Evidence of a Novel Mitochondrial Signature in Systemic Sclerosis Patients with Chronic Fatigue Syndrome 2023,van Eeden et al

PET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research (2021, Frontiers in Aging Neuroscience)

 

My impression is that few people get a diagnosis based on measuring amyloid plaque using scans. Apart from anything else, why use scans when there are no (UK) available treatments?

 

Thank you for the clarification @Jonathan Edwards, I think I misconstrued one or two elements of your post.

I agree with your frustrations regarding overuse of the word and obsession over classification accuracy without due consideration of either practicability or true clinical utility. In fact only an hour ago I raised these issues in my talk at IACFSME.. we're on the same page.

I guess it comes down to the intended purpose of potential tests/markers. Those which are *consequences* of underlying pathology, and align with symptoms will still produce value when clinician expertise or belief is lacking. Of course, those which reflect, instead, a *cause* of disease have more utility as you suggest.

This raises a crucial question that I would love to hear your thoughts about: is the former scenario (related to consequences of pathology) one worth pursuing in the interim until cause-related tests are identified, presumably much later due to the additional complexity of finding those answers?

Ie: is a less powerful test that adds little precision versus symptom presentation still worth pursuing to provide, at very least, some objectivity and credibility in scenarios where otherwise unhelpful clinicians are involved. (at least until a better test is found, potentially many years later).

 

My cell free DNA is well out of spec. Abnormally high. I have no idea why this simple, cheap and I'm assuming reliable test is not used more often in pwME and similar. The Breakspear have been testing this for a decade or so. Not sure if they have published this.

 

Is that test result broken down further? Ie nuclear or mitochondrial DNA? Clues to cell origin, eg neutrophils (NETosis)?

 

Is it a reliable test?
Breakspear don't have a reputation for being scientifically reliable.

 

It's a while since I checked the test out. Probably 8+ years ago. From memory the method was straightforward, my results were consistent and the test offered by accredited UK lab. My reports are now in our loft and not easy to access.

 

I wonder if this could be relatively low-hanging fruit for hypothesis testing about causes of PEM. Ie is high baseline but even higher post-exertion cfDNA/NETosis contributing to physiological degradation and symptoms?

Well-characterised patient group vs healthy normal vs healthy sedentary vs healthy trained athlete groups. cfDNA is low in inactive people, so if it's high in ME at baseline that's an interesting starting point. Is it all neutrophil-derived and does this point to increased baseline apoptosis/NETosis? Does it go sky high following an exercise challenge or is it just the same degree of elevation as sedentary controls? Healthy people will go high, but trained athletes show much less increase.

I'm working through reading these, but in case there's interest here are some refs —

Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes (2023, Cell Reports Medicine)
Physical Exercise Promotes DNase Activity Enhancing the Capacity to Degrade Neutrophil Extracellular Traps (2022, Biomedicines)
New Perspectives on the Importance of Cell-Free DNA Biology (2022, Diagnostics)
Physical activity specifically evokes release of cell-free DNA from granulocytes thereby affecting liquid biopsy (2022, Clinical Epigenetics)
cfDNA Changes in Maximal Exercises as a Sport Adaptation Predictor (2021, Genes)
Exploring the Potential of Cell-Free-DNA Measurements After an Exhaustive Cycle-Ergometer Test as a Marker for Performance-Related Parameters (2017, International Journal of Sports Physiology and Performance)
Increases in Circulating Cell-Free DNA During Aerobic Running Depend on Intensity and Duration (2017, International Journal of Sports Physiology and Performance)
Acute Severe Exercise Facilitates Neutrophil Extracellular Trap Formation in Sedentary but Not Active Subjects (2013, Medicine & Science in Sports & Exercise)