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The Future Today:
Advanced Modalities
James C McKee, DPM, ABPM
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Objectives
● Participants will be aware of several new technologies in the field of
woundcare.
● Participants will know what PCR is and how it might be useful in diagnosing
wounds.
● Participants will have a brief introduction to use of cellular tissue grafts.
● Participants will be introduced to the role of metabolic surgery in diabetes,
and how it will impact healing in the future.
● Participants will be introduced to use of stem cells in the wound healing
environment.
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Disclosures
None.
Opinions presented in this talk are my own and not necessarily the opinions of
MultiCare Health.
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Bariatric surgery?
● “Metabolic surgery can cause amelioration, resolution, and possible cure of
type 2 diabetes.” (Buchwald)
● Bariatric surgery not just for weight loss
● In 1995 Pories et al found that blood glucose levels normalized within 24h of
RYGB procedure.
● Possible to relapse after procedure, Arterburn showed ⅓ of patient with type
2 remission after bariatric surgery.
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● STAMPEDE trial (Surgical Treatment and Medications Potentially Eradicate
Diabetes Efficiently) looks at surgery and medical vs intensive medical
therapy alone.
● Found surgery and medical much better for lowering A1C (Schauer)
● Meta-analysis
○ 135,246 pts
○ Mean excess weight loss 55.9% excess body weight
○ 78.1 complete resolution or 86.6 improvement of DM2 (p<0.001)
(Buchwald)
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Bariatric surgery
● Surgeons now exploring not bariatric but metabolic surgery
● Not for weight loss specifically, but alters metabolic system
● Resolution or improvement of DM2
● Earlier studies showed that best time was within 5 years of DM dx
● As more data available all time-limit categories benefit
● Goal is staving off morbidity and mortality of DM
● Can’t perform surgery on the up to 30% of US population which may qualify
● Make friends with local bariatric surgeon and get further info (TEAM)
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Advanced
Wound Cultures
● Difference between a
swab culture and deep
tissue culture
● Technique
● Intro to polymerase chain
reaction (PCR)
● PCR is a molecular
method to identify a
genomic region of
interest (Spichler)
● Open article.
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PCR
● Dedicated culture tube for each
vendor/company
● Do not send to your lab
● Report will be much more
detailed
● May need to call ID
● Recommend involving ID early
anyway
● Pro
○ Identify more organisms,
especially gram -
● Limitations
○ Too much info
○ Cost $$ vs normal lab
○ Time to ship
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Even More
Advanced
● Maldi/TOF
● Uses laser to burn, then uses aromatic signature
● Mainly academic with thousands of results possible
● Narrowing to be useful in clinical practice
● Already used in hospitals for MRSA and some other
highly pathogenic strains
● Very unwieldy report
● Ge et al
● 12,202 isolates
● Processing time decreased
○ Aerobes from 32.5 to 4.1 hours
○ Anaerobes from 71.5 to 46 hours
● Reduced waste by 4.2 tons per year
● Cheaper by 3-5 fold vs standard testing
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Cellular Tissue
Products
● Lavery et al
● RCT, n=50
● Complete healing at 12
weeks
● Human viable wound matrix
● Grafix 62% vs control 21%
● Exclusion criteria!
○ Active infection
○ Osteomyelitis
○ ABI <0.7 or > 1.3
○ A1C > 12
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Cellular Tissue
Products
● Amniotic membrane / placental
membrane
● Human Viable Wound Matrix
(hVWM)
● Contains MSCs
● Large number of growth factors
● This study was on
cryopreserved product
● Now have shelf stable variant
also
● Wound bed prepared, remove
slough and non-viable tissues
● Application weekly
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Caution
● Considerations
○ Pt may react to graft
○ Never graft over infection
○ Wound bed preparation
○ Review application materials - many grafts are
over granular base only (ie no bone/tendon)
○ Stop grafting if infection, etc
○ Expensive
■ Always preauth
■ Discuss with pt
■ Be a good steward of resources
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Vancomycin
Powder
● Application of topical
vancomycin to reduce surgical
site infections (SSI)
● 81 pts
● SSI decreased 73% in active
group
● Inexpensive $5 per 1G
● **Performed on elective
surgeries for diabetic pts
● Not on pts with active infection
or undergoing amputations
● Clinical application?
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Antibiotic “beads”
● Older type is PMMA
● Polymethyl methacrylate
● Sets up then stays hard
● Never loses shape, must be
removed at later time if
problematic
● Infuse with heat stable
antibiotics
○ Vancomycin
○ Tobramycin
● May inhibit bone growth
(McKee 2010)
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Absorbable beads
● CaSO4
● Body may resorb or
remodel
● Same composition
as bone
● May infuse with heat
stable antibiotics
○ Vancomycin
○ Tobramycin
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If using multiple
antibiotics use
bigger bowl
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Stem Cells in
Wounds
● Maranda et al
● Mesenchymal Stem Cells
(MSCs)
● Differentiate into muscle,
cartilage, fat and bone
● Isolated from own tissue
● Cells have express human
leukocyte antigen (HLA) and
may become immunogenic if
from a different host
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Stem Cells in
Diabetic Wounds
● May directly differentiate and
replace lost tissue
● May induce angiogenesis
○ This is often deficient in
DM or vascular wounds
● MSCs will
○ Decrease inflammation
○ Self renew
○ Will produce new growth
factors in area to replace
depleted or missing
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MSC in DM
● Rat model
● DM MSCs found defective in
rate of mobilization vs non-DM
MSC
● May be best to apply directly to
wound (Vs injecting into
system)
● Low N-number studies
● Need real-world studies
● Cost prohibitive
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Stem cells
● Massee et al
● Dehydrated human amniotic
chorionic membrane (dHACM)
allografts
● Regulation of diabetic stem
cells in vitro
● Shows that introduction of
healthy adipose derived stem
cells were able to restore
function of existing stem cells
● Restore faulty cellular signalling
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● ADSC growth factor
secretion
● Left Type I
● Right Type II
● Partial listing
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Case
● DM pt
● Off medications - lost
insurance
● Foot evaluated and felt not
too bad initially
● Limb salvage consulted
● BG on admit >500 mg/dL
● Living in 300’s on floor
● On eval pt wants to know if
he can go to work in a few
days
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Initial
Debridement
● All areas of
abscess need to
be evaluated
● Follow where
abscess leads
● No exposed bone
● Multiple deep
sinus
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4 weeks later
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● Tried VAC
● Too wet in SNF
environment
● Purple is
methylene-blue
6 weeks
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12 weeks
● Compliant patient
● Remained in SNF
throughout recovery
**HIGH RISK FOR LIFE**
Needs long term follow
up.
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Questions
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References
1. Maranda EL, Rodriguez-Menocal L, Badiavas EV. Role of Mesenchymal Stem Cells in Dermal Repair in Burns and Diabetic Wounds. Curr Stem Cell Res Ther. 2017;12(1):61-70.
2. Wukich DK, Dikis JW, Monaco SJ, Strannigan K, Suder NC, Rosario BL. Topically Applied Vancomycin Powder Reduces the Rate of Surgical Site Infection in Diabetic Patients
Undergoing Foot and Ankle Surgery. Foot Ankle Int. 2015;36(9):1017-1024.
3. Spichler A, Hurwitz BL, Armstrong DG, Lipsky BA. Microbiology of diabetic foot infections: from Louis Pasteur to “crime scene investigation.” BMC Med. 2015;13:2.
4. Lavery LA, Fulmer J, Shebetka KA, et al. Grafix Diabetic Foot Ulcer Study Group: The efficacy and safety of Grafix (®) for the treatment of chronic diabetic foot ulcers: results of a
multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J. 2014;11:554-560.
5. Zelen CM, Serena TE, Gould L, et al. Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective, randomised, controlled, multi-centre
comparative study examining clinical efficacy and cost. Int Wound J. 2016;13(2):272-282.
6. Zelen CM, Gould L, Serena TE, Carter MJ, Keller J, Li WW. A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated
human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int Wound J.
2015;12(6):724-732.
7. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. N Engl J Med. 2017;376(7):641-651.
8. McKee MD, Li-Bland EA, Wild LM, Schemitsch EH. A prospective, randomized clinical trial comparing an antibiotic-impregnated bioabsorbable bone substitute with standard
antibiotic-impregnated cement beads in the treatment of chronic osteomyelitis and infected nonunion. J Orthop Trauma. 2010;24(8):483-490.
9. Ge M-C, Kuo A-J, Liu K-L, et al. Routine identification of microorganisms by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: Success rate, economic
analysis, and clinical outcome. J Microbiol Immunol Infect. 2017;50(5):662-668.