missing? IL-23 surprise 33:40 •    IL-17 in the 1990’s 36:44 •    The world is introduced to TH-17 39:12 •    Let’s recap what we learned 40:30 •    That is the end! 42:30 •    Thanks for listening 42:39 We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Bashyam H. J Exp Med. 2007;doi:10.1084/jem.2042fta Bennetto L, et al. J Neurol Neurosurg Psychiatry. 2004;doi:10.1136/jnnp.2003.034256 Berche P. Presse Med. 2022;doi:10.1016/j.lpm.2022.104149 El-behi M, et al. J Neuroimmune Pharmacol. 2010;doi:10.1007/s11481-009-9188-9 Gooderham MJ, et al. J Eur Acad Dermatol Venereol. 2018;doi:10.1111/jdv.14868 Hawkes JE, et al. J Immunol. 2018;doi:10.4049/jimmunol.1800013 Rogozynski N, et al. Immunol Lett. 2024;doi:10.1016/j.imlet.2024.106870 Sospedra M, et al. Annu Rev Immunol. 2005;doi:10.1146/annurev.immunol.23.021704.115707 Steinman L. Nat Med. 2007;doi:10.1038/nm1551 Disclosures: Brown reports no relevant financial disclosures.

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• History of polymyalgia rheumatica: The origin of the pain & link to giant cell arteritis

  In this episode, we dive into the history of polymyalgia rheumatica, how it was discovered and its link to giant cell arteritis. Intro 0:01 In this episode 0:10 What is polymyalgia rheumatica (PMR)? 0:24 The history of PMR 02:12 PMR in the 1950s: A formally recognized disease 04:52 What was probably PMR in the 1880s 06:27 Naming PMR: Senile rheumatic gout 07:26 1957: The witch’s shot and finally landing on polymyalgia rheumatica 08:30 Where is PMR coming from? 14:42 Injecting joins with saline 16:39 A biopsy study in 1964 19:54 Technetium bone scintigraphy in 1971 and bone scan history 23:01 First look at a PMR ultrasound in 1993 27:00 1997: First use of MRI on PMR patients in Italy 27:49 Going back to 1962: PMRs association with giant cell arteritis 30:40 A paper on muscular involvement in giant cell arteritis: 80-year-old ‘robust’ partially blind seaman 32:15 First systematic approach: The link between PMR and giant cell arteritis 35:14 80 cases of PMR 38:13 Swedish autopsy studies 41:07 Introduction of advanced imaging in the 1990s 42:40 Summing up PMR through the decades 43:28 That is the end! 45:25 Thanks for listening 45:50 We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Bruk MI. Ann Rheum Dis. 1967;doi:10.1136/ard.26.2.103. Cantini F, et al. J Rheumatol. 2001;28(5):1049-55. De Miguel E, et al. Rheumatology (Oxford). 2024;doi:10.1093/rheumatology/kead189. Dixon AS, et al. Ann Rheum Dis. 1966;doi:10.1136/ard.25.3.203. Hamrin B, et al. Ann Rheum Dis. 1968;doi:10.1136/ard.27.5.397. Salvarani C, et al. Ann Intern Med. 1997;doi:10.7326/0003-4819-127-1-199707010-00005. Shah S, et al. Rheumatology (Oxford). 2025;doi:10.1093/rheumatology/keae569. Disclosures: Brown reports no relevant financial disclosures.

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• Pulmonary hypertension, part 4: The therapeutics, with Dr. Joseph Parambil

  In the final part of this series, Joseph Parambil, MD, walks us through the approach of managing pulmonary hypertension, reviews the pathophysiology and digs into the mechanisms and the differences in the medications. Intro 0:12 In this episode 0:17 Interview with Joseph Parambil, MD 2:53 Reviewing and clarifying pathophysiology prior to initiating therapeutics 4:13 Evaluating patients in terms of their functional status and how does that play a role in initiating therapies 4:25 Vasoreactivity testing 10:21 The categories of medications 14:40 Endothelin receptor antagonists 37:07 TGF pathway 42:13 Scleroderma patient and treatment 50:19 Do patients get a repeat right-heart catheterization? 55:51 What about the TGF-beta? 56:55 Thank you, Dr. Parambil 58:34 Thanks for listening 59:17 We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. Disclosures: Brown and Parambil report no relevant financial disclosures. Joseph Parambil, MD, is a staff member in the Respiratory Institute and the director of the HHT Center of Excellence and the Vascular Anomalies Center at the Cleveland Clinic. He is associate professor of medicine at Cleveland Clinic’s Lerner College of Medicine. He is certified by the American Board of Internal Medicine with additional specialty certification in pulmonary medicine and critical care medicine.

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• Pulmonary hypertension, part 3: Early therapies and vascular physiology

  In this episode, we dive into the early therapies and how our understanding of vascular physiology drastically changed the management of pulmonary hypertension. Intro 0:12 In this episode 0:18 Recap of part 1 & 2 0:31 What part 3 is about 2:31 WHO conference in 1975: Treating pulmonary hypertension 3:48 The Discovery of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), Part 1 5:20 Epoprostenol 6:18 Prostacyclin 10:37 Endothelin antagonists 11:41 Phosphodiesterase type 5 (PDE5) inhibitors 14:08 Interaction of nerves and blood vessels 15:06 The Soups VS the Sparks 17:36 A dreamed experiment 19:06 Acetylcholine 23:23  Enter “the calabar bean” 24:45 Acetylcholine and vasodilation: 1976 26:01 Rabbit aorta 27:45 Nitric oxide 29:38 Why are we using nitric oxide to treat pulmonary hypertension? 31:31 Tachyphylaxis 33:48 TNT factories 35:09 Nitrous oxide and tachyphylaxis 36:52 Pfizer in the 1980s 38:06 Understanding the trigger of pulmonary hypertension 40:53 PDE5 and nitric oxide and pulmonary hypertension 43:07 The end of the ripping yarns 44:20 Coming up in part 4 46:17 Thanks for listening 47:29 We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Bernard C. C R Soc Biol. 1851;3:163-164. Furchgott RF, et al. Nature. 1980;doi:10.1038/288373a0. Galiè N, et al. N Engl J Med. 2005;doi:10.1056/NEJMoa050010. Ghofrani HA, et al. Nat Rev Drug Discov. 2006;doi:10.1038/nrd2030. Giordano D, et al. Biochim Biophys Acta. 2001;doi:10.1016/s0167-4889(01)00086-6. Guthrie F. Q J Chem Soc. 1859;doi:10.1039/QJ8591100245. Higenbottam T, et al. Lancet. 1984;doi:10.1016/s0140-6736(84)91452-1. Marsh N, et al. Clin Exp Pharmacol Physiol. 2000;doi:10.1046/j.1440-1681.2000.03240.x. Montastruc JL, et al. Clin Auton Res. 1996;doi:10.1007/BF02281906. Nejad SH, et al. Future Cardiol. 2024;doi:10.1080/14796678.2024.2367390. Tansey EM. C R Biol. 2006;doi:10.10116/j.crvi.2006.03.012. Warren JV. Trans Am Clin Climatol Assoc. 1988;99:10-6. Disclosures: Brown reports no relevant financial disclosures.

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• Pulmonary hypertension and the rheumatologist, part 2: The history

  In part 2, we dig into the history of pulmonary hypertension. How did this strange diagnosis first get recognized, what does it have to do with cows with thick necks and urinary catheters in the heart? Intro 0:11 In this episode 0:17 Recap of part 1 0:26 How was pulmonary hypertension discovered? 2:38 1891 3:51 1901 5:07 1935 7:02 Hilar dance 12:58 Cardiac catheterization: 1929 15:03 When did cardiac catheterization become relevant? 20:10 1965: Aminorex 24:40 World Health Organization: 1975 26:37 1980s: toxic oil syndrome of Spain 28:20 Preview of part 3 33:15  Back to cardiac catheterization 34:08 Briskets disease 35:45 1947 37:56 Pulmonary physiology and prostaglandin therapies (in the next episode) 38:41 Schistosomiasis outbreaks in Egypt 1938 40:26 Chronic thromboembolism 45:03 Thanks for listening 48:16 We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Barst RJ. Ann Thorac Med. 2008;doi:10.4103/1817-1737.37832. Bodo R. J Physiol. 1928;doi:10.1113/jphysiol.1928.sp002447. Dresdale DT, et al. Am J Med. 1951;doi:10.1016/0002-9343(51)90020-4. Egypt. Stanford.edu. Published 2015. https://schisto.stanford.edu/pdf/Egypt.pdf. Hewes JL, et al. Pulm Circ. 2020;doi:10.1177/2045894019892801. Johnson S, et al. Am J Respir Crit Care Med. 2023;doi:10.1164/rccm.202302-0327SO. Newman JH. Am J Respir Crit Care Med. 2005;doi:10.1164/rccm.200505-684OE. Weir EK, et al. Circulation. 1996;doi:10.1161/01.cir.94.9.2216. Disclosures: Brown reports no relevant financial disclosures.

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