Get a Ringside Seat for Invest in ME’s 10th International Conference on 29 May

mango · May 29, 2015

Sasha said:
I'm sure he'd be only too happy to make it easy for us all!

i've asked him on twitter, let's hope he sees it and replies. if not, maybe i could send it to you in a pm?

he's done such an amazing job today! wouldn't want to upset him in any way..!

Sasha · May 29, 2015

mango said:
i've asked him on twitter, let's hope he sees it and replies. if not, maybe i could send it to you in a pm?

he's done such an amazing job today! wouldn't want to upset him in any way..!

Yes, perhaps I'm rash in speaking for him, especially after he's done such a sterling job!

Bob · May 29, 2015

aimossy said:
What does this mean do you think, my brain is just done in now.

"Marked improvement in physical function after 15 months. Transient worsening after Rituximab in about 20 percent of patients."

Does this mean that after they have been through the process and the b cells come back again 20% got transiently worse or that 20% get transiently worse while receiving treatments? Hopefully someone might be clear on this.

I wondered about that as well. I took it to mean that 20% of patients deteriorated after receiving rituximab. I'm not sure what they mean by 'transient' - does it mean that there was a limited period during which symptoms actively deteriorated, or that the down-turn in health was short-lived and reversed after treatment?

Undisclosed · May 29, 2015

Scarecrow said:
Maybe not. Still no new tweets. Perhaps they finished quickly.

They were overtime so no plenary and no closing statements.

Undisclosed · May 29, 2015

Bob said:
I wondered about that as well. I took it to mean that 20% of patients deteriorated after receiving rituximab. I'm not sure what they mean by 'transient' - does it mean that there was a limited period during which symptoms actively deteriorated, or that the down-turn in health was short-lived and reversed after treatment?

I think it meant that the deterioration was short-lived and did not last.

Undisclosed · May 29, 2015

mango said:
i've copied all of @Mark's tweets today into a plain text document and sorted them so they aren't in reverse order. i find them much much easier to read that way. i could post them here, if it would be okay with mark?

It wasn't Mark tweeting. It was me. It's a real eye opener and very exciting for me to be able to attend IiME. You can do whatever you want with my tweets except call me an idiot because I got things wrong or misinterpreted something. It's all very hard on me, I am exhausted. Time to crash. Mark was taking extensive notes for his article.

PDXhausted · May 29, 2015

Kina said:
It wasn't Mark tweeting. It was me. It's a real eye opener and very exciting for me to be able to attend IiME. You can do whatever you want with my tweets except call me an idiot because I got things wrong or misinterpreted something. It's all very hard on me, I am exhausted. Time to crash. Mark was taking extensive notes for his article.

Huge thank you!!

mango · May 29, 2015

Kina said:
It wasn't Mark tweeting. It was me.

thank you! you did an absolutely amazing job, kina! i have no negative feedback at all, just lots and lots of gratitude!

Undisclosed · May 29, 2015

Thanks @mango My faith in ME researchers was renewed today. These people are amazing.

mango · May 29, 2015

Tweets by Kina/Phoenix Rising on Twitter https://twitter.com/aboutmecfs

Invest in ME\Conference -- starting in 10 minutes.

Dr Ian Gibson is the Conference chair.

[@meassociation/ME Association on Twitter: “That's former Norwich MP Dr Ian Gibson - who is closely involved with the IiME conferences”.]

Conference has officially started.

Dr Ian Gibson -- What a Research Park Has to Offer in Resolving a Chronic Disease such as ME.

Ian Gibson is writing a book about the politics of ME.

Research is really beginning to 'move' as evidenced by the past few days here at the Conference..

Introducing Mady Hornig who is then next speaker.

Mady Hornig -- Markers of Immunity and Metabolism in ME/CFS

Three strikes hypothesis -- intersection of genes, environment, and timing causing chronic illnesses like ME.

NIH -- planning a new microbiome/iimune profiling study.

Talking about their recently pulished study.

Subjects with more recent onset have increased plasma levels of proinflammatory cytokines. Timing is important.

Trying to understand immune signatures and how they can be applied to patients re: possible treatments.

Looked at 51 different cytokines.

They also looked at cerebral spinal fluid of patients. There is a reduction in proinflammatory cytokines in the long duration group.

Discussing interesting embargoed information -- sorry can't tweet about it.

Mady Hornig has concluded her talk.

mango · May 29, 2015

Tweets by Kina/Phoenix Rising on Twitter https://twitter.com/aboutmecfs
https://twitter.com/aboutmecfs
Professor Jonas Bergquist -- Proteomics in ME/CFS

Proteomics is the large-scale study of proteins, particularly their structures and functions.

Talking about High Resolution Mass Spectometry and protein analysis.

Many proteins occur at extremely low level so it is very important to get the 'right sample'

Cerebrospinal fluid is their interest. We produce 5-600 ml per day of CSF. Samples via lumbar puncture. They have established the proteome of normal CSF. Healthy individuals vs ME patients -- there are differences.

Low grade inflammatory reaction in ME patients, dysfunction in axonal guidance.

More embargoed information -- sorry.

Professor Jonas Bergquist says when routine tests don't reveal abnormalities, more sensitive testing needs to occur.

Professor Jonas Bergquist has finished his presentation. Hopefully the embargoed study will be published soon -- very exciting.

Prof Ian Charles

Professor Ian Charles speaking now.

Solving ME: What a Research Park Has to Offer in Resolving a Chronic Disease

Talking about the microbiome.

Do alterations in the intestinal barrier integrity and the microbiota exist in ME patients?

Showing a map of the Norwich Research Park -- very impressive. Hospital, University and research lab. Has thousands of scientists.

'Fantastic hub of top-notch researchers'. Publicly funded.

New centre for food and health will be opened in 2017 on the site.

A focused single-site centre of excellence from basic to applied research. No equivalent centre either nationally or internationally.

Dr Ian Charles is very excited about the new centre and how it will have a positive effect on ME research. He has finished his speech.

Audience member asked how Monsanto Round-Up has effected the microbiome. Answer -- nobody knows at this point.

We need to sort out the chemicals in our environment.

Break time.

After the break, Dr Luis Nacul will speak about the Incidence and Prevalence of ME

mango · May 29, 2015

Tweets by Kina/Phoenix Rising on Twitter https://twitter.com/aboutmecfs

Dr Amolak Bansal

Change in presentation order -- Dr Amolak Bansal speaking on Diagnosis and Differential Diagnosis: Combining clinic and research

Dr Amolak Bansal speaking on Diagnosis and Differential Diagnosis: Combining clinic and research

Discussing the definition of 'fatigue' and symptoms of ME

PEM is common to everybody with ME.

People have much difficulty understanding PEM.

Listing exclusionary criteria.

Discussing psychiatric exclusion criteria.

The name SEID is not very 'catchy', criteria are perhaps a bit too simple.

ME vs CFS -- ME have more significant PEM, more cognitive dysfunction ... .

Uses Sutton CFS/ME Scoring system.

Scoring system is very helpful and accurate for diagnostic purposes.

All of their study participants must score at least 10 out of 13 points to be included.

People with ME have abnormal pupil reflexes -- the abnormality is usually only found in people with autonomic neuropathy.

20 percent of patients have joint hypermobility.

80 percent have increased respiratory rate,

70 percent have cold peripheries (cold hands, feet).

Now discussing conditions that can mimic ME -- EDS-3, hypothyroidism, Addison's disease, Sjorgen's, gluten sensitivity, sleep disorders.

cardiac dysfunction, Parkinson's, TMD, persistent anxiety and depression.

Must diagnose ME vs depression properly -- ME patients have adverse reactions to anti-depressants. Depression is very different from ME.

They do extensive bloodwork when diagnosing patients -- ANA, CK, LDH, viral and Lyme disease serology. Also do sleep studies, MRI's.

Other triggering factors -- life events (impairing immune system), physical injuries, environmental toxins

Now discussing factors that perpetuate chronic fatigue -- eg -- sleep impacts memory and concentration

Bonsal has finished speaking.

Audience member -- ME has been buried under 'psychiatric influences'

Audience member -- daughter became ill after HPV vaccine jab. Had severe side-effects to HPV vaccine -- is there going to be research?

There is some research in Scandinavia re: HPV

Dr Luis Nacul

Dr Luis Nacul will now speak on the Incidence and Prevalence of ME.

Nacul believes the puzzle pieces of ME are coming together slowly.

Getting the epidemilogy of ME right is essential.

We need to define ME properly.

There have been 20 different definitions over the years, no wonder researchers are confused.

SEID is the newest definition -- it's not 'specific' enough to be used.

Prevalence of ME varies depending on what definition is being used. Prevalence even varies within a definition.

Consistent finding -- more common in females, starts in young adults, more disabling than RA, cancer.

We need to narrow down definitions to be very specific.

Now discussing management of ME patients -- NICE guidelines -- CBT and GET -- are not appropriate treatments - biased studies ... .

Cochrane conclusion -- limited evidence for CBT from poor studies.

Research priorities -- biomarkers, correct epidemiological method -- specific case definition.,

Uk biobank -- will include 25 percent of severe patients (will go to them to get blood samples).

17,000 aliquots stored as of March 2015.

Audience -- PACE trial was a failure, FINE was a failure, FUKUDA needs to go. SEID is not going to catch on -- better than CFS but too vague

Oxford criteria needs to go too.

mango · May 29, 2015

Tweets by Kina/Phoenix Rising on Twitter https://twitter.com/aboutmecfs

Prof Sonya Marshall-Gradisnik and Don Staines

Professor Sonya Marshall-Gradisnik and Don Staines Update from National Centre for Neuroimmunology and Emerging Diseases - NCNED

Don Staines now speaking -- investigation of SNP's in biological receptors in ME/CFS.

Talking about TRP Receptors

ACTH is a vital CNS transmitter.

Professor Sonya Marshall-Gradisnik now speaking.

Explaining -- Cells, Genes, and SNP's

Describing particpant recruitment -- n = 280 115 ME patients, 90 non-fatigued cotrols, exclusions = 75

Two parts of the study TRPM3 SNP's and ACTH SNP's

9 SNP's in ME group -- TRPM3 SNP's

2 SNP's were TRPA1, 2 SNP's were TRPC4

Therefore, 13 SNP's significantly associated with CFS group.

Also found significant associations with ACTH SNP's

17 SNP's in total significantly associated with ME/CFS patients.

What does this mean?

TRPA1 -- has a role in the regulation of neuropeptides, as well as pain and inflammation

TRPM3 is located in the central nervous system -- associated with pain in the absence of tissue damage, also a thermoregulatory sensor.

TRPC4 -- responsible for vasomotor function and smooth muscle funcition, memory and attention, and motor control

Present on immune cells -- ME patients have significant reduction in immune cell function.

ACTH SNP's -- AChR SNP's -- located in the GI tract, regulate insulin secretion, involved in arousal and sleep and fatigue, pain, memory.

Also involved in cognition.

Showing a diagram of the cell membrane.

Looking at TRP receptors on the diagram.

Professor Sonya Marshall-Gradisnik is winding up her speech about the SNP's common to ME patients.

Professor Simon Carding

Now Professor Simon Carding -- IiME Projects - Student Researchers The Next Generation

Students to say what they are working on -- Daniel -- first IiME funded PhD student at Norwich.

Studying gut microbiota

This area of science and how it relates to human disease has 'exploded' since 2009..

Looking at increased gut permeability in ME.

Lavina -- a medical student -- her project is the gut microbiota -- has potential to answer a lot of questions related to ME.

Another student speaking -- didn't catch name -- assessing autoimmunity against neuronal antigens. Working with Angela Vincent at Oxford

Another student Fane, works with Jo Cambrige. He is really pleased to be part of this research group.

Audience can now ask students questions.

Audience member asking about how to measure gut permeability. Daniel says they are trying to develop an assay right now.

Audience member -- concept of gut permeability has not been taken seriously by mainstream medicine until recently.

Gut permeability is now being taken more seriously related to evidence coming from research

Issue with the NHS in the UK, is there is no specific test for gut permeability which is what they will try to develop.

After the lunch break, Dr Jo Cambridge is going to speak about B-cell biology and ME.

mango · May 29, 2015

Tweets by Kina/Phoenix Rising on Twitter https://twitter.com/aboutmecfs

Dr Jo Cambridge

Jo Cambridge is now going to talk about B-cell biology and B-cell depletion.

Interested in identifying best responders to Rituximab and predicting who is going to relapse.

Looking at a slide of a B-cell -- quite complicated.

B-cell receptor = antibody

Antibodies come in different shapes and sizes -- IgM, IgA, IgG plus 2 others

When you encounter a 'bug', IgM is produced and then IgG.Antibodies bind antigens.

B-cell recognizes an antigen and shows it to a T-cell. T-cell makes cytokines which helps the B-cell produce antibodies.

Discussing cytokine research and why it is helpful in their research.

Rituximab affects antibody production, cytokine production, depletes circulating B-cells.

Treatment with Rituximab is complicated, very complicated.

ME/CFS and B-cells -- there is no clear picture from research.

They compared cohorts from 2 different centers. Measuring B-cell phenotype using flow cytometry.

Compared controls to ME patients.

Percentage of B-cells were the same in both groups. Found differences with CD24 and CD38-CD21 between the groups.

Higher CD24 percentage in patients,

Working closely with Fluge and Mella.

Dr Neil Harrison

Dr Neil Harrison will now be speaking about Immune-Brain Communication and Relationship to Inflammation.

How is body inflammation communicated to our brain.

Talking about 'sickness behaviour'. Activations of host defense mechanisms trigger stereotyped behavioral response.

Sickness behaviours to infection -- examples = fatigue, psychomotor slowing, pain, hypersensitivity

Pro-inflammatory cytokines induce sickness behaviours.

Immune brain communication -- how are immune signals communicated to the brain? Two main mechanisms -- vagus nerve and via areas of the brain where the blood brain barrier is weak.

Discussing relationship of inflammation and fatigue. Inflammation is correlated with fatigue

inflammation induced Insula activity predicts fatigue.

In a viral modal -- Hepatitis C patients given Interferon experience marked fatigue as a side-effect.

Now discussing Magnetization transfer imaging:biomarker for central effects of inflammation

People receiving Interferon -- fatigue increases quickly within 4 hours as shown by the brain imaging data.

Interferon changes sickness behaviour and brain microstructure within 4 hours.

Inflammation in the body is rapidly communicated to the brain, induces changes in sickness behaviour,

Insula and ventral striatum are involved. Outstanding question -- what are the implications for ME.

mango · May 29, 2015

Tweets by Kina/Phoenix Rising https://twitter.com/aboutmecfs

Dr John Chia

Next speaker -- Dr John Chia -- ME and Chronic Enterovirus Infection: An Update on pathogenesis

Enterovirus infections are quite common. Some remain asymptomatic, others can develop chronic diseases from infection.

Most dr's are not trained to recognize acute EV infections, are not taught they can cause chronic infections

Past evidence for EV persistance in ME patients -- Nairn, Gow, Cunningham, Douche-Aourik

Evidence of EV RNA in tissues of ME patient -- tissue removed from deceased ME patient who had committed suicide.

John Chia giving history of his own research related to EV infection. Diagnosed his own son with EV infection in1998.

Still giving history of his research -- 2005 moving from blood to tissues to look for EV -- the virus must be in tissues

Most patients have GI symptoms -- most GI specialists have no knowledge of EV infection. The stomach is a primary site of virus replication

The virus should be present if the patient is having active GI symptoms.

Found EV RNA in patients after biopsy of parietal cells in 2006/07..

How do we connect the stomach infections to the brain?

It is likely that the virus travels to the brain via the vagus nerve.

Dr Claire Hutchinson

Dr Claire Hutchinson will now speak about Biomarkers for ME: Visual Processing and ME/CFS.

ME patients consistently report visual symptoms.

Symptoms include hypersensitivity to light, tracking problems, reading difficulties.

Objectives of research -- demonstrate that ME causes a range of visual problems and identify key visual symptoms as clinical features of ME.

Examined responses from patients and collated symptoms -- commonly reported -- difficulty focusing, hypersensitivity to light,

itchy dry eyes, eye pain, loss of depth perception. The more frequent the symptoms, the greater the severity

Some visual symptoms are included in diagnostic measures of ME.

Visual hypersensitivity can represent Cortical Hyperexcitability

This is found in epilepsy, stroke patients, in MS patients. It can be measured via visual stress/pattern glare --

The study with 20 patients/17 controls will be completed in about 3 weeks.

Patients consistently report distortions.

Also looked at visual attention and ignoring irrelevant background information.

Found that patients are slower at finding targets than controls. With increased distraction, patients were more rapidly negatively affected.

This is the first experimental evidence to back up patient reports.

Visual attention - 29 patients/29 controls -- looked at processing speed, divided attention and selective attention.

Patients needed the visual information to appear longer than the controls for a response to occur.

Visual processing speed did not appear to be different between groups.

Ongoing projects -- Reading behaviour, Vision-related quality of life, and Opthamalic corrleates of ME

15 minute break followed by Professor Betsy Keller on Molecular markers before/after exercise /Activity guidelines to avoid symptom flares

mango · May 29, 2015

Tweets by Kina/Phoenix Rising https://twitter.com/aboutmecfs

Prof Betsy Keller

There are activity guidelines that should be paid attention to.

Will talk about energy currency -- short-term anaerobic (immediate stores available on demand), long term anaerobic and aerobic.

Our aerobic energy system has gone awry in ME/CFS.

PEM is a defining quality of ME. ME is not JUST fatigue.

Bateman -- pre-emptive rest on a schedule, pace yourself.

As a patient you need to redefine and focus on what works for you.

Goal -- improve range of motion, improve functional strength, and improve core stability.

Core stability is musculature that supports your spine.

With poor core stability -- you overuse your extremities.

Spinal alignment is key for good function and energy conservation.

Going through how to align the spine properly. Warm-up always begins with nose-breathing (thru the nose, 4 sec in, 6-8 sec out)

Relaxing, relieves pain. Has to become a havit.

There are 5 simple steps to align the spine. 1. Contract pelvic floor. eg for women -- eg kegel exercises

2. Draw-in or Brace ('suck belly-button into spine.) to stabilize pelvis 3, Raise ribcage - pretend ribcage is an umbrella

4. Back extension -- lie on floor in flying Superman pose - slide shoulder blades together or shoulders back and down. 5. Retract chin is the last step to aligning spine.

Giving examples of gentle exercises to strengthen to core -- eg physio ball, start with a chair first, yoga etc.

Physical activity progression -- start with stretching and core stability. Stage 2 = stretching with resistance activity

Stage 3 = Dose controlled Interval Activity Stage 4 = Maintenance Goal = improved function. These stages can take as much time as needed.

When structured physical activity does work, you can increase activity eg 10 seconds with 30 seconds rest --

Activity biofeedback is good -- monitor heartrate with a HR monitor. With ME, exceeding a certain HR will cause issues.

Can use a 'Perceive Exertion scale' to monitor responses/tolerance to activity.

Energy conservation is a MUST.

Discussing energy saving tips -- eg shower chair, pack groceries in a smart way, cook ahead, monitor calls, disabled parking placard,

learn to say no to 'energy zappers'.

Next -- Dr Oystein Fluge / Professor Olav Mella will be discussing Multi-centre Rituximab Clinical Trial for ME/CFS

mango · May 29, 2015

Tweets by Kina/Phoenix Rising https://twitter.com/aboutmecfs

Dr Oystein Fluge & Prof Olav Mella

Professor Olav Mella -- giving a brief background of the research starting with improvement of ME patient after taking Rituximab

Patient given the drug -- response after 7 months which lasted for 4-5 months.

Two more patients responded to Rituximab.

Decided to do a small study with 30 patients.

Phase two study to be published in two to three weeks.

Present Phase 2 study confirmed results from the 2011 sudy.

Marked improvement in physical function after 15 months. Transient worsening after Rituximab in about 20 percent of patients.

ME is caused by a malfunctioning of the immune system if underlying immune defect is corrected.

Maintenance therapy can give prolonged duration of response -- up to 24 months into the study.

Next, they want to confirm or refute that B-lymph depletion with Rituximab may result in a clinically significant response in patients

anywhere from 2 to 15 years in ME patients.

Talking about recruitment of patients at each of the 5 centres. Blood tests to exclude other conditions. Biobank material ... .

Double-bind randomized study.

Summer of 2017 will be when the Phase 3 study will likely be completed.

Block Randomization to ensure equal number -- treatment vs placebo

Rituximab 500 mg/m2 given at day 0 and 15, then 500 mg flat dose at 3 mths, 9 mths and 12 mths. Patients will monitor symptoms.

Blood samples will be drawn for biobank freezing at regular intervals.

Standardized, self-recorded scoring of fatigue and all major disease symptoms throughout follow-up.

Measuring changes in quality of life -- measured by SF36.

Changes in physical performance measured by electronic armbands.

Sub-study -- to see if there is evidence of endothelial dysfunction in ME patients that they found in earlier studies.

Is there a correlation between severity of ME and endothelial dysfunction.

Also will look at GI function as a sub-study.

Study officially opened in Sept 2014. Two centres have finished recruitment. Infusions should start at all centres by the end of this summer

What do they expect to find? Goal - a high quality study that gives a true answer to the questions asked.

The medical community needs to trust the results. There will be a sub-group that responds.

The response of the placebo group will be very important.

Talking about political impact of study -- have gotten public financing, hospitals are cooperating -- learning about ME

Also are getting private financing. Support from the Kavli foundation (their lifeline). A lot of public interest.

Spawning further research.

Now talking about toxicity of Rituximab. Toxicity needs to be considered.

Cost is important too.

These studies are helping to change the public view of ME.

They are doing other studies that haven't been published yet -- won't say anything about it.

Looking at the possibility of using cyclophosphamide for those who can't tolerate Rituximab -- 3 patients -- 2 have responded positively.

Cheaper than Rituximab -- may be the drug of choice -- recently have started a 40 patient study.

3 groups -- have had no response to Rituximab, those who haven't been treated with Rituximab, those who Rituximab stopped working.

Started in March 2015.

Very sick patients can be included in this trial.

Olav Mella is now thanking Invest in ME for inviting him as they are 'the best' and is very impressed with IiME.

And he thanked the patients -- most of their ideas come from listening to what the patients tell them.

mango · May 29, 2015

...and here is a link to a downloadable document with all the above tweets (.doc, 59kB)
http://www34.zippyshare.com/v/EazQc7HH/file.html

big warm thanks to @Kina, once again! <3

Sasha · May 29, 2015

Kina said:
It wasn't Mark tweeting. It was me. It's a real eye opener and very exciting for me to be able to attend IiME. You can do whatever you want with my tweets except call me an idiot because I got things wrong or misinterpreted something. It's all very hard on me, I am exhausted. Time to crash. Mark was taking extensive notes for his article.

It was you? But you're in Canada!

Scarecrow · May 29, 2015

Kina said:
It wasn't Mark tweeting. It was me. It's a real eye opener and very exciting for me to be able to attend IiME. You can do whatever you want with my tweets except call me an idiot because I got things wrong or misinterpreted something. It's all very hard on me, I am exhausted. Time to crash. Mark was taking extensive notes for his article.

Thanks, Kina. You did a great job.

Get a Ringside Seat for Invest in ME’s 10th International Conference on 29 May

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