The unique multidisciplinarity of diabetes-related foot disease.

Few diseases globally require treatment from so many different disciplines as diabetes-related foot disease. At least 25 different professionals may be involved: casting technicians, dermatologists, diabetes (educator) nurses, diabetologists, dieticians, endocrinologists, general practitioners, human movement scientists, infectious diseases experts, microbiologists, nuclear medicine physicians, orthopaedic surgeons, orthotists, pedorthists, physical therapists, plastic surgeons, podiatric surgeons, podiatrists, prosthetists, psychologists, radiologists, social workers, tissue viability physicians, vascular surgeons, and wound care nurses. A shared vocabulary and shared treatment goals and recommendations are then essential. The International Working Group on the Diabetic Foot (IWGDF) has produced guidelines and supporting documents to stimulate and support shared and multidisciplinary evidence-based treatment in diabetes-related foot disease. In this special virtual issue of Diabetes/Metabolism Research and Reviews, all 21 documents of the 2023 update of the IWGDF Guidelines are bundled, added with a further 6 reviews from multidisciplinary experts to drive future research and clinical innovations, based on their contributions to the International Symposium on the Diabetic Foot. We hope the readers will enjoy this special virtual issue, and widely implement the knowledge shared here in their daily clinical practice and research endeavours with the goal to improve the care for people with diabetes-related foot disease.

Effectiveness of a theory-based foot care education program on self-efficacy and adaptation in patients with diabetes in Turkey: a randomized controlled trial.

BACKGROUND: Persons with diabetes often face significant foot problems due to inadequate foot care, and foot care training programs could be beneficial for these patients. PURPOSE: To examine the effects of diabetic foot care training on self-efficacy and adaptation based on Social Cognitive Theory and the Roy Adaptation Model. METHODS: In this randomized controlled study, 80 patients treated in the endocrine polyclinic of an education and research hospital in Izmir, Turkey, were randomized to intervention (n = 40) or control (n = 40). The intervention group received diabetic foot care training at 1 month, 3 months, and 6 months. Using a diabetic foot model, foot care training was given on diabetic foot care practices; in addition, a foot care training booklet prepared by the researchers was provided. Foot care behaviors, self-efficacy, and adaptation were reevaluated after the training and education. Data were collected at baseline, 1 month, 3 months, and 6 months in both groups. RESULTS: Diabetic foot care training and telephone follow-up were effective in improving foot care behaviors and facilitating the coping and adaptation process of individuals with diabetes, as well as in increasing their self-efficacy regarding foot care. CONCLUSIONS: When providing theory-based diabetic foot education, the use of visual materials along with verbal instruction as well as telephone follow-ups to evaluate training effectiveness increases patients' self-efficacy and adaptation.

Effect of Buerger-Allen exercise on wound healing in patients with diabetic foot ulcers: a randomised controlled trial.

OBJECTIVE: A diabetic foot ulcer (DFU) is a complication of type 2 diabetes that is difficult to treat. Buerger-Allen exercise has shown effectiveness in improving foot circulation and neuropathy in several studies; however, to the best of our knowledge, no randomised controlled study has investigated its effectiveness for DFU healing. Therefore, this study aimed to assess the effects of Buerger-Allen exercise on the healing of DFUs in patients with type 2 diabetes. METHOD: This is a parallel-group randomised controlled trial (RCT). Of 50 patients with neuropathic DFUs, 41 completed the study. They were assigned randomly to a study group (n=21) and a control group (n=20). Patients in the study group received the standard medical treatment and semi-supervised Buerger-Allen exercise for three sessions per week for four weeks, while patients in the control group only received the standard medical treatment. The outcome measures were: ankle-brachial pressure index (ABPI); ulcer size; ulcer depth; SINBAD score; and ulcer risk for poor outcomes (based on the SINBAD score). RESULTS: The study group's mean age was 49.48±6.45 years and the control group's mean age was 49.15±5.85. The study group's ABPI increased significantly compared to the baseline (1.17±0.04 versus 1.11±0.05, respectively; p<0.001) and the control group (1.17±0.04 versus 1.14±0.05, respectively; p=0.04) post-intervention. Ulcer size also reduced significantly in the study group compared to the baseline (2.63±2.0 versus 7.48±5.55cm2, respectively; p<0.001) and the control group (2.63±2.0 versus 6.43±4.45cm2, respectively; p<0.001) post-intervention. Ulcer depth decreased significantly in the study group compared to the baseline (1.71±1.05 versus 4.19±1.74mm, respectively; p<0.001) and the control group (1.71±1.05 versus 2.80±1.57mm, respectively; p=0.01) post-intervention. Furthermore, the SINBAD score in the study group decreased significantly compared to the baseline (1.38±0.86 versus 2.14±1.06, respectively; p<0.001) and the control group (1.38±0.86 versus 2.0±0.79, respectively; p=0.02) post-intervention. Moreover, the ulcer risk for poor outcomes, based on the SINBAD score, reduced significantly only in the study group, compared to the baseline (p=0.041). The control group showed non-significant changes compared to the baseline in all outcome measures (p>0.05). CONCLUSION: From the findings of this RCT, Buerger-Allen exercise, in combination with standard wound care, may help accelerate the healing of neuropathic DFUs in patients with type 2 diabetes, and could be suggested as part of the management plan for such conditions as an easy-to-perform offloading exercise intervention.

Developing an interprofessional decision support tool for diabetic foot ulcers management in primary care within the family medicine group model: a Delphi study in Canada.

BACKGROUND: Primary care professionals encounter difficulties coordinating the continuum of care between primary care providers and second-line specialists and adhere to practice guidelines pertaining to diabetic foot ulcers management. Family medicine groups are providing primary care services aimed to improve access, interdisciplinary care, coordination and quality of health services, and reduce emergency department visits. Most professionals working in family medicine groups are primary care physicians and registered nurses. The aim of this study was to develop and validate an interprofessional decision support tool to guide the management of diabetic foot ulcers for primary care professionals working within the family medicine group model. METHODS: A one-page decision tool developed by the research team was validated by an expert panel using a three-round Delphi protocol held between December 2019 and August 2021. The tool includes 43 individual actions and a care pathway from initial presentation to secondary prevention. Data collection was realized with both paper and electronic questionnaires, and answers were compiled in an electronic spreadsheet. Data was analyzed with use of descriptive statistics, and consensus for each item was defined as ≥ 80% agreement. RESULTS: Experts from 12 pre-identified professions of the diabetic foot ulcer interdisciplinary care team were included, 39 participants out of the 59 invited to first round (66.1%), 34 out of 39 for second (87.2%) and 22 out of 34 for third (64.7%) rounds. All items included in the final version of the decision support tool reached consensus and were deemed clear, relevant and feasible. One or more professionals were identified to be responsible for every action to be taken. CONCLUSIONS: This study provided a comprehensive decision support tool to guide primary care professionals in the management of diabetic foot ulcers. Implementation and evaluation in the clinical setting will need to be undertaken in the future.

Diabetic Foot Infections in the Emergency Department.

Diabetic foot infection (DFI) is among the most common diabetic complications requiring hospitalization. Prompt emergency department diagnosis and evidence-based management can prevent eventual amputation and associated disability and mortality. Underlying neuropathy, arterial occlusion, immune dysfunction, and hyperglycemia-associated dehydration and ketoacidosis can all contribute to severity and conspire to make DFI diagnosis and management difficult. Serious complications include osteomyelitis, necrotizing infection, and sepsis. Practice guidelines are designed to assist frontline providers with correct diagnosis, categorization, and treatment decisions. Management generally includes a careful lower extremity examination and plain x-ray, obtaining appropriate tissue cultures, and evidence-based antibiotic selection tailored to severity.

Evidence-based interventions for identifying candidate quality indicators to assess quality of care in diabetic foot clinics: a scoping review.

BACKGROUND: Foot ulcers in people with diabetes are a serious complication requiring a complex management and have a high societal impact. Quality monitoring systems to optimize diabetic foot care exist, but a formal and more evidence-based approach to develop quality indicators (QIs) is lacking. We aimed to identify a set of candidate indicators for diabetic foot care by adopting an evidence-based methodology. METHODS: A systematic search was conducted across four academic databases: PubMed, Embase CINAHL and Cochrane Library. Studies that reported evidence-based interventions related to organization or delivery of diabetic foot care were searched. Data from the eligible studies were summarized and used to formulate process and structure indicators. The evidence for each candidate QI was described in a methodical and transparent manner. The review process was reported according to the "Preferred Reported Items for Systematic reviews and Meta-Analysis" (PRISMA) statements and its extension for scoping reviews. RESULTS: In total, 981 full-text articles were screened, and 322 clinical studies were used to formulate 42 candidate QIs. CONCLUSIONS: An evidence-based approach could be used to select candidate indicators for diabetic foot ulcer care, relating to the following domains: wound healing interventions, peripheral artery disease, offloading, secondary prevention, and interventions related to organization of care. In a further step, the feasibility of the identified set of indicators will be assessed by a multidisciplinary panel of diabetic foot care stakeholders.

Comment on "Effectiveness and safety of stem cell therapy for diabetic foot: a meta-analysis update".

In the study published by Sun et al., a systematic review and meta-analysis illustrated the advantageous of stem cell therapy in diabetic foot and can improve the quality of life of patients. Nevertheless, the authors had a lack of knowledge regarding the methodology of the meta-analysis, which had four main aspects: (1) The textual report is inconsistent with the forest plot results, i.e., the authors have insufficient knowledge of RevMan. (2) The "zero event" needs to be corrected for summary analysis. (3) Lack of aesthetics in the forest plots. (4) Registration is recommended for systematic reviews and meta-analyses.

Tibial cortex transverse transport promotes ischemic diabetic foot ulcer healing via enhanced angiogenesis and inflammation modulation in a novel rat model.

BACKGROUND: Tibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT. METHODS: We established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes. RESULTS: The TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity. CONCLUSION: Our innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.

The effect of hyperbaric oxygen therapy on hematological indices and biochemical parameters in patients with diabetic foot.

BACKGROUND: Diabetes Mellitus (DM) is a metabolic disease with a high morbidity and mortality and increasing in prevalence all over the world. Due to the hypoxic, ischemic, inflammatory, and infective environment in DM, diabetic foot ulcers have been treated with medico-surgical interventions and adjuvant hyperbaric oxygen Therapy (HBOT). The purpose of this study was to evaluate the effects of HBOT on hematological indices and biochemical parameters in patients with diabetic foot. METHODS: The study group was formed from the file records of 103 male patients who applied to Yunus Emre State Hospital HBOT Center between September 1, 2016 and December 31, 2020, and were treated HBOT with a multidisciplinary approach. RESULTS: There were negative low correlations between number of HBOT sessions and Mean Corpuscular Hemoglobin (MCH) (P = .037, r = -0.207) and Blood Urea Nitrogen (BUN) (P = .037, r = -0.222). White Blood Cell Count (WBC), Neutrophils (NEU), Monocytes (MON), Platelet Count (PLT), and Plateletcrit (PTC) parameters were found to be decreased, and an increase in lymphocytes (LYM), Eosinophils (EOS), Mean Corpuscular Hemoglobin Concentration (MCHC), and Red Cell Distribution Width (RDW) parameters were detected after the treatments (P < .05). Again, after the treatment, glucose (Glu), C-Reactive Protein (CRP), direct bilirubin, and total protein (TP) levels were decreased, and uric acid (UA) levels increased (P < .05). CONCLUSION: HBOT improved hematological indices in patients and had a beneficial effect on biochemical parameters, particularly Glu and CRP levels. Adjuvant HBOT alleviates diabetic inflammation and has a beneficial effect on diabetic patient treatment.

Economic burden of diabetic foot ulcer: a case of Iran.

BACKGROUND: Diabetic foot ulcer (DFU) is known as a serious complication of diabetes mellitus in patients with diabetes, imposing heavy medical costs on healthcare systems due to its chronic nature. patients with severe diabetic foot ulcer are often disabled to work, and some of them may even die, leading to associated productivity losses. Since no previous study has investigated the economic burden of DFU in Iran, this study is to estimate the economic burden of diabetic foot disease in Iran. METHODS: In this descriptive cross-sectional study, randomly selected samples consisted of 542 patients with DFU, hospitalized in the hospitals of Shahid Beheshti University of Medical Sciences. The demographic profile and cost data used in this analysis were derived from a researcher-designed checklist. Lost productivity was calculated based on Human Capital Approach, and the total economic cost of DFU was determined using patient-level data on costs and prevalence data from the global burden of diseases reports. All analyses were performed using SPSS software (Version 23), and Microsoft Excel (Version 19). RESULTS: The economic burden of DFU in Iran in two scenarios of discounting future costs and not discounting them was about $8.7 billion and $35 billion, respectively (about 0.59 and 2.41% of GDP). 79.25% of the estimated costs in this study were indirect costs and productivity losses, of which 99.34% (7,918.4 million Dollars) were productivity losses due to premature death. 20.75% (2,064.4 million dollars) of the estimated costs in this study were direct costs. The average length of stay (LOS) was 8.10 days (SD = 9.32), and 73.3% of patients recovered and were discharged after hospitalization and 7.6% died. The majority of the costs are imposed on the age group of 60-69 year (53.42% of the productivity lost due to hospital length of stay, 58.91% of the productivity lost due to premature death & 40.41% of direct costs). CONCLUSIONS: DFU represents a heavy burden to patients, Iran's health system, and the economy. Early prevention strategies need to be prioritized in making public health policies. These policies and decisions can be in the area of changing lifestyle, health education, changing people's behavior, and encouraging physical activity that targeted high-risk populations in order to reduce the prevalence of diabetic foot and resulting substantial economic burden.

HMOX1 as a therapeutic target associated with diabetic foot ulcers based on single-cell analysis and machine learning.

Diabetic foot ulcers (DFUs) are a serious chronic complication of diabetes mellitus and a leading cause of disability and death in diabetic patients. However, current treatments remain unsatisfactory. Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage-related genes in DFU and identify possible therapeutic targets. Single-cell datasets (GSE223964) and RNA-seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single-cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA-seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in single-cell analysis. Differential expression analysis yielded 743 DEGs. Thirty-seven macrophage-associated DEGs were identified by cross-analysis of marker genes with macrophage-associated DEGs. Thirty-seven intersections were screened and cross-analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU.

Gap analysis of diabetes-related foot disease management systems in Pacific Islands Countries and Territories.

BACKGROUND: Pacific Island Countries and Territories (PICTs) are known to have high prevalence of Diabetes Mellitus and high incidence of diabetes-related foot disease. Diabetes-related foot disease can lead to lower limb amputation and is associated with poor outcomes, with increased morbidity and mortality. The purpose of this study was to gain a better understanding of diabetes-related foot disease management in selected countries in PICTs and to identify potential barriers in management of diabetes-related foot disease management in the region. METHODS: A cross-sectional survey was sent to eleven hospitals across six selected PICTs. The survey instrument was designed to provide an overview of diabetes-related foot disease (number of admissions, and number of lower limb amputations over 12 months) and to identify clinical services available within each institution. Two open-ended questions (free text responses) were included in the instrument to explore initiatives that have helped to improve management and treatment of diabetes-related foot diseases, as well as obstacles that clinicians have encountered in management of diabetes-related foot disease. The survey was conducted over 6 weeks. RESULTS: Seven hospitals across four countries provided responses. Number of admissions and amputations related to diabetes-related foot disease were only reported as an estimate by clinicians. Diabetes-related foot disease was managed primarily by general medicine physician, general surgeon and/or orthopaedic surgeon in the hospitals surveyed, as there were no subspecialty services in the region. Only one hospital had access to outpatient podiatry. Common themes identified around barriers faced in management of diabetes-related foot disease by clinicians were broadly centred around resource availability, awareness and education, and professional development. CONCLUSION: Despite the high prevalence of diabetes-related foot disease within PICTs, there appears to be a lack of functional multi-disciplinary foot services (MDFs). To improve the outcomes for diabetes-related foot disease patients in the region, there is a need to establish functional MDFs and engage international stakeholders to provide ongoing supports in the form of education, mentoring, as well as physical resources.

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review.

BACKGROUND: It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design. AIMS: Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only. MATERIALS AND METHODS: For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality. RESULTS: The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence. CONCLUSION: Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.

Application of hyperbaric oxygen therapy in diabetic foot ulcers: A meta-analysis.

Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.

Antibiotic bone cement accelerates diabetic foot wound healing: Elucidating the role of ROCK1 protein expression.

Clinical studies indicate antibiotic bone cement with propeller flaps improves diabetic foot wound repair and reduces amputation rates, but the molecular mechanisms, particularly key proteins' role remain largely unexplored. This study assessed the efficacy of antibiotic bone cement for treating diabetic foot wounds, focusing on molecular impact on ROCK1. Sixty patients were randomized into experimental (EXP, n = 40) and control (CON, n = 20) groups, treated with antibiotic bone cement and negative pressure. Wound healing rate, amputation rate, wound secretion culture and C-reactive protein (CRP) changes, were monitored. Comprehensive molecular investigations were conducted and animal experiments were performed to further validate the findings. Statistical methods were employed to verify significant differences between the groups and treatment outcomes. The EXP group showed significant improvements in wound healing ( χ 2 $$ {\chi}^2 $$ = 11.265, p = 0.004) and reduced amputation rates. Elevated levels of ROCK1, fibroblasts and VGF were observed in the trauma tissue post-treatment in the experimental group compared to pre-treatment and the control group (all p < 0.05). Improved trauma secretion culture and CRP were also noted in the EXP group (all p < 0.05). The study suggests that antibiotic bone cement enhances diabetic foot wound healing, possibly via upregulation of ROCK1. Further research is needed to elucidate the underlying molecular mechanisms and broader clinical implications.

Effect of platelet-rich plasma on healing of lower extremity diabetic skin ulcers: A meta-analysis.

The aim of this research is to explore the therapeutic efficacy of platelet-rich plasma (PRP) on the cutaneous ulceration of diabetes mellitus (DM). From the beginning of the database until January 2024, we looked through several databases to obtain randomised, controlled PRP studies to treat the wound healing of DM in adult patients. The Cochrane Collaboration's Risk-Of-Bias Instrument was used to evaluate the risk of bias in randomised, controlled studies. Funnel plots, sensitivity analyses and Egger regression tests were employed to determine the reliability and effectiveness of the meta-analyses. Depending on the degree of heterogeneity, a fixed or random effect model has been used. The statistical significance was determined to be below 0.05. Altogether 281 trials were collected from the database and entered into Endnote Software for screening, and 15 trials were analysed. It was found that PRP was associated with a higher rate of wound healing (OR, 3.23; 95% CI, 2.42, 4.31 p < 0.0001). PRP was associated with a reduction in the risk of post-operative wound infection (OR, 0.46; 95% CI, 0.21, 0.99 p = 0.05). PRP was associated with a reduction in the risk of amputations amongst those with DM (OR, 0.50; 95% CI, 0.30, 0.84 p = 0.009). Overall, PRP treatment for DM is expected to improve the rate of wound healing, decrease the risk of wound infection and decrease the risk of amputations.

Topical oxygen therapy and singlet oxygen in wound healing: A scoping review.

The aim of this scoping review was to provide an overview of current research into topical oxygen therapies including the under-researched singlet oxygen for wound healing. A scoping review was undertaken using five databases. After duplicates and ineligible studies were excluded, 49 studies were included for a narrative review. Out of the included 49 studies, 45 (91.8%) were published in the past 10 years (2013-2023) with 32 (65.3%) published in the past 5 years (2018-2023). Eight of the studies were systematic reviews and/or meta-analysis and 18 were RCTs. The search identified zero human RCTs on singlet oxygen, but one human cohort study and five studies in animals. There is evidence that topical oxygen therapy may be useful for the treatment of chronic wounds, mainly diabetic foot ulcers. Singlet oxygen has shown potential, but would need further confirmation in controlled human trials, including more research to understand the bio-properties.