Coverage from IACFS/ME Florida conference, 27-30 Oct 2016

[Valentijn]

Methods: Eighteen female patients (18-50 years) fulfilling the Canadian Consensus Criteria and the International Consensus Criteria for CFS/ME and 15 controls (healthy, sedentary women; 18-50 years) performed two CPET 24 hours apart.

Mean difference in test- retest peak VO2 was -1.4 (1.1) among the patients (p<0.001), whereas no change was found in the controls (-0.9 (1.8) p=0.07). However, the mean test-retest difference in peak VO2 did not differ between the groups (p=0.33).

So ME patients did a little worse on Day 2, but it wasn't bad enough to be statistically significant compared to the controls. The sample size was fairly small, which could be why the Day 2 drop in VO2max didn't reach significance in this study, but did in other studies.

 

[Sidereal]

Furthermore, lactate accumulation on test 2 occurred earlier in the patients, and later in healthy subjects, compared to their respective lactate accumulation on test 1 (pinteraction<0.001).

This sentence destroys the notion of graded exercise therapy. Healthy people benefit from aerobic conditioning. ME patients are worsened by it. Pay attention, unnamed lunatics from the UK.

At test 1, mean (SD) peak VO2 (ml/kg/min) was lower in patients than in the controls (24.2 (4.9) vs. 36.6 (6.2), p<0.001). Mean difference in test- retest peak VO2 was -1.4 (1.1) among the patients (p<0.001), whereas no change was found in the controls (-0.9 (1.8) p=0.07). However, the mean test-retest difference in peak VO2 did not differ between the groups (p=0.33).

Whoever was tweeting about this misunderstood what this means. VO2 max was significantly lower in patients on day 2. In controls it wasn't significantly lower. But the interaction wasn't significant meaning that the difference between groups in the difference between day 1 and day 2 wasn't significantly different but that could very easily be explained by the tiny sample size (lack of statistical power).

 

[Sidereal]

Sorry, crossposted with Val.

 

[Sidereal]

Could that arterial collection be different from the other collections ie like the blood gasses artery?

Good point. Don't know the answer.

 

[Sidereal]

Subsets of ME/CFS patient responses to a 2-day CPET

Betsy Keller

Ithaca College, Ithaca, NY USA

Background: Studies to assess the efficacy of a two-day cardiopulmonary exercise test (2-d CPET) protocol to identify post-exertion malaise (PEM) in ME/CFS first revealed that ME/CFS patients often fail to reproduce peak VO2 (VO2peak) during test 2 due to PEM provoked with test 1. Subsequent research indicated that a subset of patients failed to reproduce VO2 at ventilatory/anaerobic threshold (VAT), but did reproduce VO2peak, suggesting that responses to exertion may distinguish subsets of patients. Identifying subsets of ME/CFS patient responses to exertion would enable us to further explore other potential correlates, such as metabolic markers or bacterial microbiome of the gut.

Objectives: To classify the responses of ME/CFS patients to a 2-d CPET protocol to determine if ME/CFS patients demonstrate subsets of responses in addition to failure to reproduce VO2peak or VO2@VAT.

Methods: Responses to a 2-d CPET protocol were evaluated for 94 ME/CFS patients. Patient responses were evaluated based on failure to reproduce VO2peak or VO2@VAT, as well as failure to respond normally with regard to autonomic parameters (heart rate, blood pressure), ventilatory parameters, as well as cases that reproduced CPETs within normal variation.

Results: Of 97 cases, 34% comprised a subset of responders that failed to reproduce VO2peak, and 39% failed to reproduce VO2@VAT within normal variation. Additionally, subsets were also described by autonomic anomalies (43%), ventilatory anomalies (47%), and normal reproduction of CPETs (29%). Membership in more than one subset by several cases explained the sum total of all subsets greater than 100%.

Conclusion: Assessment of PEM using the 2-d CPET protocol should consider abnormal responses to exertion that extend beyond VO2peak or VO2@VAT and consider disruption of autonomic and ventilatory responses as indicators of inappropriate recovery, or PEM, following exertion. Additionally, patients diagnosed with ME/CFS who reproduce the 2-day CPET within normal parameters may describe a unique subset that requires further study. Preliminary data will be discussed which indicates that this subset may correspond with other prognostic indicators.

Betsy Keller, Professor, Department of Exercise and Sport Sciences, Ithaca College, 318 Center for Health Sciences, Ithaca, NY 14850 keller@ithaca.edu

Funding: none
Conflicts of Interest: non

 

[aimossy]

Um can I ask you guys to state which paper your quoting. @Valentijn what paper was that one you were highlighting. sorry it's just I want to understand what you guys are saying. I value your comments.

 

[anciendaze]

I want to point out that "chronotropic incompetence" seems to run in the opposite direction from POTS, where there are exaggerated changes in heart rate. Confounding effects of mixing two different patient populations, or two different strata of seriousness, could account for decades of unimpressive results.

Good point. Don't know the answer.

What about venous pressure, as in the research by David Systrom's group on unexplained exercise intolerance? We have seen a long tradition of ignoring venous return as if it were nothing more than a kind of pipe, but there is also the vasodilation caused by ATP released in response to localized hypoxia in muscles. Do the terms "exercise intolerance", "hypoxia", "ATP", and "vasodilation" trigger any thoughts of possible relevance?

 

[aimossy]

It's frustrating that some have found decreased lactate findings. like Unger group and Armstrong group in blood. if your checking oxygen levels in blood or blood gasses you usually do it through artery for thorough testing so I wonder if it would make a difference. I could be dreaming this up.

@Jonathan Edwards I hope your following this thread. The differences in findings are frustrating to do brain gymnastics around this with slow cognition.

 

[Valentijn]

Something else which might make a difference from one CPET study to the next is how resting heart rate is measured.

Resting heart rate is important in calculating the VO2max, but in an ME patient with OI, a sitting measurement will likely be abnormally elevated at the appointment. The elevated resting heart rate would result in the calculated VO2max being higher (better) than it would be if a true resting heart rate (lying down, not elevated from travel, etc) were taken prior to the CPET starting.

So I'm a bit curious as to how/when resting heart rate was measured in the studies with different results, and if the resting heart rate was higher in some studies which showed less of an effect on Day 2 VO2max results.

 

[Valentijn]

Um can I ask you guys to state which paper your quoting. @Valentijn what paper was that one you were highlighting. sorry it's just I want to understand what you guys are saying. I value your comments.

If you click on the little upward-pointing arrow at the top of the quotation box, it takes you back to the post which was quoted.

 

[aimossy]

Thanks heaps didn't know that!

 

[Sidereal]

What about venous pressure, as in the research by David Systrom's group on unexplained exercise intolerance?

What that group did seems quite invasive but probably necessary.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860548/

Before iCPET, radial and pulmonary artery catheters were placed by standard techniques, the latter by the internal jugular approach in the cardiac catheterization laboratory under fluoroscopic guidance.

I actually thought that that study involving invasive CPET was one of the most insightful studies ever done on CFS even though it didn't mention CFS anywhere in the paper. But from the description of patients (young women, unexplained exertion intolerance, unexplained dyspnea, POTS, other dysautonomias, HPA axis issues etc.) it seems pretty clear they were studying the likes of us.

 

[Never Give Up]

Cort tweet:

Cort Johnson ‏@CortJohnson
#IACFS/ME #ME/CFS: "left shift in lactate curve" - lactate accumulation is INCREASED during second test - same found in overtrained athletes

@Hutan , didn't you once tell me that in Australia the disease onset trigger is often perceived to be overtraining?

 

[Hip]

Heck so if theres something in the serum - what is it likely to be? Kinda gotta make you think that would be easy to find if it was a microorganism.

Well if you look at the other tweet about Fluge and Mella's findings, they say studies suggest that immune system is producing anti-mitochondrial antibodies that are whacking the mitochondria.

So if these anti-mitochondrial antibodies do exist, that could well be the factor in the serum of ME/CFS patients that is affecting the muscle cells: adding the serum would disable the mitochondria in the previously healthy muscle cells, by these anti-mitochondrial antibodies attaching to and disabling the mitochondria.

 

[RL_sparky]

Well if you look at the other tweet about Fluge and Mella's findings, they say studies suggest that immune system is producing anti-mitochondrial antibodies that are whacking the mitochondria.

So if these anti-mitochondrial antibodies do exist, that could well be the factor in the serum of ME/CFS patients that is affecting the muscle cells: adding the serum would disable the mitochondria in the previously healthy muscle cells, by these anti-mitochondrial antibodies attaching to and disabling the mitochondria.

This potential is huge in my opinion and on top of Dr. Edwards saying the following in the last week is interesting to say the least:
"I would not be surprised in something significant comes out of Norway soon. The Norwegians looks if they may have realized that they may beat the rest of the world at this illness and they have a system that allows large amounts of funds to be channeled into very focused research."

 

[AndyPR]

From the Bateman Horne Centre Facebook page

Dr. Batemans fascinating assessment of the IACFSME conference:
Get ready world--- good science presented at the IACFSME meeting in Ft Lauderdale this week will launch a new era. Clear evidence of a multi system disease process that limits activity at a cellular level in ME/CFS was presented. Disrupted or reduced cellular energy metabolism, autonomic nervous system dysregulation, altered microbiome, activity induced changes in the brain, systemic inflammation, (metabolomics, gene expression, gene methylation, exercise testing, brain imaging, cognitive testing, big data computer modeling, blood cytokines, immune cell signatures, etc).

Give anyone you know with this illness complex a gentle hug and a message of hope. Please donate money to research. Publications will roll out in the next 3-18 months. Too slow! ...and please share.

 

[anciendaze]

Well if you look at the other tweet about Fluge and Mella's findings, they say studies suggest that immune system is producing anti-mitochondrial antibodies that are whacking the mitochondria.

So if these anti-mitochondrial antibodies do exist, that could well be the factor in the serum of ME/CFS patients that is affecting the muscle cells: adding the serum would disable the mitochondria in the previously healthy muscle cells, by these anti-mitochondrial antibodies attaching to and disabling the mitochondria.

Don't limit yourself to antibodies. There is a great deal of biochemical communication which does not qualify. We are still in the early stages of learning about peptide communication between cells, including immune cells. We also need to remember that purines like ATP serve multiple functions, and one of these is purinergic signalling. If you ignore the effects of purinergic signalling you can find yourself looking for a kind of biochemical ghost when the data you have already shows changes you have ascribed to metabolism without considering them as signals.

 

[Hutan]

@Hutan , didn't you once tell me that in Australia the disease onset trigger is often perceived to be overtraining?

I can't remember saying that specifically, but that means very little... My brain isn't working well this morning so I hope the following addresses your point.

There are a number of high profile Australian sports people who got something like ME and have attributed it to over-training. Also, there was something about ME being more prevalent in professional cyclists, the inference being that they push their bodies with extreme levels of physical activity and this either triggered ME or made them more vulnerable to it.

I do wonder though if it is just that very active people and particularly professional athletes are more likely to notice say a 20% decrease in energy, be worried by it and seek medical treatment. Whereas a couch potato with the same decrease in energy may not notice that on their amble to the fridge or may just attribute it to getting older/less fit/fatter/having kids. So, the threshold for being diagnosed with mild ME may be different in active vs inactive people.

It was very interesting though about that twin study mentioned above where the more active twin was the one who got ME.

It is very difficult to address this question (whether people who do a lot of physical or mental activity are more at risk of developing ME) until there are good biomarkers.

 

[viggster]

Might it be awkward? Yeah, possibly, but I still don't see that as a reason not to attend. I expect he is well used to handling researchers chasing him for funding. Does he not attend any research conferences then?

It'd be very unusual for Collins to hang out at a science conference unless he's a headline speaker. He's running a $30 billion agency.

Here are some recent conferences he attended as keynote/headline speaker - these are all meetings with 1,000's of attendees:

http://www.asbmb.org/asbmbtoday/201510/2016Meeting/Collins/
http://www.tedmed.com/speakers/show?id=6584
http://www.lupusresearchinstitute.o...upus-conference-highlights-precision-medicine
http://www.ashg.org/2015meeting/

 

[viggster]

Well if you look at the other tweet about Fluge and Mella's findings, they say studies suggest that immune system is producing anti-mitochondrial antibodies that are whacking the mitochondria.

So if these anti-mitochondrial antibodies do exist, that could well be the factor in the serum of ME/CFS patients that is affecting the muscle cells: adding the serum would disable the mitochondria in the previously healthy muscle cells, by these anti-mitochondrial antibodies attaching to and disabling the mitochondria.

An anti-mitochondrial antibody has already been described...and some of us (including me) test positive for it. It's the anti-cardiolipin antibody. Cardiolipin is part of the inner membrane of mitochondria.

From a 2009 publication: "Examination of anticardiolipin antibodies (ACAs) in the sera of patients clinically diagnosed with chronic fatigue syndrome (CFS) using an enzyme-linked immunoassay procedure demonstrated the presence of immunoglobulin M isotypes in 95% of CFS serum samples tested."

http://www.ncbi.nlm.nih.gov/pubmed/19623655