aure 🍂🌰 Profile picture
May 12, 2023 13 tweets 7 min read Read on X
Since yesterday I've been gathering my thoughts on the excellent @BhupeshPrusty talk at the #MECFSconference 🧵

The main topics were:
- Mitochondrial dysfunction
- Herpesviridae
- Autoimmunity

#MEAwarenessDay2023 #MEAwarenessMonth Leading slide of Bhupesh Pr...
The oral presentation itself was concise (this is usual in medical conferences) & has possibly saved significant novel findigs until their upcoming article is published.

This may explain why the breakdown on possible biomarkers and treatment options has been so succinct
(...)
However, this won't be an impediment to try to expand (and speculate a bit) on potential biomarker avenues exposed in Bhupesh's talk.

✅First of all, (I know this is an accepted hypothesis but bear with me) their results show strong evidence that #MECFS has an autoimmune basis: Heatmap and PCA analysis sh...
In fact, that ME/CFS patients have overlapping autoantibodies for SLE and MS*

Probably, certain autoantibodies might fulfill criteria for a good biomarker, in the future:

*SLE: Lupus
MS: Multiple sclerosis

Here's a small thread expanding on biomarkers:
ME/CFS patients have overla...
In particular, their results show a subgroup of auto-antibodies that might have enough specificity to be useful biomarkers

✅Antimitochondrial and anti-cytoskeleton antibodies

MitoGFP & mitofilin assays show how anti-cytoskeletal atbs. deform and fragment attached mitochondria Image
The talk gave an important clue regarding a disabling, not rare symptom present in #MECFS patients: Photophobia

✅Their results point to Anti-aquaporin-4 autoantibodies as associated to photophobia.
These are known to be related to optic neuropathy:

ncbi.nlm.nih.gov/pmc/articles/P…
However, autoantibodies aren't the only biomarkers in Bhupesh's talk:

✅Herpesviridae-derived dUDPase (from HSV-1, HHV-6 and EBV) is a potentially valid marker, ready for validation studies and clinical use in the short-term.

Both HV positivity and reactivation seem relevant. ImageImage
Herpesvirus-derived dUDPase seems to induce mitochondrial dysfunction due to cytoskeletal interference

HVs hijack the cytoskeleton for their own functional needs, while causing mitochondrial damage in the process. Image
Another candidate named was Fibronectin:

- a multifunctional, adhesive glycoprotein that plays an important role in tissue repair, in regulating cell attachment and motility

In layman terms, it works as a glue and is related to injury response.

fibrogenesis.biomedcentral.com/articles/10.11…
My take on Fibronectin: it might be more useful for phenotype classification than for clinical use (may be good for severity after diagnosis).

FN (plasma & cellular) levels are increased in #MECFS and #LongCovid, supporting the role of tissue injury/repair in both conditions. Image
Another powerful message from the Bhupesh Research Lab is that ME/CFS shares less molecular signatures with Long COVID than previously expected.

We must keep our eyes open, as we may expect futher differences, interactions and similarities between the two conditions. Image
For me, the outlook is optimistic:

We have biomarkers ready to be tested

Studies are very expensive: they feature multiple experiments which have to be done with optimal design and quaility

However, as more funding is available we hopefully will accelerate further discoveries.
Here's a link to the talk:

drive.google.com/file/d/1pLeuhI… Image

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More from @maureviv

May 12, 2023
An useful biomarker should have at least:

- A very good sensitivity, and a reasonable specificity,
- A very good specificity, and a reasonable sensitivity,

Or both.

But what are sensitivity and specificity?
Sensitivity: the ability of a test to correctly identify sick patients with a known disease.

Specificity: The ability of a test to correctly classify an individual as disease-free.

ncbi.nlm.nih.gov/pmc/articles/P…
A sensitive test aims for "positive classification": to identify all patients who are sick.

However, a biomarker that is sensitive but non-specific carries the cost of incorrectly classifying healthy patients as also sick.
(...)
Read 5 tweets
May 11, 2023
Excited to join in! #MECFSConf Image
Excellent talks, discussions and insights!
#WorldMEDay #MEAwarenessWeek ImageImageImageImage
Read 4 tweets
May 2, 2023
Basic thread about fingertip blood sampling for lactate levels 🧵#TheAcidTest

Lactic acid is a key molecule, part of our anaerobic fermentation, which is one way for cells to obtain energy (=ATP⚡).

Advantages:

1. Anaerobic metabolism means it doesn't need oxygen to work.
... Cori cycle
2. Lactate can go back to pyruvate->glucose (Cori cycle) to be included in the mitochondrial respiratory chain (using oxygen)

Disadvantage: anaerobic is much less efficient than the aerobic respiratory chain

➡️When we measure lactate we're usually interested in two things:
1- Lactate elevation due to tissue hypoperfusion:

It can be caused by complete occlusion of a large vessel followed by reperfusion, which releases lactate back into circulation.

Small vessel occlusions or capillary dysfunction may also lead to high lactate released in venules.
Read 18 tweets
Dec 10, 2020
I have read the whole thread, which describes a horrible situation, overlooking a vital problem with a patient, plus misdiagnosing her

That will likely repeat in other patients if nobody takes it as what it really is: a dire threat

(Read the quoted thread first)🙏#FOAMed
(1/n)
Central apnea occurs in many situations, and cranio-cervical instability is definitely the most common
Why does apnea happen?

Because the diaphragm (an essential muscle for breathing) doesn't activate Image
The breathing impulse gets carried from the brainstem respiratory centers, via brainstem and spine, until it reaches about the 4th cervical/neck vertebra (C4)

Then it exits the spine down to the diaphragm
Anything that compresses the medulla at C4 or above, affects its function ImageImage
Read 20 tweets

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