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

I think I didn’t phrase my original post clearly. I don’t mean that alone should be diagnostic of ME. I understand what you and Kitty are saying and agree, but tests are usually done so that they can help pinpoint towards something - narrow something down - and then at some point help diagnose it, together with other tests and examinations if needed etc. For example when autoimmune disease was suspected for me, ANA was picked up on certain tests and then they narrowed it down further afterwards with other tests, then questions about symptoms etc. Things aren’t always clear cut I agree, but that’s not what I meant.

My issue with the nanoneedle is right now we know very little about it. I don’t think there’s even a confirmed or published theory on what exactly the nano needle is showing? What it means? We don’t even know enough to say it could be used like ANA is, to narrow things down further. It could be picking up something that may not even be something that could help narrow things down further. We don’t know whether it’s positive in other people. How many other conditions. What those conditions have in common. To what extent. It could end up being like CRP. Sometimes when CRP is super high you get admitted to A&E as they know something is wrong. But not a lot else yet until they look further.

What if it ends up being like that? I’m not sure GP surgeries would invest in that because how does it then help then narrow anything down? What if the most they may say is - this person is sick. They can do that anyway with the examinations. It could help in disability tribunals etc - but again, it might just say that person is sick, but not to what extent, or why, or how, and it might be shared with lots of other diseases which may not even be that severe. I don’t know, maybe I’m just being overly frustrated or critical but I just wish we knew something more. At the moment it feels like we know very little and it’s hard to keep getting invested in it and getting excited and then feeling down again... I just want more substantial information first. It may end up being really indicative of something crucial going wrong in ME.. and I hope it is.. but I just hope for more information to be released.

 

I assume goodwill among GPs and that they want to help them get better. They have a patient show up saying they are tired, just not feeling well or with weird symptoms. Once all the common things are ruled out and the patient is still the same the doctor will then pass them on to MUS, FND, or CFS which they have been told is the best way to cure these patients.

A quick blood test that can be done by the nurse at the surgery which shows the patient has a biomedical problem would be a massive breakthrough.

 

Everybody knows Ron is stretched way too much for his age

For me that's a separate matter to what he said about not being able to find patients for comparison

The latter I don't believe

 

I must admit I hadn't actually thought about it being used in primary care, although of course that doesn't mean it wasn't the team's original intention.

I'd been working on the assumption that it would be used as part of a research toolkit, to ensure that participants in trials are highly likely to have ME and not another condition with symptoms in common – and possibly as a way of stratifying subgroups. We could certainly use better ways to do this over the next five years or so.

 

https://mecfsresearchreview.me/2019...d-lead-to-a-diagnostic-blood-test-for-me-cfs/

 

Haven't been able to follow the whole thread so maybe this has been covered already but isn't it premature to assume that whatever it is the nanoneedle shows actually reflects exclusively biomedical illness?
Is it not possible psychological illness could also register as 'not healthy' on the nanoneedle? Many psychological illnesses seem to have assorted non-specific biological abnormalities, too.

 

Even if it were possible for this to happen sometimes, it'd still be a matter of sensitivity and specificity, which is why everyone here is so antsy for seeing the test run on a validation cohort. If like 1% of the signals picked up by the nanoneedle were false positives from mental illness, there wouldn't all that much harm done.

But it's not like brain-behaviour map to each other in a clear-cut manner. There's a lot of degeneracy involved (different inputs leading to the same output), so it'd likely not be very sensitive to mental illness. It's not like it wouldn't be a massive sensation if the nanoneedle somehow helped in solving that problem, because God knows psychiatry hasn't managed so far. And yeah, I guess that we don't know what this measured impedance correlates to in vivo is another problem still.

 

I think that because the nanoneedle results were around the same time as the 'mystery molecule'/something in the blood/serum swap 'announcements' it gave the impression that they were somehow connected.

It would be nice if they and the other teams working on similar lines of research (ie the something in the blood) could somehow combine their efforts to show one way or the other if they are.

 

I could be wrong, but I don't see physicians/doctors offices using this device to diagnosis patients for disability purposes, we have different comorbities and too many changes as it relates to duration of illness. I'm not sure we can truly diagnose ME with this device. I know my GP wouldn't because of her attitude back in the early 90's when I asked for her assistance. She said she didn't know anything about disability and walked out the room.

My ME doctor helped patients apply for disability and took a hiatus in 2003 because I suspect from what he told me ("I haven't jumped off the bridge yet") that he was being put under the microscope.

 

The device shows biomedical anomalies so it would be useful important evidence to the people who decide who gets disability benefits. A lot of their energy goes into deciding who is "genuinely ill" from those who are just freeloaders. I have heard of people getting money after a positive result on the 2 day CPET for instance.

GPs would not give it for benefit reasons but as part of medical care.

 

Question on the science.
The nano-needle technique took PBMCs in plasma, stabilised on the sensor array and then added hyperosmotic saline to bring it up to 200 mmol/L. From 60-120 minutes there was a rise in the impedance (in-phase resistance), which was attributed to metabolic stresses / ATP use in the PBMCs of ME patients (highly specific).

Filtering plasma by size reduced the effect significantly, leading to the idea that there was something-in-the-blood.

Does anyone know if they tried that test without the white cells present?

i.e. Could micro-clots in the plasma be degrading enough to expose and amalgamate the serum amyloid A etc or otherwise changing their conformation sufficient to cause impedance changes?

 

My understanding is that the point of the experiment as to assess the impedance of the cell membranes, not the solution. However, I never understood from the description how they knew what they were measuring.

I cannot see any particular reason why macromolecular aggregation should also the result or why the presence of clots would aggravate amyloid proteins.

I think it is pretty pointless to speculate about a result when we do not have enough information to make any sense of it. If this was a real finding it would be a routine assay by now.

 

Thank you @Jonathan Edwards

 

Regardless of any development of the nanoneedle, I think it might be worth following up on the salt stress test, which could potentially reveal a great deal about ME/CFS. I would love comments from people on this thread who know a great deal more about the nanoneedle and this study than I do.

The nanoneedle salt stress test – too good a clue to leave abandoned on the lab bench?