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Jul 26, 2022 142 tweets 19 min read Read on X
1) The International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME) is hosting a 4-day Virtual Medical and Scientific Conference that starts tomorrow at 9 AM New York Time.

S4ME was invited and will live-tweet about the event in the thread below.
2) Forum members will also post comments on S4ME for each day of the conference, starting here: s4me.info/threads/iacfs.…

Although we will not be able to follow all the talks, we hope to provide snapshots and summaries of the most interesting facts and presentations.
3) Speakers at the event include Hector Bonilla (Stanford University), David Systrom (Harvard Medical School), Akiko Iwasaki (Yale University), and Vicky Whittemore (NIH).

The full schedule of the conference can be viewed here: iacfsme.org/2022-conferenc…
The IACFS/ME conference starts today with professional workshops for ME/CFS researchers.

The meeting has a virtual conference room where researchers can talk in private, watch research posters or listen to presentations.

In the first workshop Vicky Whittemore of the US National Institute of Neurologic Disorders and Stroke (NINDS) is presenting information on the different types of NIH grants with tips and advice for submitting successful applications.
Whittemore stresses that it is important to talk with NIH staff before submitting a grant because they can give advice e.g. on which type of funding opportunity is most suitable. “We don’t hear from people enough before they submit their grant.”
Whittemore also highlights the importance of describing research aims clearly. Young investigators usually submit proposals that are too complex or ambitious – it is often better to have realistic timelines and focus on something specific.
Another thing to be mindful of is to have aims that are not too interdependent. An example: If Part II and Part III depend on the results of Part I of your proposal, then the whole project might fail if Part I is unsuccessful.
Having preliminary results is not always necessary but often useful to demonstrate feasibility: it helps to shows that the project can be done by the research team.
According to Whittemore, only about 20 per cent of grants submitted to the NIH are funded.

Rejection is the rule not the exception. It’s important to not give up and keep trying.
The second part of this workshop is presented by Tim Gondré-Lewis of the National Institute of Allergy and Infectious Diseases (NIAID).

His talk focuses on specific training, fellowship and transition grants for young researchers.
During the Q&A IACFS/ME chair Fred Friedberg argued that the NIH are more open to funding ME/CFS research than ever, going back to the 1980s and 1990s.
Friedberg asked Whittemore what the rate of funding is for ME/CFS-specific grants and she replied that these are as good or even better than the overall NIH success rate of approximately 20%.
At the same time a second workshop was held by Hector Bonilla (Stanford University) and Jane McKay (University of British Columbia) on caring for Long COVID Patients.

Encouraging to see how the (virtual) room was filled with attendees for this workshop.
Lauren Stiles, the president and co-founder of Dysautonomia International, is now presenting a workshop on various forms of dysautonomia.
Stiles argues that dysautonomia is part of many diseases and that before the coronapandemic at least 13% of the US population was estimated to have some form of dysautonomia.
A few ME/CFS researchers have used a simplified “lean test” but Styles says that this approach has not been validated against a more formal tilt table test that forms the basis of POTS diagnostic criteria.
The simpler ‘lean test’ has sometimes been called the ‘NASA lean test’, but Stiles explains that NASA abandoned this test 30 years ago because it wasn’t reproducible.

Validation studies are needed to compare it against tilt table testing.
Stiles also discussed the overlap between postural orthostatic tachycardia syndrome (POTS) and ME/CFS.

Her slides stated that 48%-77% of POTS patients have ME/CFS while 19%-70% of ME/CFS patients are believed to have POTS.
But Stiles added that most patients with POTS without ME/CFS still suffer from severe fatigue.

Similarly, many patients with ME/CFS but without POTS might have other forms of dysautonomia.
In her view, there is an important overlap between dysautonomia and severe fatigue that is not fully captured by current diagnostic criteria.
Stiles also discussed three exercise studies on POTS patients.

In her view, these showed that the patients who could do the exercises, are helped by it.

But there were also major issues with some of these studies...
Stiles told that she was enrolled as a participant in one of these studies but that the authors weren't interested in her data because the treatment did not work well. So big question marks on this study.
Stiles also explained that there is a collaboration with experts from different diseases to come up with a POTS rehab protocol that takes account of co-morbidities such as ME/CFS.

The goal is a protocol that is flexible enough to serve patients with a wide range of disabilities.
Meanwhile in the other hall, there was a workshop on patient and caregiver perspectives on ME/CFS research.

It was presented by members of the Community Advisory Committee for the NIH Collaborative Research Centers: Rochelle Joslyn, Jaime Seltzer, and Susan Taylor-Brown.
@threadreaderapp unroll please
The second day of the IACFS/ME conference is about to start with a keynote lecture by David Systrom (Harvard Medical
School) on the pathophysiology of exercise intolerance in ME/CFS and long COVID.
Systrom has a background in pulmonary critical care.

His expertise is cardiopulmonary exercise testing (iCPET) where catheters measure blood flow and gasses, both venous and arterial, during an exercise test.
Around 6 years ago his research indicated that there was a subset of patients with exercise intolerance that could not be explained by intrinsic heart or lung problems.
Only later would his team test if these patients had ME/CFS, which was the case for the majority of them.
These patients were characterised by what Systrom calls 'preload failure'. They had a reduced VO2 max and a reduced right atrial pressure.
He is now seeing similar deficiencies in patients with Long Covid: "they are frighteningly similar if not identical. "
There was also a smaller subgroup of ME/CFS patients where Systrom suspects skeletal muscle mitochondrial dysfunction and poor systemic oxygen extraction.
A randomised trial is ongoing on 40 patients of this subgroup.
They will be taking the new drug ASP0367 (which targets mitochondrial function) for 6 weeks.
Systrom also found that many (approximately 30-45%) ME/CFS patients had small fiber neuropathy following a skin biopsy. But interestingly there was no relationship between CPET measures such as Peak VO2 and abnormalities of the skin biopsy.
Systrom highlighted that many patients with preload failure have dyspnea. He thinks that
dyspnea and hyperventilation are common in ME/CFS and Long COVID.
Systrom also discussed his recently published trial of Pyridostigmine. It improved VO2 peak but the effect size was small.

He thinks it might be a useful repurposed drug in the (off-label) treatment of exercise intolerance in ME/CFS.
During the Q&A Systrom also touched the controversial topic of exercise for ME/CFS.

He said his team realises that PEM is often the most incapacitating symptom of ME/CFS and that therefore he advises patients to not push themselves into a crash
Systrom says he first prescribes medication so that patients are able to do more and only then let them try (graded) exercise.

He said they had good results with this approach and that it does not seem to result in permanent worsening of symptoms.
Mark VanNess (University of the Pacific) is now talking on methods to induce symptoms of ME/CFS (mostly exercise testing) and increase understanding of its pathology.
Next up is Peter Rowe (Johns Hopkins) on the ideal protocol for tilt table testing.
In his talk, Rowe credits the work of Visser/Van Campen in the Netherlands which suggested reduced cerebral blood flow in ME/CFS patients who had neither POTS or hypotension.
Lucinda Bateman (Bateman Horne Center) is now talking on how her clinical team uses the 'NASA lean test'.

The goal is often not to make a specific diagnosis but to provide an objective test of orthostatic intolerance. It can also guide treatment.
There is a risk of the patient fainting during this test but with close monitoring the test can be quickly aborted and safely managed.

Bateman also says that a single NASA lean test is often not sufficient to induce PEM.
The next speaker is Dane Cook (University of Wisconsin).

His talk focuses on cognitive tests such as the paced auditory serial addition task (PASAT).

These are used to induce mental fatigue which is then studied using MRI scans done before and after the test.
Cook showed an interesting slide where healthy controls made less errors on cognitive tests over time.

The ME/CFS patients had the opposite pattern. They started with an equal amount of errors but these increased rather than decreased over time due to mental fatigue.
Alain Moreau (Université de Montréal) explains how his team developed a new stress test, a pressure cuff, because many ME/CFS patients are too ill to do exercise testing.
Luis Nacul (University of British Columbia) is that latest speaker on the topic of “Provocative Maneuvers”. His talk focuses on tests measuring handgrip strength. His team reported this to be a marker for ME/CFS and disease severity.
A German study showed a reduction in hand grip strength of ME/CFS patients over time suggesting a fatiguability that was not seen in controls.
Nacul suggests that handgrip strength has potential as a provocation test in ME/CFS studies as it is inexpensive, readily available, and relatively safe.
Peter Rowe (Johns Hopkins) adds that some of his ME/CFS patients reported that physical therapy
(testing range in motion for example in the neck) can also provoke fatigue and other symptoms.
During the Q&A the panellists discuss issues and risks with provocative testing.

Alain Moreau says that some patients are fine 90 minutes after the test but and become only really sick the next day.
Lucinda Bateman says that she knows patients who deteriorated (e.g.chronic pain) following exercise testing, so it is far from an ideal method.

The panellists stress that it important to prepare methods, (e.g. resting room), to alleviate PEM and symptoms afterwards.
Moderator Rochelle Joselyn asked if anyone considered cumulative provocations over time as most tests are limited to 1, 2 or 3 repeats.

The panellists found this interesting but agreed that it would be difficult to translate this into a controlled (and ethical) study design.
Another issue with provocative tests is making sure that patients and controls subjects are similar in fitness.

Bateman argued it is really hard to fully control for deconditioning.
Avik Roy of Simmaron Research is now discussing a drug-induced mouse model of ME/CFS.
Jessica Maya, a PhD Candidate from Cornell University found that the CD8+ T cells of ME/CFS patients have an exhausted subset of T cells that were not seen in healthy controls.

The sample size of the study was small though.
In the chat, Maya explains that Dr. Selin and Anna Gil work on very similar things, and "I've seen similar findings in my data that her group has found."
Kristine Aenelle (Miami VA Healthcare System) talks about Immune difference between male and female ME/CFS patients.

Females, for example, showed an increase in pro-inflammatory cytokines that was not the case for male patients.
We're off to day 3 of the IACFS/ME Conference!

Today starts with a presentation from Japan. Daiki Takewaki (National Center of Neurology and Psychiatry) will talk about changes in the gut microbiome in ME/CFS.
Takewaki shows various slides where gut bacteria species were significantly increased in ME/CFS patients compared to controls, but the sample size of the study (n = 30) was relatively small.

Some such as "Eggerthella lenta" have previously been reported to be increased in ME/CFS
According to Takewaki this “eggerthella lenta” species has previously been associated with autoimmune diseases such as rheumatic arthritis and inflammatory bowel disease.
Takewaki also reported that genes involved in tryptophan biosynthesis were depleted in ME/CFS.
Next speaker is Kenny De Meirleir (Whittemore Peterson Institute) on Phage borrelia qPCR in ME/CFS patients.
Using this test, De Meileir reports that Borrelia miyamotoi phages were more often present in ME/CFS patients (approximately 70%) vs controls (approximately 10%).
These results came from a sample of Dutch and Belgian patients from De Meirleirs clinic
Borrelia Miyamotoi is related but different to Lyme Disease and Relapsing fever. It was only first discovered in humans in 2011.

De Meirleir thinks it may cause a chronic infection underlying ME/CFS but says that the data need to be confirmed by others.
The next three presentations focus on interesting clinical cases.

Lucinda Bateman (Bateman Horne Center) is now talking about female identical twins where one had ME/CFS and the other didn't.
The other twin (without ME/CFS) developed symptoms and anxiety following COVID-19 but eventually improved.

Bateman discusses whether early intervention in this high-risk person might have prevented full-blown ME/CFS.
Melissa Siller (from the Private Practice of Susan Levine) discusses a 62-year-old female patient who had multiple symptoms and relapses. The audience was then invited to discuss different aspects of the diagnosis and treatment of this patient.
The next speaker is Leigh Jerome, a clinical psychologist from the University of Hawaii. She discusses a case of Long COVID, the importance of integrated care and how affective symptoms are often misattributed to a psychiatric disorder.
The next speaker is Geoffrey Moore (Ithaca College/Cornell University). He talks about prolonged recovery in 80 ME/CFS patients who did 2-day cardiopulmonary exercise testing.

Median recovery time was 10 days in ME/CFS subjects compared to only 1 day in controls.
Travelling may also play a role in recovery time because patients from Ithaca had a longer recovery time than those at the LA study site.
Moore says: "ME/CFS subjects: look deconditioned, but recover like they're overtrained."

He adds that the other data from his study are in line with previous 2 day CPET studies.

Although patients have prolonged recovery, he thinks that 2-day CPET is "generally safe"
The next speaker is Candace Receno, also from Ithaca College.

She measured physical activity levels of ME/CFS patients before and after the 2-day exercise testing.
Not many surprising results: ME/CFS patients were doing more sedentary activities and less moderate/vigorous activities than controls and after the exercise testing they were slower to return to previous levels of activity.
(The speaker of this talk was Betsy Keller instead of Candace Receno as was noted on the conference schedule).
There is an hour lunch break now but afterwards there is the keynote presentation by Akiko Iwasaki on the Immunology of long COVID.
Iwasaki started with general info on Long Covid. The percentage of symptomatic patients goes down after infection, she explained, but it doesn’t go down to zero. It plateaus.

We need to understand why some people fail to recover.
She also highlighted the problem that there is no universal way to define Long Covid leading to variations in studies and making it difficult to give one number of how many people are affected.
Iwasaki talked about the results of a mouse model of mild COVID.

They wanted to know if a mild respiratory infection could affect the brain.
They found that several cytokines were elevated including in the cerebrospinal fluid weeks after the mild COVID infection.
They also found reactive microglia in the brains of the mice which is interesting because they also found this in autopsies of people with a positive test for Sars-Cov-2 (some of these didn't have any COVID symptoms).
One of the elevated cytokines they found in the CSF of the mice is called CCL11.

This cytokine was also found to be elevated in the blood of long COVID patients with brain fog (not in those without brain fog)
Iwasaki concluded that infection of the central nervous system (CNS) is not required to induce significant CNS pathology.

Long COVID might be caused by circulating cytokines that impact the brain in a chronic matter because of epigenetic regulation of the microglia.
Lastly, Iwasaki also presented yet unpublished data from the Mount-Sinai Yale study (MY-Long Covid Study).

This study very extensive testing in patients with long covid, patients with covid who recovered and two groups of healthy controls up to 110 days post-infection.
Long COVID patients had increased B cell activation and increased exhausted T cells.

They also had increased anti-SARS-CoV-2 antibodies, even after controlling for vaccine doses.
There was also reactivation of some herpes-viruses (EBV).

The most striking finding, however, were decreased cortisol levels in long covid patients. They were only about half of controls and also predicted the severity of Long Covid.
Iwasaki said she hopes to extend these analyses to ME/CFS as she thinks there are many parallels and overlaps between Long Covid and ME/CFS.
The next speaker is Ali Boolani (Clarkson University). His team looked at electronic medical records of patients with a PCR-confirmed diagnosis of COVID-19 from multiple hospitals.

In total they had data on 60.000 patients.
They then looked at how many of these patients got a post-COVID ME/CFS diagnosis.

This turned out to be the case for approximately 8500 patients or around 14%.
Boolani highlighted several limitations to this data.

Not all diagnostic codes were entered correctly and when they looked at some of the records, important things were missed.
The limitations became clear when they looked at predictors of ME/CFS diagnosis.

Being older, male and Caucasian increased the odds of a ME/CFS diagnosis and classification accuracy for machine learning models was low.
Boolani briefly suggested that this could mean that getting a registered ME/CFS diagnosis is subjective: that some people are more likely to receive one than others (regardless of medical condition).
The next presentation is by Liisa Selin (University of Massachusetts) on CD8 T cell over-activation and exhaustion.
Selin says they are seeing similar immune abnormalities in Long Covid as in ME/CFS.

She thinks that Inspiritol (a new patented 5-compound drug) has potential as treatment because it has various immune-modulating effects.
The last presentation before the break is from Deborah Dubicka (Neurovision Inc) on how "Stellate Ganglion Block" might help to improve symptoms of Long Covid.

She has previously reported a retrospective case series on this.
A stellate ganglion block is an injection of local anesthetic to block the sympathetic nerves in the neck.
Dubicka says she is new to the field of ME/CFS but that she noted that stellate ganglion block improved symptoms in Long Covid patients.

The sample size, however, was limited to 11.
That's the end of tweeting for today.

There will be more presentations today at the IACFS/ME Conference.

Check out our forum threads where members will post comments and summaries of the talks. s4me.info/threads/iacfsm…
Today is the 4th and last day of the IACFS/ME Conference.

Irina Rozenfeld (IACFS/ME) starts the day by highlighting upcoming changes in the ICD-CM where ME and CFS will be listed under code G93.3 "Postviral and related fatigue syndromes" starting on 1 October 2022.
The first presenter of today, Lauren Stiles (Dysautonomia International) adds that Postural Orthostatic Tachycardia Syndrome (POTS) will have its own ICD-10 code in the US.

It will have code G90.A and will be listed under disorders of the autonomic nervous system.
Stiles hopes that this code will improve epidemiological data on POTS.

Before the COVID-19 pandemic, it was estimated that 1-3 million Americans suffered from POTS.

But the condition only receives $1 million NIH funding per year, which is less than ME/CFS.
Stiles is discussing studies that found adrenergic, muscarinic and angiotensin receptor antibodies in over 90% of POTS patients.

A pioneer of this research, Dr. David Kem, unfortunately, passed away recently due to COVID-19.

In Memoriam:
dysautonomiainternational.org/blog/wordpress…
Stiles is critical of CellTrend assays, which have been used in ME/CFS research, because one blinded study showed that it could not distinguish between POTS and healthy controls.

All controls had abnormal levels (7 units/mL) of a1 adrenergic receptor autoantibodies.
Stiles is summarising research on glucose dysregulation which she thinks might explain why some POTS patients feel better on low carb diet.
There are 5 studies ongoing into vagus nerve stimulation for POTS patients (at Vanderbilt University, Humanitas University, University of Oklahoma, and Children's Wisconsin)

Stiles thinks this is going to be a “really big deal” in POTS and ME/CFS research.
The next presentation is by Wakiro Sato (National Institute of Neuroscience, Japan).

He starts by discussing his previous findings on skewing of B cell receptor repertoire in ME/CFS.
Sato has since extended his study to patients with Long Covid.

Much like in ME/CFS, they found increased antibody-producing
B cells and increased autoantibodies (as measured with CellTrend assays) in a subgroup of patients.
This is the paper on CellTrend assays that Stiles referred to:
pubmed.ncbi.nlm.nih.gov/35766055/
The next speaker is Gunnar Gottschalk (Simmaron Research)

He found the protein ATG13 to be increased in the serum of ME/CFS patients suggesting an impairment in autophagy.

There was no difference in lysosomal proteins between patients and controls.
Gottschalk also found that serum ATG13 induced an oxidative stress response (ROS and iNOS) in microglia.
The next speaker is Brandon Cox (Ohio State University)

His research focuses on human Herpesvirus dUTPase proteins which can stimulate the production of pro-inflammatory cytokines.

In ME/CFS patients they found increased levels of antibodies against herpesvirus dUTPase.
Their main hypothesis is that these viral dUTPase are increasing the levels of Activin A and that these on their turn cause abnormal differentiation of T follicular helper cells in a subgroup of ME/CFS patients.
Activin A is a cytokine that is involved in the muscle degradation pathway therefore Cox wants to study if this is related to muscle fatigue in ME/CFS.
There is a short 15 minute break now but afterwards we will have 4 talks on the topic of Treatment.
The first speaker is Luke Liu (Neuroversion, Alaska) who provides more information on
'Stellate Ganglion Block' as means to improve ME/CFS symptoms.

Seems similar to the presentation by Deborah Duricka yesterday.
Liu and Duricka co-authored a case series on Stellate ganglion block reducing symptoms of Long COVID: pubmed.ncbi.nlm.nih.gov/34922127/

Now, Liu reports similar improvements in 5 ME/CFS patients.
The second speaker is Nicola Clague-Baker (University of Liverpool). She is one of four members of Physios for ME. They want to improve physical therapy for ME/CFS and have become more and more involved in scientific research.
They found that many ME/CFS patients pace themselves with a heart rate monitor.

The idea behind this is that, if ME/CFS patients keep their heart rate below their anaerobic threshold, it would lead to less post-exertional malaise.
Clague-Baker and colleagues set up an online survey on the experiences of ME/CFS patients with this type of heart-rate monitoring.

Patients said that the it helped them to understand their PEM triggers better .
The next speaker is Rosie Twomey (University of Calgary, Canada). She and her colleagues created the BREATHE-program a virtual self-management program for Long Covid patients.
The program includes pacing to minimize post-exertional malaise (PEM) because Twomey found that post-exertional malaise is also common in Long Covid.

A preliminary trial of the program will be published soon.
According to Twomey the BREATHE program helps patients to manage a chronic illness and to reduces social isolation. It is patient-centred and group-based.
The next presentation is by David Kaufman on his pilot study of Oxaloacetate Treatment as a treatment for ME/CFS and Long COVID.

Kaufman cautions that this was a small pilot study, not randomized and without a placebo control.
This trial is published here: …nslational-medicine.biomedcentral.com/articles/10.11…

oxaloacetate levels have been reported to be reduced in the plasma of ME/CFS patients, so the trial tested if supplementation could improve ME/CFS symptoms.
Kaufman was encouraged by the results so is now setting up a proper randomized controlled trial of Anhydrous Enol-Oxaloacetate (AEO) on 80 patients in collaboration with the Bateman Horne Center.
Kaufman stresses that his pilot trial could not provide strong evidence but it did not cost much money (almost all ME/CFS patients came from his clinic, long covid patients were recruited online). It helped to quickly query a new compound for a signal of efficacy.
Side note: On S4ME, forum members have provided a critical analysis of the Oxaloacetate trial, including potential financial conflicts of interest of the first author.

s4me.info/threads/oxaloa…
Staci Stevens of the Workwell Foundation wins the First IACFS/ME Innovator Award for developing and applying two-day cardiopulmonary exercise testing in ME/CFS.
There is a 1 hour 15 minutes lunch break now.

The presentations afterwards will focus on the topic "Public Health"
Break is over.

The next presentation is by Cathy Kline and Gloria Gray of the University of British Columbia, Canada.

They have developed a patient-led interprofessional workshop for medical students on poorly understood chronic diseases, such as ME/CFS and Lyme disease.
Students found the workshop useful because they could ask questions and interact with patients in a context where they weren’t directly responsible for their care.
The next presentation is by Erin Maughan (George Mason University School of Nursing) on
chronic absenteeism and undiagnosed ME/CFS.
The goal was to come up with tool that could help school nurses identify medical reasons for long-term school absenteeism, in particular ME/CFS.
They did a feasibility study with 6 pilot sites in 4 states. They helped nurses to reach out to students and their family to determine the reasons for their absenteeism and ask about ME/CFS symptoms.
Among hundreds of absent students, however, they could not find students that were undiagnosed with ME/CFS.

4 were suspected of having ME/CFS but turned out to have something else when referred to a physician.
One caveat is that the corona pandemic made this pilot study rather difficult to conduct.

Many of the school nurses and medical providers had also not heard of ME/CFS.

The authors will expand the study to include up to 50 districts over a period of 3 years.
The next presentation is by Nancy Klimas (Nova Southeastern University). She reports on a study, contracted by the CDC, that will apply the extensive testing of the Multi-Site Clinical Assessment study of ME/CFS (MCAM) to persons with a SARS-CoV-2 infection.
The presentation is mostly about recruitment difficulties of the study.

A mass email strategy, for example, did not work well

Of 13.000 emails sent out, only 2.4% clicked to open the email and only 0.5% signed the consent form.
That's the end of our live-tweeting.

There are 3 more presentations to follow at the Conference.

Check out the S4ME forum to see more comments and summaries of the talks.

s4me.info/threads/iacfsm…
Thanks to the IACFS/ME (in particular Lily Chu) for organising this conference and stimulating more research on ME/CFS.

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