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OMF: Muscle Biopsy and Plasma Study into Post-Exertional Malaise, David Systrom, 2022

Discussion in 'ME/CFS research news' started by John Mac, Nov 15, 2022.

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  1. John Mac

    John Mac Senior Member (Voting Rights)

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    From OMF news email

    Post Exertion Malaise (PEM): Dr. David Systrom Aims to Fill in Gaps
    Today we are pleased to highlight one of the studies included in our 2022 OMF supported research initiatives! Remember, when you give this November, your gift will be TRIPLED by generous donors. Hurry before the match runs out on November 29!

    Muscle Biopsy and Plasma Study into Post-Exertional Malaise
    One of the defining characteristics of ME/CFS that sets it apart from other conditions is intolerance to exertion, known as post-exertional malaise (PEM). Even mild exertion, like a short walk, can cause ME/CFS symptoms to suddenly worsen, often feeling like the flu, usually within 1-24 hours after exertion. This worsening may last for days or weeks or longer and is often completely debilitating. Past research has identified an effective way to measure PEM, using a 2-day cardiopulmonary exercise test (CPET), where key factors are measured at baseline, during and after an exercise challenge, and then 24 hours later in a second exercise challenge.

    CPET testing clearly shows the effects of exertion intolerance in ME/CFS. Earlier studies indicated that PEM may be due to metabolic (the process the body uses to change food and drink into energy) dysfunction and/or dysfunction in the way cells use oxygen.

    This study will compare PEM in ME/CFS patients who’ve become ill in the past two years to patients who have had ME/CFS longer, as well to healthy controls. It will use a variety of testing methods on both muscles and blood to document what happens in the body of an ME/CFS patient during and after exercise, looking at both metabolic functions and oxygen use.

    Energy production occurs inside the body’s cells in mitochondria, so this study will measure various mitochondrial functions. Red blood cells play a critical role in how the body delivers oxygen, so red blood cell function will also be examined.

    The Study Goal
    Previous studies have indicated possible deformities in red blood cells of those with ME/CFS. These factors are interrelated with inflammation and immune dysfunction, which are both significant factors in ME/CFS. Better understanding the causes and effects of exertion intolerance—and the differences between newly ill patients and long-term patients—can help to better understand the mechanisms behind the scenes in ME/CFS and exactly what is happening in the bodies of patients.

    *Please note, OMF Collaborative Research Centers operate independently and recruit participants from local clinicians. This research study is not open for volunteers at this time.
     
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  2. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    I can literally feel there is something deeply wrong with my muscles (and fascia). They feel like they've been ripped, and the tissue has tried to heal but failed. In a crash my muscles (not skin) can become so sensitive I can barely touch them. I am amazed nothing has ever shown in muscle biopsies, even at the macro scale.
     
    Last edited: Nov 15, 2022
  3. Kitty

    Kitty Senior Member (Voting Rights)

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    I thought it was odd until I realised that some of my muscle pain is probably caused by a different condition, and if I keep my sodium intake low, increase my potassium intake when needed, and don't get too cold, much of the "ripped" pain doesn't even start up.

    Painful as it is, I very much doubt it'd show up clearly on a muscle biopsy. It might be a different kind of pain to yours, but if my muscles can give me that much hell just because I ate the quantity of salt found in the average bag of crisps, I suppose it's possible there are other causes that might not involve visually detectable changes or damage.
     
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  4. Creekside

    Creekside Senior Member (Voting Rights)

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    Keep in mind that "feeling" something also involves bi-directional signalling networks and processing networks, and malfunction there can cause "feelings" even if there is nothing wrong with the actual muscles.
     
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  5. bobbler

    bobbler Senior Member (Voting Rights)

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    very interested by this. I get low ferritin which when I was working would happen after I'd been through a peak work period. I observed this over the space of many years, and if any physicians had listened to me on the 'what preceded it' it would be obvious to them too. Instead they are taught not to be interested beyond assuming it is the patients own fault or it being explained by something not an issue. Then labels stuck on us if we say anything different.

    But it felt like deaf ears (or worse them looking at me like I'm the stupid one) - I'm so fed up with the medical profession in general and think we need to completely sort the attitude that has been created by all these awful moves towards crap research that isn't proper observational science but bigotry, and telling physicians to not listen to patients at the same time as not seeing them for more than 5mins.

    The worry is that just like the CPET stuff is harder better science to anyone with anything between their ears than a big manifesto rhetoric with a few claims fished out of dodgy surveys, but most medics seem to parrot and believe the latter, even this will get lost in the tosh of the system and habits that have been forced into even those who were capable before all these pathways and edicts.

    ie how does this trickle-down when there seems a poverty of ability to understand what is good vs bad 'evidence' in the gatekeepers of the system itself?

    Why on earth they think what they do on this basis is either science or medicine I don't know, it's been one-way paternalism they've generally been taught to do - throw information down the toilet whilst insulting those who supply it (thanks to the awful research which isn't research but manifestos from BPS basically propaganda-ing the message of 'if anyone comes to you talking about symptoms, science or medicine then it is hysteria').

    How do we do a wake up call to get rid of all this from the profession and change it into an interested science, when there have been so many years of turning e.g. GPs into gatekeepers to dump everyone into bigotry/a psychsomatic box (which shockingly most don't even acknowledge or even know to themselves is what they are doing now they are so brainwashed) so their voice is never heard and their body never studied? And worse, so that when something of note is discovered they are taught to write a note 'explaining' it with a lie instead of what the patient found.

    I despair we might have a capability issue behind all of this, that needs an injection of scientists/science-capables into the profession and compulsory science classes/exams for anyone who remains, it has gone so far for so long (which surely means those who do think like scientists would move elsewhere). Otherwise these developments might be the cutting edge but if the gatekeepers and most workers don't understand or like that area (because that's what the profession attracted by only being something else for so long you end up with certain personality types choosing it) they will do anything to choose their old comfort blankets.

    A big change to medical education to at least ensure the newbies are taught by some scientists in how to think underpinning the foundations of their curriculum, and placing getting a good mark being dependent on that (scientific approaches) rather than the current weightings, not just the same old people who've thrived under the old ideologies perpetuating more of the same might at least stop the rot for future years.

    I can't help but think of how in the US students would do an undergrad which would have science major first (and which isn't delivered by med school) vs UK them getting chucked straight under med school control - and that physics is the only 'methodology/research design-heavy' science A level, but one of the less commonly taken and whether that makes some difference. But does enough research design and science on a medical degree sit under proper scientists using scientific methods instead of epidemiologists (inference-based), public health type things? And shouldn't that scientific thinking be underpinning the way things are marked throughout each area to keep them on-track (from veering off)? Maybe all medicine areas need to be paired with proper science specialists, certainly in education, to pick up the subject areas that are warping into narrative stuff?
     
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  6. Sean

    Sean Moderator Staff Member

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    These guys get it. :)

    Past research has identified an effective way to measure PEM, using a 2-day cardiopulmonary exercise test (CPET),

    The important and shitty thing to note about CPET from our perspective being that it is more than 50 years old and widely used, yet was either not used or not taken seriously for ME until relatively recently.

    To put it another way, the mainstream technology that could have objectively demonstrated unambiguous pathology has existed for the entire careers of the senior BPS people, and they never used it to assess the nature of PEM, nor their key assumptions of deconditioning and no serious underlying organic pathology.

    :grumpy:

    This study will compare PEM in ME/CFS patients who’ve become ill in the past two years to patients who have had ME/CFS longer

    This is important. :thumbup:
     
    Last edited: Nov 27, 2022
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  7. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    I actually meant I can 'feel' as in with my fingers. In specific locations, my muscles — especially the surface layers and fascia, just under the skin — are taught, lumpy, with small, localized areas of extreme sensitivity. I think there's objectively some sort of issue, at least in my case. I would love to get a muscle biopsy, but i suspect that's pie in the sky!
     
    Last edited: Nov 16, 2022
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  8. Kitty

    Kitty Senior Member (Voting Rights)

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    That's really interesting. Definitely the muscle, and not the thin layer of subcutaneous fat overlying some of them?
     
  9. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    I don't think its the subcutaneous fat because the pain/soreness feels very muscular. I think I have issues with my fascia. Even before I got symptoms consistent with ME I always felt I had muscle issues — for example I have chronic problems with the IT band (essentially fascial/connective tissue) down the side of my thigh that affected me exercising, back when I was able to. They just got worse as my ME progressed. It almst feels like the tissue is scarred and hasn't repaired itself correctly. It's quite hard to describe. I don't think I've even brought it up with my GP because I don't think I'd get anywhere.

    ETA: Oh, and I always had really bad DOMS growing up. I could barely walk some days after playing football. I would notice my friends/teammates didn't seem to be as affected. I wonder if I had some pre-existing condition or suceptibility to these sorts of issues, and my ME has just pounced on them.
     
    Last edited: Nov 16, 2022
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  10. dreampop

    dreampop Senior Member (Voting Rights)

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    As someone who has not followed Systrom's work closely, how accurate is the statement from OMF:

    My understanding, which may be incorrect, was that the 2-day CPET results were an oddity in me/cfs, but maybe not unique to it.

    I was unaware of the claim that 2-day CPET can identify PEM or measure it. Can you have PEM without the expected CPET results? Can you have the CPET results but not PEM? What is the accuracy of this claim? What about PEM delayed more than 24 hours?

    It seems like an incredibly important thing to get exactly right, especially if it's going to be guiding the Harvard omf's study.
     
    Last edited: Nov 20, 2022
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  11. alex3619

    alex3619 Senior Member (Voting Rights)

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    I was able to trace it back to at least 1949, though at that time it was a research-only tool, used primarily in cardiac testing.

    I think a simplified form of it, useless for our purposes, became popular in about 1963. The Bruce protocol if I recall correctly.
     
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  12. Hutan

    Hutan Moderator Staff Member

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    I did a 2xCPET as part of a study, but with a 48 hour gap, not 24 hours. I did the first CPET, and then had PEM for several/more? hours that night. When I say PEM, I mean, feeling terrible, like I had a bad flu, with a feeling of my body being crushed, glands up, absolutely had to lie down, chills. The next day I did not feel too bad, certainly not in PEM, I did some walking. And then, on the third day, 48 hours after the first test, I did the second test. I did not feel that I was in PEM during the test, I felt ok. I had the significant drop in workrate at VO2 max and ventilatory threshold compared to the first test that is claimed to be the ME/CFS CPET pattern.

    What that tells me is that, assuming the 'ME/CFS CPET pattern' is actually a replicable and diagnostic thing (which is still an assumption), then it is measuring some change in physiology. But, whether it is measuring PEM or not depends on how you define PEM. If you define PEM as a 'crash' with the full-on flu-like symptoms, then the 2xCPET is not measuring that. Maybe it is better to think of what is measured as a 'lowering of the threshold for PEM'.
     
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  13. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    It's exciting that this is a muscle biopsy study. We need more tissue studies.
     
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  14. Kitty

    Kitty Senior Member (Voting Rights)

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    Sorry, I missed your reply to this! I only asked because I have a subcutaneous fat disorder, and also have areas that are "taught, lumpy, with small, localized areas of extreme sensitivity". For me, areas that become painful remain so for long periods of time, presumably because abnormal changes are taking place. Many of them eventually become less acutely sensitive, leaving only a soreness like a bruise if I press on the skin. I'm not overweight, I just have additional lumpy fat in certain areas.

    I believe some fat disorders are much less prevalent in men than they are in women, though, so it's probably more likely yours are muscular.
     
  15. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    That's interesting. What is the disorder, if you don't mind my asking?
     
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  16. Louie41

    Louie41 Senior Member (Voting Rights)

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    ???
     
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  17. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    Delayed onset muscle soreness — the healthy type you get after exercise.
     
  18. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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    I was at the doctors a few days ago about my recent decline. I had to attend for blood tests, and talked to my GP about this issue of 'muscle lumps'. They are most prevalent around my bicep muscle. She seemed to think it was possibly not the muscle, but rather subcutaneous fat. It's objectively very lumpy—like bubble wrap under the skin, or perhaps it feels a bit like a load of lymph nodes (which it is not). She thought recent weight loss was perhaps the cause, but this weight loss came after I had noticed this issue.

    What would cause this? I have no idea. But it has got worse. I have google quite a bit and there are some fibromyalgia patients saying similar things, but that's it. I suspect this is some sort of connective tissue/fascia issue, but it could be due to changes in subcutaneous fat. Unless you have one large lump, it seems doctors are not that interested.
     
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  19. Hutan

    Hutan Moderator Staff Member

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    How interesting. I had a flare a couple of years ago now (I think, the years blur...) and I ended up with lumps. First one near my elbow, then I got them in quite a lot of other places, knees, ankles, more around the forearm, one at the base of a finger. The joint would get hot and sore and then I'd be left with a lump. I went to the GP, she wasn't very interested. Some of these lumps are marble sized, the ones on my ankles are the size of half golf balls. Some went away quickly, some slowly and some have stayed. Bubble wrap is not a bad description, they are firm, like a swollen lymph node.

    I still have some large lumps. With considerable help, I got to a rheumatologist who wasn't very interested. I managed to get ultra sound, but only for the ankle lumps, why they could not look at some of the other lumps as well I do not know. I was told that the ultra sound scan just found that they were fat. The lumps are substantial and still there after all this time.

    It's been so frustrating. These lumps would come up overnight, and I was really sick during that time. I know if I was a dog, the lumps would have been biopsied. I've considered paying to get them biopsied myself, privately, but it's a substantial cost and I'd need to find someone who would be curious and actually look at the tissue under a microscope.
     
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  20. Sid

    Sid Senior Member (Voting Rights)

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    Same. I remember with horror school trips to various sports activities etc. after which I'd be floored the next day whereas no one else in class was. It wasn't PEM though. At the time it was just DOMS without flu-like malaise or orthostatic issues. I feel like I've been predisposed to developing ME/CFS for as long as I can remember.
     
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