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Abstract

Lower-extremity complications of diabetes such as foot ulcers constitute a substantial burden for people with diabetes. Once healed, foot ulcers frequently recur. This fact, coupled with demographic trends, requires a collective refocusing on prevention and a reallocation of resources from simply healing active ulcers to maximizing ulcer-free days for all patients with a history of diabetic foot ulceration. Aggressive therapy during active disease combined with a focus on improving care during remission can lead to more ulcer-free days, fewer inpatient and outpatient visits, and an improved quality of life.

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... Diabetes-related foot complications such as diabetic foot ulcers (DFUs), peripheral arterial disease including critical limb-threatening ischemia (CLTI), Charcot neuroarthropathy and lower extremity amputations (LEAs) are a leading cause of global morbidity, mortality, reduced quality of life and direct and indirect healthcare costs. [1][2][3] Indeed, 5-year mortality rates associated with these complications are greater compared to many cancers. 4 Limb complications of diabetes increase in people with multimorbidity such as concomitant nephropathy and cardiovascular disease. ...
... [4][5][6] People with an history of DFUs are at increased risk of ulcer recurrence. 1 In fact, 40% of those people will develop DFU recurrence within a year, 65% within 5 years, and greater than 90% within 10 years. 1,7 Because the epidemiology of diabetes-related foot complications is comparable to that of cancer, and recurrence is common, after the initial healing of an index DFU, it is appropriate to refer to a person not as cured of DFU, but rather as being in "DFU remission". ...
... [4][5][6] People with an history of DFUs are at increased risk of ulcer recurrence. 1 In fact, 40% of those people will develop DFU recurrence within a year, 65% within 5 years, and greater than 90% within 10 years. 1,7 Because the epidemiology of diabetes-related foot complications is comparable to that of cancer, and recurrence is common, after the initial healing of an index DFU, it is appropriate to refer to a person not as cured of DFU, but rather as being in "DFU remission". 8 In addition, as with cancer, the complexities associated with management require a comprehensive and organized team approach, including the patient, their family and caregivers, to achieve the best outcomes and high quality patientcentered care. ...
Article
Nearly a decade ago, the Society for Vascular Surgery (SVS)'s wound, ischemia, and foot Infection (WIfI) classification was first developed to help assess overall limb threat. However, managing conditions such as diabetic foot ulcer and chronic limb-threatening ischemia can be complex. For instance, certain investigative findings might initially be pending such as the level of ischemia or extent of infection before the final classification is established. In addition, wounds evolve rapidly, and the current classification does not allow for tracking their progression over time during treatment. Therefore, we propose a supplemental consistent notation for scoring WifI re-assessment during treatment of a threatened limb inspired by the cancer staging before and after neoadjuvant treatment classification system. Thus, we describe the re-scoring system and how to use it. Our suggestion supports a coherent method to longitudinally communicate characteristics of a threatened limb. This has potential to support high quality interdisciplinary, patient-centered care and enhance the use of this classification in research. Further work is required to validate this modification of a common language of risk.
... Diabetic foot ulcer (DFU), a major complication of diabetes mellitus (DM), is not uncommon and is linked to highnormal levels of morbidity and mortality as well as enormous economic costs. The lifetime risk for the development of a foot ulcer in a patient with DM is estimated to be 19-34% [1]. Diabetes-related foot ulcers precede at least 60% of all nontraumatic lower limb amputations [2]. ...
... Diabetes-related foot ulcers precede at least 60% of all nontraumatic lower limb amputations [2]. Moreover, even after the resolution of a foot ulcer, recurrence is also common [1]. ...
... Abnormal biomechanical stress, including elevated vertical pressure and horizontal shear pressure, accounts for the development of a foot ulcer, especially acting on the foot during ambulation. High levels of mechanical pressure contribute to approximately 50% of DFUs during repetitive weight-bearing activity [1,[4][5][6]. Thus, foot ulceration is probably the most preventable of all the complications of diabetes [7]. ...
Article
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Objective. To reduce diabetic foot ulcer (DFU) occurrence or recurrence, diabetic therapeutic footwear is widely recommended in clinical practice for at-risk patients. However, the effectiveness of therapeutic footwear is controversial. Thus, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine whether special therapeutic footwear could reduce the incidence of DFU. Method. We systematically searched multiple electronic databases (Medline, EMBASE, and EMB databases) to identify eligible studies published from inception to June 11, 2021. The database search, quality assessment, and data extraction were independently performed by two reviewers. Efficacy (i.e., incidence of DFU) was explored using the R’meta’ package (version 4.15-1). To obtain more robust results, the random-effects model and the Hartung-Knapp-Sidik-Jonkman method were selected to assess pooled data. Metaregression analysis and sensitivity analysis were performed to explore heterogeneity, and publication bias was assessed by a visual inspection of funnel plots and the AS-Thompson test. Results. Eight RCTs with a total of 1,587 participants were identified from the search strategy. Compared with conventional footwear, special therapeutic footwear significantly reduced the incidence of DFU (RR 0.49; 95% CI, 0.28-0.84), with no evidence of publication bias ( P = 0.69 ). Unexpectedly, the effectiveness of special therapeutic footwear had a reverse correlation with the intervention time ( coefficient = 0.085 , P < 0.05 ) in the metaregression analysis. Conclusion. Special therapeutic footwear with offloading properties is effective in reducing the incidence of DFU. However, the effect may decrease gradually over time. Despite undefined reasons, the optimal utility time and renewal frequency of special therapeutic footwear should be considered.
... Diabetic foot ulcer (DFU) is a common complication in diabetes and can lead to a considerable social, psychological, and economic burden on patients and the health sector (1). DFU accounts for significant morbidity and mortality. ...
... DFU patients have a 2.5 times higher risk of death compared to diabetic patients without foot ulcers (2,3). According to the International Diabetes Federation, 9.1-26.1 billion people will develop DUFs every year (1). The prevalence of DFU has increased significantly with a recent global prevalence averaging around 6.4% (4). ...
Article
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Introduction Infected diabetic foot ulcer (IDFU) is a worldwide problem associated with diabetes mellitus. It could lead from soft tissue infection to bone infection and is a leading cause of lower limb amputation. Gram-negative and Gram-positive bacteria, including anaerobic bacteria and fungi, are considered potential causes of infection. The early diagnosis of DFU infection and appropriate treatment based on the identification of the pathogens and their antimicrobial susceptibility pattern is important for good prognosis. Therefore, the purpose of this study was to isolate the bacteria that infect foot ulcers in selected Hospitals and determine their antimicrobial resistance profile. Method An institutional-based multicenter, cross-sectional study was conducted in selected Hospitals in Addis Ababa, Ethiopia, from November 2020 to May 2021. A sterile swab was used to collect samples from the foot ulcer and a sterile needle to collect pus. Isolates were identified by culture, Gram-staining, and a series of biochemical tests. For each bacterial species identified, the antibiotic profiling was determined by the Kirby-Bauer disk diffusion method. Results one hundred and twenty-seven pathogenic bacteria were isolated from samples taken from 130 patients with a diabetic foot ulcer. Sixty-eight percent had growth of multiple microorganisms. Two-thirds (66.7%) of the isolates were gram-negative bacteria. The predominant bacterial species were S. aureus 25.19% (32/127), Pseudomonas species 18.89% (24/127), and Escherichia coli 16.53% (21/127). Overall, 92.9% (118/127) of the isolates were identified as multi-drug resistant. Gram-positive isolates were susceptible to chloramphenicol, clindamycin, and amikacin. Gram-negative isolates were also sensitive to chloramphenicol, aztreonam, and amikacin. Conclusion The majority of bacteria isolated from patients presenting with Diabetic foot ulcer infections were found to be multi-drug resistant in the study sites of the current study. The results demonstrate the importance of timely identification of infection of diabetic foot ulcers, proper sample collection for identification of the pathogens and for determining their antibiotic susceptibility pattern before initiating antimicrobial treatment
... Diabetic foot ulcers (DFU) have become a serious complication secondary to diabetic foot syndrome; it has been stated in previous research that 19-34% of patients with diabetes will develop a DFU during their life. 1 Even after ulcer resolution, patients will suffer from high recurrence rates, being an unsolved issue and rising the recurrence rates to 65% after 5 years. 1 Providing structured education about foot-specific self-care has been demonstrated to effectively prevent a first-ever or recurrent and should consist of information on wearing adequately protective footwear. 2 Among the recommended therapies for preventing diabetic foot disease, orthopedic devices such as therapeutic footwear (TF) [3][4][5] have been demonstrated to prevent foot ulcers. ...
... 1 Even after ulcer resolution, patients will suffer from high recurrence rates, being an unsolved issue and rising the recurrence rates to 65% after 5 years. 1 Providing structured education about foot-specific self-care has been demonstrated to effectively prevent a first-ever or recurrent and should consist of information on wearing adequately protective footwear. 2 Among the recommended therapies for preventing diabetic foot disease, orthopedic devices such as therapeutic footwear (TF) [3][4][5] have been demonstrated to prevent foot ulcers. ...
Article
To evaluate the ability of high-risk patients with diabetes in remission to select proper therapeutic footwear (TF) and validate a novel 3D foot scanner app for selecting the proper fitting TF. We conducted a randomized and controlled clinical trial enrolling 30 patients with a previously healed diabetic foot ulcer carried out in a specialized diabetic foot unit between November 2021 and June 2022. All patients were recommended to TF with extra depth volume and rocker sole. The control group could acquire the TF size and model according to aesthetic preferences, while the experimental group had to acquire a specific size and model according to the result of a novel mobile app 3D feet scan. TF was recommended to change when the ill-fitting reasons were found, excessive length or tightness or compromise with toes. The primary outcome measure was the requirement of TF change after prescription because of ill-fitting. A total of seven patients required TF change, one of them (6.7%) in the experimental group and six patients (40%) in the control group (p = .031, 95% CI [0.011-1.04]). Reasons for ill-fitting were as follows: four patients due to excessive length and three patients due to toe compromise. The relative risk reduction for the need to change the TF via the foot scan compared to the control group was 83%, and the number needed to treat was 20. High-risk patients with diabetes tend to select TF with inadequate fitting (length or capacity), and they should be guided hand to hand to acquire proper TF.
... Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus (DM) with a considerable lifetime incidence (19%-34%) and high recurrence rate (40%-65%) in diabetic patients [1]. Typically, DFU is known as a precipitating factor in approximately 85% of cases of nontraumatic lower extremity amputations in diabetic patients [2]. ...
... The long-term outcomes were also important for chronic disease management in the life cycle. The recurrence of DFU [61] after conservative treatments is common, with a high proportion of 40% within 1 year and 65% within 3 years [1]. In our study, rehospitalization for DFU recurrence was observed in one patient (7%) within 1 year posttreatment, and in 36% of patients within 3 years posttreatment. ...
Article
Full-text available
Background Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus that contributes to 85% of nontraumatic lower extremity amputations in diabetic patients. Preliminary clinical benefits have been shown in treatments based on mesenchymal stem cells for patients with DFU or peripheral arterial disease (PAD). However, the long-term safety and benefits are unclear for patients with both DFU and PAD who are not amenable to surgical revascularization. Methods In this phase I pilot study, 14 patients with PAD and incurable DFU were enrolled to assess the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) administration based on conservative treatments. All patients received topical and intravenous administrations of hUC-MSCs at a dosage of 2 × 10 ⁵ cells/kg with an upper limit of 1 × 10 ⁷ cells for each dose. The adverse events during treatment and follow-up were documented for safety assessments. The therapeutic efficacy was assessed by ulcer healing status, recurrence rate, and 3-year amputation-free rate in the follow-up phase. Results The safety profiles were favorable. Only 2 cases of transient fever were observed within 3 days after transfusion and considered possibly related to hUC-MSC administration intravenously. Ulcer disclosure was achieved for more than 95% of the lesion area for all patients within 1.5 months after treatment. The symptoms of chronic limb ischaemia were alleviated along with a decrease in Wagner scores, Rutherford grades, and visual analogue scale scores. No direct evidence was observed to indicate the alleviation of the obstruction in the main vessels of target limbs based on computed tomography angiography. The duration of rehospitalization for DFU was 2.0 ± 0.6 years. All of the patients survived without amputation due to the recurrence of DFU within 3 years after treatments. Conclusions Based on the current pilot study, the preliminary clinical benefits of hUC-MSCs on DFU healing were shown, including good tolerance, a shortened healing time to 1.5 months and a favorable 3-year amputation-free survival rate. The clinical evidence in the current study suggested a further phase I/II study with a larger patient population and a more rigorous design to explore the efficacy and mechanism of hUC-MSCs on DFU healing. Trial registration : The current study was registered retrospectively on 22 Jan 2022 with the Chinese Clinical Trial Registry (ChiCTR2200055885), http://www.chictr.org.cn/showproj.aspx?proj=135888 Graphical Abstract
... Diabetic foot ulcers (DFUs) are among the most common and potentially serious complications of diabetes mellitus, with an estimated 19% to 34% of diabetes patients developing a DFU during their lifetimes [1]. Around 40% of patients who have developed a DFU die within 5 years [2][3][4]. ...
... While a significant proportion of the mortality rates can be attributed to fatal cardio-vascular complications of diabetes [5][6][7], the ulcer contributes independently to mortality due to inflammatory sequelae [4,8,9]. Specifically, more than half of DFUs become infected [10], with roughly 20% to 50% of moderate-to-severe diabetic foot infections potentially leading to some grade of lower extremity amputation [1,[11][12][13][14]. Many patients who underwent a DFU-related amputation have a poor quality of life and a high risk of premature death [15]. ...
Article
Full-text available
Background While rapid healing of diabetic foot ulcers (DFUs) is highly desirable to avoid infections, amputations and life-threatening complications, DFUs often respond poorly to standard treatment. GMP-manufactured skin-derived ABCB5 ⁺ mesenchymal stem cells (MSCs) might provide a new adjunctive DFU treatment, based on their remarkable skin wound homing and engraftment potential, their ability to adaptively respond to inflammatory signals, and their wound healing-promoting efficacy in mouse wound models and human chronic venous ulcers. Methods The angiogenic potential of ABCB5 ⁺ MSCs was characterized with respect to angiogenic factor expression at the mRNA and protein level, in vitro endothelial trans-differentiation and tube formation potential, and perfusion-restoring capacity in a mouse hindlimb ischemia model. Finally, the efficacy and safety of ABCB5 ⁺ MSCs for topical adjunctive treatment of chronic, standard therapy-refractory, neuropathic plantar DFUs were assessed in an open-label single-arm clinical trial. Results Hypoxic incubation of ABCB5 ⁺ MSCs led to posttranslational stabilization of the hypoxia-inducible transcription factor 1 α (HIF-1 α ) and upregulation of HIF-1 α mRNA levels. HIF-1 α pathway activation was accompanied by upregulation of vascular endothelial growth factor (VEGF) transcription and increase in VEGF protein secretion. Upon culture in growth factor-supplemented medium, ABCB5 ⁺ MSCs expressed the endothelial-lineage marker CD31, and after seeding on gel matrix, ABCB5 ⁺ MSCs demonstrated formation of capillary-like structures comparable with human umbilical vein endothelial cells. Intramuscularly injected ABCB5 ⁺ MSCs to mice with surgically induced hindlimb ischemia accelerated perfusion recovery as measured by laser Doppler blood perfusion imaging and enhanced capillary proliferation and vascularization in the ischemic muscles. Adjunctive topical application of ABCB5 ⁺ MSCs onto therapy-refractory DFUs elicited median wound surface area reductions from baseline of 59% (full analysis set, n = 23), 64% (per-protocol set, n = 20) and 67% (subgroup of responders, n = 17) at week 12, while no treatment-related adverse events were observed. Conclusions The present observations identify GMP-manufactured ABCB5 ⁺ dermal MSCs as a potential, safe candidate for adjunctive therapy of otherwise incurable DFUs and justify the conduct of a larger, randomized controlled trial to validate the clinical efficacy. Trial registration : ClinicalTrials.gov, NCT03267784, Registered 30 August 2017, https://clinicaltrials.gov/ct2/show/NCT03267784
... 5-8 Approximately 17% to 30% of people with a DFU will ultimately require a LEA and patients with DFI have 155 times greater risk of LEA than patients without associated infection. 3,7,9,10 It is estimated that 85% of all DM-related LEA are preceded by a DFU but sometime, LEAs are an inevitable treatment. 11 The key components of successful limb salvage are to achieve a DFU-free, plantigrade foot that is functional with treatments that have minimum impact on a patient's global health. ...
... It is recognized that mortality and poor quality of life are higher in DM patients who undergo major LEAs. 3 This type of data would have been informative and represents a limitation. There are also other limitations to this study. ...
Article
There are few data comparing outcomes after hallux amputation or partial first ray resection after diabetic foot ulcer (DFU). In a similar context, the choice to perform one of these two surgeries is attributable to clinician preference based on experience and characteristics of the patient and the DFU. Therefore, the purpose of this study was to determine the more definitive surgery between hallux amputation and partial first ray resection. We abstracted data from a cohort of 70 patients followed for a 1-year postoperative period to support clinical practice. We also attempted to identify patient characteristics leading to these outcomes. Our results suggested no statistical difference between the type of surgery and outcomes such as recurrence of DFU and amputation at 3, 6, and 12 months or death. However, there was a statistically significantly increased likelihood of re-ulceration for patients with CAD who underwent hallux amputation (p = 0.02). There was also a significantly increased likelihood of re-ulceration for people with depression or a history when the partial ray resection was performed (p = 0.02). Patients with prior amputation showed a higher probability of undergoing another re-amputation with partial ray resection (p = 0.01). Although the trends that emerge from this project are limited to what is observed in this statistical context, where the number of patients included and the number of total observations per outcome were limited, it highlights interesting data for future research to inform clinical decisions to support best practices for the benefit of patients.
... Diabetic foot ulcers (DFUs) are very common in patients with diabetes mellitus, with a lifetime incidence estimated to be between 19% and 34%. 1 It is one of the most serious complications of patients with diabetes, with foot amputation required in up to 20% of these patients. 2 DFUs are associated with a 2.5-fold higher risk of death than diabetic patients without foot ulcers. 1 DFUs impose a considerable burden on patients and health care service systems. ...
... 2 DFUs are associated with a 2.5-fold higher risk of death than diabetic patients without foot ulcers. 1 DFUs impose a considerable burden on patients and health care service systems. ...
Article
Full-text available
Background: Obstructive sleep apnea is prevalent in patients with diabetic foot ulcers, while the effect of intermittent hypoxia on wound healing is unclear. The objective of this study was to investigate the effect of severe intermittent hypoxia on wound healing. Methods: C57BL/6 mice were exposed to 5 weeks of severe intermittent hypoxia or normoxia. The wound healing rate were assessed. The gene expression of CD206 and HIF-2α was tested in vivo and in vitro. Inflammatory factors in RAW264.7 macrophages were measured to investigate the effect of intermittent hypoxia on macrophage polarization. The proliferation of HUVECs and HaCaT cells was also assessed after exposure to intermittent hypoxia. Results: Severe intermittent hypoxia decreased wound healing at day 3. The expression of CD206 and HIF-2α was significantly decreased after exposure to severe intermittent hypoxia. In vitro, severe intermittent hypoxia significantly promoted M1 phenotype polarization of RAW264.7 macrophages and increased the expression of proinflammatory factors (IL-1β and TNF-α). Severe intermittent hypoxia also decreased the proliferation of HUVECs cultured in endothelial cell medium and HaCaT cells cultured in high glucose DMEM. Conclusion: Severe intermittent hypoxia could lead to M1 but not M2 macrophage polarization through downregulation of HIF-2α, and then lead to impaired wound healing.
... It is a significant health concern worldwide with a challenging clinical treatment (1,2). This highly preventable diabetes complication is the primary cause of lower-extremity amputations (3). A study found that patients with DFUs had a much 2.5-fold higher risk of death than patients without lower extremity wounds, with an estimated 5year mortality rate of 42% for patients with DFUs (4). ...
Article
Full-text available
Persistent chronic oxidative stress is a primary pathogenic characteristics of diabetic foot ulcers. Puffball spores are a traditional Chinese medicine used to treat diabetic foot ulcers infections and bedsores. However, their effects against diabetic wounds and the mechanism underlying these effects remain largely unknown. The present study explored the effectiveness of puffball spores in diabetic wound treatment and the mechanisms underlying their effects. Sprague-Dawley rats with streptozotocin (STZ)-induced diabetes were treated with puffball spores to ascertain whether they accelerated wound healing.Real-time quantitative PCR, western blotting, hematoxylin-eosin and Masson’s trichrome staining, immunohistochemistry analysis, and immunofluorescence assays were performed. As indicated by wound and serum histology and biochemical analyses, the puffball spores accelerated wound healing by activating Akt/Nrf2 signaling and promoting the expression of its downstream antioxidant genes, markedly stimulating antioxidant activity and enhanceing angiogenesis and collagen deposition. Our findings showed that puffball spores could accelerate diabetic wound healing, enhance antioxidant ability, promote the expression of vascular markers, and suppress inflammation, thus providing a theoretical basis for the treatment of diabetic and refractory wounds.
... The membrane transporter SLC7A11's identification as a molecular brake on efferocytosis is important to better understand the role of DCs in regulating tissue repair, especially for diabetic wound healing. 1 Chronic cutaneous wounds induced by inflammatory conditions impact on quality of life and constitute a substantial burden for people with diabetes. 2 Efferocytosis refers to a form of apoptotic cells cleared by phagocytes around the wound edge to resolve inflammation and accelerate wound repair. 3 Immune cells are an important function to maintain skin homeostasis. ...
... Diabetic foot ulcers are one of the most severe diabetes-related complications [3]. It is estimated that 19% to 34% of the diabetic population will develop diabetic foot ulcers in their lifetime [4]. Therefore, prevention of diabetic foot ulcers plays an essential role in the care of people with DM [5,6]. ...
Article
Full-text available
Abstract Background Walking exercise has been demonstrated to improve health in people with diabetes. However, it is largely unknown the influences of various walking intensities such as walking speeds and durations on dynamic plantar pressure distributions in non-diabetics and diabetics. Traditional methods ignoring time-series changes of plantar pressure patterns may not fully capture the effect of walking intensities on plantar tissues. The purpose of this study was to investigate the effect of various walking intensities on the dynamic plantar pressure distributions. In this study, we introduced the peak pressure gradient (PPG) and its dynamic patterns defined as the pressure gradient angle (PGA) to quantify dynamic changes of plantar pressure distributions during walking at various intensities. Methods Twelve healthy participants (5 males and 7 females) were recruited in this study. The demographic data were: age, 27.1 ± 5.8 years; height, 1.7 ± 0.1 m; and weight, 63.5 ± 13.5 kg (mean ± standard deviation). An insole plantar pressure measurement system was used to measure plantar pressures during walking at three walking speeds (slow walking 1.8 mph, brisk walking 3.6 mph, and slow running 5.4 mph) for two durations (10 and 20 min). The gradient at a location is defined as the unique vector field in the two-dimensional Cartesian coordinate system with a Euclidean metric. PGA was calculated by quantifying the directional variation of the instantaneous peak gradient vector during stance phase of walking. PPG and PGA were calculated in the plantar regions of the first toe, first metatarsal head, second metatarsal head, and heel at higher risk for foot ulcers. Two-way ANOVA with Fisher’s post-hoc analysis was used to examine the speed and duration factors on PPG and PGA. Results The results showed that the walking speeds significantly affect PPG (P
... The lifetime occurrence of a foot ulceration in diabetic patients is estimated to be up to 25% [2]. Furthermore, foot ulcers reoccur after healing, with a recurrence incidence of 40% within 1 year, 60% within 3 years, and 65% within 5 years [3]. When accompanied by diabetic neuropathy, the patient does not feel any pain and may not realize the presence Page 2 of 9 Muralidhara et al. ...
Article
Full-text available
Purpose Diabetic foot is a common complication associated with diabetes mellitus (DM) leading to ulcerations in the feet. Due to diabetic neuropathy, most patients have reduced sensitivity to pain. As a result, minor injuries go unnoticed and progress into ulcers. The timely detection of potential ulceration points and intervention is crucial in preventing amputation. Changes in plantar temperature are one of the early signs of ulceration. Previous studies have focused on either binary classification or grading of DM severity, but neglect the holistic consideration of the problem. Moreover, multi-class studies exhibit severe performance variations between different classes. Methods We propose a new convolutional neural network for discrimination between non-DM and five DM severity grades from plantar thermal images and compare its performance against pre-trained networks such as AlexNet and related works. We address the lack of data and imbalanced class distribution, prevalent in prior work, achieving well-balanced classification performance. Results Our proposed model achieved the best performance with a mean accuracy of 0.9827, mean sensitivity of 0.9684 and mean specificity of 0.9892 in combined diabetic foot detection and grading. Conclusion To the best of our knowledge, this study sets a new state-of-the-art in plantar foot thermogram detection and grading, while being the first to implement a holistic multi-class classification and grading solution. Reliable automatic thermogram grading is a first step towards the development of smart health devices for DM patients.
... Skin ulcers are the most common cause of diabetes-related amputations, causing serious distress in the lives of patients [154]. Typically, these diabetic skin ulcers can be induced by chronic diabetic wounds, resulting in reactive oxygen species (ROS) overexpression and persistent inflammatory responses [155]. ...
Article
Full-text available
Diabetes-related chronic wounds are often accompanied by a poor wound-healing environment such as high glucose, recurrent infections, and inflammation, and standard wound treatments are fairly limited in their ability to heal these wounds. Metal–organic frameworks (MOFs) have been developed to improve therapeutic outcomes due to their ease of engineering, surface functionalization, and therapeutic properties. In this review, we summarize the different synthesis methods of MOFs and conduct a comprehensive review of the latest research progress of MOFs in the treatment of diabetes and its wounds. State-of-the-art in vivo oral hypoglycemic strategies and the in vitro diagnosis of diabetes are enumerated and different antimicrobial strategies (including physical contact, oxidative stress, photothermal, and related ions or ligands) and provascular strategies for the treatment of diabetic wounds are compared. It focuses on the connections and differences between different applications of MOFs as well as possible directions for improvement. Finally, the potential toxicity of MOFs is also an issue that we cannot ignore.
... Diabetic foot ulcers (DFUs), one of the most common complications of diabetes mellitus (DM), lead to increased morbidity, mortality, and healthcare costs. Approximately 19-34% of patients with diabetes could be encountered with DFU in their lifetime, and these patients have a 2.5-fold increased risk of death at five years compared with those without foot ulcers [1]. Surprisingly, the total costs for diabetic foot care exceed those for many common cancers, including breast, colorectal, and lung cancers [2]. ...
Article
Full-text available
Diabetic foot ulcers (DFUs) and their life-threatening complications, such as necrotizing fasciitis (NF) and osteomyelitis (OM), increase the healthcare cost, morbidity and mortality in patients with diabetes mellitus. While the early recognition of these complications could improve the clinical outcome of diabetic patients, it is not straightforward to achieve in the usual clinical settings. In this study, we proposed a classification model for diabetic foot, NF and OM. To select features for the classification model, multidisciplinary teams were organized and data were collected based on a literature search and automatic platform. A dataset of 1581 patients (728 diabetic foot, 76 NF, and 777 OM) was divided into training and validation datasets at a ratio of 7:3 to be analyzed. The final prediction models based on training dataset exhibited areas under the receiver operating curve (AUC) of the 0.80 and 0.73 for NF model and OM model, respectively, in validation sets. In conclusion, our classification models for NF and OM showed remarkable discriminatory power and easy applicability in patients with DFU.
... Of the people diagnosed with diabetes, around 15-25% will develop foot ulcers during their lifetime [3]. These foot ulcers are produced from neuropathy, which leads to the formation of a callus that, as a result of frequent trauma, causes subcutaneous hemorrhage and eventual erosion to an ulcer [4]. In the United States, cost estimates for the management of diabetic foot ulcers are USD 9-13 billion [2,5]. ...
Article
Full-text available
In this paper, we present a set of algorithms to enable the development of inexpensive hyperspectral sensors capable of estimating tissue oxygenation for wound monitoring. Estimation is conducted using the extended modified Lambert–Beer law, which has previously been proven robust to differences in melanin concentration. We introduce a novel wavelength selection algorithm that enables the estimation to be performed with high accuracy using only a small number (5–10) of wavelengths. Validation performed with Monte Carlo simulation data resulted in prediction errors <1%, with no significant differences among various skin types, for as few as five wavelengths under conditions representing both high precision instrumentation and more cost-effective sensors designed with inexpensive LEDs and/or filters. Validation with in vivo data collected from an occlusion study with 13 Asian volunteers showed statistically significant separation between the estimates for the at-rest and arterial occlusion states. Additional stability testing proved the proposed algorithms to be robust to small changes in the selected wavelengths as may occur in a real LED due to manufacturing tolerances and temperature fluctuations. This work concluded that the development of an inexpensive hyperspectral device for wound monitoring in all skin types is feasible using just a small number of wavelengths.
... Management of chronic ulcerative wounds is a critical worldwide healthcare challenge, associated with a high risk of morbidity and mortality [1,2]. Diabetes is an important predisposition factor for skin ulceration, particularly on the foot, which is often complicated by infection [3,4]. Several pathogens can be found in diabetic foot infection (DFI), but Staphylococcus aureus is the most common [5][6][7]. ...
Article
Full-text available
Objective Diabetic foot infection (DFI) represents a major healthcare burden, for which treatment is challenging owing to the pathophysiological alterations intrinsic to diabetes and the alarming increase of antimicrobial resistance. Novel therapies targeting DFI are therefore a pressing research need for which proper models of disease are required. Results Here, we present an optimized diabetic mouse model of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, that resemble key features of DFI, such as pathogen invasion through wound bed and surrounding tissue, necrosis, persistent inflammation and impaired wound healing. Thus, in a time-efficient manner and using simple techniques, this model represents a suitable approach for studying emerging therapies targeting DFI caused by MRSA.
... The causes of diabetic foot wounds include repetitive trauma due to foot deformity with motor and sensory neuropathy, dry skin due to autonomic neuropathy, and peripheral arterial disease that affects wound healing. [17] Glycemic control affects the improvement of neuropathy, and cardiovascular disease including hypertension, hemodialysis, and ischemic heart disease affects the progression of peripheral arterial disease. [18] Therefore, the multiisciplinary approach is recommended for the treatment of diabetic foot wounds. ...
Article
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The degree of blood vessel stenosis significantly influences diabetic foot treatment. This study aimed to investigate the association between computed tomography angiography (CTA) stenosis and skin perfusion pressure (SPP), which are noninvasive vascular assessments used to evaluate diabetic foot wounds. Forty patients who reported diabetic foot wounds between November 2016 and December 2017 were included in the study. SPPand CTA were performed to evaluate the blood flow, and the rate of decrease in wound size was measured for the wounds corresponding to Meggitt–Wagner grade 1 at the first evaluation and 4-week intervals. The P value of the association between the degree of CTA stenosis and the SPP value was 0.915, and the P value of the association between CTA stenosis and decreasing rate of wound size was .235. There was no statistically significant association between SPP and the decreasing rate of wound size according to the degree of CTA stenosis. The association between SPP value and the decreasing rate of wound size was statistically significant (P < .05). The decreasing rate in diabetic foot wound size was significantly associated with SPP but not with CTA stenosis.
... If poorly managed, diabetes causes a number of complications. Diabetic foot is one of the most common and devastating complications of diabetes, which affects 2-6% of people with diabetes annually [7,8]. Diabetic foot accounted for more than 100,000 lower-extremity amputations in the United States alone and more than 1,000,000 lower-extremity amputations worldwide each year [9,10]. ...
Preprint
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People with diabetic foot frequently exhibit poor gait and balance. However, there is no review to inform digital biomarkers of poor gait and balance related to diabetic foot, measurable by wearables outside traditional gait laboratories. Such information could assist in designing remote patient monitoring platform to track changes in gait and balance dysfunction among people with diabetic foot for timely referral and intervention. Accordingly, we conducted a web-based review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified 20 papers in this review. We found preliminary evidence of digital biomarkers of gait and balance dysfunction in people with diabetic foot, measured by wearables, such as slow gait speed, large gait variability, unstable gait initiation, and large body sway. However, due to heterogeneities in included papers in terms of study design, movement tasks, and small sample size, more studies are recommended to confirm this preliminary evidence. Additionally, based on our review, we recommend establishing appropriate strategies to successfully implement wearable-based assessment into clinical practice for diabetic foot care.
... The likelihood of a patient developing a diabetic foot ulcer (DFU) at some point during their lifetime is 34%, with an estimated 9.1-26.1 million people worldwide developing a DFU every year. 1 In fact, more than half of all DFUs become infected, 2 with foot infections representing the most common diabetes-related complication leading to hospitalisation and amputation. [3][4][5] Furthermore, in the United States, DFUs are the leading cause of nontraumatic lower extremity amputations, accounting for greater than 80% of all major (above ankle) amputations, 6 and one-third of the annual direct cost for diabetes is associated with care of the lower extremity. ...
Article
The incidence and economic burden of diabetic foot ulcers continues to rise throughout the world. In this prospective study, a unique device designed to offload the wound, enhance circulation and monitor patient compliance was evaluated for safety and efficacy. The device provides offloading and intermittent plantar compression to improve the pedal flow of oxygenated blood and support wound healing while recording patient use. Ten patients with non‐healing diabetic foot ulcers UTgrade 1A/Wagner grade 1 were treated weekly for up to 12 weeks. The primary endpoint was complete wound closure at 12 weeks, and secondary endpoints included healing time, percent area reduction and changes in pain using the visual analogue pain scale. Eight out of ten wounds healed within 12 weeks(80%), and the mean healing time was 41 days(95% CI:24.3–58.3). The percent area reduction was 75(SD:53.9). The baseline visual analogue pain scale was 4.5(2.9) as compared with 3.3(3.4) at end of study. No device‐related or serious adverse events were reported. This unique intermediate plantar compression and offloading device may be considered as an alternative for safe and effective for treatment of non‐healing diabetic foot ulcers. During treatment, wound healing was significantly accelerated, and pain was improved. Larger randomised controlled trials are underway to validate these early findings.
... However, the post-procedure course is often complicated: even when treated with the best practices, the wounds can take months to heal, and limb circulation can deteriorate, requiring revascularization of the same vessel or different sites [4]. Moreover, even after successful healing, recurrences of previously treated wounds or the emergence of new lesions are frequent [5]. Based on wound features and ischemia severity, CLI patients with DFU are considered at high risk of adverse events such as amputation or incomplete healing [6]. ...
Article
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Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease characterized by ischemic pain, which is frequently associated with diabetes and non-healing lesions to inferior limbs. The clinical management of diabetic patients with CLI typically includes percutaneous transluminal angioplasty (PTA) to restore limb circulation and surgical treatment of diabetic foot ulcers (DFU). However, even after successful treatment, CLI patients are prone to post-procedure complications, which may lead to unplanned revascularization or foot surgery. Unfortunately, the factors predicting adverse events in treated CLI patients are only partially known. This study aimed to identify potential biomarkers that predict the disease course in diabetic patients with CLI. For this purpose, we measured the circulating levels of a panel of 23 molecules related to inflammation, endothelial dysfunction, platelet activation, and thrombophilia in 92 patients with CLI and DFU requiring PTA and foot surgery. We investigated whether these putative biomarkers were associated with the following clinical endpoints: (1) healing of the treated DFUs; (2) need for new revascularization of the limb; (3) appearance of new lesions or relapses after successful healing. We found that sICAM-1 and endothelin-1 are inversely associated with DFU healing and that PAI-1 and endothelin-1 are associated with the need for new revascularization. Moreover, we found that the levels of thrombomodulin and sCD40L are associated with new lesions or recurrence, and we show that the levels of these biomarkers could be used in a decision tree to assign patients to clusters with different risks of developing new lesions or recurrences.
... Lower limb trophic disorder in people living with diabetes, often referred to as "diabetic foot", is a common and serious complication of diabetes. It is estimated that a person living with diabetes has a 19-34% lifetime risk of developing a DFU [4]. This wound often becomes infected and in 20% of the cases the infection will lead to amputation [5], making diabetes the leading cause of non-traumatic amputation in Western countries [6]. ...
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The diabetic foot ulcer (DFU) is a common and serious complication of diabetes. There is also a strong relationship between the environment of the person living with a DFU and the prognosis of the wound. Financial insecurity seems to have a major impact, but this effect can be moderated by social protection systems. Socioeconomic and socio-educational deprivations seem to have a more complex relationship with DFU risk and prognosis. The area of residence is a common scale of analysis for DFU as it highlights the effect of access to care. Yet it is important to understand other levels of analysis because some may lead to over-interpretation of the dynamics between social deprivation and DFU. Social deprivation and DFU are both complex and multifactorial notions. Thus, the strength and characteristics of the correlation between the risk and prognosis of DFU and social deprivation greatly depend not only on the way social deprivation is calculated, but also on the way questions about the social deprivation−DFU relationship are framed. This review examines this complex relationship between DFU and social deprivation at the individual level by considering the social context in which the person lives and his or her access to healthcare.
... According to previous studies, about 25∼34% of diabetic patients have at least one-foot ulcer in their lifetime, and the amputation rate is 15 times higher than that of non-diabetic patients (3). For each additional year of diabetes history (4), the amputation risk was 1.06 to 1.15 times greater. ...
Article
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Diabetic foot ulcers (DFUs) are considered the most challenging forms of chronic ulcerations to handle their multifactorial nature. It is necessary to establish a comprehensive treatment plan, accurate, and systematic evaluation of a patient with a DFU. This paper proposed an image recognition of diabetic foot wounds to support the effective execution of the treatment plan. In the severity of a diabetic foot ulcer, we refer to the current qualitative evaluation method commonly used in clinical practice, developed by the International Working Group on the Diabetic Foot: PEDIS index, and the evaluation made by physicians. The deep neural network, convolutional neural network, object recognition, and other technologies are applied to analyze the classification, location, and size of wounds by image analysis technology. The image features are labeled with the help of the physician. The Object Detection Fast R-CNN method is applied to these wound images to build and train machine learning modules and evaluate their effectiveness. In the assessment accuracy, it can be indicated that the wound image detection data can be as high as 90%.
... People involved in self-management can help prevent/postpone the appearance of an ulcer, by detecting the corresponding signs and symptoms early on. Additionally, monitoring of existing ulcers is advised to prevent complications or recurrent ulceration [1]. During DFU monitoring, there are various signs and symptoms that should be taken under consideration including: skin color change (redness), skin temperature change, foot pressure induced injury (damage to the skin and/or underlying soft tissue), pain, swelling, or odor. ...
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Diabetic foot ulcers (DFUs) constitute a serious complication for people with diabetes. The care of DFU patients can be substantially improved through self-management, in order to achieve early-diagnosis, ulcer prevention, and complications management in existing ulcers. In this paper, we investigate two categories of image-to-image translation techniques (ItITT), which will support decision making and monitoring of diabetic foot ulcers: noise reduction and super-resolution. In the former case, we investigated the capabilities on noise removal, for convolutional neural network stacked-autoencoders (CNN-SAE). CNN-SAE was tested on RGB images, induced with Gaussian noise. The latter scenario involves the deployment of four deep learning super-resolution models. The performance of all models, for both scenarios, was evaluated in terms of execution time and perceived quality. Results indicate that applied techniques consist a viable and easy to implement alternative that should be used by any system designed for DFU monitoring.
... This together with neuropathy leads to further complications and an increase in the incidence of lower limb amputations due to non-healing diabetic foot ulcers (DFUs). 4 Globally, it is estimated that 25% of the diabetic patients develop a DFU, 5 with a high recurrence rate of up to 70% within 5 years, and with statistics showing that 85% of the amputations in diabetics starts with ulcers. 6,7 Diabetic foot amputation is one of the most common and most feared complication of diabetes. ...
Article
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Purpose: Photobiomodulation (PBM) promotes diabetic wound healing by favoring cell survival and proliferation. This study aimed to investigate the potential of PBM in stimulating cellular migration, viability, and proliferation using the transforming growth factor- β1 (TGF-β1)/Smad signaling pathway. Methods: The study explored the in vitro effects of near infrared (NIR) light on cell viability (survival) and proliferation as well as the presence of TGF-β1, phosphorylated TGF-β receptor type I (pTGF-βR1) and phosphorylated mothers against decapentaplegichomolog (Smad)-2/3 (p-Smad2/3) in different fibroblast cell models. Results: Results show a significant increase in cellular migration in wounded models, and increased viability and proliferation in irradiated cells compared to their respective controls. An increase in the presence of TGF-β1 in the culture media, a reduction in pTGF-βR1 and a slight presence of p-Smad2/3 was observed in the cells. Conclusion: These findings show that PBM at 830 nm using a fluence of 5 J/cm2 could induce cell viability, migration and proliferation to favor successful healing of diabetic wounds. This study contributes to the growing body of knowledge on the molecular and cellular effect of PBM and showcases the suitability of PBM at 830 nm in managing diabetic wounds. Keywords: diabetic wound, photobiomodulation, wound healing, hyperglycemia, NIR light
Article
Objective Diabetic foot ulcers (DFUs) are characterised by the presence of many microbes, some of which may not be identified by traditional culture techniques. Total contact casting (TCC) remains the gold-standard for offloading, yet little is known about the microbiome of wounds that progress from hard-to-heal to closed within a TCC. Method A patient with a DFU underwent weekly treatment with TCC to closure. Samples for next-generation sequencing (NGS) and bioinformatics analysis of tissue samples were collected during each visit. Detection, identification, characterisation of the microbial community and abundance of microbes in each sample were compared. Results Abundance of microbes, identified by species and strain, changed with each treatment visit. By the final week of treatment, species diversity of the wound microbiome had decreased significantly, highlighted by an observed decrease in the number of total microorganisms present. Resistance genes for tetracyclines were detected in the first sample, but not in subsequent samples. Conclusion The results of this study suggest dynamic microbiological changes associated with DFUs as they progress to healing within a TCC. As NGS becomes more readily available, further studies will be helpful to gain an improved understanding of the significance of the wound microbiome in patients with DFUs.
Article
The increase in the global diabetic population is leading to an increase in associated complications such as diabetic foot ulceration (DFU), associated amputations, morbidity, which substantial treatment costs. Early identification of DFU risk is therefore of great benefit. International guidelines recommend off-loading is the most important intervention for healing and prevention of DFU, with current research focused on pressure measurement techniques. The contribution of strain to DFU formation is not well understood due to challenges in measurement. The limited data available in the literature suggest that plantar strain is involved in ulcer formation. As a consequence, there is a need for plantar strain measurement systems to advance understanding and inform clinical treatment. A method was developed to determine plantar strain based on a Digital Image Correlation (DIC) approach. A speckle pattern is applied to the plantar aspect of the foot using a low ink transference method. A raised walkway with transparent panels is combined with a calibrated camera to capture images of the plantar aspect throughout a single stance phase. Plantar strain is then determined using 2D DIC and custom analysis summarises these data into clinically relevant metrics. A feasibility study involving six healthy participants was used to assess the efficacy of this new technique. The feasibility study successfully captured plantar surface strain characteristics continuously throughout the stance phase for all participants. Peak mean and averaged mean strains varied in location between participants when mapped into anatomical regions of plantar interest, ranging from the calcaneus to the metatarsal heads and hallux. This method provides the ability to measure plantar skin strain for use in both research and clinical environments. It has the potential to inform improved understanding of the role of strain in DFU formation. Further studies using this technique can support these ambitions and help differentiate between healthy and abnormal plantar strain regimes.
Article
Several diseases or conditions cause dermatological disorders that hinder the process of skin repair. The search for novel technologies has inspired the combination of stem cell (SC) and light‐based therapies to ameliorate skin wound repair. Herein, we systematically revised the impact of photobiomodulation therapy (PBM) combined with SCs in animal models of skin wounds and quantitatively evaluated this effect through a meta‐analysis. For inclusion, SCs should be irradiated in vitro or in vivo, before or after being implanted in animals, respectively. The search resulted in nine eligible articles, which were assessed for risk of bias. For the meta‐analysis, studies were included only when PBM was applied in vivo, five regarding wound closure, and three to wound strength. Overall, a positive influence of SC+PBM on wound closure (MD: 9.69; 95%CI: 5.78 to 13.61, p<0.00001) and strength (SMD: 1.7, 95%CI: 0.68 to 2.72, p=0.001) was detected, although studies have shown moderate to high heterogeneity and a lack of information regarding some bias domains. Altogether, PBM seems to be an enabling technology able to be applied post‐implantation of SCs for cutaneous regeneration. Our findings may guide future laboratory and clinical studies in hopes of offering wound care patients a better quality of life.
Article
Objective Diabetic foot ulcer (DFU) is recognised as a severe complication in patients with type 2 diabetes. With the increasing incidence of diabetes, it represents a major medical challenge. Several models have been proposed to explain its aetiology; however, they have never been assessed by longitudinal histopathological examination, which this study aims to address. Method Multiplex-immunofluorescence analysis was carried out with lengthwise serial skin specimens obtained from the medial thigh, lower leg, ankle, dorsum of foot and acrotarsium close to the DFU region of a patient with type 2 diabetes receiving above the knee amputation. Results Proximal-to-distal gradual loss of peripheral nerve was demonstrated, accompanied by compromised capillaries in the superficial papillary plexus and distended CD31-positive capillaries in the dorsum of foot. Neural fibres and capillaries were also significantly compromised in the sweat gland acinus in the ankle and dorsum of foot. Injuries in the superficial papillary plexus, sweat gland acinus, and sweat gland-associated adipose tissues were accompanied by significant infiltration of macrophages. These results indicated that longitudinal impairment of local blood circulation could be the cause of peripheral neuropathy, which initiated ulcer formation. Resultant chronic inflammation, involving sweat gland-associated adipose tissue, gave rise to impairment of wound healing, and thus DFU formation. Conclusion Longitudinal histopathological examination demonstrated that impairment of local microvascular circulation (rather than the systemic complication caused by type 2 diabetes) was considered the primary cause of peripheral neuropathy, which initiated ulceration. Together with chronic inflammation in the superficial papillary plexus and sweat gland-associated adipose tissue, it resulted in the development of a DFU. Although this is a study of just one individual's limb, our study provided a unique observation, contributing mechanistic insights into developing novel intervening strategies to prevent and treat DFUs.
Article
Gas-producing infections, such as clostridial and non-clostridial gas gangrene, crepitant cellulitis, and necrotizing fasciitis, are characterized in the literature by a variety of initial presentations, microbial burdens and surgical outcomes—ranging from debridement to amputation to death. The primary aim of this study was to identify the organisms cultured in gas-producing infections of the foot in patients that presented to a large academic medical center over a 10-year period. Our secondary aims were to report the prevalence of sepsis in this population upon presentation, and patient outcomes upon discharge. After a retrospective chart review of 207,534 procedures, 70 surgical cases met inclusion criteria. The most common organisms that grew in operating room cultures were Staphylococcus aureus, Group B Beta Streptococcus, and Enterococcus species. Just over half of the population presented with sepsis. After an average of two or more operations, 64% of patients underwent amputation. One death occurred. Gas-producing infections, or “gas gangrene,” are primarily polymicrobial infections, rarely due to Clostridium perfringens, that warrant surgical exploration for optimal outcomes.
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A lack of angiogenesis is the key problem in the healing of diabetic foot ulcers. Stem cells have already been proven to have a high potential for angiogenesis. The most important aspects of stem cell therapy are improving the microenvironment, cell homing and continuous factor stimulation. We investigated the effect of Klotho protein to heal wounds by promoting the proliferation and migration of bone mesenchymal stem cells and endothelial cells in vitro. Based on the above study, we produced a compound material by using poly(lactic‐co‐glycolic acid) (PLGA), chitosan microspheres and gelatin through electro spining technology. The structure of the compound material, just like a sandwich, is that two pieces of PLGA nanofiber films clamped gelatin film which contained chitosan microspheres. In the in vitro release experiment, we could detect the release of Klotho after seven days in the compound material, but the release time was approximately 40 hours for the chitosan microspheres. After seeded bone mesenchymal stem cells (BMSCs) on the surface of the compound material, we observed morphologies of the chitosan microsphere, the PLGA nanofiber and BMSCs by scanning electron microscopy. The nanofiber mesh biological tissue materials could supply an appropriate microenvironment and cell factors for the survival of BMSCs. Compared with the control group, the biological tissue material seeded with BMSCs significantly promoted angiogenesis in the lower limb of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. The compound biomaterial which could continuously stimulate BMSCs through releasing Klotho protein could accelerate wound healing in the diabetic foot and other ischemic ulcers.
Article
This study explored the clinical effectiveness of antibiotic-loaded bone cement (ALBC) combined with vacuum-assisted closure (VAC) on the treatment of Wagner 3-4 diabetic foot ulcers (DFUs). This is a retrospective study, including 32 patients with Wagner 3-4 DFUs who had undergone treatment between August 2019 and June 2021. Patient age, sex, Hemoglobin A1c (HbA1c), body mass index (BMI), ankle brachial index (ABI), white blood cells (WBC), C-reactive protein (CRP) levels, comorbidities and wound closure methods were recorded. Patients were divided into the study group and control group according to the treatment modality. Patients in the study group received the combination treatment of ALBC and VAC, while patients in the control group received single VAC treatment. Clinical endpoints were assessed and compared between the two groups, including wound complete healing time and complications after operation. All patients were followed-up 6 months postoperation. Results showed that the mean healing time of the study group (44.20 ± 16.72 days) was shorter than that of the control group (64.00 ± 29.85 days) ( P < .05). The infection rate of the study group on the 10th day postoperation was lower than that of the control group (6.67%, 47.06%, P < .05). And there were no significant statistical differences between the two groups in terms of bleeding and necrosis complications postoperation ( P = .603, P = .603). Based on the findings, we conclude that the application of ALBC combined with VAC can facilitate wound healing in Wagner 3-4 DFUs patients. It can help to control wound infections and shorten wound healing time.
Article
Objective : The purpose of this study was to estimate the value of a novel imaging technique in necrotic tissue debridement of diabetic foot ulcers (DFU), using near-infrared (NIR) fluorescence molecular imaging (FMI) of indocyanine green (ICG). Methods : The patients with DFU were included and divided into a FMI navigation debridement group and a traditional group. The FMI of the wounds and the debridement effect of each group was analyzed, including debridement frequency, length of hospital stay, and the histological examination of removed tissue. Result : A total of 40 patients with DFU (23 cases in the FMI group and 17 cases in the traditional group) were included in this study. The positive rate of wound fluorescence in the FMI group was 96%, and no patients had related side effects. The pathological examination confirmed that the tissue emitting NIR fluorescence was totally necrotic tissue. In addition, the debridement frequency in the FMI group is less than that in the traditional group, but there is no difference in the length of hospital stay between the two groups. Conclusion : ICG FMI technique can accurately illuminated necrotic tissue, with high sensitivity, easy operation and good safety, which would be a new way to precisly guide the process of debridement in clinical.
Article
Aims: Data regarding diabetic foot ulcers (DFU) in patients after solid organ transplantation, particularly kidney transplantation, are limited. Chronic immunosuppression may be associated with impaired wound healing and a higher risk of amputations. In this study we characterized the clinical presentation and outcomes of patients after kidney transplantation admitted to the diabetic foot unit, compared to non-kidney-transplant patients. Materials and methods: Data on the baseline characteristics, clinical presentation and outcomes of all patients admitted to the diabetic foot unit of a large tertiary center between the years 2014-2019 were collected. The most recent admission of each patient was considered. Primary outcomes were major amputations and one-year mortality rate. Results: During the study period 537 patients were hospitalized, 18 of them receiving immunosuppressive therapy due to kidney transplantation. Baseline characteristics of the patients were broadly similar, except that smoking was reported by 22.0% of the non-transplant patients and by none of the post-transplant patients (p=0.01). Post-transplant patients tended to be younger (59.4±11.1 vs. 65.3±12.2; p=0.07), were more likely to have type-1 diabetes (16.7% vs. 5.2%; p=0.07) and had lower glucose levels upon admission (9.4±4.3 vs. 12.0±6.4 mmol/L; p=0.07). Overall, 30% of the patients underwent major amputation, in-patient mortality rate was 9.3%, and 1-year mortality rate was 27.2%. Rates were similar in the post-transplant vs. the non-post-transplant patients (p=0.83, 1.00, 0.59 respectively). Conclusions: Post-transplant patients did not incur worse outcomes in spite of immunosuppressive therapy. Limb salvage efforts should be pursued in these patients similar to the overall population. This article is protected by copyright. All rights reserved.
Article
Patients with diabetes suffer from a variety of complications and easily develop diabetic chronic wounds. The microenvironment of diabetic wounds is characterized by an excessive amount of reactive oxygen species (ROS) and an imbalance of proinflammatory and anti-inflammatory cells/factors, which hinder the regeneration of chronic wounds. In the present study, a wound dressing with immunomodulation and electroconductivity properties was prepared and assayed in vitro and in vivo. [2-(acryloyloxy) ethyl] Trimethylammonium chloride (Bio-IL) and gelatin methacrylate (GelMA) were 3D printed onto a doxycycline hydrochloride (DOXH)-loaded and ROS-degradable polyurethane (PFKU) nanofibrous membrane, followed by UV irradiation to obtain conductive hydrogel strips. DOXH was released more rapidly under a high ROS environment. The dressing promoted migration of endothelial cells and polarization of macrophages to the anti-inflammatory phenotype (M2) in vitro. In a diabetic rat wound healing test, the combination of conductivity and DOXH was most effective in accelerating wound healing, collagen deposition, revascularization, and re-epithelialization by downregulating ROS and inflammatory factor levels as well as by upregulating the M2 macrophage ratio. Statement of Significance The microenvironment of diabetic wounds is characterized by an excessive amount of reactive oxygen species (ROS) and an imbalance of proinflammatory and anti-inflammatory cells/factors, which hinder the regeneration of chronic wounds. Herein, a wound dressing composed of a DOXH-loaded ROS-responsive polyurethane membrane and 3D-printed conductive hydrogel strips was prepared, which effectively accelerated skin regeneration in diabetic wounds in vivo with better epithelialization, angiogenesis, and collagen deposition. DOXH regulated the dysfunctional wound microenvironment by ROS scavenging and polarizing macrophages to M2 phenotype, thereby playing a dominant role in diabetic wound regeneration. This design may have great potential for preparing other similar materials for the therapy of other diseases with excessive inflammation or damage to electrophysiological organs, such as nerve defect and myocardial infarction.
Article
Wound healing and angiogenesis remain challenges for both clinical and experimental research worldwide. Periosteum-derived extracellular vesicles (P-sEVs) delivered by hydrogel dressings provide a potential strategy for wound defects to promote fast healing. In this study, we designed a NAGA/GelMA/Laponite/glycerol hydrogel wound dressing that can release P-sEVs to accelerate angiogenesis and wound healing (named [email protected]) (N-acryloyl glycinamide, NAGA). The wound dressing showed multiple functions, including efficient angiogenesis, tissue adhesion and a physical barrier. P-sEVs significantly enhanced the proliferation, migration, and tube formation of endothelial cells in vitro. The results of in vivo experiments showed that [email protected] accelerates the healing of a full-thickness defect wound model by stimulating the angiogenic process. The improved cell proliferation, tissue formation, remodeling, and re-epithelialization possibly resulted in the fast healing. This study shows that multifunctional hydrogel dressing combined with bioactive molecules can achieve fast and satisfactory wound healing in full-thickness wound defects and other related wounds.
Article
Background Diabetes Mellitus and obesity represent two chronic multifactorial conditions which may induce modifications in human motion strategy. Our study focused on gaining insight into biomechanical aspects of gait occurring in patients affected by both aforementioned pathologies. Methods One hundred subjects were recruited and divided into four groups: 25 obese-diabetic patients with peripheral neuropathy; 25 obese non-diabetic patients; 25 non-obese diabetic patients with peripheral neuropathy; 25 healthy volunteers participated as a control group. Subjects performed 3-D Gait Analysis while walking barefoot at self-selected speed, performing three consecutive trials. A multivariate analysis of variance test was used to assess spatio-temporal and kinematic data difference in the four groups. Tukey's post-hoc adjustment was applied on multiple groups' comparison. Findings Diabetic-obese subjects showed increased step width compared to controls, while step and stride length, and walking velocity were reduced. Interestingly, step width presented increased values even compared to diabetic patients. Kinematics data showed a significant reduction in ankle plantarflexion during the push-off phase of the gait cycle compared to controls, and to obese subjects. Furthermore, knee kinematics revealed a reduced peak flexion during the swing time of the gait cycle, compared to controls and diabetic subjects, which resulted in reduced knee dynamic excursion during normal walking compared to healthy subjects. Interpretation Our data demonstrated that diabetic-obese subjects present gait features typical of both such pathologies. The specific impairment of ankle and knee joint kinematics provides evidence of a synergistic effect of Diabetes Mellitus type 2 and obesity on human ambulatory function.
Article
Background Diabetic ulcers, which are characterized by chronic nonhealing wounds with a long-lasting inflammatory state, are a typical symptom in individuals with diabetes, and there is still no effective treatment for these lesions. Angelica dahurica plays a critical role in inflammatory diseases. Among numerous monomeric compounds, phellopterin has been shown to have anti-inflammatory properties. Purpose To research the bioactive constituents in Angelica dahurica and their mechanism of action in treating diabetic ulcers. Study design Chemical research of Angelica dahurica led to the identification of a new coumarin, dahuricoumarin A (1), along with seven known compounds (2 − 8). All compounds were tested for anti-inflammatory activity, and phellopterin, compound (3), significantly decreased the expression of intercellular cell adhesion molecule-1 (ICAM-1), a representative indicator of inflammation. Phellopterin can also increase SIRT1 protein, a key target for inflammation. In our research, we confirmed the anti-inflammatory effects of phellopterin on diabetic ulcers and explored the underlying mechanism of action. Methods The expression of IFN-γ, SIRT1, and ICAM-1 in human diabetic ulcer tissues was studied using immunohistochemistry. Streptozotocin was used to induce a diabetic model in C57BL/6J mice, and ulcers were surgically introduced. After phellopterin treatment, the skin lesions of diabetic mice were observed over a period of time. The protein and mRNA expression levels of SIRT1 and ICAM-1 were measured using H&E, qRT–PCR and immunohistochemical staining. A HaCaT cell inflammatory model was induced by IFN-γ. Using a lentiviral packaging technique, MTT assay, and Western blotting, the effect of phellopterin on the proliferation of HaCaT cells and the expression of ICAM-1 was evaluated under normal and SIRT1 knockdown conditions. Results High levels of ICAM-1 and IFN-γ were identified, but low levels of SIRT1 were found in human diabetic ulcer tissues, and phellopterin showed therapeutic benefits in the healing process by attenuating chronic inflammation and promoting re-epithelialization, along with SIRT1 upregulation and ICAM-1 downregulation. However, inhibiting SIRT1 reversed its proliferative and anti-inflammatory effects. Conclusion In vitro and in vivo, phellopterin exerts anti-inflammatory and proliferative effects that promote diabetic wound healing, and the potential mechanism depends on SIRT1.
Article
This meta‐analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet‐rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta‐analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta‐analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = −0.87, 95% confidence interval [CI]: −1.07 to −0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = −15.29, 95% CI: −16.05 to −14.54, P < .00001), but the differences in dressing change times (SMD = −1.27, 95% CI: −2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = −0.16, 95% CI: −13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.
Article
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium (DFC) was established in September 2018 by the NIDDK to build an organization to facilitate the highest quality of clinical research on diabetic foot ulcers (DFUs) that will answer clinically significant questions to improve DFU healing and prevent amputations. The initial focus of the DFC is to develop and validate biomarkers for DFUs that can be used in clinical care and research. The DFC consists of a data coordinating center (DCC) for operational oversight and statistical analysis, clinical sites for participant recruitment and evaluation, and biomarker analysis units (BAUs). The DFC is currently studying biomarkers to predict wound healing and recurrence and is collecting biosamples for future studies through a biorepository. The DFC plans to address the challenges of recruitment and eligibility criteria for DFU clinical trials by taking an approach of “No DFU Patient Goes Unstudied.” In this platform approach, clinical history, DFU outcome, wound imaging, and biologic measurements from a large number of patients will be captured and the in-depth longitudinal data set will be analyzed to develop a computational-based DFU risk factor profile to facilitate scientifically sound clinical trial design. The DFC will expand its platform to include studies of the role of social determinants of health, such as food insecurity, housing instability, limited health literacy, and poor social support. The DFC is starting partnerships with the broad group of stakeholders in the wound care community.
Article
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Abstract To investigate the effect of contoured insoles constructed of different insole materials, including Nora Lunalastik EVA, Nora Lunalight A fresh, Pe-Lite, and PORON Medical 4708 with Langer Biomechanics longitudinal PPT arch pads on offloading plantar pressure on the foot of the elderly with Type 1 or 2 diabetes during gait. Twenty-two elderly with Type 1 or 2 diabetes participated in the study. Their plantar pressure was measured by using an insole measurement system, while the participants walked 10 m in their bare feet or used each experimental insole in random order. The plantar surface was divided into four specific regions including the toes, forefoot, midfoot, and rearfoot. The mean peak pressure (MPP) and pressure–time integral (PTI) of ten steps with or without wearing one of the four insoles were analyzed on the dominant foot and the four specific plantar regions. After completion of the activities, the participants scored each insole from 1 (the least comfortable) to 10 (the most comfortable). The analysis of variance (ANOVA) factor of the insoles had significant effects on the MPP (P
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Diabetic foot ulcers (DFU) are a serious complication of diabetes mellitus that burden patients and health care systems. Staphylococcus aureus is prevalent and abundant in the DFU microbiome, and strain-level differences in S. aureus may drive clinical outcomes. To identify mechanisms underlying strain-specific outcomes in DFU with S. aureus, we performed high-throughput phenotyping screens on a collection of 221 S. aureus cultured isolates from clinically uninfected DFU. Of the 4 phenotypes examined (in vitro biofilm formation and production of staphylokinase, staphyloxanthin, and siderophores), we discovered that isolates from non-healing wounds produced more staphyloxanthin, a carotenoid cell membrane pigment. In a murine diabetic wound healing model, staphyloxanthin-producing isolates delayed wound closure significantly compared to staphyloxanthin-deficient isolates. Staphyloxanthin promoted resistance to oxidative stress in vitro and enhanced bacterial survival in human neutrophils. Comparative genomic and transcriptomic analysis of genetically similar clinical isolates with disparate staphyloxanthin phenotypes revealed a mutation in the Sigma B regulatory pathway that resulted in marked differences in stress response gene expression. Our findings suggest that staphyloxanthin production delays wound healing by protecting S. aureus from neutrophil-mediated oxidative stress, and may provide a target for therapeutic intervention in S. aureus-positive wounds.
Article
Diabetic neuropathy is one of the most common neurological complications of diabetes with a high risk of morbidity that affects the quality of life of individuals. Many people with diabetes do not report symptoms or problems associated with diabetic neuropathy. All patients with diabetes should be screened annually for neuropathy with a neuropathy-specific history, screening test, and physical examination. These individuals are at high risk for poor quality of life, neuropathic pain, falls, development of foot ulcers and infections, and amputation. In order to minimize complications and improve quality of life, early diagnosis of individuals with diabetic neuropathy, evaluation with valid and reliable screening tools, and management of diabetic neuropathy are important. Management of diabetic neuropathy requires a multidisciplinary team approach. Nurses, who are an important member of this team, are among the responsibilities of nurses to raise awareness of individuals with diabetic neuropathy and those at risk of developing neuropathy, to plan interventions for high-risk groups, and to ensure that they gain correct knowledge and behavior. The nurse's awareness and knowledge about the screening, diagnosis, treatment and care practices of individuals with diabetic neuropathy will be beneficial in preventing or reducing the development of negative outcomes. Keywords: Diabetic neuropathy; scanning; treatment; care; nursing.
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One of the most important and common complications of diabetes is a disorder and defect in diabetic wound healing. The aim of present study was to investigate the synergistic effects of decellularized human amniotic membrane (dHAM) engraftment and adipose-derived stem cells (ADSs) transplantation in the healing of delayed and ischemic diabetic wound. Sixty diabetic male rats were randomly divided into 4 groups (n=15), including; untreated (Control) group, engraftment by dHAM (dHAM) group, transplanted by ADSs (ADS) group, and engraftment by dHAM plus transplanted by ADSs (dHAM+ADS) group. Sampling was performed at days 7, 14, and 21 after surgery. Evaluation tests included stereology, immunohistochemistry, molecular, and biomechanical. Our results showed that the wound closure rate, volumes of newly formed epidermis and dermis, density of fibroblasts and blood vessels, collagen deposition, density of proliferation cells, expression levels of TGF-β and VEGF genes, and biomechanical characteristics were significantly higher in all treated groups compared to control group, however, these changes were considerable in the combination group. This is while that the density of neutrophils and expression levels of TNF-α and IL-1β genes in the treated groups, especially in the combination group, were significantly reduced compared to control group. Generally, the simultaneous use of dHAM and ADS accelerates healing and improves the quality of repaired diabetic wounds.
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Chronic wounds in type-2 diabetic patients present areas of severe local skin ischemia despite mostly normal blood flow in deeper large arteries. Therefore, restoration of blood perfusion requires the opening of arterial connections from the deep vessels to the superficial skin layer, that is, arteriogenesis. Arteriogenesis is regulated differently from microvascular angiogenesis and is optimally stimulated by high doses of Vascular Endothelial Growth Factor-A (VEGF) together with Platelet-Derived Growth Factor-BB (PDGF-BB). Here we found that fibrin hydrogels decorated with engineered versions of VEGF and PDGF-BB proteins, to ensure protection from degradation and controlled delivery, efficiently accelerated wound closure in diabetic and obese db/db mice, promoting robust microvascular growth and a marked increase in feeding arterioles. Notably, targeting the arteriogenic factors to the intact arterio-venous networks in the dermis around the wound was more effective than the routine treatment of the inflamed wound bed. This approach is readily translatable to a clinical setting.
Article
Objective The lifetime risk of developing a diabetic foot ulcer (DFU) in people with diabetes is as high as 25%. A trio of factors constitute the diabetic foot syndrome that characterises DFUs, including neuropathy, vascular disease and infections. Vitamin C has important functions in the nervous, cardiovascular, and immune systems that are implicated in DFU development. Furthermore, vitamin C deficiency has been observed in individuals with DFUs, suggesting an important function of vitamin C in DFU management and treatment. Therefore, this literature review evaluates the role of vitamin C in the nervous, cardiovascular and immune systems in relation to wound healing and DFUs, as well as discussing vitamin C's lesser known role in depression, a condition that affects many individuals with a DFU. Method A literature search was done using PubMed, Cochrane Library, Embase, Ovid, Computer Retrieval of Information on Scientific Projects, and NIH Clinical Center. Search terms included ‘diabetic foot ulcer,’ ‘diabetic foot,’ ‘vitamin C,’ and ‘ascorbic acid.’ Results Of the 71 studies initially identified, seven studies met the inclusion criteria, and only three were human clinical trials. Overall, the literature on this subject is limited, with mainly observational and animal studies, and few human clinical trials. Conclusion There is a need for additional human clinical trials on vitamin C supplementation in individuals with a DFU to fill the knowledge gap and guide clinical practice.
Article
Diabetic neuropathy is one of the main complications of Diabetes Mellitus, which can lead to loss of protective sensation, motor, and plantar pressure alteration, generating deformities, abnormal gait and mechanical trauma to the feet. to evaluate the distribution of plantar pressure, sensorimotor changes, balance and associated factors to plantar pressure changes in people with peripheral diabetic neuropathy. Cross-sectional study conducted with individuals registered in the primary public health service of a city in the east of São Paulo – Brazil. The sample was composed by people with Diabetes Mellitus and Peripheral Neuropathy identified by the Michigan Screening Instrument. It were investigated variables such as sensory-motor changes, static and dynamic plantar pressure using baropodometry and balance using the Berg scale. A significance level of 5% was adopted for all tests used. Of the 200 individuals evaluated, 52.55% had no plantar protective sensitivity, the static evaluation did not demonstrated changes in the peak of plantar pressure, however in the dynamics the mean in the right foot was 6.0 (±2) kgf/cm2 and 6,7 (±1.62) kgf/cm2 on the left foot, the center of static pressure on the right foot was lower (10.55 ± 3.82) than on the left foot (11.97 ± 3.90), pointing hyper plantar pressure. The risk of falling was high, ranging from 8 to 56 points, with an average of 40.9 (±10.77). The absence of protective plantar sensitivity, increased pressure, biomechanical changes lead to loss of balance and are predictive of complications in the feet due to diabetic neuropathy.
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Objective: To evaluate ambulatory clinical cases of diabetic foot ulcers (DFUs) and diabetic foot infections (DFIs) in the U.S. from 2007 to 2013 and to assess outcomes of emergency department or inpatient (ED/IP) admission, number of clinic visits per year, and physician time spent per visit. Research design and methods: A cross-sectional historical cohort analysis was conducted by using the nationally representative Centers for Disease Control and Prevention National Ambulatory Medical Care Survey data from 2007 to 2013, including patients age ≥18 years with diabetes and either DFIs or DFUs. Study outcomes were analyzed by using generalized linear models controlling for key demographics and chronic conditions. Results: Across the estimated 5.6 billion ambulatory care visits between 2007 and 2013, 784.8 million involved diabetes and ∼6.7 million (0.8%) were for DFUs (0.3%) or DFIs (0.5%). Relative to other ambulatory clinical cases, multivariable analyses indicated that DFUs were associated with a 3.4 times higher odds of direct ED/IP admission (CI 1.01-11.28; P = 0.049), 2.1 times higher odds of referral to another physician (CI 1.14-3.71; P = 0.017), 1.9 times more visits in the past 12 months (CI 1.41-2.42; P < 0.001), and 1.4 times longer time spent per visit with the physician (CI 1.03-1.87; P = 0.033). DFIs were independently associated with a 6.7 times higher odds of direct ED referral or IP admission (CI 2.25-19.51; P < 0.001) and 1.5 times more visits in the past 12 months (CI 1.14-1.90; P = 0.003). Conclusions: This investigation of an estimated 6.7 million diabetic foot cases indicates markedly greater risks for both ED/IP admissions and number of outpatient visits, with DFUs also associated with a higher odds of referrals to other physicians and longer physician visit times.
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Diabetic foot ulceration poses a heavy burden on the patient and the health care system, but prevention thereof receives little attention. For every euro spent on ulcer prevention, ten are spent on ulcer healing, and for every randomized controlled trial conducted on prevention, ten are conducted on healing. In this paper, we argue that a shift in priorities is needed. For the prevention of a first foot ulcer, we need more insight into the effect of interventions and practices already applied globally in many settings. This requires systematic recording of interventions and outcomes, and well-designed randomised controlled trials, which include analysis of cost-effectiveness. After healing of a foot ulcer, the risk of recurrence is high. For the prevention of a recurrent foot ulcer, home monitoring of foot temperature, pressure-relieving therapeutic footwear, and certain surgical interventions prove to be effective. The median effect size found in a total 23 studies on these interventions is large, over 60%, and further increases when patients are adherent to treatment. These interventions should be investigated for efficacy as a state-of-the-art integrated foot care approach, where attempts are made to assure treatment adherence. Effect sizes of 75-80% may be expected. If such state-of-the-art integrated foot care is implemented, the majority of problems with foot ulcer recurrence in diabetes can be resolved. It is therefore time to act and to set a new target in diabetic foot care. This target is to reduce foot ulcer incidence with at least 75%. This article is protected by copyright. All rights reserved.
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Annual foot risk assessment of people with diabetes is recommended in national and international clinical guidelines. At present, these are consensus based and use only a proportion of the available evidence. We undertook a systematic review of individual patient data (IPD) to identify the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes. Studies were identified from searches of MEDLINE and EMBASE. The electronic search strategies for MEDLINE and EMBASE databases created during an aggregate systematic review of predictive factors for foot ulceration in diabetes were updated and rerun to January 2013. One reviewer applied the IPD review eligibility criteria to the full-text articles of the studies identified in our literature search and also to all studies excluded from our aggregate systematic review to ensure that we did not miss eligible IPD. A second reviewer applied the eligibility criteria to a 10% random sample of the abstract search yield to check that no relevant material was missed. This review includes exposure variables (risk factors) only from individuals who were free of foot ulceration at the time of study entry and who had a diagnosis of diabetes mellitus (either type 1 or type 2). The outcome variable was incident ulceration. Our search identified 16 cohort studies and we obtained anonymised IPD for 10. These data were collected from more than 16,000 people with diabetes worldwide and reanalysed by us. One data set was kept for independent validation. The data sets contributing IPD covered a range of temporal, geographical and clinical settings. We therefore selected random-effects meta-analysis, which assumes not that all the estimates from each study are estimates of the same underlying true value, but rather that the estimates belong to the same distribution. We selected candidate variables for meta-analysis using specific criteria. After univariate meta-analyses, the most clinically important predictors were identified by an international steering committee for inclusion in the primary, multivariable meta-analysis. Age, sex, duration of diabetes, monofilaments and pulses were considered most prognostically important. Meta-analyses based on data from the entire IPD population found that an inability to feel a 10-g monofilament [odds ratio (OR) 3.184, 95% confidence interval (CI) 2.654 to 3.82], at least one absent pedal pulse (OR 1.968, 95% CI 1.624 to 2.386), a longer duration of a diagnosis of diabetes (OR 1.024, 95% CI 1.011 to 1.036) and a previous history of ulceration (OR 6.589, 95% CI 2.488 to 17.45) were all predictive of risk. Female sex was protective (OR 0.743, 95% CI 0.598 to 0.922). It was not possible to perform a meta-analysis using a one-step approach because we were unable to procure copies of one of the data sets and instead accessed data via Safe Haven. The findings from this review identify risk assessment procedures that can reliably inform national and international diabetes clinical guideline foot risk assessment procedures. The evidence from a large sample of patients in worldwide settings show that the use of a 10-g monofilament or one absent pedal pulse will identify those at moderate or intermediate risk of foot ulceration, and a history of foot ulcers or lower-extremity amputation is sufficient to identify those at high risk. We propose the development of a clinical prediction rule (CPR) from our existing model using the following predictor variables: insensitivity to a 10-g monofilament, absent pedal pulses and a history of ulceration or lower-extremities amputations. This CPR could replace the many tests, signs and symptoms that patients currently have measured using equipment that is either costly or difficult to use. This study is registered as PROSPERO CRD42011001841. The National Institute for Health Research Health Technology Assessment programme.
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This study was designed to explore whether participant-driven patient education in group sessions, compared to provision of standard information, will contribute to a statistically significant reduction in new ulceration during 24 months in patients with diabetes and high risk of ulceration. This is an interim analysis after six months. A randomised controlled study was designed in accordance with CONSORT criteria. Inclusion criteria were: age 35–79 years old, diabetes mellitus, sensory neuropathy, and healed foot ulcer below the ankle; 657 patients (both male and female) were consecutively screened. A total of 131 patients (35 women) were included in the study. Interim analysis of 98 patients after six months was done due to concerns about the patients' ability to fulfil the study per protocol. After a six-month follow up, 42% had developed a new foot ulcer and there was no statistical difference between the two groups. The number of patients was too small to draw any statistical conclusion regarding the effect of the intervention. At six months, five patients had died, and 21 had declined further participation or were lost to follow up. The main reasons for ulcer development were plantar stress ulcer and external trauma. It was concluded that patients with diabetes and a healed foot ulcer develop foot ulcers in spite of participant-driven group education as this high risk patient group has external risk factors that are beyond this form of education. The educational method should be evaluated in patients with lower risk of ulceration. Copyright © 2011 FEND. Published by John Wiley & Sons, Ltd.
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OBJECTIVE To assess the efficacy of in-shoe orthoses designed based on shape and barefoot plantar pressure in reducing the incidence of submetatarsal head plantar ulcers in people with diabetes, peripheral neuropathy, and a history of similar prior ulceration.RESEARCH DESIGN AND METHODS Single-blinded multicenter randomized controlled trial with subjects randomized to wear shape- and pressure-based orthoses (experimental, n = 66) or standard-of-care A5513 orthoses (control, n = 64). Patients were followed for 15 months, until a study end point (forefoot plantar ulcer or nonulcerative plantar forefoot lesion), or to study termination. Proportional hazards regression was used for analysis.RESULTSThere was a trend in the composite primary end point (both ulcers and nonulcerative lesions) across the full follow-up period (P = 0.13) in favor of the experimental orthoses. This trend was due to a marked difference in ulcer occurrence (P = 0.007) but no difference in the rate of nonulcerative lesions (P = 0.76). At 180 days, the ulcer prevention effect of the experimental orthoses was already significant (P = 0.003) when compared with control, and the benefit of the experimental orthoses with respect to the composite end point was also significant (P = 0.042). The hazard ratio was 3.4 (95% CI 1.3-8.7) for the occurrence of a submetatarsal head plantar ulcer in the control compared with experimental arm over the duration of the study.CONCLUSIONS We conclude that shape- and barefoot plantar pressure-based orthoses were more effective in reducing submetatarsal head plantar ulcer recurrence than current standard-of-care orthoses but they did not significantly reduce nonulcerative lesions.
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Most cases of lower extremity limb loss in the United States occur among people with diabetes who have a diabetic foot ulcer (DFU). These DFUs and the associated limb loss that may occur lead to excess healthcare costs and have a large negative impact on mobility, psychosocial well-being, and quality of life. The strategies for DFU prevention and management are evolving, but the implementation of these prevention and management strategies remains challenging. Barriers to implementation include poor access to primary medical care; patient beliefs and lack of adherence to medical advice; delays in DFU recognition; limited healthcare resources and practice heterogeneity of specialists. Herein, we review the contemporary outcomes of DFU prevention and management to provide a framework for prioritizing quality improvement efforts within a resource-limited healthcare environment.
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OBJECTIVE Custom-made footwear is the treatment of choice to prevent foot ulcer recurrence in diabetes. This footwear primarily aims to offload plantar regions at high ulcer risk. However, ulcer recurrence rates are high. We assessed the effect of offloading-improved custom-made footwear and the role of footwear adherence on plantar foot ulcer recurrence.RESEARCH DESIGN AND METHODS We randomly assigned 171 neuropathic diabetic patients with a recently healed plantar foot ulcer to custom-made footwear with improved and subsequently preserved offloading (∼20% peak pressure relief by modifying the footwear) or to usual care (i.e., nonimproved custom-made footwear). Primary outcome was plantar foot ulcer recurrence in 18 months. Secondary outcome was ulcer recurrence in patients with an objectively measured adherence of ≥80% of steps taken.RESULTSOn the basis of intention-to-treat, 33 of 85 patients (38.8%) with improved footwear and 38 of 86 patients (44.2%) with usual care had a recurrent ulcer (relative risk -11%, odds ratio 0.80 [95% CI 0.44-1.47], P = 0.48). Ulcer-free survival curves were not significantly different between groups (P = 0.40). In the 79 patients (46% of total group) with high adherence, 9 of 35 (25.7%) with improved footwear and 21 of 44 (47.8%) with usual care had a recurrent ulcer (relative risk -46%, odds ratio 0.38 [0.15-0.99], P = 0.045).CONCLUSIONS Offloading-improved custom-made footwear does not significantly reduce the incidence of plantar foot ulcer recurrence in diabetes compared with custom-made footwear that does not undergo such improvement, unless it is worn as recommended.
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Critical limb ischemia, first defined in 1982, was intended to delineate a subgroup of patients with a threatened lower extremity primarily because of chronic ischemia. It was the intent of the original authors that patients with diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems have been used to classify risk of amputation and likelihood of benefit from revascularization by subcategorizing patients into two groups: ischemic rest pain and tissue loss. Due to demographic shifts over the last 40 years, especially a dramatic rise in the incidence of diabetes mellitus and rapidly expanding techniques of revascularization, it has become increasingly difficult to perform meaningful outcomes analysis for patients with threatened limbs using these existing classification systems. Particularly in patients with diabetes, limb threat is part of a broad disease spectrum. Perfusion is only one determinant of outcome; wound extent and the presence and severity of infection also greatly impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower Extremity Guidelines Committee undertook the task of creating a new classification of the threatened lower extremity that reflects these important considerations. We term this new framework, the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. Risk stratification is based on three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). The implementation of this classification system is intended to permit more meaningful analysis of outcomes for various forms of therapy in this challenging, but heterogeneous population.
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Because neuroischemic complications are associated with a high rate of recurrence, we propose a slight shift in the mechanism by which we counsel and communicate risk daily with our patients. If the epidemiology of this problem is comparable with that of cancer, and recurrences are common, then perhaps language commensurate with such risks should follow. After initial healing of an index wound, our unit now refers to patients not as being cured but rather as being "in remission." This concept is easy for the patient and the rest of the team to understand. We believe that it powerfully connotes the necessity for frequent follow-up and rapid intervention for inevitable minor and sometimes major complications.
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To evaluate the safety and efficacy of the pan metatarsal head resection (PMHR) compared with nonsurgical management of wounds in the forefoot in people with diabetes. The authors evaluated 92 patients with diabetes (66.3% male), with ulcers classified as University of Texas grade 1A or 2A at the plantar aspect of the forefoot using a case-control model. Cases were patients treated with multiple metatarsal head resections for multiple metatarsal head wounds, and controls received standard nonsurgical care. Both groups received standard off-loading and wound care. Outcomes included time to healing, reulceration, infection, and amputation. Patients in the surgery group (SG) healed significantly faster than those in the standard therapy group (ST; 84.2 ± 39.9 days for the ST vs 60.1 ± 27.9 days for the SG; P = .003) and had fewer recurrent ulcers (39.1% for the ST vs 15.2% for the SG; P = .02; odds ratio [OR] = 3.6; 95% confidence interval [CI] = 1.3-9.7) and infections during 1 year of follow-up (64.5% for the ST vs 35.5% for the SG; P = .047; OR = 2.4; 95% CI = 1.0-6.0). There was no significant difference in the proportion of patients receiving an incident amputation in the follow-up period (13.0% for the ST vs 6.5% for the SG; P = .5). The results of this study suggest that the PMHR may be associated with shorter times to healing and lower morbidity compared with standard care alone in patients without digital gangrene and with multiple plantar forefoot ulcers.
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Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of, and risk factors for, DFU recurrence after healing during 3-year follow-up period. At our site, 93 Eurodiale enrolled patients had a healed DFU. Among these, 14 died; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study we assessed: demographic factors (age, sex, distance from hospital); diabetes-related factors (duration, HbA1c levels); comorbidities (obesity, renal failure, smoking, alcohol abuse); and DFU-related factors (peripheral arterial disease, ulcer infection, c-reactive protein [CRP]; foot deformities). During the 3-year follow-up, a DFU recurred in 42 patients (57·5%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location (odds ratio [OR] 8·62, 95% CI 2·2-33·2); presence of osteomyelitis (OR 5·17, 95% CI 1·4-18·7); HbA1c > 7·5% ([DCCT], OR 4·07, 95% CI 1·1-15·6); and CRP > 5 mg/l (OR 4·27, 95% CI 1·2-15·7). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3-year follow-up, despite intensive foot care. The findings present at diagnosis of the initial DFU that were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) appear to define those at high risk for recurrence, but may be amenable to targeted interventions.
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Context: Among persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. These ulcers frequently become infected, cause great morbidity, engender considerable financial costs, and are the usual first step to lower extremity amputation. Objective: To systematically review the evidence on the efficacy of methods advocated for preventing diabetic foot ulcers in the primary care setting. Data sources, study selection, and data extraction: The EBSCO, MEDLINE, and the National Guideline Clearinghouse databases were searched for articles published between January 1980 and April 2004 using database-specific keywords. Bibliographies of retrieved articles were also searched, along with the Cochrane Library and relevant Web sites. We reviewed the retrieved literature for pertinent information, paying particular attention to prospective cohort studies and randomized clinical trials. Data synthesis: Prevention of diabetic foot ulcers begins with screening for loss of protective sensation, which is best accomplished in the primary care setting with a brief history and the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy with biothesiometry, measure plantar foot pressure, and assess lower extremity vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, enable clinicians to stratify patients based on risk and to determine the type of intervention. Educating patients about proper foot care and periodic foot examinations are effective interventions to prevent ulceration. Other possibly effective clinical interventions include optimizing glycemic control, smoking cessation, intensive podiatric care, debridement of calluses, and certain types of prophylactic foot surgery. The value of various types of prescription footwear for ulcer prevention is not clear. Conclusions: Substantial evidence supports screening all patients with diabetes to identify those at risk for foot ulceration. These patients might benefit from certain prophylactic interventions, including patient education, prescription footwear, intensive podiatric care, and evaluation for surgical interventions.
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Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012 a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 - June 2014. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 56 papers were eligible for full text review. There were no randomized controlled trials, but there were four nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70-89%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular techniques. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of conservatively treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients. This article is protected by copyright. All rights reserved.
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In 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs; at least 33% of these costs were linked to the treatment of foot ulcers. Although the team approach to diabetic foot problems is effective in preventing lower extremity amputations, the costs associated with implementing a diabetic foot care team are not well understood. An analysis of these costs provides the basis for this report. Diabetic foot problems impose a major economic burden, and costs increase disproportionately to the severity of the condition. Compared with diabetic patients without foot ulcers, the cost of care for patients with a foot ulcer is 5.4 times higher in the year after the first ulcer episode and 2.8 times higher in the second year. Costs for the treatment of the highest-grade ulcers are 8 times higher than for treating low-grade ulcers. Patients with diabetic foot ulcers require more frequent emergency department visits, are more commonly admitted to hospital, and require longer length of stays. Implementation of the team approach to manage diabetic foot ulcers within a given region or health care system has been reported to reduce long-term amputation rates from 82% to 62%. Limb salvage efforts may include aggressive therapy, such as revascularization procedures and advanced wound healing modalities. Although these procedures are costly, the team approach gradually leads to improved screening and prevention programs and earlier interventions, and thus seems to reduce long-term costs. To date, aggressive limb preservation management for patients with diabetic foot ulcers has not usually been paired with adequate reimbursement. It is essential to direct efforts in patient-caregiver education to allow early recognition and management of all diabetic foot problems and to build integrated pathways of care that facilitate timely access to limb salvage procedures. Increasing evidence suggests that the costs for implementing diabetic foot teams can be offset over the long-term by improved access to care and reductions in foot complications and in amputation rates.
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Therapeutic footwear for diabetic foot patients aims to reduce the risk of ulceration by relieving mechanical pressure on the foot. However, footwear efficacy is generally not assessed in clinical practice. The purpose of this study was to assess the value of in-shoe plantar pressure analysis to evaluate and optimize the pressure-reducing effects of diabetic therapeutic footwear. Dynamic in-shoe plantar pressure distribution was measured in 23 neuropathic diabetic foot patients wearing fully customized footwear. Regions of interest (with peak pressure>200 kPa) were selected and targeted for pressure optimization by modifying the shoe or insole. After each of a maximum of three rounds of modifications, the effect on in-shoe plantar pressure was measured. Successful optimization was achieved with a peak pressure reduction of >25% (criterion A) or below an absolute level of 200 kPa (criterion B). In 35 defined regions, mean peak pressure was significantly reduced from 303 (SD 77) to 208 (46) kPa after an average 1.6 rounds of footwear modifications (P<0.001). This result constitutes a 30.2% pressure relief (range 18-50% across regions). All regions were successfully optimized: 16 according to criterion A, 7 to criterion B, and 12 to criterion A and B. Footwear optimization lasted on average 53 min. These findings suggest that in-shoe plantar pressure analysis is an effective and efficient tool to evaluate and guide footwear modifications that significantly reduce pressure in the neuropathic diabetic foot. This result provides an objective approach to instantly improve footwear quality, which should reduce the risk for pressure-related plantar foot ulcers.
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To identify factors that influence survival after diabetes-related amputations. We abstracted medical records of 1,043 hospitalized subjects with diabetes and a lower-extremity amputation from 1 January to 31 December 1993 in six metropolitan statistical areas in south Texas. We identified mortality in the 10-year period after amputation from death certificate data. Diabetes was verified using World Health Organization criteria. Amputations were identified by ICD-9-CM codes 84.11-84.18 and categorized as foot, below-knee amputation, and above-knee amputation and verified by reviewing medical records. We evaluated three levels of renal function: chronic kidney disease (CKD), hemodialysis, and no renal disease. We defined CKD based on a glomerular filtration rate<60 ml/min and hemodialysis from Current Procedural Terminology (CPT) codes (90921, 90925, 90935, and 90937). We used χ2 for trend and Cox regression analysis to evaluate risk factors for survival after amputation. Patients with CKD and dialysis had more below-knee amputations and above-knee amputations than patients with no renal disease (P<0.01). Survival was significantly higher in patients with no renal impairment (P<0.01). The Cox regression indicated a 290% increase in hazard for death for dialysis treatment (hazard ratio [HR] 3.9, 95% CI 3.07-5.0) and a 46% increase for CKD (HR 1.46, 95% CI 1.21-1.77). Subjects with an above-knee amputation had a 167% increase in hazard (HR 2.67, 95% CI 2.14-3.34), and below-knee amputation patients had a 67% increase in hazard for death. Survival after amputation is lower in diabetic patients with CKD, dialysis, and high-level amputations.
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To evaluate the frequency of foot prevention strategies among high-risk patients with diabetes. Electronic medical records were used to identify 150 patients on dialysis and 150 patients with previous foot ulceration or amputation with 30 months follow-up to determine the frequency with which patients received education, podiatry care, and therapeutic shoes and insoles as prevention services. Few patients had formal education (1.3%), therapeutic shoes/insoles (7%), or preventative podiatric care (30%). The ulcer incidence density was the same in both groups (210 per 1,000 person-years). In contrast, the amputation incidence density was higher in the dialysis group compared with the ulcer group (58.7 vs. 13.1 per 1,000 person-years, P < 0.001). Patients on dialysis were younger and more likely to be of non-Hispanic white descent (P = 0.006) than patients with a previous history of ulcer or amputation. Prevention services are infrequently provided to high-risk patients.
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To compare mortality rates for individuals with diabetes with and without a history of foot ulcer (HFU) and with that for the nondiabetic population. This population-based study included 155 diabetic individuals with an HFU, 1,339 diabetic individuals without an HFU, and 63,632 nondiabetic individuals who were all followed for 10 years with mortality as the end point. During the follow-up period, a total of 49.0% of diabetic individuals with an HFU died, compared with 35.2% of diabetic individuals without an HFU and 10.5% of those without diabetes. In Cox regression analyses adjusted for age, sex, education, current smoking, and waist circumference, having an HFU was associated with more than a twofold (2.29 [95% CI 1.82-2.88]) hazard risk for mortality compared with that of the nondiabetic group. In corresponding analyses comparing diabetic individuals with and without an HFU, an HFU was associated with 47% increased mortality (1.47 [1.14-1.89]). Significant covariates were older age, male sex, and current smoking. After inclusion of A1C, insulin use, microalbuminuria, cardiovascular disease, and depression scores in the model, each was significantly related to life expectancy. AN HFU increased mortality risk among community-dwelling adults and elderly individuals with diabetes. The excess risk persisted after adjustment for comorbidity and depression scores, indicating that close clinical monitoring might be warranted among individuals with an HFU, who may be particularly vulnerable to adverse outcomes.
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To study whether there is an association between cognitive impairment and the relapse rate of foot ulcers in diabetic patients and those with previous foot ulcers. This single-center prospective study assessed the association of cognitive function and risk for ulcer relapse in 59 patients with diabetes (mean age 65.1 years, diabetes duration 16.5 years, and A1C 7.4%), peripheral neuropathy, and a history of foot ulceration. Premorbid and current cognitive functions were measured (multiple-choice vocabulary test [Lehrl], number-symbol test, mosaic test [HAWIE-R], and trail-making tests A and B [Reitan]). Prevalence of depression was evaluated retrospectively (diagnoses in patient files or use of antidepressive medication). Patients were re-examined after 1 year. Three patients (5%) died during follow-up (one of sepsis and two of heart problems). The remaining 56 patients (48%) developed 27 new foot ulcerations (78% superficial ulcerations [Wagner stage 1]). Characteristics of patients with and without ulcer relapse were not different. In a binary logistic regression analysis, cognitive function is not predictive of foot reulceration. Cognitive function is not an important determinant of foot reulceration.
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This observer-blind, randomised controlled trial was designed to determine the effect of a foot care education programme in the secondary prevention of foot ulcers. People with newly healed foot ulcers attending one of three specialist clinics were allocated to receive either targeted, one-to-one education or usual care, using a computer-generated random allocation sequence that had been prepared in advance but which was concealed from the clinical researcher. The primary outcome was ulcer incidence at 12 months. Secondary outcomes were ulcer incidence at 6 months and incidence of amputation, mood (Hospital Anxiety and Depression Scale) and quality of life (Diabetic Foot Ulcer Scale) at 6 and 12 months. Protective foot care behaviours (Nottingham Assessment of Functional Footcare) were assessed at 12 months. There were 87 (mean [SD] age 63.5 [12.1] years) patients in the intervention group and 85 control patients (mean [SD] age 64.9 [10.9] years). The groups were comparable at baseline. No significant differences (p > 0.05) were observed between groups in ulcer incidence at either 6 months (intervention 30%, control 21%) or 12 months (intervention 41%, control 41%). Recommended foot care behaviours at 12 months were better in the intervention than in the control group (p = 0.03), but education had no significant (p > 0.05) effect on mood, quality of life or amputations. Even though the intervention was associated with improved foot care behaviour, there was no evidence that this programme of targeted education was associated with clinical benefit in this population when compared with usual care. The usefulness and optimal delivery of education to such a high-risk group requires further evaluation. ClinicalTrials.gov NCT00729456 Funding: Diabetes UK project grant RD02/0002535.
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Objective: We conducted a multicenter evaluation of a novel remote foot-temperature monitoring system to characterize its accuracy for predicting impending diabetic foot ulcers (DFU) in a cohort of patients with diabetes with previously healed DFU. Research design and methods: We enrolled 132 participants with diabetes and prior DFU in this 34-week cohort study to evaluate a remote foot-temperature monitoring system (ClinicalTrials.gov Identifier NCT02647346). The study device was a wireless daily-use thermometric foot mat to assess plantar temperature asymmetries. The primary outcome of interest was development of nonacute plantar DFU, and the primary efficacy analysis was the accuracy of the study device for predicting the occurrence of DFU over several temperature asymmetry thresholds. Results: Of the 129 participants who contributed evaluable data to the study, a total of 37 (28.7%) presented with 53 DFU (0.62 DFU/participant/year). At an asymmetry of 2.22°C, the standard threshold used in previous studies, the system correctly identified 97% of observed DFU, with an average lead time of 37 days and a false-positive rate of 57%. Increasing the temperature threshold to 3.20°C decreased sensitivity to 70% but similarly reduced the false-positive rate to 32% with the same lead time of 37 days. Approximately 86% of the cohort used the system at least 3 days a week on average over the study. Conclusions: Given the encouraging study results and the significant burden of DFU, use of this mat may result in significant reductions in morbidity, mortality, and resource utilization.
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Diabetic foot is a severe public health issue, yet rare studies investigated its global epidemiology. Here we performed a systematic review and meta-analysis through searching PubMed, EMBASE, ISI Web of science, and Cochrane database. We found that that global diabetic foot ulcer prevalence was 6.3% (95%CI: 5.4–7.3%), which was higher in males (4.5%, 95%CI: 3.7–5.2%) than in females (3.5%, 95%CI: 2.8–4.2%), and higher in type 2 diabetic patients (6.4%, 95%CI: 4.6–8.1%) than in type 1 diabetics (5.5%, 95%CI: 3.2–7.7%). North America had the highest prevalence (13.0%, 95%CI: 10.0–15.9%), Oceania had the lowest (3.0%, 95% CI: 0.9–5.0%), and the prevalence in Asia, Europe, and Africa were 5.5% (95%CI: 4.6–6.4%), 5.1% (95%CI: 4.1–6.0%), and 7.2% (95%CI: 5.1–9.3%), respectively. Australia has the lowest (1.5%, 95%CI: 0.7–2.4%) and Belgium has the highest prevalence (16.6%, 95%CI: 10.7–22.4%), followed by Canada (14.8%, 95%CI: 9.4–20.1%) and USA (13.0%, 95%CI: 8.3–17.7%). The patients with diabetic foot ulcer were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot ulceration. Our results provide suggestions for policy makers in deciding preventing strategy of diabetic foot ulceration in the future. • Key messages • Global prevalence of diabetic foot is 6.3% (95%CI: 5.4–7.3%), and the prevalence in North America, Asia, Europe, Africa and Oceania was 13.0% (95%CI: 10.0–15.9%), 5.5% (95%CI: 4.6–6.4%), 5.1% (95%CI: 4.1–6.0%), 7.2% (95%CI: 5.1–9.3%), and 3.0% (95% CI: 0.9–5.0%). • Diabetic foot was more prevalent in males than in females, and more prevalent in type 2 diabetic foot patients than in type 1 diabetic foot patients. • The patients with diabetic foot were older, had a lower body mass index, longer diabetic duration, and had more hypertension, diabetic retinopathy, and smoking history than patients without diabetic foot.
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Background: An increased plantar pressure is a causative factor in the development of plantar foot ulcers in people with diabetes mellitus, and ulcers are a precursor of lower extremity amputation. Methods: In this article, the evidence is reviewed that relieving areas of increased plantar pressure (ie, offloading) can heal plantar foot ulcers and prevent their recurrence. Results: Noninfected, nonischemic neuropathic plantar forefoot ulcers should heal in 6 to 8 weeks with adequate offloading. Recent meta-analyses and systematic reviews show that nonremovable knee-high devices are most effective. This is probably because they eliminate the problem of nonadherence with the use of a removable device. Studies show a large discrepancy between evidence-based recommendations on offloading and what is used in clinical practice. Many clinics continue to use methods that are less effective or have not been proven to be effective, while ignoring evidence-based methods. Strategies are proposed to address this issue, notably the adoption and implementation of recent international guidelines by professional societies and a stronger focus of clinicians on expedited healing. For the prevention of plantar foot ulcer recurrence in high-risk patients, 2 recent trials have shown that the incidence of recurrence can be significantly reduced with custom-made footwear that has a demonstrated pressure-relieving effect through guidance by plantar pressure measurements, under the condition that the footwear is worn. Conclusion: This review helps to inform clinicians about effective offloading treatment for healing plantar foot ulcers and preventing their recurrence.
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Objectives: Patients presenting to a public hospital with critical limb ischemia (CLI) typically have advanced disease with significant co-morbidities. The purpose of this study was to assess the influence of revascularization on one year amputation rate of CLI patients presenting to Los Angeles County USC Medical Center, classified according to the SVS WIfI. Methods: A retrospective review of patients who presented to a public hospital with CLI from February 2010 to July 2014 was performed. Patients were classified according to the WIfI system. Only patients with complete data who survived at least 12 months after presentation were included. Results: 93 patients with 98 affected limbs were included. The mean age was 62.8. 82 (84%) had hypertension and 71 (72%) had diabetes. 50 (57.5%) limbs had Trans-Atlantic Inter-Society Consensus (TASC) C or D femoral-popliteal lesions and 82 (98%) had significant infra-popliteal disease. The majority had moderate or high WIfI amputation and revascularization scores. 84 (86%) limbs underwent open, endovascular or hybrid revascularization. Overall OYMA rate was 26.5%. In limbs with high WIfI amputation score, the OYMA was 34.5%: 21.4% in those who were revascularized and 57% in those who weren't. On univariable analysis, factors associated with increased risk of OYMA were: non-revascularization (P=0.005), hyperlipidemia (P=0.06), hemodialysis (P= 0.005), gangrene (P=0.02), ulcer classification (P=0.05), WIfI amputation score (P=0.026) and WIfI wound grade (P=0.04). On multivariable analysis, increasing WIfI amputation score (OR 1.84, 95% CI 1.0-3.39) was associated with increased risk of OYMA while revascularization (OR 0.24, 95% CI 0.07-0.80) was associated with decreased risk of OYMA. Conclusions: The OYMA rates in this population were consistent with those predicted by the WIfI classification system. In this population, revascularization significantly reduced the risk of amputation. Co-morbidities, including DM and TASC classification did not moderate the association of WIfI amputation score with risk of one-year major amputation.
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Custom-molded orthotic devices with soft insoles are thought to reduce recurrence after healing of diabetic foot lesions. The aim of the study was to investigate the influence of specially made shoes on the incidence of foot lesions after healing of a previous lesion and patient's discharge from hospital. Study design: 46 patients (age: 66,18 years (mean)) were examined 25,49 months (mean) after discharge from hospital. Group A (24 patients) used their orthotic device regularly, group B (22 patients) used regular shoes. Results: Incidence of recurrence of foot lesions was 37,5% for 2 years. Recurrence of foot lesions occurred in 10 patients of group A (41,7%) and in 8 patients of group B (36,4%). There was no amputation in group A and 2 amputations in group B (ray amputation in one case and a below the knee amputation in the other). Conclusions: Custom-molded orthotic devices do not necessarily reduce recurrences of diabetic foot lesions.
Article
Aims: The presence of diabetic foot ulcers is strongly associated with an increased risk of death. In this study, we investigate whether the effects of diabetes-associated complications can explain the apparent relationship between diabetic foot ulcers and death. Methods: We analysed data from 414 523 people with diabetes enrolled in practices associated with The Health Improvement Network in the United Kingdom. Our methods were designed to control for potential confounders in order to isolate the relationship between diabetic foot ulcers and death. Using proportional hazards models and the area under the receiver operator curve, we evaluated the effects of diabetic foot ulcers and the covariates on death. Results: Among the patients, 20 737 developed diabetic foot ulcers; 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong with a fully adjusted hazard ratio of 2.48 (95% confidence interval: 2.43, 2.54). Geographic variance existed but was not spatially associated. Conclusions: Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow-up. This article is protected by copyright. All rights reserved.