Detailed notes from the IACFS/ME Conference + Stanford Symposium

A friend of mine attended last week's Stanford CME Symposium and IACFS/ME Conference, and took detailed notes which are reproduced below with permission. My friend wishes to remain anonymous.  If you've been reading Seacher's summaries on Phoenix Rising, or Cort Johnson's summaries on Health Rising, much of this will be review.  However, for those that like to really "geek out" on this vital information (myself included), you will find additional details in these notes. Some portions of these notes have also been published on PR forums.

My friend attended the Wednesday Stanford Symposium, the Thursday IACFS patient session, rested Friday, and then attended the professional sessions on both Saturday and Sunday.

I want to thank my anonymous friend, plus Searcher and Cort Johnson, for the valuable information they provided us over the last week.  In some cases, they sacrificed their health to bring us these summaries. 

Warning:  This is long - it was 18 pages as a Word document. 

4/7/14 Edit: here are the same notes in a Google Doc for better readability

                                                            ____________

STANFORD SYMPOSIUM

MONTOYA MORNING SESSION: 

1. Case study with the researcher with HHV6:
1. There is a clear presence of virus during symptoms peak, as well as coronal flare and other brain lesions --> improved on Valcyte; but weren't in the blood after acute period (?)
2. anti-inflammatory treatment and anti-virals reintroduced
2. disease course usually fluctuates around a set point largely variable among patients
1. Gastrointestinal, cardiovascular/autonomic, neurological, intolerance of extremes to temperature
2. cardiovascular symptoms include: lightheadedness, exertional dyspnea, palpitations, POTS (postural orthostatic tachycardia syndrome)
3. Symptoms involving several organs, chronic, fluctuating, subsets of patients, evolution of disease over time
4. Stanford's approach: 
1. cutting-edge technology: high throughput technology to study immune system and genes (HIMC, Genetics department), exponentially increase the amount that we can measure (cytokines)
2. neuroradiology, EEG, cardiology, infectious diseases
5. thoughtful and compassionate care for CFS patients is possible
6. His heart goes out particularly to patients who are bedridden, crippled by disease, sensitive to stimuli
7. Stanford got involved as a response to the suffering experienced in solitude by millions of patients who have waited for an answer form the medical research community
1. Stanford’s first patient cohort exhibited a dramatic response to Valcyte
2. Valcyte has a degree of immunomodulatory effect - monocyte and neutrophil levels changed
8. current trial: use of a stimulant Methylphenidate/Ritalin --> this study needs to be tested at a very high level
9. scientific rigor (from Montoya’s mentor Jack Remington), candid approach, multidisciplinary, clinical and translational research
10. the Wild child French film -- CFS is analogous to the deaf mute child who no one understands
11. Clinic ~ 600 patients, waiting list 300 patients, new patients currently see his Physician Assistants
12. research efforts: multidisciplinary team, weekly executive and research meetings, recruitment for trials
1. external collaborators (Ian Lipkin)
2. case control studies: 200 CFS patients v. 400 healthy controls
3. in an attempt to determine whether circulating cytokines were associated with severity, a linear regression cytokine by cytokine analysis and adjusted for matched set
4. as disease progresses, progressive worsening inflammation (circulating cytokine profile)
5. IL-17 is a cytokine that has been associated with autoimmune disease (RA, IBD, psoriasis, experimental allergic encephalitis in mice and MS in humans)
6. in an attempt to determine whether cytokines were associated, LASSO used. TGF-B (anti-inflammatory cytokine, which inhibits activation of macrophages) related to duration of illness
7. progressive increase of cytokines with disease severity, and decrease of key anti-inflammatory cytokine
8. we believe that the data opens door to the treatment with anti-inflammatory agent
9. Double blind, randomized placebo trials (as well as interventions like sleep, meditation, anti-inflammatory)

1.      BETH UNGER FROM CDC:

1.      Areas of consensus for ME/CFS:

1.      Severe fatigue, unexplained, not relieved by rest, reduces activity

2.      PEM

3.      May be accompanied by co-morbid conditions such as fibro, IBS, TMJ, interstitial cystitis, migraines (pain syndrome)

4.      MCS, Lyme, Gulf War Illness

5.      Sleep, pain, fatigue all interact

2.      Areas of disagreement for ME/CFS:

1.      Duration of fatigue (6 months)

2.      Symptoms required

3.      PEM a required symptom or not

4.      Conditions that exclude diagnosis (medical/psychiatric conditions)  

3.      FUNCTIONAL IMPAIRMENT COMPARABLE TO CONGESTIVE HEART FAILURE, MULTIPLE SCLEROSIS, CANCER, DIABETES, AND LUNG DISEASE - CONSISTENT FINDING IN MULTIPLE STUDIES

4.      INABILITY TO ATTEND SCHOOL (as many of 1% who miss at least one day of school per week) à many of these young children have ME/CFS

5.      Decreased working memory and motor speed on neurocognitive tests

Jarred Younger's speech

1. ME/CFS study: Fatigue and Leptin
1. Primary hypothesis: leptin is correlated with fatigue
2. Some correlated strongly, others did not
3. Examine different cytokines --> leptin is the only one that significantly correlated with fatigue in the group
4. Machine learning algorithm used à IL6 and leptin correlated with fatigue --> model was 78.8% accurate
5. Leptin: appetite regulatory hormone, produced by white fat tissue, increases with obesity and stress-eating, inflammatory (ability to change immune system drastically)
6. Microglia: immune system cells in brain and spinal cord; serve as the primary defense mechanisms there; interact with neurons and lower their threshold to fire if something bad is happening; pushes brain into pro-inflammatory state --> sickness response like body aches and pain, fatigue, cognitive dysfunction
7. Microglia sensitized and becomes "PRIMED" –common causes including aging, exposure to diesel gas, chronic stress, immune hit, multiple immune hits à this process is similar to that which occurs in ME
8. Leptin serves as a microglia primer (activates at both a lower threshold AND much more vehemently)
1. If introduce leptin to cells, nothing happens
2. BUT in presence of leptin + hit by trigger, then cells (microglia) react much more forcibly
9. Some solutions:
1. Leptin-antagonists  (also low glycemic index, behavioral treatment like meditation
2. Microglia modulators: Naltrexone (worked well with fibro)
3. Chinese herbs that reduce leptin: panax ginseng, tumeric, resveratrol, gastodia elàinflexin (gastrodia elata??)
10. Subtyping of patients: most important things with CFS -- grant with 200 CFS women
11. Improving methodology (for example the use of saliva)

Amit Kaushal from Stanford on Genomics and bioinformatics with Ron Davis, Wenzhong Xiao: Analyzing Data at the Genomic Level

1. 200 patients meeting 1994 case definition v. 400 controls
1. Underlying heterogeneity, can we stratify the phenotype
2. 5 dimensions: general fatigue, physical fatigue, reduced motivation, reduced activity, mental fatigue
3. 20 questions total used in patient populations like cancer, fatigue
4. Correlation between MFI components for CFS subset: however, different subsets and different manifestations of CFS
5. MFI scores result (slides)
6. Gene expression: since we're testing 470000 genes, we can plot all these p values
7. Conclusion: large number of genes are different in CFS v. Healthy controls
8. Nextbio Disease Atlas --> the disease with the highest correlation was Systemic Inflammatory Response Syndrome
9. CFS seems to be a pro-inflammatory syndrome given all the cytokine lab results
10. Compared CFS with other datasets with inflammation: ubiquitin and immunoglobulin heavy chain, protein phosphatase, dynein, immunoglobulin, La antigen (Sjogren's antigen B)
11. Molecular differences between CFS v. Non CFS (Whole blood MRNA analysis)
12. Goal is to stratify the heterogeneous patient population, correlate with other CFS datasets (CyTOF and cytokine sets)

Dr. Montoya Talk ABOUT CYTOKINES AND DISEASE SEVERITY: 

1. measured 51 cytokines at the same time, 2 serums taken 2/day to control for variations
2. 2 sided independent t-test, linear regression, linear regression, LASSO method
3. cytokines are a highly interconnected network, so very complicated
4. Healthy control cases (similar ages, gender distribution, PEM was present in 96% of patients who met the Fukada criteria)
1. 26 cytokines decreased over time, associated with age
2. important because we need to control for age
3. cytokine differences between females (Leptin, ENA78, IL1RA, Resistin are all higher) v. males 
4. certain cytokines were higher in CFS v. control (abnormal, pro-inflammatory)
5. In an attempt to determine whether there was a correlation for cytokines with disease severity, the scientists plotted a LINEAR LINE
1. Healthy patients v. Sick: less cytokines
2. Montoya also treats toxoplasmosis patients in infectious diseases clinics
3. In toxoplasmosis patients dump cytokines during early stage of infection (immune system reduce cytokines in peripheral blood) –leading to a mild shift of cytokines from blood to tissue containing inflammation
4. As inflammation progresses in tissues, then cytokines spill over back to blood  (the theory!); other theory: initial stages – characterized by immune down regulation in the acute phase
6. 13 cytokines (these were identified as increasing with CFS severity) and as related to the following responses: cell trafficking, cell activation, cell growth and differentiation, cytokine production, Th1 v. Th2 responses
7. IL-17 = cytokine associated with autoimmune disease (RA, IBD, MS); 2 cytokines are also highly associated with females (sex ratio in ME?)
8. TGF-B levels are lower in patients who experience the illness for longer periods of time (it’s a powerful anti-inflammatory cytokine)
1. as disease lasts longer, the immune system loses its capacity to suppress inflammatory T cell responses 
2. progressive increase of cytokines + decrease of anti-inflammatory cytokine with disease duration à “a perfect storm”
3. PATIENTS’ BODIES INFLAMED, SENSITIVITY TO STIMULI AND PAIN --> supported by cytokines
4. 12 cytokines identified as having a dose response behavior
5. data opens door for treatment with anti-inflammatory agents (which treat other inflammatory diseases)
9. Question and Answer
1. Q what is the definition for "untreated" patient population?
2. A: no treatment for a year (no anti-microbials or antivirals)
3. *microglasia sensitivity increases with age

IAN LIPKIN TALK: 

1. Columbia’s team includes Dr. Mandy Hornig (director of the CFS program)
2. Koch's hypothesis: microbes are in every pathogen
3. Levels of certainty in Pathogen Discovery: If find evidence of microbe --> probable (causal relationship between exposure to microbe and disease) à a few more steps to ensure certainty
1. Entered the field through the AIDS virus situation; advocacy of the community changed the situation
2. detection of serum antibodies to Borna disease virus in patients with psychiatric disorders --  took 20 years to demonstrate no evidence for link between infection and disease
3. entry into CFS, since many at the CDC suggested Borna disease agent responsible for CFS
4. Zoonotic Diseases: (PowerPoint contained a map detailing zoonotic diseases)
1. looking at the animal kingdom for agents to cause human diseases
2. most important part of pathogen discovery: clinician who recognizes disease
5. Staged strategy for pathogen discovery: 
1. analytical stage: look across the tree of life (bacteria, viruses, fungi)
2. evolution of high throughput sequencing (Roche 454, Illumina, Ion torrent, Illumina Hiseq Xten) --> feasible to look at the host in the future as technology progresses
3. use linguistic/probabilistic approaches (analogous to the pathogen discovery process)
6. consistently look for new infections outside of humans too (many originate outside)
7. high frequency sequencing (next generation sequencing)
8. models for bacterium-triggered mental illness (like schizophrenia example)
1. CNS autoantibodies in mice exposed to group A Streptococci
2. took mice prone to autoimmune disease, immune stimulant injection and streptococci  bacterium implicated, and found that had the same syndrome with antibody regions in the brain, then pulled proteins from brain, micro-sequenced them, found the protein and cloned it, then demonstrated that humans and mice reacted to the same protein
3. model: move and integrate animal and human models
9. agent could be lurking anywhere, then invoke an immune response (hence the importance of the examination of antibodies)
1. toxins can be important as well, although present as infectious diseases
10. Not all infectious disease consults are for infectious diseases 
1. Plant in Minnesota processed pork, and originally considered it as an infectious disease
2. Air hose blowing the myelin out, so workers exposed to large amounts of CNS tissue and developed antibodies to it--> exaggerated immune response to these like an allergy response
3. it's not actually an infectious disease but immune response –consider in light of ME/CFS
11. technology uses: 
1. use Peptide microarray to find diseases
2. serochip results: 
1. use human samples exposed to various viruses (SAR, CORONA)
2. effective in finding the origins of the viruses (MERS-CoV survey of Saudi camels)
12. Kawasaki disease:
1. Symptoms include inflammation of blood vessels + fever (kids die if not treated with IVIG or electrophoresis? experience death by cardiac arrest)
2. association of Kawasaki disease with tropospheric wind patterns (7-20 miles above earth) 
3. (similar in multiple various agents for CFS)
4. During the experiment, things that seem sterile are NOT: Lipkin had to eliminate contaminants that confound 16s Analysis (in equipment); treat them by getting rid of the bacteria (use restriction enzymes)
5. look 10-2 days prior to onset of K disease
6. airplanes collected filters  à scientists conducted viral sequencing of filters’ particles in order to identify major pathogen dominant in these filters from China before they were dumped in Japan and America
7. lots of Candida species (a type of fungi) in the atmosphere
8. Kawaskaki disease resulted as ***an autoimmune response to environmental trigger!!  we need to consider this case study with regards to CFS**
13. Many with CSF have gut disorder –potentially address symptoms by treating gut
14. His theory: ME/CFS is very complex, scientists should stay open to a wide range of interpretations (but not psychosomatic!)
1. Discovery of tick-borne viruses by high throughput sequencing (maybe not just borrelia but another bacterium)?
2. Collected 500 ticks, characterized through high throughput sequencing and high PCR à wide variety of viruses à whether people with chronic Lyme react to these new viruses
3. When does clinical status changes, when titers for these agents vary
4. initially got into CFS with Dan Peterson in 1980’s
1. "absence of evidence of Borna disease virus infection in Swedish patients with CFS)”
2. the patients had immune activation
3. Although there was a false lead by Judy Mikovits with XMRV à Lipkin gives her credit because the hypothesis garnered support at the NIH for pathogen search
15. Chronic Fatigue Initiative
1. Plasma study: Masstag PCR and Consensus PCR screening: found 2 HHV6 positive, 1 parovirus B19 (control)
2. extracted Nucleic acid from 486 plasma samples, found HHV6 in 6 plasma samples (very small percentages)
3. retroviral reads present in 85% of sample pools (Montoya)
4. annelloviruses found in 75% of sample pools -- associated with immune suppression and commonly found in high throughput sequencing; respond to immune stimulants –but Lipkin doesn’t think annellovirus­­­­es will be helpful
5. Each time we don’t find a relationship, IT’S STILL AS HELPFUL AS A RELATIONSHIP! (rules out external pathogens)
6. 211 PBMC samples--13% samples positive for HHV6 but 11% controls positive for HHV6
7. Plasma cytokines in long and short duration ME/CFS (DATA ARE CONVERGING WITH JARRED YOUNGER’S STUDY): elevated levels of IL 17, other inflammatory cytokines
8. Spinal fluid showed lower levels of proinflammatory cytokine (difference in the CNS department v. periphery systems)
9. dramatic increases of cytokines in long-term v. short-term CFS
16. caution - modulation of the immune system is very dangerous
17. Batch effect in CFS (RNASeq Project); the way it is set up changes the dataset
1. in science, one has to be able to replicate data
2. messed up and had to redo the experiment
3. future CFS studies: RNA Seq, CFS gastrointestinal microbiome (progress), Metabolomics, Proteomics, High-throughput sequencing of PBMC (but need funding)
4. question - why not look at tissues if doctors have found enteroviruses and endogenous retroviruses elsewhere? they're not going to be the prime mover but set off an inflammation response  (like schizophrenia, MS)
1. the prodrome seems to be an upper respiratory infection
2. originally wanted to do fecal and PBMC samples 
3. microbiome that we should access should be relatively a-traumatic
5. Autism risk factors: 
1. bowel abnormalities in children with autism as high as 25%
2. GI therapeutic strategies - worth comparing to CFS patients with bowel disorders
1. Explains why children have difficulties processing some environmental toxins (NSAIDS, wine, etc)
2. if pregnant woman gets fever, higher chance the fetus develops autism. (genetic susceptibility and environmental factors)
6. has applied for an NIH grant for ME/CFS
18. colon cancer - right side is associated with weird methylation patterns - model for butyrate defiency in colon cancer; more fiber the healthier the gut biome (you are what you eat according to grandmother)

DR. MONTOYA'S Symposium Conclusion: 

1.      super momentum in determining the pathogenesis of CFS

2.      urgency to CFS NOW and our attendance is a testament to the urgency

IACFSME SF CONFERENCE 3/19-3/23

1)     Initial Approach to Management by De Paul’s Charles Lapp, MD

a)      Energy envelope: stay within the boundaries (symptoms worsen if body functions beyond current capacities, so overtime patient will restore energy, lessen pain and other symptoms, lessen illness severity)

b)     Think about person with Me/CFS as battery with 20% (envelope theory related to perceived energy)

c)      Buddy system improved in terms of vitality and energy conservation (vitality v. baseline/post treatment timeline)

d)     Helping individuals monitor and stay within energy envelope has helped levels of functioning over time

e)      Self regulate!!!!

2)     Charles Lapp from Charlotte, NC Treatment strategies

a)      4 cardinal symptoms: pain, cognitive difficulties, fatigue, sleep disruption (non-restorative sleep)

b)     Comorbidities: IB, IBS, migraine, Sicca/Sjorgen’s complex (dry mouth and dry eyes), POTS, Gluten sensitivity, Prostatosis, chemical sensitivities

c)      Standard addressing of symptoms (sleep, pain, fatigue)

d)     Managing sleep problems: suggested list of pharmacological therapies and non – pharmacological (rest, cold/heat packs, balneotherapy, massage, PT, chiropractic, acupuncture, ENS, EMS)

e)      Characteristics: exertional, positional, hypersensitivities, stress intolerance

f)      Plan for days of recuperation after exertion

g)      Can and must be active – objective limits of aerobic interval activity, heart rate limited, pedometer

h)     Therapies:

i)       POTS: water, salt

ii)     Modified Elimination Diet (avoid gluten, dairy, SCANT – sugar, alcohol, nutrasweet, tobacco)

iii)   Viral or immunological symptoms (Valtrex, inosine, nexavir, valycte)

iv)    Human growth hormone?

v)     Ampligen

vi)    Rituxan/rituximab; TNF alpha inhibitors

i)       Theoretical approaches:

i)       Coagulation defects

ii)     Marshall protocol

iii)   Nitric oxide

iv)    Glutathione/methylation deficiency

v)     Cardiomyopathy,

vi)    Toxic exposure

vii)  Stem cell therapy

j)       Final reflections:

i)       No known cause or cure

ii)     Most important to stay within limits imposed by intervals, heart rate, steps per day

iii)   Symptomatic therapy focuses on sleep management and pain control

3)     JOSE MONTOYA TALK – ANTIVIRALS!

a)      Herpes viruses are ubiquitous, infect a significant proportion of individuals and establish life-long latency

i)       Example of HHV6-stricken researcher, detected in blood and spinal fluid during height of researcher’s symptoms, but not presented in health controls

ii)     Herpes virus is a good candidate for the trigger of the illness

iii)   life-long latency – once infected, difficult to remove them from system

iv)    8 Herpes: HSV 1, 2, VZV (chicken pox), HHV5 (Cytomegalovirus), HHV6 and 7, HHV4 (Epstein Barr), Kaposi’s sarcoma associated with herpes (8)

(1)   When genital herpes recur, then symptoms flare with the activation

(2)   Herpes viruses have been known to activate even without obvious physical lesions

(3)   Disease model: herpes 2 is reactivated periodically in health individuals, goes into the spinal fluid, causes meningitis (without individuals being immunocompromised)

v)     Antiviral approach: Acyclovir, Famciclovir, Valtrex, IV ganciclovr, Valcyte, IV foscarnet, IV cidofovir, Combination therapy

(1)   Leflunomide (CMV IgG) – immunomodulator used in RA

(2)   Infusion of CMV specific T spells (sepsis patients)

vi)    Possible candidates for Antiviral therapy:        

(1)   Ascertain patient has ME/CFS

(2)   PCR positive patients

(3)   Oral Herpes HSV1

(4)   Genital herpes HSV2

(5)   Shingles VZV

(6)   High titers against EBV VCA, EBV EA, HHV6, HSV 1, HSV 2

(7)   HHV7,HHV 8 (very rare in America)

(8)   When everything has been tried, go with fluctuating but suggestive symptoms

vii)  Dose of antiviral regimen: give lowest dose then increase as tolerated

(1)   Remarkable worsening in the beginning phase

(2)   Is duration important? Longer valcyte treatment correlated with improved response

(3)   Trial published for 5 months acyclovir not effective

(4)   Valcyte results graph: cognitive function improved significantly; many patients OVEREXERT AND GET PEM

viii)Antiviral therapy of 2 patients with chromosomally-integrated HHV6

(1)   Improvement after foscarnet

(2)   Indicative that antivirals work for CFS patients, but difficult to determine WHO needs antivirals?

4)     Nancy Klimas talk on immunomodulatory medications:

a)      Exercise stress test first, then test for cytokines compared to baseline

i)       Dynamic challenge studies

ii)     Genomic results

iii)   RedCAP platform for assessment

iv)    Computational biology/modeling analysis with data scientists

b)     Publications: homeostatic drive in perpetuation of complex chronic illness – GWI and CFS

i)       After being pushed over, CAN YOUR BODY BE PUSHED BACK INTO BALANCE?

ii)     Mining Drug-action data

(1)   Reverse directory for drugs

(2)   for example, reverse TNF drug, test on animals/humans, potential repurposing of anti-TNFa Infliximab

iii)   95% of immune system is in lymph nodes and immune system

c)      Overview of the Immune Response

i)       Immune abnormalities:

(1)   Immune activation: DR, CD 26 expression

ii)     Functional defects (NK cell dysfunction, C8 cells)

d)     Immunomodulatory:

i)       Ampligen (both immune modulator and antiviral) but failed to pass FDA

ii)     biologic response modifiers (targeted approaches) – Humera

iii)   Rituximab (phase 2); deplete B cells

iv)    Alpha and gamma interferon (chia talk)

v)     Isoprinosine (Phase 2)

e)      Reducing inflammation:

i)       Omega3 quiets TNFa, LDNF reduces neuro-inflammatory pathways

ii)     Food and allergens

f)      Antivirals: help with immune exhaustion

g)      Immunovir (Newport Pharma), Inosine (OTC) à start LOW LOW LOW dosage and titrate up because people feel ill when clearing bugs so start with small dose

5)     Jarred Younger on Fibromyalgia:

a)      Fibro patients (25% improve over an 11 year period, 39% get worse)

b)     The problem of fibro: so many levels to examine – DNA, RNA, etc; is the problem in the muscles or the central nervous system?

c)      Most people believe: Fibro is a central sensitivity disorder, despite fact that you feel it in the body

i)       Analogy of a car alarm – everything including flying bird makes you feel horrible and sets off the alarm

ii)     Pain = bodily alarm system, most important sense, tells you when you’ve gone too far (tells you when you shouldn’t be doing this)

iii)   FIBRO: threshold dramatically lowered like getting groceries/gardening , faulty alarm system

d)     New research

i)       The flu – cytokine induced sickness response (body aches, fatigue, cognitive dysfunction, sleep disturbances, depressed mood, social isolation, headache)  à results from the immune system

ii)     Microglia (cell in the brain) – responsible for protecting us from everything

(1)   Looking for cell death, bacteria, viruses

(2)   Microglia activation: When find problem, change shape and pump out chemicals affecting neurons and changing the way their function (neurons fire and make you feel “sickness”)

(3)   With Fibro/ME/CFS, the microglia are the worst instead of the best in terms of the sickness response

(4)   Primed microglia (triggered when exposed to huge immune hit like Lyme, chronic disease, aging, opiates for long term use, obesity – release of leptin from fat cells)

(5)   Sensitized microglia: overexpress receptors, keep in active state, least factor will set them off and feel horrible

(6)   Issue: can’t test theory directly because too invasive. 

(a)    Doctors can’t get into the brain for direct testing of hypothesis

(b)   ANOTHER PROBLEM: when diagnosed with fibro, all other tests cease, so fail to do external tests (small fiber peripheral neuropathy, vitamin D deficiency, central nervous leak) so it’s important to continue to do tests

(7)   Day to day variability (how to track this?)

(8)   Also tracked leptin – as people’s pain increased, leptin increased

6)     Closing keynote speaker: The physician – patient relationship in the genomic era by Abraham Verghese

a)      What ET sees: rounds removed from the living patient, rounds centered around the iPatient, no need to examine patient, bedside = toxic, point of admission is to reduce 3d patient to 2d

b)     Joseph Leopold Auenbrugger – “new invention” book was seminal of its time

i)       Physician Jean Corvisart was physician to Napoleon Bonaparte

ii)     His student discovered the stethoscope

iii)   Back then the barber surgeons treated everyone, but the carrying of the stethoscope signaled to the world the transition from barber surgeon to physician; it was a moment with tons of discoveries of medical equipment

iv)    Luke Fildes: the doctor = seminal painting (child occupies the center of the painting, the doctor is in a passive; “I was ill and you cared for me” Matthew 25:30 à calls to the Samaritan functioning of being a physician)

v)     Stanford Medicine 25 Sessions – bedside manner with real patients (hands-on session)

vi)    Relationship between doctor and patient is a human-human exchange, embody the Samaritan qualities, human understanding, empathy, human skills

(1)   Straying from this = great disservice

(2)   Questions:

(a)    The success of alternative medicine is the abundance of hands-on interaction

(b)   How do you propose to get the computer out of the exam room? It mostly is related to billing, monopolize the system

(i)     Exposing the ludicrousness of this

(ii)   Lost privileges when didn’t complete the ICD coding training in EPIC (exemplified how the medical profession is so far removed from the patient experience)

(iii) Health care in America –ordering tests instead of examining and talking to the patient

(c)    Do patients have a role in treatment guidelines: if we have a doctor physician test to examine how to examine a patient (ACTUAL TEST V. MULTIPLE CHOICE).   Who determines whether the physician is accurate and detailed during diagnosis of illness – does anyone test Varghese aside from a MC choice exam?

(i)     The multiple choice test’s easy reproducibility is the main reason for its implementation NOT its ability to measure the effectiveness of the physician(compared to the drunk who loses his keys in the dark and looks for it in the light)

(d)   HIPPA: doesn’t see the point of it

(e)    Given the multi year wait list for Montoya, and the apparent urgency of ME/CFS as a field needing physicians, how do you propose a strategy to train future Montoya’s:

(f)    Answer: the dearth of physicians is related to reimbursement issues, what is societally-valued?    

(i)     CFS is not a sexy field to enter

(ii)   Long wait list due to how unique his treatment is

------------------------------------------------------------------------------------------------

Patient Adaptive Techniques:

Heart rate monitor

Pacing

Deep breathing through the stomach, (in through nose, out through mouth), tissue box on stomach

Fred Friedberg EDM Fibromyglia study

Day 3 and 4 of IACFSME

1)     Prevalence and Health-related Characteristics of ME and EMS/MCS – results from the Canadian Community Health Survey

a)      Summary: CFS is chronic and disabling, with little change in symptom severity over time

b)     Those with the most severe initial symptoms seem to have a higher likelihood of symptom improvement, although improvement does not necessarily mean recovery or markedly improved functioning

c)      Severe initial post-exertional malaise may be an important marker of functional outcomes and long term health status

d)     Onset type is not important in the long term course of CFS

e)      Episodic remissions occur in a reasonable proportion of CFS

f)      Patients have number of comorbid, chronic conditions 

g)      Acknowledgement­­: chronic fatigue initiative clinical epidemiology study subjects – Stella Lee, Komaroff, Bateman

2)     Aims: study prevalence of cancer in patients with CFS

a)      Specific conditions including fibro, sleep apnea, bunch of other comorbidities

b)     Chi-square analysis, principal factor analysis (14 conditions à 4 comorbidity factors)

i)       Anxiety, depression, PTSD

ii)     Hypothyroidism, autoimmune disease

iii)   Narcolepsy

iv)    Neurological disease

v)     Cancer

c)      Correlation and regression analysis

d)     Top 4 conditions: Fibro, depression, anxiety, hypothyroidism

i)       Comorbidities decrease odds of better health over time, and their participation of extracurricular activities, school, etc

ii)     Comorbidities increase odds of CFS symptoms worsening over time

3)     Lucinda Bateman: Evidence from a Multi-Site Clinical Epidemiology study

i)       Patient-identified effective treatments

ii)     Initial and current severity of 9 CFS symptoms from Fukada criteria + orthostatic intolerance

iii)   Results:

(1)   Self-help strategies 65% (rest including efforts to improve sleep and pacing, diet, exercise like strength conditioning)

(2)   Traditional medicine 53% prescription medications and vitamins, OTC medications, herbal remedies, acupuncture, massage

(3)   Dan’s clinic: traditional medicine listed as the more effective treatment of major symptomology of illness v. Bateman clinic: empower patients to live with this illness (self-help strategies, value and manage health over time) à

(a)    Variables that may reflect the clinic differences including patient age, stage of disease, location?

(b)   Autoimmune diseases (including hypothyroidism) more associated with traditional medicine (since that seems to help them the best)

(c)    Neurological diseases –>  complementary medicine     

(4)   Summary: self help and traditional medicine are the most effective treatment types in CFS patient population but vary in magnitude by site

(a)    Treatment type effectiveness varies by:

(i)     Severity of initial symptoms

(ii)   Initial symptom cluster severity

(iii) Current health status and functioning

(iv)  Remission (ever)

(v)   number of comorbid conditions

(5)   Cancer diagnoses by system: skin, blood, nervous system, thyroid, colon/liver/pancreas, kidney/bladder, breast, cervix/uterus/endometrium/ovary, prostate

(a)    Prevalence of any cancer: 15.5%

(b)   Excluding skin cancer, prevalence of any cancer: 8.1%

(c)    Prevalence of any cancer in US: 4.1%

(6)   Question and Answer session:

(a)    Q: how do comorbid conditions related with CFS compare to the percentages of the normal healthy population?

(b)   A: great question and study will result soon

(c)    Q: on neurological symptoms:

(d)   A: slides depicted mild improvements across wide range of the symptoms (including neurological ones); other epidemiology studies with more granular information about neurological symptoms are taking place beyond CFS community, but they can’t definitively make any statements about neurological symptoms specifically

(e)    Q: why does it seem that most of the highest improvements corresponds with the type of clinic (Peterson’s traditional medicine v. Bateman’s lifestyle and symptom management example)

(f)     A: It’s probably just the nature of medicine and how we treat patients and practice medicine

4)     Superior Ability of a 2-day CPET Protocol to Detect Functional Impairment in ME/CFS compared to either a single CPET, submaximal exercise test, or a VO2 prediction equation

a)      CFS frequently use these types of energy: they require frequent rest breaks

i)       Short-term anaerobic (to get up with fire alarm calls, brief)

ii)     Long-term anaerobic (15-75 sec)

iii)   VO2 peak measured directly during CPET is valid, standardized, reliable in health and diseased patients

(1)   Maximal effort CPEP exacerbates symptoms of PEM so use of submaximal test is of interest à get the necessary info without max testing them and crashing them

(2)   CPET 1: measures baseline functional capacity Vo2 peak and ventilator (anaerobic threshold), induces PEM

(3)   CPET 2: determine if patient can reproduce CPET 1 results within well-established normative data variability (not compared to a matched healthy control); very well established that these are repeatable tests

iv)    Accuracy of predicting Vo2 peak:

(1)   Linear relationship between HR and oxygen consumption (as workload increases, HR increase, O2 consumption increases in a linear fashion)

(2)   Predicted maximum HR = valid for all subjects (200 – age)

(3)   Constant work economy and mechanical efficiency during exercise

(4)   Normal day to day HR variation exhibited by patients

(5)   Prediction accuracy using submaximal HR has a standard deviation (standard error)

v)     The problem:

(1)   Detecting functional impairment requires accurate measures of functional capacity

(2)   Can functional impairment accurately be detected by Vo2 during 1 and 2 CPET tests?

(3)   Summary: measured vo2 peak using 1 CPET, 2 CPET, predicted Vo2 using validated ACSM cycle ergometer equation, predicted VO2 from submax HR

vi)    Subjects and Procedures:

(1)   Oxygen consumption (VO2), heart rate (HR), workload (work), respiratory exchange ratio (RER > 1.1), functional impairment determined

vii)  Results:

(1)    Predicted VO2 peak was higher than actual VO2 peak for both CPETs

(a)    CPET VO2 actual tests dropped significantly

(2)   Predicted higher than actual VO2 peak for both CPETS

(3)   Compared to health controls, PEM really lowers our ability to reproduce the tests

viii)Summary: Validated prediction equation consistently over predicts the VO2 max in Me/CFS patients

(1)   Interesting point: HR at three submax workloads are same for CPETS 1, 2

(2)   The linear relationship between HR, Work, VO2 are not maintained in Me/CFS with PEM

(3)   Regression showed poor ability to predict VO2 peak from any single or combination of variables

(4)   Submax HR-work relationship during CPET 2 did not reflect the 13% decrease in Vo2 peak (probably due to PEM)

ix)    Cardiac failure experiment – tried to test severity of impairment

(1)   43 % of sample appeared to have some degree of functional impairment on day 1 of SPECT, but when they were tested the 2^nd day, 67% met functional impairment criteria

(2)   Takeaway: using only 1 CPET, it failed to detect 15% of those with functional impairments – then the speaker said 55% (so confusing)

(3)   It’s dangerous to over predict VO2 because patient can overexert, or patient’s exercise therapy can be overprescribed

x)     Conclusion:

(1)   2 CPETS are required to accurately detect functional impairment in ME/CFS

(2)   1 CPET is sufficient to characterize functional capacity of ME/CFS or correlate functional capacity with other objective measures

(a)    However, assessment based on 1 CPET should acknowledge the inability of 1 CPET to detect deleterious effects of PEM on functional capacity in ME/CFS

xi)    DANGERS OF PREDICTING VO2 PEAK

(1)   It’s not linear so might over predict VO2 peak from heart rate à very dangerous for reasons such as the patient over working, the physical therapist making the patient push beyond limits

5)     Diminished Pulmonary Ventilation in CFS patients – effects of deconditioning and post-exertional malaise

a)      Definition of ventilation: when one breathes in O2 and subsequently removes CO2

b)     Results from exercise test day one and retest day two

i)       Huge similar reduction in ventilation at peak exercise and at the anaerobic threshold

ii)     Greater reduction in ventilation on test 2, especially at the anaerobic threshold à shows the PEM effect on CFS patient’s ability to exchange air

c)      Ventilator anomalies in CFS – what are they attributed to?

i)       Skeletal muscle fatigue? Oxidative deficiency?

ii)     Autonomic drive? Related to dysautonomia

6)     Introduction: Potential value of Exercise testing in ME/CFS

a)      Identification of measurable physiological markers to aid or confirm diagnosis or to help classify disability

i)       A drop in anaerobic threshold on the second day of exercise testing was present in ME/CFS but not in controls

ii)     Goal is to identify discrete subtypes within ME/CFS

iii)   Why submaximal exercise testing was used: screening for other disorders such as mitochondrial dysfunction, maximal cardiopulmonary exercise tests, test people without inducing a flare (CPET consistently causes flare)

b)     CONCLUSION: submaximal exercise testing procedure didn’t clearly distinguish between ME/CFS cases and healthy controls

i)       Subset of 19% of ME/CFS patients met criteria

ii)     Greater level of self-assessed exertion at lower exercise intensity experienced in ME/CFS might be explained by central perceptions (neurology component?)

iii)   Even submaximal testing was intolerable for a subset

7)     Examining Exercise Tolerance in CFS patients

a)      Retrospective study of 6 year exercise testing

i)       Cardiac output was monitored (pulse contour analysis)

ii)     Lactate levels

b)     Conclusion:

i)       peak O2 uptake is low in CFS patients

ii)     Circulation is not different

iii)   What explains the low values?

c)      What’s the underlying reason for this??

i)       ADP, Pi, and H+ are recycled in the mitochondria

ii)     Perhaps the cause of PEM is that several com­­­­plex biological pathways might possibly go wrong:

(1)   down-regulation of the entire system – lowering of lactate and H+

(2)   a block in the system resulting in lower lactate and higher H+ production

(3)   or something goes wrong in the mitochondria and the system compensates by overproducing H+ (protons)

iii)   low lactate after exercise in several patients –similar to another doctor’s work

iv)    I think the speaker said….”the problem is the low proton à low lactate consequently”?

d)     Question and Answer session:

i)       Q: what are your thoughts about a portable CPET machine to observe an individual’s given HR and VO2 max at any time while traveling, or during the specific moment of PEM after a particular exertion? A: The researcher owns such machine which cost $30,000 !!!

ii)     Q: do other patients outside of CFS have PEM?  A: Danish Dr. Vermeulen treated a HIV patient had PEM as well – second test a lot worse than the first test

iii)   Q: do you see other patients with PEM? A: No, and we have tested many patients with cardiovascular conditions etc, and they have nothing like CFS patients – both high and low functioning (yet the closest to the PEM was the HIV patient from that Dr. Vermeulen)

iv)    Q: What defines the minimal exercise threshold that induces PEM?  A: the patient – it has to be a very individualized approach to physical activity guidelines

v)     Q: there are potent PEM responses to CPET 1 and 2 testing… A: Researchers agreed that there was a concern

(1)   Some patients relapsed for 1 month

(2)   All docs need to be very cautious about the possibility of PEM

(3)   Patients need to expect a relapse and to be surprised if there is none

vi)    Researcher comments:

(1)   Lung-wise speaking: There was nothing wrong with the pulmonary function BEFORE THE EXERCISE

(2)   It’s the diminished functional capacity of the lungs itself WITH THE PEM AFTER EXERTION

8)     PET studies with CFS patients: sectors in the anterior cingulate

a)      Correlation between severity of disease and brain anterior cingulate

b)     Functional Somatic syndromes – doctor is investigating a whole constellation of syndromes

c)      Positive correlation between something in the brain + pain

d)     C-PK 11195 binds to the translocator protein, the index of activated microglia à when activated, translocator is upregulated and binding occurs

e)      Correlation between BP and attention impairment, yes there is neuro-inflammation according to Yamamoto

f)      Brain science of fatigue: PET imaging in the patients with CFS

i)       Overdepression of brain activity in CFS patients (overprotection) – for example, when patient is stimulated in one region, the auditory region is depressed….

ii)     Mirror system of Fatigue

g)      Fatigue and motivation – they are mirror images of each other (directly proportional)

h)     Neural circuits for fatigue: from acute to chronic phase (in beginning there is oxidative stress, cytokines, maybe something changes in the brain)

i)       Future studies  - start with healthy people, then go to CFS patients and needs to recruit many people

i)       Center for Health Science Innovation recently opened in summer 2013 – I think the speaker said 50,000 people recruited

ii)     Many partnerships in Japan (large centers of research)

9)     MARCIE AND MARK ZINN EEG AND CFS

a)      50 CFS patients, 50 matched controls

b)     Measures included 19 channel EEG, measured fatigue using the Multidimensional fatigue inventory, fatigue severity scale

c)      Examined Peak Alpha frequency – found that CFS people are lower in PAF (lower energy for energy and sensory inundation)

i)       Reduction in PAF activation, this widespread and in the absence of known cerebral lesions or head injury, usually suggests a deregulation of thalamo-cortical circuits

ii)     PAR and effects of fatigue: higher scores on fatigue are associated with lower PAF scores

iii)   Implication of reduced PAF in bilateral frontal, parietal, and central areas

(1)   Associated with interruptions in goal-directed behavior (coordinate cognitive functions in formation of coherent behavioral sequences ) – hard to keep it together

(2)   Parallels mental status changes – such as alertness and attention, decision making, etc

iv)    Conclusions: CFS subjects have lower PAF and correlation with fatigue and PAF

(1)   EEG can be used to evaluate the extent and nature of the brain disregulation once a CFS diagnosis has been established – as well as monitoring disease progression and treatment response

d)     IMPLICATIONS OF ABNORMAL BETA-2 SOURCES IN CFS: primary motor deficits, reduced responsiveness, slower motor performances, delayed reaction times, andmuscle weakness – hallmark features of CFS; sensory ataxia: reduced proprioception

i)       Disturbances in pain sensation, alterations in the process in go sensory stimuli (more generalized hypersensitivity) – instead of happening at the neocortical level, it’s like a more crude processing of stimulus

ii)     Slides also discussed reduced motivation  - hypofunctioning Broca’s area consistent with studies showing deficient verbal working memory and language deficits in CFS

iii)   Summary: global expression of CNS hpoactivation was found in CFS patients

(1)   Link between CFS symptoms and brain regions with quantifiable changes in brain state and function

(2)   These can be used to evaluate nature and extent of CFS –not a diagnostic but assessment!

10)  Q and A

a)      Some of the viruses (HHV6 and EBV) have an affinity for the brainstem, so the researcher is very interested and only recently has the tech enabled us to examine the brainstem

b)     Q: Are there other diseases with similar cognitive deficiencies in EEG; A: can’t use EEG purely as a diagnostic – only to confirm the diagnosis within the scope of other information and symptoms (like epilepsy)

11)  New international Primer:

a)      Revisions include the following: handouts for patients, index, sections on prognosis and mortality, expand section on severely ill patients, Pathophysiology: immune system changes, updated use of dietary supplements including CoQ10, acknowledgements, some typos

b)     Why a primer not guidelines?

i)       Guidelines limited to info found in systemic review of literature

ii)     Well received enough to be on the HHS website next to many guidelines

c)      All revisions brought to the entire authoring committee

i)       Statements appearing in the revised primer are conseus statmeents approved by the entire authoring committee

ii)     Committee: chair = Fred Friedberg, Lucinda Bateman, Lenny Jason, Lapp, Bested, Davenport, Staci Stevens, Rosalind Underhill, and etc

iii)   Arrangements made to translate the primer into French (the committee will reconvene about various translations)

iv)    Lily Chu: there is no evidence to say that ME is NOT fatal

(1)   There are no longitudinal studies of ME population to address this question

(2)   The one study cited in primer only had 600 sample size and was not tailored to this question

(3)   Rare cases where deaths attributed to ME

(a)    2005 Sophie Mirza was the first person in UK to have CFS listed as cause of death on certificate

(b)   Emily Collinbridge – died of ME at 31 in UK

(c)    Casey Fero – mother has ME, he died in 2003 at age 9 with cardiac arrest

(d)   Dr. Knox found higher risk of non-Hodgkin’s lymphoma in ME/CFS population; Sears study needs to be replicated

(e)    CFI – 4 fold increase of cancer rates in subjects

(f)    Suicides – should not be rated as second rate deaths, but many with ME who commit suicide aren’t depressed; but rather driven to suicide due to exhaustion based on daily struggle to exist

(4)   The “lack of mortality” statement – some providers might conclude that the patients are exaggerating the severity of the illnesses

(5)   IACFSME is the only international organization dedicated to CFS – everything has to be evidence-based, qualified statements, should be listed as an underlying not direct cause of death on death certificates; documenting mortality influences issues like research and funding; survey of deaths by Leonard Jason à contact them if interested in participating

(6)   Once information gets out, hard to correct

(7)   Question and Answer

(a)    Researcher found “presence root ganglionitis in patients” – inflammation within ganglion which sits outside the spinal cord (and is part of the nervous system) shown in autopsies

(b)   Lily’s experience has experience with filling out death certificates not pathology

(c)    Mortality is on page 26

v)     Q: How can we encourage health care practitioners to read the primer?   A: we need to get it out hardcopy so that physicians have the copy in office

vi)    State medical society – get on their program for annual meetings; get on the workshop for various practitioners like Physical therapists, General Practitioners, pediatrician

12)  Conclusion by Dr. Anthony Kamaroff

a)      Questions addressed by many of the presentations

i)       Is there evidence of objective underlying biological abnormalities?

ii)     Could these theoretically explain the symptoms and do they correlate with the symptoms?

b)     Huge New CFS Databases and Biosample Banks

i)       Nova Southeastern University/U. Miami/Miami VA Medical center

ii)     Stanford Medical School

iii)   Chronic Fatigue Initiative (multicenter)

iv)    NIH Multicenter Sutdy: Columbia University (*Hornig and Lipkin)

v)     UK ME/CFS Biobank

c)      Immunology Overview 1

i)       Elevated levels of allergy –associated cytokines and chemokines and other pro-inflammatory cytokines (*CFI)

ii)     Ability of other cytokines to separate CFS from healthy control (Stanford) – Jarred Younger findings

iii)   Stanford inflammation studies: levels of 51 inflammation –related molecules – cytokine family/chemokines/hormones measured

(1)   Unparalleled study even outside of CFS

(2)   Correlation of inflammation related molecule levels with illness severity!!! (as symptoms progressed in severity, linear correlation with the inflammation molecules)

(3)   Jarred Younger’s cytokine network – primacy of leptin (hormone discovered in 1994 made by fat cells and diminishes appetite)

(a)    Leptin is closely tied to immune molecule CYTOKINES – correlate with the levels of fatigue in CFS patients

(4)   Elevated levels of Interleukin -17 – strongly associated with autoimmunity; elevated IL 17 compared with T-regulatory cells makes the risk of an autoimmune diseases worse, suggests that autoimmunity playing role in CFS

(5)   Significant decrease in mRNA’s would increase PROINFLAMMATORY molecules -- > internal biological confirmation validating Younger’s findings

(6)   Elevated levels of interferon-gamma

iv)    Interferon-gamma and CFS

(1)   Released by lymphocytes in response to viral and intracellular bacterial infections

(a)    CFI study – a HUGE difference between subsets of patients <3 years and >3

(b)   Interferon-gamma correlated with cognitive impairment (frequently associated by intracellular bacterial or viral infection – suggests an underlying infectious agent)

v)     Telemoeres: ends of chromosomes, shorter in CFS patients than healthy subjects

(1)   Length = marker for cellular aging, shorter telomeres denotes cells aging more rapidly – the short cells has divided many times and is older, hence short telomeres = > increased vulnerability to variety of disease associated with aging like atherosclerosis

(2)   Life stress associated with shorter telomeres (parents carrying for sick children)

(3)   Telomeres are shorter in patients with CFS v. healthy à suggests underlying biological process that is making us age faster

vi)    Virology and Infectious Agents

(1)   CFI study – reported no microorganisms in serum

(a)    Q: what about circulating white cells, brain, other tissue?

(b)   A: we will be investigating these

(2)   Enteroviruses: Dr. John Chia –antigen and nucleic acid found in biopsies between CFS and controls

(a)    When you took biopsy specimens with enteroviruses and injected into the mice, you found enteroviral infection in mice

(b)   Indicative of an infectious agent (since mice were infected)

(c)    Impressive research, yet it is depressing that no one else has used the existing CFS biopsies to do this on a mass scale.  Dr. Komaroff hopes that it changes in the future

(3)   Public health /epidemiology

(a)    Canadian Community Health Survey estimates that 411,500 of 35 M Canadians (1.1%) have CFS

(b)   Nearly a third has experienced at least one remission, which had lasted 1 year (median)

(c)    Rest/exercise/diet are more likely to reduce symptoms than medications or alternative treatments

(d)   CFI study reported that patients more comorbid illnesses than healthy controls

(4)   Case definition

(a)    Need to be precise: the way each component (mild, moderate, severe) need to be specified

(b)   Empirically derived case definitions are superior to consensus-drive case definitions

(i)     Better at defining subgroups – use statistical subgroup through the big data

(ii)   Better at predicting an endpoint – prognosis, a laboratory finding thought to define the pathology of the illness­

(5)   Exercise provocation studies:

(a)    A stressor that makes a patient feel worse should also bring out the underlying pathology, and a 2x dose of stressor should bring it out even more

(b)   On a single exercise study CFS patients did not consistently perform below normal, a second test the next day found abnormal VO2 max in 9% patients – not even people with heart and lung disease experienced this degradation à in their experience, exercise physiologists haven’t seen this before, indicative of the uniqueness of PEM

(c)    Low peak oxygen extraction relative to increase in cardiac output

(6)   Pediatric CFS:

(a)    Surprisingly high prevalence of delayed milk protein sensitivity in kids – changing dietary patterns might be able to alleviate some of the suffering in kids

(b)   Combination of widely available/inexpensive laboratory tests may predict which people with mono go on to post-mono CFS

(i)     15 years of research show post-mono CFS

(ii)   WHICH TESTS ARE THESE?  Very inexpensive!

(c)    Depression was found only in 25% of pediatric CFS patients – even after onset of illness

(i)     Teenagers – background healthy sample’s prevalence of depression à15%, so it seems only marginally higher in CFS teens

(7)   Neurology:

(a)    qEEG changes in CFS – peak alpha wave frequency significantly reduced over 58% of cerebral cortex, delta wave frequency increased particularly in frontal and limbic areas of the brain

(b)   Correlated linearly with the SYMPTOMS (fatigue or pain)!! Validates the symptoms!

(c)    Indicating likely disruptions of information transfer across cortical networks, and inhibition of ascending arousal systems

(d)   Neuro-inflammation by PET Scan –

(i)     iv injection of compound that binds to a translocator protein in microglial cells and astrocytes, image uptake by PET scan à show increased signal in multiple areas of the brain

(ii)   Intensity of the signal correlated with cognitive impairment

(8)   Conclusion: yes, abnormalities in fact do theoretically explain symptoms and DO CORRELATE with the symptoms 

(a)    Case control studies comparing CFS to health and disease-comparison groups (fatiguing ones) find robust evidence of an underlying biological process involving brain and autonomic, immune system, energy metabolism, oxidative and nitrosative stress

(b)   Illness is not simply the expression of somatic symptoms by people with a primary psychological disorder

(i)     It was fair to ask 30 years ago to ask whether it was psychiatric stress, amplifying normal body sensations

(ii)   But today, it’s no longer a valid question!

(9)   Q and A

(a)    Q: are we at the point where we can have biomarkers?

(b)   A: EEG might be a biomarker, since it showed near-perfect correlation between CFS and healthy controls

(c)    Q: What about NK cells and biomarkers?

(d)   A: immune based biomarkers are reasonable places to define subgroups; Dr. Klimas believes confidently that NK cell function can be used to determine severity

[3/30/14 Update: Since posting this, I've come across some additional summaries of the IACFS proceedings from someone who I consider one of the best ME/CFS bloggers, Christopher Cairns. I was beginning to lament that the notes above don't include much on Dr. Chia's presentations, but Mr. Cairns has taken care of that.  His is a more editorialized account of certain lectures, which I find refreshing.  For more, please see:

http://cfspatientadvocate.blogspot.co.uk/2014/03/iacfsme-and-then-mission-delores.html

and

http://cfspatientadvocate.blogspot.co.uk/2014/03/dr-jose-montoya-and-stanford-mecfs.html ]

  

[4/3/14 Update:  Got 51 minutes to spare?  Health Rising posted a video of Dr. Komoroff's closing speech, which is traditionally a summation of all the presentations at the IACFS Conference.  http://www.cortjohnson.org/blog/2014/04/02/report-san-francisco-ii-komaroff-summary/]