A nanoelectronics-blood-based diagnostic biomarker for ME/CFS (2019) Esfandyarpour, Davis et al

They have a plan


Just about every other "potential biomarker" has faded away . What is encouraging about this one is both the dramatic difference between patients and controls, and the fact that they have a clear plan to develop it.


First, they aim to test the performance of the assay on other similar condition diseases (I had missed this the first time I read the paper). (I am guessing the diseases don't include depression, though for me it is important to substantiate the claims this is a clear biomedical problem).


Second, they have said elsewhere that they are aiming to replicate the results on a larger cohort of patients.


In addition they plan further experiments to understand the specific biological mechanisms underlying the impedance differences.


They are also working on adapting the technology to a platform for preclinical testing of drugs/therapies on cells from ME/CFS patients "leading towards development of a portable, hand-held, and easy-to-use platform that can be operated by researchers and clinicians at any skill level." I think the replication and use of sick controls is importance to do first, to validate the test, before moving to drug development.


I am not sure if this phrasing includes an easy-to-use diagnostic, but elsewhere in the paper they made clear they are trying to modify the technology so that the test could be done in a Dr's office.


Plus, Open medicine Foundation have the funds to see this work through and I imagine publication of this paper will help secure further funding.


This work should progress through to a result, hopefully an effective diagnostic and ideally something that will also help to reveal underlying biological mechanisms of the disease.
 
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Simon M said:
First, they aim to test the performance of the assay on other similar condition diseases (I had missed this the first time I read the paper). (I am guessing the diseases don't include depression, though I think that is essential to substantiate the claims this is a clear biomedical problem).
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Thanks for that summary - I've been unable to read the paper and therefore hadn't read the plan!

In terms of comparison groups, isn't it likely that serious depression (not just a reaction to temporary bad circumstances) is a biomed problem, though a different one to ours?
 
rvallee said:
Not particularly. He says that a test is not particularly relevant since it can be diagnosed without it, when that's literally the most important problem we have and however Wessely and his colleagues think they can diagnose ME patients, they cannot and do not, which makes his comment particularly absurd. It would be the biggest game-changer, as CT scans were for MS.
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I’m not quite sure how I’ve ended up defending someone whose work and views I hold in such low regard but, as we have discovered to our cost, making inaccurate criticisms can be counterproductive, and I don’t believe that is an accurate reflection of what SW said. What he said was:
SW said:
It is also regrettable that it is claimed that such a test would give “scientific proof” of the existence of the condition, and prove it is “not imaginary”. You don’t need a blood test to prove that an illness exists, and nor does the absence of such a test mean that it is “all in the mind”.
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I do not underestimate the desperate need for diagnostic tests, and it is unfortunate that SW does not make that need clear in his comments (which may be because he doesn’t understand it). But he doesn’t say that finding a diagnostic test is “not particularly relevant”. What he says is that we don’t need a test in order to know that people are unwell and to define the condition, which is true and what many pwME having been saying for decades. At this time we do not have a diagnostic test. SW says that doesn’t mean ME/CFS does not exist or that it is “all in the mind”. Taking these comments in isolation I agree with them – although I think that biomarkers are desperately needed to improve the accuracy of diagnosis, as well as to improve understanding of the condition(s).

Barry said:
As stand alone comments I think they were. But of course none of his comments are ever really stand alone. e.g. Yes, he is right to say that the test results could be due to either the cause or consequence of whatever ME/CFS turns out to be, and that it is important we know. Well yes ... and no ... to the importance aspect. From the perspective of finding a diagnostic marker, it may not be so important, even though it will become important to know when seeking a cure. It's classic SW smoke and mirrors. I imagine medical history must have many examples where reliable diagnostic markers were discovered well before cause and effect relationships were unravelled.
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As I’ve said above, if it’s an effect, it’s important to know if it’s an effect which is specific to ME, to some or all fatiguing illnesses, or just to chronic inactivity. If it turns out to be a unique marker for ME/CFS then it wouldn’t matter from a diagnostic point of view whether it was a cause or effect, but it would still be interesting and useful to know.

I completely agree on your point about stand alone comments.

Keebird said:
At this point, whether this tests positive in other illnesses is irrelevant
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I have great respect for Ron Davis, and I’m hugely appreciative of his work, but I don’t agree with that comment. It seems highly relevant to me.

strategist said:
Wessely is probably trying to say, without actually saying it, that the observed effect is due to deconditioning.
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He may well be. But until it is proved otherwise it would be unwise to discount the possibility that the results may be an effect of prolonged inactivity. We must be careful not to give him ammunition to discredit us if this test turns out to be unhelpful for diagnostic purposes.

James Morris-Lent said:
I'd be curious to see results for the so-called mild patients such as myself, who are plainly not 'deconditioned' (in the way the word is used in this context) but still have profound deficits in stamina and vigor (not to mention all the other shit...).
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Yes, I think Ron Davis’s idea of using severe patients in the first instance was sensible because they wanted to find the strongest possible signal, but from here on mild/moderate could be more useful as it will be much easier to find controls who are similarly physically active/inactive.

One of my concerns is that the results could be too good: 100% accurate at differentiating CFS from healthy controls, with a minuscule p value. I hope this may be due to the small sample size and the patient selection criteria. But it makes me wonder if it is more likely to be a test that just shows that someone is fatigued or has been incapacitated for a long time – or whether there may be some other explanation for the results which would render the test unuseful as a diagnostic tool.
 
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Robert 1973 said:
What he says is that we don’t need a test in order to know that people are unwell and to define the condition, which is true and what many pwME having been saying for decades. At this time we do not have a diagnostic test. SW says that doesn’t mean ME/CFS does not exist or that it is “all in the mind”.
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The problem with SW comment is not the actual words, but the context and the the underlying meaning which are not obvious to the average reader. A person has to really lack any self awareness to make that comment (It is also regrettable that it is claimed that such a test would give “scientific proof” of the existence of the condition, and prove it is “not imaginary”. You don’t need a blood test to prove that an illness exists, and nor does the absence of such a test mean that it is “all in the mind”.).

Not because it's not true, but because he's the reason why doctors still think that it's all in the mind. Also, I'm sure that in his view, deconditioning+unhelpful illness beliefs surely count as a real illness, which may be a good thing to those who suffer from it (that doesn't include pwME), but it sure doesn't count as a real illness in most physicians' minds. Essentially, he's just saying the same old. Psychogenic illness is a real illness, no need for a test, and it's not all in the mind.

Also, let's not forget that there are likely more countries where this illness is not diagnosed at all/misdiagnosed as somatisation, than where it is diagnosed and scientific test WOULD absolutely change that.

Edited: lack self-awareness
 
Now that enough time has passed for the psychosocial lobby to voice its opinion, it's pretty shockingly clear how naked their self-interest is and that they couldn't care less what actually happens to us, that they are perfectly content to keep us in misery and suffering for the mere benefit of extending their reign of error by a few years.

Even more remarkable that they are so stuffed inside their own bubble of self-interest that they can't see how ghoulish it will look in sober hindsight. They do not want to see any progress made in this field whatsoever and they are making it loud and clear. "We do not need better diagnostic tools!", say people who have no ability to properly diagnose a disease they have spent decades sabotaging.

Shocking, yet utterly unsurprising. What a weird state of affairs.
 
Sasha said:
In terms of comparison groups, isn't it likely that serious depression (not just a reaction to temporary bad circumstances) is a biomed problem, though a different one to ours?
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That is unknown, though “just a reaction to being circumstances” seems to be underplaying the problem. Certainly some cases seem to be caused by immune problems, and that’s an active area of investigation. But non biomedical problems can cause very serious depression.
 
Simon M said:
That is unknown, though “just a reaction to being circumstances” seems to be underplaying the problem. Certainly some cases seem to be caused by immune problems, and that’s an active area of investigation. But non biomedical problems can cause very serious depression.
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Sorry, didn't mean to appear to minimise the results of depression being caused by events rather than being endogenous (I've seen the former and it was horrific) - I didn't express myself well there!
 
Robert 1973 said:
Yes, I think Ron Davis’s idea of using severe patients in the first instance was sensible because they wanted to find the strongest possible signal, but from here on mild/moderate could be more useful as it will be much easier to find controls who are similarly physically active/inactive.
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The exact opposite of the BPS lot who steer clear of the severely ill as there is no money to be made from bed bound 'customers'. As far as they are concerned they don't exist.
 
anyone else feel the urge to throw themselves in the ocean since this came out? ;) the Simons will prolly say it's being out of shape that causes the cell stress if it turns out we're the only ones with this outcome
 
Simon M said:
Just about every other "potential biomarker" has faded away . What is encouraging about this one is both the dramatic difference between patients and controls, and the fact that they have a clear plan to develop it.
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I did wonder if someone else could replicate with a different microfluidic chip that measures impedance. There seems to be quite a bit of research in this area although its not using nano scale engineering. I'm not sure if what they are doing with impedance matches with what others are doing though.
 
Barry said:
Yes, I understand and appreciate that. My concern is that until the cellular stress differences can be proven due to something other than deconditioning, then team PACE can still just say they have never disagreed there is something physically wrong with pwME - just that they believe it is deconditioning. I would think (and sincerely hope) it a high probability the cellular stress difference will be proven to be something other than deconditioning, but until it is proven, not just hypothesised, I'm not sure this gives us much more to argue at the PACE advocates. In terms of pure science of course (which is what this should ideally all be about), then Ron Davis' team are doing some great work.
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Unfortunately, my personal analysis of the history of medicine concluded that progress is more likely to correlate with mortality rates of physicians than patients. Most seem to pass a threshold when they graduate and are licensed, after which their beliefs change little and slowly. Multiple honors make changes in opinion less likely, not more. If you are depending on changing beliefs of the BPS crowd you are setting yourself up to be disappointed.

On a more positive note, we are finally getting research which directly addresses problems with the source and control of energy in muscles and nerve cells. Ion channels and transporter molecules are ubiquitous in living organisms and associated in some way with just about any pathological condition you can name. I've been waiting for a new approach to the subject of Na/K ATPase interactions for some time, but couldn't see a great deal happening. When I looked for patients with more extreme examples of these problems, I found them in several forms of the rare conditions periodic paralysis and episodic ataxia, that are classed as channelopathies. These can be with high or low levels of potassium (K) or with sodium (Na). While trying to help one patient on another forum, I realized her problem was actually with a calcium channel, yet she was grouped with patients having very different biochemical problems.

Calcium channels are active in every example I can think of where cells release the contents of vesicles by fusing these with cell walls. This is another ubiquitous process which deserves to be measured clinically, and I believe an assay like this one might well serve as a quick way to distinguish patients with different problems. You don't want to give a patient with such a problem a calcium channel blocker, which is a standard treatment for conditions that appear similar.

We are still a considerable distance from common clinical tests in every doctors office, but we are finally dealing with fundamental physiology.
 
Pechius said:
Also, let's not forget that there are likely more countries where this illness is not diagnosed at all/misdiagnosed as somatisation, than where it is diagnosed and scientific test WOULD absolutely change that.
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I am desperate for a diagnostic test but we should be mindful that such a test would only change things for those who test positive for that particular test. Even if the nanoneedle proves to be useful as a diagnostic tool there may still be a significant proportion of people who are currently diagnosed with ME/CFS who do not test positive because they are in a different sub-group or have a different illness. We must ensure that they/we are not thrown under the BPS bus just because they they do not have a particular biomarker.

The irony has not escaped me that I am agreeing with a point that has been made by SW in order to protect people from being run over by the bus that he is driving. To clarify, I agree with SW that people can and should be diagnosed in the absence of known biomarkers (albeit imperfectly), but I strongly disagree with him about how such patients should be treated thereafter. The notion that patients should be treated as though their illness is perpetuated by their own beliefs and reversible by their own efforts just because there is no diagnostic test is both unscientific and unethical.

strategist said:
Vogt and that cardiologist demonstrate why we need an diagnostic test: to put an end to the baseless psychogenic illness theories.
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Unfortunately, no single diagnostic test will put an end to baseless psychogenic theories. Diagnostic tests for MS, epilepsy and other conditions to which these theories were previously applied did not put an end to them and nor will a test for ME. The same or similar theories will just be applied to different groups of people. If we want to defeat baseless psychogenic illness theories for good we need to expose the bad science and woolly thinking upon which they are based.
 
Robert 1973 said:
SW says that doesn’t mean ME/CFS does not exist or that it is “all in the mind”.
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He and the others keep changing their tune to try and save face.
There are many instances where SW has more than inferred that ME doesn't exist, and one of the prime reasons for 'changing the name' to CFS was to 'reclassify' it as a mental illness.

I am reminded of Nigel Speights comments in his recent interview with Gary Burgess on the ME show

"If one had a kind of fairy godmother wish it would be that we find a cure quickly, and once we find a cure, a medical cure, then the psychiatrists would just wither away and say this is what we always said it was anyway, a physical illness and we were only trying to help. "

eta: The Countess of Mar sums up Simon Wessely quite well in her speech in the HoL debate of 2002
...since 1987 Dr—now Professor— Simon Wessely has been relentless in his proposition that ME does not exist. For example, in the journal of psychological medicine in 1990 he claimed that M E exists only because well-meaning doctors have not learned to deal effectively with what he called "suggestible patients". I have mentioned the article about non-diseases in the British Medical Journal of 13th April. I refer the Minister to a letter in the same journal, headed: What do you think is a non-disease? Pros and cons of medicalisation". It is signed by Simon Wessely, Professor.
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Wessely is responsible for the accuracy, honesty, impartiality, quality and scientific integrity of the research which he has published.

There are many documented instances in which he is in direct conflict with other competent medical opinion. His tactics include manipulation, distortion, invention, misquotation, suppression, exploiting public ignorance and deliberately constructing his presentations to fit his audience. Rather than his having orchestrated a campaign against patients and their credibility, he claims it is patients who are orchestrating a campaign of vilification against him.
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Professor Wessely seems to have taken it upon himself to reclassify ME as a mental disorder in the WHO Guide to Mental Health in Primary Care in his capacity as a member of the UK WHO Collaborating Centre for Research and Training for Mental Health. He has disingenuously amalgamated his own definition of chronic fatigue syndrome with ME by stating that ME may be referred to as CFS and is thus, he claims, a mental disorder.
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https://api.parliament.uk/historic-hansard/lords/2002/apr/16/chronic-fatigue-syndromeme
 
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Robert 1973 said:
I am desperate for a diagnostic test but we should be mindful that such a test would only change things for those who test positive for that particular test. Even if the nanoneedle proves to be useful as a diagnostic tool there may still be a significant proportion of people who are currently diagnosed with ME/CFS who do not test positive because they are in a different sub-group or have a different illness. We must ensure that they/we are not thrown under the BPS bus just because they they do not have a particular biomarker.

The irony has not escaped me that I am agreeing with a point that has been made by SW in order to protect people from being run over by the bus that he is driving. To clarify, I agree with SW that people can and should be diagnosed in the absence of known biomarkers (albeit imperfectly), but I strongly disagree with him about how such patients should be treated thereafter. The notion that patients should be treated as though their illness is perpetuated by their own beliefs and reversible by their own efforts just because there is no diagnostic test is both unscientific and unethical.
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I tend to think this work is less interesting as a biomarker but as a demonstration that something changes when a cell is put under stress and its probably more important when they publish the plasma switch results. In this way the work hints that there is a change in something in a cells function when energy is required vs with ME vs non-ME patients. I say hints because its only been tested on 20 patients and its hard to associate the effect with symptoms hence this could be something that happens with a number of diseases as part of a symptom rather than any form of cause.

Maybe what would be nice is if they looked more at what was happening to the cells in this process (but I've not kept up with the talk they did recently with their talk that mentions exosomes).
 
I think this is a different report on the same process:

Source: HealthDay

Date: April 30, 2019

Author: Dennis Thompson

URL:
https://consumer.healthday.com/dise...diagnose-chronic-fatigue-syndrome-745703.html

Ref: https://www.pnas.org/content/early/2019/04/24/1901274116

Blood test might diagnose Chronic Fatigue Syndrome
--------------------------------------------------

TUESDAY, April 30, 2019 (HealthDay News) -- Chronic fatigue syndrome is such a mysterious illness that it took years to be recognized as a legitimate ailment, and doctors still struggle to accurately diagnose it. Now, an experimental blood test has successfully spotted the syndrome, also known as CFS, in a finding that hopefully provides new insights into the inscrutable illness.

The test tracks changes in the electrical pattern of a person's cells, and it accurately flagged all CFS patients in a small group of 40 people, researchers report. 'When we stress the cells, we can easily differentiate them based on the signal they are showing,' said lead author Rahim Esfandyarpour. 'It's a huge difference.' Esfandyarpour worked on the test with a team while at Stanford University in California. He's now an assistant professor of electrical engineering and computer science at the University of California, Irvine.

More at link.
 
Adrian said:
I tend to think this work is less interesting as a biomarker but as a demonstration that something changes when a cell is put under stress and its probably more important when they publish the plasma switch results. In this way the work hints that there is a change in something in a cells function when energy is required vs with ME vs non-ME patients. I say hints because its only been tested on 20 patients and its hard to associate the effect with symptoms hence this could be something that happens with a number of diseases as part of a symptom rather than any form of cause.
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Isn’t the hint from both the PNAS paper and Fluge and Mella’s paper that there doesn’t seem to be any difference between ME/CFS cells and healthy ones? My limited understanding is that these studies hint that the difference seems to be in the plasma or serum, and that cells in ME/CFS plasma or serum act differently to cells put in healthy plasma or serum when they are made to work harder.

Apologies if I’ve misunderstood your point.
 
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