The Future Today:

Advanced Modalities

James C McKee, DPM, ABPM

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.

Disclosures

None.

Opinions presented in this talk are my own and not necessarily the opinions of

MultiCare Health.

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.

● 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)

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)

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.

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

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

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

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

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

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?

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)

Absorbable beads

● CaSO4

● Body may resorb or

remodel

● Same composition

as bone

● May infuse with heat

stable antibiotics

○ Vancomycin

○ Tobramycin

If using multiple

antibiotics use

bigger bowl

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

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

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

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

● ADSC growth factor

secretion

● Left Type I

● Right Type II

● Partial listing

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

Initial

Debridement

● All areas of

abscess need to

be evaluated

● Follow where

abscess leads

● No exposed bone

● Multiple deep

sinus

4 weeks later

● Tried VAC

● Too wet in SNF

environment

● Purple is

methylene-blue

6 weeks

12 weeks

● Compliant patient

● Remained in SNF

throughout recovery

**HIGH RISK FOR LIFE**

Needs long term follow

up.

Questions

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.