Discussion in 'BioMedical ME/CFS Research' started by John Mac, Dec 6, 2018.
Such consistency is rare in ME/CFS studies. Encouraging.
I also like how this study talks about "victims of ME/CFS" and "Its constellation of symptoms has silently ruined the lives of millions of people around the world."
There will be no mistakes in Maureen's work, she is as thorough as they come imo.
If M.E is a metabolic disease, are there any other metabolic diseases caused by a perturbed immune system whose treatments might benefit us? Again, I hope my question makes sense?@Jonathan Edwards @alex3619 or anyone else!!
The authors seem happy that the results of their work are consistent with the results from previous ME/CFS metabolomic studies. So that's good.
But the differences between patients and controls in the nine molecules that they have picked out from their very large survey (more than 800 molecules) look depressingly small to me. There's such a lot of overlap in the ranges.
Is it possible that the variability in a single patients' metabolomics over time is so great that differences between patients and controls are going to be largely obscured? Do the patients actually need to be experiencing PEM in order to show clear differences?
Maybe we need metabolomics analyses done for these nine molecules on a set of patients every day for a month, with the first half of the month spent resting and the second half of the month spent being as active as possible, with the results correlated with symptoms.
Not a criticism (the study is what it is) but we need much bigger numbers of study participants before we know if there is anything significant here or not.
I am probably being incredibly stupid, not having much biochemistry, but to me small differences are not the issue. Given the common nature of expression , surely in a system s condition it is not the individual difference s, but the cumulative effect of them that is as important?
How do these differences affect rate limited processes/ signalling when combined.
What is their impact on reactions downstream ?
Would low blood volume impact the functional capabilities of any of these small differences?
Even with the biomarker papers from this week, the Activin B/Acitvin A ratio still seems the most realistic if it were replicated. https://www.s4me.info/threads/serum-activin-b.6951/
That was my feeling too. It doesn't seem realistic to talk of these metabolites as biomarkers when there is so much overlap with healthy controls, unless perhaps the pattern of all 9 metabolites taken together can clearly discriminate between groups. I would imagine that a next step would be to do a focused test of the 9 metabolites in much much bigger samples of pwME and healthy controls and people with other chronic health conditions.
Perhaps, rather than trying to call these potential biomarkers, it might be more useful to look closely at the biochemical pathways they are involved in and combine it with the genetic indications coming from other studies to try to home in on what exactly is going wrong so drugs can be targeted for treatments. I'm hoping some very clever biochemists are looking into this.
Noddy question about Biomarkers - based on metabolites is there actually going to be something that always distinguishes correctly between people that have ME and those who don’t. If it is something everyone should have in their blood isnt it likely there will be an overlap.
AUC of ~0.75 is interesting, but quite poor as far as biomarkers go. On the other hand, I'm glad they did this analysis - it should be mandatory for anyone doing a study on prospective biomarkers.
I think with a lot of diseases there is a pattern of things wrong before they home in on a biomarker or diagnostic test. Even when I was pregnant in 1976, an elderly doctor said to me that if a woman thought she was pregnant there was a good chance she was. 20 years ago MS was diagnosed by a pattern of responses and symptoms and migraine still has no test.
Though I agree that the real value of these results is that they are a map to what is going wrong for us at a basic level.
If you wanted to convince a medical sceptic, which metabolomics paper would you use?
ME Association summary of this paper, https://www.meassociation.org.uk/20...s-implicate-redox-imbalance-02-february-2019/
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