Research Research Digest Research Digest 5/04/19 Welcome to the 20th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles. You can also join our community and choose to have the Digest delivered straight to your inbox every fortnight on a Friday afternoon by signing up at the bottom of this page. We appreciate the support of everyone who reads the Digest – we encourage regular subscribers to support us with a monthly suggested donation of $2. You can sign up for monthly giving here. Chronotropic intolerance: an overlooked determinant of symptoms and activity limitation in myalgic encephalomyelitis/chronic fatigue syndrome? Authors: Davenport TE, Lehnen M, Stevens SR, et al. Link: https://www.frontiersin.org/articles/10.3389/fped.2019.00082/full Chronotropic intolerance (CI) is the heart’s inability to increase its rate in line with an increase in activity. The relationship between heart rate and workload is highly predictable, and is a good indicator of the level of physical exertion for both healthy people and those with chronic illnesses. The authors of this review have analysed multiple studies that have shown people with ME/CFS have CI and reduced maximal heart rate (MHR). The severity of CI also correlates with the severity of ME/CFS with more severe patients exhibiting lower MHR. Further, due to CI, ME/CFS patients with lower MHR may be classified as working at submaximal rates during testing, when in fact they may be performing at super-maximal levels, which can represent a clear risk to the individual. The review recommends that pacing self-management plans, based on age-predicted heart rates, should be viewed with caution due to the presence of CI, and more research should be done to establish a healthy MHR for people with ME/CFS to ensure safe management plans. Myalgic encephalomyelitis or chronic fatigue syndrome: How could the illness develop? Authors: Morris G, Maes M, Berk M, Puri BK. Link: https://link.springer.com/article/10.1007%2Fs11011-019-0388-6?fbclid=IwAR0ZtmpxfgcS8LiZfZc78HEZ29Nkvt0WAW4hhvgtrvq4T02qPq7WAuA-saU This paper theorises that the development of ME/CFS could occur when a patient develops chronic inflammation due to an infection. It is proposed that ME/CFS patients experience oxidative and nitrosative stress. This stress is prolonged by damage-associated molecular patterns (DAMPs), which are biomolecules that extend non-infectious inflammatory responses within the body. The stress eventually leads to intestinal permeability, translocation of antigens (a substance which triggers an immune response) into circulation, and the development of dysfunction of the autonomous systems, neuroinflammation, and neurocognitive abnormalities. ME/CFS patients have exhibited both pro- and anti-inflammatory patterns. This can be explained by the different stages of the illness, since the theory hypothesises that patients initially have a pro-inflammatory phase, which eventually triggers anti-inflammatory systems within the body. B-lymphocyte depletion in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A randomised, double-blind, placebo-controlled trial Author: Fluge Ø, Rekeland IG, Lien K, et al. Link: https://annals.org/aim/article-abstract/2729813/b-lymphocyte-depletion-patients-myalgic-encephalomyelitis-chronic-fatigue-syndrome-randomized Study results from the RituxME trial showed no effects for ME/CFS patients. Rituximab is a drug used to treat certain autoimmune diseases and types of cancer. The trial involved 151 patients, aged 18 to 65 years of age, who have had ME/CFS from between two to 15 years. Participants were randomly allocated to the rituximab or placebo group. Participants were given doses over a 12-month period and, when compared to the placebo control group, showed no improvement. The trial results could, however, assist in future research for treatments and symptom mechanisms. The ME Show with Gary Burgess Link: https://www.meassociation.org.uk/themeshow/ In the final episode of season two, Gary Burgess interviews Australian medical researcher Dr Mark Guthridge, who has lived with M.E. since 2015. Mark now devotes much of his time to promoting awareness and understanding of M.E. and is about to begin a new research project, which could lead to a diagnostic test. Mark also chats about the recent Emerge Australia ME/CFS International Research Symposium.