Volume 31, Issues 2–4, June–December 2018, Pages 43-48  https://doi.org/10.1053/j.semvascsurg.2019.02.001Get rights and content Foot-related disorders, including infection, ulceration, and gangrene, are a frequent indication for hospitalization of diabetic patients. The diabetic population in the United States continues to increase; more than 100 million US adults are now living with diabetes or prediabetes. As of 2015, the Centers for Disease Control and Prevention reported that 30 million Americans (9% of the population) have diabetes [1]. It is estimated that up to 20% of these patients will require hospitalization for a diabetic foot condition. Epidemiologic studies indicate the risk of developing a foot ulcer is 2.5% per year [2]. The development of skin ulceration in the foot of a diabetic is a serious medical condition, which, if not healed promptly, can lead to amputation. Annually, nonhealing diabetic foot wounds account for >100,000 amputations, and in 60% of patients, the inciting event was a foot ulcer. The societal impact of the diabetic foot is significant in terms of individual disability, ensuing hospitalizations, and health care costs—estimated to be in excess of $1 billion annually [2]. The development of multidisciplinary care programs that include surgeons can reduce both the number and extent of lower extremity amputations [3], [4], [5]. The prevalence of diabetic foot problems is expected to increase due to the aging US population and the problem of obesity in the population, with its concomitant development of type 2 diabetes. Significant peripheral artery disease is present in more than half of diabetic patients presenting with a foot ulcer [4]. Thus, the vascular surgeon needs to be involved in the care of these patients and remain informed with updated data on the pathophysiology, diagnostics, management, and prevention of diabetic foot problems. A triad of neuropathy, trauma with secondary infection, and arterial occlusive disease account for the pathophysiology of the diabetic foot ulcer (Table 1). Peripheral neuropathy produces intrinsic muscle atrophy, leading to functional anatomical changes of hammer-toe formation and development of high-pressure zones on the plantar surface of the foot at the metatarsal heads (Fig. 1). Repetitive trauma with walking, in concert with decreased sensation and proprioception, predisposes to skin A thorough patient history and physical examination with special consideration for co-existing renal and cardiac conditions initiate a comprehensive assessment of foot anatomy, neurosensory dysfunction, and vascular perfusion. Recent foot trauma, including the possibility of a foreign body being present, should be queried, as well as the duration and prior treatment of an ulcer or foot wound. Both lower extremities should be inspected for skin trauma (redness, induration, edema), ulceration, The goals of diabetic foot treatment are to achieve tissue healing while maintaining adequate function and weight-bearing for ambulation. Antibiotic treatment of invasive infection in conjunction with tissue debridement or amputation and off-loading foot pressure until healing is achieved are the essential management principles. In patients presenting with advanced ischemia, control of infection takes precedent over limb revascularization. The risk of limb amputation can be estimated using the
There are more references available in the full text version of this article. Diabetic foot ulcer (DFU) is a complicated condition with symptoms of neuropathic pain, immunological and biochemical impairments promotes delayed wound healing processes and foot amputations. Currently available therapeutic options for the management of DFU are excruciating and expensive; hence affect the global socioeconomic burden. An optimal therapy for DFU should exhibit easy acceptability, reliability and cost-efficient feature. Interestingly, quercetin displays excellent antidiabetic, anti-inflammatory, antioxidant, antimicrobial and wound healing properties which makes it a promising molecule for the management of diabetic wounds. It enhances the process of angiogenesis by activating multiple factors such as Msr-1, Arg-1, VEGF-α, HO-1, PECAM-1 as well as known for its action on PI3K/Akt/eNOS pathway to promote the cell proliferation, collagen deposition and angiogenesis. Despite numerous therapeutic benefits of quercetin, its use in DFU is limited owing to pharmaceutical challenges such as low aqueous solubility (0.48 ± 0.1 μg/mL), poor permeability (log P 1.82 ± 0.3), instability in gastro-intestinal tract, average terminal half-life (3.5 h), poor oral bioavailability (4%) and extensive first past metabolism. Further, lacking of clinical data and insufficient understanding of mechanism of action have listed the quercetin only as a complementary and alternative medicine or a nutraceutical. Therefore, in present review, we have discussed complete etiology of diabetic foot, available therapies and their shortcomings. In addition, an attempt has also been undertaken to enlist the possible target sites for quercetin to boost the wound healing process along with application of artificial intelligence (AI)-based techniques for the development of stable, cost-effective and patient-friendly topical drug delivery systems for better management of DFU in future. To effectively treat diabetic wounds, the development of versatile medical dressings that can long-term regulate blood glucose and highly effective anti-oxidative stress, antibacterial and anti-inflammatory are critical. Here, an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) was developed via the dynamic Schiff base reaction between the amino groups on quaternized chitosan (QCS) and the aldehyde groups on benzaldehyde-terminated F108 (F108-CHO) micelles. CORM-401 (an oxidant-sensitive CO-releasing molecules) was encapsulated in the hydrophobic core of F108-CHO micelles and insulin was loaded in the three-dimensional network structure of ICOQF. The dynamic Schiff base bonds not only endowed ICOQF with good tissue adhesion, injectability and self-healing, but also gave it sustained and controllable insulin release ability. In addition, ICOQF could quickly generate CO in inflamed wound tissue by consuming reactive oxygen species. The generated CO could effectively anti-oxidative stress by activating the expression of heme oxygenase; antibacterial by inducing the rupture of bacterial cell membranes and mitochondrial dysfunction and inhibiting the synthesis of adenosine triphosphate; and anti-inflammatory by inhibiting the proliferation of activated macrophages and promoting the polarization of the M1 phenotype to the M2 phenotype. Due to these outstanding properties, ICOQF significantly promoted the healing of STZ-induced MRSA-infected diabetic wounds accompanied by good biocompatibility. This study clearly shows that ICOQF is a versatile hydrogel dressing with great application potential for the management of diabetic wounds. The development of some versatile hydrogel dressings that can not only provide a prolonged and controlled insulin release property but also utilize a non-antibiotic treatment modality for highly effective antibacterial, anti-inflammatory, and anti-oxidative stress effects is vital for the successful treatment of diabetic wounds. Herein, we developed an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) with sustained and controllable insulin release abilities. Moreover, ICOQF could not only quickly release CO in the inflamed wound tissue by consumption of reactive oxygen species but also utilize the generated CO to highly effectively anti-oxidative stress, antibacterial, and anti-inflammatory. ICOQF therapy substantially promoted the healing of STZ-induced MRSA-infected diabetic wounds. Overall, this work provides a multifunctional hydrogel dressing for the management of diabetic wounds. Patients with diabetes mellitus are at elevated risk for secondary complications that result in lower extremity amputations. Standard of care to prevent these complications involves prescribing custom accommodative insoles that use inefficient and outdated fabrication processes including milling and hand carving. A new thrust of custom 3D printed insoles has shown promise in producing corrective insoles but has not explored accommodative diabetic insoles. Our novel contribution is a metamaterial design application that allows the insole stiffness to vary regionally following patient-specific plantar pressure measurements. We presented a novel workflow to fabricate custom 3D printed elastomeric insoles, a testing method to evaluate the durability, shear stiffness, and compressive stiffness of insole material samples, and a case study to demonstrate how the novel 3D printed insoles performed clinically. Our 3D printed insoles results showed a matched or improved durability, a reduced shear stiffness, and a reduction in plantar pressure in clinical case study compared to standard of care insoles. Diabetes Mellitus (DM) belongs to the ten diseases group with the highest mortality rate globally, with an estimated 578 million cases by 2030, according to the World Health Organization (WHO). The disease manifests itself through different disorders, where vasculopathy shows a chronic relationship with diabetic ulceration events in distal extremities, being temperature a biomarker that can quantify the risk scale. According to the above, an analysis is performed with standing thermography images, finding temperature patterns that do not follow a particular distribution in patients with DM. Therefore, the modern medical literature has taken the use of Computer-Aided Diagnosis (CAD) systems as a plausible option to increase medical analysis capabilities. In this sense, we proposed to study three state-of-the-art deep learning (DL) architectures, experimenting with convolutional, residual, and attention (Transformers) approaches to classify subjects with DM from diabetic foot thermography images. The models were trained under three conditions of data augmentation. A novel method based on modifying the images through the change of the amplitude in the Fourier Transform is proposed, being the first work to perform such synergy in the characterization of risk in ulcers through thermographies. The results show that the proposed method allowed reaching the highest values, reaching a perfect classification through the convolutional neural network ResNet50v2, promising for limited data sets in thermal pattern classification problems. This study aimed to evaluate the effects of foot ulcers on male patients diagnosed with type-2 diabetes, foot care and treatment, and the difficulties, experiences, feelings, and perspectives of male patients regarding foot ulcers. This study designed as a qualitative descriptive study. The study sample included 14 male patients diagnosed with a diabetic foot ulcer. Data were analysed using thematic analysis. Three main themes were identified from the interviews: diabetic foot ulcer development, diabetic foot ulcer effects, and healthcare experiences with the diabetic foot ulcer. The results of this study may serve to provide a guideline for healthcare professionals to develop foot care strategies. While the patients who participated in the study were well-informed about foot care and diabetes management, their self-care practices were poor. Good management of diabetes and external factors were correlated with the development of foot ulcers. Diabetic polyneuropathy (DPN) is a progressive disorder that is common in both types 1 and 2 diabetes mellitus and can be recognized at the bedside using a focused history and neurological examination. This chapter focuses on the main symptoms and signs of DPN available to the clinician, a snapshot of several larger and selected trials in the past 5 years and overall thoughts on how translation might be directed. DPN targets sensory axons in particular rendering sensory loss involving both small and larger myelinated axons, each with characteristic clinical features. Pain and predisposition to insensate ulcers are problematic complications of DPN. While several newer trials have been completed, wide use of all of the clinical and laboratory tools to evaluate DPN have often not been exploited. Newer approaches focusing on preclinical molecular evidence combined with rigorous trials will be essential in reversing DPN. For generations, the use of techniques to defer skin pressure and protect the lower-extremity wound has been a cardinal goal to achieve therapeutic success and healing. Choosing the appropriate postoperative offloading device or shoe is often difficult, as it is challenging to merge optimal mechanical protection with clinical realities and patient needs. The gold standard for offloading remains the total contact cast, yet it receives minimal utilization in the clinical setting. Other devices have shown benefit, including the removable cast walker, instant total contact cast, and depth inlay shoes, for preventative measures. Ultimately, any plantar, lower-extremity wound must receive some form of external pressure reduction to reach acceptable rates of healing. Future technologies will aid these measures by providing body-worn constant monitoring systems and more effective offloading via patient-specific exoskeletons. This review is a supplemental update on the available wound offloading modalities based on logic-driven research regarding pressure relief across the diabetic neuropathic or impaired perfusion foot. After the invention of the balloon catheter by Fogarty in 1963, surgical thromboembolectomy was considered the gold standard treatment for many years in patients with acute lower limb ischemia (ALLI). ALLI is a dramatic event, carrying a high risk of amputation and perioperative morbidity and mortality. The evolution of endovascular technologies has resulted in a variety of therapeutic options to establish arterial patency. In the 1970s, Dotter first introduced the idea of clot lysis in the treatment of ALLI, which was modified to catheter-directed thrombolysis, and now clot aspiration techniques. Currently, the majority of ALLI (about 70%) is arterial thrombosis, which generally occurs in the setting of preexisting vascular lesion. This condition is very common in patients with diabetes. Clinical presentation in case of thrombosis on atherosclerotic stenosis (so called “acute on chronic ischemia”) may be less severe, but treatment is generally more challenging than ALLI due to embolism, considering the complexity in device trackability through the diseased vessels, potential vessel injury, incomplete revascularization, and need of correction of underlying vascular lesions. Although surgery is still a treatment option, especially for ALLI, endovascular interventions have assumed a prominent role in restoring limb perfusion. In this review, the treatment options for ALLI are detailed from surgical thromboembolectomy to thrombolysis and current endovascular techniques, including mechanical fragmentation, rheolytic thrombectomy, and aspiration thrombectomy. The evolution to endovascular therapies has resulted in improved clinical outcomes and lower rates of morbidity. Diabetic Foot Ulcers (DFUs) are major complications associated with diabetes and often correlate with peripheral neuropathy, trauma and peripheral vascular disease. It is necessary to understand the molecular and genetic basis of diabetic foot ulcers in order to tailor patient centred care towards particular patient groups. This review aimed to evaluate whether current literature was indicative of an underlying molecular and genetic basis for DFUs and to discuss clinical applications. From a molecular perspective, wound healing is a process that transpires following breach of the skin barrier and is usually mediated by growth factors and cytokines released by specialised cells activated by the immune response, including fibroblasts, endothelial cells, phagocytes, platelets and keratinocytes. Growth factors and cytokines are fundamental in the organisation of the molecular processes involved in making cutaneous wound healing possible. There is a significant role for single nucleotide polymorphism (SNPs) in the fluctuation of these growth factors and cytokines in DFUs. Furthermore, recent evidence suggests a key role for epigenetic mechanisms such as DNA methylation from long standing hyperglycemia and non-coding RNAs in the complex interplay between genes and the environment. Genetic factors and ethnicity can also play a significant role in the development of diabetic neuropathy leading to DFUs. Clinically, interventions which have improved outcomes for people with DFUs or those at risk of DFUs include some systemic therapeutic drug interventions which improve microvascular blood flow, surgical interventions, human growth factors, and hyperbaric oxygen therapy, negative pressure wound therapy, skin replacement or shockwave therapy and the use of topical treatments. Future treatment modalities including stem cell and gene therapies are promising in the therapeutic approach to prevent the progression of chronic diabetic complications. Foot ulceration and Charcot neuroarthropathy (CN) are well recognized and documented late sequelae of diabetic peripheral, somatic, and sympathetic autonomic neuropathy. The neuropathic foot, however, does not ulcerate spontaneously: it is a combination of loss of sensation due to neuropathy together with other factors such as foot deformity and external trauma that results in ulceration and indeed CN. The commonest trauma leading to foot ulcers in the neuropathic foot in Western countries is from inappropriate footwear. Much of the management of the insensate foot in diabetes has been learned from leprosy which similarly gives rise to insensitive foot ulceration. No expensive equipment is required to identify the high risk foot and recently developed tests such as the Ipswich Touch Test and the Vibratip have been shown to be useful in identifying the high risk foot. A comprehensive screening program, together with education of high risk patients, should help to reduce the all too high incidence of ulceration in diabetes. More recently another very high risk group has been identified, namely patients on dialysis, who are at extremely high risk of developing foot ulceration; this should be preventable. The most important feature in management of neuropathic foot ulceration is offloading as patients can easily walk on active foot ulcers due to the loss of pain sensation. Infection should be treated aggressively and if there is any evidence of peripheral vascular disease, arteriography and appropriate surgical management is also indicated. CN often presents with a unilateral hot, swollen foot and any patient presenting with these features known to have neuropathy should be treated as a Charcot until this is proven otherwise. Most important in the management of acute CN is offloading, often in a total contact cast. Foot ulceration in diabetes mellitus is common. Foot problems remain the commonest cause of hospital admission amongst patients with diabetes in Western countries. The lifetime risk of a patient with diabetes developing an ulcer is 25%, and up to 85% of all lower limb amputations in diabetes are preceded by foot ulcers. As many as 50% of older patients with type 2 diabetes have risk factors for foot problems and regular screening by careful clinical examination is essential; those found to be at risk should attend more regular follow-up together with education in foot self-care. The key to management of diabetic neuropathic foot ulceration is aggressive debridement with removal of callus and dead tissue, followed by application of some form of cast to offload the ulcer area. Most ulcers will heal if pressure is removed from the ulcer site, if the arterial circulation is sufficient and if infection is managed and treated aggressively. Any patient with a warm swollen foot without ulceration should be presumed to have acute Charcot neuroarthropathy (CN) until proven otherwise. The optimal approach to reducing ulceration requires regular screening, patient education and a team approach to management, both in the community and in hospital. |
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