Day 2 :
Ocean Springs Hospital Singing River Health System, USA
Matthew B. Carroll is a board-certified Rheumatologist who is clinically active and currently employed by the Singing River Health System. He has had a passion for clinical research and has been an active member of the growing research team at his community hospital. He retired from the United States Air Force in 2017 but during his active duty service developed over 15 protocols and has published over 20 articles. A recent passion has been exploring the possible beneficial role of an IL-6 blockade on acute myocardial infarction. He launched an ambitious protocol studying the short-term effects on major adverse cardiac events which though it was eventually ended after futility analysis suggested no benefit, did enroll over 20 subjects and provided 180-day follow-up of data collection. He continues to actively lobby the study of an IL-6 blockade in other areas of Cardiology.
Statement of the Problem: Tocilizumab (TCZ) is an important biologic response modifier that Rheumatologists routinely employ in the treatment of several systemic autoimmune diseases. TCZ binds to interleukin (IL)-6 receptors, inhibits cellular activation, and mitigates inflammation by IL-6. In mid-2017 TCZ was approved by the U.S. Food and Drug Administration for its first non-rheumatologic condition, the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in patients 2 years of age or older. With this approval and with the increasing use of TCZ off-label for other nonrheumatologic conditions such as Castleman’s Disease and its variant TAFRO syndrome, where else might TCZ be successfully utilized as treatment? Recently interesting data has been published regarding the possible use of TCZ in the treatment of myocardial infarction. This review will focus on the role of IL-6 and it’s receptor in myocardial inflammation and association with adverse clinical outcomes. Discussed are results from one animal study and two human trials have been published that studied the effect of TCZ in patients with acute myocardial infarction. Finally, this review summarizes the current data and makes recommendations for future clinical trial development in what hopefully will be a promising application of TCZ for a serious non-rheumatologic condition.
Galea Professional Medical Inc., Canada
Anthony Galea practices sport medicine in Toronto and is considered one of the pioneers in the uses and applications of platelet rich plasma in musculoskeletal disorders. He has functioned as a sport physician for many professional and Olympic competitions and his clients includes some of the worlds best athletes. He is also an author and researcher, his current research focuses on autologous cytokines for the treatment of osteoarthritis. He is married with seven children.
Statement of the Problem: Osteoarthritis (OA) is degenerative joint disease characterized by cartilage damage and synovial inflammation. Autologous blood-derived products target special inflammatory molecular pathways and have a beneficial therapeutic effect for inflammatory pathologies. The purpose of this study was to assess the in vitro and in vivo anti-inflammatory/catabolic and regenerative potential of a novel autologous blood product (Cytorich).
Materials and methods: Blood samples from healthy donors were incubated using different techniques for 24h and analyzed for the presence of anti-inflammatory (IL-1ra), anti-catabolic (tissue inhibitors of metalloproteinases, TIMPs), regenerative, pro-inflammatory (TNF-α, IL-1) and catabolic (matrix metalloproteinases, MMPs) molecules. Double-blinded controlled clinical study was conducted to evaluate clinical effectiveness and safety of the final product using VAS and WOMAC scales.
Results: The highest concentration of therapeutic molecules targeting inflammatory and degeneration pathways in OA, as well as platelet-derived growth factor, was found in 24h 37C incubated blood. However, the increased production of catabolic MMP9 and TNF-α and IL-1 was detected in the product. We have found that this negative effect could be blocked by adding citric acid making future OA treatment more safe and effective. Double-blinded controlled clinical study has shown a safety and efficiency of this new product. The analysis of WOMAC and VAS scores revealed improvement in pain and daily activities parameters.
Conclusion & Significance: Cytorich is an efficient and safe autologous product for OA treatment since it has been reported a a source of human bioactive molecules playing a key role in the fundamental processes stimulating tissue repair and regeneration.