>>I'M AT THE NCCIH, NIH.
ON BEHALF
OF THE ENTIRE NIH-WIDE PLANNING
COMMITTEE FOR THIS WORKSHOP I
WANT TO WELCOME YOU TO DAY 2 OF
UNDERSTANDING AND RESTORING
WHOLE JOINT HEALTH IN PAIN
MANAGEMENT AN NIH HEAL
INITIATIVE WORKSHOP. BEFORE WE
BEGIN I WOULD LIKE TO COVER A
FEW LOGISTICS FOR THIS MEETING.
REMINDER FOR ZOOM ATTENDEES TO
MUTE YOURSELF WHEN NOT SPEAKING
AND RAISE YOUR DIGITAL HAND IF
YOU HAVE COMMENTS AND MAKE SURE
YOUR VIDEO IS ON DURING YOUR
SESSION PARTICULARLY WITH WHEN
SHARING COMMENTS OR THOUGHTS AND
FOR OUR NIH VIDEOCAST VIEWERS A
WARM WELCOME AND REMINDER THAT
YOU MAY SUBMIT A QUESTION AT ANY
TIME USING THE VIDEOCAST
FEEDBACK FORM. THE LINK FOR
THAT FORM WILL BE DIRECTLY BELOW
THE SCREEN WHERE YOU ARE VIEWING
THE SLIDE STREAM. NOW, OUR
QUESTION AND ANSWER PERIODS ARE
NOT HUGE, PARTICULARLY FOR
AUDIENCE AND ZOOM PARTICIPANT
QUESTIONS.
WE WILL TRY TO GET TO AS MANY
QUESTIONS OF YOURS AS WE
POSSIBLY CAN DURING THAT TIME.
BUT, IF WE DON'T GET TO YOUR
QUESTION, DON'T WORRY. WE WILL
ACTUALLY AGGREGATE ALL OF THE
QUESTIONS THAT YOU POSE AND WE
WILL SHARE THEM WITH YOUR
PLANNING TEAM MEMBERS.
FINALLY, THIS MEETING IS BEING
RECORDED. IT WILL BE ARCHIVED
ON THE NIH VIDEOCAST WEBSITE FOR
FUTURE VIEWING IN THE PAST EV
EVENTS SECTION. IF YOU HAVE TO
COME AND GO TODAY WATCHING THE
LIVESTREAM THAT IS FINE. WE ARE
RECORDING FOR LATER VIEWING AND
REMINDERS COVERED, I'M PLEASED
TO INVITE DR. WALTER KORISHETZ
TO WELCOME OUR PARTICIPANTS AND
OFFER OPENING REMARKS FOR DAY 2.
DR. KOROSHETZ, WE ARE GRATEFUL
YOU COULD JOIN TODAY. WE WILL
TURN THINGS OVER FOR YOUR
COMMENTS.
THANK YOU.
>>THANK YOU SO MUCH, CATHERINE.
MY PLEASURE. [INDISCERNIBLE] TO
JOIN AND I GUESS I THINK IT WAS
ANNA MARIE SAID THAT THE DRG AND
[INDISCERNIBLE] IS FAR AWAY BUT
AXONS AND DENDRITES AND NERVE
ENDINGS ARE JOINTS AND REALLY
APPRECIATE IT. WE WILL TALK A
LITTLE TODAY ABOUT
NEUROSCIENTISTS AND I WANTED TO
JUST FILL OUT A LITTLE ABOUT
WHAT HEAL IS DOING IN THE PAIN
SPACE.
AND SO JUST TO SAY THAT HEAL IS
TRYING TO ATTACK A MAJOR PROBLEM
WHICH IS CHRONIC PAIN AND MAIN
THING TO KNOW IS CHRONIC PAIN IS
REALLY LIMITING WHAT PEOPLE CAN
DO AND PERCENTAGE OF PEOPLE
WORSE IN RURAL AREAS AND URBAN
AREAS AND THERE IS A LOT OF
COMORBIDITIES IN PEOPLE WITH
SEVERE CHRONIC PAIN THAT IS A
REALLY COMPLICATED PROBLEM TO
SOLVE. THAT IS WHAT HEAL IS ALL
ABOUT. IT IS -- YOU KNOW, IT
WAS INITIATED AT FIRST BECAUSE
IT WAS TRYING TO TREAT PAIN THAT
PHYSICIANS GOT REALLY OVERBOARD
IN TERMS OF [INDISCERNIBLE] AND
OVERDOSE CRISIS, WHICH IS NOW,
YOU KNOW, LESSENED IN TERMS OF
PRESCRIPTION DRUGS AND
FORTUNATELY STIMULATED AN ENTIRE
INDUSTRY OF ILLEGAL DRUGS AND
FENTANYL AND DEATHS KEEPS GOING
UP AND HEAL STANDS FOR ADDING
ADDICTION LONG TERM AND ONLY WAY
TO DO THAT IS REALLY TO DEVELOP
DRUGS AND BETTER WAYS FOR PAIN
LIMITED RISK OF ADDICTION AND
WHAT HEAL IS ALL ABOUT.
NOW, MANY KNOW AS WELL AS I DO
THAT MAIN MANAGEMENT IS
CHALLENGING FOR LOTS OF
DIFFERENT ASPECTS. IT IS
COMPLEX FOR SURE.
CLEARLY, THE WORK THAT YOU TALK
ABOUT YESTERDAY INDICATES HOW
COMPLEX IT IS AT THE JOINT LEVEL
AND COMPLEX IT IS IN DRG AND
SPINAL CORD AND BRAIN LEVEL AS
WELL. I DON'T THINK WE HAVE THE
WORKFORCE WE NEED TO ATTACK THIS
PROBLEM.
TRAINING, YOU KNOW, BECAUSE IT
IS A VERY CROSS-DISCIPLINARY
PROBLEM.
IT IS REALLY CHALLENGED. I CAN
TELL YOU RIGHT NOW IN TRYING TO
DO EARLY PHASE TRIAL AND
OSTEOPATH AND OSTEOARTHRITIS AND
HAVING TREMENDOUS
[INDISCERNIBLE] IN ROLLING
PATIENTS AND NETWORK IN PHASE 2
TRIAL AND GOING AT THE RATE AND
WORKFORCE TO DO THIS RIGHT NOW.
THERE IS A LOT OF ISSUES WITH
ACCESS TO PAIN THERAPY FOR A
VARIETY OF DIFFERENT REASONS AND
SOME IS A LACK OF REALLY GOOD
PAIN [INDISCERNIBLE] AROUND THE
COUNTRY. THERE IS ALSO BIAS AND
STIGMA PEOPLE WITH PAIN AND
SUFFERING BECAUSE THEY CAN'T DO
WHAT THEY WANT TO DO BUT THEY
DON'T LOOK ANY WORSE THAN
ANYBODY ELSE AND THEY COMPLAIN
OF THEIR PAIN AND KIND OF SHRUG
THEM OFF. THERE IS A LOT OF
BIAS THERE AND REIMBURSEMENT TO
TAKE CARE OF CHRONIC PAIN IS NOT
PROCEDURES BUT IS REALLY TOUGH
TO GET TO COVER YOUR COSTS.
SO, YEAH. WHAT WE ARE TRYING TO
DO IN HEAL IS ACCELERATE
DISCOVERY AND DEVELOPMENT OF
NONADDICTIVE PAIN TREATMENTS AND
REASON THAT IT IS ACTUALLY
STARTING IN THE FIRST PLACE AND
TRUTH OF THE MATTER IS THAT, YOU
KNOW, WITHOUT NIH IN THIS SPACE,
VERY LITTLE WILL HAPPEN IN PAIN
THERAPEUTICS THAT IS PALTRY,
REALLY. AND IT IS -- YOU KNOW,
IT IS ACTUALLY MUCH WORSE THAN
IT WAS A COUPLE YEARS AGO
BECAUSE OF THE BIG FAILURES OF
LARGE PAIN TRIALS AND, YOU KNOW,
EVEN GOING INTO, YOU KNOW, THE
BIOCS ISSUE WHERE
[INDISCERNIBLE] AND DRUG OUT.
SO, [AUDIO SKIPPING].
>>DR. KOROSHETZ, I HATE TO
BOTHER YOU. YOU SEEM TO BE
BREAKING UP ON YOUR AUDIO A
LITTLE BIT.
DO YOU WANT TO TRY GETTING A
LITTLE CLOSER TO THE MICROPHONE?
MIGHT THAT BE THE ISSUE?
>>OKAY.
>>ALSO COULD BE VPN, DR.
KOROSHETZ IF YOU ARE ON VPN?
>>I'M HOOKED UP TO A NETWORK.
>>OH, DEAR. LET'S KEEP GOING
DR. KOROSHETZ. MAYBE, YOU KNOW,
JUST BE AWARE IT IS BREAKING UP
A LITTLE BIT AND WE WILL SEE IF
IT IMPROVES.
>>OKAY. MAYBE PUT YOUR FINGER
THUMB UP OR DOWN IF IT IS BAD.
>>IT IS GETTING A LITTLE
BETTER. LET'S KEEP GOING.
>>OKAY. ALL RIGHT. SO
DEVELOPING NONADDICTIVE PAIN
TREATMENTS IS ONE OF THE BIG
PRIORITIES OF HEAL.
THEN ADVANCING THROUGH CLINICAL
[INDISCERNIBLE] AND OUTPATIENTS
WORKING WITH THE INDUSTRY TO
COMMERCIALIZE DISCOVERIES THAT
HAVE BEEN MADE IN THE LABS AND
BIG PART OF HEAL IS INFORMING
[AUDIO BREAKING UP].
THIS IS USING THERAPIES THAT ARE
AVAILABLE BUT USING THEM IN A
MORE EFFECTIVE FASHION AND
PAYING ATTENTION RISK OF
ADDICTION AND IN TERMS OF
UNDERSTANDING, I'M SURE WE ARE
ONLY A SHORT PERCENTAGE OF THE
WAY OF UNDERSTAND IING TARGETS D
WHICH TARGETS TO PURSUE AND KNOW
IN HUCHL ANS IF THEY WILL HAVE A
ROBUST EFFECT TO A CLINICAL
TRIAL AND NOBEL PRIZE IN 2021
WAS IN MOLECULAR DISCOVERIES IN
CHILD AND PAIN AND INTERESTING
DISCOVERIES AND RELATED TO
SENSITIVITY AND [INDISCERNIBLE]
SENSITIVITY TO PAIN.
SYSTEM IS COMPLEX. PAIN SYSTEM
WAS BUILT. IT IS A REALLY OLD
SYSTEM. BASICALLY EVERY ANIMAL
HAS A PAIN SYSTEM THAT IS
BASICALLY TO PROTECT THE ANIMAL
FROM INJURY AND I'M SURE THAT
GIVEN THE MECHANICS FOR A JOINT
AND THE -- THE REAL DOWNSIDE OF
HAVING JOINT DEFORMITY FROM
HUNTING OR GATHERING.
YOU KNOW, SYSTEMS THAT HAVE BEEN
PUT TOGETHER TO REALLY PROTECT
YOUR JOINTS.
SO, PAIN, THE PAIN SYSTEM IS
CRITICAL FOR THE LIFE OF THE
JOINT.
THE OTHER THING TO KNOW IS THAT
PAIN HAS A SIMPLISTIC VIEW AND
COMPONENT AND STIMULUS YOU FEEL
PAIN AND GO AWAY AND THAT IS NOT
ALL IT IS TRYING TO DO.
IT HAS AN AMAZING MEMORY SYSTEM
SO WHEN YOU FEEL PAIN YOU WON'T
GO BACK TO SAME SITUATION AND
YOU ARE JOINED IN ANOTHER INJURY
POTENTIAL POSITION BECAUSE PAIN
STOCHS YOU FROM DOING THAT PAIN
AND PREVENTS YOU FROM DOING
THAT. THAT MEMORY SYSTEM IS
REALLY WHAT IS PRODUCED BY THE
PLASTICITY IN THE NERVOUS SYSTEM
TO CREATE THAT SENSE OF
BASICALLY SUFFERING THAT WILL
DRIVE YOU AWAY FROM THAT
STIMULUS AGAIN.
AND UNFORTUNATELY LONG TERM CAN
BECOME CHRONIC. IT IS NOT
ENTIRELY CLEAR WHERE FIRES ARE
COULD BE IN PLASTICITY THAT IS
DEVELOPED IN MEMORY PAIN BUT
CERTAINLY PEOPLE HAVE CHRONIC
PAIN DUE TO KNEE AND OSTEOCAN
ARTHRITIS AND 80 PERCENT OF THEM
HAVE PAIN IN [INDISCERNIBLE] AND
EFFECTING THE IN SYSTEM
SOUTHBOUND FOR 80% OF THE PEOPLE
AND FOR EVERYBODY AND THAT IS
THE BIG QUESTION IS WHETHER
PEOPLE DEVELOP CHRONIC PAIN EVEN
AFTER YOU TAKE CARE OF THE
PERIPHERAL ISSUE, WHETHER THAT
IS SOMETHING THAT IS STILL
REGARDING AND DUE TO SOME
DISFUNCTION AT THE PERIPHERY OR
WHETHER THERE IS A CENTRAL
FUNCTION THAT HAS HAPPENED.
AT THE NERVES BASICALLY --
>>WE ARE ACTUALLY REALLY LOSING
YOU DR. KOROSHETZ. WANT TO TRY
SOMETHING FOR ME AND TURN OFF
YOUR VIDEO QUICKLY TO SEE IF
THAT TAKES CARE OF THE BANDWIDTH
ISSUE WE ARE EXPERIENCING?
>>OKAY.
>>YOU CAN KEEP SHARING YOUR
SLIDES.
THAT IS FINE.
MAYBE STOP THE VIDEO FOR A
SECOND WHILE YOU ARE SPEAKING
AND SEE IF IT HELPS TO BRING
YOUR CONCLUSION TO THE LAST FEW
SLIDES HERE.
HOW ABOUT I GO AHEAD AND WILL
STOP YOUR VIDEO TEMPORARILY
SEEING IF IT HELPS. YOU CAN GO
AHEAD AND SHARE THE FULL SCREEN
ON YOUR SLIDES AGAIN AND KEEP
GOI
GOING.
>>ONE SECOND.
>>IF IT DOESN'T IMPROVE THE
AUDIO YOU CAN JUST GO TO.
>>HOW ABOUT NOW?
>>WE CAN HEAR YOU MUCH BETTER
NOW DR. KOROSHETZ, THANK YOU.
>>OKAY.
>>SLOOID SHARE PRESENTATION
MODE DOWN AT THE -- THAT IS
PERFECT.
>>OKAY.
>>OKAY. GREAT. KEEP GOING
THERE. THANK YOU, DR.
KOROSHETZ.
>>OKAY. SORRY ABOUT THAT. SO,
THE QUESTION I THINK FOR THE
GROUP IS TO WORK IN THIS SPACE
TO TRY TO UNDERSTAND ALL OF THE
DIFFERENT MEDIATORS OF
ACTIVATION OF THESE PAIN FIBERS
IN THE JOINT AND IN THE BONE AND
TISSUES AND THAT IS REALLY
IMPORTANT BECAUSE INTERVENING AT
THE PERIPHERY IS PROBABLY MORE
LIKELY TO BE SUCCESSFUL GOING
MORE CENTURY IN TARGET EFFECTS
EFFECTING OTHER NEUROSYSTEMS AND
EFFORTS YOU ARE WORKING ON WILL
REALLY PAY OFF IF WE TRY TO
UNDERSTAND HOW TO INTERCEPT PAIN
SIGNALS COMING FROM THE TISSUES
TO ACTIVATE THE NOSE RECEPTORS
AND THINK THAT THE IMPORTANCE OF
THE JOINT AS THE ORGAN OF
INTEREST IS CRITICAL AND AS WAS
MENTIONED YESTERDAY, ES CAPPADE
INTO ANTI-NERVE GROWTH FACTOR
FOR PAIN WAS A REALLY GOOD
LESSON WHERE WE PROBABLY GOT
BETTER PAIN CONTROL BUT AT THE
RISK OF WORSE JOINT DISEASE.
SO CENTRALLY THERE IS LOTS OF
THINGS GOING ON IN THE SPINAL
CORD AND BRAIN AND EXAMPLE THAT
IS EASIEST TO UNDERSTAND WHICH
IS PROBABLY DRG OR SPINAL CORD
MEDIATED IS WHEN YOU HAVE A
PAINFUL STIMULUS AND ONE ZONE.
YOU KNOW, WHAT HAPPENS IS AREAS
AROUND IT BECOME HYPERSENSITIVE
AS WELL. STIMULI THAT DON'T
USUALLY TRIGGER PAIN NOW TRIGGER
PAIN.
THAT IS A SIGN OF THIS
PLASTICITY THAT WE SEE ON THE
SKIN ALL THE TIME AND I'M SURE
IT GOES ON IN THE JOINT AS WELL
AND CERTAINLY DON'T UNDERSTAND
WHAT THAT PROCESS LOOKS LIKE IN
TERMS OF PARALLEL TO WHAT
HAPPENS IN THE SKIN. THAT WOULD
BE REALLY INTERESTING TO TRY TO
GET AT.
I GUESS TO ALSO MENTION THAT
THERE IS A LOT OF WORK GOING ON
IN THE BRAIN CIRCUITS AND SPINAL
CORD CIRCUITS THAT HAS TO DO
WITH ADVANCES IN TECHNOLOGY THAT
ARE COMING OUT OF THE BRAIN
INITIATIVE THAT ALLOW FOR VERY,
KIND OF, PRECISE TARGETING OF
SPECIFIC NEURAL GROUPS.
SO, YOU CAN -- YOU KNOW, THE
BEST EXAMPLES ARE AREAS IN THE
AMYG DOULA WHERE YOU TURN CELLS
OFF AND ANIMALS WITHDRAW FROM
PAIN AND HAVE NO SUFFERING
ASSOCIATED WITH IT.
THERE IS WORK GOING ON IN THAT
SPACE THAT IS FAR FROM THE JOINT
BUT IMPORTANT TO UNDERSTAND IN
TERMS OF THE CONTEXT OF WHAT
YOUR JOINT IS ALL ABOUT CH.
A BIG PROBLEM DEVELOPING PAIN
THERAPEUTICS IS LACK OF
BIOMARKERS AND RELIANCE ON A 1
TO 10 SUBJECTIVE PAIN SCALE.
SO, ANYTHING THAT YOU ARE
WORKING ON THAT WOULD LOOK LIKE
A POTENTIAL MARKER OF TARGET
ENGAGEMENT IN A THERAPEUTIC
TRIAL WOULD BE IMPORTANT TO
EXPLORE AND HAVE IN HEAL
BIOMARKER PROGRAMS TO VALIDATE
BIOMARKERS ANALYTICALLY AND
CLINICALLY BECAUSE IT WOULD BE A
TREMENDOUS HELP IN MOVING PAIN
THERAPEUTIC FORWARD.
AS I SAID, THERE IS LACK OF
TARGETS AND QUESTION IS HOW DO
YOU KNOW IF THEY ARE DOING WHAT
YOU THINK THEY ARE DOING GOING
INTO HUMANS AND THERE WE REALLY
NEED BIOMARKERS.
IN THE TRIAL WE ARE DOING WITH
OSTEOARTHRITIS PLAN WAS TO GET
FLUID OUT OF THE JOINT AND LOOK
AT WHETHER THE DRUG COULD REDUCE
INFLAMMATION WITHIN THE SYNOVIAL
FLUID AND PROBLEM IS LOTS OF
PLACES DON'T FEEL COMFORTABLE
STICKING NEEDLES IN JOINTS
ANYMORE AND THAT UNFORTUNATELY
IS NOT WORKING OUT AS WE WISH
AND SOMETHING THAT ALLOWS YOU TO
KNOW THAT YOUR DRUG IS DOING
WHAT YOU HOPE IT IS DOING AT THE
JOINT LEVEL WOULD BE INCREDIBLY
IMPORTANT TO SOME KIND OF
MEASUREMENT THAT MAY BE TEACHING
PEOPLE HOW TO DO JOINT
ASPIRATIONS THAT USED TO BE
PRETTY COMMON IN THE OLD DAYS.
WE HAVE THERAPEUTIC PROGRAMS AS
WELL THAT PEOPLE CAN COME IN FOR
IT AND HAVE SOMETHING THAT LOOKS
LIKE IT WILL BE A TREATMENT OR
JOINT PAIN.
THEY GO THROUGH MULTIPLE
DIFFERENT LEVELS AND FINAL GOAL
IS GETTING TO AN IND AND EVEN
INTO A PHASE 1 TRIAL.
SO HEAL SUPPORTS THIS WHAT WE
CALL DERISKING OF DISCOVERY AND
HOPING INDUSTRY WILL PICK UP
PROGRAMS AS THEY MOVE ALONG INTO
IND PHASE AND BIOMARKERS AS I
MENTIONED AND CLINICAL TRIALS WE
HAVE IN HEAL AND NUMBER OF
CLINICAL TRIALS GOING ON AND
SOME OF THESE ARE IN THE PRISM
SPACE WHERE TESTING PRIMARILY
NON-PHARMACOLOGICAL THERAPIES
AND WE HAVE ALSO THE
EFFECTIVENESS RESEARCH NETWORK
THAT IS TESTING A COMBINATION OF
PHARMACOLOGICAL AND NONFARM
CALOGICAL THERAPIES IN PAGE
CONDITIONS AND ACUTE PAIN
TRANSITION PROGRAM THAT IS GOING
ON IN THE COMMON FUND LOOKING AT
SAY, IMPORTANTLY, THE RISKS
PROFILE OF PEOPLE THAT GO ON TO
CHRONIC PAIN AFTER TOTAL KNEE
REPLACEMENT.
SO, HEAL IS REALLY A PRETTY
AMAZING PROGRAM FOR ANYONE THAT
IS INTERESTED IN THE PAIN
PROBLEM. WE DON'T HAVE AN
INSTITUTE FOR PAIN. HEAL IS A
PRETTY GOOD CONVENER FOR
MULTIPLE ICS IN PAIN SPACE AND
OFFERS THE ABILITY TO KIND OF
MOVE THINGS FROM DISCOVERY PHASE
TO ACTUALLY IMPROVE THE
TREATMENT OF PATIENTS.
REJOIN IS CLINICALLY IMPORTANT.
IT IS A SPACE WHERE WE THINK
LOTS OF ADVANCES COULD BE MADE
BY DOUBLING DOWN ON THE KIND OF
THINGS YOU FOLKS WERE TALKING
ABOUT YESTERDAY AND REALLY
UNDERSTANDING THE PAIN SYSTEM AT
THE JOINT LEVEL AND WHOLE JOINT
LEVEL WITH ALL OF THE RELEVANT
TISSUES AND REALLY LOOKING
FORWARD TO THE TALKS TODAY AND
WORKING WITH YOU IN THE FUTURE.
THANKS VERY MUCH.
>>WELL, THANKS SO MUCH, DR.
KOROSHETZ. WE REALLY APPRECIATE
YOU JOINING US TODAY AND WILL
INVITE YOU TO TURN BACK ON YOUR
VIDEO SINCE I TURNED IT OFF FOR
YOU. THANKS SO MUCH. WE ARE SO
GLAD YOU COULD JOIN US. THANKS
FOR THAT PRESENTATION TO REALLY
SET THE TONE FOR TODAY AND HELP
US BEGIN DAY 2 WITH SOME GREAT
CONTEXT.
NOW, I'M GOING TO TURN THINGS
OVER TO OUR SESSION 4 CHAIRS AND
SESSION 4 REMINDING YOU THIS IS
INTERVENTIONS TO ADDRESS JOINT
PAIN AND DISEASE AND CHAIR FOR
THE SESSION IS DR. ALEX TUTLE OF
NCCIH AND CO-CHAIRS ARE MICHAEL
OF NINDS AND DR. KATHLEEN SLUKA
WITH UNIVERSITY OF IOWA AND WE
ARE PLEASED THEY WILL TAKE US
THROUGH SESSION 4.
ALSO, ALEX, DID YOU WANT TO GO
AHEAD AND INTRODUCE OUR SPEAKERS
FOR SESSION 4 AND OUR PANELISTS?
PLEASE TAKE IT AWAY, ALEX.
>>ABSOLUTELY. THANK YOU
CATHERINE AND DR. KOROSHETZ FOR
ILLUMINATING AND OPENING DAY 2
OF THE WORKSHOP. -- AND CENTRAL
NERVOUS SYSTEM IN WAYS THAT THE
PERIPHERY CAN LEAD TO
AFTERERIENT SIGNAL IN CENTRAL
NERVOUS SYSTEM AND TARGETING
THOSE AFTER FERANT SIGNAL IS
SOMETHING TO THINK ABOUT OVER
THE COURSE OF THE WORKSHOP AND
PLEASURE TO INTRODUCE SESSION 4
INTERVENTIONS TO ADDRESS JOINT
PAIN AND DISEASE AND THANKS TO
CO-CHAIRS.
WE WILL HAVE FOLLOWING
PRESENTATIONS.
EXTERNAL CO-CHAIR DR. KATHLEEN
SLUKA WILL GIVE THE FIRST TALK
TODAY FROM UNIVERSITY OF IOWA
FOLLOWED BY DAN RHON FROM
UNIVERSITY OF HEALTH SCIENCES
AND THEN FROM STEPHEN MESIER
FROM WAIK FOREST AND PREETI FROM
JOHNS HOPKINS AND PANELISTS
TODAY INCLUDE DR.
GUNNARBROLINSON AND KATIE
BUTERA. 2K3W6789 ERTBRONFORT
FROM UMN AND CHRISTINE GOERTZ
AND BRIAN NOEHREN. I WELCOME
YOU TO LOOK IN THE PROGRAM
BOOKLET INCLUDED IN THE WORKSHOP
TO SEE A FULL SUMMARY AND BIOAND
RESEARCH INTEREST FROM ALL
SPEAKERS AND PANELISTS TODAY AND
WITH THAT INTRODUCING KATHLEEN
SLUKA AND INVITE HER TO TAKE IT
AWAY. THANK YOU DR. SLUKA.
>>LET'S SEE IF I CAN DO THIS.
ALL RIGHT. THANKS, ALEX, FOR
PUTTING THIS TOGETHER AND
INVITING ME TO PARTICIPATE.
I WILL TRY TO SHARE MY SCREEN.
SEE IF I CAN GET IT.
ALL RIGHT. SO, I WILL TALK
ABOUT TRANSCUTANEOUS SELECTIVE
NERVE STIMULATION OR TENS AN OLD
MODALITY THAT HAS BEEN AROUND
SINCE -- IT HAS BEEN AROUND
SINCE INVENTION OF ELECTRICITY
IN ONE FORM OR ANOTHER AND CAME
INTO MEDICAL ATTENTION IN THE
1960S IN RESPONSE TO THE GATE
CONTROLLED THEORY OF PAIN. I
WON'T GIVE YOU A BIG LONG
HISTORY BUT WILL SHOW YOU A
LITTLE BIT ABOUT HOW IT WORKS
AND TALK ABOUT CLINICAL
LITERATURE AND WHY OR WHY IT MAY
NOT SHOW EFFECTIVENESS IN
CLINICAL CONDITIONS.
I WILL ACKNOWLEDGE MY TEAM AND
WORK I HAVE PRESENTED HAS BEEN A
JOURNEY OF A COUPLE DECADES OF
RESEARCH FROM VARIOUS DIFFERENT
PEOPLE ACROSS THE WORLD WHO
PARTICIPATED AND SUBSTANTIAL
FUNDING FROM NATIONAL INSTITUTES
OF HEALTH AND ARTHRITIS
FOUNDATION. I HAVE A SLIDE ON
MECHANISMS THAT I WANT TO
SUMMARIZE IT. THESE WERE SERIES
OF EXPERIMENTS WE HAVE DONG OVER
MANY YEARS AND SHOWING THAT TENS
DOES THIS PRIMARILY IN CENTRAL
NERVOUS SYSTEM ENHANCING CENTRAL
INHIBITION AND ACTIVATES
DESCENDING INHIBITORY PATHWAYS.
IN PARTICULAR, IT DOES IT IN A
FREQUENCY DEPENDENT MANNER AND
TENS COULD BE GIVEN AT LOW
FREQUENCIES THAT IS 10 HERTZ OR
LESS OR HIGH FREQUENCIES OF 60
TO 150 HERTZ OF APPLIED
STIMULATION TO THE SKIN AND
PORTABLE DEVICES ARE OVER THE
COUNTER.
THEY ARE INEXPENSIVE AND EASY TO
USE WITH MINIMAL SIDE-EFFECTS
THAT I WILL SHOW YOU.
HIGH FREQUENCY PRODUCES EFFECTS
OF OPIOID RECEPTORS AT SITES AS
WELL AND LOW FREQUENCY AT
NEOOPIOID RECEPTORS AND ANOTHER
NUMBER OF TRANSMITTERS
DISCOVERED TO CONTRIBUTE TO ANAL
GEEZIA AS WELL AND IN ADDITION
TO ACTIVATING PATHWAYS IT
REDUCES CENTRAL EXCITABILITY OR
CENTRALIZATION WE HEARD ABOUT.
SO, ALL STUDIES I SHOULD POINT
OUT WERE DONE IN ANIMALS WITH
JOINT INFLAMMATION AND WE KNOW
THERE ARE CENTRAL SENSITIZATION
AFTER JOINT INFLAMMATION AND
TENS REDUCES SENSITIZATION BACK
TOWARDS BASELINE LEVELS THAT IS
A EXAMPLE OF A REPORTING FROM A
HIGH THRESHOLD NEURON IN DORSAL
[INDISCERNIBLE] AND YOU CAN SHOW
BEFORE AND AFTER REDUCTION IN
CENTRAL SENSITIVITY THAT REDUCES
GLUTAMATE RELEASE AND GLIAL CELL
ACTIVATION AND IS WORKING ON
MULTIPLE PATHWAYS TO CHANGE THE
CENTRAL NERVOUS SYSTEM. DESPITE
KNOWING ALL THIS, SYSTEMATIC
REVIEWS ARE A BIT MIXED.
SOME SHOW EFFECTIVENESS AND SOME
DON'T SHOW EFFECTIVENESS.
AND I PUT LIKE LITTLE RED DOTS
THAT CONCLUDED THAT TENS WAS
EFFECTIVE AND GREEN DOTS TO SHOW
THEY INCLUDED AN APPROPRIATE
DOSE.
ONE OF THE BIGGEST PROBLEMS WITH
THE MIXED RESULTS AND IN FACT
FOR OSTEOARTHRITIS, CLINICAL
GUIDELINES RECOMMEND NOT USING
TENS THAT I WILL SUGGEST TO YOU
THAT IS MAYBE BASED ON SOME
FLAWED LITERATURE.
MOST OF THE STUDIES FOR A RATHER
POOR QUALITY AND HIGH RISK OF
BIAS.
THEY HAD VERY LOW NUMBERS OF
SUBJECTS IN RANDOMIZED
CONTROLLED TRIALS AND MOST
IMPORTANTLY MOST USE INADEQUATE
DOSING AND DIDN'T TURN INTENSITY
UP ENOUGH TO HAVE AN APPROPRIATE
DOSE.
THAT IS LIKE GIVING, SAY,
MORPHINE AT A LOW DOSE THAT WE
WOULDN'T EXPECT TO BE EFFECTIVE
AND THEN ASKING WHETHER OR NOT
IT WORKS OR THEY TIMED THE
OUTCOME IN ODD WAYS AND GIVE THE
TENS AND TWO WEEKS LATER ASKED
DID IT WORK AND DOESN'T MAKE
SENSE GIVEN WE KNOW THERE IS A
PHARMACOLOGICAL MECHANISM OF
ACTION. I WILL GO THROUGH A
COUPLE OF EXAMPLES OF HOW OVER
THE YEARS US AND OTHERS HAVE
ADDRESSED THIS TO KIND OF SHOW
YOU THAT THERE REALLY DOES
MATTER HOW YOU GIVE IT, WHEN YOU
GIVE IT, AND WHAT ARE FACTORS
THAT EFFECT ITS EFFICACY. THE
FIRST ONE IS DOSE.
THIS IS HARD. WE HAVE TO THINK
ABOUT INTENSITY AND THINK ABOUT
FREQUENCY. WE HAVE TO THINK
ABOUT ALL OF THE PARAMETERS OF
ELECTRICAL STIMULATION AND WHERE
DO YOU APPLY IT?
IT TURNS OUT ONE OF THE MOST
IMPORTANT FACTORS OF DOSING IS
INTENSITY OF THE STIMULATION AND
AS A NEUROPHARMACOLOGIST, I
WANTED TO ACTUALLY DO A DOSE
RESPONSE COURSE AND WE DID THREE
DOSES OF TENS THAT YOU CAN SEE A
NICE INCREASE ANAL GEEZIA WITH
INCREASING DOSES AND DOSE WE
GIVE IS STRONG SENSORY
STIMULATION THAT IS STRONG BUT
NOT PAINFUL.
IN A SYSTEMATIC REVIEW DONE BY
JOHN IN NORWAY WE DID LITERATURE
ON POST-OP ITERATIVE PAIN AND
PUT PEOPLE INTO WHETHER THEY HAD
EFFECTIVE AND ADEQUATE DOSE OR
INADEQUATE DOSE AND CONSUMPTION
WAS ANALGESIC CONSUMPTION AND
THOSE WITH INADEQUATE DOSE IT
WAS NOT EFFECTIVE SUGGESTING WE
HAVE TO LOOK AT ACTUAL
LITERATURE AND DOSING
REQUIREMENTS BEFORE WE DECIDE
WHETHER OR NOT SOMETHING IS
EFFECTIVE.
TENS WORKS THROUGH OPIOIDS AND
ASKED THE QUESTION WHAT HAPPENS?
IS THERE INTERACTION WITH
OPIOIDS?
WHEN YOU GIVE TENS, THIS IS A
KIND OF EXAMPLE OF AN ANIMAL
MODEL WHERE YOU HAVE A THRESHOLD
RESPONSE AND AFTER JOINT
INFLAMMATION YOU GET DECREASE IN
THRESHOLD AND HIGH OR LOW
FREQUENCY IN TENS AND WE GET A
FULL REVERSAL. IF WE GIVE EXACT
SAME DOSE FOR SEVERAL DAYS WE
GET ANALGESIC TOLERANCE AND BY
DAY 4 IT IS NO LONGER WORKING IT
IS WORKING IN OPIOID RECEPTORS
IN CENTRAL NERVOUS SYSTEM AND
THEY DEVELOP TOLERANCE TO THE
OPIOID.
IF YOU TAKE ANIMALS MAKING THEM
TOLERANT TO OPIOIDS --
LASTLY WE DID A STUDY COMBINING
LOW AND HIGH FREQUENCY OF TENS
BASIC SCIENCE LITERATURE IF YOU
GIVE IT SIMULTANEOUSLY IT
REACHES ANALGESIC TOLERANCE AND
ABLE TO MAINTAIN EFFICACY OUT
WAY PAST THE 4 DAY TIME PERIOD
BY GIVING MIXED FREQUENCIES AND
WE ARE SAYING THIS IS ALSO PART
OF DOSING CONSIDERATIONS.
THE OTHER THING TO THINK ABOUT
IS OUTCOME MEASUREMENT AND
DESIGN.
WHAT ARE WE MEASURING?
LET'S TALK FIRST ABOUT THE
TIMING OF THE OUTCOME IF YOU
MEASURE DURING OR IMMEDIATELY
AFTER TENS IT TENDS TO HAVE BEST
EFFECT AND THOSE ARE LOW BACK
PAIN SHOWED THERE WAS
EFFECTIVENESS WHEN GIVEN AND
MEASURED DURING TENS AND 1 TO 3
MONTHS LATER IT DIDN'T WORK AND
SHORT TERM EFFECT AND WORKS
WHERE TENS UNIT IS ON OR
IMMEDIATELY AFTER BUT NOT LATER.
THIS IS AN ADEQUATELY POWERED
SYSTEMATIC REVIEW FOR MARK
JOHNSON WHERE HE TOOK ALL
STUDIES ON PAIN AND TENS AND IN
THIS CASE HE HAS 91RCTS WITH
OVER 4 THOUSAND PEOPLE LOOKING
AT TENS VERSUS PLACEBO AND TENS
VERSUS NO TREATMENT AND TENS
VERSUS STANDARD OF CARE THAT ALL
SHOW EFFICACY. IF COMPARING TWO
DIFFERENT TYPES OF TENS THEY
WORK THE SAME.
SO, HE IMPORTANTLY ONLY DID THIS
DURING OR IMMEDIATELY AFTER TENS
AND HE ONLY USED THOSE WHO HAD
ADEQUATE INTENSITIES.
SO, CONTENDING THAT IT MATTERS
THAT WE USE THE RIGHT DOSE AND
LOOK AT TIMING OF OUTCOME AND WE
LOOK AT THE RIGHT OUTCOME.
OKAY. WHAT IS THE RIGHT
OUTCOME?
IN A NUMBER OF DIFFERENT
STUDIES, THERE HAS BEEN A NUMBER
OF PEOPLE THAT LOOKED AT
DIFFERENT TYPES OF OUTCOMES AND
IS NOT PEOPLE WITH
OSTEOARTHRITIS AND LOOKING AT
PAIN THRESHOLDS AT THE KNEE, YOU
SEE WE GET A NICE REDUCTION AT
TENS AT KNEE JOINT AND PAIN
PRESSURE THRESHOLDS AND IS
LOOKING AT INDIVIDUALS WITH
FIBROMYALGIA AND LOOKING AT
RESTING PAIN VERSUS MOVEMENT
PAIN YOU GET REDUCTION IN
MOVEMENT NOT RESTING PAIN AND
HOLDS TRUE IN OSTEOARTHRITIS AS
WELL AND TENDS TO MOVE BETTER ON
MOVEMENT PAIN AND THIS IS IN
PEOPLE WITH NEUROPATHIC PAIN
THAT IS REDUCING ALODINIA
ASSOCIATED WITH NEUROPATHIC PAIN
THAT ARE ALL INVOKED RESPONSES
TO PAIN THAT MIGHT BE MORE
EFFECTIVE ON THAT TYPE OF
STIMULUS THAN IT IS ON RESTING
PAIN.
SO, I WANTED TO QUICKLY SHOW YOU
ABOUT A STUDY THAT WE DID THAT
WAS FUNDED BY NIAMS CALLED THE
FAST STUDY. WE LOOKED AT TENS
IN INDIVIDUALS WITH FIBROMYALGIA
ADDRESSING THOSE FACTORS AND
MIXED DOSE FREQUENCIES SO
WOULDN'T GET TOLERANCE AND
HIGHEST INTENSITY THEY COULD DO
THAT WASN'T PAINFUL AND ASKED
THEM TO WEAR TENS UNIT A COUPLE
HOURS PER DAY AND USE IT WHEN
ACTIVE AND PRIMARY OUTCOME WAS
MOVEMENT EVOKED PAIN AND
MEASURED IT DURING TENS AND
AFTER A SINGLE OR ONE AND THEN
WE SENT THEM HOME AND MEASURED
AFTER ONE MONTH OF USE.
WE HAD A BUNCH OF SECONDARY
OUTCOMES THAT I PROBABLY WON'T
TALK ABOUT.
WE ADEQUATELY POWERED IT
NOTICING WE HAD OVER 100 PEOPLE
PER GROUP THAT IS RARE IN
NON-PHARMACOLOGICAL RESEARCH TO
HAVE HIGHLY POWERED LARGE SAMPLE
SIZES.
WE COMPARED TO ACTIVE TENS TO
PLACEBO AND NO TENS WITH
STANDARD OF CARE TREATMENT AND
ALL PEOPLE WERE STILL TAKING
MEDICATIONS AND DOING NORMAL
THERAPIES.
SO, WHAT WE WERE ABLE TO SHOW IS
TENS REDUCED MOVEMENT PAIN.
THIS FIRST SESSION ON VISIT 2 IS
AFTER A SINGLE TREATMENT ON
VISIT 3.
THAT IS AFTER A MONTH OF
TREATMENT.
YOU CAN SEE THERE IS A NICE
NEARLY 2 POINT REDUCTION IN
MOVEMENT EVOKED PAIN MEASURED
DURING 6 MINUTE WALK TEST OR SIT
TO STAND TEST AND IS A
SIGNIFICANT REDUCTION IN
MOVEMENT EVOKED FATIGUE AND
SMALLER BUT SIGNIFICANT
REDUCTION IN RESTING PAIN.
WHEN WE MEASURED IT WHILE TENS
UNIT WAS ON, YOU CAN SEE A BIT
OF A CUMULATIVE EFFECT WITH
REPEATED USE.
GIVEN THIS, WE MEASURED ADVERSE
EVENTS AND I WANTED TO SHOW YOU
THESE NUMBERS.
SO, THIS IS NUMBER NEEDED TO
TREAT AND NUMBER NEEDED TO HARM.
I WILL LET YOU KNOW THAT IN
CLINICAL STUDIES WITH
PHARMACEUTICAL AGENTS APPROVED
WITH FIBROMYALGIA NUMBER TO
TREAT IS AROUND 8 OR 9 AND
NUMBER TO HARM IS SIMILARLY IN 9
TO 12 RANGE.
YOU CAN SEE THAT OUR NUMBER
NEEDED TO TREAT IS SOMEWHERE
BETWEEN 4 AND 5 FOR PAIN AND
FATIGUE WHEN COMPARED TO PLACEBO
OR NO TENS GROUP AND NUMBER
NEEDED TO HARM IS ESSENTIALLY
NONEXIST YENLT AND WINDOW SERIES
ADVERSE EVENTS IN ALL 300 PEOPLE
AND WORSE ONES WE GOT WERE LIKE
ITCHINESS AND SKIN IRRITATION
AND ANXIETY WITH TENS THAT CAN
BE ALLEVIATED BY REMOVING THE
TENS.
SO, I'M GOING TO SUMMARIZE BY
SAYING THAT TENS IS SAFE AND IS
EFFECTIVE AND INEXPENSIVE. IT
IS A METHOD THAT A PATIENT COULD
USE TO CONTROL THEIR PAIN DURING
ACTIVITY TO HOPEFULLY ALLOW THEM
TO BE MORE ACTIVE AND
PARTICIPATE IN EFFECTIVE
EXERCISE PROGRAMS.
SO, WHAT I HAVE PREPARED OVER
THE LAST TWO SLIDES THAT I WILL
THROW OUT THERE FOR DISCUSSION.
BUT, MY RECOMMENDATIONS ARE THAT
WE NEED FUTURE CLINICAL TRIALS
THAT TAKE ALL OF THESE
CONSIDERATIONS INTO THE TRIAL
ITSELF AND NEED TO THINK ABOUT
THE TIMING OF THE OUTCOME AND
DOING IT DURING OR IMMEDIATELY
AFTER TENS.
WE NEED TO THINK ABOUT THE
INTENSITY OF STIMULATION MAKING
SURE IT IS A STRONG BUT
COMFORTABLE INTENSITY.
WE HAVE TO THINK ABOUT SAMPLE
SIZES.
I WILL CONTENT THAT WE NEED, YOU
KNOW, RATHER LARGE SAMPLE SIZES
SO THEY COULD BE TRANSFERRED TO
THE GREATER POPULATION BETTER
AND WE MIGHT NEED MULTISIGHT
TRIALS TO DO THIS OR PRAGMATIC
TRIALS TO DO THIS AND NEED
PRAGMATIC TRIALS TO GET THIS
INTO THE CLINIC MORE AND USED TO
BE USED AND NOT USED BECAUSE
PEOPLE DON'T THINK IT IS
EFFECTIVE AND NOW KNOWING THAT
SCIENCE IS COMING BACK A LITTLE
BIT AND KNOW MORE IT IS BEING
PICKED UP A LITTLE BIT MORE.
WE NEED TO CONTROL FOR ALL RISKS
AND BIAS IN TRIALS.
MEASURE AND REPORT ADVERSE
EVENTS THAT GOES FOR ALL
NON-PHARMACOLOGICAL TREATMENTS
AND NEED TO DO THIS AND DO A
RESPONDER ANALYSIS WE DID IN THE
STUDY THAT I DON'T HAVE TIME TO
TALK ABOUT IT TODAY.
WE HAVE TO FIGURE OUT WHO WILL
BE BEST RESPONDER TO THIS
TREATMENT TO MOVE THEM FORWARD.
NOBODY RESPONDS TO EVERY
TREATMENT.
[INDISCERNIBLE] THIS IS REALLY
PROBLEMATIC AND SYSTEMATIC
REVIEWS WE TEND TO INCLUDE EVERY
STUDY EVER PUBLISHED IN THE
AREA. REMEMBER, THESE STUDIES
HAVE BEEN GOING ON SINCE 1960S
AND CLINICAL TRIAL METHODOLOGY
HAS GREATLY IMPROVED SINCE 1960S
THAT I WOULD SAY IS MUCH MORE
ROBUST TODAY THAN IT WAS EVEN 20
YEARS AGO.
SO, WE SHOULD BE LOOKING AT NOT
ONLY INCLUDING THINGS THAT ARE
RELATED TO DOSE AND TIMING OF
OUTCOMES AND SAMPLE SIZE. WE
SHOULD ALSO BE LOOKING AT
THINKING ABOUT SHOULD WE BE
INCLUDING OLDER TRIALS THAT MAY
OR MAY NOT HAVE USED ADEQUATE
BLINDING AND ADEQUATE CONTROL
FOR ADEQUATE RISK OF BIAS IN
THOSE.
SHOULD WE BE DOING METAANALYSIS
ON SAMPLES OF 100, SHOULD WE
WAIT UNTIL WE HAVE LARGE ENOUGH
POOL OF SAMPLE SIZE LIKE MARK
JOHNSON DID WITH HIS AND INCLUDE
RTCS WITH SMALL SAMPLE SIZES OR
WAIT UNTIL WE HAVE ENOUGH RTCS
WITH ADEQUATE SAMPLE SIZES TO
INCLUDE IN THESE AND SMALL
SAMPLE SIZES, YOU KNOW, PUT US
IN A POSITION OF HAVING FALSE
POSITIVES AND FALSE NEGATIVES
AND IT -- IT IS DIFFICULT TO
INTERPRET THE DATA.
>>ALL RIGHT. DR. SLUKA, WE
HAVE TO MOVE TO THE NEXT
SPEAKER. THANKS VERY MUCH.
>>ALL RIGHT. THAT IS IT.
THANK YOU.
>>THANK YOU.
>>YOU DIDN'T GIVE A WARNING.
>>WE WILL MAKE SURE WE ARE
DOING IT FOR FOLT OWING
SPEAKERS.
>>OKAY. SORRY ABOUT THAT.
>>NO, NO, NO. THANK YOU VERY
MUCH. DR. RHON?
THANK YOU VERY MUCH.
>>HERE WE GO. ALL RIGHT. I'M
GRATEFUL FOR THE INVITATION AND
OPPORTUNITY TO SHARE A LITTLE
BIT ABOUT OUR WORK LOOKING AT
MANUAL THERAPY FOR TREATING
LOWER EXTREMITY OSTEOARTHRITIS
IN PARTICULAR KNEE
OSTEOARTHRITIS AND LOOK AT THE
EFFECTIVENESS AND PROBABLY NOT
AS MUCH THE PROPOSED MECHANISMS
JUST BECAUSE THIS TIME PERIOD IS
REALLY SHORT.
LET'S SEE. THERE WE GO.
DISCLAIMERS.
BURDEN OF KNEE OSTEOARTHRITIS
AND THINK WHY WE CHOSEN THIS
CONDITION GLOBALLY 291
CONDITIONS HIP [INDISCERNIBLE]
RANKED HIGHEST CONTRIBUTOR TO
GLOBAL DISABILITY AND 3 EIGHTH
HIGHEST DISABILITY ADJUSTED IN
LIFE YEARS AND LOOKING AT JUST
NORTH AMERICA IT IS EIGHTH MOST
EXPENSIVE OUT OF 154 HEALTH
CONDITIONS TO MANAGE.
SO, SOMETHING THAT REALLY NEEDS
TO TAKE SOME OF OUR ATTENTION.
IT IS HELPFUL TO START WITH SOME
WORKING DEFINITIONS OF MANUAL
THERAPY.
THIS IS A SYSTEMATIC REVIEW DONE
BY SOME OF MY STUDENTS FOR
REVIEW AND BACK PAIN OUT OF
176RCTS THERE WAS 169 UNIQUE
TERMS LABELED AS MANUAL THERAPY.
IF LOOGING AT -- THEIR
DEFINITION OF MANUAL THERAPIES
INCLUDING TRIGGER POINT DRY
NEEDLING, CUPPING,
INSTRUMENT-ASSISTED DEVICES AND
MASSAGE AND ALL OF THESE THINGS.
A LOT OF THE TRIALS FOR LOW BACK
PAIN AND NECK PAIN LESS THAN 5%
PROVIDED ANY SORT OF LEVEL OF
DESCRIPTION THAT ALLOWED IT TO
BE REPRODUCED.
SO, BECAUSE OF THIS, I THINK IT
IS JUST AN IMPORTANT STEP BACK
AND LOOK AT THIS HOW WE DEFINE
MANUAL THERAPY AS MORE OF A
TREATMENT APPROACH.
SO, IT IS AN INTEGRATION OF
ACTIVE AND PASSIVE STRATEGY AND
WHOLE PURPOSE OF THE MANUAL
THERAPY APPROACH IS TO GET THE
PATIENT TO MOVE BETTER AND MORE
EXERCISE AND WE KNOW PHYSICAL
ACTIVITY IS A CORE INTERVENTION
THAT IS RECOMMENDED IN MOST
CLINICAL PRACTICE GUIDELINES FOR
OSTEOARTHRITIS. PATIENTS WILL
COME IN.
THERE IS A LOT OF MOTIONS WITH
EXERCISE AND REGULAR
PHYSIOLOGICAL MOTIONS AND
FLEXION EXTENSION AND WHAT NOT.
THEY ARE PROBABLY ABLE TO GET
LOTS OF ACCESSORY MOTIONS IN
THAT JOINT GETS STIFFER AND
ANTERIOR AND POSTERIOR TIBULAR
ROTATION AND THOSE TYPES OF
THINGS CAN BENEFIT FROM MANUALLY
ASSISTED MOBILIZATIONS AND POINT
IS WITH PATIENTS WHAT A SECTION
MIGHT LOOK LIKE THEY COME IN AND
DO A FUNCTIONAL SQUAT AND THEY
HAVE PAIN AND WE MOBILIZE TIBIO
FEMORAL JOINT AND REDUCE PAIN
AND HAVE THEM SQUAT A LOT BETTER
AND TRANSITION INTO ACTIVITY AND
EXERCISE AND OVER A COURSE OF
PHYSICAL THERAPY AND 8 TO 10
SESSIONS AND FIRST COUPLE
SESSIONS MIGHT HAVE MORE
MANUALLY APPLIED INTERVENTIONS
THAT NEAR THE END THEY ARE
EXERCISING MORE AND FALLING
CLINICAL REASONING FRAMEWORK AND
TUNE UP BOOSTER VISITS AND GOAL
OF THIS IS TO GET PATIENTS TO
MOVE MORE AND BE ACTIVE GET
BENEFITS OF PHYSICAL ACTIVITY
AND EXERCISE AND RESEARCH
STARTED BACK WITH FIRST
PUBLICATION BACK IN YEAR 2000.
AND WHERE -- WHERE MANUAL
PHYSICAL THERAPY WAS COMPARED TO
PLACEBO ULTRA SOUND.
AND SUBTHERAPEUTIC ULTRA SOUND.
WE COULD SEE EFFECT SIZES HERE.
IT WAS EFFECTIVE WOMBAC
OSTEOARTHRITIS INDEX AND
[INDISCERNIBLE] COMPARED TO
PLACEBO AND IMPROVEMENTS IN 6
MINUTE WALK TEST A FEW YEARS
LATER ANOTHER FOLLOW ON TRIAL
THIS TIME COMPARING MANUAL
PHYSICAL THERAPY TO EXERCISE
PROGRAM AND HOME EXERCISE
PROGRAM AND THEY WOULD COME IN
AND GET EXERCISES PRESCRIBED AND
BE ABLE TO DEMONSTRATE. THEY
COULD DO IT AND KEPT A LOG AT
HOME AND ABLE TO FOLLOW UP WITH
PHYSICAL THERAPISTS.
WITH BOTH INTERVENTIONS YOU SAW
MANUAL PHYSICAL THERAPY THAT WAS
ROUGHLY ABOUT 8 SESSIONS THAT
WAS ONE OF THE OVERALL TREATMENT
DOSE.
YOU COULD SEE IT WAS
SIGNIFICANTLY -- THERE WAS A
GOOD EFFECT SIZE THERE COMPARED
TO HOME EXERCISE PROGRAM AND
FAST FORWARD A FEW YEARS.
THIS PAPER THAT CAME OUT WHERE
WE LOOKED AT INJECTION STEROID
INJECTION AND LOOKED AT
LITERATURE AND FOUND THAT, YOU
KNOW, ROUGHLY A LOT MORE
PATIENTS GETS INJECTIONS AND
ROUGHLY 50% ACROSS THE BOARD
THAT IS A COMMON INTERVENTION
DOING COMPARATIVE EFFECTIVENESS
TRIAL TO SEE LET'S COMPARE THIS
TO MANUAL PHYSICAL THERAPY
APPROACH SEEING WHAT DIFFERENCES
ARE AND MAYBE THIS WILL HELP
WITH THE UPTAKE OF THIS. AGAIN,
WE SAW IT WAS EFFECTIVE THAT IS
LONG TERM OUT TO ONE YEAR AND
DID COST EFFECTIVENESS ANALYSIS.
ISSUE IS LOTS OF PATIENTS THINK
THAT THEY HAVE -- THEY WILL ONLY
GET ONE INJECTION THAT IS ONE
VISIT COMING IN TO PHYSICAL
THERAPY AND TAKES A LITTLE MORE
TIME AND MAYBE A LITTLE -- A FEW
MORE OUT OF POCKET COSTS AND IN
THE SHORT TERM COULD BE MORE
COSTLY. HOWEVER, WE FOUND THAT
THE MEDIAN NUMBER OF INJECTIONS
THAT PEOPLE ACTUALLY ENDED UP
HAVING. LOTS OF PEOPLE COME
BACK HAVING MORE AND 2.3
INJECTIONS OR -- SO, A LOT OF
PEOPLE COME IN GETTING
ADDITIONAL INJECTIONS AND WAS 4
INDIVIDUALS THAT HAD SURGERY
BETWEEN ARTHROSCOPY AND TOTAL
KNEE REPLACEMENT IN INJECTION
GROUP AND 0 IN PHYSICAL THERAPY
GROUP AND OVER PERIOD OF A YEAR,
FOLLOW UP, THERE IS MORE UP
FRONT COSTS THAT MIGHT ACTUALLY
BE CHEAPER IN THE LONG RUN. YOU
MIGHT UTILIZE LESS HEALTH CARE
AND INTERESTING IS STABILITY OF
THIS EFFECT. YOU CAN SEE IN
BLACK THERE, THERE ARE TWO
TRIALS SUPERIMPOSED FIRST ONES
IN 2000 AND 2005 AND RED LINE IS
MOST RECENT ONE THAT IS A STABLE
INTERVENTION THAT ALMOST A 20
YEAR PERIOD IN DIFFERENT TRIALS
THAT HAS HAD A VERY SIMILAR AND
VERY STABLE EFFECT SIZE.
IF YOU COULD TAKE THIS EFFECT
SIZE WITH SUCH MINIMAL
SIDE-EFFECTS AND PUT IT IN A
BOTTLE AND MARKET THIS,
PHARMACEUTICAL INDUSTRY WOULD BE
VERY, VERY EXCITED ABOUT
TREATMENT EFFECTS YOU ARE ABLE
TO SEE WITH THIS.
SO, WHEN WE TALK ABOUT, YOU
KNOW, WHY THIS WORKS, REAL
QUICKLY, THERE IS -- THIS COULD
BE A WHOLE OTHER TALK IN AND OF
ITSELF AND KNOW THAT EXERCISE
AND PHYSICAL ACTIVITY IS THE
CORE RECOMMENDATION INTERVENTION
THAT PATIENTS WITH KNEE
OSTEOARTHRITIS SHOULD BE
RECEIVING AND ONE OF THE
CHALLENGES IS THAT TOO MUCH
LOADING OF THE JOINT THAT IS
TYPICALLY THE CONCERN AND TOO
MANY COMPRESSION FORCES.
THEY CAN -- THEY CAN MAKE THE
JOINT WORSE.
ALSO, UNDERLOADING THE JOINT IS
ALSO SEEMING TO BE EQUALLY IF
NOT MORE SORT OF THESE CATABOLIC
EFFECTS OF THE -- THE JOINT CART
LITH.
THAT IS ONE OF THE BIGGEST
CHALLENGES.
WE HAVE REALLY A LOT OF EVIDENCE
CONTRARY TO PROBABLY PATIENT
BELIEFS AND CLINICIAN BELIEFS.
YOU KNOW, WE ARE PROBABLY ON THE
ERRING ON THE SIDE OF DOING TOO
LITTLE RATHER THAN DOING TOO
MUCH AND MIGHT BE PROTECTIVE FOR
KNEE OSTEOARTHRITIS IN SOME
CASES AND HIGHER INTENSITY
STRENGTH TRAINING THAT LOADED
THE JOINT WASN'T ANY WORSE THAN
LOWER INTENSITY STRENGTH
TRAINING.
SO, THESE ARE MESSAGES THAT
PATIENTS ARE PROBABLY NOT
GETTING AND LOTS OF CLINICIANS
ARE NOT GETTING AND YOU TEND TO
BE A LITTLE MORE RISK AVERSE AND
NOT WANT TO DO A LOT OF
ACTIVITY.
GETTING INTO MECHANISMS OF PAIN
REDUCTION. AGAIN, THIS CAN BE
PRETTY COMPLEX AND WOULD POINT
YOU TO SOME WORK DONE BY JOE
BILOSKI. HE PROPOSED MECHANISMS
FROM PAIN MODULATION AND MANUAL
THERAPY. REALLY IS A GREAT AND
INTERESTING STUFF THERE. AGAIN,
I WON'T GET INTO DETAILS TOO
MUCH.
BUT, I WOULD JUST PROPOSE THAT
MAYBE THE -- THAT IS NOT THE
PROBLEM.
YOU KNOW, THE PROBLEM IS NOT TO
QUESTION. SOLUTION IS NOT THE
ANSWER.
SO, NOT TO GET TOO PHILOSOPHICAL
HERE AND TO STEAL FROM THE MATH
LITERATURE TO FIND THIS TOPIC.
YOU KNOW, HOW MANY PATIENTS WITH
OA IN UNITED STATES RECEIVE
PHYSICAL THERAPY AND NEOA AND
PRIOR TO GETTING A JOINT
REPLACEMENT THAT IS ULTIMATE
TREATMENT AND WON'T WAIT ON
ANSWERS SINCE WE ARE SHORT ON
TIME AND 10 TO 15% GOING TO
PHYSICAL THERAPY AND POINT THEY
GET KNEE REPLACEMENT IT ENTO 15%
TRY OR HAD PHYSICAL THERAPY AT
SOME POINT. I THINK IT IS
OUTRAGEOUS AND NO THE THAT WE --
WE KNOW WHAT WORKS AND MAYBE THE
QUESTION IS HOW TO GET PEOPLE TO
UTILIZE IT.
LOOKING AT UTILIZATION OF
PHYSICAL THERAPY AND SEE THAT
REFERRAL RATES ARE LESS THAN 5%
FOR PRIMARY CARE. THEY HAVE
BEEN GOING DOWN BETWEEN 2007 AND
2015 AND A LITTLE BETTER FOR
ORTHOPEDIC SURGEONS 9 TO 15%.
THAT IS A BIG PROBLEM. AT THE
SAME TIME, PHARMACEUTICAL
INTERVENTIONS HAVE BEEN GOING
UP, YOU KNOW, SUBSTANTIALLY IN
THE SAME PERIOD.
SO, YOU KNOW, WHEN YOU LOOK AT
COCHRAN REVIEW MIXED METHODS
THAT IS REALLY INTERESTING AND
PEOPLE BELIEFS ABOUT CHRONIC
PAIN AND HOW TO MANAGE PAIN AND
KNEES ARE DELICATE AS A
CONSEQUENCE. YOU KNOW, THEY
AVOID ACTIVITY FOR FEAR OF
CAUSING HARM. THEY NEED TO
REALLY PROVIDE ASSURANCE AND
CLEAR ADVICE ABOUT VALUE OF
EXERCISE AND PAPER WAS REALLY
INTERESTING IN CLINICAL
ORTHOPEDICS -- WAITING TO GET
KNEE REPLACEMENT INTERVIEWED
BONE ON BONE BELIEFS IDENTITY
BELIEFS AND MOST BELIEVED THAT
LOADING KNEE WOULD MAKE THEM
VULNERABLE AND EXERCISE PHYSICAL
THERAPY WOULD INCREASE PAIN AND
MAKE THEM WORSE.
THEY PREFERRED SURGICAL AND
EXPERIMENTAL TREATMENTS OVER,
YOU KNOW, LOTS OF EXERCISES.
YOU CAN SEE HERE IN THE LITTLE
FIGURE HERE THAT WEAR AND TEAR
AND BONE ON BONE.
>>IN A MINUTE. OKAY?
>>THEY GO TO THEIR TREATMENT
BELIEFS AND LEAD THEM TO THE
POINT THAT SURGERY IS REALLY THE
ONLY OPTION.
WHY AM I GOING TO GO TO PHYSICAL
THERAPY AND DO EXERCISE THAT
WILL ONLY GET IT WORSE?
SO, THERE IS SOME POTENTIAL FOR
LOW UPTAKE BOTH FROM THE PATIENT
BELIEFS PERSPECTIVE BUT FROM THE
CLINICIAN. I THINK THE QUESTION
IS NOT WHAT WORKS.
WE HAVE A REALLY POWERFUL
INTERVENTION. AGAIN, IT WON'T
WORK FOR EVERYONE, BUT IF WE
ONLY HAVE 10 TO 15% OF PATIENTS
GETTING THIS INTERVENTION BEFORE
THEY GO AND HAVE A KNEE JOINT
REPLACEMENT THERE IS ROOM FOR
IMPROVEMENT AND GETTING UPTAKE
UTILIZATION FOR WHAT WE KNOW
WORKS.
AS A DAD, I HAVE TO THROW IN A
LITTLE DAD JOKE THERE. THANK
YOU.
>>THANK YOU SO MUCH.
DR. MESSIER, YOU ARE WELCOME TO
SHARE YOUR SLIDES.
>>OKAY. CAN ANYONE SEE THAT?
>>YES. WE CAN SEE YOU. YUP.
>>OKAY.
>>ALL RIGHT. WELL, FIRST,
THANKS FOR INVITING ME HERE FOR
THIS WONDERFUL WORK SHOP. I
REALLY APPRECIATE IT. BEFORE WE
GET GOING, I WOULD LIKE TO
ACKNOWLEDGE AN OUTSTANDING GROUP
OF INVESTIGATORS.
WELL, OBESITY AND JOINT PAIN ARE
RELATED.
AS OBESITY INCREASES FROM
OVERWEIGHT TO CLASS 3 OBESITY,
ODDS RATIO IS FOR JOINT PAIN
INCREASE.
FOR EXAMPLE, FEMALES WITH CLASS
3 OBESITY ARE FOUR TIMES AS
LIKELY TO HAVE JOINT PAIN AS
FEMALES WITH NORMAL WEIGHT.
ABOUT HALF OF ALL OF THE WOMEN
WITH CLASS 2 OR CLASS 3 OBESITY
SHOWN HERE IN THE PURPLE BARS
REPORTS SUBSTANTIAL JOINT PAIN
THAT THIS INCREASES WITH AGE.
DOES GEOGRAPHY MATTER?
WELL, APPARENTLY, IT DOES.
PEOPLE WITH OBESITY AND KNEE
OSTEOARTHRITIS LIVING IN RURAL
COMMUNITIES HAVE SIGNIFICANTLY
MORE JOINT PAIN THAN A SIMILAR
COHORT THAT LIVES IN URBAN
COMMUNITIES OBESITY IS
ASSOCIATED WITH JOINT PAIN.
GEOGRAPHY MATTERS THOSE WITH
NEO-A AND OBESITY LIVING IN
RURAL COMMUNITIES REPORT MORE
JOINT PAIN THAN THOSE PEOPLE WHO
LIVE IN MORE URBAN AREAS.
THE TWO MOST COMMON EXERCISES IN
TRIALS OF ADULTS WITH KNEE PAIN
ARE WALKING AND TO A LESSER
EXTENT, WEIGHT TRAIN. FITNESS
ARTHRITIS AND SENIORS TRIAL SHOW
THAT 18 MONTHS OF EITHER AEROBIC
WALKING EXERCISE OR RESISTANCE
EXERCISE SLOWED PROGRESSION AND
DISABILITY THAT IS COMMON IN
OLDER ADULTS WITH KNEE
OSTEOARTHRITIS COMPARED TO
HEALTH EDUCATION CONTROL GROUP
AND HELP ESTABLISH EXERCISE
STANDARD OF CARE FOR PEOPLE WITH
KNEE OSTEOARTHRITIS.
WEIGHT TRAINING GROUP IN AEROBIC
WALKING GROUP HAD SIGNIFICANTLY
LESS PAIN INTENSITY AFTER 18
MONTHS COMPARED TO HEALTH
EDUCATION THAN CONTROL GROUP.
--
SHOWING THAT 12 WEEKS OF
[INDISCERNIBLE] STRENGTH
TRAINING SIGNIFICANTLY DECREASE
KNEE PAIN VERSUS CONTROL IN KNEE
OSTEOARTHRITIS PATIENTS AND
STRENGTH TRAINING FOR ARTHRITIS
TRIAL OR START RANDOMIZE 377
PARTICIPANTS TO ONE OF 3 GROUPS
AND HIGH INTENSITY STRENGTH
TRAINING, LOW INTENSITY STRENGTH
TRAINING OR RETENTION CONTROL
AND ALL THREE INTERVENTIONS WERE
18 MONTHS IN DURATION PERCENT
REDUCTION IN PLAIN WAS LOW OF 2
SEVEN% FOR HIGH INTENSITY
STRENGTH TRAINING GROUP TO HIGH
OF 39% FOR LOW INTENSITY
STRENGTH TRAINING GROUP WITH
CONTROL GROUP BEING IN-BETWEEN
WITH TLE 3% REDUCTION IN PAIN.
PERCENT OF PATIENTS USING PAIN
MEDICATION DECREASED ACROSS ALL
THREE GRIPES AND LOW INTENSITY
PATIENTS WERE 3 TIMES MORE
LIKELY NOT TO USE PAIN
MEDICATION BY 18 MONTH FOLLOW UP
VERSUS THE CONTROL.
RECOMMENDATIONS SUGGEST THAT
EXERCISE COMPARED FAB RABLY TO
ACETAMINOPHEN AND EFFECT SIZE
FOR PAIN. HOWEVER, EFFECT SIZE
FOR EXERCISE DECLINE IN PEOPLE
WITH KNEE KNEE OSTEOARTHRITIS AS
SAMPLE SIZE AT THE TIME
DECREASES FROM TWO MONTHS WITH
EFFECT SIZE OF .54 ALL THE WAY
DOWN TO AN EFFECT SIZE OF .09
FOR 18-MONTH INTERVENTION.
THIS MAY HELP EXPLAIN RESULTS OF
A RECENT SYSTEMATIC REVIEW AND
METAANALYSIS AND FIRST PLOT
SHOWS DIFFERENCE BETWEEN
EXERCISE AND CONTROL ON 0 TO 100
SCALE.
OVERALL, THERE WAS A MODEST
DIFFERENCE OF ABOUT 3.4 POINTS
AND 3.4% FAVORING IMPROVEMENT IN
PAIN.
HOWEVER, THIS DIFFERENCE IS OF
QUESTIONABLE CLINICAL
IMPORTANCE.
SO, THEN EXERCISE AND OBESITY.
EXERCISE REDUCES JOINT PAIN IN
PEOPLE WITH OBESITY AND KNEE
OSTEOARTHRITIS AND EFFECT SIZE
DECREASES AS LENGTH OF
INTERVENTION INCREASES.
NUMEROUS STUDY SHOWS EXERCISE
HAS MANY POSITIVE EFFECTS.
HOWEVER, LONG-TERM EFFECT ON
PAIN IN THIS POPULATION IS MOD
EST AND OF UNCERTAIN CLINICAL
IMPORTANCE AND MECHANISTIC MODEL
SHOWS WEIGHT LO S AND EXERCISE
IMPACT BIOMECHANICAL AND
INFLAMMATORY DISEASE PATHWAYS
RESULTING IN DECREASE KNEE JOINT
LOANS AND DECREASE IN
INFLAMMATORY CYTOKINE ACTIVITY
AND DECREASE IN TISSUE DAMAGE
AND [INDISCERNIBLE] AND LESS
[INDISCERNIBLE].
ALL RESULTING IN WHAT IS
IMPORTANT TO THE PATIENT IS A
DECREASE IN PAIN.
AND IMPROVED FUNCTION.
INTENSIVE DIET AND EXERCISE FOR
ARTHRITIS TRIAL OR IDEA HAD
THREE INTERVENTION BOOTHS AND
EXERCISE IN COMPARISON GROUP AND
DIET ONLY GROUP AND DIET PLUS
EXERCISE GROUP AND DIET GOING
FOR TWO DIET GROUPS AT LEAST A
10% WEIGHT LOSS OVER 18 MONTH
INTERVENTION.
THIS IS A MONTH BY MONTH WEIGHT
LOSS FOR DIET ONLY AND DIET PLUS
ASKER SIZE GROUP.
YOU CAN SEE ADDITION OF EXERCISE
TO DIET ADDS 2% MORE IN WEIGHT
LOSS OVER 18 MONTH INTERVENTION
PERIOD.
ALL THREE GROUPS REDUCED PAIN BY
SAME AMOUNT OVER FIRST 6 MONTHS
AND WASN'T UNTIL 8 TA ENMONTHS
THAT DIET PLUS EXERCISE GROUPS
SEPARATED ITSELF FROM OTHER TWO
GROUPS WITH 51% DECREASE IN
PAIN.
YOU CAN REDUCE PAIN BY 50% WITH
LONG TERM DIETARY WEIGHT LOSS
AND MODERATE EXERCISE AND
INFLAMMATORY OUTCOME IO6 WAS
SIGNIFICANTLY REDUCED IN TWO
DIET GROUPS 13 AND 14%
REDUCTIONS COMPARED TO 3%
INCREASE IN EXERCISE-ONLY
COMPARISON GROUP.
KNEE COMPRESSOR FORCES WERE
REDUCED IN DIET ONLY GROUP
COMPARED TO EXERCISE GROUP WITH
DIET AND EXERCISE GROUP BEING
IN-BETWEEN.
DIET PLUS EXERCISE REDUCES
ABNORMAL STRESS DECREASING KNEE
JOINT LOADS AND [INDISCERNIBLE]
PHYSIOLOGY BY LOWERING
INFLAMMATION RESULTING IN LESS
PAIN AND LESS DISABILITY.
NOW WE KNOW THAT 10% WEIGHT LOSS
IS EFFECTIVE IN REDUCING PAIN
AND NEXT LOGICAL QUESTION WOULD
BE THERE IS MORE WEIGHT LOSS
BETTER?
THIS TABLE SHOWS MEAN DOSE
RESPONSE TO WEIGHT LOSS FOR PAIN
AT 18 MONTH FOLLOW UP.
AS WEIGHT LOSS INCREASED FROM
GREATER THAN 5% TO GREATER THAN
10% TO GREATER THAN 20%.
IT IS A SIGNIFICANT DECREASE IN
PAIN.
IN FACT, ACROSS ALL METHODS OF
WEIGHT LOSS AND WEIGHT LOSS
INCREASES AND PAIN REDUCTION
INCREASES.
BUT WHAT HAPPENS AFTER DIET AND
EXERCISE INTERVENTION HAS ENDED?
THERE IS BIOLOGICAL CHANGES THAT
ATTEMPTS TO MAINTAIN WEIGHT
LOSS. BODY ACTS IN STARVATION
MODE INCREASING FEELINGS OF
HUNGER SUPPRESSES
[INDISCERNIBLE] AND SLOWS
METABOLIC RATE AND ATTEMPTS TO
DEFEND HIGHER BODY WEIGHTS AT
ALL COSTS.
THIS FIGURE SHOWS THE CHANGE IN
WEIGHT AT 3.5 YEARS AFTER THE
IDEA 18 MONTH INTERVENTION HAD
ENDED OR FIVE YEARS FROM
BASELINE.
EXERCISE ONLY GROUP SHOWN IN THE
BLACK LINE HAD ZERO WEIGHT
REGAIN FROM THE END OF THE
INTERVENTION HAVING A WEIGHT
LOSS OF 3% FROM BASELINE.
DIET PLUS EXERCISE GROUP HAD 65%
WEIGHT REGAIN FROM END OF
INTERVENTION AND ABLE TO
MAINTAIN WEIGHT LOSS FROM 4%
FROM BASELINE AND DIET ONLY
GROUP HAD 38% WEIGHT REGAIN FROM
END OF INTERVENTION THAT WAS
ABLE TO MAINTAIN A WEIGHT LOSS
FROM 6% FROM BASELINE OR FIVE
YEARS LATER.
>>YOU HAVE ABOUT TWO MINUTES.
THANK YOU.
>>OKAY.
ALL THIS RESULTS IN 1.5 UNIT
REDUCTION IN PAIN AT 5 YEAR
FOLLOW UP WITH NO SIGNIFICANT
DIFFERENCE BETWEEN THE GROUPS.
SO, THEN, MULTIPLE CLINICAL
TRIALS HAVE BEEN SUCCESSFUL IN
REDUCING BODY WEIGHT WITH PEOPLE
WITH KNEE [INDISCERNIBLE] AND
OBESITY AND WEIGHT REDUCTION LED
TO SIGNIFICANT REDUCTIONS IN
PAIN AND IMPROVEMENTS IN
CLINICAL AND MECHANISTIC
OUTCOMES. HOWEVER, WEIGHT
REGAIN CONTINUES TO BE A
PROBLEM. AN IMPORTANT TOPIC FOR
FURTHER RESEARCH.
SO, ASIDE FROM KNEE REPLACEMENT,
THERE IS NO CURE FOR KNEE
OSTEOARTHRITIS.
THEN IS PREVENTION BETTER THAN
TREATMENT?
SEVERAL GROUPS ADDRESSING NEO-A
PREVENTION AS WE SPEAK AND
OSTEOARTHRITIS PREVENTION STUDY
WILL BEGIN RECRUITING
PARTICIPANTS LATER IN THE FALL.
WE WERE RANDOMIZED 1 THOUSAND
230 PEOPLE AT RISK FOR KNEE
OSTEOARTHRITIS IN ONE OF 2
GROUPS DIET PLUS EXERCISE OR
CONTROL AND STUDY POPULATION
WOULD BE ALL FEMALE AGE GREATER
THAN OR EQUAL TO 50 YEARS AND
BMI GREATER THAN OR EQUAL TO
THRT WITH NO X-RAY OR MRIOA AND
ON ONE OR BOTH KNEES AND NO
INFREQUENT KNEE PAIN.
THANK YOU.
>>THANKS SO MUCH, DR. MESSIER.
ALEX, ARE WE READY FOR DR.
RAGHAVAN TO TAKE OVER?
>>YES, DR. RAGHAVAN.
>>WE NEED YOU TO DO THE FULL
SCREEN, PLEASE, OF YOUR SLIDE.
SLIDESHOW.
>>UNMUTE. CAN YOU HEAR ME NOW?
>>YES, WE CAN HEAR YOU.
>>TERRIFIC.
>>YES IF YOU CAN GO AHEAD AND
DO THE SLIDESHOW, THAT WOULD BE
WONDERFUL.
>>CAN YOU SEE?
>>THAT WORKS. THANK YOU.
>>THANK YOU VERY MUCH FOR
HAVING ME.
IT HAS BEEN A FANTASTIC
CONFERENCE. BEFORE I BEGIN, I
NEED TO MAKE SOME DISCLOSURES
AND WILL DISCUSS THE OFF LABEL
USE OF ENZYME [INDISCERNIBLE]
FOR MUSCLE STIFFNESS AND PAIN.
SO, AS WE HAVE HEARD OVER THE
LAST DAY AND A FEW HOURS,
MUSCLES ARE ALSO INTEGRAL TO
JOINT HEALTH. WE HAVE OVER 600
MUSCLES IN OUR BODY.
IN FACT, IT HAS BEEN SHOWN THAT
A LARGE PROPORTION OF JOINT PAIN
IS MUSCLE RELATED.
IN FACT, IT IS CALLED MYOFASH YO
PAIN AND 100% OF PATIENTS WITH
NECK PAIN HAVE BEEN SHOWN TO
HAVE MIOFASHIAL PAIN. WHAT IS
MIOFASHIAL PAIN THAT WAS DEFINED
IN 1950S AS LOCALIZED TENSION
AREA IN THE SKELETAL MUSCLE AND
FASCIA -- ELICITED IN THE
TRIGGER POINT. THIS IS
DESCRIBED IN THE 1990S BY HONG
ET AL WHERE THEY PUT A NEEDLE
INTO THE MUSCLE TENSION AREA AND
THEY DETECTED EMG ACTIVITY.
AND THEY SURMISED THAT A LOCAL
TWITCH RESPONSE NEEDS AN IN TACT
CENTKREN
KR
CENTRAL INNERVATION AND NERVE
BLOCK TO AMELIORATE LOCAL TWITCH
RESPONSE AND REDUCE PAIN AND
THEY DID A STUDY WHERE THEY GAVE
DRY NEEDLING VERSUS LIEDO CANE
INJECTION AND WOULD EXPECT THAT
PERHAPS LIEDO CANE INJECTION
BECAUSE IT AMELIORATES LOCAL
TWITCH RESPONSE DUE TO CENTRAL
INNERVATION WOULD GET RID OF THE
PAIN. TURNS OUT THAT THE DRY
NEEDLING ALSO [INDISCERNIBLE]
THE PAIN LIEDZO CANE REDUCED
SORENESS FROM THE PROCEDURE --
THIS CREATES A DEGREE OF
CONFUSION BECAUSE IT IS NOT
CLEAR WHETHER IT IS JUST THE
NERVOUS SYSTEM OR NERVE
INNOVATION THAT IS LEADING TO
THIS TWITCH RESPONSE OR WHETHER
IT IS SOMETHING ELSE THAT IS
LOCAL IN THE MUSCLE.
IN FACT, THERE ARE SEVERAL
COMMON TREATMENTS USED BUT ALL
TREATMENTS HAVE BEEN FOUND TO BE
MODERATELY EFFECTIVE OR IN ONE
STUDY IN 201054% OF PHYSICIANS
CHARACTERIZED INAVAILABLE OPTION
TREATMENTS AS INSUFFICIENT AND
INJECTION THERAPIES IS NOT CLEAR
WHAT IS BEST TREATMENT AND IN
FACT IN 20201 REVIEW ARTICLE
SUGGESTED THAT OVERALL THERE WAS
NO CONSENSUS IN ETIOLOGY AND
PATHOGENESIS OF MYOFASCIAL PAIN
SYNDROME AND NO UNIFIED
DIAGNOSIS OF TREATMENT STANDARD
AND IN 1997, GER WIN WROTE THERE
WAS POOR RATE OF RELIABLE THE OF
THE LOCAL TWITCH RESPONSE.
WHAT ARE THE KEY GAPS THAT ARE
WHAT IS THE TRIGGER POINT MADE
OF? BEGS US TO TAKE CLOSER LOOK
AT MUSCLE ARCHITECTURE.
WE HEARD YESTERDAY THAT MUSCLE
IS MADE OF MUSCLE FIBERS AND
NETWORK CONSISTING OF EXTRA
CELLULAR MATRIX AS WELL IN EXTRA
CELLULAR MATRIX THAT NERVE
FIBERS AND VASCULAR VASCULATURE
ENTERS MUSCLE.
IT HAS BEEN FOUND THAT EXTRA
CELLULAR MATRIX IS COMPOSED OF
SUGAR MOLECULE AND IN SLIDE YOU
SEE QUADRICEPS MUSCLE SHOWS
BINDING PROTEIN THAT STAINS
BROWN. YOU CAN SEE IT IS AROUND
THE MUSCLE FIBER RIGHT WHERE YOU
EXPECT THE ENDOMYOSIN WITH
COLLAGEN AND IN PERIMYSIUM
SURROUNDING BUNDLES OF MUSCLE
FIBERS WASHED OUT BY
[INDISCERNIBLE] AS YOU SEE IN
THE LOWER PANEL.
TURNS OUT IT IS NOT EXTRA
CELLULAR MATRIX BUT ALSO STRETCH
RECEPTORS IN THE MUSCLE THAT ARE
LOCATED ACTUALLY IN PERIMYSIUM
THAT ARE RICH IN HIGH LURE ONIC
ACID THAT IS BROWN STAINING AND
STRUCTURES AND MUSCLE SPINDLE
THAT IS STRETCH RECEPTOR AND
PERINEURAL SPACE IS ALSO RICH IN
HIGH LURE ONIC ACID AND
DISRUPTION IN THRESHOLD OF THE
GRADIENT BETWEEN HIGH LURE ONIC
ACID INSIDE AND OUTSIDE MIGHT
DISRUPT SENSITIVITY OF MUSCLE
SPINDLE AND MIGHT LEAD TO
DISRUPTION IN NERVE ACTIVATION.
SO, [INDISCERNIBLE] AS I
MENTIONED PREVIOUSLY IS A SUGAR
MOLECULE AND CONCENTRATIONS ACT
AS -- TWO MUSCLE FIBERS WITH
THIN LAYER IN BETWEEN AND WHEN
MUSCLE CONTRACTS FORCE IS
TRANSMITTED ACROSS MULTIPLE
MUSCLE FIBERS THAT SLIDE AGAINST
EACH OTHER FOR TRANSMISSION TO
[INDISCERNIBLE].
HOWEVER, WHEN TOO MUCH HIGH LURE
ONIC ACID IT AGGREGATES LEADING
TO INCREASED VISCOSITY DECREASE
IN LUBRICATION AND TISSUE
SLIDING AND CONCENTRATION OF
HIGH LURE ONIC ACID INCREASES
VISCOSITY OF EXTRA CELLULAR
MATRIX EXPONENTIALLY INCREASES
THAT CAN FORM ACTUALLY
STRUCTURES THAT LITERALLY BIND
AREA TOGETHER.
NOW, IF YOU LOOK AT SAME MODEL
WITH LAYER OF [INDISCERNIBLE]
YOU FIND THAT YOU KNOW THERE IS
IF NOT MUCH MOVEMENT OR SLIDING
OF THE MUSCLES THAT MUSCLES ARE
STUCK AND MAY FEEL STIFF AND
PRODUCE REDISTANCE TO MOVEMENT
AND THAT COULD YOU KNOW IF YOU
TRIED TO STRETCH A STUCK MUSCLE
THAT MAY ACTIVATE STRETCH REFLEX
CAUSING A TWITCH. WE HAD
PROPOSED HIGH LURE OWN
HYPOTHESIS OF MUSCLE STIFFNESS
WHERE IN PATIENTS OF IMMOBILITY
AND PARESIS DUE TO NEUROLOGICAL
CONDITION OF STROKE DECREASED
DEGRADATION OF HA AND SIMILARLY
OVERUSE OF EXCESSIVE
INFLAMMATION CAN PRODUCE HA AND
LEADING TO INCREASED
ACCUMULATION.
WE SUMMARIZED THIS IN A TEXTBOOK
JUST PUBLISHED RECENTLY AND NOW
CAN USE IMAGING TO ACTUALLY
IMAGE IN VIVO THIS ACCUMULATION.
YOU SEE HERE IN PATIENTS WITH
SPAS TICK PARESIS DUE TO STROKE
COMPARED TO CONTROL IN TOP PANEL
AND MIDDLE PANEL YOU SEE LOTS OF
RED AND MORE RED SIGNALS MORE
HIGH LURE ONIC ACID ACCUMULATION
AND SEE MUSCLE LOOKS KIND OF
STUCK TOGETHER WHERE SHAPE IS
TRIANGULAR RATHER THAN CIRCULAR
AND BOTTOM PANEL YOU SEE THE
SAME PATIENT AND SAME MUSCLES
BUT AFTER TREATMENT WITH ENZYME
HIGH LURE ONO DAZE YOU SEE LEFT
HIGH LURE OWNIN AND CHANGES IN
SHAPE OF THE MUSCLE.
NOW, HERE IS A EXAMPLE OF SAME
IMAGING TECHNIQUE BEING USED
PATIENTS WITH OVERUSE AND TENNIS
ELBOW AND IF YOU LOOK AT TOP
PANEL YOU SEE THERE IS HIGH LURE
OWNIAN ACCUMULATION IN EPIMICE
YO REGION ON BOTH SIDES AND POST
PANEL YOU SEE HIGHAL YOU ARE OWN
AN SEEMS TO DECREASE AND AREAS
TREATED WITH MANUALWITH MANUAL
ANOTHER EXAMPLE OF THE SAME T1
ROW IMAGING TECHNIQUE WHERE YOU
CANNIM AN HYALURONAN
ACCUMULATION IN PATIENTS WITH
MYOFASHIAL SHOULDER PAIN AND
EFFECTED SIDE IS LOTS OF RED
SIGNALING HYALURONAN
ACCUMULATION IN PECTORALIS MAJOR
MINOR PARTICULARLY AT INTERFACE
OF TWO MUSCLES AND HARD TO REACH
THAT BIOMANUAL THERAPY.
JUST VERY BRIEFLY WHAT THIS IS
SHOWING YOU IS THAT YOU CAN LOOK
AT THE FASCIA INTERFACE FWEN
PECTORALIS MAJOR AND MINOR SHOWN
HERE WITH COLORS RED AND BLUE
AND LOWER GRAPH, HERE THE
PATIENT IS MOVING AND YOU SEE ON
UNAFFECTED SIDE THAT THE RED AND
BLUE MOVE SEPARATELY AND
ACTUALLY DURING EXTERNAL AND
INTERNAL ROTATION AND PECTORALIS
MUSCLE DOESN'T MOVE AND YOU SEE
RED LINE CHANGING AND BLUE LINE
IS STATIC.
WHEN YOU LOOK AT SHEER BETWEEN
TWO MUSCLES YOU SEE A NICE BLACK
LINE WHEREAS ON THE EFFECTED
SIDE YOU SEE THAT BOTH MUSCLES
MOVE TOGETHER.
WHICH ACTUALLY DISRUPTS THE
MOVEMENT OF THE TWO MUSCLES
AGAINST EACH OTHER AS IT SHOULD
BE FUNCTIONALLY.
SO, WHAT IS THE CONSEQUENCE?
HOW CAN WE REDUCE MUSCLES FROM
BEING STUCK TOGETHER LIKE THIS?
TURNS OUT THAT ENZYME HIGHAL YOU
ARE ON AN DAYS HAS BEEN
AVAILABLE FOR A LONG TIME AND
USED TO INCREASE AND IMPROVE
DRUG LIVERY OF AGENTS HIGHAL YOU
ARE ONIDAYS WAS IMPROVED IN
2005.
THINKING IT WAS SOMETHING THAT
COULD DECREASE -- DISRUPT THIS
CASCADE OF DISABILITY WE OFTEN
SEE IN PATIENTS.
>>YOU HAVE A COUPLE OF MINUTES.
SO, IN K SERIES THAT WE FIRST
DID, WE SAW DRAMATIC REDUCTION
IN DEGREE OF MUSCLE STIFFNESS
ACROSS MULTIPLE JOINTS BETWEEN
T0 AND T1. THIS IS WHERE
INJECTIONS WERE GIVEN.
AND WE SAW IMPROVEMENTS IN
PAIN-FREE MOVEMENT ACROSS
MULTIPLE JOINTS.
NOW, MOST RECENTLY IN A
CLINICAL TRIAL THAT IS STILL
ONGOING, WE TOOK A SNEAK PEAK
BECAUSE PATIENTS ARE GETTING
BOTH PLACEBO AND THE TREATMENT
BETWEEN -- IN THE STUDY.
WE SEE THAT WHEN WE LOOK AT THE
HYPERREFLEXIA USING A TENDON
TAP, YOU SEE THAT IN SUBJECTS
WITH UNILATERAL HYPERREFLEX AREA
EFFECTED BASELINE THERE IS GREAT
DMG ACTIVITY AND AT END OF THE
TRIAL AFTER THERE IS BOTH DRUG
AND PLACEBO YOU SEE THERE IS AN
EFFECT ON EMG AND THEY DON'T
SHOW HYPERREFLEXIA ANYMORE.
SO, WHAT WE BELIEVE WE HAVE
GOTTEN TO IS THAT HYALURONIDASE
ACTS ON STRETCH REFLEX MECHANISM
AND ACTUALLY RELAXES THE REGION
AROUND THE MUSCLE SPINDLE AND
THEREFORE IT EFFECTS THE
AFTERERIENT ARM OF THE STRETCH
REFLEX SO MUSCLE SPINDLE IS LESS
SENSITIVE TO STRETCH AND THE
NERVOUS SYSTEM DOESN'T HAVE TO
BE AS RESPONSIVE TO THE STRETCH.
IT TURNS OUT IN POST STROKE
SHOULDER PAIN AS WELL THAT LARGE
PORTIONS OF THE PAIN IS
MUSCULOSKELETAL.
IN OUR STUDIES IN PATIENTS WITH
STROKE WE HAD FOUND THAT NOT
ONLY DOES PAIN-FREE MOVEMENT
INCREASE BUT PAIN PRESSURE
THRESHOLDS ALSO DECREASE.
CHANGE IN PAIN PRESSURE
THRESHOLDS IS DIFFERENT ACROSS
DIFFERENT MUSCLES AND PERHAPS
THEY HAVE DIFFERENT DEGREES OF
DIFFERENT DOSES OF THE
TREATMENT. YOU CAN SEE OVERALL
ACROSS ALL MUSCLES THERE IS A
REDUCTION IN PAIN PRESSURE
THRESHOLDS AND IN ANOTHER STUDY
WAS FOUND THAT WHEN THEY
COMPARED HYALURONIDASE AGAINST
LIDOCAINE THEY FOUND THAT
HYALURONIDASE AND LIDOCAINE HAD
A RESPONSE AND EFFECT AND
LIDOCAINE HAD SHORT-TERM EFFECTS
AND HYALURONIDASE HAD LONG TERM
EFFECT IN 2 TO 4 WEEKS.
SUMMARIZING -- EXTRA CELLULAR
MATRIX OF THE MUSCLE MIGHT BE
CHIEF [INDISCERNIBLE] OF TRIGGER
POINT IN MYOFASCIAL PAIN BUT
COULD MODULATE STIFF NNS PAIN
AND NEURAL REFLEX INDUCED MUSCLE
ACTIVITY WHICH WE SEE IN
NEUROLOGICAL PATIENTS AND HIGH
ALLURE ON AN -- AND MAY LEAD TO
PAIN RELIEF IN MYOFASCIAL PAIN
BUT RESULTS HAVE TO BE CONFIRMED
IN RANDOMIZED CONTROLLED TRIALS
AND WOULD LIKE TO END BY
ACKNOWLEDGING ALL CONTRIBUTORS
AND COLLABORATORS AND FUNDING
SOURCES THAT MADE THIS WORK
POSSIBLE. THANK YOU.
>>THANK YOU DR. RAGHAVAN AND
APPRECIATE THIS TALK AND
CONCLUDES OUR SPEAKER SECTION
FOR SESSION 4 AND WOULD NEXT
LIKE TO TURN OVER OUR ATTENTION
TO THE PANELISTS SO DR. GUNNAR
BROLINSON COULD INTRODUCE
YOURSELF LEADING OFF THIS PANEL
INTRODUCTION SECTION? THANK
YOU.
>>HI, THERE I'M GUNNAR AND VICE
PROVOST OF RESEARCH AND
PROFESSOR OF FAMILIES
[INDISCERNIBLE] AT VCOM.
WE HAVE FOUR CAMPUSES.
AND DR. KOROSHETZ WILL BE HAPPY
TO KNOW I WILL START MY VIDEO
AND THERE IT GOES, HOPEFULLY.
YOU WILL BE HAPPY TO KNOW WE ARE
A RURALLY DISTRIBUTED MEDICAL
EDUCATION SYSTEM AND RECRUIT AND
RETAIN STUDENTS FROM RURAL AREAS
AND ARE TRYING TO REALLY BUILD
BETTER MEDICAL STUDENTS
PRIMARILY CARE PHYSICIANS WITH
-- RECEIVING SIGNIFICANT
TRAINING IN OSTEOPATIC MAN IP
YOU'LLATIVE THERAPIES AND TEAM
PHYSICIAN IN UNIVERSITY OF
TOLEDO AND CAME TO VIRGINIA TECH
AND -- AS WELL AS AT VIRGINIA
TECH AND DR. KORSHETZ WOULD BE
HAPPY TO KNOW WE ARE INJECTING
AND ASPIRATING AND DOING ALL
KINDS OF THINGS HAVEN'T FORGOT
TO TRAIN FELLOWS AND RESIDENTS
WITH PAIN ASPIRATION AND
INJECTION.
AND WORKING WITH SKI TEAM FOR
YEARS AND VAST MAJORITY OF
CAREER I HAD THE GREAT GOOD
FORTUNE TO WORK WITH LOTS OF
FERRARIS BUT ALSO I RUN INTO
SOME REAL TRAIN WRECKS.
IF WE CAN ADVANCE TO THE NEXT
SLIDE, I WOULD LIKE TO SHOW YOU
A LITTLE CLINICAL VERB AVIGNETT
THAT IS NOT A FERRARI BUT CHITTY
CHITTY BANG BANG AND PARTNER
THAT IS A FORMER FELLOW WORKING
WITH US HERE AND AT VIRGINIA
TECH AND THIS IS THE PATIENT
THAT WALKS INTO YOUR OFFICE.
SHOUTOUT TO DR. RUSSICK IN OG
AND EMPHASIS WHAT HAPPENS ON
CLINICAL SIDE OF THINGS PATIENT
COMES IN DON'T SAY I FEEL GREAT
BUT HAVE THIS PAIN AND HAVE TO
FIGURE IT OUT. THIS WOMAN CAME
IN AND WAS TOLD NOTHING COULD BE
DONE FOR HER PRETTY MUCH AND HAD
THAT HAPPEN A LOT OVER THE
COURSE OF MY CAREER. YOU SEE
SHE IS 58 AND HIGH BMI AND
UNABLE TO AMBULATE EXCEPT WITH A
WALKER WAND HE HAVE RADIO GRAPHS
HERE AND SHE HAD QUITE A BIT OF
LATERAL ANKLE PAIN AND FEELINGS
OF INSTABILITY. SHE HAS SEVERE
[INDISCERNIBLE] AS A LITTLE GIRL
SHE WAS TOLD SHE WAS NOT -- MANY
CLINICIANS ON THE CALL WE CALL
THIS THE MISERABLE MALALIGNMENT
SYNDROME THAT IS PROGRESSIVELY
WORSENED AND IMPORTANT TO DO A
REALLY GREAT FUNCTIONAL CLINICAL
EXAM TO FIND OUT WHAT IS GOING
ON AND WHAT IS BEATING UP THESE
TISSUES AND WHAT IS THE KINETIC
CHAIN THAT IS WORKING HERE AND
TRY TO SAY WHAT WE CAN DO TO
IMPROVE THAT KINETIC CHAIN THAT
IS A TYPICAL MULTIMODAL APPROACH
AND AREA OF GREATEST CONCERN WAS
AREA THAT [INDISCERNIBLE] LERRA
ON -- SHE DIDN'T HAVE ACUTE
SPRAIN AND SEE PRETTY
SUBSTANTIAL TEAR AND DYNAMIC
MOTION SHOWED SIGNIFICANT LAXITY
OF LATERAL LIGAMENT OF COMPLEX
AND FROM TREATMENT PERSPECTIVE
DID ULTRA SOUND GUIDE 3D
[INDISCERNIBLE] AND IN PLAINS
AND DISTANCE TO TENDON AND PRP
WAS INJECTED AND 2CCS OF MICROFA
THE THAT WAS MENTIONED YESTERDAY
AND FUNCTIONS PRIMARILY AS A
TISSUE SCAFFOLD AND APPROPRIATE
PROCEDURE REHAB AND PUT IN A
BOOT AND PHYSICAL THERAPY AND
ADDRESSED MULTIPLE MODAL ISSUES
BROUGHT UP BY DR. RUSIC
YESTERDAY AND FELT WAS IMPORTANT
COMPONENT OF THIS APPENDICULAR
AND SKELETAL MANIPULATIONS WERE
DONE TYPICALLY 2 TIMES A WEEK
SHE WAS IN PHYSICAL THERAPY OR
EXCUSE ME PHYSICAL THERAPY TWO
TIMES A WEEK AND OMT TWICE
MONTHLY AND SHE IMPROVED
SUBSTANTIALLY AND 12 WEEKS GATE
WAS REALLY IMPROVED WITH
MODERATE IMPROVEMENT TO LEFT
KNEE VALGUS YOU SEE 8 TO 10
DEGREES AND HAD MUCH BETTER
BILATERAL FOREFOOT SENSATION AND
MOTION WAS MUCH BETTER AND
OVERALL, AGAIN, SHE DID VERY
WELL.
NOW, THIS WAS A GREAT OUTCOME
FOR HER. SHE WAS REALLY
PLEASED. I THINK WHEN YOU LOOK
AT THIS CASE AND THINK ABOUT
WHAT WE HAVE SEEN YESTERDAY AND
TODAY, SHE PRETTY MUCH
DEMONSTRATES KIND OF ALL OF THE
STUFF THAT IS GOING ON THERE.
TYPICALLY IN THESE KINDS OF
CASES AND IN SPORTS MEDICINE WE
TAKE A KITCHEN SINK APPROACH AND
THROWING EVERYTHING WE CAN AT IT
MEDICAL THERAPY PHYSICAL THERAPY
DRY NEEDLING INJECTIONS AND PRP
AND WE DO ALL KINDS OF THINGS
BECAUSE WE ARE REALLY TAKING A
MULTIMODAL APPROACH.
>>THANK YOU DR. BROLINSON WE
CAN TALK ABOUT THE LAST SECTION
GETTING INTO PANEL DISCUSSION
AND WANT TO MAKE SURE WE HAVE
ENOUGH TIME TO ACTUALLY DISCUSS
SOME OF THE ISSUES.
THANKS SO MUCH.
>>GREAT. THANKS.
>>DR. BUTERA INTRODUCE
YOURSELVES PLEASE AND REMINDER 2
MINUTE INTRODUCTION AND TRY TO
BE BRIEF.
>>YES. NO PROBLEM.
>>ALL RIGHT. I WILL SHARE MY
SCREEN REAL QUICK. THERE WE GO.
THANK YOU SO MUCH FOR ASKING ME
TO BE PART OF THE PANEL AND WILL
LET AUDIENCE KNOW I'M A PHYSICAL
THERAPY IPT AT UNIVERSITY OF
DELAWARE WHAT STRUCK ME BASED ON
TODAY'S TALKS AND YESTERDAY'S
WAS THINKING ABOUT CHRONIC PAIN
IN PARTICULAR COMING TO JOINT
HEALTH THINKING ABOUT CHRONIC
PAIN AS A DISEASE IN AND OF
ITSELF WITH DISTINCT CHANGES
OCCURRING THROUGHOUT THE NERVOUS
SYSTEM. I HAVE BEEN REALLY
IMPRESSED WITH ALL OF THE TALK
AND REALLY I APPLAUD ORGANIZERS
OF WORKSHOP TO REALLY BE
THINKING ABOUT WHOLE JOINT
HEALTH. WHEN WE ARE THINKING
ABOUT TREATING PAIN CONDITIONS
WE ARE OFTEN TREATING THE ENTIRE
PERSON.
SO, I THINK THAT, THAT HAS BEEN
REALLY HIGHLIGHTED AND I WON'T
GO INTO ALL OF THESE THINGS THAT
WERE JUST SOME OF MY IMPORTANT
TAKEAWAYS THAT WE NEED TO REALLY
CONSIDER MULTIPLE PERIPHERAL AND
CENTRAL TARGETS WITH
INTERVENTIONS AND MANY
INTERVENTIONS OR DISCUSSIONS WE
HAVE HAD TODAY HAVE HAD REALLY
HIGHLIGHTED THERE IS MULTIPLE
TARGETS.
THESE MAY VARY ACROSS CONDITIONS
AND FOR EXAMPLE WITH AKEELIS
TENDONOPATHY THERE IS INCREASED
PAIN WITH LOADING AND NO PAIN
WHILE AT REST MAYBE. HOW CAN WE
TARGET MAYBE WE ARE TARGETING
TENDON IN PARTICULAR AND THOSE
AND IN THAT CONDITION VERSUS
THINGS LIKE NONSPECIFIC OR KNEE
OSTEOARTHRITIS THERE IS RESTING
PAIN AND KNEE PAIN AND ALSO WHAT
I TOOK AWAY FROM TODAY WITH SOME
CONSIDERATIONS OF APPLYING
EVIDENCE AND THERE WAS
DEFINITELY DISCUSSION IN THE
CHAT TODAY TO ADDRESS IN THE
PANEL DISCUSSION WITH REGARDS TO
OVERCOMING IMPLEMENTATION
BARRIERS AND CONSIDERING
INTERACTIONS BETWEEN THE
TREATMENT. THANK YOU.
>>THANK YOU. ALEX, YOU ARE
MUTED NOW.
>>SORRY MY BAD.
DR. BRONFORT YOU ARE NEXT AND
THANK YOU DR. BUTERA FOR
COMMENTS.
>>I'M A RESEARCH PROFESSOR AT
UNIVERSITY OF MINNESOTA AND
THANKS FOR THE SLIDES IS THIS
BRIEF SUMMARY SOMETHING YOU
NEED?
>>IT IS AVAILABLE IN THE
PROGRAM BOOK.
>>OKAY. NO NEED FOR THAT.
SO, MY PERSPECTIVE COMES FROM
BEING A CLINICAL TRIALIST FOR
MANY YEARS ASSESSING A NUMBER OF
DIFFERENT NONSURGICAL TREATMENTS
FOR BACK PAIN AND NECK PAIN.
IN THIS SPACE FACING UPHILL
BATTLE DUE TO DISABILITY AND
MUSCULODISORDERS ESTIMATED
INCREASED ESTIMATED 50 P RS IN
LAST 30 YEARS.
WITH INCREASINGLY OBESE AND
SEDENTARY AND AGING SOCIETIES IS
EXPECTED TO INCREASE MORE IN
YEARS TO COME AND AGAINST THIS
BACKDROP ONE COULD HARDLY SAY
THAT INTRODUCTION OF
BIOPSYCHOSOCIAL AND WHOLE PERSON
MODEL IN RESEARCH AND PRACTICE
AND MORE THAN 30 YEARS AGO HAS
BEEN A PUBLIC HEALTH SUCCESS.
IN FACT, ALONGSIDE WITH
INCREASING RATES OF DISABILITY
AND AGAINST GUIDELINE ADVICE ARE
INCREASED IN DIAGNOSTIC IMAGING
AND PROVISION AND MOST WILL I
BIOLOGICAL MONOTHERAPIES WITH
LIMITED EFFECTIVENESS AND
QUESTION THEREFORE IS WHETHER IT
IS A MODEL ITSELF THAT IS FAILED
TO DELIVER OVER THE SCIENTIFIC
AND HEALTH CARE COMMUNITIES HAVE
FAILED TO ADOPT THE MODEL.
IT IS NOT WIDELY RECOGNIZED THAT
BACK AND NECK PAIN ARE
ACCOMPLISHED CONDITIONS
INFLUENCED BY SEVERAL
INTERRELATED PHYSICAL
PSYCHOLOGICAL AND SOCIAL FACTORS
AND MOST TREATMENTS STILL FOCUS
ENTIRELY ON SYMPTOM MANAGEMENT
USING A ONE-SIZE FITS ALL BASED
ON MEAN DIFFERENCES OF
EFFECTIVENESS FROM SYSTEMATIC
REVIEWS AND GUIDELINES THAT
DOESN'T HELP CLINICIANS AND
PATIENTS VERY MUCH TO CHOOSE
WHICH TREATMENT TO TRY.
SO,UM THE TREATMENT IS
FREQUENTLY CHARACTERIZED BY
PERSISTIENT USE MARGINALLY
EFFECTIVE AND POTENTIALLY
HARMFUL THERAPIES LARGELY
IGNORING PSYCHOSOCIAL ASPECT OF
BACK PAIN.
FOR EXAMPLE, USE OF INJECTIONS
OPIOID PRESCRIPTIONS SPINAL
SURGERY INCREASED AT
ACCELERATING RATE IN PAST FEW
YEARS WITH LITTLE POSITIVE
IMPACT ON PATIENT OUTCOMES AND
PARTICULAR CONCERN THAT HAS BEEN
MENTIONED OVER-RELIANCE ON
OPIOIDS THAT IS USED BY
ESTIMATED 30% OF CHRONIC BACK
PAIN PATIENTS.
IN SPITE OF RECOMMENDATIONS
FROM CLINICAL GUIDELINES THAT
OTHER TYPES OF PHARMACOLOGICAL
TREATMENT OPTIONS WOULD BE MORE
APPROPRIATE AND REDUCING
BACKPAIN BURDEN PATIENTS SHOULD
HAVE GREATER ACCESS TO FRONTLINE
CARE ADDRESSING PHYSICAL AND
PSYCHOSOCIAL NEEDS ACCOMPLISHING
THIS HAS BEEN INCREASED STUDIES
MULTIMODAL INDIVIDUAL -- TO MEET
PATIENTS WHOLE PERSON NEEDS.
THAT IS MY -- I HAVE ANOTHER
THING I MIGHT BRING UP ABOUT
SOMETHING I HAVEN'T HEARD ABOUT
YET IN THIS WORKSHOP THAT IS
ONTOLOGIST MESOCHIMAL STEM CELL.
MAYBE SOMEONE HAS MENTIONED IT
OR MENTIONED IT IN PASSING AND
OTHERWISE MAYBE WE CAN TALK
ABOUT THAT A LITTLE BIT.
>>THANK YOU. LET'S FINISH
INTRODUCING THE PANELISTS.
DR. GOERTZ.
>>MORNING, EVERYONE. IT IS A
PLEASURE TO BE WITH YOU AND HAVE
AN OPPORTUNITY TO ATTEND THIS
WORKSHOP AND THANKING NIH
ORGANIZERS AND REALLY ALL OF THE
PANELISTS FOR YOUR EXCELLENT
PRESENTATIONS.
THE PERSPECTIVE I BRING TO THIS
DISCUSSION IS CLIN KALILY I AM A
DOCTOR OF CHIROPRACTIC AND MY
FOCUS NOW AT DUKE UNIVERSITY
SCHOOL OF MEDICINE IS REALLY
BIMODAL AND I SPEND PART OF MY
TIME TRYING TO FIGURE OUT HOW WE
CAN FILL GAPS IN KNOWLEDGE
REGARDING BEST PRACTICES FOR
NONPHARMACOLOGICAL TREATMENT
APPROACHES MANAGEMENT OF JOINT
RELATED DISORDERS WITH FOCUS ON
LOW BACK PAIN AND OTHER PART OF
MY POSITION IS TRYING TO FIGURE
OUT HOW WE IMPLEMENT KNOWLEDGE
THAT WE ALREADY KNOW.
SO, I HAVE THREE NIH FUNDED
CLINICAL TRIALS THAT I'M
CURRENTLY WORKING ON AND THEY
RANGE FROM TRYING TO FIGURE OUT
DOSING OF CHIROPRACTIC IN
VETERANS WITH LOW BACK PAINS AND
HOW MANY VISITS SHOULD THEY OR
ARE OPTIMAL TO TRY TO DISCOVER
WHAT HAPPENS IF WE ASK PATIENTS
WHO ARE CALLING LARGE ACADEMIC
HEALTH CENTER TO MAKE
APPOINTMENTS WITH PRIMARY CARE
PHYSICIAN AND IF WILLING TO SEE
A CHIROPRACTOR OR PHYSICAL
THERAPIST AND FIRST LOOKING AT
HAVING A PLANNING GRANT AND
LOOKING AT WHAT HAPPENS IF WE
ASK PATIENTS TO USE A
MINDFULNESS APP AND HAVACU
PUNCTURE BEFORE AND AFTER SPINE
SURGERY.
AND SO THAT IS THE RESEARCH SIDE
OF WHAT I'M WORKING ON IN THE
CLINICAL IMPLEMENTATION SIDE.
WE ARE COMMITTED TO IMPLEMENTING
AMERICAN COLLEGE OF PHYSICIAN
GUIDELINE FOR LOW BACK PAIN
WITHIN DUKE UNIVERSITY HEALTH
SYSTEM AND IT RECOMMENDS
NONPHARMACOLOGICAL TREATMENT
APPROACHES PRIOR TO OTHER
TREATMENTS AND SPECIFICALLY
PRESCRIPTION MEDICATIONS.
WE HAVE DEVELOPED A NUMBER OF
EDUCATION MODULES AND TOOLS FOR
BOTH CLINICIANS AND PATIENTS AND
WE HAVE DEVELOPED ALSO A
CLINICAL DATA REGISTRY FOR LOW
BACK PAIN THAT ALLOWS US TO
TRACK UTILIZATION AND OUTCOMES
AND TO MEASURE WHETHER THEY ARE
CONSISTENT WITH BEST PRACTICES
AND TO MEASURE TRENDS OVER TIME.
WE ARE STILL IN THE EARLY PHASES
OF IMPLEMENTATION.
OUR EARLY INDICATIONS ARE THAT
IT IS POSSIBLE TO -- TO CHANGE
HEALTH CARE DELIVERY WHEN IT CAN
BE DIFFICULT.
>>OKAY.
>>MY -- I HAVE 10 QUICK
TAKEAWAYS FROM THIS CONFERENCE
SO FAR.
THE FIRST IS THAT WHOLE JOINT
PAIN.
>>I THINK WE SHOULD DISCUSS
TAKEAWAYS AS PART OF THE
DISCUSSION AND FINISH LAST
INTRODUCTION WITH THE LAST
PANELIST, PLEASE.
>>GOOD MORNING, EVERYBODY.
I WILL TRY TO KEEP COMMENTS
SUPER BRIEF. WE HAVE HOPEFULLY
ROBUST CONVERSATIONS I'M BRIAN
NOEHREN AND WOULD LIKE TO THANK
CONFERENCE ORGANIZERS FOR
INVITING ME TO JOIN THIS PANEL
AND LEARNED SO MUCH FROM
LISTENING.
I WANT TO CENTER THOUGHTS
PROVIDED HERE ON OBSERVATIONS I
HAD FROM LISTENING TO EVERYBODY.
FIRST, IN EXERCISE TRIALS WE
HAVE NOT ALWAYS ACCOUNTED FOR
VARIOUS SOURCES OF PAIN OR
ORIGIN OF DEVELOPMENT OF
OSTEOARTHRITIS TO LEVEL
DISCUSSED YESTERDAY IN THE
CONFERENCE AND BRING IT UP AS
RECENT REVIEW IN LANCET CALLED
IN QUESTION WHETHER EXERCISE IS
EFFECTIVE VERSUS INTENTIONAL
CONTROL TREATING CHRONIC PAIN
CONDITIONS ESPECIALLY
OSTEOARTHRITIS AND THIS HAS LED
TO GROUPS PUBLISHING EDITORIALS
ALONG THE SIMILAR LINES AND IN
TERMS OF A QUESTION FOR THE
GROUP, I WONDER IS IT POSSIBLE
TO HAVE INTERVENTIONS TO
SUBGROUPS AND IDENTIFY
RESPONDERS AND NONRESPONDERS TO
EXERCISE TO TARGET INTERVENTIONS
BETTER.
IS IT TRULY NOT THE SAME EFFECT
WE HOPE FOR BRINGING US TO LEVEL
OF METAANALYSIS AND OTHER TWO
QUICK POINTS ALONG THOSE LINES
IS I HAVE BEEN WONDERING
LISTENING TO EVERYONE ARE THERE
WINDOWS THAT PEOPLE MIGHT BE
MORE RESPONSIVE TO A TREATMENT
THAT WE DIRECT TREATMENTS TO
BASED UPON POTENTIAL SYMPTOM
STATE AND BUILDING ON THE GREAT
TALK, COULD WE DISCUSS MORE
ABOUT [INDISCERNIBLE] OF FUTURE
TRIALS AND SOME OF THE
CHALLENGES THAT FOR EXAMPLE THE
CONTROL GROUP AND WHAT IT SHOULD
LOOK LIKE AND CONTROLLING FOR
SOURCES OF BIAS AND NEED FOR
FUNDING FOR LARGER TRIALS THAT
ARE REALLY QUITE EXPENSIVE AND
HARD TO PULL OFF. MY LAST POINT
THAT I JUST WOULD LIKE TO BRING
UP REAL QUICK IS AS WE EXPLORE
AND TALK ABOUT TREATMENTS IN
THIS SESSION I WONDER ABOUT
APPROACHES TO CLINICAL TRIALS
WHERE WE -- MANAGED TO MUTE
MYSELF AND WHERE WE INTEGRATE
PSYCHOSOCIAL AND PHYSICAL
INTERVENTIONS TOGETHER AND GIVEN
ALL WE KNOW ABOUT PSYCHOSOCIAL
ASPECTS OF OSTEOARTHRITIS AND
OTHER CONDITIONS RELATED TO PAIN
WHAT WE SHOULD BE TREATING IN
EXERCISED TRIALS AND BELIEVE A
POINT WAS RAISED YESTERDAY AND
CAN'T RECALL PERSON THAT BROUGHT
IT UP TO GIVE APPROPRIATE CREDIT
AND ALONG SAME LINES WHAT THEY
BROUGHT UP IN TERMS OF PHYSICAL
INTERVENTION SHOULD -- WE ARE
LOOKING TO COMBINE THESE IN
FUTURE TRIAL DESIGNS AND WOULD
LOVE TO HEAR FROM THE SPEAKERS
TO SPECULATE ABOUT THEIR
THOUGHTS ON THIS.
THANK YOU.
>>THANK YOU VERY MUCH. I WOULD
LIKE TO INTRODUCE QUICKLY NIH
CO-CHAIR DR. MICHAEL OSHH CHIN
SKI THAT IS OFFICE OF
PRECLINICAL PAIN RESEARCH
HELPING IT GUIDE MODERATION
SESSION WITH ME. I THINK
HOWEVER A LITTLE EXERCISE
CHAIR'S PRIORITY FOLLOWING UP ON
DR. NOEHREN'S FIRST QUESTION
WITH THESE EXERCISE TRIALS, IS
IT -- SHOULD WE BE TARGETING
SPECIFIC SUBPOPULATIONS AND NOT
REALLY A ONE-SIZE FITS ALL AND
WHERE IS CRITICAL WINDOW TO
EXERCISE THERAPY AND SHOWING
DIMINISHING RETURNS OVER TIME
AND WHAT ARE COMPARATIVE GROUPS
TO INCLUDE IN AN EXERCISE TRIAL
OR PHYSICAL THERAPY TRIAL AND
SHOULD THIS -- SHOULD IT BE
SUFFICIENT TO DEMONSTRATE THAT
EXERCISE IS EFFECTIVE OR IS IT
EFFECTIVE ALONE IN TREATING
CHRONIC PAIN OR BE COMBIN
ATORIAL WITH OTHER
INTERVENTIONS?
I WOULD LIKE TO DO A BROAD SET
OF QUESTIONS TO INVITE PANELISTS
AND SPEAKERS TO COME ON CAMERA.
IF YOU HAVE SOMETHING TO ADD OR
RESPOND, PLEASE RAISE YOUR HAND.
>>ALEX, I SEE DR. MESSIER
BROUGHT UP HIS VIDEO.
>>GREAT. WOULD YOU LIKE TO
RESPOND?
>>SURE. I AM NOT SURE WITH SO
MUCH WHAT TO DO WITH THE
INTERVENTION AS IT IS WITH WHAT
TO DO WITH THE CONTROL GROUP.
I AM -- BACK IN 1997 WHEN WE
PUBLISHED THE FAST TRIAL, YOU
COULD SEE AND -- THAT THE --
THAT THE TWO EXERCISE GROUPS GOT
A LITTLE BETTER.
CONTROL GROUP GOT A LOT WORSE.
ALL RIGHT? AND I HAD PEOPLE SAY
YOU ARE LUCKY THAT THE CONTROL
GROUP DIDN'T DO WELL.
THEY WERE 65 YEARS AND OLDER AT
THAT POINT. I SAID, WELL, THIS
IS WHAT HAPPENS TO PEOPLE THAT
ARE 65 AND OLDER IF THEY DON'T
DO ANYTHING.
THEY GET WORSE.
FROM A PUBLIC HEALTH
PERSPECTIVE.
BUT, AS WE HAVE GONE ON, OUR
STUDIES HAVE GOTTEN YOUNGER AND
YOUNGER.
OBESITY HAS DRIVEN
OSTEOARTHRITIS DOWN IN AGE NOW.
WHAT WE USED TO SEE AT 65 WE SEE
NOW AT 50 OR 45.
AND SO THAT FIRST TRIAL, IT WAS
A CONTROL GROUP NOT ATTENTION
CONTROL GROUP AND HAD VERY
LITTLE INTERACTION WITH THE
CONTROL GROUP.
ONE, FACE-TO-FACE A MONTH FOR
THE FIRST THREE MONTHS AND AFTER
THAT FROM MONTHS 4 TO 18, THERE
WAS JUST A PHONE CALL.
AS WE HAVE GONE ON, WE HAVE DONE
MORE ATTENTION CONTROL.
SO, WE HAVE -- WE PAY MORE
ATTENTION TO THE CONTROL GROUP.
I THINK WHAT IS HAPPENING IS
THAT WE SEE THE CONTROL GROUP
GETTING BETTER AS WELL. 25 TO
45% REDUCTION IN PAIN THAT IS
PRETTY MUCH WHAT EXERCISE DOES.
SO, MY FEELING IS THAT A GOOD
PART OF EXERCISE IN THIS
POPULATION, RESULTS ARE MORE THE
FACT THAT WE ARE PAYING
ATTENTION TO PEOPLE NOT THE
EXERCISE ITSELF.
IT IS MORE CONTEXTUAL.
REALLY TO GET A GOOD BANG FOR
YOUR BUCK WITH PAIN REDUCTION,
YOU HAVE TO ADD WEIGHT LOSS TO
THE EXERCISE.
>>OKAY. THANK YOU DR. MESSIER.
I SEE TWO HANDS RAISED.
>>YEAH. OKAY. SO, MY THOUGHTS
WERE -- I AGREE ABOUT WHAT WE DO
WITH THE CONTROL GROUP AND WHAT
I'M THINKING ABOUT IS, YES. WE
HAVE TO DO THEM AS PART OF A
STANDARD OF CARE THAT WE ARE
ALREADY DOING AND WE NEED TO NOT
DO THEM AS INDEPENDENT ENTITIES
IN THESE TRIALS ANYMORE. NOT
HOW PEOPLE RECEIVE TREATMENT AND
NOT HOW THEY WORK FORWARD IN
THEIR TREATMENT. IF IT WILL
WORK, IT WILL HAVE TO BE DONE.
I DON'T THINK WE HAVE ENOUGH
DATA YET TO KNOW WHETHER OR NOT
WE HAVE SUBGROUPINGS AND WE NEED
LARGE ENOUGH TRIALS THAT WE CAN
THEN DO RESPONDER ANALYSIS.
BRIAN BROUGHT UP A REALLY NICE
QUESTION THAT WE NEED THE MONEY
TO DO THOSE TRIALS; RIGHT?
IN ORDER TO DO THEM OF
SUFFICIENT QUALITY SO WE CAN
BEGIN TO DO RESPONDER ANALYSIS.
IF WE DON'T KNOW WHO RESPONDS TO
WHAT TREATMENTS, WE CAN'T BEGIN
TO PICK THOSE THAT WILL BE THE
BEST RESPONDERS OR WHICH
SUBGROUPS WE HAVE TO BE WORKING
ON.
WE DON'T HAVE THAT FOR EXERCISE
AND OA YET AND WE DON'T HAVE IT
FOR EXERCISE AND PROBABLY
ANYTHING YET AT THAT LEVEL. DR.
MESSIER IS DOING LARGE STUDIES
AND PERHAPS SECONDARY ANALYSIS
ON HIS STUDIES WILL BE ABLE TO
HELP US IDENTIFY SOME OF THE
FACTORS AND WE NEED MORE TRIALS
OUT THERE DOING THAT.
>>ALEX I'M SEEING DR. RAGOVHN'S
HAND WAS RAISED.
>>THANK YOU. I WANTED TO SHARE
A PERSPECTIVE FROM
NEUROLOGICALLY IMPAIRED
POPULATION IN TERMS OF CRITICAL
WINDOW WE FIND THAT EXERCISE IS
ALSO VERY CRITICAL IN
NEUROLOGICAL POPULATION.
IT RELEASES GROWTH FACTORS AND
QUESTION IS WHEN DO YOU GET THAT
INTERVENTION?
AND WHAT -- YOU KNOW, SOME OF
OUR DATA SHOWED THAT I SHARED IS
THAT IMMOBILITY LEADS TO CHANGES
IN THE TISSUE STRUCTURE.
WE WANT TO PREVENT THOSE CHANGES
THAT WOULD BE REALLY IMPORTANT
TO GIVE THOSE EARLY AND
INTERVENTIONS EARLY ON RATHER
THAN LATER.
IN THE REAL WORLD IT IS HARD TO
KNOW.
PATIENTS COME TO US AT DIFFERENT
TIMES AND WONDER IF WHEN DOING
CLINICAL TRIALS IS WORTHWHILE TO
SEPARATE THOSE THAT HAVE ACUTE
FROM CHRONIC PAIN.
WE KNOW WHEN THEY HAVE CHRONIC
PAIN THEY HAVE CHANGES IN
CENTRAL NERVOUS SYSTEM AND
SENSITIZATION AND MEMORY OF PAIN
GETS RE-ENFORCED.
PERHAPS THAT TIMING AND
MECHANISMS THAT ARE UNDERLYING
WHAT IS REALLY HAPPENING AT THE
TISSUE LEVEL THAT COULD ALSO
HELP US DETERMINE WHEN AND WHAT
INTERVENTION.
>>THANK YOU DR. RAGHAVAN AND
FOLLOW UP DISCUSSION IN Q & A I
SEE IN CHAT ABOUT LEVERAGING
PATHWAYS DISCUSSED YESTERDAY
SORT OF HOW TO DEVELOP
INTERVENTIONS TO TARGET THESE OR
DO WE HAVE TO UNDERSTAND THESE
BETTER TO TAILOR INTERVENTIONS
TO THIS AREA. I WOULD LIKE TO
CIRCLE BACK TO THAT A LITTLE BIT
LATER AND DR. BUTERA, YOU HAVE A
QUICK COMMENT?
>>YEAH. THANKS SO MUCH. I
WANTED TO PIGGYBACK OFF WHAT DR.
SLUKA WAS TALKING ABOUT GETTING
FUNDING TO DO THESE SORTS OF
TRIALS AND THINK THAT THIS IS
DEFINITELY SOMETHING THAT DR.
GOERTZ IS ALSO DOING AT DUKE AND
THINKING MORE ABOUT THIS
IMPLEMENTATION AND WE HAVE SO
MANY INTERVENTIONS.
AND, YOU KNOW, BUT THINKING
ABOUT WHEN DO WE APPLY THESE AND
IN WHAT ORDER AND WITH WHAT
DOSING.
SO, I THINK IT IS NOT JUST ABOUT
NEEDING FUNDING BUT ALSO
EXPERTISE AND EDUCATION FOR
RESEARCHERS THEMSELVES THAT
THERE IS IMPLEMENTATION TRIAL
DESIGNS AND THERE ARE SMART OR
ADAPTIVE TRIAL DESIGNS TO LOOK
AT ORDER OF INTERVENTIONS TO
MIMIC WHAT HAPPENS IN HEALTH
CARE SYSTEM AND NOT JUST ABOUT
GETTING FUNDING FOR LARGE TRIALS
AND HIGHLIGHTING IMPORTANCE
ACROSS RESEARCH COMMUNITY THAT
OFTEN TIMES WHEN WE START TO
TALK ABOUT IMPLEMENTATION
STUDIES WE GET PUSHBACK FROM
RESEARCHER WHO'S ARE TRADITIONAL
TRIALISTS SAY YOU CAN'T DO THIS
YOU ARE NOT CONTROLLING FOR THIS
OR THAT.
THAT IS KIND OF THE POINT AND
THINKING MORE ABOUT WHAT IS
NEEDED FOR IMPLEMENTATION AND
SURE THERE IS A LOT OF OTHER
PANELISTS WITH THOUGHTS ON THIS
AS WELL.
>>THANK YOU. DR. BOLIN?
>>THANK ENRICHING DISCUSSION
YESTERDAY AND TODAY. IDEAS
WHERE FIELD NEEDS TO GO AND WE
HAVE TO GO BIG OR GO HOME WHEN
IT COMES TO EXERCISING DOSING
TRIALS AND UNDERSTANDING
INDIVIDUAL DIFFERENCES AND HOW
THEY RESPOND IS A REALLY KEY
DIRECTION AND WOULD SAY THAT
WHAT I HEARD FROM THIS GROUP AND
HAVE SEEN AS A THEME THROUGHOUT
THIS IS, YOU KNOW, IF IT IS
EXERCISE, ANSWER REALLY IS
ALWAYS AND OFTEN. IT IS -- WHAT
IT BOILS DOWN TO, WE HAVE NO
EVIDENCE IT IS A NEGATIVE.
THE ISSUE BECOMES HOW DO WE DOSE
IT APPROPRIATELY FOR THE PERSON?
DOES IT REQUIRE COMBIN ATORIAL
TREATMENT TO GET THE INDIVIDUAL
TO RESPOND OPTIMALLY?
I THINK THERE IS A GREAT FUTURE
IF FOR COMBIN ATORIAL TREATMENT
TRIALS AND STARTING TO TEASE
APART FENOMIC AS WELL AS
MOLECULAR AND BIOLOGICAL INDICES
WHAT MAKES A PERSON RESPOND THAT
IS A KEY QUESTION THAT IS GOING
FORWARD AND THIS IDEA OF
MULTIMODALITY TREATMENT IS I
THINK WHERE WE HAVE TO GO AND
THAT DOES REQUIRE LARGE-SCALE
WORK FOR SURE.
>>THANK YOU DR. BAMMAN.
PICKING UP ON THAT KS. I
NOTICED IN THE CHAT QUESTIONS
FOR CHANGING ADIPOSE SECRETE OHM
OR TRANSCRIPT OHM OF FAT IN
JOINT AND PERIPHERAL MILIEU OR
CYTOKINE MAKEUP OR MORE GENERAL
OR BIOMEDICAL OR REDUCTION IN
WEIGHT AND WOULD LOVE TO HEAR
PANELS WAYS TO INTEGRATE
BIOLOGICAL MECHANISMS DISCUSSED
YESTERDAY WITH ONGOING TRIALS
AND INTERVENTIONS AND ARE THERE
OTHER AREAS THAT WE CAN EXPLORE
LIKE THAT EXAMPLE THAT DR.
WILLIAMS AND DR. KELSEY DID A
FOLLOW-UP QUESTION AND DO WE
KNOW ANYTHING ABOUT SECRETE OHM
IN THAT IT IS SOMETHING THAT IS
SPECIFIC HAPPENING IN THE AREA
OF THE JOINT?
ARE THERE OTHER THOUGHTS ABOUT
WAYS TO INCORPORATE TOPICS THAT
WERE DISCUSSED YESTERDAY?
DR. SLUKA?
>>I'M A STRONG BELIEVER WE NEED
TO KNOW WHAT INTERVENTIONS ARE
DOING TO BEST APPLY THEM. IF WE
CAN'T JUST APPLY THEM IN A BLACK
BOX AND SAY THIS WORKS SO WE DO
IT.
REASON I SPENT 20 YEARS OR 10 OR
15 YEARS TRYING TO FIGURE OUT
HOW IT WORKS IS IMPROVING
EFFICACY AND IN THE CLINIC AND
SIMILAR FOR EXERCISE IT CHANGES
-- EXERCISE CHANGES PERIPHERAL
NERVOUS SYSTEM AND DOES ALL OF
THE ABOVE AND IS A WONDERFUL
MULTIMODAL TREATMENT WORKING
WITH A NUMBER OF DIFFERENT
MECHANISMS TRANSLATING THEM BACK
INTO HUMAN STUDIES MAKING SURE
WE ARE SEEING SIMILAR THINGS
WOULD BE WONDERFUL. WE NEED
PEOPLE WHO LOOK AT MECHANISMS IN
CLINICAL TRIALS THEY ARE DOING
AS WELL AS MECHANISMS IN ANIMAL
WORK AND STUDIES TO SEE WHAT
EXERCISE IS DOING TO BETTER
INFORM HOW WE WOULD APPLY IT.
IS RESISTANCE TRAINING SAME AS
AEROBIC TRAINING AND STRETCHING
OF MYOFASCIAL TECHNIQUES THE
SAME AND WHAT IS MANUAL THERAPY
DOING AND IS THAT SUPER
IMPORTANT TO BETTER USE
INTERVENTIONS TO KNOW HOW TO DO
IT AND WE KNOW HOW
PHARMACEUTICAL INTERVENTIONS
WORK AND ARE APPLIED BASED ON
UNDERLYING MECHANISTIC
HYPOTHESIS AND WE DON'T APPLY
YOU KNOW ANTIDEPRESSANTS TO
PEOPLE AND I WILL TALK ABOUT
DEPRESSION AND ANXIETY NOT ABOUT
PAIN RIGHT NOW AND WE DON'T HAVE
ANTIDEPRESSANTS TO PEOPLE THAT
ARE NOT DEPRESSED UNLESS FOR
PAIN AND THEY HAVE TO HAVE
CENTRAL MECHANISMS FOR THAT. WE
NEED SAME THOUGHT PROCESS WHEN
WE START TO APPLY NON-DRUG
TREATMENTS AND WILL LEAVE IT AT
THAT.
>>I TOTALLY AGREE. YOU KNOW,
SINCE YOU KNOW YOU BROUGHT UP
THIS IDEA OF COMPARING
TREATMENTS OR INTERVENTIONS TO
SMALL MOLECULES AND HOW THEY ARE
DEVELOPED AND YOU MENTIONED
DURING YOUR TALK.
YOU MENTIONED THAT THE TIMING
AND USING THE RIGHT DOSE OF TENS
OR ELECT TROE SUIT CALS FOR LACK
OF A BETTER TERM OVER THERE.
HAVE YOU LOOKED AT OR IS THERE A
GOOD WAY TO ASSESS WHETHER OR
NOT TARGET ENGAGEMENT OF
ELECTRICAL STIMULATION IS REALLY
HITTING THE NERVE WE WANT? AT,
YOU KNOW, AT THAT RIGHT DOSE AND
WITH THE RIGHT TIMING?
IF THAT IS -- YOU KNOW, IF IT
COULD REALLY HELP US DEFINE
WHETHER OR NOT INTERVENTION IS
APPROPRIATE FOR PATIENT. YOU
CAN IMAGINE IF YOU ARE USING A
NON-INVASIVE STIMULATION
TECHNIQUE AND PERSON HAS A BMI
OF 39 OR 40 IT WOULD BE
DIFFERENT THAN IF THE
INTERVENTION AND IF THEY HAD BMI
OF SAY 23. WHAT DO YOU THINK,
CATHERINE?
>>PERHAPS FROM A CLINICAL
PERSPECTIVE IT WOULD BE HARD TO
REALLY FIGURE THAT OUT. YES.
SUPPOSING YOU PUT ELECTRICAL
STIMULATION THROUGH THE SKIN
TALKING ABOUT STRONG
UNCOMFORTABLE INTENSITY YOU ARE
GETTING PAST THE SKIN AND TO
RIGHT TARGET [INDISCERNIBLE] AND
THERE ARE WAYS TO DO IT. WE DO
NEED -- THAT IS PART OF
APPROPRIATE DOSING AND WILL SAY
WE HAVE HAD RESPONDERS IN OUR
CLINICAL TRIALS WITH
FIBROMYALGIA WITH TENS WITH HIGH
BMIS AND STILL RESPONDED BECAUSE
WE GAVE IT AN AT AN ADEQUATE
DOSE AND THINK THAT IS PATIENT
SPECIFIC.
YES. WE NEED TO DO THAT AND
MAKE SURE WE ARE GIVING RIGHT
DOSE THAT ACTUALLY IS NOT BASED
ON NUMBER ON THE UNIT BUT RATHER
THE PERSON RESPONSE TO THAT
DOSE.
THAT IS TRUE FOR EVERYTHING WE
DO. WHAT IS THE DOSE? HOW IS
IT INDIVIDUALIZED TO THE PERSON
ITSELF?
>>PERFECT. MAKES SENSE.
FOLLOW-UP QUESTION TO THAT IS
FOR DR. ROHN IF MANUAL THERAPY
LIKE WE SAID EARLIER COULD BE
EXERCISE IN SOME WAY AND YOU
MENTIONED IN YOUR TALK THAT
LOADING OF THE JOINT IS
CORRECTLY SOMETHING TO LOOK AT
MONITORING THE PATIENT. COULD
IT BE THAT MONITORING THE
SENSORY FEEDBACK AND REALLY
ELECT TROE PHYSIOLOGICAL CENSOR
OF THE SENSORY NERVE COULD HELP
US IN THESE ELECTROTHERAPIES OR
YOU KNOW INTERVENTIONS TO TRY TO
REPRODUCE A CORRECT SENSORY
FEEDBACK TO THIS CNS FROM THAT
JOINT?
>>YEAH. THIS IS A GOOD
QUESTION. I THINK THERE IS A
LOT ABOUT THE SPECIFIC M
MECHANISMS OF MANUAL THERAPY WE
DON'T UNDERSTAND AND EXPLORING
THERE TO BETTER UNDERSTAND
DOSING OR TAILORING OF THE
LOADING AND INDIVIDUALIZED
RESPONSES AND HOW THEY VARY.
MAYBE THESE TAILORED TREATMENTS
IF WE CAN UNDERSTAND THAT
INTERACTION BETTER I THINK THAT
VERY PLAUSIBLE HYPOTHESIS TO
BETTER UNDERSTAND THAT MAYBE WE
CAN UNDERSTAND DOSING AND HOW WE
INTERVENE AND CAN TAILOR THAT
FOR PATIENTS A LITTLE BETTER AND
YEAH. I THINK THERE IS A LOT
THERE THAT IS STILL UNTAPPED.
>>EXCELLENT. THANKS.
>>YOU KNOW, IT IS A FOLLOW UP
TO THAT TO UNDERSTAND WHAT IS
THIS FEEDBACK THAT IS HAPPENING
FROM THE PERIPHERY TO THE CNS
THAT LEADS PERCEPTION OF PAIN OR
CHANGE IN PERCEPTION OF THE
JOINTS AND THIS QUESTION IS FOR
DR. RAGHAVAN IF IT DISRUPTS
SPINDLE AND FEEDBACK FROM THE
SPINDLE COULD IT LEAD TO MORE
FALLS OR LACK OF, YOU KNOW,
APPRO RIO CREPTOR CONTROL OR
CHANGE OF DATE OF THOSE WITH
INCREASED LEVEL OF HIGH ALLURE
ONIC ACID IN MUSCLES AROUND THE
SPINDLE?
>>EXCELLENT QUESTION.
WE ANECDOTALLY WE ARE SEEING
THAT PATIENTS HAVE BETTER
SENSATION WHEN WE REMOVE THEIR
STIFFNESS.
WHEN WE REDUCE STIFFNESS WE SEE
THAT PATIENTS WHO MIGHT HAVE
POOR BALANCE TO START WITH
BECAUSE OF NEUROLOGICAL DEFICITS
ARE ABLE TO MORE FLEXIBLY ALTER
THEIR STANCE WHEN THEY OR THERE
IS -- WHEN THEY MEET WITH A PER
TUR BASING AND WE ARE PART OF A
CLINICAL TRIAL WE ARE RUNNING WE
WILL LOOK AT CHANGES IN
PROPRIOCEPTION AS WELL AND THINK
THAT BECAUSE OF THE LOCATION OF
THE SPINDLE RECEPTORS AND NERVES
THAT ENTER MUSCLE WITHIN THE
MUSCLE WE THINK THAT, YOU KNOW,
ALTERATIONS IN STIFFNESS OF THE
TISSUE CAN CHANGE YOUR -- CAN
ACTUALLY IMPINGE ON SYMPATHETICS
RUNNING WITH VASCULAR AND
IMPINGE ON STRETCH RECEPTORS AND
MECHANICAL LOADING OF JOINTS.
MUSCLES ARE STUCK TOGETHER. YOU
TRY TO GENERATE FORCES THAT WILL
CHANGE LOADING ON JOINTS.
SO, YOU KNOW, THERE IS MANY
POTENTIAL WAYS THAT THIS COULD
EXPLAIN SOME OF WHAT WE ARE
SEEING.
>>EXCELLENT. THANKS SO MU.
THIS IS A QUESTION FOR DR.
MESSIER.
WE MENTIONED THIS IDEA OF WEIGHT
AND DIET AS, YOU KNOW,
INTERRELATED IN SOME WAY THAT
COULD INFLUENCE PAIN OUTCOMES
DEPENDING ON THE JOINT.
SO, YOU KNOW, DOES AN
INFLAMMATORY DIET, COULD THAT
MAKE A DIFFERENCE?
ISN'T IT SPECIFIC ASPECTS OF THE
DIET, MEANING NOT JUST
INFLAMMATORY OR INFLAMMATORY
DIET IN GENERAL BUT MAYBE
SPECIFIC LIPID MEDIATORS THAT
CHRIS WHO IS AN INTRAMURAL
RESEARCHER AT NIH HAS SHOWN
DECREASED INFLAMMATION IN THE
JOINTS AND MUSCLES AND IS THAT
GOAL HERE WITH THE DIET OR JUST
DECREASING CALORIES AND ADIPOSE
TISSUE IN THE JOINT? WHAT IS
THE GOAL HERE?
>>FOR US, THE LATTER.
THERE ARE TWO PATHWAYS THAT I
THINK I SHOWED THAT AS
BIOMECHANICAL PATHWAY THAT IS
THE LOAD. YOU DECREASE WEIGHT
AND LOAD.
WHILE YOU ARE DECREASING THE
WEIGHT YOU ARE DECREASING
ADIPOSE TISSUE AND DECREASING
INFLAMMATORY CYTOKINES AS WELL.
SO, WE GET WHAT WEIGHT LOSS DOES
IS IT IMPACTS BOTH INFLAMMATORY
-- BOTH OF THE PATHWAYS,
BIOMECHANICAL AND INFLAMMATORY.
WE DO A BALANCED DIET AND EAT
FEWER CALORIES.
AND ADDING EXERCISE HELPS YOU
MAINTAIN WEIGHT LOSS.
THOSE ARE TWO THINGS.
YOU KNOW, THE OTHER THING I WILL
SAY ABOUT THE EXERCISE AND I'M
IN DEPARTMENT OF HEALTH AND
EXERCISE SCIENCE. IT IS HARD
FOR ME TO COME OUT AND SAY
EXERCISE HAS A LIMITED EFFECT ON
PAIN IN THIS POPULATION. I
THINK IT DOES HAVE A VERY LIMIT
-- THAT IS NOT TO SAY WHAT I
WANT OUR PATIENTS TO EXERCISE.
ABSOLUTELY.
THEY WILL GET 25 TO 35%
REDUCTION IN PAIN AND SO WILL
PAYING ATTENTION TO PEOPLE IN
OTHER WAYS.
WHAT WE WANT TO DO IS GET BEYOND
THAT 25 OR 35% REDUCTION IN
PAIN. 50%. 75% TO REALLY SEE A
DIFFERENCE.
THE BIGGEST DIFFERENCE THAT WE
HAVE SEEN IS THE WEIGHT LOSS.
THAT IS -- IT HAS THE BIGGEST
IMPACT WE HAVE SEEN FROM A
NONPHARMACOLOGIC POINT OF VIEW.
THAT IS NOT TO SAY THAT IT
DEPENDS WHAT YOUR OUTCOME
MEASURE IS; RIGHT?
PATIENTS, WHAT THEY CARE ABOUT
IS PAIN.
>>OF COURSE.
>>RIGHT?
FROM A PAIN PERSPECTIVE, IT
DOESN'T MATTER FROM WHAT -- FROM
OUR EXPERIENCE THAT WE HAVE BEEN
DOING CLINICAL TRIALS FOR OVER
30 YEARS.
IT DOESN'T MATTER WHAT KIND OF
EXERCISE.
YOU WILL GET SAME RESULT, ABOUT
35% REDUCTION PAIN. CONTROL
GROUPS PAYING ATTENTION TO THEM,
YOU GET 33% REDUCTION IN PAIN.
ALL RIGHT?
>>RIGHT.
>>ONLY THING THAT TAKES YOU
ABOVE THAT IS WHAT -- ADDING
WEIGHT LOSS TO IT AND HOW MUCH
WEIGHT LOSS MAKES A DIFFERENCE
AND 5% WEIGHT LOSS IS GREAT AND
10% IS ACTUALLY TWICE AS GOOD
AND 20% IS NOT TWICE AS GOOD AS
10% BUT IT IS -- IT IS BETTER.
SO, THAT IS WHERE WE COME FROM.
AND I GUESS YOU COULD GO AHEAD
WITH THE DIETS AND LOOK AT HIGH
INFLAMMATORY PARTS OF DIET AND
TAKE THAT OUT.
BUT, I DON'T KNOW IF YOU WILL
GET THIS BIGGER IMPACT THAT WE
ARE TRYING TO GET.
>>GOT IT.
>>YOU HAVE SMALL INCREMENTAL
IMPACTS.
BUT, WE ARE TRYING TO GET HUGE
IMPACTS AND 50% AND 75%.
>>RIGHT.
>>AND ANYWAY.
>>SO, I JUST HAVE ONE QUESTION.
THIS IS REALLY FOR -- OH, YEAH.
YOU KNOW, DR. BAMMAN, PLEASE.
>>I DON'T WANT TO INTERRUPT
YOU. I CAN WAIT. GO AHEAD.
>>I HAVE A FINAL QUESTION HERE
THAT IS REALLY FOR THE WHOLE
GROUP.
DO THESE INTERVENTIONS, MANUAL
THERAPIES, EXERCISE AND WEIGHT
LOSS AND ELECTRICAL STIMULATION,
ALL THOSE PUT TOGETHER OR
INDIVIDUALLY DEPEND ON THE TYPE
OF PAIN NO SUSSEPTIVE AND
INFLAMMATORY AND NEUROPATHIC AND
CHRONIC PAIN OPOSED TO CUE PAIN
AND DO THEY HAVE TO BE ARE THESE
GENERAL INTERVENTIONS OR ARE
THEY SPECIFIC FOR THE TYPE OF
PAIN?
ANYBODY WANT TO GRAB THAT ONE?
IS IT TOO BROAD? DR. BAMMAN,
YOU CAN DO IT IF YOU WANT OR
KATHLEEN, FEEL FREE.
>>REALLY TOUGH ONE.
>>WASN'T MEANT TO BE TSTUMP PE.
>>YEAH. I WILL DEFER TO THE
PANELISTS IT WAS TO BE AS
SPECIFIC AND MECHANISTIC AND
TARGETED AS WE COULD GET. I
WOULD SAY THERE ARE PROBABLY
DIFFERENT MECHANISMS AND
THEREFORE INTERVENTIONS HAVE TO
BE TARGETED IN DIFFERENT WAYS
WOULD BE MY GENERAL COMMENT ON
THAT AND WANTED TO MAKE A QUICK
COMMENT ABOUT AND HEARD OTHERS
BRING THIS ISSUE UP.
IN ANY FORM OF INTERVENTION
TRIAL, WE ALL ARE CHALLENGED BY
WHAT IS THE CONTROL.
GOING FORWARD, I THINK WE NEED
TO THINK CAREFULLY ABOUT HOW
BEST WE DEFINE THAT GROUP.
IN THIS CONTEXT, YOU KNOW, WE
DID A TRIAL WHERE WE RANDOMIZED
PEOPLE AFTER TOTAL JOINT
ARTHROMRAFTY TO INTERVENTION
VERSUS USUAL CARE AND HAD TO
DEFINE CONTROL GROUP AS USUAL
CARE. THERE IS A WIDE RANGE IN
WHAT THEY ACTUALLY EXPERIENCED.
YOU KNOW, SOME HAVE RIGOROUS
PHYSICAL THERAPY FOR 6 WEEKS
POST-OP AND SOME HAVE NONE AND
TWO WEEKS OF MODERATE THERAPY
AND IS A HUGE RANGE AND
THEREFORE THERE IS NO STANDARD
OF CARE AND HAD TO CALL IT USUAL
CARE AND CARE FROM SPEAKERS AND
PREOPERATIVELY AND PRIOR TO THE
END STAGE DISEASE ONLY 10 TO 15%
GET REFERRED FOR PHYSICAL
THERAPY.
ON PREOPERATIVE SIDE EARLIER IN
THE DISEASE PROGRESSION YOU
STILL HAVE A WIDE RANGE WHAT YOU
MIGHT TRY TO TAP INTO AS A
CONTROL CONDITION.
I THINK WE HAVE TO THINK
CAREFULLY ABOUT HOW DO WE
QUANTIFY A GROUP OF PEOPLE WHO
ARE NOT IN THE INTERVENTION FOR
ANY OF THESE TRIALS.
AND HOW BEST CAN WE COMPARE
THEM? YOU KNOW, WE NEED TO
PROBABLY DO A BETTER JOB WITH
WEARABLE TECHNOLOGIES AND NEED
TO DO A BETTER JOB WITH OTHER
MEANS OF MONITORING WHAT PEOPLE
ARE ACTUALLY DOING AND DATA GETS
PRETTY SLOPPY WHEN TRYING TO GET
A RIGOROUS INTERVENTION TRIAL
THAT YOU HAVE ESSENTIALLY NO
CONTROL OVER THIS OTHER GROUP OF
PEOPLE YOU WANT TO COMPARE IT TO
AND JUST TO MAKE THAT COMMENT
AND WE HAVE TO THINK ABOUT IT AS
A GROUP WHEN WE WANT TO GO LARGE
SCALE.
>>I LIKE THE WEARABLE
TECHNOLOGIES OVER THERE AND
FIGURING OUT A WAY TO DEAL WITH
LARGE AMOUNTS OF DATA WE WILL
HAVE THERE ALSO FROM MANY
PATIENTS THAT WE NEED IN TRIALS
TO DIFFERENTIATE.
THANKS SO MUCH.
DR. SLUKA?
>>I WILL GO BACK AND ANSWER
YOUR MECHANISM QUESTION AND
QUESTION IS DO WE NEED TO KNOW
MECHANISM -- DOES IT MATTER WHAT
MECHANISM PATIENT HAS AND
NOSICEPTIVE AND PLASTIC PAIN AND
TO SOME EXTENT YES AND LEARNING
ABOUT HOW INTERVENTIONS WORK IT
MAY BE LESS. EXERCISE CAN
PROMOTE HEALER OF PERIPHERAL
NERVES OF NEUROPATHIC PAIN AND
CHANGE CAPS YUM CHANNELS AND
REDUCE CAPS YUM AND SODIUM
CHANNELS CHANGING FROM
INFLAMMATORY TO ANTIINFLAMMATORY
STATE IN JOINT LEVEL AND IN
MUSCLE AND SYSTEMICALLY AND ON
CENTRAL NERVOUS SYSTEM IN GLIA
AND REDUCE CENTRAL
[INDISCERNIBLE] AND REDUCE
CENTRAL INHIBITION AND CHANGES
FUNCTION. WE ALL KNOW THAT.
IT WORKS ACROSS MULTIPLE
MECHANISMS.
MANUAL THERAPY IS SIMILARLY
DOING THAT.
KNOWING HOW OUR TREATMENTS WORK.
WHAT MECHANISMS THEY ARE AT
HELPS US.
DR. MESSIER SAID INDEED IT
DIDN'T MATTER WHAT EXERCISE THEY
USE THEY ALL SEEM TO WORK
EQUALLY WELL AND AGREE WITH
THAT. WE ARE WORKING ACROSS
MULTIPLE MECHANISMS AND SAME IS
TRUE FOR LOOKING FOR OTHER
INTERVENTIONS UNDERSTANDING HOW
THEY WORK AND UNDERSTANDING WHAT
IS GOING ON WITH YOUR PATIENT
INDIVIDUALIZING THAT TREATMENT
AND PICKING THEM APPROPRIATELY
MATTERS AND GOOD THING IS MANUAL
THERAPIES WORK ACROSS MULTIPLE
MECHANISMS AND ARE NOT A SINGLE
BUT MULTITARGET AND GREAT
MULTIMODAL TREATMENTS THAT IS
WHY THEY ARE WORKING ACROSS MORE
OR CROSS-EFFECTIVELY.
>>GOOD POINT.
WHOLE PERSON AND WHOLE HEALTH
WORKING IN THEME OF CONFERENCE.
THANKS SO MUCH AND DR. TUTLE
WILL BRING QUESTIONS FROM THE
GENERAL AUDIENCE.
>>YEAH. WE APPRECIATE EVERYONE
GOING A LITTLE LONG. WE WANTED
TO MAKE SURE WE HAD A ROBUST
DISCUSSION AND A FEW QUESTIONS
FROM THE AUDIENCE WE WOULD LIKE
TO ASK THE PANEL BEFORE WE BREAK
FOR LUNCH. FIRST IS WHAT IS
LIKELY EFFECT OF NEW HIGHLY
EFFECTIVE WEIGHT LOSS DRUGS ON
OSTEOARTHRITIS AND HOW WILL IT
EFFECT TRIALS LOOKING AT OTHER
TYPES OF NON-PHARMACOLOGICAL
INTERVENTIONS AND QUESTION IS
REFERRING TO OSDEM PICK OR
[INDISCERNIBLE] AND MARKET
DECREASE IN BODY WEIGHT THAT WE
ARE SHOWING SO FAR?
THIS TIES INTO MY EARLIER
QUESTION TO A CERTAIN EXTENT IS
IT OVERALL BIOMECHANICAL WEIGHT
REDUCTION OR WOULD DRUGS ALSO
MAYBE BE CHANGING, YOU KNOW,
LOCAL FACTORS IN ADIPOSE TISSUE
PROXIMAL TO THE JOINT AND
CURIOUS BEFORE ROHN OR MESSIER
OR OTHER PANELISTS THAT WOULD
LIKE TO CHIME IN ABOUT THIS?
>>GO AHEAD, DAN.
>>I DON'T SEE DAN COMING OFF
CAMERA. DR. MESSIER, WOULD YOU
LIKE TO TAKE THIS?
>>THE TREATMENT AND WEIGHT LOSS
IS REMARKABLE AND WE HAVE BEEN
THINKING TO DO A COMPARATIVE
EFFECT IN THIS TRIAL LOOKING AT
DIET AND EXERCISE VERSUS WEIGHT
LOSS DRUG AND IN PEOPLE WITH
KNEE OSTEOARTHRITIS SEEING IF
YOU GET THE SAME EFFECT AND
WHERE ONE LASTS LONGER THAN THE
OTHER. YOU KNOW?
WITH -- WITH PAIN AND FUNCTION.
BUT I WILL HAVE TO SAY THAT
STUDIES SO FAR HAVE BEEN DONE
CAREFULLY PUBLISHING GREAT
JOURNALS IN MEDICINE AND IN JAMB
AND EVERY ONE OF THEM AND
RESULTS ARE IMPRESSIVE.
THEY ARE -- IT LOOKS TO US LIKE
THEY ARE GETTING -- THEY ARE
HITTING BOTH PATHWAYS AND
HITTING BIOMECHANICAL PATHWAY
AND HITTING INFLAMMATORY PATHWAY
AT THE SAME TIME AND LOOKS LIKE
IMPACT IS IN THE SAME PATHWAYS
THAT DIET AND EXERCISE WOULD DO
AND QUESTION IS WHETHER --
WHETHER -- WHETHER YOU GET THE
SAME EFFECT.
OTHER THING IS COST
EFFECTIVENESS OF IT.
OUR LARGE TRIALS WE DO COST
EFFECTIVENESS ANALYSIS AND
SOMETHING I HAVEN'T BROUGHT UP
DIET AND EXERCISE LONG TERM IS
HIGHLY COST EFFECTIVE AND
WHETHER THE DRUG WOULD COME UP
WITH SAME COST EFFECTIVENESS I
DON'T KNOW. IT IS ABOUT $1,000
A MONTH RIGHT NOW.
>>WOULD YOU DO THE TRIAL IN
THOSE WITH METABOLIC DISORDERS
OR DIABETES OR JUST USE IT IN
PATIENTS THAT WERE INDEPENDENT
OF THAT AND JUST USING IT FOR
THE WEIGHT LOSS.
>>YEAH. WE DO OSTEOARTHRITIS.
>>OKAY.
>>WE WOULD DO IT. IN FACT,
THERE IS A --
>>I HAVE OSTEOARTHRITIS BUT IT
COULD BE A PATIENT WITH DIABETES
OR WITHOUT.
>>OH, YEAH IN FACT WEIGHT LOSS
DRUGS STARTED WITH PEOPLE WITH
DIABETES.
>>I'M ASKING THE QUESTION. YOU
HAVE CONFOUNDING VARIABLE OF
PAIN DISORDERS IN INDIVIDUALS
WITH DIABETES POTENTIALLY
WHEREAS IF YOU DO IT IN
INDIVIDUALS WITHOUT DIABETES.
>>YEAH.
>>IT IS A CLINICAL TRIAL.
>>YEAH, IT IS. IT IS TOUGH TO
DO WHEN YOU HAVE -- WHEN YOU ARE
GETTING PEOPLE WHO WITH BMIS
OVER 40.
A LOT OF THEM HAVE TYPE 2
DIABETES GOING WITH IT AND
WEIGHT LOSS GETS RID OF DIABETES
MOST OF THE TIME. IT IS
REMARKABLE IT DOES THAT.
>>THANK YOU DR. MESSIER.
DR. SLOOUKA QUESTION FOR YOU.
CAUSE INSTABILITY IN PATIENTS
WITH UNSTABLE JOINTS AND
DEPENDING ON INPUT FOR
MAINTAINING UNSTABLE JOINT?
>>I'M NOT SURE I HAVE EVER SEEN
DATA OF INTERRUPTION OF
PROPRIOCEPTION WITH TENS AND
THAT IS IF I THINK ABOUT IT AND
PEOPLE DON'T SEEM TO UNSTABLE
AND DON'T HAVE INCREASED FALLS
OR PEOPLE USING TENS IN ACTIVE.
WE DON'T SEE IT AS AN OUTCOME.
WE HAVE LOOKED AT THE SPECIFIC
QUESTION ON ADVERSE EVENT FORMS
AND DON'T SEE THAT.
I'M NO THE SURE THAT THAT IS
ACTUALLY HAPPENING AND I --
UNLESS OTHER EVIDENCE THAT
PEOPLE HAVE, WE DOECHT SEE IT AS
AN ISSUE.
REDUCTION IN PAIN HELPS THEM
MOVE BETTER SO MAYBE THEY ARE
MOVING BETTER IN A MORE
COORDINATED MANNER ANYWAYS AND
MAYBE IT MAKES UP FOR IT.
>>THANK YOU DR. SLUKA.
I WOULD LIKE TO CIRCLE BACK TO
DR. GOERTZ WHO HAD TAKE-HOME
MESSAGES I WOULD LIKE TO HEAR
BUT DIDN'T HAVE TIME IN
INTRODUCTION AND WOULD YOU LIKE
TO SHARE YOUR LAST PORTION OF
YOUR THOUGHTS FROM THE WORKSHOP?
>>I WOULD BE HAPPY TO. THANKS
SO MUCH, ALEX. THIS HAS BEEN A
TERRIFIC SESSION. I REAL
ENJOYED THE RICH DISCUSSION.
I THINK IT ILLUSTRATES THE
COMPLEXITY WE FACE CONSIDERING
WIDE RANGE OF TREATMENTS
AVAILABLE TO PATIENTS THAT WE
ARE ALL STUDYING AND YOU
COULDN'T HAVE PICKED A BETTER
REPRESENTATION OF THE BROADNESS
OF THOSE THAN EVERYTHING FROM
DIET TO EXERCISE TO -- TO
INJECTIONS AND ONE PROBLEM WE
FACE IS THAT RESEARCH HAS BEEN
MENTIONED SEVERAL TIMES ALREADY
THAT TENDS TO FOCUS ON ISOLATED
TREATMENTS RATHER THAN
MULTIMODAL APPROACHES THAT
PATIENTS ARE MORE LIKELY TO FACE
CLINICALLY.
AND THE OTHER THING THAT -- THAT
I FEEL THAT WE TEND TO SHALL
THAT, YOU KNOW, THOSE OF US WHO
ARE NIH SUPPORTED SCIENTISTS
ABOUT YOU CLINICALLY AS WELL WE
ARE STILL TENDING TO FOCUS MUCH
MORE ON BIOPART OF THE
BIOPSYCHOSOCIAL MODEL AND NOT ON
THE SOCIAL PART OF THE MODEL AT
ALL.
I THINK THAT, THAT LACK OF FOCUS
MAY BE RESPONSIBLE FOR SOME OF
THE GAPS THAT WE HAVE BEEN
DISCUSSING SO FAR AT THIS
MEETING.
I'M INSPIRED AND CHALLENGED BY
THAT AND IDEAS AND WORK OF THE
WORKSHOP PARTICIPANTS AND ALSO
FROM A SCIENTIFIC PERSPECTIVE
AND ALSO BECAUSE OF THE
CONVERSATIONS THAT HAVE OCCURRED
THROUGHOUT THIS ENTIRE WORKSHOP
ABOUT THE NEED TO FOCUS MORE AND
IMPLEMENTATION AND, YOU KNOW,
IMPLEMENTATION SCIENCE.
I THINK THERE ARE REAL
OPPORTUNITIES FOR CROSS-CUTTING
COLLABORATIONS THAT NIH ACTUALLY
PROVIDES A UNIQUE OPPORTUNITY TO
FACILITATE COLLABORATIONS AND
THIS WORKSHOP IS A GREAT STEP IN
THE RIGHT DIRECTION AND I'M
HOPING THERE ARE WAYS TO -- THAT
WE ARE ABLE TO CONTINUE THESE
CONVERSATIONS.
>>VERY GOOD. THANK YOU FOR THE
REST OF THE THOUGHTS AND I WOULD
LIKE TO CONCLUDE THIS SESSION
AND THANKS ALL FOR STAYING ON
AND THIS IS A ROBUST DISCUSSION
AND WANT TO THANK ALL SPEAKERS
AND PANELISTS FOR THE
PARTICIPATION TODAY AND WOULD
LIKE TO THANK DR. SLUKA AND
OSHINSKY WHO SERVED AS CO-CHAIRS
PUTTING THIS TOGETHER AND WE
WILL BREAK FOR LUNCH AND RETURN
AT 1 P.M. STOP YOUR VIDEO AND
MUTE YOURSELF THAT WOULD BE
GRAEK AND WE WILL COME BACK AND
HAVE NEXT SCIENTIFIC SESSION
EMERGING TECHNOLOGIES AND
EMERGING MODELS AND THANK YOU,
EVERYONE.
>>WELCOME BACK.
WE ARE NOW KICKING OFF SESSION 5
OF OUR WORKSHOP TODAY.
THIS SESSION IS CHAIRED BY DR.
DUAN.
NATIONAL INSTITUTE OF BIOMEDICAL
IMAGING AND BIOENGINEERING.
OUR CO-CHAIRS ARE DR. BACHMAN OF
NINDS AND DR. LATTANZI OF NEW
YORK UNIVERSITY.
I'M GOING TO MOVE TO SPEAKER
SLIDE TO INTRODUCE SPEAKERS
BRIEFLY FOR OUR SESSION.
>>THANK YOU.
WE HAVE FOUR SPEAKERS FOR THIS
SESSION, FIRST SPEAKER IS MY
CO-CHAIR, DR. LATTANZI FROM NEW
YORK UNIVERSITY.
NEXT IS DR. PEDOIA FROM
UNIVERSITY OF CALIFORNIA, SAN
FRANCISCO.
DR. KEVIN KOCH FROM MEDICAL
COLLEGE OF WISCONSIN FOLLOWED BY
DR. YIN FROM MAYO CLINIC.
NEXT SLIDE.
WE HAVE FOUR PANELISTS FOR
ADDITIONAL PERSPECTIVES, DR.
SCOTT BANKS FROM UNIVERSITY OF
FLORIDA, DR. KOGAN FROM STANFORD
UNIVERSITY, DR. CEVIDANES
UNIVERSITY OF MICHIGAN, AND DR.
SIKDAR FROM GEORGE MASON
UNIVERSITY.
WITH THAT I PASS TO THE CO-CHAIR
FOR THE FIRST TALK.
THANK YOU.
>>OKAY.
LET ME SHARE MY SCREEN.
YOU SHOULD BE ABLE TO SEE IT
NOW.
SO GOOD AFTERNOON.
I NEED DISCLOSE I HAVE A PATENT
RELATED TO THE TOPIC OF THE
PRESENTATION, SO WHAT DO WE
MEAN?
QUANTITATIVE MRI IS WHEN THE
SCANNER IS NOT USED AS A CAMERA
TO TAKE PHYSICAL PICTURES BUT AS
A SCIENTIFIC MEASURING
INSTRUMENT TO GENERATE
QUANTITATIVE MAPS THAT CAN SHOW
SPECIFIC BIOLOGICAL CHANGES.
THIS IS A HIP JOINT SHOWN FROM
AN IMAGE ACQUIRED ALONG A
RADIOSECTION OF THE HIP, YOU SEE
ACETABULUM, THE LABRUM.
IT CALCULATES A THIN STRUCTURE,
TO DETECT LESIONS, REPORTING THE
CARTILAGE AS NORMAL BECAUSE IT
LOOKS NORMAL.
HOWEVER, THE PATIENT -- THE
SURGEON FOUND HUGE PORTION WAS
COMPLETELY DELAMINATED.
IF WE LOOK AT THE STANDARDIZED
MAP, SUPERIMPOSED, WE SEE THE
CARTILAGE LESION STANDS OUT.
THIS IS AN EXAMPLE TO QUANTIFY
LOSS OF LIGANDS, AN EARLY CHANGE
IN CALCULATION.
IT CAN DETECT EARLY CHANGES WITH
A SCORE OF 1 IN WHICH THE
CALCULATION LOOKS INTACT BUT
DAMAGE AT THE MECHANICAL LEVEL.
EARLY CHANGES ARE REVERSIBLE SO
EARLY DETECTION COULD ENABLE THE
SURGEON TO INTERVENE WHEN IT'S
POSSIBLE TO PREVENT DAMAGE THAT
WOULD LEAD TO OSTEOARTHRITIS.
THERE ARE MANY QUANTITATIVE
PARAMETERS USED TO CHARACTERIZE
(INDISCERNIBLE) AND MANY
TECHNIQUES TO MEASURE THEM
DEVELOPED OVER THE YEARS.
IT'S ALSO BEEN SHOWN
QUANTITATIVE MRI CAN BE
EFFECTIVE IN CHARACTERIZING
JOINT DISEASES.
WHY IT'S NOT USED CLINICALLY?
THERE ARE SEVERAL REASONS FOR
THAT.
ONE IS CERTAINLY SCAN TIME, A
SINGLE PARAMETER IS NOT
SUFFICIENT TO COMPLETELY
CHARACTERIZE STATUS OF CARTILAGE
AND SURROUNDING STRUCTURE SO WE
NEED TO MAP MULTIPLE PARAMETERS,
THAT CAN TAKE TIME.
AND TECHNIQUES PROPOSED OFTEN AT
THE DISPENSE OF ACCURACY.
MANY BOTTLE NECK IS REGISTRATION
AND SEGMENTATION.
FINALLY QUANTITATIVE MR
PARAMETERS CORRELATED WITH
CLINICAL FINDINGS AND OUTCOME
BUT INTERPRETATION IS LACKING,
SO TODAY I WOULD LIKE TO FOCUS
ON A MODEL BASED QUANTITATIVE
MRI TECHNIQUE ADDRESSING THE
FIRST TWO BULLET POINTS TO HELP
BOTH OF THE OTHER TWO
CONSIDERABLY.
IT WAS INTRODUCED TEN YEARS AGO,
MOST REMAIN LIMITED.
WHAT IS MR FINGERPRINTING?
IF YOU THINK OF TRADITIONAL MR
PARAMETER MAPPING WHAT WE DO IS
TRY TO MAKE BEHAVIOR BE
EXPLAINED USING SIMPLIFIED
MODEL.
MR FINGERPRINTING IS A
COMPLETELY DIFFERENT APPROACH.
WE LET IT THE SPINS DANCE FREELY
TO UNDERSTAND WHAT THEY ARE
TELLING US.
AND WE WILL SEE MORE OF THIS BUT
HAVE A TIME-SERIES OF HIGHLY
UNDERSTAMPED IMAGES THAT CAPTURE
TIME-DEPENDENT SPIN EVOLUTION,
THE FINGERPRINT, AND IDENTIFIED
THE UNDERLYING TISSUE
PROPERTIES.
M PROSECUTORS PARAMETER MAPS --
MR PARAMETER MAPS ARE
RECONSTRUCTED.
AND THIS IS THE MRF SHALL, I
WANT TO POINT OUT THERE ARE TWO
KEY CONCEPTS IN MR
FINGERPRINTING, FIRST IS
TEMPORAL INCOHERENCE, WE WANT
THE SIGNAL FROM DIFFERENT
TISSUES TO LOOK DIFFERENT IN
TIME.
WE DID THAT BY VARYING THE
POSITIONS, THESE PARAMETERS CAN
BE OPTIMIZED FOR SPECIFIC TISSUE
PROPERTIES.
WE WANT SPATIAL INCOHERENCE,
DIFFERENT SPATIAL LOCATION TO
LOOK DIFFERENT IN TIME.
IN THIS CASE THE TRAJECTORY WAS
SPIRAL, YOU CAN ENFORCE BY
ROTATING SPIRALS.
AND NEEDS TO BE FAST.
BECAUSE OF THE HIGH DEGREE OF
UNDERSAMPLING, FOR EXAMPLE THIS
IMAGE FROM THE PUBLICATION
SUPPOSED TO SHOW A BRAIN BUT YOU
NEED SOME IMAGINATION TO SEE A
BRAIN IN THESE IMAGES.
WHAT WE OBTAIN IS THESE IMAGES.
BECAUSE OF THE INCOHERENCE THAT
WAS ENFORCED DURING ACQUISITION
ARTIFACT WAS (INDISCERNIBLE)
FILTERED OUT BY THE FOLLOWING
STEPS.
ONCE WE HAVE THE STACK OF
IMAGES, THE VOXEL, CORRESPONDING
SIGNAL FINGERPRINT WHICH ENCODES
QUANTITATIVE INFORMATION.
WE USE BLOCK EQUATIONS WE'RE
INTERESTED IN QUANTIFYING, AND
ONCE WE HAVE THIS DICTIONARY WE
TAKE THE SIGNAL AND FIND THE
MOST SIMILAR ONE IN THE
DICTIONARY AND ONCE WE MEASURE
FINGERPRINT WE KNOW EXACTLY WHAT
ARE THE TISSUE AND REPEAT FOR
ALL VOXEL AND OBTAIN MR MAPS.
OUR GROUP WAS THE FIRST TO USE
FOR ASSESSMENT OF CALCULUS,
DEVELOPED A SEQUENCE FOR
MULTI-PARAMETER ASSESSMENT OF
CARTILAGE TARGETING RESOLUTION
IN PLANE AND USE RADIAL SECTIONS
OF THE HIP TO ELIMINATE PARTIAL
(INDISCERNIBLE) ALONG THE
THICKNESS, WITH 7-MINUTE SCAN
OBTAIN MAPS ALONG SIX RADIAL
SECTIONS COVERING THE ENTIRE
JOINT.
SIMILAR MR FINGERPRINTING
TECHNIQUE WAS DEVELOPED, ALSO
WITH TIME OF 7 MINUTES, CAN
PROVIDE INFORMATION ABOUT
LIGANDS, COLLAGEN, HYDRATION,
MORE COMPREHENSIVE ASSESSMENT OF
CARTILAGE IN A SINGLE SCAN,
RECONSTRUCTIVE FROM THE SAME
ACQUISITION.
AND EVALUATED AGAINST THE GOLD
STANDARD METHODS SHOWING
QUANTIFIED PARAMETERS ARE HIGHLY
ACCURATE, MATCHING ON THE AXIS.
IT IS MODEL BASED.
DICTIONARY GENERATED WITH BLOCK
EQUATIONS, MATCHED ON SIGNAL, IT
IS ALSO HIGHLY REPRODUCIBLE
ACROSS DIFFERENT MR SYSTEMS AND
REPEATED SCANS.
THE IN VIVO REPRODUCIBILITY
STUDIES SHOW THE PARAMETER
VALUES ARE NEARLY IDENTICAL
ACROSS MR SYSTEMS AND REGULAR
SCANS.
SO, THOSE ARE MR FINGERPRINTING
CAN ALSO HELP WITH OTHER
CHALLENGES CURRENTLY PREVENTING
THE CLINICAL CALCULATION OF
QUANTITATIVE MRI TECHNIQUES.
FOR EXAMPLE, MR FINGERPRINTING
ACQUISITION CONTAINS A LOT OF
DATA AND GENERATES MULTIPLE MAPS
SAME JOINT STRUCTURES HAVE
DIFFERENT DISTRIBUTION OF VALUE,
EXPLOITED FOR AUTOMATIC
CALCULATED SEGMENTATION USING
MACHINE LANGUAGE AN OPEN
CHALLENGE FOR THE HIP AT LEAST.
IN ORDER TO CHARACTERIZE WITH
QUANTITATIVE MRI WE ALSO NEED TO
UNDERSTAND WHAT MR PARAMETERS
TELL US ABOUT UNDERLYING
BIOLOGY.
THIS MEANS WE NEED TO PROCESS
ANNUAL ANALYZE CLINICAL
INFORMATION.
ON THE LEFT DOESN'T PROVIDE MUCH
INSIGHT INTO STANDARDIZED MAPS
THAT ENABLE DETECTION AND
QUANTIFICATION OF EARLY CALCULUS
DAMAGE.
RELIES ON TIME CONSUMING AND
COMPLEX PROCEDURE.
TRANSLATION CAN ONLY HAPPEN I
WOULD SAY WITH AUTOMATIC
PROCESSING PIPELINES.
AND WE HAVE NOT DONE MUCH IN THE
DIRECTION YET BUT
MUSCULOSKELETAL IMAGING TEAM AT
UCSF HAS BEEN AT THE FOREFRONT
AND THE NEXT SPEAKER IS A
PIONEER IN DEVELOPING MACHINE
LEARNING TECHNIQUES.
I WANT TO BRIEFLY HIGHLIGHT HER
GROUP'S WORK ON VOXEL BASED
RELAX OMETRY.
ANOTHER INTERESTING THING WE CAN
DO WITH MR FINGERPRINTING TO USE
SIMULTANEOUSLY ACQUIRED MR MAPS
TO GENERATE SYNTHETIC MORE
THANOLOGIC IMAGES.
THERE ARE SEVERAL ALGORITHMS FOR
THIS AND CLINICAL VALIDATION IS
ONGOING.
THE CLEAR ADVANTAGE WE COULD RUN
A 7-MINUTE FINGERPRINTING
ACQUISITION, IN ADDITION
QUANTITATIVE MAPS GENERATE ALSO
ALL THE STANDARD MR IMAGES
WITHOUT ADDITIONAL SCAN TIME.
THIS COULD FACILITATE CLINICAL
TRANSLATION OF QUANTITATIVE MRI.
>>TWO MINUTES.
>>YES.
I WANT TO CONCLUDE BY SHOWING IN
ADDITION TO USING QUANTITATIVE
MRI, IN CHARACTERIZE OF JOINT
USING MORPHOLOGIC MRI, IN THIS
PAPER THE ACETABULUM SEGMENTED
FROM 3D MRI DATA, MODEL TRAINED
TO DISCRIMINATE WITH AND WITHOUT
WITH 97% SENSITIVITY AND
SPECIFICITY, HIGHER THAN THE
PERFORMANCE OF RADIOLOGIC
METHODS.
FINALLY MORPHOLOGIC MRI CAN BE
USED TO GENERATE 3D MODELS OF
THE JOINT TO PERFORM SHAPE AND
TOPOLOGY ASSESSMENT OR TO
EVALUATE JOINT BIOMECHANICS, AND
THIS IS IMPORTANT BECAUSE JOINT
DISEASE INVOLVE THE WHOLE JOINT.
QUANTITATIVE MAPS OF PHYSICAL
PARAMETERS SUCH AS RELAXATION
TIMES CAN ASSESS UNDERLYING
BIOLOGICAL CHANGES, MODEL-BASED
TECHNIQUES HAVE ENABLED RAPID
AND RELIABLE ACQUISITION OF
MULTIPLE COMPLEMENTARY
QUANTITATIVE MR PARAMETERS.
AND AUTOMATIC PROS EGGS POOP
LINES MAKE CLINICAL TRANSLATION
OF QUANTITATIVE COMPOSITIONAL
MRI A MORE TANGIBLE GOAL AND
QUANTITATIVE INFORMATION
EXTRACTED CAN BE COMBINED WITH
QUANTITATIVE MRI.
I WILL ACKNOWLEDGE MY RESEARCH
SUPPORT, SOME OF MY
COLLABORATORS, AND THANK YOU FOR
YOUR KIND ATTENTION.
>>THANK YOU.
DR. PEDOIA, THE FLOOR IS YOURS.
>>YOU SHOULD BE ABLE TO SEE MY
SCREEN, NOT MY SLIDES YET, BUT
IN A SECOND.
NOW YOU SHOULD SEE MY SLIDES AND
HEAR ME.
THANK YOU FOR THE INVITATION TO
TALK TODAY.
I'M GOING TO ALSO TALK ABOUT
QUANTITATIVE MRI, APPLICATION TO
KNEE OSTEOARTHRITIS, IN
PARTICULAR HOW MODERN TECHNOLOGY
AND MACHINE LEARNING CAN HELP
ADDRESS SOME OF THE PROBLEMS
THAT RICCARDO SHOWED IN THE
PREVIOUS TALK.
AND I'LL START WITH A LITTLE BIT
OF INTRODUCTION ON
OSTEOARTHRITIS, WE ALL KNOW THE
PATHOGENESIS IS STILL LARGELY
UNKNOWN.
THERE ARE FEW THINGS WE KNOW,
CARTILAGE CHANGES AT EARLY
STAGES, INCLUDING HYDRATION,
DESTRUCTION OF COLLAGEN, AND
THIS PROCESS CAN BE PROBED USING
QUANTITATIVE MRI TECHNIQUE, ONE
IS T2 RELAXATION TIMES.
THERE ARE SEVERAL OTHERS BUT
THIS IS ONE THAT PROBED THE
COLLAGEN MATRIX OF THE
CARTILAGE.
WE KNOW IN THE LATER STAGE WE
OBSERVE DEHYDRATION, LOSS OF
CARTILAGE, MRI SCAN IS HIGH
RESOLUTION, HIGHLY RELIABLE
QUANTIFIABLE FROM AN MR, WHILE
THIS HAPPENS AT THE CARTILAGE
LEVEL WE MODELING ALSO MAKES
BONE SHAPE AN IMPORTANT MARKER
TO COMPLETE THE WHOLE JOINT
DISEASE PICTURE.
THOSE CHANGES ARE ALL
INTERCONNECTED AND THE
MECHANISTIC RELATIONSHIP ARE NOT
WELL MODELED YET.
AS WELL THE RELATIONSHIP WITH
CHRONIC PAIN.
AND IF THOSE ARE ALL VERY
EXPENSIVE MARKERS, LONG SCAN
TIME, VERY INTENSIVE
POST-PROCESSING, IT'S DIFFICULT
TO JUSTIFY CLINICAL TRANSLATION
EVEN IF THE SCAN TIME GETS
SHORTER, EVEN IF THE PROCESSING
GETS FULLY AUTOMATIC.
AND DURING THIS TALK I'LL TRY TO
DRAW A PICTURE ON HOW MACHINE
LEARNING CAN HELP IN MAKING THIS
CLOSER TO ACTUAL TRANSLATION,
USABLE FOR PATIENT MANAGEMENT.
DEFINITELY FIRST APPLICATION IS
AUTOMATIC SEGMENTATION, AS WE
SAID THE PROBLEM ON TOP OF LONG
SCAN TIME THESE MAPS NEED TO BE
PROCESSED, SEG MEN TAIGS --
SEGMENTATION IS THE FIRST STEP.
SINCE 2017 GOING ON, TO DEFINE
SEGMENTATION, WELL TRANSLATABLE
AND WELL PERFORMED ON SEVERAL
TISSUE.
IN PARTICULAR, IF ACQUISITION IS
STANDARDIZED,
STANDARDIZED, IN THIS CASE WE
CAN DEVELOP AUTOMATIC PROCESSING
USING CONVOLUTION, 100%
INTERCHANGEABLE WITH HUMAN
PROCESSES.
WE COULD OBTAIN 3D THICKNESS
MAP, THIS IS ONE PATIENT ON THE
OSTEOARTHRITIS INITIATIVE IN
JUST A MATTER OF SECONDS,
EXACTLY AS I CAN OBTAIN THIS ONE
I CAN OBTAIN 45,000 THICKNESS
MAPS YOU'LL OBTAIN ON THE
OSTEOARTHRITIS INITIATIVE WITH
TEN YEARS OF FOLLOW-UP.
AND IF YOU LOOK AT THIS MAP YOU
WILL APPRECIATE THE INFORMATION
IN THE THICKNESS MAP, THIS IS
TRUE FOR THICKNESS, T2
RELAXATION TIMES, MOST OF THE
QUANTITATIVE MARKERS.
BUT WE WANT A WAY TO AGGREGATE
THIS INFORMATION IN A WAY THAT
IS TRACTABLE, USEFUL FOR
POPULATION ANALYSIS, AND WE WANT
TO HAVE EITHER A SINGLE NUMBER
OR SET OF NUMBERS THAT CAN
DESCRIBE THE STATUS OF THIS
CARTILAGE.
WHAT'S DONE IS TO DEFINE REGION
OF INTEREST, BASED ON ANATOMY,
BAGSED ON WHAT -- BASED ON
BIOMECHANIC, MEDIAL SIDE,
LATERAL SIDE, WEIGHT BEARING,
AND TAKE AVERAGES OF THIS
COMPARTMENT.
THIS DOESN'T SOUND NEARLY CLOSE
TO WHAT WE SHOULD DO CONSIDERING
THE RICHNESS OF INFORMATION IN
THIS MAP, AND ALSO HOW MUCH WORK
WAS DONE TO TRY TO GET A PERFECT
SEG
SEGMENTATION, AT ANY VOXEL,
OBTAIN HIGH RESOLUTION IMAGE TO
DESCRIBE THE RICHNESS OF
INFORMATION WITH SIX NUMBERS
THAT COMES WITH AVERAGE.
LIKELY FOR US, DESIGNED TO SOLVE
EXACTLY THIS PROBLEM, DESIGNED
TO AGGREGATE THE INFORMATION IN
THE BEST POSSIBLE WAY TO TRY TO
SOLVE A SPECIFIC TASK,
SUPERVISION OF CONVOLUTION IS
EXACTLY IN EXTRACTING THE
FEATURE, LEARNING THE FEATURES
THAT BETTER DESCRIBE A CERTAIN
PROCESS.
AND WITH THIS IN MIND, WE COULD
ASK A CONVOLUTION TO AGGREGATE
INSTEAD OF DECIDING A PRIORI THE
BEST BIOMARKER IS IN A CERTAIN
COMPARTMENT OR ANY OTHER
PRE-DEFINED MARKER.
THIS IS TRUE FOR ALL THE
BIOMARKERS THAT I SHOULD USE,
WITH THAT WE TRIED WITH A
PROJECT THAT WE RUN A COUPLE
YEARS AGO TO USE CONVOLUTION
BIOMARKER DISCOVERY AND DISCOVER
BETTER WAYS OF AGGREGATING
INFORMATION.
A LITTLE BIT OF TECHNICAL NOTE,
THOSE MAPS NOT EXACTLY SONG THAT
IS EASY TO BE HANDLED IN A
CLASSICAL CONVOLUTION, BECAUSE
BOTH SHAPE IS 3D SURFACE,
THICKNESS IS ALSO MATCHED WITH
VALUES ASSOCIATED WITH THICKNESS
ON SURFACE OF THE CARTILAGE, AND
T2 RELAXATION TIMES IS 3D VOLUME
THAT CAN BE TRANSLATED TO A
MATCH WITH PROJECTION ON
ARTICULAR SURFACE, TO BETTER
WORK ON 2D IMAGES, WE USE
ENCODING BY GOING IN THE CENTER
OF THE BONE, IN THIS CASE FEMUR
BUT WORKS FOR THE HIP AND
ANYTHING THAT HAS SPHERICALL
TOPOLOGY AND UNWRAP
OBTAIN 2 DIMENSIONAL MAPPING, X
AND Y, SPHERICAL ENCODING, THE
VALUE IS THE DISTANCE FROM THE
CENTROID FROM BONE SHAPE, VALUE
OF THICKNESS AT THAT POINT AND
VALUE OF T2.
WITH THAT WE OBTAIN AN IMAGE IN
WHICH EACH SINGLE
(INDISCERNIBLE) LOAD THICKNESS
AND T2 DESCRIBED IN THIS
PARTICULAR POINT, WHAT IS THE
SHAPE OF THE BONE, WHAT IS THE
THICKNESS AND T2 RELAXATION MAP.
CAN I DO ANYTHING BETTER THAN
WHAT AVERAGE BIOMARKER WILL DO,
TRYING PREDICT CHRONIC PAIN?
AND WE USE DATA FROM THE
OSTEOARTHRITIS INITIATIVE,
SELECTED 7,000 PARTICIPANTS.
WE DEFINE CHRONIC PAIN AS
REPORTED KNEE PAIN FOR MORE THAN
50 DAYS OF THE MONTH FOR MORE
THAN SIX MONTHS, WE EXCLUDED
WIDESPREAD BRAIN SYNDROME AND WE
MATCHED SUBJECTS FOR NO PAIN.
AND WE USE THIS TRIPLET AND ALL
THE COMBINATION OF BIOMARKERS.
THIS IS THE SENSITIVITY
SPECIFICITY OF THIS MODEL, SO
UNSEEN IMAGE, A COUPLE THINGS TO
REPORT THE INTERACTION OF THE
BIOMARKERS, SO WHEN I USE THE
THREE BIOMARKERS TOGETHER, IS
WHEN I ACTUALLY MAXIMIZE
SENSITIVITY AND SPECIFICITY AND
AUC OF THIS MARKER, AND WITHIN
DIFFERENT BIOMARKERS WHEN I USE
SINGLE PLANE CARTILAGE T2 BETTER
EXPLAINS BETTER.
WHAT I WANT TO DO IS DISCOVER
THE BIOMARKER, NOT REALLY JUST
TO HAVE A MODEL THAT PREDICT
CHRONIC PAIN.
AND BECAUSE OF THAT WE USE
GRADIENT CLASS ACTIVATION MAP.
THIS IS PROPAGATION TECHNIQUE
IDENTIFY PIXEL MORE IMPORTANT
FOR THE MODEL TO TAKE THE
DECISION ON WHERE -- TAKE THE
DECISION ON THE PATIENT TO BE IN
PAIN OR NOT IN PAIN, AND SO WE
THE WAY IT WORKS WE PASS THROUGH
EACH SUBJECT TO OUR MODELING, WE
OBTAIN PROBABILITY MAP, THAT IS
TELLING US IF THAT PIXEL IS
IMPORTANT OR THAT -- I SHOULD
SAY THAT VERTEX ON THE SURFACE
IS IMPORTANT OR NOT FOR THE
MODEL TO TAKE THE DECISION IF
THIS PATIENT IS IN PAIN OR IS
NOT IN PAIN.
EVERYTHING WE DID ON ENCODING IS
INVERTIBLE, WE CAN GO BACK ON
THE SURFACE.
AND THOSE MAPS ARE DIFFERENT FOR
EACH PATIENT.
SO EACH PATIENT HAS HIS OWN
DIFFERENT CLASS ACTIVATION MAP,
WE CAN RELUCE IN THE SAME SPACE,
AND WE CAN DIVIDE THEM IN TWO
GROUPS, TRUE POSITIVE, THROWS
SUBJECTS IN PAIN AND MODEL
CORRECTLY CLASSIFIED THEM TO BE
IN PAIN, AND THERE I SHOULD FIND
THE FEATURES THAT ARE SENSITIVE
FOR THE PRESENCE OF PAIN.
AND THE TRUE NEGATIVE CASES, AND
ALL THOSE CASES ARE NOT IN PAIN,
MODEL CORRECTLY CLASSIFYING THEM
TO NOT BE IN PAIN.
THERE I SHOULD FIND THE FEATURES
THAT ARE SPECIFIC FOR THE
ABSENCE OF PAIN.
AND THOSE ARE SOME OF THE
RESULTS ON OUR ENTIRE TEST SET,
AND DIVIDED BY THE DIFFERENT
BIOMARKER, AND IF YOU LOOK AT
BONE SHAPE THIS IS THE SIMPLEST
OF THE SITUATION, SO THE MODEL
IS LOOKING IN SPECIFIC LOCATION
TO ASSIGN THE PRESENCE OF PAIN
AND ABSENCE OF PAIN, SO THAT
IS -- WE CAN INTERPRET THE
EXPRESSION OF A CERTAIN FEATURE
IN PARTICULAR IN THE LATERAL
SIDE IN THE TROCHLEA,
PARTICULARLY IMPORTANT FOR BONE
SHAPE, IDENTIFIED THIS PATIENT
IS IN PAIN, NOT IN PAIN, BUT FOR
BOTH THE CARTILAGE BIOMARKER,
THE DISTRIBUTION OF THE FEATURES
THAT ARE SENSITIVE FOR PAIN ARE
DIFFERENT THAN THE FEATURES THAT
ARE SPECIFIC FOR PAIN SO THAT
MEANS IF YOU HAVE CERTAIN
FEATURE IN THE MEDIAL WEIGHT
BEARING REGION, THE MODEL WILL
HIGHLY CONFIDENCE SAY THIS
PATIENT IS IN PAIN BUT WITH
OTHER FEATURE IN THE LATERAL
SIDE IN THE TROCHLEA WILL VERY
WELL CONFIDENT SAY IT IS NO
PAIN.
IT'S NOT EASY TO JUST GET A
SIMPLE AVERAGE THAT THEN
CORRELATES WITH PAIN.
BUT WITH ALL THAT I DIDN'T
REALLY SOLVE MY PROBLEM.
I STILL HAVE THIS MAP.
BUT WHAT I HAVE NOW IS I CAN
INFER THIS MODEL ON ANY NEW
PATIENT AND HAVE A CLASS
ACTIVATION MAP THAT TELL ME WHAT
THE MODEL WOULD LOOK, WHERE THE
MODEL WOULD LOOK TO CLASSIFY
THIS PATIENT AS IN PAIN OR NOT
AND VERY SIMPLY CAN JUST TAKE A
WEIGHTED AVERAGE INSTEAD OF A
SINGLE AVERAGE OF A CERTAIN
QUANTITATIVE MRI TECHNIQUE, AND
GET POSSIBLY A MARKER THAT IS
SIMPLE AGAIN BECAUSE NOW I HAVE
A SINGLE NUMBER, CAN USE THE
OUTCOME FOR CLINICAL TRIAL, BUT
SPECIFICALLY PRECISE FOR THE MAP
OF THIS PATIENT.
>>A MINUTE OR TWO.
>>WE COMPARE THE RESULTS IN
REGRESSING PRESENCE OF PAIN,
CLASSICAL METHOD VERSUS WHAT WE
CALL DL-GUIDED THICKNESS MAP AND
ASSOCIATION WITH PAIN IS MUCH
STRONGER.
THOSE ARE DATA THAT ARE NOT SEEN
IN ANY CLASS OF THE TRAINING OF
THIS MODEL.
WHAT I PRESENTED IS JUST FOR THE
FEMUR FOR SIMPLICITY BUT
EVERYTHING TRANSLATE FOR TBI,
PATELLA, WE HAVE EXAMPLE ON THE
HIP AS WELL.
IN CONCLUSION, WHAT I HOPE I
SHOW TODAY THAT MACHINE LEARNING
CAN SERVE US AS A WAY TO
AUTOMATE THE PROCESS, TO BETTER
AGGREGATE THE INFORMATION, AND
TO DISCOVER NEW WAY OF
AGGREGATING THE INFORMATION THAT
ARE MORE PRECISE AND TAILOR
AROUND THE CHARACTERISTIC OF
EACH SINGLE PATIENT INSTEAD OF
GENERAL FEATURES LIKE AVERAGES
AND CERTAIN COMPARTMENT THAT ARE
CORRECT IN GENERAL BUT NOT
PRECISE ON THE SINGLE PATIENT.
THIS IS THE WORK OF A LOT OF
PEOPLE AT THE CENTER IMAGING AT
UCSF, IN PARTICULAR THIS PERSON
HERE, ALEJANDRO MORALES, MY
Ph.D. STUDENT A COUPLE YEARS
AGO, NOW HAVING FUN IN AMAZON,
THE MAIN PERSON THAT DEVELOPED
THIS PROJECT.
AND THANK YOU VERY MUCH FOR YOUR
ATTENTION.
>>THANK YOU.
NEXT WE HAVE DR. KOCH.
>>I'LL SHARE MY SCREEN HERE.
THANK FOUR THE OPPORTUNITY TO
PARTICIPATE IN THIS SYMPOSIUM.
OUR PROJECT IS LOOKING TO
DEVELOP MRI PROFILES OF CARPAL
BONE MOVEMENTS, LOOKING TO
DEVELOP A TOOL THAT WOULD BE
CAPABLE OF STUDYING COMPLEX
BIOMEDICAL NETWORK IN THE WRIST.
YOU CAN SEE FROM THE FIGURE
EXTRACTED FROM REVIEW ARTICLE ON
DIAGNOSTIC IMAGING THE WRIST,
THE WRIST IS AN INTRICATE
NETWORK OF BONES AND LIGAMENTS,
COMPLEX CONNECTED PROFILE OF
CARPAL DYNAMICS.
CHARACTERIZED BY DISTURBANCE IN
ALIGNMENT AND COORDINATED
MOVEMENT OF BONES AND LIGAMENTS
IN THE WRIST.
THE OVERARCHING GOAL OF OUR
DYNAMIC WRIST IMAGING PROGRAM TO
DEVELOP DIAGNOSTIC TOOLS TO
QUANTITY INTERCARPAL BONE
DYNAMICS TO VERY MANY A TOOL
USED TO ASSESS, TREAT, MONITOR
CARPAL INSTABILITY.
CARPAL IMAGE CAN IDENTIFY IN
DIFFERENT WRIST POSITIONS.
SUSPECTED SOURCES OF LIGAMENT
DAMAGE CAN BE VISUALIZED ON
STATIC MRI.
HOWEVER, LONG AGO REALIZED
LIMITED IN ABILITY IN CAUSE AND
EFFECTS.
OVER 40 YEARS AGO CLINICIANS
STARTED EXPERIMENTING WITH
DYNAMIC IMAGING AS A DIAGNOSTIC
TOOL FOR CARPAL INSTABILITY.
THE ONLY TECHNOLOGY AVAILABLE AT
THAT TIME WAS X-RAY, IN CASE
REPORTS THAT APPROACH PINPOINTED
SPECIFIC CARPAL BONE MOVEMENTS
THAT CAUSED INSTABILITY
SYMPTOMS.
UNFORTUNATELY, 2D IMAGING IS
LIMITED, THEREFORE OVER 20 YEARS
AGO CRISCO AND WOLFE BEGAN USING
DYNAMIC CT TO PERFORM VOLUMETRIC
DYNAMIC ANALYSES OF CARPAL
BONES.
ENSUING DECADES THAT HAS GIVEN
US INSIGHT.
QUANTIFIABLE TRACKING AND
PROFILING OF CARPAL BONE MOTION
HAS BEEN DEMONSTRATED WITHIN
THESE PREVIOUS CT STUDIES.
AND EXPANDING UPON THIS WORK OUR
DYNAMIC IMAGING HAS TWO GOALS,
FIRST TO USE 4D MRI INSTEAD OF
CT, MOST PATIENTS WILL UNDERGO A
CLINICAL MR EXAM, IN ADDITION MR
IS A NON-IONIZING FORM OF
IMAGING, FACILITATING EASIER
STUDIES, USED FOR LONGITUDINAL
ASSESSMENTS.
OUR TEAM DEVELOPED AND APPLIED
DYNAMIC MR APPROACH FOR
CHARACTERIZING CARPAL BONE
MOTION THAT COULD BE INTEGRATED
INTO EXISTING CLINICAL
DIAGNOSTIC IMAGING WORK FLOWS,
IN THAT STUDY DEMONSTRATED THAT
HEALTHY PATHOLOGIC WRIST
KINEMATIC PROFILES EXIST AND CAN
BE DETECTED USING THIS APPROACH.
TODAY TO DATE OUR EXEMPTS HAVE
BEEN DONE AT THREE TESLA USING
THE ACQUISITION POSITIONING
SHOWN IN THIS IMAGE.
SUBJECT'S ARMS FIXED WITH
PADDING, LARGE COIL TO GIVE
RANGE OF MOTION FOR MOVEMENT WE
ANALYZED IN OUR WORK.
NO PHYSICAL MOTION CONSTRAINTS
ARE UTILIZED.
WE DO GIVE PARTICIPANTS A VIDEO
WHICH YOU SEE HERE TO GUIDE
THEIR MOTION AND PACE THEM.
YOU CAN SEE THE MOTION IS PRETTY
SLOW.
THIS IS REALLY IMPORTANT TO GIVE
SUBJECTS A SENSE OF HOW FAST TO
MOVE.
OUR STATIC AND DYNAMIC IMAGES
USE A 2-POINT SEQUENCE, TO GIVE
GOOD CONTRAST TO THE BONES.
I'LL TALK ABOUT WHY THAT'S
IMPORTANT.
WE COLLECT 40 DYNAMIC VOLUMES
FOR EACH MOTION.
SUBJECT IS VISUALLY CUED TO MAKE
THREE CYCLES, INDICATED MOTION
DIRECTION WITHIN 90-SECOND
ACQUISITION, AND HERE YOU CAN
SEE A SINGLE SLICE CAPTURED
THROUGH A FULL DEVIATION MOTION
CYCLE, BUT THESE ARE 3D VOLUMES
THAT WERE ACQUIRED.
THIS IS JUST A SINGLE SLICE
THROUGH THE VOLUMES.
BASIC APPROACH FOR OUR CARPAL
BONE TRACKING IS SIMPLE IN
CONCEPT.
WE SEGMENT BONES.
USING A 3D NEURAL NETWORK,
IMPORTANT TO MAKE THIS VIABLE
AND NOT HAVE PEOPLE SPENDING
DAYS SEGMENTING INDIVIDUAL BONES
THROUGH THE MULTIPLE VOLUMES
THAT ARE COLLECTED.
WE THEN REGISTER THE BONES TO A
STATIC REFERENCE SO WE TAKE
DYNAMIC VOLUMES AND REGISTER TO
STATICS.
AND WE DO THAT THROUGH A POINT
CLOUD SYSTEM.
WE ALSO CONSTRUCT A RADIAL
SYSTEM IN THE WRIST.
SO IN THE END, WHAT THAT GIVES
US IS A REFERENCED SET OF CARPAL
BONE MOTIONS AND MOVEMENTS WITH
6 DEGREES OF FREEDOM IN A RADIAL
CORONET SYSTEM CONSISTENT ACROSS
EACH SUBJECTING.
WE CAN TRACK THREE TARGET BONES,
FOR TWO BASIC MOTIONS WE'RE
INVESTIGATING NOW.
WE AUTOMATICALLY DETECT THE
INDEPENDENT SEPARATE MOTION
CYCLE DOMAINS, SHOWN HERE IN THE
COLORS HERE, AND THAT ALLOWS US
TO LOOK AT REPEAT MEASURES IN
EACH SUBJECT.
WE BASICALLY GET THREE CYCLES OF
MOTION FOR ALL OF THESE METRICS
THAT WE'RE CAPTURING.
IT'S BEEN ESTABLISHED THE
CAPITATE AND THIRD MET A CAR MAL
BONE MOVE SYNCHRONOUSLY, THIS
GIVES A MECHANISM FOR
SELF-REFERENCE ANALYSIS.
WE USED THIS IN TRACKING
METHODOLOGY.
WE LOOKED AT ALL OF OUR METRICS
THIS WAY AND FOUND THAT MOST OF
THOSE DEGREES OF FREEDOM METRICS
SHOWED A LOWER BEHAVIOR, IN THE
PLOTS SHOWING A SUBSET OF
COHORT, EACH SUBJECT REPRESENTED
BY DIFFERENT COLOR.
YOU CAN SEE CLEAR POLYNOMIAL
TRENDS OF INDIVIDUAL SUBJECT
PLOTS HERE.
WE USED THIS TO DERIVE BATTERY
ACROSS MOTION, BONES, KINEMATIC
PARAMETERS.
SEPARATELY LINEAR AND QUADRATIC
FITS PERFORMED FOR EACH MOTION,
WE INDICATE AS PATH.
WE SEE EXPECT THE VARIANCES IN
PATHWAYS, ANTICIPATED AND
ULTIMATELY THE REASON WE COLLECT
MULTIPLE CYCLES OF MOTION IN
EACH EXPERIMENT.
AND THIS APPROACH GIVES US 120
TOTAL CHARACTERISTICS MOTION
METRICS FOR EACH SUBJECT.
OUR INITIAL EXPLORATORY STUDIES
USING THIS APPROACH COLLECTED
DATA ON 49 SUBJECTS, 20 HAD A
HISTORY OF WRIST INJURY, 29 NO
HISTORY OF INJURY OR SYMPTOMS.
IMAGED DOMINANT HAND IN
ASYMPTOMATIC, INJURED HAND IN
INJURED CO-HURT, 29 RECRUITED TO
SAYS STABILITY OF DYNAMIC MR
METRICS.
BECAUSE OF THE HIGHLY
EXPLORATORY NATURE OF THE STUDY
THE INJURED COHORT WAS RECRUITED
OVER SEVERAL MONTHS, BROADLY
RECRUITED BUT BASED ON A
SELF-REPORTED HISTORY OF PRIOR
INJURY.
INITIAL GOAL TO EXPLORE GROUP
CHANGES BETWEEN THE SUBJECTS
WITHOUT HISTORY OF INJURY AND
THOSE WITH HISTORY OF TRAUMA.
OUR INITIAL ANALYSIS LOOKED AT
CONSISTENCY OF METRICS ACROSS
THE FULL COHORT, 17 HAD ICC
VALUES GREATER THAN 7,
MODERATELY CONSISTENT WITHIN
SUBJECTS.
IMPORTANCE OF THIS INTRASUBJECT
STABILITY IS INTERESTING GIVEN
PERCEIVED ABUNDANCE OF WITHIN
SUBJECT INSTABILITY ACROSS THE
METRICS.
HOWEVER, WE DON'T REALLY FULLY
UNDERSTAND THE IMPACT OF HOW
PATHOLOGY OR INJURY INDUCED
CHANGES ARE GOING TO IMPACT
THESE METRICS, WE STILL DON'T
UNDERSTAND HOW THIS INTRASUBJECT
STABILITY FACTORS INTO THINGS.
TO START LOOKING AT THE METRIC
CONSISTENCY ACROSS THE COHORTS
WE USED ICC, LOOKED ACROSS
SUBJECTS WITHIN THOSE SPECIFIC
INJURY COHORTS.
AND IF WE LOOK AT DISTRIBUTION
YOU CAN SEE IMPORTANT TRENDS
HERE.
BASICALLY WE FOUND THAT THE
INJURED SUBJECTS HAD A LOT MORE
VARIATION IN THEIR METRICS, AND
THAT THE SUBJECTS WITHOUT A
HISTORY OF INJURY WERE MUCH MORE
STABLE.
AND WE REALLY ONLY SAW THAT THE
HIGHER LEVELS OF CONSISTENCY IN
METRICS, THAT TOLD US THAT THE
DYSFUNCTION WAS ADDING SOME
INSTABILITY INTO OUR METRICS,
WHICH WAS A GOOD PRELIMINARY
SIGN.
WE ALSO PERFORMED PRELIMINARY
ANALYSES OF THESE DYNAMIC
MEASURES AGAINST RADIOLOGY
IDENTIFYING LIGAMENT AND
CARTILAGE DONE ON A SUBSET OF
OUR STUDY COHORTS USING CLINICAL
STATIC MRI, ON 20 SUBJECTS.
ASSESSED POTENTIAL COVARIATE
IMPACT OF CARTILAGE DAMAGE, SIX
KEY ZONES, CLASSIFIED.
IMAGES SHOWN HERE FROM OUR STUDY
COHORT DEMONSTRATING HOW STATIC
CLINICAL MR USED TO IDENTIFY
PATHOLOGY INCLUDING TEARS,
ABSORPTIONS, ABSENCE OF
LIGAMENTS, AND THE DEGENERATION
THAT MANIFESTED AS PLASTIC
DEFORMATION.
THE ULTIMATE GOAL TO BUILD
MODELS THAT USED MULTIPLE
METRICS TO MODEL COMPLEX
INSTABILITY, HIGHLY ANATOMIC
SOURCES OF INSTABILITY, AS A
PRELIMINARY TEST PERFORMED
INDIVIDUAL CORRELATION TESTS OF
METRICS AGAINST RADIOLOGY,
PATHOLOGY CLASSIFICATIONS OF
LIGAMENTS.
TO REDUCE TESTS FOR EACH WE
REDUCED TEST OF MOST STABLE
WITHIN A SUBCOHORT WITH MINIMAL
DAMAGE TO CARPAL LIGAMENT OR
CARTILAGE, 30 OF THEM WERE FOUND
TO BE SIGNIFICANT WITH P-VALUES
LESS THAN .05, THREE WERE BELOW
OR CLOSE TO SIGNIFICANCE LEVEL.
ALL THREE OBSERVATIONS PROVIDE
CONNECTION BETWEEN DYNAMIC MR
METRICS AND LIGAMENT DAMAGE
CLASSIFICATIONS.
STRONGEST CORRELATION WAS
RELATED TO SCAPHOID POSITION,
PROVIDING ENCOURAGEMENT THESE
DYNAMIC MR MEASURES ARE
INDICATIVE OF UNDERLYING CARPAL
PATHOLOGY.
>>A MINUTE LEFT.
>>OKAY.
COMING TO THE END.
WE PERFORMED A PRELIMINARY
INVESTIGATION INTO USE OF
DYNAMIC MR TO MODEL DIAGNOSTIC
PATHOLOGY.
WE UTILIZE STANDARDIZED
REGRESSION AND IN THE END WE
FOUND THAT WE GOT LIGAMENT
DAMAGE WITH AUC OF .79, THIS
SUBJECT HAD CONFIRMED SCAPHOID
TEAR, WHERE DO WE GO FROM HERE?
WE KNOW MR CAN BE USED TO
COLLECT DYNAMIC 3D IMAGES AND
TRACK BASIC WRIST MOTIONS,
DEVELOPED A MECHANISM TO COMPARE
METRICS ACROSS COHORTS, FUNCTION
OF SYMPTOMS FOR PATHOLOGICAL
CLASSIFICATIONS.
PRELIMINARY ANALYSIS USED THOSE
METRICS, SHOWN LINK BETWEEN THE
DYNAMIC TO RELEVANT MEASURES OF
WRIST DAMAGE.
NOW WE'RE POISED TO ASK
IMPORTANT QUESTIONS ABOUT THE
UTILITY OF THOSE METRICS,
SPECIFICALLY ARE THE METRICS
MORE SPECIFIC TO SENSITIVE
INJURIES, AND INSTABILITY,
PARTICULARLY RELATIVE TO
EXISTING STATIC IMAGING METHODS?
FURTHERMORE, ARE THOSE METRICS
CAPABLE OF IMPROVING DIAGNOSTICS
AND IMPROVING OUTCOMES OR
MONITORING.
I'D LIKE TO ACKNOWLEDGE MY KEY
COLLABORATORS AND OUR SOURCE OF
FUNDING FOR THE STUDY.
THANK YOU FOR YOUR TIME.
>>NEXT WE HAVE DR. YIN.
>>LET ME SHARE MY SCREEN.
I'M HOPING YOU'RE SEEING
PRESENTATION MODE.
>>YES.
>>THANK YOU.
THIS TWO DAYS HAS BEEN AMAZING
LEARNING EXPERIENCE FOR ME.
NOW I REALLY APPRECIATE THIS
OPPORTUNITY TO INTRODUCE THE
SLIP INTERFACE TECHNIQUE THAT
WE'VE BEEN WORKING ON WITH
POTENTIAL TO ASSESS MOBILITY OF
THE MYOFASCIAL INTERFACE.
AS WE LEARNED FROM THE GREAT
TALKS, THERE ARE MANY COMPONENT
CONTRIBUTING TO JOINT
BIOMECHANICS INCLUDING FASCIA
SYSTEM WHICH INCLUDES THE FIRST
LAYER OF LUMBAR FASCIA AND MANY
STRUCTURES SURROUNDING THE
SKELETAL MUSCLES, THE
INTERCONNECTED NETWORK TO
FACILITATE MOVEMENT AND OBTAIN
POSTURE.
IN HEALTHY STATE CAN TRANSMIT
FORCES FOR MOVER.
AND GLIDING SURFACE FOR MUSCLES
TO MOVE AGAINST NEIGHBORING
STRUCTURES, AS WE LEARNED FROM A
TALK THIS MORNING THIS IS DUE TO
NATURAL ELASTICITY AND
LUBRICATING OF HYALURONIC ACID
IN CONNECTIVE TISSUE OF THE
FACTOR.
OVERUSE, MISUSE OR INJURY COULD
DISRUPT AND CAUSE DEGRADE AND
BECOME ENTANGLED WHICH INCREASES
ITS VISCOSITY AND AS A RESULT
THE FASCIA COULD BECOME LESS
MOBILE AND MORE ADHESIVE.
SO, IF WE CAN FIND A WAY TO
RELIABLY MEASURE THE FASCIA
MOBILITY IT COULD OFFER IMAGING
BIOMARKER TO DIFFERENTIATE
BETWEEN HEALTHY FREE-MOVING
FASCIA AND IMPAIRED ADHESIVE
FASCIA IN THE PATIENT WITH
MYOFASCIAL PAIN.
AND TO ASSESS MOBILITY OF FASCIA
I'D LIKE TO INTRODUCE SII, MR
ELASTOGRAPHY MRE-BASED METHOD
FOR TISSUE ADHERENCE.
TWO ADJACENT LAYERS, VIBRATION,
EXHIBIT MORE MOVEMENT, WILL --
CAUSING DISRUPTION ACROSS THE
BOUNDARY.
AND WE CALCULATE SHEAR STRENGTH,
WE NOTICE POTENTIAL VALUES OF
INTERFACE, MRE CALCULATED A
METRIC AS NORMALIZED, AND
ORIGINALLY DEVELOPED SI, TO
EXAMINE THE ADHERENCE, SHOWING
EXAMPLES, NON-ADHERENT HIGH NOSS
VALUES, BUT ADHERENT TUMORS DO
NOT HAVE SLIP INTERFACE.
WE NOTED ALL THE VIBRATIONS
WE'RE WORKING WITH HERE ARE IN
THE MICRO METER RANGE, OUR
TECHNIQUES ARE EXTREMELY
SENSITIVE TO EVEN THE SLIGHTEST
CHANGES IN DISPLACEMENT ACROSS
THE INTERFACE.
AND WE HAVE ALSO ADVANCED OUR
TECHNIQUE BY INCORPORATING
MACHINE LEARNING-BASED APPROACH
TO QUANTIFY ADHESIONS
AUTOMATICALLY IDENTIFIED SLIP
AND NON-SLIP PARTS OF INTERFACE,
AND EXAMPLE WE CAN CALCULATED A
HEARINGS PERCENTAGE OF MENINGEAL
MASS AND HAVE FULLY ADHERENT
TUMORS FROM NON-ADHERENT IN THE
SURGICAL EVALUATION REFERENCE
STANDARD.
EXCITING PART IS WE CAN ALSO
VISUALIZE TUMOR ADHESION IN 3D
VIEW PROVIDING NEUROSURGEONS
VALUABLE VISUAL GUIDE DURING
THEIR SURGICAL PROCEDURES.
SO WE STARTED THIS STUDY BY
ASKING WHETHER IT IS POSSIBLE TO
A
ADAPT USE SI, TO INTERFACE IN
HEALTHY VOLUNTEERS FIRST.
JUST A QUICK RUNDOWN HOW MRE
WORKS, IN GENERAL MRE IS BASED
ON THE IDEA FIRST YOU PUT
MECHANICAL WASTE IN, IMAGE WAYS
WITH MRE SEQUENCE, APPLY
ALGORITHM TO CALCULATE TISSUE
MECHANICAL PROPERTIES LIKE
STIFFNESS, DAMPING OR NOSSED A
HEARINGS.
THE TRICKY PART IS HOW TO
INTRODUCE WAYS TO ENSURE
PROPAGATE NOT ONLY IN TARGET
TISSUE BUT IN DESIGN MANNER THAT
ALLOWS VISUALIZE SLIP INTERFACE.
BY SAYING, FOR EXAMPLE, IN THE
FOREARM, TO KNOW WHETHER SII CAN
BE USED TO LOCALIZE AND
VISUALIZE THE FUNCTIONAL
COMPARTMENTS OF THE FLEXOR
MUSCLES OF THE HAND SUCH AS
FLEXOR DIGITORUM PROFUNDUS, DID
NOT HAVE DISTINCT COMPARTMENTS,
SO TO VISUALIZE IT WITH THE
DRUM-LIKE DRIVER TO CREATE
VIBRATION TO VIBRATION EACH
INDIVIDUAL FINGER, AND VIBRATION
TRAVELS THROUGH THE TENDON
CONNECTED TO THE FOREARM
MUSCLES.
AND YOU'RE SEEING HERE NOSS MAP
DURING VIBRATION OF INDEX
FINGER, AND MIDDLE, RING, LITTLE
FINGER INDIVIDUALLY VIBRATED.
DIFFERENT REGIONS ACTIVATE
ALLIANCE WITH EACH FINGER
FUNCTIONALITY, WE CALL IT
FUNCTIONAL SLIP INTERFACE.
WHEN THERE'S NO EXTERNAL
VIBRATION APPLIED, NOW VISIBLE.
AND MOVING TO THE LEG MUSCLE
LOOKING AT THE DEEP ENTER
MUSCULAR FASCIA, USING DIFFERENT
DRIVING MECHANISMS EMPLOYING
PNEUMATIC AROUND THE THIGH,
ACQUIRED WAVE, YOU CAN SEE HOW
WAVES UPWARD AND DOWNWARD.
MEMORY SCANS WITH KNEE BAND TO
AND LEG STRAIGHT AFFECTING
INTERFACE BETWEEN MUSCLES.
WE KNOW SOME INTERESTING
PATTERNS, FOR EXAMPLE, WHEN THE
KNEE WAS BENT, AND WITH THE
STRAIGHT LEG WE SAW CLEANER
INTERFACES THERE.
WE THINK THIS INTERFACE BECOMES
MUCH CLEARER DURING MUSCLE
CONTRACTION, SO, FOR EXAMPLE, IN
THE BENT KNEE AND KNEE FLEXOR
MUSCLES IN CONTRACTION BUT
EXTENSOR MUSCLES ARE RELAXED,
AND CONVERSELY WHEN KNEE IS
STRAIGHT THE QUADRICEPS IN
CONTRACTION, FROM NOSS MAPS WE
CAN SEE CLEARLY THE CONTRACTED
MUSCLES.
AND SIMILARLY IN THE STRAIGHT
LEG WHERE THE HIP JOINT EXTENDS,
SLOPE INTERFACE OBSERVED AROUND
HIP EXTENSOR MUSCLES, AND KNEE
RELAXATION, THE MUSCLE IN
QUADRICEP ACTS IN HIP FLEXOR AS
SLOPE INTERFACE.
THIS FINDINGS INDICATE S.I. HAS
ABILITY TO DIFFERENTIATE
MYOFASCIAL INTERFACE BETWEEN
DIFFERENT MUSCULAR STATES
SHOWING HOW SENSITIVE OUR
TECHNIQUE IS WHEN IT COMES TO
STUDY MUSCLES.
AND WHEN IT COMES TO LOWER BACK
WE'RE INTERESTED IN STUDY
INTRAMUSCULAR FASCIA INTERFACE
AND THORACOLUMBAR TLF.
WE SAW NOTHING, NOT THE SLOPE
INTERFACE WE WERE EXPECTING, WE
THINK THIS COULD BE DUE TO
UNIQUE CHALLENGES FOR THE LOW
BACK, FOR EXAMPLE THE FAT
SUPPRESSION CAN MAKE IT
DIFFICULT TO VISUALIZE THE
FASCIA STRUCTURES WE'RE
INTERESTED, AND ALSO DEEP FASCIA
OF THE TRUNK BEHAVIOR
DIFFERENTLY FROM THE LIMBS.
WE NEED TO TAILOR TO TRIGGER
RELATIVE MOTION BETWEEN THE
DIFFERENT FASCIAL LAYERS TO
VISUALIZE THE INTERFACE HERE.
FIRST WE DEVELOPED OUR VAST
ACQUISITION TECHNIQUE THAT
ALLOWS WATER AND FAT SIGNALS TO
ENHANCE, ON THE RIGHT, TO
ENHANCE THE CONTRAST, THE
SIGNALS WE COULD LIKE TO SEE
FROM THE FASCIA STRUCTURE.
ALSO GIVING LOW BACK MUSCLES THE
LONGITUDINALLY AND AS A MUSCLE
GROUPS WITH MULTIPLE MUSCLE
BUNDLES WITH DIFFERENT
ORIENTATION, EXTENSIVELY TEST
THE DRIVER VERSIONS AND
EVENTUALLY DISCOVERED A BELT
DRIVER WRAPPED AROUND L4/L5 DISC
PROVED TO BE THE MOST EFFECTIVE
SOLUTION.
AND AS A RESULT OF THIS
ADAPTION, IMPROVEMENT IN THE
ALGORITHM, WE HAVE ACHIEVED
POTENTIAL IMPROVEMENTS FROM
NOTHING TO A CLEAR DETAILED
DEPICTION OF THE POSTERIOR,
MID-ING, ANTERIOR LAYERS OF TLF
ASKER WITH AS OTHER
INTRAMUSCULAR INTERFACES.
IN HEALTHY VOLUNTEERS, WE DO SEE
THAT SUCCESS FOR ADAPTION FROM
THE BRAIN TO MUSCLE, VISIBILITY
OF VISUALIZING AND CODIFYING THE
MYOFASCIAL ENTER INTERFACE HAS
SENSITIVITY TO DIFFERENT MUSCLE
STATES WHICH IS GOOD, BUT ALSO
POSE CHALLENGES IN CONTROLLING
FOR VARIATIONS IN THE MUSCLE
STATES ACROSS THE DIFFERENT
HEALTHY INDIVIDUALS AND PATIENT
COHORTS.
AND THE OPTIMIZATION OF
COLLABORATIVE (INDISCERNIBLE) IS
A KEY ROLE, WORKING FURTHER WITH
DRIVERS, EVENTUALLY DEVELOPED
HIGH RESOLUTION IMAGING
PERFORMING TESTS SCANS TO
UNDERSTAND AND DO THE PILOT
CLINICAL SCANS WITH THE CLINICAL
PHYSICAL TIME FRAME.
WE HOPE THAT THIS COULD PAVE THE
WAY FOR APPLYING SII TO
DIFFERENTATE BETWEEN HEALTHY
FASCIA AND INJURED OR IMPAIRED
FASCIA IN PATIENTS WITH
MYOFASCIAL PAIN.
I'D LIKE TO THANK MY COLLEAGUES
AND THE EMORY LAB AND MY OWN
TEAM, ESPECIALLY THE BIOMARKER
PROGRAM, AND THANK YOU FOR YOUR
ATTENTION.
>>THANK YOU.
NOW WE MOVE INTO THE PANELIST
COMMENTS SECTION.
FIRST DR. BANKS.
>>GOOD AFTERNOON.
JUST A BRIEF INTRODUCTION, SCOTT
BANKS, UNIVERSITY OF FLORIDA,
PROFESSOR OF MECHANICAL AND
AEROSPACE ENGINEERING, 40 YEARS
WORKING WITH ORTHOPEDIC SURGEONS
AND MEDICAL DEVICE COMPANIES TO
HELP SURGEONS GET BETTER
RESULTS, WORK FOCUSED ON JOINT
ARTHROPLASTY, KNEES AND SOME
EXTENT SHOULDERS, THE WORK HAS
BEEN INVOLVING NEW IMAGING
TECHNIQUES, DYNAMIC FLUOROSCOPY,
3D MEASUREMENTS, COMPUTATIONAL
MODELS, A LOT OF IMPLANT DESIGN.
I HAVE A LOT OF RELEVANT
CONFLICTS IF WE TALK ABOUT JOINT
REPLACEMENTS. YESTERDAY THE
COMMENT WAS MADE KNEE
REPLACEMENTS ARE REALLY GOOD,
80% OF PEOPLE ARE PRETTY
SATISFIED.
IT'S THE 20% THAT KEEP ME UP AT
NIGHT, TO BE HONEST.
THAT'S WHAT DRIVES OUR FOCUS
THAT, MAKING THAT A MORE
REPRODUCIBLE AND BENEFICIAL
OUTCOME.
RIGHT NOW THERE'S 2 2 250,000E
WITH A WIDGET IN THEM OFF MY
DESK, I'M CONCERNED ABOUT THAT
COHORT.
I APPRECIATE THE OPPORTUNITY AS
A SORT OF HEAVY METAL
ORTHOPEDICS PERSPECTIVE TO
PARTICIPATE IN THIS.
AND I DO HAVE SOME COMMENTS AND
QUESTIONS WHEN WE GET TO THAT
WITH OUR PANEL.
>>THANK YOU.
DR. KOGAN?
>>HI.
THANKS FOR HAVING ME ON THE
PANEL.
I'M ASSISTANT PROFESSOR OF
ROILING AT STANFORD, MY FOCUS ON
IMAGING METHODOLOGY MRI,
RECENTLY PET MRI.
I THOUGHT TALKS WERE GREAT AND
LIKED THIS SESSION.
I WANT TO ADD TWO KEY AREAS THAT
I THINK WILL FOLLOW WITH WHAT WE
HEARD A LOT TODAY AND YESTERDAY
AS WELL, WHICH IS SOME FOCUS ON
FUNCTION AND WHOLE JOINT
DISEASE.
IMPORTANT TO NOTE MOST OF OUR
IMAGING METHODOLOGIES ARE
ACQUIRED IN A STATIC AND
OFTENTIMES UNLOADED
CONFIGURATION, AND SO THE MORE
WE CAN DO TO ASSESS FUNCTION
WITH IMAGE AING, KEVIN GAVE A
GREAT TALK, SORT OF HOW TISSUE
PROPERTIES CHANGE UNDER LOAD.
AND OTHER MODALITIES SUCH AS
DUAL CHEMICAL FLUOROSCOPY, PET
METHODS, SO THERE'S REALLY GOOD
WORK COMING OUT AND I HOPE IT
CONTINUES, AS WELL AS GUIDANCE
ON HOW THAT CAN BE USED TO
REALLY GUIDE CLINICAL DECISIONS.
THE SECOND POINT, WHOLE JOINT
DISEASE FOR A LONG TIME WE
FOCUSED ON CARTILAGE.
WE'VE GONE AWAY FROM THAT IN THE
LAST DECADE BUT CAN DO MORE.
WE HEARD ON THE MRI SIDE WE CAN
LOOK AT MULTIPLE TISSUES.
I'VE BEEN PARTICULARLY
INTERESTED IN HOW WE CAN ADD
MOLECULAR INFORMATION TO THAT
WITH PET, POSSIBILITIES TO LOOK
AT INFLAMMATION AND BONE
REMODELING WITH THE STRUCTURE
AND COMPOSITION WE GET WITH MRI.
LASTLY THE FOCUS ON PAIN, THIS
CAME UP A LOT YESTERDAY THAT
IMAGING OF STRUCTURE DOESN'T
REALLY CORRELATE PARTICULARLY
WELL WITH PAIN.
AND SO IF WE CAN SOMEHOW ASSESS
BETTER THOSE MARKERS OF PAIN TO
BE ABLE TO SEPARATE OUT WHAT IS
PAIN, WHAT IS PSYCHOSOMATIC, WHO
IS O.A., WHAT MAY BE SOMETHING
ELSE IN THE JOINT, AGAIN I THINK
THERE SORT OF PET IMAGING OF
NEUROPATHIC SOURCES OF PAIN AS
WELL AS NEWER TRACES THAT ARE
COMING OUT TO LOOK AT SPECIFIC
UPREGULATED PAIN RECEPTORS SUCH
AS SIGNAL 1 ARE PROMISING THERE.
>>THANK YOU.
DR. CEVIDANES.
>>MAY I SHARE MY SCREEN
BRIEFLY?
>>SURE.
>>OKAY.
SO JUST BRIEF BACKGROUND, I
THINK I'M THE ONLY DENTIST IN
THE PANEL, FOCUSED ON A SMALL
JOINT, THE TEMPOROMANDIBULAR
JOINT, WHICH HAS A DIFFERENT
PHYSIOLOGY AND ANATOMY B
ECAUSE -- THAN LARGER JOINTS,
IT'S EVEN MORE SUSCEPTIBLE FOR
BONE CHANGES, A GOOD MODEL TO
STUDY BONE CHANGES.
THANK YOU SO VERY MUCH FOR NIH
ORGANIZATION OF THIS SUPER
IMPORTANT SYMPOSIUM.
MY WORK, HOPEFULLY WHAT I CAN
ADD TO THE DISCUSSION IN THIS
PANEL, HAS FOCUSED ON
INTEGRATING IMAGING BIOLOGICAL
AND IMAGING MARKERS, WE HAVE
IDENTIFIED BIOMARKERS OF ADULT
TMJ OSTEOARTHRITIS OR
DEGENERATIVE JOINT DISEASE.
AS WELL AS WORK ON PREDICTIVE
MODELS OF ADULT PROGRESSION AND
WITH REGARD TO THAT RECENT WORK
HAS DEVELOPED IN ENSEMBLE MODEL,
TOP PERFORMING MODELS FOR
CROSS-VALIDATION, WHAT WE'VE
FOUND IS THAT THE TOP
CONTRIBUTING PREDICTORS OF
IMPROVED OR WORSE PROGNOSIS AT
THE CONSERVATIVE TREATMENT IN A
TWO-YEAR FOLLOW-UP WERE ACTUALLY
CO-MORBIDITS, INTERESTINGLY
COMORBID PAIN CONDITIONS AS WELL
AS MOUTH OPENING WERE AMONG TOP
CONTRIBUTORS, LOOK FORWARD TO
FURTHER DISCUSSION WITH THE
PANEL, WITH MY BACKGROUND.
THANK YOU.
>>THANK YOU.
DR. SIKDAR?
>>GOOD AFTERNOON.
THANK YOU FOR HAVING ME ON THIS
PANEL.
I'M A PROFESSOR OF
BIOENGINEERING, GEORGE MASON
UNIVERSITY.
I'M PART OF AN INTERDISCIPLINARY
GROUP, MYOFASCIAL PAIN.
AND THE POINT I WOULD LIKE TO
MAKE IS THAT WE'VE HEARD A LOT
ABOUT THE COMPLEXITY OF THE
PROBLEM FROM MULTIPLE
PERSPECTIVES, INCLUDING
BIOPSYCHOSOCIAL.
THE CHALLENGE FOR BIOMARKER
DISCOVERY IS THAT WHEN IT COMES
TO CHRONIC PAIN WE'RE TRYING TO
DIFFERENTIATE NORMAL ADAPTATION
VERSUS MALADAPTATION, WHOLE
JOINT LEVEL, PERHAPS WHOLE HUMAN
LEVEL.
LOOKING AT INDIVIDUAL
STRUCTURES, EVEN DYNAMICS OF
INDIVIDUAL STRUCTURES, ONLY
GIVES US A PIECE OF THE PUZZLE.
WHAT WE REALLY WOULD LIKE TO
KNOW IS HOW THE DIFFERENTIATE
WHAT NORMAL PROCESS OF
ADAPTATION TO INJURY,
INFLAMMATION, TO AGING, AS WELL
AS OTHER FACTORS ARE COUNTER
BALANCED BY PLASTICITY, AT WHAT
POINT DOES EQUILIBRIUM BECOME
UNSTABLE, WE WOULD LIKE TO TRY
TO UNDERSTAND TRANSITION TO
CHRONIC PAIN.
INDIVIDUAL BIOMARKERS ARE ONLY
GIVING US A SNAPSHOT OF THIS
COMPLEX PROBLEM.
SO WHAT WE REALLY NEED IS MODELS
TO INTERPRET MULTIMODAL
BIOMARKERS.
I LOOK FOR WASHED TO THE --
FORWARD TO THE DISCUSSION.
>>THANK YOU.
NOW WE MOVE INTO THE PANEL
DISCUSSION SEGMENT.
FIRST, SCOTT?
>>FOUR YEARS INTO THIS WHEN ARE
WE GOING TO LEARN TO UNMUTE?
I WANT TO COMPLIMENT THE
SPEAKERS.
FABULOUS TECHNOLOGIES.
AND REALLY EXCITING PROSPECTS.
I WANTED TO SHARE A LITTLE
PERSPECTIVE AND KIND OF ASK THE
SPEAKERS FOR THEIR PERSPECTIVES.
IT WAS IN THE LATE '80s THAT I
REPORTED A METHOD TO MEASURE
KNEE REPLACEMENT MOTION IN THREE
DIMENSIONS, A LOT OF EXCITEMENT
WITH SURGEONS, SCOTT, THAT'S
GREAT, BUT THERE'S ALWAYS A
"BUT."
YOU REPORTED ON STAIR CLIMBING,
MY PATIENTS ALSO WALK OR TRY TO
HAVE DEEP FLEXION.
OR THERE WAS -- I'M TREATING THE
KNEE BUT I THINK THE PROBLEM IS
FOOT, ANKLE, HIP, LOW BACK.
AND SO ONE QUESTION FOR THE
SPEAKERS IS CONTEXTUALIZING
THEIR REGION OF INTEREST WHERE
THEY ARE MAKING MEASUREMENTS
EITHER FOR A GAMUT OF DYNAMIC
OBSERVATIONAL OPPORTUNITIES OR
INTEGRATING IT INTO SORT OF THE
WHOLE PERSON AND SYMPTOM
SOMETHING.
THE OTHER THINK, FEEDBACK FROM
SURGEONS, IS THAT'S GREAT, VERY
INTERESTING STUDY.
I DON'T REALLY DO THAT.
HOW CAN I USE THIS METHOD ON MY
PATIENTS?
SO IF THE PANELISTS WOULD BE
WILLING TO MAYBE COMMENT ON THE
PATHWAY OR TRAJECTORY, MAYBE NIH
FUNDING THEY NEED A VERY
PROMISING IMAGE AND ANALYSIS
METHOD TO SOMETHING CLINICALLY
IMPLEMENTABLE AND PRACTICAL.
THANK YOU.
>>I CAN COMMENT.
I HAVE THOUGHT ABOUT THIS A LOT
WITH OUR DYNAMIC WRIST PROGRAM.
ESPECIALLY IN A PAST LIFE, I WAS
ONCE IN THE DEVICE INDUSTRY.
I THINK HOW THINGS WILL ACTUALLY
GET OUT THERE.
IT'S A BIG CHALLENGE.
I DON'T KNOW IF I HAVE THE RIGHT
ANSWER FOR WHAT THE NEXT SORT OF
NIH FUNDING IS TO TAKE IT THERE
BECAUSE A LOT OF THE THINGS YOU
NEED TO DO TO TRANSLATE IT AND
GET IT TO THE POINT WHERE IT
COULD BE USED WIDELY IN THE
CLINIC ARE NOT THINGS THAT SELL
WELL IN AN R01 PROPOSAL.
AND SO ONE KEY IS I THINK YOU
HAVE TO HAVE AN INDUSTRY TARGET,
SOMEBODY TO PARTNER WITH,
WHETHER IT'S A BIG VENDOR OR
SMALL BUSINESS, WITH A SMALL
BUSINESS YOU CAN GO INTO THE
SMALL BUSINESS FUNDING
OPPORTUNITIES AND THINGS.
THAT'S PART OF IT.
THAT'S REALLY NUTS AND BOLTS
LOGISTICS ISSUES.
FROM A MORE TECHNICAL
STANDPOINT, ONE OF THE THINGS
I'VE NOTICED IS FOCUSING, LIKE
YOU SAID, FOCUSING ON SPECIFIC
QUESTIONS AND TARGETS THAT ARE
HOPEFULLY BROADLY APPLICABLE IN
THE WRIST CASE, THE REASON I
ACTUALLY GOT INTO THIS, THIS WAS
A WEIRD THING FOR ME TO GET INTO
SEVERAL YEARS AGO.
I JUST HAD, YOU KNOW, A SURGEON
AND RADIOLOGIST ASK ME IF WE
COULD DO DYNAMIC IMAGING OF THE
WRIST BECAUSE THEY HAVE ALWAYS
STRUGGLED TO UNDERSTAND THE ROLE
OF THE INTRINSIC AND EXTRINSIC
CARPAL LIGAMENTS MANAGING
INSTABILITY.
THAT'S BEEN THE GUIDING FOCUS OF
THE ENTIRE PROGRAM.
IT'S A VERY TARGETED QUESTION.
IT'S CARPAL INSTABILITY, AND
IT'S THE ROLE OF THESE
LIGAMENTS, AND THE SURGEONS HAVE
VERY SPECIFIC TARGETS ON IT.
I MEAN, THEY GO IN WITH SPECIFIC
APPROACHES, AND KNOWING WHICH
LIGAMENTS ARE GOING TO BE
IMPACTED AND MAYBE SOMEDAY
HAVING SOME GUIDANCE ON HOW THEY
MIGHT BE ABLE TO STRATEGICALLY
PERFORM THOSE REPAIRS, OR WHEN
TO PERFORM REPAIRS.
IT'S A VERY FOCUSED QUESTION
BECAUSE I AGREE WITH YOUR
CONCERN.
IF IT'S TOO BROAD AND NOT
CLEARLY APPLICABLE, THE UPTAKE
IS GOING TO BE TOUGH.
EVEN IF YOU ARE ABLE TO
COMMERCIALIZE IT.
NOBODY'S USES IT, RIGHT?
SO THOSE ARE MY TWO CENTS ON IT.
>>LET ME TRY TO ADD SOMETHING
ON THE CLINICAL TRANSLATION
SIDE.
I FIGURE THAT TECHNICAL
INVESTIGATORS THAT WORKS A LOT
ON MAKING IMAGING FASTER, MAKING
THE PROCESS AUTOMATIC, AND OFTEN
WE START, WHEN ONE DESCRIBED,
YOU KNOW, BULLET POINTS ON WHY
THIS TECHNIQUE IS NOT CLINICAL
TRANSLATABLE, SORE NOT
CLINICALLY TRANSLATED YET OFTEN
STARTS WITH TECHNICAL OBSTACLES.
WE FOCUS ON SOLVING TECHNICAL
OBSTACLE FORCE, AND OFT WEAN
FORGET TO IMAGINE THE SCENARIO,
OKAY, LET'S IMAGINE SCENARIO IN
WHICH ALL OF THESE ARE SOLVED,
WHAT WILL BE THE -- IS THIS
ACTIONABLE FOR REAL?
EVEN IF IT WILL BE A SECOND
ACQUISITION, EVEN IF THE PROCESS
WILL BE COMPLETELY AUTOMATIC, SO
WHAT?
WHAT ARE RADIOLOGISTS OR
ORTHOPEDIC SURGEON WILL CHANGE
THE CLINICAL MANAGEMENT, NOW
THAT HE HAS THIS ADDITIONAL
INFORMATION ON THE PLATE?
AND OFTEN THE DISCUSSION COMES
EITHER AFTER OR IS NOT THE FIRST
QUESTION TO ASK, AS, OKAY, THE
PROBLEM, WHY MRI IS NOT
TRANSLATED, BECAUSE IT'S SLOW,
BECAUSE THE PROCESS IS LONG, AND
I'M NOT SURE THE PROBLEM IS
THERE.
WE KNOW OR WE CAN SOLVE THAT,
BUT MAKING IT ACTIONABLE IS
WHERE THE REAL PROBLEM IS.
AND I THINK THERE IS A VERY
IMPORTANT APPLICATION IN
RESEARCH WHICH STILL MAKES
INCREDIBLY VALUABLE, SO THE
ABILITY OF PREDICTING WITH
CERTAIN PROBABILITY, INCIDENCE
OF OSTEOARTHRITIS IN A SUBJECT
WITH KNOW RADIOGRAPHIC EVIDENCE
COULD BE GAME CHANGING
INCLUSION
IN CLINICAL TRIALS, RELIABLE
DATA, INCLUSION CRITERIA FOR A
LARGE EPIDEMIOLOGY STUDY
PROBABLY WILL BE ABLE TO OBSERVE
THE PATHOGENESIS OF THE DISEASE
BETTER BECAUSE WE CAN ACTUALLY
PREDICT WHO IS GOING TO
PROGRESS.
YEAH, SO PROBABLY THOSE ARE MY
TWO POINTS ON THE TRANSLATION.
>>IF I CAN ADD, I AGREE WITH
VALLENTINA, TO ACT ON THE
INFORMATION IS IMPORTANT BUT FOR
THAT NOT ONLY WE NEED
PARTNERSHIP WITH INDUSTRY, WE
NEED PARTNERSHIP WITH SURGEONS
BECAUSE OFTEN THE MAIN ISSUES
THAT SURGEONS ARE NOT VERY
WILLING TO COLLABORATE, DON'T
KNOW WHAT THEY NEED.
BUT IT'S HARD TO UNDERSTAND
THEIR NEEDS AND MAYBE WE SHOULD
DO IT ALL THE WAY AROUND, WE
TELL THEM WHAT TO DO BY USING
OUR FINDINGS, AND ALSO I MEAN A
LOT OF THE CORRELATION WITH
CLINICAL MRI, OFTEN BASED THAT
GROUND TRUTH IS GROUND TRUTH,
BUT SOMETIMES IT'S NOT A GROUND
TRUTH, OFTEN IF IT'S NOT
SOMETHING THAT'S GOING TO
CHANGE, PAY A LOT OF ATTENTION
IN DOING THIS ANNOTATION, ALL OF
THE SAME, IMPOSSIBLE FOR TEN
PATIENTS, SO I THINK IF THEY
REALLY WANT US TO DEVELOP
SOMETHING THAT'S NEEDED
TRANSLATED CLINICALLY, THEY NEED
TO BE PARTNER TO BE INVOLVED IN
KIND OF GRANT SUBMISSION AND
INVOLVED IN THE WORK.
>>I CAN FOLLOW UP A LITTLE BIT
ON ALSO SORT OF WHAT VALENTINA
TALKED ABOUT, AS WE HEARD TODAY
SCANS ARE BECOMING SO MUCH MORE
EFFICIENT IN TERMS OF NOT ONLY
SORT OF HOW FAST THEY ARE BEING
RUN BUT AMOUNT OF DATA THAT'S
BEING COLLECTED.
YOU CAN DO A SINGLE SCAN AND GET
MULTIPLE MAPS, VOLUME RENDERING,
BONE SHAPE, SO THIS IS GREAT FOR
DATA STANDPOINT OF STUDYING
DISEASE.
IT'S NOT NECESSARILY GREAT FROM
LIKE AN OVERLOADING THE
CLINICIAN STANDPOINT.
SO I THINK THERE NEEDS TO BE
MORE DONE ON ANALYSIS FRONT TO
SORT OF SAY THIS IS THE MEASURE
THAT YOU SHOULD BE USING, AND
PARTICULARLY CARRYING TO THE
APPLICATION.
I WILL SAY THAT PARTICULARLY FOR
QUANTITATIVE IMAGING THE
CLINICAL ROLE MAY NOT BE THERE
YET, BUT I THINK THERE WILL BE A
TIME WHEN THERE WILL BE A ROLE
FOR QUANTITATIVE IMAGING, AND
FOR ME THAT I THINK WILL COME
WHEN THERE ARE TREATMENTS.
PARTICULARLY FOR D MODES, THEY
ARE ALL TARGETING CARTILAGE,
BONE REMODEELING, INFLAMMATION,
BEING ABLE TO SELECT WHICH
PATIENTS ARE GOING TO BENEFIT
FROM DRUGS I THINK WILL BE A BIG
ROLE NOT ONLY IN HELPING THE
SORT OF TRIALS BUT ALSO ONCE
THEY GET INTO THE CLINICS TO BE
ABLE TO SAY LIKE THIS PERSON
WILL BENEFIT FROM THIS, AND
MONITORING SHORTLY AFTER SO THEY
ARE NOT ON A VERY EXPENSIVE
BIOLOGIC FOR SUPER LONG.
THE SYSTEMS QUESTION, I THINK
THAT ONE IS REALLY HARD, BECAUSE
I THINK A LOT OF THESE THINGS
ARE SYSTEMS-TYPE, YOU KNOW,
REASONS WHY YOU MIGHT BE HAVING
PAIN.
BUT YOU COME IN WITH KNEE PAIN
AND THE IDEA OF DOING LIKE A
WHOLE LOWER LIMB SCAN, YOU KNOW,
I THINK WE'RE REALLY FAR AWAY
FROM THAT.
SO, AGAIN, I THINK THAT WOULD BE
INTERESTING TO PUT MORE EMPHASIS
ON THAT FROM A RESEARCH
STANDPOINT BECAUSE I DON'T THINK
WE'RE THERE YET ON RESEARCH
BASIS BUT CLINICALLY, AGAIN, THE
ONLY THING I'VE SEEN IS LIKE
MAYBE BACK PAIN LOOKING FOR
NEUROPATHIC PAIN SOURCES.
BUT IT'S VERY LIMITED.
>>THANK YOU.
THERE'S ANOTHER QUESTION FOR THE
PANELISTS, RELATED TO WHAT WHAT
JUST MENTIONED.
IN LIGHT OF BIOLOGICAL AND
MOLECULAR MECHANISMS THAT HAVE
BEEN DISCUSSED OVER THE TWO
DAYS, CAN YOU DESCRIBE
PRIORITIES IN TERMS OF
ADDITIONAL DATA OR METHOD THAT
COULD ENHANCE PREDICTIVE
VALIDITY OR AC ACCURACY OF YOUR
APPROACH AND IDEAL COMPOSITE TO
PREDICT PATIENT PAIN OR
FUNCTION?
>>MAYBE I CAN WEIGH IN.
SO, I THINK WE HEARD FROM REALLY
EXCELLENT TALKS ON DIFFERENT
BIOMARKERS AND DIFFERENT REALLY
AMAZING IMAGING METHODS.
ALSO LOOKING AT MULTIPLE
DIFFERENT TYPES OF TISSUES.
I THINK THAT CRITICAL THING
WE'RE LACKING IS ABILITY TO
STUDY THESE THINGS OVER TIME,
AND UNDERSTAND WHAT IS A NATURAL
PROGRESSION AND NATURAL
ADAPTATION VERSUS WHAT IS
ABNORMAL ADAPTATION.
SO THAT, TO ME, IS A VERY TRICKY
CHALLENGE BECAUSE OBVIOUSLY
BEING ABLE TO DO SERIAL IMAGING
SCANS ON THE SAME PERSON OVER A
LONG PERIOD OF TIME IS
LOGISTICALLY CHALLENGING AND
CLINICALLY NEARLY IMPOSSIBLE,
PERHAPS.
SO THE QUESTION IS HOW CAN WE
FIGURE OUT WHAT IS A MINIMAL SET
OF DATA WE CAN TRACK OVER TIME
TO REALLY UNDERSTAND THE SORT OF
TRAJECTORY OF THE PAIN SYNDROME,
AND TRY TO UNDERSTAND WHAT IS AN
ABNORMAL ADAPTATION.
>>AND CONNECTING WHAT YOU'RE
SAYING WITH WHAT FELIKS WAS
SAYING, ANSWERING THE MINIMUM
VALUABLE SET OF DATA WE SHOULD
COLLECT ON A PATIENT, I THINK
THE PROBLEM IS MORE ON HAVING
SOMETHING THAT IS ABLE TO
PHENOTYPE THE PATIENT FIRST, AND
THEN TRIAGE THE MINIMUM SET OF
DATA BECAUSE FOR A CERTAIN
PATIENT, THOSE DATA MIGHT BE
RELATED TO THE SHAPE OF THE BONE
AND FOR THAT PATIENT YOU MIGHT
WANT TO INVEST IN A PET SCAN AS
WELL BECAUSE IT'S REALLY ABOUT
INFLAMMATION, AND IT'S REALLY
ABOUT BONE REMODELING FOR HIM OR
FOR HER.
AND FOR ANOTHER PATIENT IT'S ALL
CARTILAGE.
AND HAVING FIRST TRIAGING AND
PHENOTYPING, IT'S PROBABLY WHAT
WE ARE LACKING AND BEING ABLE TO
PHENOTYPE CORRECTLY THE PATIENT
WILL SOLVE A LOT OF THE OTHER
PROBLEM IN OVERLOADING OF
INFORMATION, DECIDING WHAT IS
BEST, MAKING SCANNER SHORTER,
BUT PERSONALIZE THE DATA
COLLECTION IS PROBABLY WHAT CAN
SOLVE A LOT OF THE DOWNSTREAM
PROBLEM THAT WE'RE DESCRIBING.
>>COLLAGEN SCANNING, RIGHT?
YOU SCAN AND DO MORE SCANS AS
YOU LEARN BETTER METHODS.
>>IF I CAN FOLLOW UP, ONE MORE
POINT TO THAT, SO I THINK WHEN
WE TALK ABOUT CHRONIC PAIN
OBVIOUSLY CENTRAL SENSITIZATION
IS ONE OF THE KEY DRIVING --
UNDERLYING MECHANISMS.
IT IS VERY DIFFICULT TO
SOMETIMES DISASSOCIATE WHAT IS
THE PRIMARY DRIVER FOR CENTRAL
SENSITIZATION VERSUS SECONDARY
DOWNSTREAM EFFECT.
AND THIS IS, AGAIN, SOMETHING
THAT NEEDS TO BE INVESTIGATED A
LITTLE BIT MORE TO UNDERSTAND
WE'RE FINDING DIFFERENCES
BETWEEN PAIN GROUP AND NON-PAIN
GROUP.
BUT WHAT EXACTLY IS PRIMARY
DRIVER FOR THE UNDERLYING
CENTRAL SENSITIZATION, WHAT IS
SECONDARY MANIFESTATION.
>>I WOULD JUST LIKE TO BRING UP
A QUESTION FOLLOWING UP TO
VALENTINE'S A INTERESTING
PRESENTATION, SHE PRESENTED
SALIENT MAPS, CAN OCCUR BY
CHANCE WITH THE CHALLENGES OF
THE IMAGE ANALYSIS PERCEIVED BUT
MOVING BEYOND WHAT YOU ARE
MENTIONING OF BINARY PAIN VERSUS
NO PAIN, IS IT POSSIBLE TO FOCUS
ON TESTING CORRELATIONS WITH
PAIN LEVELS IN THE ASSOCIATED
COMORBIDITIES WHICH I THINK IS A
NEEDED STEP, RIGHT?
ANY COMMENTS, VALENTINA?
>>THERE IS -- IT'S A TRICKY
BECAUSE THEN YOU GO BACK TO THE
MOVING TARGET OF GROUND TRUTH
BECAUSE -- IN THAT SPECIFIC
PROJECT, WE CHOOSE CHRONIC PAIN,
PRESENCE OF CHRONIC PAIN IN
PARTICULAR, CHRONIC PAIN AS
PROLONGATED PERIOD OF TIME, THAT
MAKES THE OUTCOME WAY MORE
RELIABLE.
AND IF YOU START MOVING FROM
THAT TO A CONTINUOUS PAIN, YOU
HAVE SO MUCH SUBJECTIVITY GOING
INTO THE PICTURE, AND YESTERDAY
WAS SOME INTERESTING TALKS AND
SOME WORK DOING ALSO HERE AT
UCSF ON THE LOWER BACK PAIN
PROJECT TO TRY TO OBJECTIFY
PAIN, FUNCTIONAL MRI, FUNCTIONAL
CONNECTIVITY INTO THE PICTURE,
SO WHEN WE START GOING TO LEVEL
OF PAIN I THINK WE NEED TO ALSO
WORK ON MAKE THE OUTCOME MORE
RELIABLE THAN SUBJECT
PATIENT-REPORTED LEVEL OF PAIN.
AND EVERYTHING THAT WE HEARD
YESTERDAY AND AS I SAID SOME
WORK WE'RE DOING ON FUNCTIONAL
CONNECTIVITY INTO THE PICTURE,
MIGHT HELP, MIGHT NOT BE THE
FINAL RESULT, BUT IT MIGHT HELP
>>I FEEL LIKE I'M CONSTANTLY
DAUNTED ABOUT THIS QUESTION
ABOUT HOW DO YOU IDENTIFY PAIN
SOURCES BECAUSE PAIN, I MEAN, IT
CAN COME FROM SO MANY DIRECTIONS
IN TERMS OF, YOU KNOW, TRYING --
THERE ARE GREAT STUDIES ON
NEUROCONNECTIVITY, HOW THAT
RELATES TO NOCICEPTIVE VERSUS
NEUROPATHIC VERSUS OTHER TIMES
-- TYPES OF PAIN.
SOMEONE MAY HAVE PAIN TWICE A
WEEK AND THEY ARE SAYING I'VE
GOT THIS PAIN, AND THAT'S VERY
DIFFERENT THAN SOMEONE WHO HAS
HAD EIGHT OUT OF TEN PAIN FOR
FIVE YEARS STRAIGHT.
AND SO IT SEEMS LIKE FOR ALL OF
THESE WE ARE NOT EQUIPPED TO
SORT OF SAY THIS IS THE SOURCE
OF YOUR PAIN.
IT HAS TO BE MORE DIRECTED FROM
THE CLINICAL PRESENTATION AND
THE MORE WE CAN TARGET, YOU
KNOW, OUR IMAGING METHODS AND
ESPECIALLY ANALYSIS METHODS
TOWARDS A PARTICULAR
PRESENTATION, I THINK THE BETTER
THESE WILL BE.
BUT I MEAN IT SEEMS TOO DAUNTING
TO SAY THIS PERSON IS COMING
WITH KNEE PAIN, IMAGING MIGHT BE
HELPFUL TO PARTICULARLY RULE OUT
BUT THE IDEA IS LIKE WE'RE GOING
TO BE RELIABLY LIKE DIAGNOSING
THE SOURCE OF PAIN SEEMS REALLY
FAR OFF AT THE MOMENT, UNTIL WE
CAN SORT OF BETTER CLASSIFY
THESE PEOPLE COMING IN AND
BETTER FIT THEM TO THE
APPROPRIATE, YOU KNOW, MODEL OR
WHATEVER IT MAY BE, THAT CAN
HELP WITH THAT.
BUT TO JUST BROADLY KNEE PAIN
WILL BE REALLY TOUGH TO
DETERMINE ANY MODEL FOR.
>>YEAH, AND THE TECHNOLOGY, NOT
NECESSARILY WILL SOLVE THE
PROBLEM BUT CAN SURFACE A LOT OF
THE SHORTCOMINGS OF QUESTIONER
AND THE WAY WE ASSESS PAIN.
THE MODEL THAT I PRESENTED TODAY
HAD SUPER SIGNIFICANT BIAS IN
THE NUMBER OF TRUE POSITIVE AND
THE FIRST PREDICTOR OF BEING
TRUE POSITIVE WAS RACE, WHICH
MEANS THE MODEL LOOK AT YOUR
KNEE, THINKS YOU SHOULD REPORT
PAIN, BUT THE QUESTIONER SAID
THAT THE PAIN WAS NOT REPORTED.
AND THOSE TYPE OF THINGS CAN BE
QUANTIFIED, QUANTIFIED AND VERY
STRONGLY STATISTICALLY ASSESSED
WITH THE TECHNOLOGY THAT WE ARE
DEVELOPING.
EVERYTHING ABOUT YOUR DATA
PROFILE SAID SOMETHING, AND
YOU'RE SAYING SOMETHING ELSE.
SO TO UNDERSTAND THIS
DISCREPANCY CAN HELP US
DEFINITELY UNDERSTANDING THE
SHORT COMING ALSO OF OUR
ASSESSMENT, ASSESSMENT OF PAIN,
THAT IS ABSOLUTELY, YOU KNOW,
FULL OF SHORTCOMINGS, IN A WAY.
>>THE NEXT QUESTION IS KIND OF
RELATED TO THE POINT RICCARDO
BROUGHT UP EARLIER, IN THE
CLINICAL VALIDATION OF THE
QUANTITATIVE MR WE USUALLY, YOU
KNOW, GIVEN THE FACT GROUND
TRUTH IS NOT THAT RELIABLE
SOMETIMES, AND BASED ON SURGICAL
REPORT MAY NOT BE CONSISTENT
ACROSS PATIENT OR DOCTORS,
SOMETIMES THERE ARE LACK OF
DETAIL AND SO WHAT COULD BE
ALTERNATIVE COMPARE IMAGING
BIOMARKERS AGAINST OBJECTIVE
QUANTITATIVE GROUND TRUTH DATA.
>>IN MY OPINION IT WOULD BE
NICE TO USE LIKE TRUE BIOLOGICAL
MEASURES LIKE HISTOLOGY OR
PATHOLOGY, AND TRY TO CONNECT
ALL THESE THINGS ON A MULTIPLE
SCALE TO THE OTHER.
AND TRY TO MAYBE DESIGN OUR
IMAGING ACQUISITION AND PROBE
THESE PARTICULAR THINGS IN
HISTOLOGY AND PATHOLOGY WITH MRI
WHICH CAN BE DONE, YOU JUST NEED
A LOT OF DATA TO UNDERSTAND HOW
TO TRAIN THEM AND USE, NOT JUST
USE WITH GROUND TRUTH BUT TRY TO
PHYSICALLY UNDERSTAND WHAT THESE
PARAMETERS MEAN AT THE
BIOLOGICAL LEVEL BY USING MAYBE
MACHINE LEARNING TO DEVELOP
MODELS WHICH LOOK AT THE
MULTIPLE SCALES.
LIKE SOMETHING LIKE COMBINING
ALL THESE DIFFERENT TYPE OF DATA
TOGETHER AND TRAIN TO UNDERSTAND
WHAT THEY MEAN SO YOU DON'T NEED
ANYMORE SUBJECTIVE SURGICAL
REPORT, YOU CAN SEE THIS
DISTRIBUTION OF MY MR PARAMETERS
MEANS THAT THIS CONCENTRATION OF
LIGANDS, IF THE COLLAGEN
METRICS, IF DONE THIS WAY, AT
THIS LEVEL.
AND THIS CAN BE DONE.
WE DON'T HAVE THE DATA YET BUT
IN PRINCIPLE IT'S NOT
IMPOSSIBLE.
>>MAY I ASK A FOLLOW-UP
QUESTION TO THAT?
I THINK I'M A LITTLE BIT MORE
SKEPTICAL HERE THAT T2 AND T1,
EVEN SOME OF THE OTHER CARTILAGE
METRICS, THEY REALLY FEEL LIKE
ARE NEVER GOING TO REALLY BE
SPECIFIC TO ANY PARTICULAR
METRIC, EVEN IF YOU ACQUIRE
MULTIPLE I DON'T THINK YOU EVER
GET TO THE POINT YOU'RE GOING
HAVE THIS KIND OF COLLAGEN
CHANGE, PROTEOGLYCAN CHANGE.
IS THERE A WAY TO REFRAME THAT
QUESTION TO REALLY SORT OF SAY,
I DON'T KNOW , WHAT IS THE STUDY
THAT'S NEEDED WHEN YOU SEE A
CHANGE IN T2, WHATEVER IT MAY BE
THAT'S GOING TO BE USEFUL
CLINICALLY?
BECAUSE I FEEL LIKE WE'VE
FOCUSED SO LONG ON PROTEOGLYCAN
COLLAGEN CHANGES, I DON'T SEE
THOSE AS BEING SPECIFIC TO
EITHER ONE BUT STUDIES SAY THEY
ARE PREDICTIVE OF FUTURE DISEASE
PROGRESSION, CARTILAGE, IS THAT
GOOD ENOUGH, LIKE WHAT ELSE DO
WE NEED TO SHOW FOR THEM TO BE
UTILIZED IN, AGAIN, APPLICATION
NEEDS TO BE DETERMINED
CLINICALLY.
>>I AGREE.
I'M NOT SAYING SPECIFIC BUT ONLY
A FEW ARE SPECIFIC, SODIUM
IMAGING IS SPECIFIC TO GLYCANS,
ALL THE OTHERS ARE A MIX LIKE
BLT 1 IT'S ALMOST POSSIBLE MAYBE
T1 IN TISSUES, IF YOU CAN BUILD
A MODEL THAT SEE HOW CAN THAT BE
TRANSLATED TO HISTOLOGY OR
PATHOLOGY, THEN MAYBE YOU CANNOT
SAY SPECIFICALLY THIS PARAMETER
BUT IF IMAGE ACQUISITION WITHOUT
EVEN BUILDING PARAMETER MAP CAN
GO TO HISTOLOGY AND SAY IT GIVES
ME THIS ACTION OF THE
INFORMATION, WE KNOW IF IT'S
ONLY GLYCAN LOSS THEN IT'S
REVERSIBLE, IF THE COLLAGEN
MATRIX IS GOING BAD THERE'S
NOTHING CAN YOU DO EVEN IF THE
CARTILAGE LOOKS OKAY YOU'RE NOT
GOING TO REPAIR IT, UNTIL PEOPLE
FIND LIKE HOW TO MAKE CARTILAGE
REPAIR, RIGHT?
WE WERE SAYING BEFORE, I THINK
WHAT WE NEED TO REALLY PROVE,
IMPORTANCE OF QUANTITATIVE MRI,
BUT, YEAH, I AGREE THEY ARE NOT
SPECIFIC, YOU COMBINE THEM YOU
CAN GET INFORMATION OUT OF THEM.
>>I GUESS MY THOUGHT IS MAYBE
WE NEED TO TRY TO GO BACK TO
MORE OF THE BASIC VALIDATION
APPROACH, THE BENCH-TIME
VALIDATIONS METHODS.
I MEAN, THESE GO BACK TO LIKE
THE QUANTITATIVE WATER QUANTITY
IF
QUANTIFICATION, BENCH GOLD
STANDARDS.
AND SO I FEEL LIKE NOWADAYS WE
LOSE THAT A LITTLE BIT, WE THINK
IT'S TOO FAR SEPARATED FROM WHAT
WE SEE IN THE IN VIVO TISSUE
CLINICALLY.
ONCE UPON A TIME THAT DID WORK.
THERE'S ACTUAL QUANTITATIVE M.R.
TECHNIQUES VALIDATED IN PHANTOMS
AND WITH WELL-CONTROLLED BENCH
EXPERIMENTS.
SO I WONDER IF SOME METRICS CAN
BE DISTILLED BACK TO SIMPLE
BENCH VALIDATION APPROACHES, NOT
ALL CAN.
HOW DO YOU MAKE A PHANTOM THAT'S
GOT GOLD STANDARD T1 ROW, THAT'S
A GOOD PHYSICS OR CHEMISTRY
QUESTION.
BUT I WONDER IF THERE'S MAYBE
SOME SORT OF GOING BACK IN TIME
THAT MIGHT HELP A LITTLE BIT
WITH THIS MASSIVE FLUX OF
QUANTITATIVE TECHNIQUES THAT WE
HAVE NOW THAT DO NEED TO GET
VALIDATED SOMEHOW.
>>YEAH, AND MAYBE WHAT I'M
ABOUT TO SAY IS ALL ON THE OTHER
SIDE OF THE SPECTRUM FROM WHAT
KEVIN IS SAYING, HOW SIMILAR TO
WHAT RICCARDO WAS SAYING.
IN OTHER APPLICATION, WE CAN SEE
MODELS, FOR EXAMPLE, IN BRAIN
CANCER, WE CAN SEE MACHINE
LEARNING MODEL, TAKING INPUT,
T1, T2, AND FLARE, AND DO
PROJECTION OF GENETIC SUBTYPE OF
BRAIN TUMOR.
AND THERE'S NOTHING SPECIFIC OR
SENSITIVE IN THE SIGNAL OF T1 OR
SIGNAL OF THE FLARE THAT IS
DIRECTLY RELATED TO THE GENETIC
SUBTYPE, BUT IS ALL THE ADDITION
OF ENTIRE -- THE SHAPE OF THE
TUMOR AND THE SIGNAL, AND ALL
THE PICTURE TOGETHER ACTUALLY
BECOME PREDICTIVE.
SO MAYBE SPINE, IF THEY ARE NOT
DIRECTLY -- IF THE SINGLE VALUE
OF THE SINGLE VOXEL OF A T2
RELAXATION TIME DOES NOT
CORRELATE WITH COLLAGEN, IT'S
FINE.
IF WE CAN DO WHAT RICCARDO WAS
SAYING, PREDICTING HISTOLOGY MAP
FROM ALL OF THEM, AND LET
EVERYTHING CONTRIBUTE THE SHAPE
OF THE BONE WITH THE STATUS OF
CARTILAGE, THE T2 MAP, WHATEVER
YOU CAN ACQUIRE.
AND CAN ACCEPT THE FACT THE
SINGLE VOXEL DIDN'T CORRELATE,
WILL NEVER CORRELATE.
>>TO PUSH THIS TO EXTREME ONCE
WE HAVE FINGERPRINTING POSITION
YOU CAN OPTIMIZE, YOU DON'T EVEN
NEED IMAGES.
THE INFORMATION YOU USE TO
CONSTRUCT IMAGES ARE IN THE
SIGNAL.
AND ACTUALLY MORE INFORMATION
WHICH WE THROW AWAY, YOU JUST
BUILD A MODEL, USE THE
ACQUISITION, AND GET FOR
HISTOLOGICAL IMAGES YOU NEED.
>>I HAVE A FEW COMMENTS.
KEVIN, I TOTALLY AGREE.
AT THE SAME TIME THOSE ARE
REALLY HARD TO DO, RIGHT?
EX VIVO EXPERIMENTS TO LOOK AT
PROTEOGLYCAN CONTENT DEGRADE THE
CARTILAGE, DOING MORE.
IT'S REALLY HARD TO COME UP WITH
AN EX VIVO TEST TO CORRELATE
WITH PARAMETERS BECAUSE WHEN ONE
THING CHANGES, A BUNCH OF THINGS
CHANGE, AND FIGURING OUT WHICH
ONE IS DRIVING YOUR QUANTITATIVE
IMAGING METRIC IS DIFFICULT.
ONCE YOU GO TO IN VIVO AND
INCREASE LIKE INTRODUCE LIKE
BLOOD FLOW AND SYNOVIAL
DIFFUSION, PERFUSION TO THESE,
SOME 6 THESE STRUCTURES, IT'S A
REALLY BIG CHALLENGE.
SORT OF THE FLIP SIDE IS EVEN IF
YOU COULD DO THAT, I DON'T THINK
WE HAVE A GOOD ENOUGH
UNDERSTANDING OF LIKE IF YOU HAD
HISTOLOGY ON EVERYONE'S
CARTILAGE WOULD THAT REALLY
DRIVE CLINICAL DECISION MAKING
RIGHT NOW?
I'M NOT CLEAR THAT WE KNOW
ENOUGH ABOUT CHANGES TO
CARTILAGE TO MAKE A DECISION
THAT LIKE THIS PERSON NEEDS
PREEMPTIVE.
I'M SURE IT WOULD BE, YOU KNOW,
REALLY HELPFUL, BUT THAT'S WHY I
WONDER, LIKE, AGAIN, YOU KNOW,
PUTTING THESE IN SITUATIONS
WHERE THEY MIGHT HAVE FUTURE
APPLICATION JUST ON THE CHANGES,
AND MAYBE NOT SO MUCH ON THE
CORRELATES WILL PROBABLY GO
POTENTIALLY FURTHER THAN HIS
DISTINCT HISTOLOGICAL CORRELATES
WHICH I'M NOT SURE THAT WE CAN
GET.
>>THANK YOU.
ANOTHER QUESTION IS WE HAVE
TECHNOLOGY, EMERGING TECHNOLOGY
HERE, THE QUESTION IS HOW CAN
WE, YOU KNOW, HOW THE IMAGING
BIOMARKERS CAN BE INTEGRATED
WITH COMPUTATIONAL BIOMECHANICS
MODELS TO CREATE COMPLEX MODEL
TO ASSESS OR PREDICT SIMULATE AT
SCALES.
>>THAT'S A VERY IMPORTANT
QUESTION.
I DON'T KNOW IF WE HAVE ABILITY
TO DO THAT YET.
PART OF THE CHALLENGE AS WE WERE
DISCUSSING JUST NOW IS THAT WE
DON'T KNOW ENOUGH ABOUT THE
ENTIRE SYSTEM TO BE ABLE TO DO
THOSE KIND OF LINKAGES.
I'M CURIOUS TO HEAR WHAT OTHERS
HAVE TO SAY BUT THAT'S A
PRESSING NEED TO DEVELOP THAT.
>>YES, MY SENSE IS THAT STEP
ONE IN THE ACHIEVABLE, IN THE
FIRST INTEGRATION BETWEEN THIS
IMAGING TECHNIQUE AND
COMPUTATIONAL MODELING IS ON
PERSONALIZING BIOMECHANICS MODEL
ON ANATOMY OF PATIENTS, WITH MR
AND FIND, FOR EXAMPLE, IF ONE
HAS COMPLETE SEGMENTATION OF
VERTEBRAE, DISC, MUSCLE, CAN
HAVE LOADING MODEL THAT IS NOW
PERSONALIZED ON THE ACTUAL
ANATOMY OF THE PATIENT INSTEAD
OF USING GENERAL RULES, SO THAT
IS PROBABLY THE EASIEST --
SOUNDS EASY BUT IT'S NOT,
EASIEST ENTRY LEVEL.
ONE IS TO MAKE THE END OF
COMPUTATIONAL MODEL PAPER MORE
THAN TWO, THREE SUBJECTS, AND
MAYBE WE CAN PERSONALIZE ON
ANATOMY OF REAL PATIENT INSTEAD
OF USING GENERAL ANATOMY FOR
BIOMECHANICS COMPUTATION
MODELING.
>>MAYBE I CAN COMMENT AS A
MECHANICAL ENGINEER HERE.
SO, THERE'S A TREMENDOUS AMOUNT
OF WORK IN OTHER NIH SPONSORED
SYMPOSIA ON SUBJECT-SPECIFIC
MODELING.
THE STANFORD HAS LED THE WAY
WITH THE SYMBIO PROJECT,
UNIVERSITY OF UTAH, GETTING
TOWARDS SUBJECT-SPECIFIC JOINT
LEVEL AND TISSUE MODELING.
AS YOU EXPECT, THE EXPENSE IS
GETTING THOSE SUBJECT-SPECIFIC
MODELS, INVOLVING EXPENSIVE
SEGMENTATION, MODEL
CONSTRUCTION, SO THE WORK HERE
SEEMS VERY CONDUCIVE TO
AUTOMATICALLY HAVE INPUTS FOR
THOSE SUBJECT-SPECIFIC MODELS,
REALLY GOING IN PARALLEL
PATHWAYS, VERY COMPLEMENTARY.
AND I COULD EXPECT TO HAVE
USEFUL SUBJECT-SPECIFIC MODELS
SIMILAR BUT READILY AVAILABLE
ULTIMATELY INTEGRATED IN
CLINICAL PATHWAY, NOT TOO FAR
ALONG.
>>SO I THINK WHAT SCOTT SAID
BRINGS UP THE ISSUE THAT SINCE
QUANTITATIVE MRI IS NOT
AVAILABLE CLINICALLY, IMAGE
ANALYSIS FOR MORPHOLOGICAL
IMAGING THAT INCLUDES
SEGMENTATION AND REGISTRATION
CRUCIAL FOR GENERALIZABLE AND
OPENLY AVAILABLE
PATIENT-SPECIFIC MODELS.
IN A A PRESENTATION, THE USE OF
OTHER METHODS FOR REGISTRATIONS
BUT DOES ANYBODY WANT TO COMMENT
ON WAYS OF DETERMINING PRECISION
OF THIS IMAGE FOR REGISTRATION
APPROACHES AND PARTICULARLY IF
WE'RE USING FOR REGISTRATION
METHODS SUCH AS ITERATIVE
CLOSEST POINTS, REGIONS IN TERMS
OF IMAGE ANALYSIS PERSPECTIVE
FOR AUTOMATED IMAGE PROCESSING
MODELS?
>>THEY NEED TO BE REPEATABLE,
FIRST OF ALL.
AND THEN THERE ARE MATRIX FOR
ACCURACY, BY THE IMAGING
PROCESSING BOOK, BOTH FOR
REGISTRATION, SEGMENTATION,
OVERLAP BETWEEN GROUND TROOP
SEGMENTATION AND AUTOMATIC
SEGMENTATION, AND FOR
REGISTRATION, YOU NEED TO BE
ABLE TO IDENTIFY.
FOR CERTAIN APPLICATION,
MILLIMETER ERROR IN REGISTRATION
IS OKAY, FOR OTHER APPLICATION
IT'S NOT OKAY.
IT'S WAY TOO MUCH.
SIMILARLY FOR SEGMENTATION YOU
HAVE 95 SCORE FOR BONE
SEGMENTATION SEND YOU BACK TO
THE BOARD AND UNDERSTAND WHAT
YOU DID WRONG AND IF YOU ADD THE
SAME FOR CARTILAGE OF THE HIP,
SO THE FINAL GOAL WOULD BE TO GO
FAR AS EXTRACTING BIOMARKER OF
INTEREST AND THAT IS THE GOLD
STANDARD.
YOUR PROCESSING DOESN'T MATTER
THE DIFFERENCE BUT WHAT ARE YOU
TRYING TO MEASURE?
ARE YOU TRYING TO MEASURE THE
CURRENT THICKNESS, HOW RELIABLE
ARE YOU IN DOING THAT?
OR YOU ARE TRYING TO MEASURE THE
POSITION OF THE JOINT AND
DYNAMIC SCAN, HOW GOOD ARE YOU
IN DOING THAT?
THAT EXACT TASK.
I THINK THE MATRIX ALWAYS NEED
TO BE RELATED TO THE DOWNSTREAM
TASK, AND IT'S ONLY THE
PRECISION ON THE DOWNSTREAM TASK
AND THE MINIMUM DETECTABLE
DIFFERENCE CLINICALLY ON THE
DOWNSTREAM TASK BIOMARKER THAT
THE MARKER THAT SET RULES ON HOW
PRECISE THE WHOLE PIPELINE NEED
TO BE.
>>ONE ADDITIONAL COMPONENT TOO,
THERE ARE ESTABLISHED METRICS
FOR HOW WELL YOUR SEGMENTATION
AND THINGS GO BUT HOW IT IMPACTS
WHAT YOU'RE TRYING TO DO IS
CRUCIAL.
IN OUR CASE FOR OUR DYNAMIC
WRIST IMAGING HAD A LOT TO DO.
IF YOU DIDN'T HAVE COVERAGE OF
YOUR CARPAL BONES NOT ABLE TO
TRACK BACK TO STATIC REFERENCE.
SO WE IN OUR FIRST PAPER ON THIS
IN PLOS ONE DID A MONTE CARLO
ANALYSIS TO OPTIMIZE OUR
ACQUISITION, TO DO THE BEST WE
POSSIBLY COULD IN ORDER TO
COMPUTATIONALLY FIGURE OUT WHAT
WE COULD DO IN TERMS OF FINAL
ACCURACY TRACKING DEGREES OF
FREEDOM OF THE BONES BASED ON MR
AC
AX.
WE WEREN'T LOOK AT THE ICP, WE
WERE LOOKING AT HOW WELL WE
COULD ACTUALLY TRACK THE BONES
AGAINST AN IN SILICO GOLD
STANDARD.
SO THERE ARE COMPUTATIONAL WAYS
TO DO IT.
TO US, THAT SEEMED LIKE A MORE
SENSIBLE WAY THAN TO MAKE SOME
SORT OF CONTRIVED PHANTOM, YOU
KNOW, AND ACTUALLY MOVE IT
AROUND AND TRACK THEM BECAUSE
THAT'S NOT THE REAL WORLD.
THE ACTUAL IMAGE CONTRAST AND
THINGS WE GET OUT OF REAL
IMAGING DATA IS DIFFERENT THAN
WHAT WE COULD GET IN PHANTOM
EXPERIMENT, I THINK
COMPUTATIONAL VALIDATION
APPROACHES USING REAL DATA IS A
GOOD WAY TO GO.
ONE FINAL COMMENT FOR ANY OF
THESE THINGS THAT TRANSLATE, AT
THE END OF THE DAY THE FDA IS
GOING TO BE ASKING FOR DESIGN
CONTROLS ON HOW YOU'RE DOING
EVERYTHING.
THEY ARE GOING TO BE LOOKING AT
APPROACHES AND WHERE APPROPRIATE
YOU'LL HAVE TO HAVE APPROPRIATE
VALIDATION STRATEGIES TO SHOW
THINGS ARE WORKING.
NOW AGAIN YOU CAN GO TO THE
ENDPOINTS AND VALIDATE THERE,
BUT A LOT OF TIMES THE DESIGN
CONTROLS ARE ALSO GOING TO HAVE
YOU PUTTING SOME OF THE
INCREMENTAL COMPONENTS WITHIN
YOUR ALGORITHM INTO THOSE
VALIDATION STRATEGIES AS WELL.
>>IF I MAY ADD ONE COMMENT, I
THINK WE'RE TALKING ABOUT
PATIENT-SPECIFIC MODELING, BUT
THE COMPLEXITY OF A SYSTEM IS SO
LARGE THAT I AM VERY PESSIMISTIC
WE MIGHT BE ABLE TO DO THIS
ROUTINELY IN A CLINICAL SETTING,
YOU KNOW, THE AMOUNT OF DATA YOU
NEED GATHER FROM THE PATIENT TO
BE ABLE TO COME UP WITH A
PERSONALIZABLE MODEL IS TOO
DAUNTING.
WE HAVE SO MANY DIFFERENT
MECHANISMS THAT ARE IN PLAY.
IT IS NEARLY IMPOSSIBLE TO
COLLECT ALL THE DATA.
SO I'M NOT SURE HOW WE CAN COME
UP WITH ROBUST MULTI-SCALE YET
SPARSE WAYS OF MODELING THESE
SYSTEMS, THAT MIGHT BE
TRANSLATABLE.
>>JUST TO FOLLOW UP ON THAT, A
LOT OF THE MUSCULOSKELETAL
MODELS ARE ACTIVITY SPECIFIC,
RIGHT?
GETTING STATIC DATA OF SOMEONE
LYING SUPINE ISN'T THAT HELPFUL.
WE'VE BEEN WORKING WITH
VOLLEYBALL PLAYERS, THEIR
SHOULDER IS BACK HERE, SO THE
MODEL WOULD FAIL BECAUSE IT --
LIKE JUST GETTING SOME OF THESE
POSITIONS AND LIKE WHERE MUSCLES
AND TENDONS ATTACH REALLY
HELPFUL TO THE MUSCULOSKELETAL
MODELS TO UNDERSTAND WHAT THEIR
GENERIC MODEL SHOULD BE HELPING,
TRYING TO DETERMINE; YEAH, ON
ONE LAND I AGREE.
ON THE OTHER HAND I WILL SAY I'M
REALLY EXCITED BECAUSE I THINK
IN THE LAST LIKE FIVE YEARS AS
VALENTINA POINTED OUT WE MADE
HUGE STRIDES ON AUTOMATED
SEGMENTATION.
IN THE MUSCULOSKELETAL WORDS
LARGE STRIDES ON NOT NEEDING A
GIGANTIC GEAT GAIT WEB.
I AGREE IT'S DAUNTING.
ON THE OTHER HAND THINGS ARE
MOVING FAST AND I'M EXCITED
ABOUT WHERE WE THE ROLE OF
IMAGING CAN TIE IN TO HELP
ENHANCE THESE MUSCULOSKELETAL
MODELS AND MAYBE IT'S NOT
SPECIFICALLY AT POINT OF CARE
CENTER.
ON THE OTHER HAND MAYBE IT IS.
MAYBE WE CAN SAY, LIKE, WE CAN
DO A WALKING TEST OR SIT TO
STAND TEST AND TAILOR OUR
ACQUISITION TOWARDS SOMETHING
LIKE THAT, THAT COULD ENHANCE
IT.
YEAH, LIKE A GENERAL LIKE SCAN
SOMEONE AND FIGURE EVERYTHING
OUT SEEMS COMPLETELY
UNATTAINABLE.
>>THANK YOU.
WE HAVE A QUESTION FROM AUDIENCE
FOR DR. PEDOIA, IF YOU HAVE SEEN
ASSOCIATIONS OF BONE MARROW
LESIONS WITH PAIN METER MODELS.
>>SO THE MODEL THAT I SHOWED
DOES NOT TAKE INTO CONSIDERATION
BONE MARROW BUT WE HAD OTHER
MODEL BASED ON MRI PHENOTYPE.
WHILE THE PHENOTYPE IS BONE WITH
PRESENCE OF BONE MARROW, AND
IT'S DEFINITELY STRONG, STRONG
PREDICTOR OF PAIN.
BUT EVEN MORE IS THE
INFLAMMATION PHENOTYPE.
SO PRESENCE OF SYNOVITIS AND
OTHER MARKER OF INFLAMMATION.
THIS IS IN EVERYTHING THAT I DID
IN THE OSTEOARTHRITIS INITIATIVE
DEFINITELY THE STRONGEST
PREDICTOR OF PRESENCE AND
PROGRESSION, PROGRESSION OF PAIN
AND VERY CLOSE SECOND IS THE
PRESENCE OF BONE MARROW, SO THE
MARKER OF INFLAMMATION IS --
THEY NEED A PLACE IN MODELING
AND PAIN PROGRESSION.
>>THANK YOU.
WE'RE AT THE ASSIGNED TIME SO I
WOULD LIKE TO THANK EVERY
SPEAKER AND PANELIST FOR THE
DISCUSSION AND PRESENTATION.
I'LL PASS TO CATHERINE.
>>THANK YOU SO MUCH, DR. DUAN
AND CO-CHAIRS WHO PUT TOGETHER A
GREAT SET OF SPEAKERS AND
PANELISTS.
THANK YOU SO MUCH FOR YOUR
CONTRIBUTIONS FOR SESSION 5.
WITH THAT BEING SAID I'M GOING
TO TAKE US INTO A BREAK.
WE HAVE 30 MINUTES.
WE'RE GOING TO BE REGATHERING AT
3:15 PROMPTLY TO BEGIN SESSION
6.
SO PLEASE GO AHEAD AND MUTE YOUR
AUDIO AND YOU CAN STOP YOUR
VIDEO FEEDS AND WE'LL BE GOING
INTO BREAK.
>>THANK YOU FOR THE VERY
INFORMATIVE SESSIONS.
>>THANK YOU.
WELCOME BACK.
I'M PLEASED TO WELCOME YOU TO
SESSION 6, OUR FINAL SESSION FOR
TODAY.
I'M VERY PLEASED TO INTRODUCE
OUR TWO SESSION CHAIRS, CHAIR
AND CO-CHAIR FOR SESSION 6, DR.
HELENE LANGEVIN, AND DR. GAYLE
LESTER OF NIAMS, WHO I BELIEVE
IS THE DIRECTOR OF THEIR
DIVISION OF EXTRAMURAL RESEARCH.
SO WITH THAT SAID, I'M GOING TO
STOP MY SCREEN SHARE, HELENE AND
TURN THINGS OVER TO YOU TO TAKE
IT AWAY FOR SESSION 6.
>>OKAY.
WE'RE LITERALLY DOING THIS ON
THE FLY RIGHT NOW.
AND THESE ARE JUST SOME NOTES
THAT GAYLE AND I WITH THE HELP
OF ALEX AND WEN HAVE BEEN KIND
OF HUDDLING OVER DURING THE
BREAK.
AND SO THIS IS REALLY MEANT TO
BE A STARTING POINT FOR OUR
DISCUSSIONS, SO I'M GOING TO BE,
FIRST OF ALL, SHOWING JUST A
COUPLE THOUGHTS ON WHAT WERE THE
THINGS THAT WE HEARD LOUD AND
CLEAR, WHAT DID PEOPLE RESONATE,
WHAT ARE THEMES THAT RESONATED,
THERE WAS A LOT OF DISCUSSION,
ESPECIALLY WHEN IT ADDRESSED THE
THEMES OF THIS WORKSHOP OF WHOLE
JOINT HEALTH.
THEN I'M GOING TO MENTION A
COUPLE THINGS THAT I FELT
PERHAPS WE DID NOT HEAR QUITE SO
LOUD AND CLEAR.
AND WHERE WE MIGHT WANT TO THINK
ABOUT IS THIS REALLY A GAP THAT
WE KNOW SO LITTLE ABOUT THAT WE
DIDN'T TALK ABOUT IT OR IS THIS
JUST SOMETHING THAT WE COULD
HAVE ADDRESSED AND THAT WE HAVE
ACTUALLY MORE INFORMATION THAN
ACTUALLY CAME THROUGH.
SO, LET ME SHARE MY SCREEN.
FOR A SECOND.
ALL RIGHT.
SO, LOUD AND CLEAR.
CAN YOU SEE THIS?
>>YES, WE CAN, HELEN.
>>SO I THINK IT'S FAIR TO SAY
FIRST OF ALL I KNOW I'M NOT
ALONE IN BEING VERY, VERY
PLEASED WITH HOW THE WHOLE --
THE ENTIRE WORKSHOP REALLY
ADDRESSED VERY, VERY NICELY THE
THEME OF UNDERSTANDING THE WHOLE
JOINT.
I THINK THAT PEOPLE JUST REALLY
GOT IT.
THERE WAS A LOT OF TALK, BOTH ON
THE MECHANISM SIDE AND ALSO ON
THE CLINICAL SIDE OF THE
IMPORTANCE OF NOT JUST LOOKING
AT SEPARATE PARTS OF A JOINT,
REALLY THINKING ABOUT THE WHOLE
JOINT AS WE HEARD TALK ABOUT THE
JOINT AS AN ORGAN, AND GOING
BEYOND THE JOINT EVEN.
YOU KNOW, INCLUDING OTHER
ASPECTS, YOU HEARD ABOUT THE
DRG, NERVOUS SYSTEM.
SO I'M GOING TO FIRST MENTION A
COUPLE THINGS WHICH WE REALLY
FELT RESONATED ON A MECHANISTIC
SIDE, THE WHOLE THEME OF
INTERTISSUE COMMUNICATION, VERY
RICH DISCUSSION, ESPECIALLY
ABOUT THE ROLE OF ADIPOSE TISSUE
AND VARIOUS TYPES OF
INFLAMMATORY MEDIATORS,
CROSS-TALK BETWEEN THE DIFFERENT
TISSUES WITH RESPECT TO
INFLAMMATION, ROLE OF BONE, VERY
IMPORTANT, ALSO ROLE OF
CELLULOSENESCENCE, NICELY
BROUGHT UP.
THERE WAS NICE DISCUSSION ABOUT
THE INTERFACE BETWEEN MOLECULAR
COMPONENTS OF THE EXTRACELLULAR
MATRIX AND TISSUE MECHANICS.
MATRIX ASPECTS OF MATRIX
SYNTHESIS, BREAKDOWN, MATRIX
FRAGMENT, NICE DISCUSSION OF OF
THE ROLE OF HYALURONIC ACID,
AGGREGATION, AS RELATES TO
MECHANICS OF THE TISSUES,
STIFFNESS, LAXITY, ADHERENCE,
MENTION OF THESE SORT OF
TISSUES, TOGETHER, MECHANICS OF
THE JOINT, FASCINATING
DISCUSSION YESTERDAY ABOUT
HEALTHY VERSUS UNHEALTHY LOADS
ON JOINTS, SPECIFICALLY SI JOINT
DISCUSSED, VERY INTERESTING HOW
LITTLE WE KNOW, NICELY
DISCUSSED, ALSO IMPORTANCE OF IN
VIVO DYNAMIC MEASUREMENT
METHODS, NOT JUST STATICS,
BROUGHT UP A LOT TODAY.
AND NICE DISCUSSION ALSO OF
INTEGRATION OF MOLECULAR AND
STRUCTURAL IMAGING, A WAY TO
BRING -- A BRIEF MENTION, BUT
HOW TO BRING THE MOLECULAR
ASPECTS OF JOINT PATHOLOGY AND
HEALTH ALSO INTO THE STRUCTURE
USING COMBINATIONS OF SAY, FOR
EXAMPLE, PET-CT.
AND THEN YESTERDAY WE TALKED
ABOUT THE CHALLENGE OF
INTEGRATING VARIOUS -- A LOT OF
TYPES OF DATA, AND HOW IMPORTANT
THAT IS TO DO THIS AT THE OUTSET
OF RESEARCH, WITH THAT IN MIND.
AND OF COURSE NOW WE'RE ALL VERY
WELL AWARE, THIS WHOLE AREA OF
PUSH ON UNDERSTANDING WHAT TO DO
WITH THE DATA, AND USING
ADVANCED COMPUTATIONAL METHODS
INCLUDING MACHINE LEARNING, ET
CETERA.
SO WE ALL UNDERSTAND
INCREASINGLY HOW IMPORTANT THAT
IS TO THINK ABOUT THAT FROM THE
START.
NOW LET'S MOVE TO THE CLINICAL
SIDE.
AGAIN, I THINK THAT THE WHOLE
PERSON APPROACH WAS VERY CLEAR
THAT THE BIOPSYCHOSOCIAL
APPROACH THAT'S BEEN REALLY KIND
OF VERY WELL ESTABLISHED, AND
THE USE, THE IMPORTANCE OF USING
MULTI-MODAL THERAPIES, IF YOU
WANT TO ADDRESS THE PLURALITY OF
ASPECTS, ALL THE ASPECTS THAT
CONSTITUTE A HEALTHY OR NOT SO
HEALTHY JOINT, THERE WAS A VERY,
VERY NICE DISCUSSION OF THE
INTERPLAY OF DIET AND EXERCISE,
AS WELL AS PASSIVE AND ACTIVE
MECHANICAL THERAPIES.
NOW, I WAS VERY HAPPY ALSO TO
SEE THERE WAS SOME MENTION THAT
BOTH ANALGESIA AND RESTORATION
OF JOINT HEALTH GO HAND IN HAND,
TRANSCUTANEOUS NERVE STIMULATION
TO REDUCE PAIN DURING MOTION CAN
ENCOURAGE PEOPLE TO EXERCISE AND
MOVE MORE IS VERY IMPORTANT.
AND THAT WAS A REALLY NICE
EXAMPLE OF THAT.
SO THAT ENHANCED MOVEMENT WOULD
THEN BE BENEFICIAL NOT JUST FOR
THE JOINT BUT FOR THE WHOLE
PERSON.
THERE WAS A LOT OF DISCUSSION ON
CHALLENGES OF IMPLEMENTS WHAT WE
KNOW, THE SHOCKING STATEMENT
THAT ONLY 15% OF PATIENTS ARE
REFERRED TO PHYSICAL THERAPY
BEFORE JOINT REPLACEMENT
SURGERY.
THIS IS SOMETHING THAT NEEDS TO
CHANGE, CLEARLY THIS IS JUST
NOT -- WE'RE NOT OPTIMALLY
UTILIZING OUR KNOWLEDGE IF THIS
IS WHAT'S CONTINUING TO HAPPEN.
THERE WAS SOME DISCUSSION ABOUT
THE IMPORTANCE OF EVALUATING THE
WHOLE JOINT IN CLINICAL TRIALS,
MAYBE THAT'S WHY WE'RE NOT
REALLY GETTING THE RESULTS THAT
SOME TREATMENTS LOOKED AT THAT
ARE NOT WORKING BUT WE'RE ONLY
EVALUATING A LIMITED ASPECT OF
THE JOINT, MAYBE WE'RE ONLY JUST
LOOKING AT PAIN, AND WE'RE NOT
LOOKING AT FUNCTION.
WE'LL GET AT THAT LATER.
AND THEN THERE WAS AN
INTERESTING DISCUSSION ABOUT
USING MULTI-SCALE MODELING,
WHETHER THAT'S FEASIBLE FOR
PATIENT CARE.
WHAT DID WE HEAR NOT SO CLEARLY?
I FEEL LIKE THIS IS A WORKSHOP
NOT ABOUT JOINT PAIN, IT'S A
WORKSHOP ABOUT WHOLE JOINT
HEALTH.
WE HEARD A LOT ABOUT PAIN.
NOT SURPRISING.
IT IS IT'S MORE CHALLENGING TO
UNDERSTAND JOINT HEALTH THAN IT
IS TO STUDY PAIN.
BUT WE REALLY NEED TO BE SET UP,
TO DO MORE RESEARCH ON FUNCTION
AND OTHER ASPECTS OF JOINT
HEALTH, SOME WERE MENTIONED,
MOBILITY, PROPRIOCEPTION,
COORDINATION OF MOVEMENT, THESE
ARE ALL THINGS THAT ARE VERY
IMPORTANT THAT INVOLVE JOINTS,
AND THERE WAS EVEN A LITTLE BIT
OF TALK ABOUT POSTURE, NOT MUCH.
WE NEED TO -- SO CAN WE DEVELOP
PERSONALIZED SIGNATURES, FOR
EXAMPLE, OF JOINT HEALTH, NOT
JUST PAIN, THAT CAN BE FOLLOWED
OVER TIME WITHIN EACH INDIVIDUAL
MOVING EITHER TOWARD HEALTH OR
AWAY FROM HEALTH.
AND THAT'S THE NICE THING ABOUT
DOING LONGITUDINAL MEASUREMENT,
BECAUSE NOW YOU'RE DOING
MEASUREMENTS WITHIN A PERSON.
AND SO IT MIGHT BE -- IT MIGHT
BE FEASIBLE SOMETIME IN THE
FUTURE TO FOLLOW SOMEBODY.
THERE WAS NICE DISCUSSION ABOUT
ADAPTIVE VERSUS MALADAPTIVE
CHANGES, IF YOU WERE ABLE TO
FOLLOW SOMEBODY OVER TIME USING
A SET OF MEASUREMENTS, AND BE
ABLE TO DETECT WHETHER THIS
PERSON IS ADAPTING IN A GOOD OR
NOT SO GOOD WAY, AND GUIDE THE
PERSON'S MULTI-MODAL THERAPY,
RIGHT?
ACCORDING TO HOW WELL THEY
ARE -- HOW WELL THESE
MEASUREMENTS ARE, WHAT THE
MEASUREMENTS ARE TELLING US.
WHICH CAN BE I THINK THIS IS
SOMETHING WE'RE ALL THINKING
ABOUT IN TERMS OF
SUBJECT-SPECIFIC GUIDED
TREATMENT.
NOW, THIS IS ANOTHER ASPECT
WHICH I THINK WE DID NOT TOUCH
VERY MUCH ON, IS PREVENTION.
THERE WAS A LITTLE BIT OF
MENTION OF PREVENTION, MOST OF
THE DISCUSSION WAS FOCUSED ON
PATHOGENESIS AND TREATMENT OF
ESTABLISHED DISEASE.
THERE WAS A LITTLE BIT OF
DISCUSSION ON QUANTITATIVE MRI
FOR DETECTION OF EARLY AND
REVERSIBLE CARTILAGE LESION, ONE
TRIAL OF DIET AND EXERCISE FOR
O.A. PREVENTION, SOMETHING WE
NEED A LOT MORE OF.
ESPECIALLY IF WE THINK THAT BY
DEVELOPING MORE SOPHISTICATED
DIAGNOSTIC TECHNIQUES TO FOCUS
ON VERY EARLY CHANGES, WE MAY BE
ABLE TO DETECT ABNORMALITIES,
YOU KNOW, WHILE WE STILL CAN
REVERSE THEM USING, YOU KNOW, A
VARIETY OF DIFFERENT
PHARMACOLOGICAL OR
NON-PHARMACOLOGICAL TREATMENTS
TO RESTORE THE FUNCTION.
I WANT TO ALSO POINT OUT THAT
SOFT TISSUE IMAGING IS
DEFINITELY STILL LAGGING BEHIND.
YOU KNOW, WE'RE CLEARLY STILL
HAVE A LOT MORE EXPERIENCE IN
UNDERSTANDING AND DEVELOPING
TECHNIQUES AND INTERPRETING
IMAGING OF HARD TISSUE,
CARTILAGE, BONE, NOT SO MUCH
SOFT TISSUES.
SO WHEN WE'RE MAKING MODELS OF
WHOLE JOINTS, WE GOT TO MAKE
SURE THE ENTIRE JOINT IS IN
THERE.
IF PART OF WHAT WE'RE DOING IS
IMAGING, IF WE'RE NOT DETECTING,
FOR EXAMPLE, THE SUBTLE
DIFFERENCES BETWEEN JOINT
CAPSULE AND THE FASCIA THAT ARE
INVEST THE AS DR. STEEKEL WAS
POINTING OUT IF WE DON'T HAVE
IMAGING METHODS TO DIFFERENTIATE
WE'RE NOT GOING TO BE ABLE TO
ASSIGN THE CORRECT MEASUREMENT
AND ESPECIALLY LOOKING AT
INNERVATION, ALL THESE NICE
STUDIES OF WHOLE JOINT
INNERVATION, WE'VE GOT TO MAKE
SURE ALL THE TISSUES ARE
REPRESENTED IN THERE.
THERE WAS ONE COMMENT YESTERDAY
ABOUT UNDERSTANDING EFFECTS OF
EXERCISE, THERE'S THIS VERY
EXTENSIVE STUDIES OF MOTOR PACK
COMMON FUND PROJECT THAT SHOULD
BE LEVERAGED IN THIS AREA,
UNDERSTANDING EFFECT OF EXERCISE
ON THE WHOLE BODY BUT CERTAINLY
WOULD APPLY TO JOINTS.
AND THEN I ALSO ALREADY
MENTIONED ADAPTIVE AND
MALADAPTIVE PHENOTYPIC
EVOLUTIONS.
THESE WERE MY REMARKS.
I'M GOING TO STOP SHARING AND I
WILL LET GAYLE CHIME IN AND SEE
WHAT DID I MISS AND WHAT ELSE
SHE FOUND OR WHERE DID SHE AGREE
WITH ME.
>>GAYLE, DO YOU NEED US TO DO
ANYTHING ON YOUR BEHALF OR ARE
YOU READY TO SHARE YOUR SLIDES?
>>I'M READY.
I JUST COULDN'T GET MY MUTE OFF.
>>WE'RE SUPER QUICK ON OUR
ENDS.
>>YOU ARE.
OKAY, LET'S SEE.
I THOUGHT I WAS SHARING.
LET'S SEE.
SHARE.
OH, OKAY, THERE WE GO.
I THINK IT WORKED.
DID IT?
>>YES, JUST GO TO THE SLIDE
SHOW.
>>YES.
>>SLIDE SHOW MODE AND IT SHOULD
PICK UP.
THERE WE GO.
>>SO, I THINK HELENE DID AN
EXCELLENT JOB OF SUMMARIZING
SOME OF THE OBSERVATIONS THAT
I'M SURE MANY PEOPLE FELT
THROUGHOUT THE LAST TWO DAYS.
I WOULD LIKE TO SECOND HER
COMMENTS ABOUT HOW ABSOLUTELY
FABULOUS THE LAST TWO DAYS HAVE
BEEN.
THE PRESENTATIONS WERE SUCH HIGH
QUALITY AND SO HELPFUL FOR
UNDERSTANDING BETTER THE
PROBLEMS THAT ARE ENCOUNTERED
NOT ONLY BY THOSE OF US STUDYING
THE DISEASE OF OSTEOARTHRITIS
BUT ALSO BY THE PATIENTS WHO
HAVE THIS DISEASE, AND HOW THEY
ARE SUFFERING AND STRUGGLING
WITH THEIR ABILITY TO MANAGE THE
DISEASE ITSELF.
SO, I'VE MADE A FEW OBSERVATIONS
HERE IN THE LAST -- I'VE GOT
THREE SLIDES, I'LL WORK THROUGH
THEM.
AND THESE ARE ARE IN PART BASED
ON MY OBSERVATIONS.
AND FOR THOSE WHO AREN'T AWARE
I'M DIRECTOR OF I'M DIRECTOR OF
EXTRAMURAL RESEARCH AT NIAMS,
BUT PREVIOUSLY THE DIRECTOR,
PROGRAM DIRECTOR FOR CLINICAL
OSTEOARTHRITIS RESEARCH, AND
UNDER MY GUIDANCE WE DEVELOPED
ENTIRE RESEARCH COMMUNITY, THE
OSTEOARTHRITIS INITIATIVE, A
RESOURCE NOW BECAUSE IT'S NO
LONGER ENROLLING, WE'RE
FOLLOWING OUTCOME MEASURES.
BUT NO MORE FOLLOW-UP MEASURES
ON SUBJECTS OTHER THAN WHETHER
THEY HAD A TOTAL JOINT
REPLACEMENT OR NOT.
IT REMAINS A WONDERFUL RESOURCE
FOR THE COMMUNITY.
IT MAY LACK A LITTLE BIT OF THE
HOLISTIC APPROACH IN THE FIRST
BULLET BUT I WOULDN'T UNDERSELL
IT.
IT DOES HAVE ACTIVITY AND OTHER
DISEASES AND DOES DEAL WITH
DEPRESSION.
WE HAVE INDICES ON ALL THOSE
THINGS.
I THINK THE HOLISTIC APPROACH IS
NOT SO MUCH JUST LOOKING AT THE
PATIENT AS IT IS PROVIDING AS
HELENE WAS TALKING ABOUT VERY
HOLISTIC APPROACHES TO THE
TREATMENT AND HAVING INDIVIDUALS
BE FOLLOWED UP AND KIND OF
SUPERVISED WITH REGARD TO THE
MAINTAINING EXERCISE AND DIET
AND WEIGHT LOSS,
POST-INTERVENTIONS, OR JUST
EARLY ON IN DIAGNOSIS.
SO, THOSE ARE THE THINGS THAT I
THINK ARE REALLY HELPFUL FROM
THE LAST COUPLE OF DAYS'
DISCUSSION.
I THINK WE'RE MISSING DEFINITELY
MISSING INTERVENTIONS.
AND THIS IS SOMETHING I LEARNED
FROM THE OSTEOPOROSIS AREA, THAT
WHEN INTERVENTIONS BECOME
AVAILABLE THAT ARE EFFECTIVE IN
OSTEOARTHRITIS PREVENTING HIP
FRACTURE, THEN YOU BEGIN TO
UNDERSTAND BETTER WHAT THE
REALLY PIVOTAL POINTS ARE IN THE
ONSET, PROGRESSION, AND
MANAGEMENT OF THE DISEASE.
UNFORTUNATELY, WE HAVEN'T GOTTEN
THERE WITH O.A.
I THINK I WAS ENCOURAGED THAT
TMJ DISEASE MOVED BETTER, LOOKED
TO ME, THEIR ABILITY TO MANAGE
THAT DISORDER IN MANY PATIENTS.
I THINK WITH O.A. WE'RE STILL
VERY MUCH IN NEED OF EITHER
SURGICAL, MANUAL, OR
PHARMACEUTICAL INTERVENTIONS
THAT ARE HIGHLY EFFECTIVE.
THE OTHER THING I LEARNED IN THE
LAST COUPLE DAYS ARE THESE
TREATMENT TRIALS.
THANK YOU, CATHLEEN, VERY MUCH
FOR THAT.
THEY REALLY DO NEED TO BE
CAREFULLY DESIGNED.
NIAMS SUPPORTS A NUMBER OF
TRIALS IN O.A. AND HAS OVER THE
YEARS, AND CERTAINLY THE BIGGEST
PROBLEM IS THE SIZE AND LENGTH
OF FOLLOW-UP.
EAST -- OSTEOARTHRITIS IS A SLW
DISORDER, COMES ON SLOWLY AND
BECOMES CHRONIC.
REGENERATIVE MEDICINE, NON-HUMAN
MODELS FOR DISEASE ARE
RELATIVELY MIX AND SOMEWHAT
INADEQUATE, SEEMS LIKE A GAP,
SEEMS LINE AN AREA WE CAN
UNDERSTAND FROM THE MOUSE, SOME
OF THE CHANGES THAT ARE
OCCURRING IN THE TISSUES, BUT
IT'S VERY DIVERSITY DOLT T. -
DIFFICULT TO HAVE MECHANICAL
UNDERSTANDING FROM THE MODELS
ALTHOUGH WE ARE IMPROVING.
I WAS SIMULTANEOUSLY AT A
MUSCULOSKELETAL CONFERENCE IN
UTAH, AND WE'VE SEEN OVER THE
DAYS PRIOR TO THIS WHEN I WAS
ABLE TO GO TO THAT MEETING THAT
THERE ARE SOME MODELS THAT ARE
BEING DEVELOPED THAT DO MIMIC
SOME OF THE BIOMECHANICAL IMPACT
THAT THE BONES ARE SUBJECTED TO,
AND THAT CAUSE BONE REMODELING
AND CHANGES.
BUT THE NON-HUMAN MODELS SEEM TO
ME TO BE AN AREA WHERE WE COULD
MAYBE MAKE SOME SIGNIFICANT
STRIDES.
THE OTHER ISSUE IS REALLY MORE
RELATED TO CLINICAL BUT
CERTAINLY HAS AN IMPACT ON
ANIMAL MODELS, OUTCOME MEASURES,
OTHER THAN PAIN WHERE WE'VE GOT
BETTER AT ASSESSING PAIN AND
PAIN SENSITIVITY, BUT WE STILL
HAVEN'T GOT A VERY GOOD OUTCOME
MEASURE FOR O.A. AND CERTAINLY
ANYONE WHO TRIED TO DO CLINICAL
STUDIES WELL AWARE OF THAT, SO
THAT'S AN AREA THERE ARE
CERTAINLY GAPS.
AND THEN THE POINT THAT I
THOUGHT WAS REALLY EXCELLENT WAS
MADE YESTERDAY, YOU KNOW,
OSTEOARTHRITIS IS NOT REALLY A
SINGLE DISEASE.
IT HAS VARIATIONS IN THE
MANIFESTATIONS AND CAUSATIONS
FROM PATIENT TO PATIENT.
SO IT'S RELATIVELY HARD TO
CATEGORIZE IT VERY SUCCINCTLY AS
YOU CAN OTHER DISEASES.
ANOTHER POINT THAT I LEARNED
FROM THESE DISCUSSIONS AND THIS
GOES BACK TO ONE OF HELENE'S
COMMENTS RECENTLY IN THE LAST
PART OF HER TALK ABOUT
STIFFNESS, AND THE LACK OF
FLEXIBILITY OR LACK OF EXERCISE
LEAN NOT ONLY TO FURTHER JOINT
DEGRADATION OR ONSET OF DISEASE
BUT LOSS OF FUNCTION OR
STABILITY IN THE PATIENT.
SO THIS IS A VERY BIG IMPACT ON
LIFE AND ON YOUR ABILITY TO TAKE
CARE OF YOURSELF.
SO THE DEVELOPMENT DISABILITY IS
HIGHLY ASSOCIATED WITH
OSTEOARTHRITIS.
SO, IF WE CAN UNDERSTAND
STIFFNESS BETTER, WE COULD
POSSIBLY UNDERSTAND HOW TO
ALLEVIATE SOME OF THAT.
WE DO KNOW THAT EXERCISE HELPS A
LOT.
BUT I HEARD SOMEONE SAY THAT IN
SOME CASES EXERCISE, IF YOU'RE
IN THE WRONG STATE, EXERCISE CAN
MAKE IT WORSE.
SO THAT NEEDS TO BE TEASED OUT A
LITTLE BIT MORE.
I THINK THE TALK BY KELSEY
COLLINS WAS INFORMATIVE AND I'VE
SEEN HER WORK BEFORE AND FIND IT
QUITE FASCINATING.
AND TAMARA ALLISON, UNIVERSITY
OF CALIFORNIA, SAN FRANCISCO
CROSS-TALK BETWEEN CELL
POPULATIONS AND JOINTS, REALLY
HOPING THIS WOULD LEAD TO SOME
NEW TREATMENT TARGETS THAT MAY
BE HELPFUL AND MAY BE THAT WE
NEED THIS MULTI-MODAL TYPE OF
TREATMENT WHERE NOT ONLY ARE WE
TAKING A PHARMACEUTICAL AGENT TO
CONTROL THE CROSS-TALK ASPECTS
BUT THERE ARE ALSO AND PHYSICAL
THERAPY ASPECTS AS WELL.
NON-HUMAN MODELS OF O.A. ARE
LIMITED, I SAID THAT PREVIOUSLY
BUT WE MADE THESE SLIDES IN
ABOUT THREE MINUTES A LITTLE
WHILE AGO.
I FOUND TODAY'S DISCUSSION OF
MACHINE LEARNING AND ARTIFICIAL
INTELLIGENCE THROUGH THE IMAGING
TO BE INCREDIBLY HELPFUL AND
ENCOURAGING TO ME THAT WE MAY BE
ABLE TO REALLY LEARN A LOT FROM
THE LARGE DATASETS THAT WE HAVE,
AND SOME OF THE M.R. IMAGING
THAT WE'VE DONE IN THE CLINICAL
O.A. ARENA, BUT THEN THE FINAL
BULLET, HARMONIZATION OF
DATASETS AND INCLUSION OF COMMON
DATA ELEMENTS IS REALLY CRITICAL
FOR THAT TO BE EFFECTIVE.
AND SO THOSE TWO BULLETS COULD
NEED AN INITIATIVE TO JUST TRY
TO GET -- THERE ARE A NUMBER OF
LARGE COHORT STUDIES ON OA, TO
GET THEM HARMONIZED AND HAVE THE
OUTCOME MEASURES STANDARDIZED OR
AT LEAST FIGURE OUT WHAT COULD
BE USED FROM THESE LARGER
DATASETS.
SO I WAS HAVING STARTED REALLY
THINK BEEN INVOLVED IN SOME OF
THE EARLY DAYS OF M.R. IMAGING
IN O.A. WAS EXCITED TO SEE
PRESENTATIONS FROM THE IMAGERS
TODAY SO THANKS SO MUCH FOR
THAT.
LET'S GO TO MY LAST SLIDE.
THESE ARE QUESTIONS TO THROW OUT
THERE.
HOW CAN THE LARGER RESEARCH
COMMUNITY ADDRESS THESE GAPS AND
OPPORTUNITIES THAT HELENE AND I
HAVE SUMMARIZED FOR YOU, HAVE WE
MISSED SOMETHING?
DO WE NEED MORE BASIC STUDIES?
WE DO KNOW WE NEED MORE IMPROVED
CLINICAL STUDIES.
ARE THERE ANY EFFECTIVE -- WELL,
THIS WAS MY POINT BEFORE THAT
EFFECTIVE TREATMENTS ARE NEEDED
TO ENABLE THE FULL -- MORE FULL
UNDERSTANDING OF DISEASE, AND
DISEASE PROGRESSION.
AND CAN WE IDENTIFY SOME NEXT
STEPS, AND THIS IS WHAT THIS
SESSION IS FOR, SO I HOPE
EVERYONE, ONCE I'VE STOPPED
TALKING, WILL PROVIDE THEIR
INPUT ON THIS.
IDENTIFY SOME NEXT STEPS BASED
ON THE DISCUSSIONS OF THE PAST
TWO DAYS.
I'D LIKE TO THANK EVERYBODY FOR
THEIR ATTENTION AND OPEN IT UP,
SEND IT BACK TO HELENE FOR HER
COMMENTS.
>>THANK YOU, GAYLE.
THERE WERE SO MANY, YOU KNOW,
SUCH A DIFFERENT ASPECT OF HOW
WE INTERPRETED THE DISCUSSIONS
BUT THERE ARE A LOT OF VERY
COMMON, YOU KNOW, POINTS BETWEEN
WHAT GAYLE AND I HEARD.
SO, WHO IS GOING TO PANEL THE
QUESTIONS NOW?
>>WE HAVE SUBMITTED QUESTIONS,
CATHERINE CAN POPULATE THEM IN
THE CHAT.
ALSO SEEMS LIKE THIS IS AN
OPPORTUNITY IF MEMBERS,
PANELISTS AND SPEAKERS, WOULD
LIKE TO REACT TO WHAT THEY JUST
SAW.
>>ABSOLUTELY.
IF THERE'S SOMETHING THAT YOU
DISAGREE, FEEL LIKE OH MY GOD,
YOU FORGOT ABOUT THIS, FEEL FREE
POINT IT OUT.
>>HELENE I'M GOING TO DROP IN A
QUESTION THAT WAS SHARED,
SENDING IT TO EVERYONE IN THE
CHAT NOW, WHERE HE'S ASKING
ABOUT HOW TO RESEARCH
MULTI-MODAL INTERVENTIONS OF
MUSCULOSKELETAL MEDICINE TO
MIMIC HOW CLINICIANS ACTUALLY
TREAT PATIENTS AND HOW DO WE GET
AWAY FROM THE REDUCTIONIST
APPROACH AND GET TO A MORE
COMPREHENSIVE APPROACH.
I'VE DROPPED THAT INTO THE CHAT
IF YOU WANT TO KICK OFF OR TAKE
THINGS FROM THE FLOOR AND I'LL
KEEP CHATTING IN QUESTIONS.
>>DO YOU WANT TO ELABORATE ON
EXACTLY WHAT YOU MEAN HERE?
>>AS CLINICIANS, WE SEE THE
PATIENT COME IN AND THEY'VE GOT
A COMPLAINT, KNEE PAIN, BACK
PAIN, ET CETERA, AND TYPICALLY
WE DON'T TREAT IT WITH JUST ONE
THING.
THAT WAS SORT OF ONE OF THE
THINGS I WAS TRYING TO EMPHASIZE
WITH THE CLINICAL VIGNETTE I
SHARED, WE MIGHT BE TREATING
WITH MORPHOBIOLOGICS, MANUAL
THERAPY, ADDING PHYSICAL THERAPY
TO THAT.
AS I OFTEN TELL MY FELLOWS,
SOMEBODY THAT COMES WITH KNEE
PAIN, KNEE PAIN IS A RESULT OF A
BAD FOOT OR BAD HIP
BIOMECHANICS, YOU'VE LOST MOTION
IN ONE OR BOTH OF THOSE AREAS
THE KNEE GETS OVERLOADED.
IF YOU'RE JUST TREATING THE KNEE
YOU'RE ZOOMED TO FAILURE, YOU
HAVE TO FIND OUT BIOMECHANICAL
DRIVER FOR THAT PARTICULAR
TISSUE OR JOINT TO BE
OVERLOADED.
SO WE TYPICALLY DON'T JUST DO
ANTI-INFLAMMATORY MEDICINE,
INJECTIONS, BUT A LOT OF THE
TRIALS SORT OF FOCUS ON
INTERVENTION, DO THEY LOOK AT
LEG LEANING EQUITY, VARUS VALGUS
ISSUES, GAIT.
COMPREHENSIVE FUNCTIONAL BODY IS
KEY, CAN WE IMAGE AND FIGURE
THIS OUT?
WE HAVE A LOT OF CLINICAL TOOLS
RIGHT NOW THAT COULD HELP US
WITH THAT IN TERMS OF LOOKING AT
JOINT RANGE OF MOTION,
STRUCTURE-FUNCTION RELATIONSHIP,
TO FIGURE OUT WHAT'S IMPORTANT
FROM IMAGING PERSPECTIVE, FROM,
YOU KNOW, YOU'VE GOT THE
PATIENT, PHENOTYPE IN FRONT OF
YOU, BUT A LOT OF TALK ABOUT
OTHER TYPES OF BLOOD TESTING
THAT MIGHT BE DONE SO, AGAIN,
I'M GETTING OFF SUBJECT HERE BUT
JUST TRYING TO LOOK AT HOW DO WE
CONSTRUCT THESE APPROACHES TO
MIMIC WHAT CLINICIANS ARE
ACTUALLY DOING.
AND SO THAT'S HOPEFULLY, I DON'T
KNOW IF I CONFUSED YOU OR MAYBE
HOPEFULLY --
>>WELL, NO, THERE IS -- AMANDA,
DO YOU WANT TO ELABORATE,
AMANDA?
WHERE IS AMANDA?
>>LOVE TO HEAR FROM HER, YEAH.
AMANDA, CAN YOU GET YOUR MUTE
OFF?
>>I'M TRYING.
THERE I AM.
YEAH, SO THERE ARE -- THIS WAS
ALLUDED TO IN AN EARLIER TALK,
THERE ARE ADVANCED STUDY DESIGNS
THAT ALLOW USE OF MULTI-MODAL
INTERVENTIONS THAT CAN CHANGE
ALONG THE WAY SO RATHER THAN
ASSIGNING PEOPLE AT THE VERY
BEGINNING OF A TRIAL AND SENDING
THEM DOWN AN ARM THEY ARE GOING
TO BE STUCK IN FOR 18 MONTHS,
YOU CAN CHANGE, RIGHT?
IF THEY DON'T RESPOND TO FIRST
INTERVENTION, YOU MOVE TO THE
SECOND OR INCREASE DOSE OF THE
FIRST INTERVENTION, WHATEVER IT
IS.
IT COULD BE ANY OF THOSE THINGS,
ADDING ON A NEW INTERVENTION.
AND THEY ARE ADAPTIVE OVER TIME,
USED IN ASTHMA AND OTHER AREAS,
CREEPING INTO OUR WORK.
ONE OF OUR COLLEAGUES AT UNC
USES THEM IN GERIATRICS, WEIGHT
LOSS, MAINTAINING FUNCTIONAL
MOBILITY.
THAT'S ONE THING.
ENROLLING THE RIGHT PEOPLE AT
THE BEGINNING MORE ADEQUATELY
PHENOTYPING THE WHOLE PATIENT
WE'VE TALKED ABOUT A FEW TIMES.
SO THAT YOU'RE ADJUSTING THESE
THINGS FOR THE RIGHT REASONS AND
RIGHT PEOPLE.
>>SO, ANOTHER THING TO DR.
BROLIN'S QUESTION, I THINK YOU
WERE TALKING MORE ABOUT HAVING
ENOUGH TIME AS A CLINICIAN TO
ACTUALLY EXAMINE THE PATIENT
THROUGH ALL THESE DIFFERENT
DIMENSIONS, AND THEN TO HAVE
ENOUGH TIME TO IMBIBE IN PART
WHAT NEEDS TO BE DONE, THAT'S A
HUGE PROBLEM FOR CLINICIANS, THE
THINGS WE'RE TALKING ABOUT,
NON-PHARMACOLOGICAL
INTERVENTIONS, REQUIRE TIME AND
EFFORT.
I KNOW I'M LOOKING AT STEVE
MESSIER, HE KNOWS FULL WELL HOW
MUCH WORK IT TAKES FROM THE
TEAM.
IF YOU'RE ONLY A SINGLE DOC OUT
THERE TRYING TO TREAT YOUR
PATIENTS, THAT'S A BIG LOAD.
YOU'RE NOT GETTING REIMBURSED
FOR ALL THOSE THINGS.
SO WE ARE THINKING ABOUT THIS
FROM THE HEALTH DISPARITIES
POINT OF VIEW, AND HOPING TO
BRING TOGETHER SEVERAL PARTNERS
TO TRY TO FIGURE OUT HOW TO BE
SURE THAT DOCTORS TREATING
PATIENTS FROM UNDERSERVED
COMMUNITIES HAVE ADEQUATE
REIMBURSEMENT TO BE ABLE TO
IMPART GUIDELINES THAT ARE
CURRENTLY AVAILABLE.
A GOOD POINT.
>>CUTTY, -- KATIE?
>>I THINK AMANDA IS ALLUDING TO
ADAPTIVE TRIALS.
MY PERSPECTIVE FROM LOW BACK
PAIN, NOT NECESSARILY
OSTEOARTHRITIS SPECIFICALLY, YOU
ABOUT THERE'S NICE WORK BY JULIE
FRITZ, DIFFERENT PATHWAYS
STARTING WITH A PHYSICAL THERAPY
INTERVENTION, SWITCHING TO
MINDFULNESS INTERVENTION THROUGH
PSYCHOLOGICAL SERVICES.
AND SO AGAIN NOT BEING STRUCK IN
ONE PATH.
I THINK SOME OTHER THINGS WE CAN
CONSIDER ARE LOOKING AT CLUSTER
RANDOMIZED TRIALS WHERE YOU'RE
LOOKING AT THE TRIAL FROM THE
CLINICAL -- LIKE THE CLINICAL
SITE PERSPECTIVE, SO THE
RANDOMIZATION IS DONE AT THE
CLINICAL SITE.
SEE THEN YOU AREN'T COMPARING
INTERVENTION TO INTERVENTION BT
PRACTICE TO PRACTICE, TRAINING
THE WHOLE ENTIRE GROUP OF
CLINICIANS TO APPROACH IT, TO
APPROACH THE INTERVENTION IN A
CERTAIN WAY OR DELIVER A PACKAGE
TO INTERVENTION.
AND THEN WHAT CAN YOU DO ON THE
BACK END WITH SOME OF THOSE
IMPLEMENTATION TYPE TRIALS LIKE
AHYBRID DESIGN, YOU'RE LOOKING
AT THE EFFECTIVENESS OF THE
INTERVENTION BUT ON THE BACK END
DO SECONDARY ANALYSES THAT LOOK
AT DIFFERENCES ACROSS THE
CLINICS AND TRACK SOME OF THOSE
ADAPTATIONS THAT MAYBE THE
CLINICIANS MADE TO THE
INTERVENTION BECAUSE OF THEIR
WORK FLOW OR BECAUSE OF THE TYPE
OF SUPPORT OR RESOURCES THEY HAD
AND THOSE CAN BE REALLY NICE
WAYS TO UNDERSTAND HOW TO GO
FORWARD NEXT IN ACTUALLY
IMPLEMENTING.
>>THANK YOU.
RICHARD, YOU HAVE A COMMENT?
>>YES, I WAS GOING TO SWITCH
THE CONVERSATION A BET TO
ADDRESS A COUPLE THINGS GAYLE
BROUGHT UP THAT I THINK ARE
REALLY IMPORTANT.
ONE IS ANIMAL MODELS.
AND BASIC SCIENCE RESEARCH.
FOR ANIMAL MODELS, I THINK A LOT
OF THE ISSUES HAVE BEEN AGE OF
ANIMALS RELATED TO
OSTEOARTHRITIS.
IN MICE IT'S BEEN EITHER MANY
TIMES, KNOCK OUTSTUDIES,
INJECTING INTO MOUSE JOINTS.
ALMOST ALWAYS THESE ARE LIKE
REALLY YOUNG MICE.
EQUIVALENT TO A TEENAGER.
YOUNG HUMANS REPAIR JOINTS MUCH
BETTER AS OPPOSED TO PEOPLE THAT
HAVE COMPLETED SKELETAL
DEVELOPMENT.
AND SO I THINK A LOT OF THE
ISSUES WITH PRE-CLINICAL STUDIES
HAVE BEEN RELATED TO THE AGE OF
THE ANIMALS AND THEN OF COURSE
IN MICE, MALE MICE GET MORE
SEVERE O.A. THAN FEMALE MICE,
MANY STUDIES ARE DONE MALE MICE.
WHEN YOU DO SOMETHING IN BOTH
SEXES YOU FIND SOME INTERESTING
DIFFERENCES.
SO, BOTH AGE AND SEX ARE REALLY
IMPORTANT, I THINK, FACTORS TO
CONSIDER IN THE PRE-CLINICAL
MODELS.
AND ALMOST ALL THE MODELS ARE
SINGLE MODEL WHERE IT'S A
SURGICALLY INDUCED O.A.
OBESITY MODELS ARE SO MUCH
HARDER TO STUDY BECAUSE IT TAKES
A LONG TIME FOR ANIMALS TO GET
OBESE ON HIGH FAT DIET, THERE
ARE WAYS TO SPEED IT UP.
WE NEED MORE BASIC SCIENCE
RESEARCH.
WE'VE IDENTIFIED TONS OF
CYTOKINES AND INFLAMMATORY
MEDIATORS PRESENT IN
OSTEOARTHRITIC JOINT COMING FROM
THESE TISSUES INVOLVED.
WE DON'T KNOW THE DRIVING
FACTOR.
WE DID STRANGE THINGS FOR FOR
PEOPLE WITH RHEUMATOID
ARTHRITIS, PARAFFIN BATHS, WENT
AWAY WHEN TNF INHIBITORS CAME
ALONG, MADE A HUGE DIFFERENCE IN
PEOPLE WITH RHEUMATOID ARTHRITIS
IN PAIN AND STRUCTURE.
I FEEL LIKE WE JUST HAVEN'T GOT
THERE YET IN TERMS OF WHAT IS
THE DRIVING FACTOR OR FACTORS IN
O.A. THAT IF WE CAN BLOCK THOSE
WE'LL HAVE A SIGNIFICANT EFFECT
ON PAIN AND STRUCTURE AND FOR
THAT REASON I FEEL LIKE WE DO
NEED MORE BASIC SCIENCE RESEARCH
SO THAT WE COULD IDENTIFY THAT.
AS YOU BROUGHT UP, SEVERAL
PEOPLE BROUGHT UP, INTERTISSUE
COMMUNICATION WITHIN THE JOINT
PROBABLY IS REALLY IMPORTANT IN
THAT TYPE OF DISCOVERY APPROACH.
SO I'LL STOP THERE.
>>THANK YOU.
>>THANKS, RICHARD.
>>YES, LET'S SEE.
LESLIE IS NEXT I THINK.
>>YEAH, I WANT TO COME BACK TO
THE ISSUE OF TREATMENT AND BACK
TO PREVENTION, PUT IN A PLUG IT
WOULD BE REALLY NICE TO BE ABLE
TO HAVE AN ANNUAL PREVENTIVE
CARE PHYSICAL THERAPY EVALUATION
FOR PATIENTS SO WE CAN IDENTIFY
PROBLEMS WHEN THEY ARE SMALL
BEFORE THEY GET TO THE BAD
PROBLEMS, THAT I'LL SOMETIMES
SEE PATIENTS HYPER MOBILE WHO
AREN'T SYMPTOMATIC YET, USUALLY
PARENTS BRINGING THEM IN BECAUSE
THEY ARE WORRIED ABOUT IT.
OH, WELL, BECAUSE YOU'VE GOT
IMBALANCES YOU'RE VULNERABLE TO
PROBLEMS, HERE ARE EXERCISES.
IF YOU FEEL THIS DEFINITELY LOOK
INTO IT.
WE COULD DO A BETTER JOB
PREVENTING AND PHYSICAL THERAPY
COULD BE INTEGRATED IN TO THAT
PREVENTIVE CARE.
>>THAT'S A GREAT IDEA, IF THIS
CAN BE LIKE YOUR ANNUAL DENTAL
EXAM OR SOMETHING.
AND IF WE HAD MEASUREMENTS,
OBJECTIVE MEASUREMENTS THAT
COULD BE COUPLED TO FOLLOW
PEOPLE OVER TIME, GREAT IDEA.
>>EVEN AS SIMPLE AS LEG LENGTH
DISCREPANCIES AND GAIT
ABNORMALITIES, YOU CAN SEE IN
THE PATIENT COULD BE ADDRESSED.
THAT'S A GREAT IDEA.
>>GREAT IDEA, YEAH.
ANN-MARIE?
>>THANK YOU.
I WANT TO GO BACK TO RICHARD'S
COMMENTS.
OF COURSE, I AGREE WITH RICHARD,
WE DO NEED TO HAVE MORE AND MORE
SOPHISTICATED BASIC SCIENCE
APPROACHES.
I JUST WANTED TO NUANCE A LITTLE
BIT, I DO NOT THINK WE HAVE
CURED O.A. IN ANIMALS ALL THE
TIME.
IF WE DO PROPER STUDIES IN
ANIMALS, IT'S EQUALLY HARD TO
EVEN ADDRESS THAT PAIN OR TO
AFFECT O.A. PROGRESSION, IT
RELATES TO EVERYTHING YOU
POINTED OUT, SO WE HAVE JUST ALL
MALE MICE AND DO THEM IN YOUNG
MICE AND IT'S ALL, YOU KNOW,
IT'S ALL QUITE EASY THE WAY IT'S
USUALLY DONE AND PEOPLE DO
PREVENTIVE PROPHYLACTIC
INTERVENTIONS, AND SO I WOULD
JUST ADD TO WHAT RICHARD SAID
THAT WE SHOULD REALLY HAVE THE
PATIENTS TO STUDY SLOWLY
PROGRESSIVE MODELS, EVEN IN
RODENTS TO COME IN AT TIME
POINTS AND DO THIS CAREFULLY
SO -- BECAUSE IF WE DO IT THAT
WAY, IT'S VERY DIFFICULT TO
REALLY CURE O.A. AND EVEN IN
MICE, EVEN WITH VERY GOOD
COMPOUNDS, WHAT WE SEE FOR
PROTECTION OF THE JOINTS AND ALL
THAT OVERALL IF YOU LOOK IN THE
LITERATURE IT'S NOT SO EASY TO
REALLY RESTORE THIS EVEN IN AN
ANIMAL.
AND SECONDLY, SOMETHING MAYBE
THAT WE HAVEN'T TALKED ABOUT,
ALSO RICHARD HIGHLIGHTED AND
THIS HAS COME UP OF COURSE A
LOT, INTERACTION BETWEEN THE
DIFFERENT TISSUES IS THAT WHAT
WE DIDN'T TALK ABOUT IS THAT
THERE ARE A LOT OF EFFORTS GOING
ON WHERE PEOPLE NOW DO THIS NOT
USING ANIMALS.
SO PEOPLE DEVELOP JOINTS ON A
CHIP.
IT'S ALL VERY EARLY DAYS,
LARGELY, BUT I THINK THAT WILL
ALSO HOLD A LOT OF PROMISE FOR
PEOPLE TO GO LOOK AT IN THE
FUTURE.
THOSE WERE MY TWO COMMENTS.
THANK YOU FOR THAT.
AND THANK YOU, EVERYBODY, FOR
THE PAST TWO VERY INTERESTING
DAYS.
>>THANK YOU.
>>GREAT.
ALEX?
>>YEAH, SO WE RECEIVED SOME
QUESTIONS FOR THIS GENERAL
DISCUSSION PRIOR TO THIS
AFTERNOON, AND I NOTICED SOME
COMMENTS RELATE TO QUESTION OR
FUTURE OPPORTUNITIES THAT DR.
STONE PRESENTED.
I'D LIKE TO INVITE DR. STONE IF
SHE'S AVAILABLE TO MAYBE ALSO
TALK ABOUT THE TRANSITION FOR
PRE-CLINICAL FINDINGS FROM
CLINICAL TRANSLATION AS WELL AS
MAYBE USE OF OTHER NON-RODENT
MODELS.
DR. STONE?
>>YEAH, THERE SHE IS.
>>YOU'RE MUTED, LAURA, IF YOU
COULD UNMUTE.
>>SO THERE WAS TWO QUESTIONS
THERE.
THE FIRST ON FACILITATING
TRANSLATIONAL FROM PRE-CLINICAL
STUDIES TO TRANSLATIONAL PICKSES
UP ON WHAT ANNE-MARIE JUST, I
THINK ONE OF THE BIG CHALLENGES
WITH OUR PRE-CLINICAL STUDIES BE
THEM IN RODENTS OR OTHER SPECIES
IS WE'RE NOT MODELING THE
CLINICAL SITUATION.
SO WE STUDY ONE DRUG AT A TIME
OR ONE INTERVENTION AT A TIME
WHERE INDIVIDUALS ARE DOING
MULTIPLE THINGS AT A TIME.
WE'RE STUDYING ANIMALS THAT ARE
NOT AT THE APPROPRIATE AGE.
WE'RE STUDYING MODELS THAT YOU
INDUCE A MODEL AND STUDY THE
ANIMAL A WEEK OR TWO LATER,
WHEREAS WE'RE TRYING TO MAKE
INFERENCES TO THESE COMPLEX
LONG-TERM PROGRESSIVE DISORDERS.
OUR TREATMENTS ARE NOT ON THE
RIGHT TIME FRAME AS WELL, SO NOT
ONLY ARE OUR MODELS NOT
REPRESENTING THE TIME FRAMES
BUT, YOU KNOW, THE COMMON
PRE-CLINICAL EXPERIMENT, INJECT
A DRUG, A WEEK
HUMAN.
I KNOW THE HEAL INITIATIVES HAS
CALLS OUT FOR NOT ONLY KIND OF
MORE VALID PRE-CLINICAL MODELS
THAT COULD BE RODENT OR NOT BUT
SPECIFICALLY FOR NON-RODENT SO I
REALLY HOPE YOU GET SOME GREAT
APPLICATION THERE IS BECAUSE WE
NEED SOMETHING IN BETWEEN, LIKE
WE'RE NOT REALLY TAKING
ADVANTAGE OF COMPANION ANIMAL
STUDIES, FOR EXAMPLE, FOR O.A.
OR BACK PAIN THE WAY THAT WE
REALLY COULD BE.
AND THAT'S AN OPPORTUNITY TO
TRANSITION PRE-CLINICAL STUDIES
INTO A MORE COMPLEX CLINICAL
UNIVERSE, PRIOR TO GOING TO
HUMANS.
AND SO IT WOULD BE REALLY NICE
TO SEE MAYBE SOME INITIATIVES, I
DON'T KNOW IF THIS IS SOMETHING
THAT COVERS "HEAL" FROM THE
COMMUNITY SHIFTS IN THIS
DIRECTION, BUT TO SEE MORE WORK
DONE AFTER RODENTS IN DOGS OR
CATS OR EVEN HORSES OR PIGS.
>>THANK YOU, LAURA.
SUCH AN IMPORTANT QUESTION ABOUT
THE ROLE OF LARGE ANIMAL MODELS,
ESPECIALLY SITUATIONS WHERE THE
MECHANICS ARE COMPARABLE TO
THAT.
THEY DON'T HAVE THE UPRIGHT
POSTURE, STILL IT'S A HUGE
INCREMENT BUT SO EXPENSIVE.
BUT VERY IMPORTANT.
SO, YEAH, THANK YOU.
KELSEY?
YOU HAD A DISMOMENT.
>> -- YOU HAD A COMMENT?
>>THINK WITH THINKING ABOUT
iPS CELLS AND EDITING THEM,
GREAT STUFF, IN MY MIND THE
BARRIER IS THAT JUST LIKE WHAT
WAS JUST MENTIONED THAT GETS US
ONE STEP AWAY FROM BEING ABLE TO
INCORPORATE THE PAIN OUTCOMES,
I'M CURIOUS FROM PEOPLE THAT ARE
THINKING ABOUT THIS AS AN
OPPORTUNITY HOW DO YOU SEE
BRIDGING THAT GAP OF GETTING ONE
STEP TOWARD MAYBE
HIGH-THROUGHPUT FEASIBILITY, WE
HAVE SOME TARGETS AND PATHWAYS
IN MIND FOR PAIN MEDIATORS BUT
MIGHT NOT BE THERE YET BUT I
AGREE THAT SUCH AN EXCITING
CONCEPT TO THINK ABOUT
ESPECIALLY IN THIS CAPACITY.
>>WELL, MAYBE FOCUSING ON
TISSUE HEALTH IS AN OPPORTUNITY
HERE, RIGHT?
THAT WHAT IS THE HEALTH OF A
CHIP, I DON'T KNOW, BUT THAT
WOULD -- ONE POSSIBILITY IS TO
USE THE CHIPS TO UNDERSTAND
BETTER THE INTERPLAY BETWEEN
VARIOUS DIFFERENT TISSUES, YOU
KNOW, UNDER VARIOUS AMOUNTS OF
VARIOUS DIFFERENT TYPES OF
MECHANICAL ENVIRONMENTS WHICH
YOU CAN DO NOW.
AND REALLY FOCUSING ON THAT AND
NOT SO MUCH ON -- WELL, YOU CAN
ADD SENSORY NEURONS TO IT BUT
CAN'T OBVIOUSLY MEASURE THE PAIN
OF A CHIP.
SO, YOU KNOW, THERE'S A LOT THAT
CAN BE DONE IN THESE IN VITRO
MODELS, BUT, YEAH, ANNE-MARIE,
YOU HAVE THOUGHTS?
>>YOU'RE MUTED.
YOU'RE MUTED.
>>YEAH, SORRY ABOUT THAT.
THIS SOUNDS CRAZY BUT I THINK IN
THE LONG RUN I HAVE HOPES THAT
WE MAY SEE THE PAIN ON THE CHIP.
AND I THINK THAT'S PARTIALLY
BECAUSE THAT'S PARTIALLY, I SAID
IN THE LONG RUN, BECAUSE IT'S
PARTIALLY WHAT, FOR EXAMPLE,
RE-JOIN IS TRYING TO DO.
IF WE ARE REALLY GOING TO SPEND,
AND WE ARE, A LOT OF -- MANY OF
US SPENDING A LOT OF MONEY TO
REALLY PROFILE AND VERY DETAILED
MANNER WE'RE PROFILING THE
MOLECULAR SIGNATURES OF THE
JOINTS, ALL THE TISSUES THE
JOINTS, DORSAL ROOT GANGLIA OF A
WHOLE NUMBER OF PATIENTS,
DIFFERENT SEXES, WE HAVE PAIN
INFORMATION OF THESE PEOPLE,
ANIMALS, WE'LL MAP ALL THIS.
SO HOPEFULLY FIVE YEARS FROM NOW
WE'LL HAVE ALL THAT.
IT MAY BE NAIVE BUT HOPEFULLY
LOOK AT A PROFILE.
ONE THING SO DIFFICULT WITH
PAIN, PEOPLE ALWAYS SAY WE HAVE
NO BIOMARKERS.
BUT THIS WOULD BE A VERY
SOPHISTICATED WAY OF SAYING WE
CAN LOOK AT THIS DRG PROFILE
STATE AND IT WILL TELL US
EXACTLY WHAT'S HAPPENING TO THAT
PATIENT, MAYBE TO THE JOINT.
I KNOW THAT'S VERY SIMPLIFIED
AND TAKES AWAY THE WHOLE, YOU
KNOW, THE PATIENT AS A PERSON,
BUT IN A VERY, YOU KNOW, IT'S
REDUCTIONIST AND AT THE SAME
TIME IT ISN'T.
IT'S ONE WAY WHERE WE CAN GO AND
THAT MAYBE IS OPTIMISTIC.
ONE REASON WE'RE DOING, RE-JOIN,
RIGHT?
MULTIPLE TARGET IDENTIFICATION,
ALSO TO REALLY PROFILE
EVERYTHING GOING ON IN PEOPLE,
UH-HUH.
>>YOU WOULD HAVE TO BUILD A
CHIP BASED ON ALL THAT
INFORMATION, WHY NOT?
>>GOOD POINT.
YES.
WHO ELSE HAS COMMENTS?
REACTIONS TO THIS?
OR TOPICS THAT WERE NOT YET
BROUGHT UP?
LET'S SEE.
>>I CAN DROP IN THE COMMENT
THAT DR. MESSIER HAD ABOUT
CHALLENGE BARRIER, NOTING THE
DILEMMA OF WEIGHT REGAIN.
>>OH, YEAH.
>>DID YOU WANT DR. MESSIER TO
EXPAND BEFORE WE --
>>SURE, SURE.
>>DR. MESSIER, ARE YOU
AVAILABLE TO UNMUTE?
AND BRING UP YOUR VIDEO?
THERE YOU ARE.
>>YES.
WE HAD SOME SUCCESS IN THE
IDeA TRIAL, 3.5 YEARS AFTER
INTERVENTION, NO CONTACT WITH
THE PEOPLE.
AND THEY REGAINED ESSENTIALLY A
LITTLE OVER HALF THEIR WEIGHT
BACK.
SO THE QUESTION BECOMES REALLY
EVEN THOUGH 4, 6% WEIGHT LOSS
THAN FIVE YEARS BEFORE THAT, ARE
THEY REALLY HEALTHIER?
AND IN OTHER WORDS WAS IT WORTH
THEM GOING THROUGH THE WEIGHT
LOSS INTERVENTION?
3 1/2 YEARS AFTER IT WAS DONE?
AND SO TO ME, THERE WERE VARIOUS
WEIGHS, ESPECIALLY NOW WITH THE
PHARMACOLOGIC METHODS WE HAVE, I
THINK WE CAN GET PEOPLE TOE LOSE
WEIGHT.
I MEAN, WE'VE DONE IT A NUMBER
OF TIMES.
OTHER STUDIES HAVE DONE IT.
IT'S MAINTAIN THE WEIGHT LOSS
THAT IS THE HUGE QUESTION.
WHETHER IT IS -- WHETHER IT'S
WITH PEOPLE WHO ALREADY HAVE A
DISEASE OR PEOPLE WHO WE'RE
TRYING TO PREVENT A DISEASE FROM
HAPPENING.
AND SO THERE'S GOT TO BE A BIG
PSYCHOLOGICAL COMPONENT TO THAT.
BUT IT'S BAFFLING.
YOU KNOW, WE'RE NOT THE ONLY
ONES THAT TRIED TO DO THIS.
>>WELL, MAYBE IS IT POSSIBLE,
PEOPLE MAY NEED ONGOING SUPPORT.
MAY NOT BE REALISTIC TO ASSUME
PEOPLE CANNOT ONLY LOSE WEIGHT
BUT MAINTAIN THE WEIGHT LOSS
WITHOUT SUPPORT.
WE DON'T PROVIDE THAT.
WE DON'T REIMBURSE IT.
>>RIGHT.
>>THINK ABOUT HOW COST
EFFECTIVE THAT MIGHT BE.
>>THAT'S EXACTLY RIGHT.
AND OUR TRIALS WE HAVE A BIG
COST EFFECTIVE ANALYSIS IN ALL
OF OUR TRIALS.
>>YEAH, YOU PRESENTED THAT,
YEAH.
>>AND SO THE QUESTION IS, IF
YOU PROVIDE THAT SUPPORT THREE,
FIVE YEARS DOWN THE ROAD AFTER
THE INTERVENTION IS OVER, THEN
YOU ARE GOING TO GET CRITICIZED
FOR SAYING THAT'S NOT REALISTIC.
>>YEAH, BUT IF IT CAN BE SHOWN
ECONOMICALLY THAT IT SAVES SO
MANY HEALTH CARE COSTS LATER
DOWN THE ROAD, SAVE KNEE, JOINT
REPLACEMENT, ET CETERA, ET
CETERA, THAN THAT'S THE IDEA,
YOU COULD SHOW AN INVESTMENT IN
THE BEHAVIORAL CHANGE AND
MAINTENANCE OF THE BEHAVIORAL
CHANGE IS WORTH IT ECONOMICALLY
IN THE END.
>>YEAH, WE FEEL THAT WAY.
BUT OTHER PEOPLE DON'T.
>>HEALTH COACHING FOR EXAMPLE,
SOMEBODY'S MAKING A COMMENT IN
THE CHAT ABOUT HEALTH COACHING.
IT'S A RELATIVELY INEXPENSIVE
INTERVENTION THAT IF PROPERLY,
YOU KNOW, SUPPORTED AND
REIMBURSED COULD MAKE A BIG
DIFFERENCE LONG TERM.
SO, YES.
LET'S SEE.
DID SOMEBODY ELSE WANT TO
COMMENT ON THIS?
PREETI?
>>YEAH, HI.
I THINK THIS IS WHERE WE ARE
GOING WITH ALL OF THESE CHRONIC
DISEASES AND PAIN SEEMS TO BE
THAT THERE ARE PATIENTS AT HIGH
RISK, THAT MAY ACTUALLY NEED
INTERVENTIONS THAT ARE NOT JUST
ONE INTERVENTION BUT SOME KIND
OF LIFESTYLE COACH BECAUSE THAT
SEEMS TO BE ONE OF THE HARDEST
THINGS TO CHANGE BEHAVIOR.
>>YEAH.
EXACTLY.
YEAH, YEAH, YEAH.
KATIE?
>>YEAH, THANK YOU.
I WANTED TO COMMENT, THINK IT'S
A GREAT POINT THAT DR.
MESSIER -- DID I SAY IT RIGHT?
>>IT'S OKAY.
>>SO SORRY.
I'M MESSING UP EVERYONE'S NAME
TODAY.
THE POINT THAT THESE
INTERVENTIONS ARE NOT REALISTIC,
YOU KNOW, I THINK YOU BRING UP A
GREAT POINT BUT I THINK IF WE
CAN -- IT BECOMES A PROBLEM OF
HAVING -- OF TREATING A DISEASE
THAT ISN'T SEEN AS HAVING LIKE A
HIGH MORBIDITY OR MORTALITY
RATE, RIGHT?
SO LIKE IF WE'RE TREATING
CANCER, CANCER IS CONSIDERED
ESPECIALLY BREAST CANCER,
CONSIDERED LIKE LIFE-LONG
CONDITIONS THAT NEED TO BE
MANAGED, MONITORED, YOU'RE
LOOKING FOR RECURRENCE ALL THE
TIME.
AND NOBODY'S QUESTIONING
FOLLOWING UP WITH YOUR
ONCOLOGIST TEN YEARS LATER,
RIGHT?
SO YOU CAN -- THAT'S JUST HOW IT
IS.
AND CANCER-RELATED DISEASES.
SO I THINK HAVING A SHIFT IN
TERMS OF THINKING ABOUT PAIN AS
A DISEASE, JOINT HEALTH AS
DISEASES THAT REALLY AFFECT
MULTIPLE ASPECTS OF HUMAN
HEALTH, THINKING HOW WE CAN
PREVENT THAT.
I AGREE SOMETIMES WE'RE JUST
PUNISH -- - WHETHER IT'S HEALTH
CARE COMMUNITY OR SOCIETY WE'RE
NOT THERE YET IN TERMS OF
ACKNOWLEDGING THE HUGE BURDEN
THAT CHRONIC PAIN PUTS ON OUR
SOCIETY.
>>TOUCHED UPON SOMETHING VERY
IMPORTANT HERE, THAT AN
INTERVENTION LIKE HEALTH
COACHING, FOR EXAMPLE, MAY HELP
WITH PREVENTING, YOU KNOW, PAIN,
BUT IT COULD DO SO MUCH ELSE.
IT COULD PREVENT CARDIOVASCULAR
DISEASE, DIABETES, YOU KNOW,
PERHAPS EVEN DEPRESSION.
WE KNOW, FOR EXAMPLE, EXERCISE
IS PROTECTIVE FOR ALL THESE
FACTORS.
AND SO IT'S A BANG FOR THE BUCK,
AMAZING HOW EFFECTIVE IT COULD
BE IF IT COULD BE INVESTED UP
FRONT.
YEAH, LESLIE?
>>TO FOLLOW UP, THE U.S. RANKS
NEAR THE BOTTOM IN TERMS OF
HEALTH CARE QUALITY AND ACCESS
TO CARE, COMPARED TO OTHER
DEVELOPED COUNTRIES IN SPITE OF
THE MONEY WE SPEND.
I WORK WITH A LOT OF PEOPLE IN
EUROPE.
SOCIALIZED MEDICINE HAS SOME
GOOD THINGS IN TERMS OF
INTERPRETING OF PREVENTIVE CARE
LIKE HEALTH COACHING, PERHAPS WE
SHOULD BE LOOKING AT SOME OF THE
COUNTRIES THAT ARE MORE
SUCCESSFUL AT PROVIDING HEALTH
CARE THAN WE ARE.
AND SEE WHAT THEY ARE DOING
RIGHT.
>>PRETI, ANOTHER COMMENT?
>>DR. MESSIER'S FINDINGS ON
ATTENTION CONTROL BEING EQUALLY
EFFECTIVE, I DON'T KNOW THE
DETAILS, BUT THE IDEA OF
SOMEBODY BEING THERE TO HELP YOU
MAKE SURE YOU'RE DOING WHAT
YOU'RE SUPPOSED TO DO.
SOME PEOPLE NEED THAT FOR ANY
KIND OF -- THEY NEED THAT
STRUCTURE, NEED ACCOUNTABILITY.
AND SO PERHAPS THAT, THE
BEHAVIORAL, YOU KNOW,
MISSINGNESS THAT SOME PATIENTS
ABSOLUTELY NEED.
>>VERY, VERY GOOD POINT.
THIS PLACEBO, WHICH IS SUPPOSED
TO REALLY -- ATTENTION CONTROL
MAY BE ESSENTIALLY WHAT A HEALTH
COACH DOES.
YOU KNOW, MAYBE GIVING ADVICE
BUT MORE IMPORTANTLY A TOUCH
POINT FOR THE PERSON TO GET IN
TOUCH WITH NOW AND THEN.
>>WELL, ARE YOU TALKING
ABOUT -- WE'VE THOUGHT ABOUT
THIS, I'M NOT SKILLED IN THIS
AREA, BUT IMPLEMENTATION
SCIENCE.
>>YEAH.
>>YOU KNOW, SO WE HAVE DATA.
WE KNOW THESE THINGS WORK.
NOW CAN WE GET THEM INTO HEALTH
CARE SYSTEMS TO REALLY BE ABLE
TO MONITOR THESE PEOPLE LONG
TERM.
WE TRIED ONCE WE WENT THROUGH A
LOCAL HOSPITAL HERE IN NORTH
CAROLINA, AND THE CEO WAS ALL IN
ON IT.
AND WE DID A PILOT STUDY, AND
THEY WERE SO EXCITED ABOUT
GETTING DIET AND EXERCISE IN.
THEN HE RETIRED.
AND THAT WAS THE END.
YOU KNOW, BECAUSE THE NEXT
PERSON CAME IN, OH, NO, WE'RE
NOT GROWING -- GOING TO DO THI.
IT'S ALMOST LIKE YOU HAVE TO GET
SOMEONE AT THE TOP WHO BUYS IN,
HELPING TO RUN THE WHOLE THING.
IT WAS SUCH A DISHEARTENING
THING, YOU KNOW.
>>EVEN BETTER, SOMEBODY AT
CENTER FOR MEDICARE SERVICES.
>>RIGHT, YEAH.
>>THAT'S BEGINNING TO HAM.
I DON'T KNOW IF ANY OF YOU ARE
AWARE BUT THERE ARE TWO NEW
REIMBURSEMENT CODES NOW, CMS, IN
PLACE FOR ABOUT SIX MONTHS.
AND REIMBURSE PRIMARY CARE
PROVIDERS FOR DOING THE
EVALUATION AND REFERRALS TO THE
MULTIPLE DIFFERENT KINDS OF
PROVIDERS, YOU KNOW, NUTRITION,
PHYSICAL THERAPIST, HEALTH
COACH, ET CETERA.
DOESN'T GO AS FAR AS PAYING FOR
THOSE BUT SOME ARE ALREADY
REIMBURSED.
SOMEBODY WAS TALKING ABOUT THAT
EARLIER, ABOUT TAKING THE TIME
TO EVALUATE THE PATIENT.
I THINK DR. BROLINSON.
IT TAKES TIME, RIGHT, TO DO THE
BIOPSYCHOSOCIAL EVALUATION,
THAT'S RIGHT NOW, UNTIL NOW,
ESPECIALLY BUSY PRIMARY CARE
PROVIDERS ARE NOT REIMBURSED FOR
THAT BUT NOW THEY ARE.
IT'S VERY INTERESTING WHO IS
USING THESE CODES, PRIMARILY THE
PRIMARY CARE, NOT SO THE PAIN
SPECIALISTS.
SO INTERESTING TO FOLLOW WHAT
HAPPENS WITH THAT.
>>LOTS OF COMMENTS HERE.
KELSEY?
DO YOU WANT TO SAY YOUR COMMENT,
KELSEY?
>>SURE.
I WANTED TO CIRCLE BACK TO WHAT
WAS SAID ABOUT ROLE FOR ANIMAL
STUDIES ON A CHIP SYSTEM AND
OPPORTUNITY TO INTEGRATE
INTERVENTIONS AND MECHANISTIC
STUDIES, I WANTED TO EXPLORE A
LITTLE BIT MORE, SEE WHAT PEOPLE
THOUGHT GIVEN ALL OF THESE
CONFOUNDERS AND AGE, SEX, ALL OF
THIS GOOD STUFF, HOW WE COULD
MAYBE THINK ABOUT THIS TOGETHER
AND TAKE MORE COLLABORATIVE
APPROACH INSTEAD OF PROCEEDING
IN SILOS BY NECESSITY BECAUSE OF
FUNDING MECHANISM.
>>YES, I THINK YOUR RESEARCH
AND OTHERS WHO ARE DOING THIS
CROSS-SYSTEM, CROSS-TISSUE
CROSS-TALK IS REALLY OPEN BEING
A WHOLE AREA WHERE WE NEED THESE
KINDS OF APPROACHES TO DO THIS
JUSTICE.
AND TO MOVE THIS FORWARD.
ABSOLUTELY.
THIS NEEDS TO BE, ESPECIALLY IN
THE FIELD OF OBESITY, THE SEX
DIFFERENCES AND COMORBIDITIES
ARE SO BORN.
DOES ANYBODY ELSE HAVE THOUGHTS
ON THIS?
>>I WAS GOING TO SAY, KELSEY,
YOU KNOW, I THINK THESE ARE GOOD
IDEAS TO TAKE TO YOUR SOCIETY
RESEARCH SOCIETIES THAT YOU'RE
INVOLVED WITH AND TRY TO PUT
TOGETHER SOME WORKSHOPS, EVEN
PUTTING IN AN R13 TO NIH TO DO A
WORKSHOP, GETTING THESE GROUPS
TOGETHER TO GET
CROSS-FERTILIZATION OF IDEAS AND
APPROACHES IS REALLY A GOOD WAY
TO GO.
TEAM SCIENCE IS ANOTHER TERM FOR
WHAT YOU'RE TALKING ABOUT WHERE
YOU'VE GOT THE BASIC SCIENCE
FOLKS INFORMING THE CLINICAL AND
ANIMAL RESEARCH FOLKS, AND THEN
RESULTS COMING BACK TO THE BASIC
SCIENCE FOLKS AND KIND OF, YOU
KNOW, FORMING A TEAM THAT WORKS
TOGETHER AND TRIES TO SOLVE THE
PROBLEM.
SO I THINK YOU HAVE TO KIND OF
GENERATE A LITTLE BIT OF THAT
AND I DO THINK NIH IS REALLY ON
TO TEAM SCIENCE IN THAT REALM.
AND CERTAINLY INNOVATION.
SO I WOULD ENCOURAGE YOU TO
THINK ABOUT DOING THAT BECAUSE
CERTAINLY HAVE YOU THE
AMMUNITION WITH THE WORK YOU'RE
DOING.
>>THIS WAS ONE OF THE THEMES OF
THIS WORKSHOP, TO GET TOGETHER
PEOPLE FROM DIFFERENT FIELDS,
DIFFERENT AREAS, BOTH ON THE
BASIC SCIENCE SIDE AS WELL AS
CLINICAL SIDE, TO TALK.
I THINK FROM EVERYTHING THAT
WE'VE HEARD, I REALLY FEEL WE'VE
ACHIEVED THAT.
I DIDN'T POINT THAT OUT IN MY
REMARKS, TWO THREADS, TWO AREAS,
A NICE RESONANCE BETWEEN
YESTERDAY'S TALKS AND TODAY'S
TALKS.
ONE WAS IN THE AREA OF OBESITY
BECAUSE THAT GOT ADDRESSED AT
THE CELLULAR LEVEL, IN TERMS OF
PROFOUND INFLUENCE THAT ADIPOSE
TISSUE, ADIPOSE CELLS FROM
SYSTEMIC ASPECT IN TERMS OF
MECHANICAL ASPECT AS WELL AS
LOCAL PARACRINE ASPECT, HAVING
THAT ECHOED TODAY IN THE
CLINICAL STUDIES OF WEIGHT LOSS
AND EXERCISE.
AND THEN ANOTHER THREAD THAT WAS
CARRIED THROUGH ACROSS THE TWO
DAYS EXTRACELLULAR MATRIX
MECHANICAL ASPECTS, MOLECULAR
COMPONENT BUT AS WELL AS THE
SORT BIOMECHANICAL GROSS
CHARACTERISTICS OF THE TISSUE
IMAGING, SHEAR FORCES AND
STRENGTH.
I THINK FOR THOSE TWO, AND
OTHERS, JUST AN EXAMPLE OF TWO
AREAS WHERE I FELT THERE WAS A
NICE TRANSLATION ACROSS
DIFFERENT PARTS OF THE WORKSHOP,
I'M CURIOUS IF OTHER PEOPLE
NOTICED ANY OTHER AREAS WHERE
YOU FELT, OH, YOU KNOW, WHAT I
HEARD ON THE MECHANISTIC DAY,
DAY 1, OR MORE BASIC RESEARCH,
REALLY PLAYED INTO THE CLINICAL
AND VICE VERSA.
>>WE HAVE SOME QUESTIONS FROM
THE AUDIENCE, DR. LANGEVIN.
>>PLEASE GO AHEAD.
>>GREAT.
FIRST QUESTION, WHAT ROLE DO YOU
SEE FOR NON-TRADITIONAL
PRACTICES OR INTERVENTION IN
EARLY PREVENTION AND LATER
TREATMENT OF OSTEOARTHRITIS IN
FOR EXAMPLE, YOGA MOVEMENT COULD
BE HELPFUL IN DEVELOPING OR
CORRECTING BODY MECHANICS, AND
WHAT ABOUT THE WHOLE INDUSTRY OF
SUPPLEMENTS INCLUDING HERBAL
THERAPIES, ET CETERA?
>>I THINK THAT'S YOUR QUESTION,
HELL EARNINGS?
>>HERBAL THERAPIES?
WE DIDN'T TALK ABOUT THAT MUCH,
CERTAINLY AN AREA, THE WHOLE
THING WITH HERBAL, THE
INTERESTING THING ABOUT
BOTANICALS AND DIETARY
SUPPLEMENTS IS THAT THERE'S A
DIFFERENCE BETWEEN TAKING A
SUPPLEMENT AS A REPLACEMENT TO
CORRECT LIKE A DEFICIENCY AND
ALSO OR TAKING IT IN LARGER DOSE
TO ACT MORE LIKE A DRUG, YOU
KNOW, HAVING A TARGETED
BIOLOGICAL EFFECT.
AND SO THERE'S TWO DIFFERENT
WAYS TO THINK ABOUT THIS.
WE DIDN'T COVER A LOT TODAYN
THIS WORKSHOP, BUT IT'S AN AREA
WHEN YOU THINK ABOUT
MULTI-COMPONENT INTERVENTIONS
YOU COULD HAVE NUTRITIONAL
COMPONENT THAT WOULD NOT BE
SIMPLY BALANCED DIET AND CUT
BACK CALORIES, COULD BE
NUTRIENTS OR NON-NUTRIENTS,
COMPONENTS OF DIET THAT COULD BE
TESTED AS WELL.
I JUST SAW -- OOPS.
>>THE OTHER PART OF THE
QUESTION WAS THE PERSON ASKING
ABOUT GENERALLY THE ROLE FOR
NON-TRADITIONAL PRACTICES OR
INTERVENTIONS IN EARLY
PREVENTION, THEY ALSO NOTED
SOMETHING LIKE YOGA.
>>EXERCISE THERAPY.
>>WE TALKED ABOUT EXERCISE.
THERE WAS NOT ANY DISCUSSION OF
YOGA TODAY.
BUT CERTAINLY YOGA INCORPORATION
A LOT OF ELEMENTS.
THERE'S BASICALLY THE PHYSICAL
ACTIVITY COMPONENT, A STRETCHING
COMPONENT.
WE DIDN'T TALK ABOUT STRETCHING
TODAY BUT WHEN YOU TALK ABOUT
TISSUE PLANES THAT MAY HAVE
BECOME STIFF OR ADHERENT,
APPLYING STRETCHING THAT, YOU
KNOW, CREATES SOME SHEAR STRAIN
BETWEEN THE LAYERS OF TISSUE
ESPECIALLY CONNECTIVE TISSUE,
THAT COULD HAVE SOME VERY
IMPORTANT EFFECTS THAT WE DON'T
KNOW.
ONE COMPLEMENTARY MODALITY SHOWN
OVER AND OVER AGAIN TO BE
BENEFICIAL IS TAI CHI, EVEN MORE
THAN YOGA, THE THING ABOUT TAI
CHI IS THAT IT'S NOT EXTREME
STRETCHING, GOES THROUGH A RANGE
OF BEYOND PERHAPS WHAT THEY DO
IN THEIR EVERYDAY LIVES, BUT
DOESN'T STRETCH THE TISSUES TO
THE POINT OF INJURING THEM WHICH
SOMETIMES HAPPENS WITH YOGA, SO
IT'S VERY SAFE AND THERE'S ALSO
A CARDIOVASCULAR COMPONENT TO
TAI CHI, THAT HAS BEEN SHOWN TO
BE BENEFICIAL.
THE OTHER THING ABOUT YOGA AND
TAI CHI, THERE'S A NEURAL
COMPONENT, AWARENESS, SENSORY
AWARENESS THAT PROBABLY FEEDS
INTO PROPRIOCEPTION, WE TALKED
ABOUT THAT YESTERDAY.
WE TALKED ABOUT BECOMING AWARE
OF ONE'S JOINT POSITION IN
SPACE, AND THERE HASN'T BEEN
DETAILED STUDIES OF THIS BUT
CERTAINLY HELPS WITH BALANCE, SO
PROBABLY HELPS WITH
PROPRIOCEPTION AS WELL, WOULDN'T
BE SURPRISED IF THAT WAS
MEASURED IN DETAIL IN TERMS OF
EFFECT ON JOINT PROPRIOCEPTION,
MIGHT HAVE AN EFFECT BUT NO
SPECIFIC RESEARCH THAT I KNOW OF
ON THIS.
IS THAT THE WHOLE QUESTION?
A LOT OF QUESTIONS.
>>THAT IS THE QUESTION.
ANOTHER QUESTION FROM DR.
WILLIAMS, DR. BROOKS.
ALEX, DID YOU WANT TO POSE THAT
QUESTION?
>>DR. BROOKS MENTIONED MAYBE A
FRAME SHIFT TO CONSIDER NOT ONLY
THE JOINT AS AN ORGAN BUT ALL OF
THE MUSCULOSKELETAL JOINTS AS
COMPONENTS OF ORGAN SYSTEM
GENERATING HUMAN POSTURE AND
MOVEMENT.
IS THERE AN OPTIMAL OR HEALTHY
AMOUNT OF MOVEMENT OR POSTURE AS
A WHOLE SYSTEM?
IS THAT SOMETHING THAT THE
PANELISTS COULD MAYBE DISCUSS OR
THINK ABOUT?
I THOUGHT OF IT WITH TAI CHI.
>>INTERESTING QUESTION.
ANYBODY HAVE THOUGHTS?
YOU'RE TALKING WHOLE BOUGHT, NOT
JUST WHOLE JOINT, RIGHT?
>>RIGHT.
>>WHOLE BODY.
>>LIKE A JOINT SYSTEM, YES.
>>YEAH, YEAH.
LESLIE?
>>YEAH, THERE'S A FAIR AMOUNT
OF RESEARCH THAT SHOWS THAT
THOSE FULL BODY MOVEMENT ARTS
ARE BENEFICIAL FOR THINGS LIKE
BALANCE, BUT ALSO FOR DECREASING
STRESS WHICH CAN BE HELPFUL FOR
DECREASING PAIN AND POTENTIALLY
DECREASING INFLAMMATION, SO FULL
BODY MIND-BODY MOVEMENT ARTS
DEFINITELY HAVE A ROLE, AND
PHYSICAL THERAPISTS ARE
INTEGRATING THEM BECAUSE THEY
ARE HOLISTIC AND PEOPLE CAN
CONTINUE ON THEIR OWN AND NOT
NEED THE HEALTH HEALTH CARE SYO
PARTICIPATE IN.
>>ANYBODY ELSE?
THERE'S A GENERAL QUESTION THAT
THE CHAIRS MIGHT BE ABLE TO
ANSWER, FROM KAREN.
INTERESTED IN HOW PATIENTS AND
OTHER INTERESTED PARTIES CAN
CONTRIBUTE TO THE SCIENCE AND
IMPROVING PATIENT CARE BEYOND
PARTICIPATING DIRECTLY IN
CLINICAL TRIALS.
>>I'M SORRY, CAN YOU REPEAT
THAT?
>>INTERESTED MEMBER OF THE
PUBLIC HOW THEY CAN BE INVOLVED
IN SCIENCE BESIDES DOING
CLINICAL TRIALS.
>>OH, HOW THE PUBLIC CAN BE
INVOLVED?
WELL, THERE'S A BIG -- THERE'S A
LOT OF INCREASED AWARENESS OF
THE IMPORTANCE OF PATIENT --
PUBLIC ENGAGEMENT, RIGHT?
IN DOING EXACTLY WHAT YOU'RE
DOING NOW, PARTICIPATING IN
THESE TYPES OF CONFERENCES AND
REALLY HELPING YOU ILLUMINATE
IMPORTANT RESEARCH QUESTIONS
THAT MATTER TO YOU, AS A
PATIENT, SO PATIENT ENGAGEMENT
IN RESEARCH IS EXTREMELY
IMPORTANT, NOT JUST IN BEING A
VOLUNTEER OR PARTICIPANT BUT
ALSO HELPING TO ASK THE RIGHT
QUESTIONS.
>>I THINK THERE ARE ROLES FOR
THE PUBLIC IN ORGANIZATIONS LIKE
ARTHRITIS FOUNDATION,
FOUNDATIONS THAT ARE FOCUSED ON
ALMOST EVERY DISEASE AND
DISORDER.
AND THIS DO A LOT OF TRYING TO
REACH OUT TO OTHER PEOPLE WITH
DISEASE HELP THEM GET
INFORMATION, DO ADVOCACY FOR THE
PARTICULAR DISEASES WITH THE
CONGRESS.
THAT IS A HUGELY IMPORTANT ROLE
IN GETTING MORE RESEARCH FUNDING
FOR THESE GROUPS.
FOR THESE TOPICS OF RESEARCH AND
DOING IT THROUGH THESE
FOUNDATIONS IS REALLY EFFECTIVE
WAY IN MOST CASES.
I DON'T KNOW ABOUT YOUR FEELINGS
ON THAT, HELENE.
>>WELL, YEAH.
WE ACTUALLY JUST STARTED OUR OWN
STAKEHOLDER -- WE HAD A
STAKEHOLDER MEETING LAST FALL
OPEN TO ANYBODY WHO WANTED TO
PARTICIPATE WHO WAS INTERESTED
IN WHOLE PERSON HEALTH.
AND SO WE HAD MEMBERS OF THE
PUBLIC, SOME ADVOCATES BUT ALSO
JUST PEOPLE INTERESTED.
SO HOPEFULLY WE'LL HAVE MORE OF
THOSE TYPES OF MEETINGS.
SO, YEAH.
LET'S SEE.
ANYTHING ELSE, ALEX?
>>MARCUS POSTED A QUESTION A
WHILE AGO, APPRECIATE YOUR
PATIENCE.
WOULD YOU LIKE TO MAYBE POSE
THIS QUESTION TO THE PANEL?
>>THANK YOU, ALEX.
I BROUGHT THIS UP BECAUSE IT'S
BEEN TOUCHED ON A FEW TIMES, THE
WHOLE IDEA OF INTERINDIVIDUAL
RESPONSE HETEROGENEITY.
WE TALKED IN THE CONTEXT OF
TREATMENT BUT WE DIDN'T TALK
ABOUT IT SO MUCH IN THE CONTEXT
OF DISEASE PROGRESSION, AND I
THINK BOTH ARE EQUALLY IMPORTANT
AND FRANKLY OPEN FOR SCIENTIFIC
DISCOVERY.
I THINK, YOU KNOW, THE CHALLENGE
THAT WE HAVE FOR THOSE WHO ARE
ACTUALLY INTERESTED IN THIS
TOPIC, WHEN WE LOOK AT DATASET,
WE'RE INTERESTED IN THE RANGE OF
THE DATA, INTERESTED IN THE
VARIANTS, THE PEOPLE ON THE END
OF THE SPECTRUM THAT DON'T
RESPOND AS WELL AS THOSE WHO
RESPOND IN A ROBUST WAY, THOSE
TWO EXTREMES ARE VERY
INTERESTING SCIENTIFICALLY AND I
THINK IF WE LEARN FROM BOTH OF
THOSE WE CAN REALLY ADVANCE THE
FIELD FOR THOSE IN THE MIDDLE.
BUT THE CHALLENGE WE HAVE AS
RESEARCHERS IS, YOU KNOW,
WHETHER IT'S FUNDING AGENCIES OR
WHETHER IT'S REVIEW PANELS, THE
FIELD AS A WHOLE CONTINUES TO BE
FOCUSED ON THE ME, DID YOU SEE A
GROUP-WIDE CHANGE, IS YOUR
GROUP-WIDE CHANGE DIFFERENT FROM
GROUP WITTED -WIDE CHANGE IN THL
GROUP, NON-DISEASE GROUP.
IF YOU WANT TO MOVE TOWARDS
PRECISION MEDICINE OR PRECISION
RE
REHABILITATION WE HAVE TO STUDY
IT WELL, I THINK THAT'S A MIND
SHIFT CHANGE IN SOME RESPECTS,
TO REALLY OPEN UP TO THIS
DISCOVERY OPPORTUNITY THAT
REQUIRES QUITE LARGE DATASETS AS
WELL AS INNOVATIVE METHODS TO
GET AT THE -- YOU KNOW, THE CORE
DIFFERENCES.
SO JUST OPEN THAT UP FOR
DISCUSSION.
>>IT'S AN EXCELLENT POINT.
ANYBODY HAS ANY FURTHER THOUGHTS
ON THIS?
VERY IMPORTANT.
THERE WAS ALSO A COMMENT,
SUPPLEMENTS AND DIETS, COULDN'T
AGREE MORE.
THERE'S ALSO A LOT OF NEGATIVE
EVIDENCE MEANING TRIALS THAT
SHOW THERE'S NO EFFECT AND THESE
ARE VERY IMPORTANT BECAUSE
PEOPLE SHOULD NOT BE WASTING
THEIR MONEY ON SUPPLEMENTS,
VITAMINS AND DIFFERENT
SUPPLEMENTS, WHEN BASICALLY
EATING A BALANCED, YOU KNOW,
DIET PROVIDES ALL THE NUTRIENTS
AND MINERALS, ET CETERA, THAT WE
NEED.
SO VERY IMPORTANT, YES, INDEED.
COULDN'T AGREE MORE.
>>I BRING THAT UP BECAUSE OF
THE GLUCOSAMINE STORY, LOOK AT
THE EVIDENCE, PRETTY CLEAR FROM
CLINICAL TRIALS AND FROM LOTS OF
IN VITRO STUDIES HAS NO EFFECT
BUT STILL A BILLION DOLLAR
BUSINESS.
>>OH MY GOODNESS.
SO MANY OTHER PRODUCTS THAT ARE
BEING SOLD THAT PEOPLE ARE
TAKING.
NOT ONLY UNNECESSARILY BUT ALSO
WHEN THE DOSES SOME OF THESE
PRODUCTS ARE SOLD AT CAN BE
DOWNRIGHT HARMFUL, SOME OF
THESE.
SO IT'S VERY IMPORTANT THAT WE
AT LEAST STUDY THESE PROPERLY.
BECAUSE PEOPLE ARE TAKING THEM.
YEAH.
>>I HAD A COMMENT ON WHAT DR.
BOWMAN SAID ABOUT ADDRESSING
INTERINDIVIDUAL VARIABILITY.
I DON'T THINK THAT THE WAY
FORWARD IS TAKE INTO ACCOUNT
THAT EVERY PATIENT HAS A MIX OF
THE RISK FACTORS, AND THAT IF
WE, YOU KNOW, I KEEP GOING BACK
TO DR. MESSIER'S WORK WHERE HE
SHOWED THAT, YOU KNOW, IF A
PATIENT IS OBESE THEN CLEARLY
OBESITY LEADS TO A CERTAIN
DEGREE OF INFLAMMATION, AND SO
REDUCING FAT CONTENT WILL MAKE
THE BIGGEST DIFFERENCE.
WE ALSO KNOW THAT EXERCISE IS
ANTI-INFLAMMATORY BUT IF YOU
EXERCISE TOO MUCH YOU CAN CAUSE
INJURY.
AND THAT INJURY COULD LEAD TO
INFLAMMATION, REPAIR MECHANISMS
AS WELL.
SO THIS WHOLE IDEA OF TAKING ALL
THESE VARIOUS COMPONENTS INTO
CONSIDERATION REALLY CALLS FOR
THESE SINGLE PERSON OR PRECISION
TRIALS WHICH MIGHT BE ANOTHER
DESIGN THAT WE NEED TO EMBRACE
WHERE, YOU KNOW, AN N-of-1
MIGHT STILL BE IN THE WHOLE
STUDY BUT N-of-1 STUDY, HOW
DO WE DO THOSE?
>>STEVE, ARE YOU WANTING TO
ANSWER OR DO YOU HAVE A
DIFFERENT QUESTION?
>>I WAS GOING TO SUGGEST FOR
MARCAS, HOW DO YOU STUDY THE
OUTLIERS?
WHICH IS A GREAT QUESTION,
MARCAS.
MAYBE THIS IS JUST OFF THE TOP
OF MY HEAD, MAYBE YOU DO THE
TRADITIONAL THING FOR THE
PRIMARY OUTCOME BUT THEN WITHIN
THE SAME STUDY YOU HAVE
SECONDARY OUTCOMES WHERE YOU
LOOK AT THE OUTLIERS.
SO YOU DON'T BECOME TOO MUCH OF
A REBEL, JUST HALF OF A REBEL.
>>I AGREE WITH YOU.
I AGREE WITH YOU AND THINK SOME
OF THE WORK THAT WE'VE BEEN
DOING ADDRESSING IT IN JUST THE
WAY YOU JUST DESCRIBED.
I THINK THOUGH AS A COMMUNITY WE
NEED TO BE THINKING ABOUT TO
REALLY UNDERSTAND THIS, THIS
REQUIRES MORE THAN YOUR SAMPLE
SIZE CALCULATION FOR YOUR RCT.
SO THAT'S THE HURDLE, RIGHT?
HOW DO WE GO FROM ANSWERING THE
PRIMARY QUESTION TO EMBRACING
THIS VARIABILITY THAT WE CAN
THEN LEVERAGE TO REALLY GO AT
THIS WHOLE IDEA OF PRECISION
MEDICINE OR PRECISION
REHABILITATION.
I MEAN, IT'S A TALL TASK,
REQUIRES A LOT OF DATA.
WE'VE GOT TO FIGURE OUT HOW TO
GET THERE.
YOU KNOW, A LOT OF THE DATA YOU
PRESENTED, YOU'VE DONE A
FABULOUS LONG-TERM WORK, YOU
PROBABLY ALREADY LOOKED BUT IF
YOU LOOK AT DATA ON WEIGHT
REBOUND, SOME PEOPLE
SUCCESSFULLY MAINTAIN THE LOSS,
SOME PEOPLE MAY HAVE REGAINED
ALL THE WEIGHT, MAYBE SOME WENT
HIGHER THAN WHERE THEY ENDED THE
TRIAL, WHAT MADE THEM DIFFERENT
IN THREE YEARS OF FOLLOW-UP, A
LOT TO BE DONE.
>>ABSOLUTELY.
KELSEY HAS A COMMENT ABOUT THE
REBOUND BIOLOGY?
>>I WAS CHIMING IN, COMMENTING
TOO MUCH, REALLY EXCITED ABOUT
THIS TOPIC, LISTENING TO WHAT
DR. MESSIER SAYS, HIS COHORT AND
OTHERS LIKE THE BIGGEST LOSER
COHORT, METABOLIC DYSREGULATION
PERSISTS, IF THE REMAINING FAT
IS DYSREGULATED IN A WAY WE
DON'T TOTALLY UNDERSTAND WHAT
DOES THAT MEAN?
THE WAY WE'RE THINKING ABOUT
THESE PROBLEMS?
>>I WANT TO FOLLOW UP ON WHAT
KELSEY SAID, SO TRUE BECAUSE
THERE ARE MULTIPLE MECHANISMS OF
EITHER REPROGRAMMING
EPIGENETICALLY YOUR CELLS SO YOU
LOSE WEIGHT BUT EVERYTHING'S
BEEN MODIFIED AND REALLY GROWING
EVIDENCE THAT THOSE CHANGES CAN
BE TRANSMITTED
INTERGENERATIONALLY, THE
EPIGENETIC CHANGES.
SO NOT CHANGING YOUR DNA
SEQUENCE BUT EPIGENETIC CHANGES
THAT PREDISPOSE YOU TO FURTHER
OBESITY OR OSTEOARTHRITIS CAN GO
DOWN AT LEAST TWO GENERATIONS,
EVEN IF YOU'RE ON A NORMAL DIET
AFTER THAT.
SO THESE ARE FACTORS WE DON'T
THINK ABOUT, WHAT DID YOUR
GRANDPARENTS EAT CAN AFFECT YOUR
HEALTH RISK BROADLY AND NOW
EVIDENCE IT CAN AFFECT YOUR
ARTHRITIS RISK, HOW DO WE ERASE
AND RESET THE EPIGENETIC CLOCK,
REMOVE THE IMMUNE DYSFUNCTION
THAT YOU'VE PUT INTO YOUR SYSTEM
BY BEING OVERWEIGHT FOR HALF A
LIFETIME OR EVEN UP TO
ADOLESCENCE, IT'S HARD TO
DEPROGRAM IF YOU'RE OBESE IN
YOUR ADOLESCENT YEARS, VERY HARD
TO DEPROGRAM YOUR CELLS AND YOUR
IMMUNE SYSTEM FROM THAT.
SO THESE ARE THINGS THAT WILL
CARRY ON, TIES INTO WHAT DR.
MESSIER SAID AND WHAT WE'VE SEEN
IN THESE STUDIES, YOU LOSE
WEIGHT, MAY NOT STICK BECAUSE
YOU HAVE PROPENSITY TO GAIN IT
BACK BUT AS KELSEY SAID MAY HAVE
ADDITIONAL IMMUNE DYSFUNCTION
EVEN WITHOUT THE WEIGHT.
>>ONE MORE COMMENT AND WE'LL
HAVE TO TRANSITION SOON.
MARCAS?
>>I THINK IT'S A REALLY
IMPORTANT TOPIC, ALSO
TRANSGENERATIONAL BENEFITS THAT
CARRY OVER FROM THINGS LIKE
EXERCISE TRAINING AND SO THAT'S
A WHOLE AREA OF INTERESTING
BIOLOGY, EPIGENETIC
MODIFICATIONS, ASSOCIATED WITH
ANY BEHAVIOR THAT CONTINUE TO
THE NEXT, YOU KNOW, OFFSPRING,
TWO TO THREE GENERATIONS DOWN
THE LINE, SOME NEW DATA AND
EXERCISE SHOWING NOT ONLY
MATERNAL BUT ALSO PATERNAL
EPIGENETIC MODIFICATIONS IN
EXERCISING ANIMALS AND SO THAT'S
DEFINITELY SOMETHING THAT NEEDS
TO BE CONSIDERED AS WELL.
>>THAT'S THE OPTIMISTIC SIDE OF
THINGS, RIGHT?
>>YEAH.
>>RIGHT IN BECAUSE -- RIGHT.
WHAT WE TRANSMIT TO OUR
OFFSPRING MIGHT BE SORT OF, YOU
KNOW, NEGATIVE BUT ALSO COULD BE
POSITIVE.
PERHAPS THE BALANCE BETWEEN THE
TWO, YOU KNOW, THERE'S SOME
THINGS YOU CAN'T DO ANYTHING
ABOUT.
BUT BEHAVIOR CHANGES IS
SOMETHING YOU CAN DO SOMETHING
ABOUT.
SO I JUST WANTED TO POINT OUT
THAT MANY OF THE ISSUES THAT WE
DISCUSSED IN TERMS OF CLINICAL
TRIAL DESIGN, ESPECIALLY WITH
REGARD TO MULTI-COMPONENT
INTERVENTIONS AND MULTI-SYSTEM
OUTCOMES, WE DISCUSSED AT A VERY
INTERESTING WORKSHOP THAT WE HAD
TWO YEARS AGO ON WHOLE PERSON
RESEARCH, AND JUST LIKE THIS
WORKSHOP IS VIDEO RECORDING,
RECORDING AVAILABLE ON OUR
WEBSITE, THE WHOLE PERSON
RESEARCH WORKSHOP IS AVAILABLE
AND WE'VE HAD A LOT OF PEOPLE
VIEW IT, AND IT REALLY DELVED
INTO THE COMPLEXITY OF DESIGNING
TRIALS THAT ARE NOT JUST ONE
DRUG, ONE MOLECULE.
SO ANYWAY, I GUESS I WANT TO
THANK EVERYBODY FOR THIS
WONDERFUL DISCUSSION AND SUCH A
WONDERFUL EXCELLENT ARRAY OF
PRESENTERS.
THANK YOU, CATHERINE, FOR
PUTTING THE LINK IN THE KTLA --
CHAT AND I WILL LET ALEX WRAP UP
AND SEND US ON OUR WAY.
>>CAN I TAKE A MOMENT BEFORE
YOU CLOSE OUT TO SAY HOW
FANTASTIC THIS HAS BEEN.
I WANT TO THANK ALEX AND
CATHERINE, THE ENTIRE TEAM.
IT WAS A CROSS-NIH TEAM WHO PUT
THIS TOGETHER BUT IT'S BEEN MUCH
MORE THAN ONE WOULD HAVE EVER
EXPECTED.
SO THANK YOU ALL FOR ALL YOUR
EFFORTS.
THANKS TO ALL THE PRESENTERS
WHICH I KNOW CATHERINE IS GOING
TO SAY.
>>THANK YOU, DR. LESTER AND DR.
LANGEVIN FOR A WONDERFUL JOB OF
SUMMARIZING, WHAT YOU HEARD,
WHAT YOU ARE EXCITED TO SEE,
GAPS, THANK YOU BOTH FOR A
WONDERFUL SESSION 6 AND GENERAL
DISCUSSION TO BRING US NOW TO
TURNING THINGS OVER TO DR. ALEX
TUTTLE, PROGRAM DIRECT GALORE
NCCH DIVISION OF EXTRAMURAL
RESEARCH, TO BRING OUR WHOLE
JOINT HEALTH WORKSHOP TO A CLOSE
WITH CONCLUDING REMARKS.
ALEX, I'M TURNING IT OVER TO
YOU.
PLEASE UNMEET.
>>I GOT THE MUTE.
THANK YOU VERY MUCH FOR THE
INTRODUCTION AND THANK YOU FOR
ALL MODERATION OVER THE PAST TWO
DAYS.
IT WAS SEAMLESS AND I THINK WE
HAD A LOT OF GREAT DISCUSSIONS.
GREAT SCIENTIFIC TALKS.
A LOT TO THINK ABOUT.
RATHER THAN REHASHING WHAT WE'VE
JUST BEEN DISCUSSING IN TERMS OF
TAKEHOME MESSAGES AND HIGH
PRIORITY OR MUCH-DISCUSSED
TOPICS I'LL THANK EVERYONE WHO
MADE THIS WORKSHOP POSSIBLE.
NIH SPEAKERS, DR. REBECCA BAKER
FOR SETTING ETHICS OFF, DR.
LANGEVIN FOR OPENING COMMENTS
AND, DR. CRISWELL WHO ALSO
PROVIDED OPENING COMMENTS AND
DR. EMMELINE EDWARDS, FOR
PROVIDING CLOSING COMMENTS
YESTERDAY.
I THANK DR. KOROSHETZ, NINDS
DIRECTOR, FOR OPENING DAY 2 THIS
MORNING AND DR. LESTER FOR HER
PARTICIPATION AND MODERATION OF
SESSION 6.
THANK YOU TO ALL OF OUR NIH
LEADERS.
I WANT TO THANK THE SCIENTIFIC
PLANNING COMMITTEE MEMBERS.
THIS WAS A VERY LARGE EFFORT
ACROSS SEVEN I.C.s INTERESTED
IN THIS TOPIC.
IN PARTICULAR I WANT TO THANK
DR. WEN CHEN WHO HELPED ME
DEVELOPED THE PROGRAM INITIALLY
AND PRESENTED TO OTHER
INSTITUTES AND CHAIRS AND
CO-CHAIRS ACROSS THE NIH WHO
REALLY HELPED TO DEVELOPED
PROGRAMS, SELECT SPEAKERS,
EXTERNAL CO-CHAIRS, , SET THE
PROGRAM, NOT POSSIBLE WITHOUT
DEDICATED MEMBERS SUPPORTING
THIS EFFORT.
LAST BUT NOT LEAST I WANT TO
THANK THE NCCIH LOGISTICS TEAM,
THIS INVOLVES PEOPLE IN THE
DIVISION OF EXTRAMURAL RESEARCH
WHO WORK WITH ME, OUR ANALYST,
OUR BRANCH CHIEF, ANITA WHO
PROVIDED OUTREACH SUPPORT AND
EMMELINE EDWARDS TO HELP APPROVE
THE PROGRAM AND CIRCULATE ALL OF
THE MATERIALS AS WELL AS OFFICE
OF COMMUNICATIONS STAFF,
CATHERINE LAW, DIRECTOR, WHO
MODERATED, LED HER TEAM DOING A
GREAT JOB, IRENE LIU, AILEEN
AMADOR, SUPPORT WITH MODERATING
QUESTIONS, AND BRYAN WHO
PROVIDED ALL THE MATERIALS,
BACKDROPS OVER THE PAST TWO
DAYS.
THANKS TO SOPHIA AND TEAM FOR
PUTTING TOGETHER PROGRAM BOOK
AND FINAL A AGENDA.
THIS IS THE REAL LAST, THANK YOU
TO EVERYONE WHO PROVIDED
SCIENTIFIC TALKS, PARTICIPATED
AS PANELISTS, MEMBERS WHO SIGNED
ON AND PARTICIPATED WITH US OVER
THE PAST TWO DAYS.
YOUR VIEWERSHIP AND QUESTIONS
WERE A LARGE PART AND GAVE US A
LOT TO THINK ABOUT.
THANK YOU FOR YOUR PARTICIPATION
AND CONTRIBUTIONS, I'LL TURN
THINGS BACK OVER TO CATHERINE
LAW TO TAKE US OUT.
>>THANK YOU SO MUCH, ALEX.
I HAVE A WONDERFUL TASK OF
REMINDING VIEWERS, I THANK THEM
FOR JOINING US AND SHARING
WONDERFUL QUESTIONS, FROM OUR
AUDIENCE TODAY.
AND NOW I'M GOING TO REMIND YOU
ALL WE HAVE RECORDED THIS, IT
WILL BE ARCHIVED FOR FUTURE
VIEWING, YOU CAN SHARE THIS WITH
COLLEAGUES AND MAKE SURE
EVERYBODY WATCHES IT.
AND WITH THAT SAID, I WANT TO
ALSO ECHO ALEX'S THANKS TO
EVERYBODY HERE TODAY, PLANNING
TEAM MEMBERS, AND THE WONDERFUL
SPEAKERS AND PANELISTS, AND I
THINK WE HAD A VERY RICH
DISCUSSION ACROSS ALL OF OUR
SESSIONS SO I CONGRATULATE YOU
ALL ON TACKLING VERY FASCINATING
TOPICS.
SO WITH THAT, I'M GOING TO BRING
OUR MEETING TO A FINAL CLOSE.
THANK YOU AND GOOD EVENING.
I HOPE TO SEE YOU ON ANOTHER
ZOOM IN THE FUTURE OR MAYBE IN
AN IN-PERSON MEETING EVEN.
WITH THAT, I WISH YOU ALL WELL .
HAVE A WONDERFUL EVENING.
THANK YOU.
BYE-BYE.