Development and validation of blood-based diagnostic biomarkers for [ME/CFS] using EpiSwitch®… 2025, Hunter et al. (Oxford Biodynamics)

[MelbME]

We have no indication whatsoever that this is the case. It’s pure speculation.

Every single trial for POTS interventions have failed or been subject to so much bias that it’s impossible to get anything meaningful from it. People are eager to interpret causality into everything they do. If we’re to listen to that we should also listen to those that say that their medallion helped them.

The burden of proof goes the other way. The proponents of POT as a syndrome are the ones that have to argue why it must be. They have not.

You probably know this but my understanding is that POT is postural orthostatic tachycardia, it occurs in healthy people too. You stand and your HR jumps up and stay up by 20bpm from resting for over 10 minutes.

POTS is that you have a suite of symptoms along with POT.
Clinicians are confident a patient has POTS when they use a treatment to fix the POT (midodrine, mestinon) and all the other symptoms (fatigue, brain fog, etc) get significantly better or completely resolve.

Because POT can just exist in people without symptoms, it is possible that you just happen to have POT and it doesn't bother, then you get ME/CFS or another syndrome with a suite of symptoms that means you can now meet a POTS diagnosis. Makes it quite messy though, as the average person isn't tested for POT until they show symptoms of the syndrome.

 

[ChronicallyOverIt]

You probably know this but my understanding is that POT is postural orthostatic tachycardia, it occurs in healthy people too. You stand and your HR jumps up and stay up by 20bpm from resting for over 10 minutes.

We could probably move this to an entirely new thread but I was always told it was 30 bpm. Along with that most POTS patients bpm trend up over that 10 min instead of down.

POTS for me was rather sudden after a particularly bad crash and not a gradual thing that crept overtime. Suddenly not being to tolerate being up right was a very scary thing.

I find it interesting that people here think POTS is not treatable? It seems to me to be one if the only things that can be treated with a measured effect? Take medication = postural heart rate go down == patient feel better. Also isn’t it part of the CCC criteria? If we say there’s no CFS treatment, does that include not treating POTS?

 

[Utsikt]

You probably know this but my understanding is that POT is postural orthostatic tachycardia, it occurs in healthy people too. You stand and your HR jumps up and stay up by 20bpm from resting for over 10 minutes.

I thought tachycardia referred to a resting HR above 100 bpm? So POT would be resting HR > 100 bpm while standing but not lying down?

POTS is that you have a suite of symptoms along with POT.
Clinicians are confident a patient has POTS when they use a treatment to fix the POT (midodrine, mestinon) and all the other symptoms (fatigue, brain fog, etc) get significantly better or completely resolve.

Is there any reliable evidence that the HR is directly tied to symptoms? Do you have any examples?

And do you have any evidence from properly controlled trials wrt the treatments?

Because POT can just exist in people without symptoms, it is possible that you just happen to have POT and it doesn't bother, then you get ME/CFS or another syndrome with a suite of symptoms that means you can now meet a POTS diagnosis. Makes it quite messy though, as the average person isn't tested for POT until they show symptoms of the syndrome.

This makes no sense to me, and just illustrates how useless the concept of POTS is. Why would you centre the syndrome around POT when POT can frequently occur without the other symptoms?

 

[ChronicallyOverIt]

Sorry, only POTS is.

POTS implies that there exists a syndrome where tachycardia upon standing is key to the syndrome. That doesn’t seem to be the case, and regardless it’s pure speculation.

OI is just «intolerance to not being horisontal». The use of HR to measure OI is flawed for much of the same reasons as for POTS - HR might not be relevant at all.

If you can’t call it Postural orthostatic tachycardia syndrome what do you call it? All POTS patients have the same symptom of heart rate staying abnormally elevated after standing, that not a syndrome?

Syndrome: a group of symptoms which consistently occur together, or a condition characterized by a set of associated symptoms.

 

[ChronicallyOverIt]

I thought tachycardia referred to a resting HR above 100 bpm? So POT would be resting HR > 100 bpm while standing but not lying down?

That is not POTS. If that was the criteria everyone would have POTS. The postural and orthostatic part you are completely ignoring.

It’s defined a jump in 30 BPM sustained over 10 minutes when going from lying to standing. Key is sustained.

 

[Utsikt]

If you can’t call it Postural orthostatic tachycardia syndrome what do you call it?

Call it what it is: OI. That’s the important part, that you get unwell when not horisontal.

All POTS patients have the same symptom of heart rate staying abnormally elevated after standing,

Yes, because POTS has been defined that way. That argument is circular.

that not a syndrome?

There is nothing that indicated that >30 bpm HR increase when standing is the sensible defining or diagnostic feature when trying to pick out people that feel unwell then standing/sitting and where it might be for the same reasons. There is also nothing to indicate that lowering the HR of the patient helps with their OI.

 

[Utsikt]

That is not POTS. If that was the criteria everyone would have POTS.

I was responding to a question about POT there, not POTS.

The postural and orthostatic part you are completely ignoring.

Where?

 

[ChronicallyOverIt]

Call it what it is: OI. That’s the important part, that you get unwell when not horisontal.

Yes, because POTS has been defined that way. That argument is circular.

POTS is under OI but it is with the increase of BPM. OI does not have to have the increase in BPM. Again it’s a syndrome since it has a collection of distinct symptoms, one of those being that increase in BPM.

 

[DMissa]

Right, and since the molecules picked out are cell type specific it makes interpretation particularly fraught.

I should have mentioned that this was my reasoning!

 

[DMissa]

That aside, it's nice to see some of the immune hits they got. It's encouraging that they did training, test and validation.

One thing is that if we take immune cells and then the pathway hits are broadly immune related that isn’t really saying much, since it’s what would be expected by chance.

 

[jnmaciuch]

Looking at the methodology, this seems like exactly the same information that a Hi-C assay would be able to give you, but even less so since it’s only looking at chromosome “loops” and not general structural proximity. I had a chance to attend a lecture on Hi-C a few months ago by someone who has put out a lot of studies since the technology was developed, and it was one of the first times I’ve heard a scientist admit that the last decade of work with their method of choice has by and large failed to deliver on the promised insights. I can’t imagine that proprietary Hi-C Lite would do much better.

Interpretation-wise, a chromosome loop just tells you that there are probably more CTCF linkages in the vicinity of certain genes, which is itself probably downstream of any number of transcription factors. It might indicate that something is being transcriptionally regulated in that general area but even in that regard, a run-of-the-mill ATAC-seq would probably give you more specific and useful information.

From prior chromatin studies I’ve worked on, I can confirm that a massive amount of chromatin remodeling happens in myeloids just as a result of normal aging. It’s a pretty safe bet that age and comorbidities are going to be driving a huge amount of the variance here—if those weren’t controlled for, I wouldn’t even spend time speculating on any genes that may have popped up here.