Healio Rheuminations

It's that time of year again, everyone rolling up their sleeves to get a flu shot. This throwback episode dives into the history of the struggles pinning down the causative agent of flu and the journey to the vaccine!

• Intro 0:40
• In this episode 1:11
• The history of the flu: 1892 1:41
• What do we know about viruses? 6:29 
• Rabies and dead virus 11:17
• A Sickness in the Serum, Part 2 14:43
• 1918 16:44
• Vaccines and trials 19:13
• Pig influenza 23:12
• Influenza: a filterable agent we can’t see 27:01
• The trials of 1942 33:02
• PS: 1918 influenza 38:57
• Thanks for listening 47:42

Disclosures: Brown reports no relevant financial disclosures.

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:

Hicks DJ, et al. Clin Exp Immunol. 2012;doi:10.1111/j.1365-2249.2012.04592.x.

Rosenau MJ. Experiments Upon Volunteers to Determine the Cause and Mode of Spread of Influenza, Boston, November and December, 1918. https://quod.lib.umich.edu/f/flu/3750flu.0016.573. Published February 1921. Accessed December 6, 2023.

Rosenau MJ, et al. JAMA. 1925;doi:10.1001/jama.1925.02670070040019.

Taubenberger JK, et al. Antivir Ther. 2007;12(4 Pt B):581-91.

Tobin J. The first flu shot. https://heritage.umich.edu/stories/the-first-flu-shot/. Accessed December 6, 2023.

In the third episode of the NSAIDs saga, we focus on COX-2 inhibition! Did the hopes and dreams of selective COX-2 inhibition pan out? What can the rise and fall of VIOXX teach us about physiology?

• Intro 0:11
• Recap of part 1 & 2 0:28
• In this episode 1:44
• Cyclooxygenase 2 (COX-2) and the rat experiment 3:12
• What do we know about the prostaglandins? And what about COX-2 7:54
• What does prostacyclin do? 10:33
• The first COX-2 inhibitor: VIOXX 10:56
• What is COX-2 doing?: Pfizer and Merck 12:15
• Two more NSAID studies: colon cancer, Alzheimer’s disease and COX-2 inhibitors 18:41
• VIOXX: Why is myocardial infarction risk occurring? 22:34
• Animal models and the Goldilocks theory of thromboxane and prostacyclin 23:49
• PRECISION trial 30:25
• Rheum + Boards 37:14 
• Thanks for listening 37:32

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:

Anderson GD, et al. J Clin Invest. 1996;doi:10.1172/JCI118717.

Funk CD, et al. J Cardiovasc Pharmacol. 2007;doi:10.1097/FJC.0b013e318157f72d.

Hennan JK, et al. Circulation. 2001;doi:10.1161/hc3301.092790.

Krumholz HM, et al. BMJ. 2007;doi:10.1136/bmj.39024.487720.68.

Nissen SE, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1611593.

Disclosures: Brown reports no relevant financial disclosures.

In this episode, we dive into the story of aspirin and the development of ibuprofen, ending with the experiments that showed the mechanism of how aspirin actually works.

• Intro 0:12
• Review of part 1 0:28
• In this episode 1:04
• Blocking prostaglandins and willow leaves 2:26
• Edward Stone 3:45
• Johann Andreas Buchner 4:16
• The chemical structure of salicylic acid and creating the synthetic compound 4:44
• Dr. TJ MacLagan: The first trial in 1876 and treating acute rheumatism 5:16
• Felix Hoffmann: manipulating salicylic acid and aspirin 8:47
• How widespread was the use of aspirin for rheumatoid arthritis? 12:04
• 1938: problems with aspirin and endoscopies 14:58
• 1950s: long-term use of aspirin and chronic renal impairment 17:12
• Dr. Lawrence Craven: the use of aspirin to treat myocardial infarction 18:13
• Overview of what we’ve learned so far 20:48
• Stewart Adams: the development of ibuprofen 21:40
• A paper lost to time 23:29
• How do you test if a drug is anti-inflammatory? 25:25
• How do you make better aspirin? 26:55
• 1960: a trial comparing ibuprofen, baby aspirin and prednisone in patients with rheumatoid arthritis 30:03
• Aspirin, ibuprofen and other NSAIDs 32:49
• Nobel Prize winner Dr. John Vane 33:40
• Dr. Vane: what triggered prostaglandin production? 35:42
• Another guinea pig experiment 37:37
• Nobel Prize winner Dr. Bengt Samuelsson 39:00
• Interesting tidbits: early studies looking at the side effects of NSAIDs 40:01
• 1968: gastric ulcer formation and prostaglandins in rats 40:25
• 1973: renal blood flow and prostaglandins in dogs 41:53
• 1974: aspirin vs ibuprofen vs indomethacin for the heart 44:03
• Aspirin vs ibuprofen vs indomethacin 44:20
• On the next episode 46:09
• Thanks for listening 46:37

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:

Adams SS. Inflammopharmacology. 1999;doi:10.1007/s10787-999-0002-3.

https://www.aspirin-foundation.com/history/the-aspirin-story/.

Buchanan WW, et al. J Rheumatol. 2002;29(6):1321-3.

Cryer B, et al. Gastroenterology. 1999;doi:10.1016/s0016-5085(99)70545-7.

Desborough MJR, et al. Br J Haematol. 2017;doi:10.1111/bjh.14520.

Halford GM, et al. Platelets. 2012;doi:10.3109/09537104.2011.632032.

Harris SC, Fosdick LS. Theoretical considerations of the mechanisms of antipyretic analgesia. NWU Bull. 1952;53: 6–9.

Jasani MK, et al. Ann Rheum Dis. 1968;doi:10.1136/ard.27.5.457.

Robert A, et al. Gastroenterology. 1968;55(4):481-7.

Disclosures: Brown reports no relevant financial disclosures.

Humans have had an insatiable appetite for inhibiting production of prostaglandins for centuries! This series delves into the history of aspirin and NSAIDs, looking at the understanding of the prostaglandin pathway.

·       Intro 0:12

·       In this episode 0:23

·       What are NSAIDs? 0:53

·       Prostaglandins 5:50

·       What are prostaglandins? 7:19

·       Where do prostaglandins come from? 8:45

·       So, what do we do with prostaglandins? 13:15

·       How did they figure out prostaglandins? 13:55

·       Naming the prostaglandin 21:25

·       Phospholipids 24:46

·       Arachidonic acid 25:28

·       Arachidonic acid into prostaglandins: how do you prove it? 26:32

·       How does arachidonic acid turn into prostaglandins? 27:27

·       Cyclo-oxygenase 28:36

·       mRNA and COX-2 32:50

·       On the next episode 35:55

·       Summary 36:38

·       Thanks for listening 37:49

Disclosures: Brown reports no relevant financial disclosures.

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:

Botting RM. Pharmacol Rep. 2010;doi:10.1016/s1734-1140(10)70308-x.

Flower RJ. Br J Pharmacol. 2006;doi:10.1038/sj.bjp.0706506.

Flower RJ. Br J Pharmacol. 2019;doi:10.1111/bph.14588.

Kurzrok R, et al. Exp Biol Med. 1930;doi:10.3181/00379727-28-5265.

https://www.nobelprize.org/prizes/medicine/1970/euler/biographical/.

von Euler US. J Physiol. 1936;doi:10.1113/jphysiol.1936.sp003433.

This episode digs into the pathophysiology of urticaria vasculitis from anti-C1q to the story of bradykinin.

·       Intro 0:11

·       In this episode 0:22

·       Review of episode 83 1:23

·       Listen to previous episode, The Complement System for Dunces 4:09

·       Anti-C1q antibodies 6:26

·       Lupus, anti-C1q and lupus nephritis 9:33

·       What happens when you inject anti-C1q in a mouse? 12:56

·       The allergy component: anti-C1q, urticaria and angioedema 17:36

·       Bradykinin-mediated angioedema and C1q deficiency 24:20

·       What is the kinin kallikrein system? 26:21

·       French researchers in 1909: human urine injected in dogs 27:30

·       How is this relevant to urticarial vasculitis? 31:08

·       SERPING1 gene mutation 31:23

·       Summary 32:06

·       COPD association with urticarial vasculitis 33:51

·       Coming up in episode 85 35:28

·       Thanks for listening 35:45

Disclosures: Brown reports no relevant financial disclosures.

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:

Busse P, et al. J Allergy Clin Immunol Pract. 2022;doi:10.1016/j.jaip.2021.11.011.

Davis MDP, et al. J Allergy Clin Immunol Pract. 2018;doi:10.1016/j.jaip.2018.05.006.

Dorn JM, et al. Ann Allergy Asthma Immunol. 2023;doi:10.1016/j.anai.2023.06.014.

Marzano AV, et al. J Allergy Clin Immunol. 2022;doi:10.1016/j.jaci.2022.02.007.

Siegert CE, et al. Clin Immunol Immunopathol. 1993;doi:10.1006/clin.1993.1066.

Stojan G, et al. Lupus. 2016;doi:10.1177/0961203316645205.

Venzor J, et al. Clin Rev Allergy Immunol. 2002;doi:10.1385/CRIAI:23:2:201.

Wisnieski JJ, et al. Medicine. 1995;doi:10.1097/00005792-199501000-00003.

Is it an allergy or an autoimmune vasculitis, or a little of both? Find out the story of urticarial vasculitis, how this disease was recognized and eventually sorted out from other types of urticaria.

·       Intro 0:12

·       In this episode 0:21

·       Case study 1:22

·       Chronic spontaneous urticaria, hives and nettles 7:57

·       Dermatographism and witchcraft? 10:15

·       Causes of urticaria 11:17

·       Theory of inflammation and histamines 11:40

·       Urticaria and treatments with histamines 12:09

·       Types of urticaria 13:02

·       Mayo Clinic study 13:39

·       Chronic urticaria as a manifestation of necrotizing venulitis 16:10

·       Connection between types of urticaria and leukocytoclastic vasculitis 20:02

·       More case studies 20:38

·       What do we know about treatments? 22:23

·       In conclusion 24:15

·       Coming up in part two 25:08

·       Thanks for listening 25:47

Disclosures: Brown reports no relevant financial disclosures.

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:

Czarnetzki BM. Int J Dermatol. 1989;doi:10.1111/j.1365-4362.1989.tb01314.x.

Kolkhir P, et al. J Allergy Clin Immunol. 2019;doi:10.1016/j.jaci.2018.09.007.

McDuffie FC, et al. Mayo Clin Proc. 1973;48(5):340-8.

Natbony SF, et al. J Allergy Clin Immunol. 1983;doi:10.1016/0091-6749(83)90096-9.

Soter NA. N Engl J Med. 1977;doi:10.1056/NEJM197706232962505.

What should rheumatologists know about what we've learned about COVID-19 and long COVID in 2023? Hosted by Dr. Leonard Calabrese.

·       Intro 0:11

·       In this episode 0:21

·       2023: current status and controversies 0:35

·       What is going on with COVID-19? 01:53

·       What do we know about vaccine responses? What should we be telling our patients about vaccines in our immunocompromised population? 2:58

·       Lancet Rheumatology MELODY study summary 3:08

·       What about patients within the rheumatic and autoimmune disease space? 4:15

·       Who is immunocompromised and why does it matter? 5:11

·       What is the immunosuppression we are giving them? 6:39

·       What to tell patients about getting vaccinated 8:56

·       Long COVID 10:09

·       What is long COVID? 10:26

·       JAMA Network Open study on prevalence and characteristics associated with post-COVID conditions 14:19

·       In the clinical arena, what should rheumatologists be thinking about? 16:38

·       What about pathogenesis? What do we know about the controversies in this area? 18:58

·       Autoimmunity: COVID-19 and autoimmune response 20:45

·       What about therapies? 22:22

·       The next generation of rheum agents: Immunomodulation with neonatal Fc receptor targeting? 24:40

·       A question for the rheumatology community: do patients with immune mediated diseases get more long COVID than the control population? 25:40

·       In conclusion 27:37

·       Thanks for listening 28:38

Leonard H. Calabrese, DO, is the chief medical editor, Healio Rheumatology, and professor of medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic.

Disclosures: Calabrese reports professional relationships with AbbVie, AstraZeneca, Bristol Myers Squibb, Galvani, Genentech, GlaxoSmithKline, Janssen, Novartis, Regeneron, Sanofi and UCB..

We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

It's that time of year again, everyone rolling up their sleeves to get a flu shot. This episode dives into the history of the struggles pinning down the causative agent of flu and the journey to the vaccine!

·       Intro 0:12

·       In this episode 0:17

·       The history of the flu: 1892 3:10

·       Rabies and dead virus 10:52

·       A Sickness in the Serum, Part 2 14:31

·       Vaccines and trials 19:13

·       Pig influenza 23:21

·       Influenza: a filterable agent we can’t see 27:10

·       The trials of 1942 33:18

·       PS: 1918 influenza 39:13

·       Finding the 1918 influenza vaccine 39:54

·       Thanks for listening 47:54

Disclosures: Brown reports no relevant financial disclosures.

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:

Hicks DJ, et al. Clin Exp Immunol. 2012;doi:10.1111/j.1365-2249.2012.04592.x.

Rosenau MJ. Experiments Upon Volunteers to Determine the Cause and Mode of Spread of Influenza, Boston, November and December, 1918. https://quod.lib.umich.edu/f/flu/3750flu.0016.573. Published February 1921. Accessed December 6, 2023.

Rosenau MJ, et al. JAMA. 1925;doi:10.1001/jama.1925.02670070040019.

Taubenberger JK, et al. Antivir Ther. 2007;12(4 Pt B):581-91.

Tobin J. The first flu shot. https://heritage.umich.edu/stories/the-first-flu-shot/. Accessed December 6, 2023.

What is silica? How does it impact your risk of developing autoimmunity if you inhale it, inject it or even snort it up your nose? Listen and find out!

·       Intro 0:12

·       In the previous episodes 0:28

·       The Ajax incident of 1979 1:15

·       Silica and its association with autoimmune disease 4:11

·       The history of silica and the health risks 5:21

·       Rheumatoid scleroderma, etc. 8:14

·       Cardiff pneumoconiosis medical panel 9:49

·       Databases 12:51

·       Silica exposure and the development of serologies 15:02

·       What would happen if you injected silica into the veins? 16:51

·       Anca vasculitis 18:33

·       Thanks for listening 23:23

Disclosures: Brown reports no relevant financial disclosures.

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:

Blanc PD, et al. Am J Med. 2015;doi:10.1016/j.amjmed.2015.05.001.

Boudigaard SH, et al. Int J Epidemiol. 2021;doi:10.1093/ije/dyaa287.

Conrad K, et al. Lupus. 1996;doi:10.1177/096120339600500112.

Hoy RF, et al. Allergy. 2020;doi:10.111/all.14202.

Klockars M, et al. Br Med J (Clin Res Ed). 1987;doi:10.1136/bmj.294.6578.997.

Park CG, et al. Environ Health Perspect. 1999;doi:10.1289/ehp.99107s5793.

Pollard KM. Front Immunol. 2016;doi:10.3389/fimmu.2016.00097.  

In this episode, we dig through the data of lupus in Africa and speak with experts on the Lupus Gradient, the impact of malaria and what we can learn from it all.

·       Intro 0:12

·       In the previous episode 0:30

·       Lupus Gradient 2:01

·       Back to Dr. Brian Greenwood 3:48

·       Polyarthritis 4:04

·       Rates of autoimmune diseases 6:00

·       Malaria and mouse models 7:33

·       Back to lupus 8:48

·       First case of lupus 15:14

·       Prevalence of lupus 17:15

·       Papers on lupus 21:23

·       Dr. Mickael Essouma 23:38

·       Dr. Essouma, how did you conduct this study? 24:01

·       Did you ever believe there was a gradient? 26:09

·       Dr. Sandro Vento 30:56

·       Dr. Vento, do you believe there was a lupus gradient? 31:51

·       What are the connections to infectious disease? 38:51

·       That’s a wrap! 43:04

·       Coming up in part 4 44:55

·       Thanks for listening 45:05

Disclosures: Brown reports no relevant financial disclosures. Healio could not confirm relevant financial disclosures for Essouma and Vento at the time of posting.

Mickael Essouma, MD, is physician from Cameroon specialized in internal medicine at the University of Yaounde I in Cameroon, with a complimentary certificate on rheumatology from the EULAR online course and a certificate on lupus from the European Lupus Society (SLEuro). He is an advocate of lupus and other autoimmune diseases in Africans.

Sandro Vento, MD, is the dean of faculty of medicine at the University of Puthisastra, Phnom Penh, Cambodia and a consultant and collaborating specialist at Mayo Clinic Center for Tuberculosis, WHO Collaborating Center.

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:

Bae SC, et al. Arthritis Rheum. 1998;doi:10.1002/1529-0131(199812)41:123.0.CO;2-D.

Bryc K, et al. Am J Hum Genet. 2015;doi:10.1016/j.ajhg.2014.11.010.

Essouma M, et al. J Autoimmun. 2020;doi:10.1016/j.jaut.2019.102348.

Gilkeson GS, et al. Lupus. 2011;doi:10.1177/0961203311404915.

Micheletti SJ, et al. Am J Hum Genet. 2020;doi:10.1016/j.ajhg.2020.06.012.

Symmons DP. Lupus. 1995;doi:10.1177/096120339500400303.

Vento S, et al. Front Med. 2020;doi:10.3389/fmed.2020.00202.