Literature review on the management of diabetic foot ulcer

Diabetic foot ulcer (DFU) is the most costly and devastating complication of diabetes mellitus, which affect 15% of diabetic patients during their lifetime. Based on National Institute for Health and Clinical Excellence strategies, early effective management of DFU can reduce the severity of complications such as preventable amputations and possible mortality, and also can improve overall quality of life. The management of DFU should be optimized by using a multidisciplinary team, due to a holistic approach to wound management is required. Based on studies, blood sugar control, wound debridement, advanced dressings and offloading modalities should always be a part of DFU management. Furthermore, surgery to heal chronic ulcer and prevent recurrence should be considered as an essential component of management in some cases. Also, hyperbaric oxygen therapy, electrical stimulation, negative pressure wound therapy, bio-engineered skin and growth factors could be used as adjunct therapies for rapid healing of DFU. So, it’s suggested that with appropriate patient education encourages them to regular foot care in order to prevent DFU and its complications.     

Choice of wound care in diabetic foot ulcer: A practical approach

Diabetic foot ulcers are the consequence of multiple factors including peripheral neuropathy,decreased blood supply,high plantar pressures,etc.,and pose a significant risk for morbidity,limb loss and mortality.The critical aspects of the wound healing mechanism and host physiological status in patients with diabetes necessitate the selection of an appropriate treatment strategy based on the complexity and type of wound.In addition to systemic antibiotics and surgical intervention,wound care is considered to be an important component of diabetic foot ulcer management.This article will focus on the use of different wound care materials in diabetic foot.From a clinical perspective,it is important to decide on the wound care material depending on the type and grade of the ulcer.This article will also provide clinicians with a simple approach to the choice of wound care materials in diabetic foot ulcer.     

The role of surgical debridement in healing of diabetic foot ulcers

An estimated 15% of patients with diabetes mellitus will develop a foot ulcer during their lifetime. Debridement is included in multiple guidelines and algorithms for the care of patients with diabetic neuropathic foot ulcers, and it has long been considered an essential step in the protocol for treating diabetic foot ulcers. In addition to altering the environment of the chronic wound, debridement is a technique aimed at removing nonviable and necrotic tissue, thought to be detrimental to healing. This is accomplished by removing abnormal wound bed and wound edge tissue, such as hyperkeratotic epidermis (callus) and necrotic dermal tissue, foreign debris, and bacteria elements known to have an inhibitory effect on wound healing. While the rationale for surgical debridement seems logical, the evidence for its role in enhancing healing is deficient. In this paper, we systematically review five published clinical trials, which met the criteria and investigated surgical debridement of diabetic foot ulcers to enhance healing. Most existing studies are not randomized clinical trials optimized to test the relationship between debridement of diabetic foot ulcers and wound healing. Therefore, a focused, well‐designed study is needed to elucidate the effect of surgical debridement on the healing status of chronic wounds.     

Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing

Type 2 diabetes mellitus (T2DM) increases the risk of many lethal and debilitating conditions. Among them, foot ulceration due to neuropathy, vascular disease, or trauma affects the quality of life of millions in the United States and around the world. Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase. Despite advanced treatment, diabetic foot ulcers (DFUs) are associated with a risk of amputation. Thus, there is a need for novel therapies to address chronic inflammation, decreased angiogenesis, and impaired granulation tissue formation contributing to the non-healing of DFUs. Studies have shown promising results with resolvins (Rv) and anti-inflammatory therapies that resolve inflammation and enhance tissue healing. But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency, tissue targetability, and immunogenicity. This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs. The articles discussing the T2DM disease state, current research on Rv for treating inflammation, the role of Rv in enhancing wound healing, and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy. The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with anti-inflammatory agents as promising therapeutic agents in ulcer healing.     

Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing

HYPOTHESIS: In patients with diabetic foot and pressure ulcers, early intervention with biological therapy will either halt progression or result in rapid healing of these chronic wounds. DESIGN: In a prospective nonrandomized case series, 23 consecutive patients were treated with human skin equivalent (HSE) after excisional debridement of their wounds. SETTING: A single university teaching hospital and tertiary care center. PATIENTS AND METHODS: Twenty-three consecutive patients with a total of 41 wounds (1.0-7.5 cm in diameter) were treated with placement of HSE after sharp excisional debridement. All patients with pressure ulcers received alternating air therapy with zero-pressure alternating air mattresses. MAIN OUTCOME MEASURE: Time to 100% healing, as defined by full epithelialization of the wound and by no drainage from the site. RESULTS: Seven of 10 patients with diabetic foot ulcers had complete healing of all wounds. In these patients 17 of 20 wounds healed in an average of 42 days. Seven of 13 patients with pressure ulcers had complete healing of all wounds. In patients with pressure ulcers, 13 of 21 wounds healed in an average of 29 days. All wounds that did not heal in this series occurred in patients who had an additional stage IV ulcer or a wound with exposed bone. Twenty-nine of 30 wounds that healed did so after a single application of the HSE. CONCLUSIONS: In diabetic ulcers and pressure ulcers of various durations, the application of HSE with the surgical principles used in a traditional skin graft is successful in producing healing. The high success rate with complete closure in these various types of wounds suggests that HSE may function as a reservoir of growth factors that also stimulate wound contraction and epithelialization. If a wound has not fully healed after 6 weeks, a second application of HSE should be used. If the wound is not healing, an occult infection is the likely cause. All nonischemic diabetic foot and pressure ulcers that are identified and treated early with aggressive therapy (including antibiotics, off-loading of pressure, and biological therapy) will not progress.     

Light therapy and advanced wound care for a neuropathic plantar ulcer on a Charcot foot

Light therapy is a relatively novel modality in wound care. I used a light-emitting diode (LED) and superluminous diode (SLD) to deliver low-intensity laser light as an adjunctive treatment to a patient with a chronic diabetic foot ulcer. Standard treatment of conservative sharp debridement, off-loading, bioburden management, and advanced dressings was delivered in a WOC clinic setting. This combination of therapies resulted in closure of the neuropathic plantar ulcer within 8 weeks.     

The effects of peripheral vascular disease with osteomyelitis in the diabetic foot.

BACKGROUND: Osteomyelitis in the diabetic foot is a difficult problem with multiple etiologies. The effects of peripheral vascular disease, neuropathy, and repetitive trauma all interact to produce complex lesions with exposed bone, surrounding cellulitis, and gangrenous changes. METHODS: We performed a retrospective study over a 14-year period at a community hospital looking at osteomyelitis in the diabetic foot. We looked at the contributing factors, organisms involved, most common locations, physical findings, and surgical procedures necessary to treat this condition. The purpose of the study was to determine the incidence and effect of peripheral vascular disease in diabetic patients with foot ulcers. RESULTS: There were a total of 150 patients requiring 278 hospitalizations over the 14-year period who represented 14% of all diabetic admissions. A total of 438 surgical procedures were necessary in these patients, with the most common being debridement (39%) and toe amputation (19%). There were 6 deaths (4%) in this series, and leg amputation was necessary in 21 patients (14%). A vascular bypass was necessary for healing and limb salvage in 36 patients (24%). Most of the bypasses (85%) were with autogenous tissue to the distal leg in order to limit the extent of amputation and to preserve a functional limb. CONCLUSION: Ischemia is often a contributing factor in the diabetic foot ulcer that must be recognized and treated to avoid prolonged hospitalization, spreading infection, and unnecessary amputation.     

Vascular evaluation and arterial reconstruction of the diabetic foot

Findings of diminished or absent pulses, pallor on elevation, redness of the foot on lowering of the leg, sluggish refilling of the toe capillaries, and thickened nails or absence of toe hair are consistent with impaired arterial perfusion to the foot. When ischemia is recognized as contributing to pedal ulceration and infection in the diabetic foot, quantitation of its severity may be difficult. Standard clinical evaluation of trophic changes is limited in an infected foot with its accompanying swelling, edema, and erythema. A palpable pedal pulse does not preclude the possibility of the presence of limb-threatening ischemia. Additional non-invasive vascular studies should be undertaken for these patients. Management of the diabetic foot is often a complex clinical problem. However, the principles of care are simple, including correction of systemic factors, such as blood glucose control, cardiovascular risk factor management, and smoking, as well as local factor correction, such as debridement, pressure relief, infection control, and revascularization when indicated. When a patient presents with evidence of infection, adequate drainage and antibiotic therapy are mandatory. The next step should be performed to differentiate the more common neuropathic ulcerations from the truly ischemic ulceration. Symptoms of rest pain or claudication are not often helpful because many of these patients are asymptomatic as a result of the presence of their neuropathy and inactivity. If an infected foot requires debridement or open partial forefoot amputation, observing the wound on a daily base is also important. Once infection is eradicated, there should be prompt signs of healing, including the development of wound granulation within several days. If wounds are not showing signs of prompt healing, arteriography is necessary. Early aggressive drainage, debridement, and local foot amputations combined with liberal use of revascularization results in cumulative limb salvage of 74% at 5 years in high-risk groups. Others report that pedal bypass to the ischemic infected foot is effective and safe as long as infection adequately controlled. These studies strongly suggest that early recognition and aggressive surgical drainage of pedal sepsis followed by surgical revascularization is critical to achieving maximal limb salvage in the high-risk population. Patients who have diabetes present a unique challenge in lower extremity revascularization because of the distal origination of many bypasses, distal distribution of the occlusive disease, and the frequently calcified arterial wall. An aggressive multidisciplinary approach to foot disease associated with diabetes involving the primary care provider, medical specialists, interventional radiology, and podiatric, plastic, and vascular surgeons will provide optimal medical and surgical care. Peripheral vascular disease is highly treatable if intervention is instituted in a timely and collegial fashion.     

Diabetic foot ulcers--a comprehensive review.

As the incidence of diabetes mellitus is increasing globally, complications related to this endocrine disorder are also mounting. Because of the large number of patients, foot ulcers developing in the feet of diabetics have become a public health problem. The predisposing factors include abnormal plantar pressure points, foot deformities, and minor trauma. Vulnerable feet usually already have vascular insufficiency and peripheral neuropathy. The complex nature of these ulcers deserves special care. The most useful prognostic feature for healing remains the ulcer depth, ulcers heal poorly if they clearly involve underlying tendons, ligament or joints and, particularly, when gangrenous tissue is seen. Local treatment of the ulcer consists of repeated debridement and dressing. No 'miraculous' outcome is expected, even with innovative agents like skin cover synthetics, growth factors and stem cells. Simple surgery like split skin grafting or minor toe amputations may be necessary. Sophisticated surgery like flap coverages are indicated for younger patients. The merits of an intact lower limb with an abnormal foot have to be weighed against amputation and prosthesis in the overall planning of limb salvage or sacrifice. If limb salvage is the decision, additional means like oxygen therapy, and other alternative medicines, might have benefits. The off-loading of footwear should always be a major consideration as a prevention of ulcer formation.     

糖尿病足的外科一站式治疗

目的 探讨糖尿病足外科一站式治疗的临床价值.方法 175例(206条肢体)糖尿病足患者,根据患肢的不同情况,灵活组合应用球囊扩张和(或)支架成形术、局部清创术、持续负压引流术、特殊敷料换药、人工血管旁路术、自体静脉旁路术、杂交手术、截肢(趾)术、单纯保守治疗等各种治疗措施.结果 腔内治疗和旁路术治疗的糖尿病足患者术后1...     

Lower extremity bypass in patients with diabetic foot ulcers

The assessment and management of ischemia for the diabetic patient must be a part of an evidence-based treatment algorithm for wound healing. In 1999, the American Diabetes Association published a consensus position to provide guidance to health care professionals who manage foot wounds in patients with diabetes. The consensus panel recognized six approaches that are supported by clinical trials or well-established principles of wound healing: off-loading, debridement, dressings, antibiotics, vascular reconstruction, and amputation or reconstructive foot surgery when necessary. Adjunctive medical therapies include normalization of blood glucose, treatment of comorbid conditions, control of edema, nutritional repletion, and physical and emotional therapy. Education and prevention of recurrence are essential in any treatment algorithm. Box 1 and Box 2 are algorithms developed by the author and used in clinical management of diabetic lower extremity wounds. The author's multidisciplinary team approach is evidenced based with documented healing and a reduction in amputation at every level. For the patient, it best allows a return to function and well-being. Focusing on quality maximizes the cost/benefit ratio.     

The role of surgical debridement in healing of diabetic foot ulcers

A critical question in the treatment of chronic wounds is whether and when debridement is needed. The three most common chronic wounds are the diabetic foot ulcer (DFU), the venous leg ulcer, and the pressure or decubitus ulcer. Surgical debridement, aimed at removing necrotic, devitalized wound bed and wound edge tissue that inhibits healing, is a longstanding standard of care for the treatment of chronic, nonhealing wounds. Debridement encourages healing by converting a chronic nonhealing wound environment into a more responsive acute healing environment. While the rationale for debridement seems logical, the evidence to support its use in enhancing healing is scarce. Currently, there is more evidence in the literature for debridement for DFUs than for venous ulcers and pressure ulcers; however, the studies on which clinicians have based their rationale for debridement in DFUs possess methodologic flaws, small sample sizes, and bias. Thus, further studies are needed to develop clinical evidence for its inclusion in treatment protocols for chronic wounds. Here, the authors review the scientific evidence for debridement of DFUs, the rationale for debridement of DFUs, and the insufficient data supporting debridement for venous ulcers and pressure ulcers.     

The use of a dermal substitute to preserve maximal foot length in diabetic foot wounds with tendon and bone exposure following urgent surgical debridement for acute infection

In this study, we evaluated the utility of a dermal substitute for preserving maximal foot length after urgent surgical debridement. Patients referred to our Diabetic Foot Center with foot lesions were assessed for sensory–motor neuropathy, infection and critical limb ischaemia. The presence of acute foot infection indicated the need for immediate surgical debridement. The degree of amputation, if necessary, was based on the amount of apparently non infected vital tissue. When vital tendon/bone tissue remained exposed, the lesion was covered with a dermal substitute. From January to December 2008, 393 patients underwent surgical treatment for diabetic foot syndrome; 30 patients underwent immediate surgical debridement resulting in exposed tendon and/or bone tissues. An average of 4·4 ± 2·1 days following surgical debridement, all 30 patients underwent dermal regeneration template grafting to cover‐exposed healthy tendon and bone tissues, instead of achieving primary wound closure with a proximal amputation. After 21 days, a skin graft was performed. Complete wound healing occurred in 26 patients (86·7%). In these patients, the amputation level was significantly more distal (P < 0·003) with respect to that potentially required for immediate wound closure. The average healing time was 74·1 ± 28·9 days. Four patients underwent a more proximal amputation. No patients underwent major amputation. The use of the dermal substitute for treating exposed tendon and bone tissues allowed timely wound healing and preserved maximal foot length. Continued follow‐up will allow assessment of long‐term relapse and complication rates. Such treatment could constitute part of the comprehensive management of diabetic wounds.     

Limb salvage surgery

The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.KEY WORDS: Limb salvage, limb trauma, lower limb reconstruction, foot ulcers     

Diabetic foot disease:From the evaluation of the “foot at risk” to the novel diabetic ulcer treatment modalities

The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.     

Debridement performance index and its correlation with complete closure of diabetic foot ulcers

In recent years there has been wider acceptance of aggressive surgical debridement as a means to accelerate closure of diabetic foot ulcers. In a clinical trial by Steed et al.1 involving the use of a topically applied growth factor, thorough surgical debridement of surrounding callus, necrotic ulcer bed, and undermined ulcers' edges was associated with greater incidence of healing and effectiveness of the therapeutic agent. However, at present there is no established way to judge the appropriate extent of debridement and its performance. Here we describe a scoring system to assess whether debridement has been performed adequately. Our scoring system consists of the following three categories: debridement of a) callus; b) ulcer's edge undermining; and c) wound bed necrotic tissue. We assigned a score of 0-2 to each of these categories using the following criteria: 0 = debridement needed but not done, 1 = debridement needed and done, and 2 = debridement not needed. These three scores are then added to give a total ranging from 0 to 6, with the highest number being the optimal score. This instrument, the Debridement Performance Index, evaluates both the adequacy of debridement and whether the ulcer has been or is being properly debrided. To initiate the validation of this scoring system and determine its predictive value for wound closure by week 12, we applied it to 143 patients with diabetic foot ulcers who had been treated in a clinical trial involving either standard therapy (n = 65) or the application of a bioengineered skin construct (n = 78). We blindly evaluated sequential digital photographs of each diabetic foot ulcer and applied the Debridement Performance Index score at day 0, before initiation of either treatment. We found that the lower the baseline Debridement Performance Index the lower the incidence of ultimate wound closure by week 12 ( p = 0.0276). Patients with a Debridement Performance Index between 3 and 6 were 2.4 times more likely to heal than those with a score of 0-2. After controlling for treatment, the Debridement Performance Index was found to be an independent predictor of wound closure (odds ratio = 2.4 95% confidence interval = 1.0-5.6). In conclusion, this novel scoring system for debridement performance appears to be very promising as a predictive tool for determining outcome in clinical trials and, most likely, in clinical practice.     

壳聚糖及其复合物在治疗下肢慢性溃疡中的研究进展

下肢慢性溃疡(CLU)是一种常见的外科疾病。在人群中发病率为0.12%～1.1%,其中60岁以上发病率为0.5%～3%,80岁以上则高达5%。根据溃疡病因,可将其分为血管源性溃疡、糖尿病足溃疡、压力性溃疡、创伤性溃疡、神经营养性溃疡、恶性溃疡等。伤口的愈合包括炎症反应期、增生期和修复期,适当的微环境能促进细胞的增殖和迁移,有利于早期伤口愈合,防止炎症和疤痕产生。溃疡创面的处理对愈合过程有着至关重要的作用。目前针对CLU的治疗主要包括清创、植皮、负压封闭引流、抗感染、局部活性因子、干细胞移植及敷料覆盖等。选择合适的伤口敷料对促进CLU创面的愈合起至关重要的作用,这类敷料除具有良好的吸收伤口渗液能力外,还应保持伤口的适宜的微环境、抑菌、止血、镇痛等能力和促进伤口愈合能力。壳聚糖化是甲壳素经强碱作用脱去部分乙酰基的产物。其具有抗感染、止血、免疫调节、诱导组织修复和细胞增殖,以及良好的生物相容性和生物降解性。同时壳聚糖对白细胞和巨噬细胞具有趋化作用,增强巨噬细胞吞噬作用,其可刺激中性粒细胞及巨噬细胞分泌白细胞介素和肿瘤坏死因子,进而促进创面进行"自净"。壳聚糖在治疗CLU中的良好前景。     

Surgical soft tissue closure of severe diabetic foot infections: a combination of biologics, negative pressure wound therapy, and skin grafting

Creative surgical strategies are often warranted for long-term closure of diabetic foot wounds. This article provides a case report describing the successive use of negative pressure wound therapy, advanced biologics, and split thickness skin grafting for healing an extensive surgical wound. Although the success of these therapies is enticing, their use should be based on careful patient selection in a multidisciplinary setting.     

Debridement of the diabetic foot: a podiatric perspective

High plantar pressures are a risk factor for diabetic foot ulcers that are common chronic wounds. In patients with peripheral neuropathy, plantar ulcers may be managed by debridement of callus, a process that has been shown to reduce peak plantar pressures. Callus debridement is clearly an important ulcer prevention strategy. The scalpel skills used by the podiatrist to remove callus are best suited to achieve safe, local sharp wound debridement. Current podiatric practice in the United Kingdom is based on sound theoretical principles. However, good scientific data recommending its efficacy are scarce. The role of podiatry in debridement and wound management needs careful examination, a major aim of this article.     

Chapter V: Diabetic foot

Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed. This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade.