Recent advances in treatments for diabetic foot ulcers have allowed for limbs to be healed that were previously thought unsalvageable, provided a variety of individualized treatment options, and reduced healing times. Key factors that impair wound healing in diabetics include peripheral arterial disease, neuropathy, infection, and structural foot problems. Advanced treatments such as growth factors, skin substitutes, negative pressure therapy, and hyperbaric oxygen can enhance healing when wounds are not responding to traditional care. Recurrent ulcers can be prevented through education, good foot care, appropriate footwear, and surgical correction of deformities when needed.

1. Advances in healing of diabetic ulcers J. Palmer Branch, DPM Comprehensive Foot and Ankle, LLC www.comprehensivefootandankle.net DrCuboid@aol.com Lilburn, GA (770-921-8800) Cumming, GA (770-886-6833) 1

3. What happens in the normal healing process?

4. Why do diabetic patients not heal as well as non-diabetics?

5. How do you examine the wound for potential problems?- What can be done to enhance / expedite the healing process? - What types of advanced treatments and products are available? - When should advanced treatments be used? - How can recurrent diabetic ulcers be prevented? 2

6. Overview – Additional comments Recent advances in treatments for diabetic foot wounds have: Allowed the ability to heal limbs previously thought to be unsalvageable (e.g. Interventional arteriography / arterial stenting) Enhanced the variety of treatment options to better individualize care for each situation and wound. Provided a better recognition of the wound healing process. Reduced the healing time Reduces risk of infection – less window of opportunity Can reduce overall treatment cost 3

7. Demographics - USA In the US Diabetes has reached epidemic proportions Over 16 million people diagnosed with diabetes 8 million estimated undiagnosed 15% of all diabetics will have a foot ulcer at some point in their lives PAD risk 2-6 times greater in diabetics. 6% of all diabetics undergo amputation 75% of all diabetic amputations are preventable Increased 5 year mortality rate (18 to 55% higher in ischemic ulcers) 4

8. Costs of diabetic limb amputation Costs – average cost per amputation over $40,000 (Surgeon procedure fees only $750 – 1200) Estimated Cost - diabetic amputations in US $1 billion (2007) Medical cost factors: Hospitalization - Home nursing Surgical procedures - Skilled nursing facilities Prosthetic limbs - Recurrent problems Other cost factors Lost wages – short-term and long-term Lost income tax revenues to federal / state / local government Dependence on public assistance – Medicaid, Social Security Depression, despondency, disruption of family. 5

9. Cardiac disease and foot ulcers Increased cardiac workload after partial foot or leg amputation – should not be quick to do this. Cardiovascular disease has been found to be increased by amputation alone in populations not controlled for diabetics. Modnay & Peles -21.9 % vs. 12.1% over a 21-year time period in lower extremity traumatic amputees in military veterans Question not answered well in literature: Is the increase in mortality from cardiac disease due to inactivity vs. the cardiac strain or some combination of factors? 6

10. Risk factors for impaired wound healing PAD (peripheral arterial disease) – 2-6 times more prevalent in DM. Neuropathy – lack of protective sensation, motor imbalance Immunocompromised status Structural problems – focal pressure sites Contractures of toes, bunion deformities Equinus contractures – tightness of the Achilles tendon Charcot joint / arthropathy Other health factors 7

11. PAD and wound healing The threshold circulation necessary for wound healing in the diabetic foot is systolic toe pressure 30-45mm Hg or ankle pressure 50-80mm Hg (ABI 0.40 – 0.66) Arteriosclerosis in diabetics can cause noncompressibleartertiesleading to falsely elevated pressures on lower extremity arterial Doppler evaluation. TcPO2 of 30mm Hg also mentioned frequently as a threshold value for wound healing. 8

12. Consider not only the quantity of blood getting to the wound, but also the quality of the blood. Evaluate for systemic factors anemia (CBC with differential) hypovolemia malnutrition (albumin/prealbumin, total protein) hyperglycemia 9

13. Causes of ulcers - Neurologic Loss of protective sensation (LOPS) Motor imbalances – Dropfoot and other motor function alteration Autonomic neuropathy Charcot Arthropathy / Charcot Joint 10

14. Venous Ulcers Venous - Lack of return of venous blood to the heart - Fluid buildup / edema in the legs - Skin necroses due to underlyling venous pressure and buildup of waste products – produces an ulceration. - Stasis dermatitis often noted in chronic cases - Compression a key to treatment 11

15. Evaluation of the diabetic ulcer 12

16. Evaluation of the diabetic ulcer Size – length, width and depth Probe to bone or visible bone clinical osteomyelitis Grayson - 75 patients, 76 ulcers Sensitivity of 66% for osteomyelitis Specificityof 85% Positive predictive value of 89% Negative predictivevalue of 56%. 13

17. Evaluation of the diabetic ulcer Cellulitis – not always present in patients with PAD or immune compromise Wound base quality – eschar, granular, fibro-fatty Malodor Surrounding skin and wound margins 14

18. Evaluation of the diabetic ulcer Location Abscess visible or palpable tissue crepidus Drainage type Purulent vs. serous Amount – Healthy granular tissue normally has mild to moderate drainage. Heavy drainage – may have venous and/or infectious component Little to no drainage – may have ischemic component 15

19. 16 Ulcer associated with brown recluse spider bite, skin necrosis, underlying abscess Digital ulcer in diabetic with PAD, ischemic base, atrophic skin

20. Radiographic / Imaging for infection X-rays osteomyelitis (bone erosions, periostitis) soft tissue gas MRI Useful if X-rays not definitive Nuclear Medicine 3 phase bone scan – more sensitive than plain X-rays for osteomyelitis, less specific Often false positive with Charcot joint, Arthritis, fracture, recent injury, recent bone surgery (6 or more months) Labeled scan (Indium, Gadolinium, Ceretec) may be more specific 17

21. Classifications of diabetic ulcers Wagner – most commonly used and recognized. Stage 0 - No active ulcer, but risk factors present (pre-ulcerative callous, history of foot ulcer, foot deformity) Stage 1 - Superficial ulcer , to subcutaneous fat. Stage 2 - Ulcer to tendon, ligament, joint capsule, or deep fascia, no major abscess Stage 3 -Ulcer to bone (or deep abscess) Stage 4 - Ulceration with forefoot ischemia. Stage 5 - Ulceration with ischemia of entire foot. University of Texas – San Antonio Others 18

22. Basics of wound healing

23. General principles of good wound care KISS principle (Keep It Simple, Stupid) Be sure to not overlook the obvious Evaluate and treat infection if present fully Removal of nonviable and infected tissue when possible In osteomyelitis, all infected bone should be removed See if the wound will rapidly respond to simple, basic treatments. If it isn’ t broken, don’t fix it. Continue basic treatments and regular observation. 20

24. Treatments / wound care Traditional products Saline, betadine, gauze, etc. Pressure relief Braces (e.g. Podus boots) Pillows Ambulatory bracing 21

25. Other wound care products Chemical debriders Unna boots, multi-layered compression wraps Leg compression pumps May be helpful with venous ulcers Debriding / wound lavage instruments Pulse lavage Ultrasonic and hydrosurgicaldebriders 22

27. Helpful particularly in cases where limb perfusion cannot be enhanced by vascular intervention.

28. Have to be cautious of hypotension particularly in elderly and/or those with cardiac disease– apply thin layer.23

29. Surgical procedures - traditional Incision and drainage / surgical debridement “The solution to pollution is dilution”. Removal of infected / nonviable tissue. All infected bone in osteomyelitis should be removed. Amputation levels BKA/ AKA – goal is to avoid Symes, Chopart’s, Transmetatarsal, LisFranc’s Digital – partial or complete Surgical Wound closure / coverage Flaps (Advancement, rotational) Skin Grafts Other complex wound 24

30. Surgical procedures -Amputations Considerations in amputation selection level Vascular supply - Is it adequate for healing? - Is the patient a candidate for revascularization? Consider how the limb and patient will function Nonambulatory patients may be better served with a more proximal amputation Patients with otherwise impaired isolated limb function need individualized consideration Dropfoot Flexion Contracture Preservation of as much of a functional limb as possible. - Decreased cardiac workload Plan bone and soft tissue resection and closure carefully to prevent further problems 25

31. Advanced treatments and products 26

32. Newer wound dressings Advanced wound dressings – more absorbent, hydrating, and/or antimicrobial than gauze Alginates– very absorbent (e.g. Fibracol) Hydrogels – maintain optimal wound hydration, Silver – antimicrobial vs. MRSA contamination / colonization Silver alginates – e.g. Acticoat rope Silver Hydrogels – e.g. Silvasorb, Aquacel Ag Silver sheet dressings – e.g. Acticoat Honey Collagen dressings (Promogran) – release collagen into wound base which is helpful in wound healing. 27

33. Topical - Growth Factors Stimulate the healing process Dermagraft– Vicryl sheet with Fibroblasts Apligraf – similar product – bilayered absorbable mesh with keratinocyteson one layer, fibroblasts on the other. Regranex – Topical gel with smaller amounts of growth factors. Procuren - Older product Future Stem cell-derived products, Additional bilayered skin equivalents 28

35. Provides a collagen scaffold for ingrowth of granulation tissueBrigido - Compared single application of GraftJacket to sharp debridement, weekly dressing changes - 85.7% healed with GraftJacket at 12 weeks vs. 28.6% healed at 12 weeks without. Integra – dermal replacement, bilayered – allows for ingrowth of new skin Oasis – Porcine intestinal subucosa Pegasus (OrthoAdapt) – equine pericardium Rejection a possibility 29

36. SCAFFOLD CONCEPT – HEALING TISSUE GROWS INTO THE GRAFT – GRAFT REPLACED WITH PATIENT’S OWN TISSUE OVER TIME

37. GraftJacket – Sample case After debridement Infected wound dehiscence ulcer– 6 weeks s/p I & D, & IV antibiotics GraftJacket applied in OR (Osteoset antibiotic beads and VAC also used.) 31

38. GraftJacket – Sample case 1 week post-op Osteoset absorbable antibiotic beads also noted 2 weeks post - op 8 weeks post-op Wound healed around 16 weeks post - op 32

40. Prevents macerationCan reduce wound volume by suction effect Enhances capillary ingrowth Daily dressing changes not necessary –1-2 times a week. Classic article – Morykwas and Argenta, 1997. Also frequently used with split-thickness skin grafts and freeze-dried dermis graftsto enhance adherence of the graft to the wound base. 33

41. Business Template 34

42. Hyperbaric Oxygen Mechanisms of action: wound healing is enhanced by increased fibroblast proliferation, increased collagen production, increased capillary angiogenesis, and release of growth. 100% oxygen in a pressurized full-body treatment chamber Usually pressurization should be at least 1.4 atmabs (usually 2 – 2.5 atm abs) Can enhance wound healing, particularly in debilitated patients Effects on the oxygen saturation of the blood may be more important that local effects on the wound. Useful in infections – antimicrobial effects, particularly in anaerobic infections (bacteriostatic), osteomyelitis 35

43. Advanced Treatments – When to use If the wound is not responding well to traditional care Sheehan- 203 patients (prospective, randomized) study Median healing percentage at 4 weeks – was 53% -If > 53% healed @ 4 weeks, then 58% chance of full wound healing at 12 weeks -If < 53% healed, then only 9% were healed at 12 weeks. Conclusion – if not 53% healed at 4 weeks, then additional care needed. Anticipated difficulty in healing / high complication potential Size/ depthAnatomicLocation Patient risk factors Cost-Effectiveness Considerations: Is the potential cost of not doing something more aggressive going to be more expensive than the cost of the advanced therapy? 36

44. Questions to ask when considering advanced and / or new treatments Are there other treatable reasons the ulcer is not healing? Infection – adeqaute medical and surgical treatment Vascular supply – is it adequate or can it be improved? Patient factors - (overall health, noncompliance, etc.) Pressure relief – offload the wound site Would additional consults be appropriate? Is there adequate evidence based medicine that the treatment or product is effective, particularly for the situation? 37

45. Selection of appropriate advanced therapy How can the healing process be best enhanced for the ulcer? Applying medical expertise and judgment to each situation Medicine is often more an art than a science. Know what each product can do – particular indications and benefits of each device or treatment. Are there any reasons why advanced treatments cannot be used in the situation? 38

46. The Healed Diabetic Foot – What next? Crane M, Branch P. Clin Pod Med Surg. v. 15, n 1, Jan 1998, p. 155-74. 39

47. Prevention of diabetic foot ulcers Education risk of foot ulcers and importance of early treatment. Patients should examine their feet daily Annual foot exam -more frequent if high ulcer risk (previous ulcer,neuropathic, PAD). - Diabetic neurologic evaluation (PQRI #G8404) - Evaluation for appropriate diabetic foot wear (PQRI #G8410) Recommended by the American Diabetes Associationas well as annual eye exam. relative risk for ulceration 40

48. Diabetic Nail and Callous care Prevention / early treatment of ingrown nails and pre-ulcerative callouses Prevention of patients cutting the skin when cutting their own nails 41

49. PAD – Follow-up Follow-up for progressive PAD Clinical exam Arterial ultrasound Ensure maintenance of adequate vascular status. Particularly important after vascular intervention (stenting, bypass, etc.) to examine for patency of the treated arteries. 42

50. Protective devices for foot ulcer prevention Custom Braces AFO (Ankle – Foot Orthosis) Dropfoot braces Rigid AFO for severe flatfoot or other deformities Patellar Tendon brace – shifts some pressure to patellar tendon Protective shoes Extra Depth shoes with custom molded protective foam insoles to balance pressure Custom Molded shoes – made from a plaster mold of the patient’s foot Commonly used in severe foot deformities – e.g. Charcot Rocker- bottom foot 43

51. Diabetic shoes - Characteristics Medicare Therapeutic Shoe Bill covers protective shoes for diabetics annually. Also covered by many private insurers and Medicaid providers Extra-depth shoes vs. True Custom-molded shoes Documented success CDC has proven that they reduce the incidence of foot amputation In patients with a history of foot ulcers, 80% without diabetic shoes, 20% with properly fitted protective diabetic shoes. At minimum are cost-neutral Should be professionally fitted by individuals with proper training (DPM, C Ped, CO) 44

52. Elective surgical procedures Surgical intervention For pain and/or ulcer prevention from foot deformities Conservative measures should be exhausted first Example elective minor procedures Hammertoe and Bunion correction 45

53. Elective surgical procedures Tendon lengthening or tenotomy procedures for contractures Exostectomy procedures (reduction of bony prominences) Reconstructive surgery (e.g. Charcot joint reconstruction / realignment) Should be only as a last resort and undertaken with great caution and careful patient selection. Patient MUST be thoroughly evaluated before surgery for adequate circulation and other risk factors for wound healing problems. 46

54. “Those who suffer losses due to diabetes are not just statistics on a chart. They are people whose talents and wisdom are needed and whose problems deserve our unified efforts. Together we can make life more just and more joyful for generations to come” D Satcher 47

55. THANK YOU J. Palmer Branch, DPM – DrCuboid@aol.com Comprehensive Foot & Ankle, LLC www.comprehensivefootandankle.net Lilburn, GA (770-921-8800); Cumming, GA (770-886-6833) 48

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57. Bibliography Armstrong DG, Lavery LA, Wu S, Boulton AJ. Evaluation of removable and Irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial. Diabetes Care. 2005, v 28 , n 3, p. 551-54. Rogers LC, Lavery LA, Armstrong DG. The right to bear legs – an amendmentt to healthcare; how preventing amputations can save billions to the US healthcare system. J Am Podiatr Med Assoc. 2008, v. 98, n 2, p. 166-68. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W,: Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plant Surg 1997, v. 38. P. 553-62. Brigido SA. The use of an acellular dermal regenerative tissue matrix in the treatment of lower extremity wounds: A prospective 16- week pilot study. Accepted to International Wound Journal., 2006. Moulik PK, Mtonga R, Gill GV. Amputation and mortality in new onset diabetic foot ulcers stratified by etiology Diabetes Care. 2003. v. 26, n 2, p. 491-4 Boyko EJ, Ahroni JH, Smith DG, Davignon D. Increased mortality with diabetic foot ulcer. Diabetic Medicine. V 13, issue 11, p. 967-72. Padberg FT, Back TL, Thompson PN, Hobson RW. Transcutaneous oxygen (TcPO2) estimates probability of healing in the ischemic extremity. J of Surgical Research. 1996. v 60. p. 365-9. Bunt TJ, Holloway AJ. TcPO2 as an accurate predictor of therapy in limb salvage. Annals of Vascular Sugery. 1996. v 10, n. 3. p. 224-7. Knighton DR, Fiegel VD, Douchette M. Treating diabetic foot ulcers. Diabetes Spectrum. 1990. v. 3, p. 51-6. 50

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59. Bibliography Sheehan P, Jones P, Giurini JM, Caselli A, Veves A. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. PlastReconstrSurg 2006 Jun; 117(7 Suppl):239S-244S. Grayson ML, Gibbons GW, Baloh K, Levin E, Karchmer AW: Probing to bone in infected pedal ulcers: a clinical sign of underlying osteomyelitis in diabetic patients. JAMA 273:721-723, 1995. Fife C, Buuykcakir C, Otto G; Sheffield P, Warriner A, Love T, Mader J. The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective analysis of 1144 patients. Wound Repair & Regeneration. 10(4):198-207, July/August 2002. Crane M, Branch P. The Healed Diabetic Foot – What next? Clin Pod Med Surg. v. 15, n. 1, Jan 1998, p. 155-74. 52