18 ms·

Biomarker for chronic fatigue syndrome identified

397 points by lichtenberger 7y ago

Smaug123 7y ago
Paper at https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf https://www.pnas.org/content/pnas/early/2019/04/24/190127411... Pleasantly surprised to discover that it was legally available! The test appears to be ridiculously good. Perfect separation of 40 subjects into those who have been diagnosed with CFS and those who are known to be healthy, from blood samples. I want to see this replicated, by people who are not the original authors; but if this test is anything like as good as it looks, it's revolutionary.
- danieltillett 7y ago
  I have to agree with you here - the separation is too good. You just never get anything in the real world that works this well with complex diseases.
  - rfugger 7y ago
    This is true, but everything is complex only up to the point when you begin to understand it. Scurvy was a complex disease until the discovery that it was cured and prevented by citrus fruit(1). Now we have the technology to skip right to the discovery of vitamin C, a miraculous 100% accurate test for scurvy. I know I'm oversimplifying, but I think the point is valid. This is why discovery of a biomarker is so crucial -- it begins to "decomplexify" the disease so we can properly define it and start to find treatments for it. (1) Ok, it's never really that simple: http://mentalfloss.com/article/24149/how-scurvy-was-cured-then-cure-was-lost http://mentalfloss.com/article/24149/how-scurvy-was-cured-th...
    - rjsw 7y ago
      Maybe link to the original blog article [1], your link is just a summary. [1] http://idlewords.com/2010/03/scott_and_scurvy.htm http://idlewords.com/2010/03/scott_and_scurvy.htm
      - rfugger 7y ago
        Thanks -- I just copied the first link I found in a search engine.
  - gwern 7y ago
    It is suspicious but look at the scatterplots: https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf#page=4 https://www.pnas.org/content/pnas/early/2019/04/24/190127411... It really is pretty much perfect separation on their metric. When the effect size is that large...
    - ufo 7y ago
      One thing that would be interesting to investigate in the future would be to see how the test behaves for CFS patients who are not as severely ill, or for non-CFS patients that are currently ill from a different disease.
    - mirekrusin 7y ago
      Exacly, just sorting it would show it better, it feels like it should just output percentage with (arbitrary/based on population %age/whatever) threshold that is outside of the test.
  - deleted 7y ago
    [deleted]
  - kurthr 7y ago
    AIDS was once considered a very complex disease, but it has a very accurate (HIV) test today. My big concern would be if, like cancer, there are really many diseases and Chronic Fatigue symptoms are common, not differentiating.
    - erentz 7y ago
      That could still be very interesting. Eg. There are some other illnesses like MS where patients can get fatigued in a similar way to CFS, but not always. If we find a similar response between the fatigued and non fatigued MS patients for example, that could still point to something that is going on causing the fatigue in both cases. Ron Davis’s line on this was to point out having one disease doesn’t mean you can’t have any others. There are a lot of other interesting overlaps showing up. One of the more interesting to me (because I have it) is that about 40% of CFS patients are testing positive for small fiber polyneuropathy on punch biopsies that appear to be autoimmune in origin. Is that itself an underlying cause of some 40% of CFS cases or is it just a common comorbid condition that whatever triggers CFS also triggers?
    - GordonS 7y ago
      I've done a lot of reading on CFS and fibromyalgia, and this has been my opinion too. For starters, these are both diagnosis of exclusion; these labels are also used by lazy doctors who lack a deeper understanding of their field (anecdotally, both personal and otherwise), or who are reluctant to run expensive tests for rarer conditions; and many people with these conditions have been found to have small fiber neuropathy.
    - Someone 7y ago
      AIDS, like CFS, was never considered a disease in the medical sense. They both are called “syndrome”, which is medical short-hand for “interesting enough to study further, but frankly, we don’t know shit about what’s causing this”. https://en.wikipedia.org/wiki/Syndrome https://en.wikipedia.org/wiki/Syndrome: ”A syndrome is a set of medical signs and symptoms that are correlated with each other and, often, with a particular disease or disorder.” That’s why AIDS became “HIV infection” when medical science discovered what caused AIDS. If this research gets confirmed, and a mechanism is found, that will happen here, too. However, as you say, if that happens, there’s a good chance there are people currently diagnosed with CFS who don’t show this biomarker. If so, those people run the risk of getting stigmatized even more than current CFS sufferers do. The real solution to that problem, I think, would be for the world to accept that, if you have a mental problem, a) that doesn’t imply you put it there, and b) it doesn’t imply you should be able to get it out without outside help. Only a few centuries ago, people were being blamed of being “unfaithful to god” when they got sick, be it due to a bacterial infection or due to mental illness. I see blaming people for their mental problems as a remnant of that.
  - ipunchghosts 7y ago
    Who care is the separation is "too good." It's a lead. This is what science is. You find leads and followup on them. Lots of dead ends in the process.
    - sagebird 7y ago
      You should care if it “too good” because it could be a sign of overfitting or tampering with data during analysis to reach a desired conclusion. Replication should shed some light here.
  - Gatsky 7y ago
    Of course skepticism is warranted however an important distinction to make is that they are measuring a whole cell phenotype, rather than some surrogate such as gene expression or a circulating molecule. I work on cancer biomarkers, and phenotypic readouts work much better than you might expect.
- erentz 7y ago
  I’m also very interested in seeing how strong the effect is when tested on mild and moderately ill patients. I hope they follow up with that. (The study group OMF have been using has been 20 severely sick patients, which is a good plate to start.)
  - rtp 7y ago
    From the paper: Of the 20 ME/CFS patients studied, 5 were severely ill and 15 were moderately affected by their condition
    - erentz 7y ago
      Oh! That’s good news. (I’ve been following the OMFs work for a while now and somewhere along the way I got it into my head they were all severely ill.)
- GordonS 7y ago
  Keep in mind that CFS is a currently a diagnosis of exclusion - many people labelled with CFS may in fact have another, undiagnosed illness. For example, it's been found that a lot of CFS (and fibromyalgia) patients turn out to have small fiber neuropathy (damage to he nerve fibers that signal pain), and neurotoxins have been shown to cause general fatigue (I'm in mobile, so no references for now I'm afraid). The skin biopsy test for small fiber neuropathy isn't routinely done because there aren't that many labs capable of testing the sample, and it's relatively expensive. Of course, for all we know neuropathy could be a symptom of CFS... but the point is there is a lot of cross-over, and there is no diagnostic test specifically for CFS.
  - wavepruner 7y ago
    I found out last year the root cause of my CFS is life-long mercury toxicity (a well understood neurotoxin). I am responding very positively to treatment. I rarely talk about it because people get very upset when I tell them about the evidence of where the mercury came from.
    - febeling 7y ago
      Nice curiosity gap there. Where did the mercury come from?
      - thom 7y ago
        Going to assume given the way this is phrased that the poster means a vaccination.
      - everly 7y ago
        IMO he is clearly implying it came from a vaccine(s) but he is trying to do it without being seen as an anti-vaxxer.
        p1necone 7y ago
        Surely you'd have to have a lot of vaccines for it to compare to the amount you get from other sources (mostly seafood afaik?)
- kens 7y ago
  Thanks for the paper link. I read the paper and it's really a semiconductor sensor engineering paper, not a biology paper. The paper seems very preliminary; it shows that CFS and non-CFS sample have widely different impedances under osmotic stress, but the mechanism behind this is entirely hand-waving. If I'm reading the paper correctly, the samples were peripheral blood mononuclear cells (i.e. lots of different cell types) in their own plasma. It would be nice to have samples that weren't so heterogeneous, since it's unclear what type of cell is causing the effect, or if it is something in the plasma. It would be nice if the paper gave the actual measured resistances, rather than % deviation from normalized impedance which is an unusual unit. The paper's use of machine learning seems entirely pointless, basically drawing the obvious line between the two sets of points. The discussion section didn't seem to have anything concrete. It reminded me of a patent application where you try to list everything that might possibly turn out to be vaguely related. I apologize for the negativity; the paper's result is very exciting so I hope it pans out, but I found the paper itself disappointing.
  - sagebird 7y ago
    The use of machine learning needs to be explained. I’m half expecting it to boil down to “we evolved the neural nets until it perfectly separated the two groups” — overfitting “learning”.
    - ufo 7y ago
      I also had that impression at first but it seems that they are just using Support Vector Machines to draw the separating boundary between the two group of points.
    - Smaug123 7y ago
      If you look at the graphs by eye, there is an extremely obvious divide. SVM just let them find it automatically, but if you gave a human those graphs, they could instantly point out where the line is.
    - thereisnospork 7y ago
      Why does it need to be explained if the test can be proven to be extensible? Asprin worked for nearly 100 years before anyone had any clue how (ditto with many, many more modern drugs).
DiseasedBadger 7y ago
But which is the cause? Perhaps someone convinced they're ill, weakens their own immune system - either through some psychosomatic mechanism, or through associated behaviors.
- ufo 7y ago
  No one knows the cause yet, which is why studies like this are important. Please don't idly suggest that CFS is just something psychosomatic or behavioral. The disease is much more debilitating than that, and this very common psychological misdiagnosis most often leads to dangerous advice. For example, CFS patients are often told by doctors to excercise, which actually only makes the symptoms even worse.
  - benatkin 7y ago
    This reminds me of this quote from an article about Phil Libin, former CEO of Evernote: > Eventually he (Phil Libin) pinpointed the source. "It was the carbs," he said. https://www.businessinsider.com/phil-libin-fasting-routine-2017-10 https://www.businessinsider.com/phil-libin-fasting-routine-2... I think bad eating habits, eating unhealthy food, too much, too often, and too erratically has something to do with the uptick in these conditions.
    - ufo 7y ago
      I think that this suggestion that CFS might be caused by bad diet is even more irresponsible than telling it is psychological. CFS patients would wish that it were that simple. CFS onset is often abrupt, and can often happen to otherwise very healthy and active people. For example, a common story is that the patient becomes sick from a viral infection and then gets stuck with chronic fatigue syndrome even after the infection goes away.
      - benatkin 7y ago
        > No one knows the cause yet If we can determine for sure that it's happening a at a much higher rate than in the past, we have a pretty good idea that the cause is the conditions that we live in. Diet that is one thing in which the changes over the years have been similar across different regions. If it was air pollution, the increased rates would show up in some regions but not others. Ditto radiation. I don't think this is like autism in that we were mostly oblivious to it in the past, but I could be wrong. Enlighten me.
jaxgeller 7y ago
If you are living with CFS i recommend giving https://cfsremission.com/ https://cfsremission.com/ a look.
- rfugger 7y ago
  Also check out http://recoveryfromcfs.org/ http://recoveryfromcfs.org/.
  - majkinetor 7y ago
    Orthomolecular approach. Nice.
- colordrops 7y ago
  Crazy, I basically self diagnosed myself with CFS and got rid of my symptoms over time by discovering most of the recommendations on this page myself. I figured it had something to do with a funky immune system and gut bacteria, and changed my diet and took supplements and probiotics, and it's mostly gone. I even take bacopa, wild. This is really heartening to see that I was on the right track. My wife thinks I'm a hypochondriac with a bunch of placebos.
- jchw 7y ago
  Woah, I’m now wondering if CFS might be what’s been wrong with me for a while, but I’m not sure. I definitely have terrible sleep, I can barely stay awake during meetings, and I have some of the other symptoms sometimes associated with this (tender lymph nodes in neck, IBS, tinnitus.) I’ve been in and out of the doctor for a couple years, with weird pains, and most recently a lymph node that is a little enlarged in the neck. Obviously there are some scary (but unlikely) potential explanations. But, my sleep quality degrading over the years is something that has been happening much slower, and started much earlier. Not a huge fan of self diagnosis but maybe some of the proposed dietary changes would be worth trying, since they seem fairly innocuous. I’m sure eating more apples won't hurt. If anyone has experience with CFS and has advice, I’m all ears. I’d kill to sleep like I did when I was 18.
  - 7y ago
daedalus_f 7y ago
This looks very promising, but it’s too early to say how accurate this test truly will be. Even if this papers methodology is replicated and the test again perfectly selects ME/CFS from healthy controls, it may perform terribly when used in a real clinical setting where the test has to distinguish CFS from the spectrum of other disorders that it will encounter. In other words while the current paper suggests the tests sensitivity is likely to be high it’s much harder to come to any conclusion about it’s real world specificity.
leemailll 7y ago
So what they measure and where is the paper? I read the linked pr but find nothing about them
- ufo 7y ago
  I don't understand the details but here is the link to the paper https://www.pnas.org/content/early/2019/04/24/1901274116 https://www.pnas.org/content/early/2019/04/24/1901274116
  - leemailll 7y ago
    Thanks for the link. I read the paper and it seems that they just measure the impedance (or resistance) of the cell membrane with an artificial increase of NaCl in the extracellular environment (ie plasma in the text). The final NaCl concentration looks like to be doubled than the normal range. This might be an intersting finding, but I can't figure out why the impdecance of membrane need to be measured with increased NaCl in the plama. And whether it is only related with Na+ or Cl- change.
    - ufo 7y ago
      The salty plasma removes water from inside the cells by osmosis. The authors say that this technique is a common model for studying cellular response to stress.
      - leemailll 7y ago
        The thing is if they just want to create a hyperosmotic solution they can add something won't be transported across the membrane, the way they did will change a lot of things on the membrane and inside the cell rather than stress introduced by hyperosmotic stress
derefr 7y ago
Does it say anywhere in the paper what the “promising drug” that decreases the effect might be?
- ufo 7y ago
  No. They are intentionally keeping that information secret to prevent people from trying to self-treat with it before more studies have been done.
- vaelin 7y ago
  Not in the paper, but Ron gave a talk where he mentioned an MS drug (I have forgotten which) and a new drug that targets mitochondria which is not yet licensed for anything. Sorry I can't be more specific. I don't remember the details.
- rufus85 7y ago
  SS31, copaxone and suramin. Suramin is used for African sleeping sickness. They found that African sleeping sickness closely resembled CFS in terms of gene expression.
whalabi 7y ago
I'm just astonished by this. Millions of people (in the US alone!) suffer from this illness and I think everyone has wondered, or heard it wondered, if it's imaginary. For all these people to know there's something actually physically wrong with them is massive. It'll shift the thinking of everyone in the profession, of their families and friends and colleagues, and of themselves. It's a huge, huge breakthrough.
- Twirrim 7y ago
  I've known several people over the years who have had Chronic Fatigue Syndrome, and most of them have at some stage or another had to deal with discrimination from people that told them it was a made up illness. Having a solid test like this will make a phenomenal difference.
  - e-m-p 7y ago
    Yes
- daedalus_f 7y ago
  This is promising data but it’s very early. The authors are not really sure what the test is measuring on a cellular level, though they speculate a lot in the discussion, and we can’t yet truly infer a causal link between what’s causing the test result and disease status. It’s is going to take a lot more validation before we get to the stage where this is clinically useful. For instance, the control group were healthy, what if instead you compared test results in CFS to another disease condition that can mimic CFS, would it still work as well? In the extreme case, the test could just be a generic flag that someone is non-specifically unwell, we just can’t tell from this data alone.
  - vaelin 7y ago
    It could also be measuring the result of extreme inactivity. I am bedridden, and I have no doubt that lying in bed for years has had a profound effect on my physiology independently of my ME/CFS. The acid test will be when we compare ME/CFS patients to matched MS patients. However, as Ron Davis has stated, it might also be the case that MS patients have ME/CFS, as ME/CFS is highly heterogenous and may be arrived at from multiple directions. There are lots of details that need to be ironed out. Nevertheless, this is exciting news.
freeradical13 7y ago
Why did they need machine learning? It seems from Figures 2B-G that there's a clear cut off. "Moreover, to create a classifier for ME/CFS patients capable of identifying new patients, required for a robust diagnostic tool, we developed a trained kernel Support Vector Machine (SVM), a supervised machine-learning algorithm, using our experimental data. To classify new patients based on whether they fall to the right of the decision boundary, we initially selected the two features with the largest significance: change from the baseline to the plateau and change from the minimum to the plateau for the in-phase components of the impedance. Using these features, a cubic polynomial kernel SVM was able to classify the two populations, although the two features are highly correlated, as shown in Fig.2H." https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf https://www.pnas.org/content/pnas/early/2019/04/24/190127411...
- L2R 7y ago
  Nothing wrong with an SVM. How else would they create a decision boundary for classifying patients? The choice of the polynomial kernel is interesting, but I don't think it causes any issues given the data.
  - freeradical13 7y ago
    I see, so basically instead of intuiting a simple threshold (e.g. >X% change), they apply an SVM which is able to discover more accurate thresholds (and error ranges). Do you have any suggested resources on learning more about SVM? I guess my question comes from the observation that these advanced statistical techniques such as machine learning haven't been around for long and yet medicine has often created decision boundaries, presumably just looking at the data and making a reasonable cutoff. Is all the extra effort in a case like this worth the time investment?
    - verroq 7y ago
      SVMs are as old school ML as they get. They guarentee the maximum separation at the decision boundary. However it doesn’t scale very well for higher dimensional data. The standard used to be to use some dimensionality reduction technique like PCA to preprocess before feeding it into the SVM. This is all before deep learning.
NautilusWave 7y ago
This biomarker seems incredibly general; I suspect people with certain presentations of a mitochondrial disease would have the same biomarker.
- GordonS 7y ago
  Agreed, but it's still great to have evidence of a physical condition, as many CFS patients have been made to feel like crackpots at some point, and indeed some doctors use it as a convenient label for people they believe to be mentally ill. Of course, this also raises a question about how those with mental illness are often treated.
  - rfugger 7y ago
    To be fair, if someone is overly anxious and neurotic about minor physical symptoms, to the point that the anxiety is making things worse, often the best thing a doctor can do is reassure them that they are fine, to stop worrying, and send them home. Taking those patients' physical symptoms too seriously may be the worst thing to do. I can see that it must be hard for doctors, especially if they only really have about 12 minutes to make a determination...
    - GordonS 7y ago
      Hypochondriasis is real, sure. But I'm not talking about cases like that, I'm talking about patients behaving perfectly rationally, but insistently.
johnchristopher 7y ago
Wait... does it mean chronic fatigue syndrom is recognized now ?
- johnchristopher 7y ago
  Thanks for the downvote but where I live it's still not recognized and patients are either told it's a depression or some kind of fibroid-myalgia.
UglyToad 7y ago
This sounds brilliant if it can be replicated. From what I've read and heard large parts of the medical establishment still treats ME/CFS patients as lazy/making it up. For there to be a positive diagnosis rather than a diagnosis of exclusion is the first step to getting these people the help they deserve.
ipunchghosts 7y ago
Journalists, this is quite the story. Here you have a bunch of really sick patients with docs around the world saying it's in there head. Then a UK study comes out (PACE) saying patients should engage in activity to help themselves. This only makes the patients worse and eventually so bad that the study was pulled. In comes dr ron davis. His son acquired me cfs while traveling in india. Completely unsatisfied with the lack of care provided by his doctors, he ventured off to research the disease himself assembling a team of esteemed scientists. They all begin to promptly kick ass and take names making more headway on understanding the disease more than anytime in history. Meanwhile, they have open conferences which are posted on YouTube for patients to watch (and see hope) and other scientists to learn from. Davis and his collaborators discover all sorts of cfs links and debunk a bunch of myths.really interesting research is occurring on trypanosomes, metabolic traps, and the microbiome. Eventually a large signal is found when the cells are stressed and voila, we arrive at the test mentioned in the link. This folks is how science is supposed to unfold and it all happening right in front of our eyes for everyone to see in real time. Quite astonishing. These folks will eventually win the Nobel, im sure of it.
- heavenlyblue 7y ago
  >> This folks is how science is supposed to unfold and it all happening right in front of our eyes for everyone to see in real time. Quite astonishing. So you imply that only scientists with money and direct personal interest in the research are supposed to work on the given topic?
  - ipunchghosts 7y ago
    Not at all. What i mean is that scientists discovered a problem and 1) pursued it regardless of what the major funding agencies thought of it 2) encouraged patients to get involved and 3) informed the public of their progress regularly allowing for open discussion and collaboration.
    - cpach 7y ago
      Amazing!
soulofmischief 7y ago
Medicine is a must for any empathetic society. However I wonder if the dawn of modern medicine was the end of natural human evolution. Now that people with diseases such as CFS and diabetes can receive help, we are no longer breeding these diseases out of the gene pool. As a result, we are actually spreading them epigenetically over time. We will be forced to turn to science, such as vaccines and pre- and post-birth biological modification, in order to continue the progression of our species in our battle against ailments and germs. As a side note, what is the best way to get tested for CFS? Is it possible to devlop CFS after contracting certain immuno-suppressant diseases? In my youth I was constantly sleeping in class, but I chalked it up to a combination of insomnia and 24/7 forced consumption of amphetamines to treat ADHD. I mean I would sleep literally anywhere if I had more than half an hour to kill with nothing to do, much to the embarrassment of my guardians. At the time I was not interested in getting tested for narcolepsy and adding yet another item to my list of mental illnesses. Then right after high school, I contracted mononucleosis. I was completely bed-ridden for almost six months, and for about two years I basically had no energy at all. Always sleeping. Those two years went by in a flash. And now I still feel that to a degree, years later. I'm Bipolar II, and when I'm in my manic phase I have near unlimited energy, but when I'm at baseline or in my depressive phase I basically crawl into a permanent coma for two weeks punctuated by work. A lot of people intentionally allow their children to contract mono in their youth, similarly to chicken pox, so that the virus comes at a more manageable period in their life. It can be devastating/disruptive to an adult life. I was homeless and unable to work for a long time. I wonder if any research has been done towards the link between early contraction of these diseases and CFS.
- GordonS 7y ago
  I was diagnosed with CFS after being prescribed an immunosuppressant. I reacted badly to it, developing chronic pain and fatigue, so it's possible that's a vector (I say possible as CFS is a diagnosis of exclusion, and it's highly likely thatany people diagnosed with CFS have some other, undiagnosed condition of which fatigue and pain are a symptom).
  - soulofmischief 7y ago
viburnum 7y ago
That you can measure stress response in blood cells doesn’t rule out that the disease is psychological in origin (although I doubt CFS is).
- rfugger 7y ago
  At this point, I don't care about the origin nearly as much as finding an effective treatment :)
  - Erik816 7y ago
    Agreed, people are very hung up on the mind/body problem. It's a pretty interesting philosophical question, but not that relevant to helping truly sick people get better.
thrrrrrway 7y ago
I had CFS like symptoms so bad I was stuck in bed for several years and the doctor basically would not help me. Eventually I decided to treat it myself with antibiotics and anti parasitic medication. I basically came to the conclusion that for my specific case I had an unknown blood parasite and the fatigue was being caused by neurotoxins. I don't think all CFS are caused by an infection but mine definitely was and I have my life back. If you a researcher looking for a cure, try to test medications that flush neurotoxins out to see if the disease goes away and then try figuring out what is creating them in the first place to treat them.
jxramos 7y ago
Can anyone explain the idea of salt as a cell stressor? > The idea is to stress the samples from both healthy and ill patients using salt, and then compare how each sample affects the flow of the electrical current. Is this an osmotic pressure change that stresses the cytoskeleton or something? Does a cell under a hypertonic solution change its cell membrane channel’s behavior?
- deleted 7y ago
  [deleted]
- reubens 7y ago
  They were bumping the Na to 200mOsm/L, which is insanely high compared to our plasma. Hypertonicity like this causes the cell to shrink, which spoils the delicate relationships and ionic bonds between molecules in the cell. This causes a litany of issues, but one thing is an increase in production of reactive oxygen species, a byproduct of normal metabolism. ROS, otherwise known as free radicals, is what they use to measure cell stress.
- xkcd-sucks 7y ago
  While a cell is alive, it maintains differential concentration of ions across its membrane, so by definition changing the [Na+] is changing the membrane potential. The stress on the cell is basically it needs to work extra hard moving ions around to maintain itself. This is typically pumping ions against a concentration gradient which takes energy.
daegloe 7y ago
Off topic, but does anyone know why this post didn’t match up with my submission from last week [0]? I know scheme and querystring can throw it off. But in this case the links appear to be the same? Not sore about it, genuinely curious what the matching rules look like! [0] https://news.ycombinator.com/item?id=19783668 https://news.ycombinator.com/item?id=19783668
- GordonS 7y ago
  Sometimes the mods let dupes through, if they feel it's an important story that didn't get any/enough attention last time round.
not_a_moth 7y ago
Since poor sleep quality is a core symptom of CFS I can't help wonder if sleep is the underlying component. I think we've all underestimated the critical nature of sleep in immune, metabolic, stress, cognitive aspects, etc. It's also hard to self-assess the quality of your sleep, eg. clock-time at each phase, central apnea events, 02 saturation, noise/ light/ movement disturbances while you are asleep, etc.
- rfugger 7y ago
  A sleep study is critical to ruling out sleep issues before getting a proper diagnosis of ME/CFS. No good doctor would diagnose CFS without a sleep study.
  - not_a_moth 7y ago
    That could rule out apneas but not the overall possibility, based on typical sleep studies anyways. e.g. you regularly go to bed thinking about the stuff you have to do tomorrow, so your brain doesn't enter deep sleep phases for long; your doctor thinks 6-7 hours of sleep is good, when you in particular need more like 8.5 ; your neighborhood is noisy, etc.
deleted 7y ago
[deleted]
olliej 7y ago
40 people isn’t a super large sample size. Given there are huge numbers of people who claim to have cfs I would have expected much larger.
- nosianu 7y ago
  This is a poor statement since you leave out important qualifiers that would give it some beef. you can't just auto-post "sample size too low" whenever you don't see a thousand people, you have to go deeper to justify your opinion. This sample size can be way to low or it can be very high, completely depends on the population and what you want to show and with what confidence. Summary here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876926/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876926/ But a study like this one here, i.e. if one were to be made, would have plenty of power with a sample size of 40: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ (also consider the opposite, how many participants it would take before you believe the result, but that kind of study would not be permitted; how many does it take to be saved before you believe it) This study - or the lack thereof, which the paper is about - nicely shows that when there is confidence about the underlying mechanism you feel much less (here: no) need for statistics and an RCT.
  - olliej 7y ago
    Ok, the sample size was 20 cfs, and 20 non cfs. The problem I have is that the sample size means the there are reasonably good odds that their a significant genetic difference between the two groups. I am making no claim as to whether it’s real - I’ve known people who say they have it, and to me seems plausible, but I’ve also known people who are just not 20 any more, and have children, who also claim to have it - it seems plausible in the latter case that people have been sold on a message of “eat healthy and you won’t feel age”. The problem with weak sample sizes is that it has a significant negative impact whether CFS exists or not: * if it’s a real disease it could be an incorrect marker - for example let’s say the CFS positive group were all Bostonians living in California. It’s highly likely that a random sample of California natives will have at least some uniform marker. Now people who have the disease, but aren’t from Boston may not have the marker, so are told they’re not sick. * the disease doesn’t exist, but you’ve got a marker now. People who happen to have the bogus marker are now diagnosed with something that they don’t have. Now they have a diagnosis that prevents an actual diagnosis of real issues. So I don’t believe it is justifiable to publish a press release on something that effects millions of people, based on a sample that is so small. The initial small sample size might justify a larger sized sample looking at specifically that marker. Then you also have better science (you have a “this marker indicates cfs” hypothesis), and more statistical robustness.
drchewbacca 7y ago
There's a movie called "Unrest" which, in part, covers Dr Davis and his son I think. I thought it was a pretty interesting movie, it's on Netflix in the UK, not sure about elsewhere.
rufus85 7y ago
I have some doubts that this will be 100% specific to CFS, but as professor Davis said at this point it's important to demonstrate that these patients have something wrong with them. Davis called this the last major disease we know almost nothing about. It's 2-3 as common as multiple sclerosis with worse impact on the person's life. It's also the most underfunded illness when the number of patients and the severity is taken into account.
rufus85 7y ago
There is something akin to a daily exertion limit in CFS. When patients exceed it, they have a relapse. It is very easy to have these relapses because the exertion limit is so low. There must be a biological mechanism behind this limitation. It could be something to do with energy generation in cells and this test may be measuring the associated impairment.
starchild_3001 7y ago
YouTube talk about the same: https://www.youtube.com/watch?v=bXGCQPLUtdQ https://www.youtube.com/watch?v=bXGCQPLUtdQ
lsiebert 7y ago
My mom has this. While I'm hopeful this may lead to an effective treatment, it won't give her back the many years she's lived with the disease.
hourislate 7y ago
Ron Davis has worked on this day and night for years. I remember reading about his effort to figure out CFS to save his son. I'm not even sure this was his field of expertise. He just wanted to save his sons life and gave his every waking moment to try and figure it out. It makes me very happy that he seems to have accomplished it. I'm curious if his son is still with him, he was in really bad shape back in 2016.
ipunchghosts 7y ago
Look over at r/medicine about this topic. https://www.reddit.com/r/medicine/comments/blc7tv/stanford_laboratory_claims_to_identify_robust/ https://www.reddit.com/r/medicine/comments/blc7tv/stanford_l... Doctors seem to be overly critical and ignorant. Any reason for this?
cpach 7y ago
For the record, here’s a permalink that uses HTTPS: https://med.stanford.edu/news/all-news/2019/04/biomarker-for-chronic-fatigue-syndrome-identified.html https://med.stanford.edu/news/all-news/2019/04/biomarker-for...

397 points by lichtenberger 7y ago

Paper at https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf https://www.pnas.org/content/pnas/early/2019/04/24/190127411... Pleasantly surprised to discover that it was legally available! The test appears to be ridiculously good. Perfect separation of 40 subjects into those who have been diagnosed with CFS and those who are known to be healthy, from blood samples. I want to see this replicated, by people who are not the original authors; but if this test is anything like as good as it looks, it's revolutionary.

danieltillett 7y ago
I have to agree with you here - the separation is too good. You just never get anything in the real world that works this well with complex diseases.
- rfugger 7y ago
  This is true, but everything is complex only up to the point when you begin to understand it. Scurvy was a complex disease until the discovery that it was cured and prevented by citrus fruit(1). Now we have the technology to skip right to the discovery of vitamin C, a miraculous 100% accurate test for scurvy. I know I'm oversimplifying, but I think the point is valid. This is why discovery of a biomarker is so crucial -- it begins to "decomplexify" the disease so we can properly define it and start to find treatments for it. (1) Ok, it's never really that simple: http://mentalfloss.com/article/24149/how-scurvy-was-cured-then-cure-was-lost http://mentalfloss.com/article/24149/how-scurvy-was-cured-th...
  - rjsw 7y ago
    Maybe link to the original blog article [1], your link is just a summary. [1] http://idlewords.com/2010/03/scott_and_scurvy.htm http://idlewords.com/2010/03/scott_and_scurvy.htm
    - rfugger 7y ago
      Thanks -- I just copied the first link I found in a search engine.
- gwern 7y ago
  It is suspicious but look at the scatterplots: https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf#page=4 https://www.pnas.org/content/pnas/early/2019/04/24/190127411... It really is pretty much perfect separation on their metric. When the effect size is that large...
  - ufo 7y ago
    One thing that would be interesting to investigate in the future would be to see how the test behaves for CFS patients who are not as severely ill, or for non-CFS patients that are currently ill from a different disease.
  - mirekrusin 7y ago
    Exacly, just sorting it would show it better, it feels like it should just output percentage with (arbitrary/based on population %age/whatever) threshold that is outside of the test.
- deleted 7y ago
  [deleted]
- kurthr 7y ago
  AIDS was once considered a very complex disease, but it has a very accurate (HIV) test today. My big concern would be if, like cancer, there are really many diseases and Chronic Fatigue symptoms are common, not differentiating.
  - erentz 7y ago
    That could still be very interesting. Eg. There are some other illnesses like MS where patients can get fatigued in a similar way to CFS, but not always. If we find a similar response between the fatigued and non fatigued MS patients for example, that could still point to something that is going on causing the fatigue in both cases. Ron Davis’s line on this was to point out having one disease doesn’t mean you can’t have any others. There are a lot of other interesting overlaps showing up. One of the more interesting to me (because I have it) is that about 40% of CFS patients are testing positive for small fiber polyneuropathy on punch biopsies that appear to be autoimmune in origin. Is that itself an underlying cause of some 40% of CFS cases or is it just a common comorbid condition that whatever triggers CFS also triggers?
  - GordonS 7y ago
    I've done a lot of reading on CFS and fibromyalgia, and this has been my opinion too. For starters, these are both diagnosis of exclusion; these labels are also used by lazy doctors who lack a deeper understanding of their field (anecdotally, both personal and otherwise), or who are reluctant to run expensive tests for rarer conditions; and many people with these conditions have been found to have small fiber neuropathy.
  - Someone 7y ago
    AIDS, like CFS, was never considered a disease in the medical sense. They both are called “syndrome”, which is medical short-hand for “interesting enough to study further, but frankly, we don’t know shit about what’s causing this”. https://en.wikipedia.org/wiki/Syndrome https://en.wikipedia.org/wiki/Syndrome: ”A syndrome is a set of medical signs and symptoms that are correlated with each other and, often, with a particular disease or disorder.” That’s why AIDS became “HIV infection” when medical science discovered what caused AIDS. If this research gets confirmed, and a mechanism is found, that will happen here, too. However, as you say, if that happens, there’s a good chance there are people currently diagnosed with CFS who don’t show this biomarker. If so, those people run the risk of getting stigmatized even more than current CFS sufferers do. The real solution to that problem, I think, would be for the world to accept that, if you have a mental problem, a) that doesn’t imply you put it there, and b) it doesn’t imply you should be able to get it out without outside help. Only a few centuries ago, people were being blamed of being “unfaithful to god” when they got sick, be it due to a bacterial infection or due to mental illness. I see blaming people for their mental problems as a remnant of that.
- ipunchghosts 7y ago
  Who care is the separation is "too good." It's a lead. This is what science is. You find leads and followup on them. Lots of dead ends in the process.
  - sagebird 7y ago
    You should care if it “too good” because it could be a sign of overfitting or tampering with data during analysis to reach a desired conclusion. Replication should shed some light here.
- Gatsky 7y ago
  Of course skepticism is warranted however an important distinction to make is that they are measuring a whole cell phenotype, rather than some surrogate such as gene expression or a circulating molecule. I work on cancer biomarkers, and phenotypic readouts work much better than you might expect.
erentz 7y ago
I’m also very interested in seeing how strong the effect is when tested on mild and moderately ill patients. I hope they follow up with that. (The study group OMF have been using has been 20 severely sick patients, which is a good plate to start.)
- rtp 7y ago
  From the paper: Of the 20 ME/CFS patients studied, 5 were severely ill and 15 were moderately affected by their condition
  - erentz 7y ago
    Oh! That’s good news. (I’ve been following the OMFs work for a while now and somewhere along the way I got it into my head they were all severely ill.)
GordonS 7y ago
Keep in mind that CFS is a currently a diagnosis of exclusion - many people labelled with CFS may in fact have another, undiagnosed illness. For example, it's been found that a lot of CFS (and fibromyalgia) patients turn out to have small fiber neuropathy (damage to he nerve fibers that signal pain), and neurotoxins have been shown to cause general fatigue (I'm in mobile, so no references for now I'm afraid). The skin biopsy test for small fiber neuropathy isn't routinely done because there aren't that many labs capable of testing the sample, and it's relatively expensive. Of course, for all we know neuropathy could be a symptom of CFS... but the point is there is a lot of cross-over, and there is no diagnostic test specifically for CFS.
- wavepruner 7y ago
  I found out last year the root cause of my CFS is life-long mercury toxicity (a well understood neurotoxin). I am responding very positively to treatment. I rarely talk about it because people get very upset when I tell them about the evidence of where the mercury came from.
  - febeling 7y ago
    Nice curiosity gap there. Where did the mercury come from?
    - thom 7y ago
      Going to assume given the way this is phrased that the poster means a vaccination.
    - everly 7y ago
      IMO he is clearly implying it came from a vaccine(s) but he is trying to do it without being seen as an anti-vaxxer.
      - p1necone 7y ago
        Surely you'd have to have a lot of vaccines for it to compare to the amount you get from other sources (mostly seafood afaik?)
kens 7y ago
Thanks for the paper link. I read the paper and it's really a semiconductor sensor engineering paper, not a biology paper. The paper seems very preliminary; it shows that CFS and non-CFS sample have widely different impedances under osmotic stress, but the mechanism behind this is entirely hand-waving. If I'm reading the paper correctly, the samples were peripheral blood mononuclear cells (i.e. lots of different cell types) in their own plasma. It would be nice to have samples that weren't so heterogeneous, since it's unclear what type of cell is causing the effect, or if it is something in the plasma. It would be nice if the paper gave the actual measured resistances, rather than % deviation from normalized impedance which is an unusual unit. The paper's use of machine learning seems entirely pointless, basically drawing the obvious line between the two sets of points. The discussion section didn't seem to have anything concrete. It reminded me of a patent application where you try to list everything that might possibly turn out to be vaguely related. I apologize for the negativity; the paper's result is very exciting so I hope it pans out, but I found the paper itself disappointing.
- sagebird 7y ago
  The use of machine learning needs to be explained. I’m half expecting it to boil down to “we evolved the neural nets until it perfectly separated the two groups” — overfitting “learning”.
  - ufo 7y ago
    I also had that impression at first but it seems that they are just using Support Vector Machines to draw the separating boundary between the two group of points.
  - Smaug123 7y ago
    If you look at the graphs by eye, there is an extremely obvious divide. SVM just let them find it automatically, but if you gave a human those graphs, they could instantly point out where the line is.
  - thereisnospork 7y ago
    Why does it need to be explained if the test can be proven to be extensible? Asprin worked for nearly 100 years before anyone had any clue how (ditto with many, many more modern drugs).

DiseasedBadger 7y ago

But which is the cause? Perhaps someone convinced they're ill, weakens their own immune system - either through some psychosomatic mechanism, or through associated behaviors.

ufo 7y ago
No one knows the cause yet, which is why studies like this are important. Please don't idly suggest that CFS is just something psychosomatic or behavioral. The disease is much more debilitating than that, and this very common psychological misdiagnosis most often leads to dangerous advice. For example, CFS patients are often told by doctors to excercise, which actually only makes the symptoms even worse.
- benatkin 7y ago
  This reminds me of this quote from an article about Phil Libin, former CEO of Evernote: > Eventually he (Phil Libin) pinpointed the source. "It was the carbs," he said. https://www.businessinsider.com/phil-libin-fasting-routine-2017-10 https://www.businessinsider.com/phil-libin-fasting-routine-2... I think bad eating habits, eating unhealthy food, too much, too often, and too erratically has something to do with the uptick in these conditions.
  - ufo 7y ago
    I think that this suggestion that CFS might be caused by bad diet is even more irresponsible than telling it is psychological. CFS patients would wish that it were that simple. CFS onset is often abrupt, and can often happen to otherwise very healthy and active people. For example, a common story is that the patient becomes sick from a viral infection and then gets stuck with chronic fatigue syndrome even after the infection goes away.
    - benatkin 7y ago
      > No one knows the cause yet If we can determine for sure that it's happening a at a much higher rate than in the past, we have a pretty good idea that the cause is the conditions that we live in. Diet that is one thing in which the changes over the years have been similar across different regions. If it was air pollution, the increased rates would show up in some regions but not others. Ditto radiation. I don't think this is like autism in that we were mostly oblivious to it in the past, but I could be wrong. Enlighten me.

jaxgeller 7y ago

If you are living with CFS i recommend giving https://cfsremission.com/ https://cfsremission.com/ a look.

rfugger 7y ago
Also check out http://recoveryfromcfs.org/ http://recoveryfromcfs.org/.
- majkinetor 7y ago
  Orthomolecular approach. Nice.
colordrops 7y ago
Crazy, I basically self diagnosed myself with CFS and got rid of my symptoms over time by discovering most of the recommendations on this page myself. I figured it had something to do with a funky immune system and gut bacteria, and changed my diet and took supplements and probiotics, and it's mostly gone. I even take bacopa, wild. This is really heartening to see that I was on the right track. My wife thinks I'm a hypochondriac with a bunch of placebos.
jchw 7y ago
Woah, I’m now wondering if CFS might be what’s been wrong with me for a while, but I’m not sure. I definitely have terrible sleep, I can barely stay awake during meetings, and I have some of the other symptoms sometimes associated with this (tender lymph nodes in neck, IBS, tinnitus.) I’ve been in and out of the doctor for a couple years, with weird pains, and most recently a lymph node that is a little enlarged in the neck. Obviously there are some scary (but unlikely) potential explanations. But, my sleep quality degrading over the years is something that has been happening much slower, and started much earlier. Not a huge fan of self diagnosis but maybe some of the proposed dietary changes would be worth trying, since they seem fairly innocuous. I’m sure eating more apples won't hurt. If anyone has experience with CFS and has advice, I’m all ears. I’d kill to sleep like I did when I was 18.
- 7y ago

daedalus_f 7y ago

This looks very promising, but it’s too early to say how accurate this test truly will be. Even if this papers methodology is replicated and the test again perfectly selects ME/CFS from healthy controls, it may perform terribly when used in a real clinical setting where the test has to distinguish CFS from the spectrum of other disorders that it will encounter. In other words while the current paper suggests the tests sensitivity is likely to be high it’s much harder to come to any conclusion about it’s real world specificity.

leemailll 7y ago

So what they measure and where is the paper? I read the linked pr but find nothing about them

ufo 7y ago
I don't understand the details but here is the link to the paper https://www.pnas.org/content/early/2019/04/24/1901274116 https://www.pnas.org/content/early/2019/04/24/1901274116
- leemailll 7y ago
  Thanks for the link. I read the paper and it seems that they just measure the impedance (or resistance) of the cell membrane with an artificial increase of NaCl in the extracellular environment (ie plasma in the text). The final NaCl concentration looks like to be doubled than the normal range. This might be an intersting finding, but I can't figure out why the impdecance of membrane need to be measured with increased NaCl in the plama. And whether it is only related with Na+ or Cl- change.
  - ufo 7y ago
    The salty plasma removes water from inside the cells by osmosis. The authors say that this technique is a common model for studying cellular response to stress.
    - leemailll 7y ago
      The thing is if they just want to create a hyperosmotic solution they can add something won't be transported across the membrane, the way they did will change a lot of things on the membrane and inside the cell rather than stress introduced by hyperosmotic stress

derefr 7y ago

Does it say anywhere in the paper what the “promising drug” that decreases the effect might be?

ufo 7y ago
No. They are intentionally keeping that information secret to prevent people from trying to self-treat with it before more studies have been done.
vaelin 7y ago
Not in the paper, but Ron gave a talk where he mentioned an MS drug (I have forgotten which) and a new drug that targets mitochondria which is not yet licensed for anything. Sorry I can't be more specific. I don't remember the details.
rufus85 7y ago
SS31, copaxone and suramin. Suramin is used for African sleeping sickness. They found that African sleeping sickness closely resembled CFS in terms of gene expression.

whalabi 7y ago

I'm just astonished by this. Millions of people (in the US alone!) suffer from this illness and I think everyone has wondered, or heard it wondered, if it's imaginary. For all these people to know there's something actually physically wrong with them is massive. It'll shift the thinking of everyone in the profession, of their families and friends and colleagues, and of themselves. It's a huge, huge breakthrough.

Twirrim 7y ago
I've known several people over the years who have had Chronic Fatigue Syndrome, and most of them have at some stage or another had to deal with discrimination from people that told them it was a made up illness. Having a solid test like this will make a phenomenal difference.
- e-m-p 7y ago
  Yes
daedalus_f 7y ago
This is promising data but it’s very early. The authors are not really sure what the test is measuring on a cellular level, though they speculate a lot in the discussion, and we can’t yet truly infer a causal link between what’s causing the test result and disease status. It’s is going to take a lot more validation before we get to the stage where this is clinically useful. For instance, the control group were healthy, what if instead you compared test results in CFS to another disease condition that can mimic CFS, would it still work as well? In the extreme case, the test could just be a generic flag that someone is non-specifically unwell, we just can’t tell from this data alone.
- vaelin 7y ago
  It could also be measuring the result of extreme inactivity. I am bedridden, and I have no doubt that lying in bed for years has had a profound effect on my physiology independently of my ME/CFS. The acid test will be when we compare ME/CFS patients to matched MS patients. However, as Ron Davis has stated, it might also be the case that MS patients have ME/CFS, as ME/CFS is highly heterogenous and may be arrived at from multiple directions. There are lots of details that need to be ironed out. Nevertheless, this is exciting news.

freeradical13 7y ago

Why did they need machine learning? It seems from Figures 2B-G that there's a clear cut off. "Moreover, to create a classifier for ME/CFS patients capable of identifying new patients, required for a robust diagnostic tool, we developed a trained kernel Support Vector Machine (SVM), a supervised machine-learning algorithm, using our experimental data. To classify new patients based on whether they fall to the right of the decision boundary, we initially selected the two features with the largest significance: change from the baseline to the plateau and change from the minimum to the plateau for the in-phase components of the impedance. Using these features, a cubic polynomial kernel SVM was able to classify the two populations, although the two features are highly correlated, as shown in Fig.2H." https://www.pnas.org/content/pnas/early/2019/04/24/1901274116.full.pdf https://www.pnas.org/content/pnas/early/2019/04/24/190127411...

L2R 7y ago
Nothing wrong with an SVM. How else would they create a decision boundary for classifying patients? The choice of the polynomial kernel is interesting, but I don't think it causes any issues given the data.
- freeradical13 7y ago
  I see, so basically instead of intuiting a simple threshold (e.g. >X% change), they apply an SVM which is able to discover more accurate thresholds (and error ranges). Do you have any suggested resources on learning more about SVM? I guess my question comes from the observation that these advanced statistical techniques such as machine learning haven't been around for long and yet medicine has often created decision boundaries, presumably just looking at the data and making a reasonable cutoff. Is all the extra effort in a case like this worth the time investment?
  - verroq 7y ago
    SVMs are as old school ML as they get. They guarentee the maximum separation at the decision boundary. However it doesn’t scale very well for higher dimensional data. The standard used to be to use some dimensionality reduction technique like PCA to preprocess before feeding it into the SVM. This is all before deep learning.

NautilusWave 7y ago

This biomarker seems incredibly general; I suspect people with certain presentations of a mitochondrial disease would have the same biomarker.

GordonS 7y ago
Agreed, but it's still great to have evidence of a physical condition, as many CFS patients have been made to feel like crackpots at some point, and indeed some doctors use it as a convenient label for people they believe to be mentally ill. Of course, this also raises a question about how those with mental illness are often treated.
- rfugger 7y ago
  To be fair, if someone is overly anxious and neurotic about minor physical symptoms, to the point that the anxiety is making things worse, often the best thing a doctor can do is reassure them that they are fine, to stop worrying, and send them home. Taking those patients' physical symptoms too seriously may be the worst thing to do. I can see that it must be hard for doctors, especially if they only really have about 12 minutes to make a determination...
  - GordonS 7y ago
    Hypochondriasis is real, sure. But I'm not talking about cases like that, I'm talking about patients behaving perfectly rationally, but insistently.

johnchristopher 7y ago

Wait... does it mean chronic fatigue syndrom is recognized now ?

johnchristopher 7y ago
Thanks for the downvote but where I live it's still not recognized and patients are either told it's a depression or some kind of fibroid-myalgia.

UglyToad 7y ago

This sounds brilliant if it can be replicated. From what I've read and heard large parts of the medical establishment still treats ME/CFS patients as lazy/making it up. For there to be a positive diagnosis rather than a diagnosis of exclusion is the first step to getting these people the help they deserve.

ipunchghosts 7y ago

Journalists, this is quite the story. Here you have a bunch of really sick patients with docs around the world saying it's in there head. Then a UK study comes out (PACE) saying patients should engage in activity to help themselves. This only makes the patients worse and eventually so bad that the study was pulled. In comes dr ron davis. His son acquired me cfs while traveling in india. Completely unsatisfied with the lack of care provided by his doctors, he ventured off to research the disease himself assembling a team of esteemed scientists. They all begin to promptly kick ass and take names making more headway on understanding the disease more than anytime in history. Meanwhile, they have open conferences which are posted on YouTube for patients to watch (and see hope) and other scientists to learn from. Davis and his collaborators discover all sorts of cfs links and debunk a bunch of myths.really interesting research is occurring on trypanosomes, metabolic traps, and the microbiome. Eventually a large signal is found when the cells are stressed and voila, we arrive at the test mentioned in the link. This folks is how science is supposed to unfold and it all happening right in front of our eyes for everyone to see in real time. Quite astonishing. These folks will eventually win the Nobel, im sure of it.

heavenlyblue 7y ago
>> This folks is how science is supposed to unfold and it all happening right in front of our eyes for everyone to see in real time. Quite astonishing. So you imply that only scientists with money and direct personal interest in the research are supposed to work on the given topic?
- ipunchghosts 7y ago
  Not at all. What i mean is that scientists discovered a problem and 1) pursued it regardless of what the major funding agencies thought of it 2) encouraged patients to get involved and 3) informed the public of their progress regularly allowing for open discussion and collaboration.
  - cpach 7y ago
    Amazing!

soulofmischief 7y ago

Medicine is a must for any empathetic society. However I wonder if the dawn of modern medicine was the end of natural human evolution. Now that people with diseases such as CFS and diabetes can receive help, we are no longer breeding these diseases out of the gene pool. As a result, we are actually spreading them epigenetically over time. We will be forced to turn to science, such as vaccines and pre- and post-birth biological modification, in order to continue the progression of our species in our battle against ailments and germs. As a side note, what is the best way to get tested for CFS? Is it possible to devlop CFS after contracting certain immuno-suppressant diseases? In my youth I was constantly sleeping in class, but I chalked it up to a combination of insomnia and 24/7 forced consumption of amphetamines to treat ADHD. I mean I would sleep literally anywhere if I had more than half an hour to kill with nothing to do, much to the embarrassment of my guardians. At the time I was not interested in getting tested for narcolepsy and adding yet another item to my list of mental illnesses. Then right after high school, I contracted mononucleosis. I was completely bed-ridden for almost six months, and for about two years I basically had no energy at all. Always sleeping. Those two years went by in a flash. And now I still feel that to a degree, years later. I'm Bipolar II, and when I'm in my manic phase I have near unlimited energy, but when I'm at baseline or in my depressive phase I basically crawl into a permanent coma for two weeks punctuated by work. A lot of people intentionally allow their children to contract mono in their youth, similarly to chicken pox, so that the virus comes at a more manageable period in their life. It can be devastating/disruptive to an adult life. I was homeless and unable to work for a long time. I wonder if any research has been done towards the link between early contraction of these diseases and CFS.

GordonS 7y ago
I was diagnosed with CFS after being prescribed an immunosuppressant. I reacted badly to it, developing chronic pain and fatigue, so it's possible that's a vector (I say possible as CFS is a diagnosis of exclusion, and it's highly likely thatany people diagnosed with CFS have some other, undiagnosed condition of which fatigue and pain are a symptom).
- soulofmischief 7y ago

viburnum 7y ago

That you can measure stress response in blood cells doesn’t rule out that the disease is psychological in origin (although I doubt CFS is).

rfugger 7y ago
At this point, I don't care about the origin nearly as much as finding an effective treatment :)
- Erik816 7y ago
  Agreed, people are very hung up on the mind/body problem. It's a pretty interesting philosophical question, but not that relevant to helping truly sick people get better.

thrrrrrway 7y ago

I had CFS like symptoms so bad I was stuck in bed for several years and the doctor basically would not help me. Eventually I decided to treat it myself with antibiotics and anti parasitic medication. I basically came to the conclusion that for my specific case I had an unknown blood parasite and the fatigue was being caused by neurotoxins. I don't think all CFS are caused by an infection but mine definitely was and I have my life back. If you a researcher looking for a cure, try to test medications that flush neurotoxins out to see if the disease goes away and then try figuring out what is creating them in the first place to treat them.

jxramos 7y ago

Can anyone explain the idea of salt as a cell stressor? > The idea is to stress the samples from both healthy and ill patients using salt, and then compare how each sample affects the flow of the electrical current. Is this an osmotic pressure change that stresses the cytoskeleton or something? Does a cell under a hypertonic solution change its cell membrane channel’s behavior?

deleted 7y ago
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reubens 7y ago
They were bumping the Na to 200mOsm/L, which is insanely high compared to our plasma. Hypertonicity like this causes the cell to shrink, which spoils the delicate relationships and ionic bonds between molecules in the cell. This causes a litany of issues, but one thing is an increase in production of reactive oxygen species, a byproduct of normal metabolism. ROS, otherwise known as free radicals, is what they use to measure cell stress.
xkcd-sucks 7y ago
While a cell is alive, it maintains differential concentration of ions across its membrane, so by definition changing the [Na+] is changing the membrane potential. The stress on the cell is basically it needs to work extra hard moving ions around to maintain itself. This is typically pumping ions against a concentration gradient which takes energy.

daegloe 7y ago

Off topic, but does anyone know why this post didn’t match up with my submission from last week [0]? I know scheme and querystring can throw it off. But in this case the links appear to be the same? Not sore about it, genuinely curious what the matching rules look like! [0] https://news.ycombinator.com/item?id=19783668 https://news.ycombinator.com/item?id=19783668

GordonS 7y ago
Sometimes the mods let dupes through, if they feel it's an important story that didn't get any/enough attention last time round.

not_a_moth 7y ago

Since poor sleep quality is a core symptom of CFS I can't help wonder if sleep is the underlying component. I think we've all underestimated the critical nature of sleep in immune, metabolic, stress, cognitive aspects, etc. It's also hard to self-assess the quality of your sleep, eg. clock-time at each phase, central apnea events, 02 saturation, noise/ light/ movement disturbances while you are asleep, etc.

rfugger 7y ago
A sleep study is critical to ruling out sleep issues before getting a proper diagnosis of ME/CFS. No good doctor would diagnose CFS without a sleep study.
- not_a_moth 7y ago
  That could rule out apneas but not the overall possibility, based on typical sleep studies anyways. e.g. you regularly go to bed thinking about the stuff you have to do tomorrow, so your brain doesn't enter deep sleep phases for long; your doctor thinks 6-7 hours of sleep is good, when you in particular need more like 8.5 ; your neighborhood is noisy, etc.

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olliej 7y ago

40 people isn’t a super large sample size. Given there are huge numbers of people who claim to have cfs I would have expected much larger.

nosianu 7y ago
This is a poor statement since you leave out important qualifiers that would give it some beef. you can't just auto-post "sample size too low" whenever you don't see a thousand people, you have to go deeper to justify your opinion. This sample size can be way to low or it can be very high, completely depends on the population and what you want to show and with what confidence. Summary here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876926/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876926/ But a study like this one here, i.e. if one were to be made, would have plenty of power with a sample size of 40: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ (also consider the opposite, how many participants it would take before you believe the result, but that kind of study would not be permitted; how many does it take to be saved before you believe it) This study - or the lack thereof, which the paper is about - nicely shows that when there is confidence about the underlying mechanism you feel much less (here: no) need for statistics and an RCT.
- olliej 7y ago
  Ok, the sample size was 20 cfs, and 20 non cfs. The problem I have is that the sample size means the there are reasonably good odds that their a significant genetic difference between the two groups. I am making no claim as to whether it’s real - I’ve known people who say they have it, and to me seems plausible, but I’ve also known people who are just not 20 any more, and have children, who also claim to have it - it seems plausible in the latter case that people have been sold on a message of “eat healthy and you won’t feel age”. The problem with weak sample sizes is that it has a significant negative impact whether CFS exists or not: * if it’s a real disease it could be an incorrect marker - for example let’s say the CFS positive group were all Bostonians living in California. It’s highly likely that a random sample of California natives will have at least some uniform marker. Now people who have the disease, but aren’t from Boston may not have the marker, so are told they’re not sick. * the disease doesn’t exist, but you’ve got a marker now. People who happen to have the bogus marker are now diagnosed with something that they don’t have. Now they have a diagnosis that prevents an actual diagnosis of real issues. So I don’t believe it is justifiable to publish a press release on something that effects millions of people, based on a sample that is so small. The initial small sample size might justify a larger sized sample looking at specifically that marker. Then you also have better science (you have a “this marker indicates cfs” hypothesis), and more statistical robustness.

drchewbacca 7y ago

There's a movie called "Unrest" which, in part, covers Dr Davis and his son I think. I thought it was a pretty interesting movie, it's on Netflix in the UK, not sure about elsewhere.

rufus85 7y ago

I have some doubts that this will be 100% specific to CFS, but as professor Davis said at this point it's important to demonstrate that these patients have something wrong with them. Davis called this the last major disease we know almost nothing about. It's 2-3 as common as multiple sclerosis with worse impact on the person's life. It's also the most underfunded illness when the number of patients and the severity is taken into account.

rufus85 7y ago

There is something akin to a daily exertion limit in CFS. When patients exceed it, they have a relapse. It is very easy to have these relapses because the exertion limit is so low. There must be a biological mechanism behind this limitation. It could be something to do with energy generation in cells and this test may be measuring the associated impairment.

starchild_3001 7y ago

YouTube talk about the same: https://www.youtube.com/watch?v=bXGCQPLUtdQ https://www.youtube.com/watch?v=bXGCQPLUtdQ

lsiebert 7y ago

My mom has this. While I'm hopeful this may lead to an effective treatment, it won't give her back the many years she's lived with the disease.

hourislate 7y ago

Ron Davis has worked on this day and night for years. I remember reading about his effort to figure out CFS to save his son. I'm not even sure this was his field of expertise. He just wanted to save his sons life and gave his every waking moment to try and figure it out. It makes me very happy that he seems to have accomplished it. I'm curious if his son is still with him, he was in really bad shape back in 2016.

ipunchghosts 7y ago

Look over at r/medicine about this topic. https://www.reddit.com/r/medicine/comments/blc7tv/stanford_laboratory_claims_to_identify_robust/ https://www.reddit.com/r/medicine/comments/blc7tv/stanford_l... Doctors seem to be overly critical and ignorant. Any reason for this?

cpach 7y ago

For the record, here’s a permalink that uses HTTPS: https://med.stanford.edu/news/all-news/2019/04/biomarker-for-chronic-fatigue-syndrome-identified.html https://med.stanford.edu/news/all-news/2019/04/biomarker-for...