**8. The essential role of multidisciplinary approach in ischemic ulcer healing**

Increasing clinical evidence suggests that despite "well-suited" revascularization efforts, at least 25% of DFS ulcers will eventually not heal, and around 28% may end however with some form of amputation [58, 120].

It appears unmistakable that no current *single* therapy can enhance *alone* profitable healing results in a majority of CLI ulcers [1, 27, 58] without concomitant management of all risk factors, including ischemic, metabolic, septic, local pressure, neuropathic, and adequate off-loading appointed treatment [1–3, 120–123]. Wound healing embodies a complex cascade of molecular and clinical events in continuous dynamic interaction [34, 48]. It was stated that because CLI wound etiology is always multidimensional [1, 27, 58], specific therapy in turns requires a parallel multidisciplinary application [1–3, 120, 121].

Every individual risk factor requires accurate identification and management and represents a fundamental task for any multidisciplinary wound center to encourage [124]. Investing *healing* as the primary endpoint in care acts as a real benchmark for all collective therapeutic efforts [57, 87, 124].

All these briefly schematized *arterial-arterial* communications constitute but a small part of the whole natural foot compensatory system against ischemic aggression [23, 24, 35]. Although severely compromised in distinct CLI categories of patients (diabetes, ESRD, and inflammatory arteritis) [59–61, 104], all these "rescue branches" [35, 59, 101, 102] or "choke-vessels" [23, 24] provide noticeable flow assistance during miscellaneous ischemic injuries. Their appropriate evaluation affords valuable diagnostic and therapeutic knowledge for better tissue preserva-

In this exhaustive "regional view" of ischemic tissue perfusion, albeit more precise than blunt angiographic assessment (Section 4.5), it appears that *not all foot areas may express similar ischemic affliction* [59–61, 104]. Even more surprisingly, the ulcer's area could not always stand for the lowest perfusion point in the ischemic limb, since severe neuropathy, inflammatory swelling, sepsis, and local skin trauma may add complementary hindrance to main CLI threat [26, 27,

Future diagnostic tools focusing on *superficial* and *deep* tissue "wound-oriented" arterial flow may eventually complete this unique holistic view of the neuro-ischemic diabetic foot [33, 39,

We know today that diabetic and renal CLI patients express serious tissue regeneration handicap, inflicted by specific infragenicular arterial collateral depletion [29–31]. This significant decay in tissue regeneration also appears proportionate with the *type* and *time* of ischemic suffering [1, 2, 27, 30, 59]. In this perspective, recent researchers advise reasonable adaptation of current revascularization indications upon individual *macro* [3, 41] and *microvascular* CLI characteristics [29–31, 39], weighted in patients *with* and *without* available

**8. The essential role of multidisciplinary approach in ischemic ulcer**

Increasing clinical evidence suggests that despite "well-suited" revascularization efforts, at least 25% of DFS ulcers will eventually not heal, and around 28% may end however with some

It appears unmistakable that no current *single* therapy can enhance *alone* profitable healing results in a majority of CLI ulcers [1, 27, 58] without concomitant management of all risk factors, including ischemic, metabolic, septic, local pressure, neuropathic, and adequate off-loading appointed treatment [1–3, 120–123]. Wound healing embodies a complex cascade of molecular and clinical events in continuous dynamic interaction [34, 48]. It was stated that because CLI wound etiology is always multidimensional [1, 27, 58], specific therapy in turns requires a

Every individual risk factor requires accurate identification and management and represents a fundamental task for any multidisciplinary wound center to encourage [124]. Investing

tion and limb salvage [39, 56–59].

266 Wound Healing - New insights into Ancient Challenges

collateral reserve [29, 39, 59].

form of amputation [58, 120].

parallel multidisciplinary application [1–3, 120, 121].

31, 33].

53, 59].

**healing**

The recent guidelines document of the Society for Vascular Surgery connecting with the American Podiatric Medical Association and the Society for Vascular Medicine acts as a great reference to current evidence of ischemic wound treatment [120]. This noteworthy analysis addresses best available proofs and guidelines to date on the following main indicators: (1) prevention of diabetic foot ulceration, (2) off-loading, (3) diagnosis of sepsis and foot osteomyelitis, (4) specific wound care, and (5) peripheral arterial disease in DFS [120].

*Prevention* following evidence-based program includes the patient and the referral General Practitioners (GP) as active members of the multidisciplinary group [120–123]. Knowing that peripheral neuropathy can generate about 45–65% of DFS ulcers, patients with neuropathy hold >3.5-fold complementary risk for iterative neuro-ischemic ulceration [26, 71, 87, 120]. Adequate *laboratory tests* surveillance also represents a critical method as to minimize detrimental obstacles in tissue regeneration [120–123]. It has been recorded that for every additional 1% increase in HbA1C, there is a 0.028 cm/day healing decay in DFS wounds [120–125]. The major importance of *off-loading* devices in the global healing process is acknowledged [57, 58, 120–122]. Pressure reduction is reputed to allow superior healing effects to any revascularization strategy [2, 57, 58, 120–124]. Early diagnostic and treatment of *foot infection* also have paramount consequences in correct tissue regeneration [2, 57–59, 120–122]. Expeditious *local wound debridement* following timely reevaluation schedule bears huge implications for maintaining tissue viability, parallel to revascularization [57–59]. Since aggressively applied, early debridement can save millimeters of "time-dependent" irreversible damage [2, 57, 58, 61, 87, 120–124].

Appropriate *wound dressing* should help by maintaining a moist wound bed, providing exudate drainage, and urging granulation of tissue defect [53, 57, 120, 126].

The adapted dressing should match each specific CLI pathology, wound features and location, and individual amount of exudates, inflammation, and pain [87, 88, 120, 126].

New *complementary therapies* including negative pressure therapy, living cellular therapy, extracellular matrix products, and hyperbaric oxygen therapy were equally developed in the last years [57, 127]. Their application should follow multidisciplinary team advises [88, 120, 127] in ulcers that fail to demonstrate >50% area reduction per month, using standard therapy [120, 127].

Although revascularization still holds specific postoperative indicators [33, 39], the global efficacy of multidisciplinary approach can be timely rated by percentage reduction in wound extent as an early predictor of clinical success [120, 126]. Wound surface diminution of 10–15% per week, or >50% in 4 weeks strongly suggests increased likelihood of healing and diminished probability for amputation [120, 121, 126].

### **8.1. Ischemic wound healing as an integrated medicine concept**

The contemporary practitioner becomes aware that every ischemic ulcer presentation should be carefully weighted and treated alike *distinct pathological prototype*. It appears reasonable that for every single ulcer puzzling (in various amounts) possible neuropathic, ischemic, hyperglycemic, uremic, venous hypoxic, septic, hypoproteic, or pressure threats, only a multimodal team approach may afford better healing expectations [121–126, 128, 129]. Every chronic ulceration case can be theoretically approached alike a 3-D graphical mold assembling in different proportions of some or the whole of the determinants mentioned above. The vital role of any multidisciplinary team is to decode each clinical presentation into basic pathological influences and treat them upon best available knowledge granted by all participant specialties [121, 123, 126].
