Diabetic foot ulcers (DFUs) pose a significant challenge in diabetes care. Yet, a comprehensive understanding of the underlying biological disparities between healing and non-healing DFUs remains elusive. We conducted bioinformatics analysis of publicly available transcriptome sequencing data in an attempt to elucidate these differences. Our analysis encompassed differential analysis to unveil shifts in cell composition and gene expression profiles between non-healing and healing DFUs. Cell communication alterations were explored employing the Cellchat R package. Pseudotime analysis and cytoTRACE allowed us to dissect the heterogeneity within fibroblast subpopulations. Our findings unveiled disruptions in various cell types, localized low-grade inflammation, compromised systemic antigen processing and presentation, and extensive extracellular matrix signaling disarray in non-healing DFU patients. Some of these anomalies partially reverted in healing DFUs, particularly within the abnormal ECM-receptor signaling pathway. Furthermore, we distinguished distinct fibroblast subpopulations in non-healing and healing DFUs, each with unique biological functions. Healing-associated fibroblasts exhibited heightened extracellular matrix (ECM) remodeling and a robust wound healing response, while non-healing-associated fibroblasts showed signs of cellular senescence and complement activation, among other characteristics. This analysis offers profound insights into the wound healing microenvironment, identifies pivotal cell types for DFU healing promotion, and reveals potential therapeutic targets for DFU management.

Diabetes-related foot complications, including neuropathic plantar forefoot ulcers, are a significant contributor to morbidity and increased healthcare costs. This retrospective clinical audit examines the characteristics of people accessing pedorthics services who are at risk of neuropathic plantar forefoot ulcer (re)occurrence and the pathways and funding models used to access these services. A clinical record audit was conducted on all patients accessing a pedorthics service who had diabetes and neuropathy with a history of plantar forefoot ulceration. The data included demographics, diabetes and neuropathy duration, main forefoot pathology and other comorbidity, footwear and insole interventions, and health fund access status. A total of 70 patient records were accessed, and relevant data was extracted. The mean age of participants was 64.69 (standard deviation (SD) 11.78) years; 61% were male and 39% female. Duration of diabetes ranged from one to 35 years, with a mean of 14.09 years (SD 6.58). The mean duration of neuropathy was 8.56 (SD 4.16) years. The most common forefoot conditions were bony prominences at 71% (n = 50), rigid flat foot and limited joint mobility (53%, n = 37), and hallux abductovalgus at 47% (n = 33). All participants had hyperkeratosis; 34% (n = 24) had forefoot amputation, and around 34% (n = 24) had a history of digital amputation. Various publicly funded packages and private health insurance were accessed. This study investigates the sociodemographic and medical profiles of individuals with diabetes-related foot complexities prone to neuropathic plantar forefoot ulcers. It is the first to examine patients receiving pedorthic services, informing practitioner surveys and preventive care strategies. Understanding patient characteristics aids in optimising multidisciplinary care and reducing ulcer incidence. Further studies are warranted to explore the field to establish an effective multidisciplinary care approach between medical professionals, podiatrists and pedorthists to optimise patient outcomes.

This study aims to examine the association between the occurrence of diabetic foot and air quality (SO2, CO, NO2, O3). Open data were collected to conduct a big data study. Patient information was gathered from the National Health Insurance Service, and the National Institute of Environmental Science\'s air quality data were used. A total study population of 347,543 cases were reviewed (case = 13,353, control = 334,190). The lag period from air quality changes to the actual amputation operation was calculated for each factor. The frequency of diabetic foot amputation in each region was identified and analyzed using a distributed lag non-linear model. Gangwon-do showed the highest relative risks (RRs) for SO2 and CO, while Chungcheongnam-do exhibited the highest RR for NO2. Jeju had the highest RR for O3. Regions like Incheon, Busan, and the capital region also showed significant risk increases. These findings emphasize the importance of tailored air quality management to address diabetic foot complications effectively.

BACKGROUND: Diabetic foot ulcers in developing countries often become infected. The healthcare systems are often not equipped to conduct the culture and the sensitivity tests required for prescribing a targeted antibiotic treatment for diabetic foot infection (DFI).
METHODS: We evaluate antibiotic stewardship programmes for DFIs, at every level of health care, with an emphasis on resource-poor settings such as in Africa.
RESULTS: The management of DFI very often is adapted to the financial and practical realities of the resource-poor regions. The application of the point-of-care Gram stain of deep tissue samples is efficient, rapid, low cost and ubiquitously available. Upon the identification of the predominant pathogen in the Gram stain, a semi-quantitative preemptive antibiotic treatment can be started in accordance with the World Health Organization Aware, Watch and Restrict Essential Medicine List. This list is catered to every country and is a powerful tool. However, some basic knowledge of the local microbiological epidemiology is necessary to choose the most appropriate agent. We report our experience on using the rapidly available Gram stain for narrowing the preemptive choice of listed antibiotic agents, as an economic tool for antibiotic stewardship in DFIs.
CONCLUSIONS: In the practical and resource-saving management of DFI, the \'therapeutic\' use of Gram stains is not common in resource-rich countries but should be added to the arsenal of the general efforts for antibiotic stewardship.

Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here, we focused on Alcaligenes faecalis, a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes reepithelialization of diabetic keratinocytes, a process that is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.

The most important vascular lesion associated with diabetes is arteriosclerosis obliterans (ASO). Differential diagnosis from diabetic foot lesions that produce neurogenic ulcers is important, and the presence of ischemia must be diagnosed as soon as possible. It has been reported that diabetes makes ASO more severe and often leads to lower extremity amputation. In addition to the need for appropriate early control of diabetes, vascular surgeons are required to perform immediate revascularization in cases of ulcer and necrosis, and to aggressively use surgical treatment with good long-term prognosis. (This is a translation of Jpn J Vasc Surg 2023; 32: 105-109.).

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Background: Charcot neuro-osteoarthropathy (CNO) is a rare but devastating complication of diabetes associated with high rates of morbidity; yet, many nonfoot specialists are unaware of it, resulting in missed and delayed diagnosis. Clinical practice guidelines (CPGs) have proven useful in improving quality of care and standardizing practice in diabetes and diabetic foot care. However, little is known about the consistency in recommendations for identification and management of active CNO. Aim: The aim of this study is to review European national diabetes CPGs for the diagnosis and management of active CNO and to assess their methodological rigor and transparency. Methods: A systematic search was performed to identify diabetes national CPGs across Europe. Guidelines in any language were reviewed to explore whether they provided a definition for active CNO and recommendations for diagnosis, monitoring, and management. Methodological rigor and transparency were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool, which comprises 23 key items organized within six domains with an overall guideline assessment score of ≥ 60% considered to be of adequate quality to recommend use. Each guideline was assessed by two reviewers, and inter-rater agreement (Kendall\'s W) was calculated for AGREE-II scores. Results: Seventeen CPGs met the inclusion criteria. Breadth of CNO content varied across guidelines (median (IQR) word count: 327; Q1 = 151; Q3 = 790), and 53% provided a definition for active CNO. Recommendations for diagnosis and monitoring were provided by 82% and 53%, respectively, with offloading being the most common management recommendation (88%). Four guidelines (24%) reached threshold for recommendation for use in clinical practice (≥ 60%) with the scope and purpose domain scoring highest (mean (SD): 67%, ± 23%). The remaining domains had average scores ranging between 19% and 53%. Inter-rater agreement was strong (W = 0.882; p < 0.001). Conclusions: European national CPGs for diabetes provide limited recommendations on active CNO. All guidelines showcased deficits in their methodology, suggesting that more rigorous methods should be employed for diabetes CPG development across Europe.

BACKGROUND: To evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings.
METHODS: We built a cohort of people with a first DFD episode during 2010-2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events.
RESULTS: Overall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7-22.6, HR: 15.1, 95% CI: 13.8-16.5, respectively) was found.
CONCLUSIONS: Although DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.

Diabetic foot ulcer (DFU) is a leading cause of high-level amputation in DM patients, with a low wound healing rate and a high incidence of infection. Vascular endothelial growth factor (VEGF) plays an important role in diabetes mellitus (DM) related complications. This study aims to explore the VEGF expression and its predictive value for prognosis in DFU, in order to provide basis for the prevention of DFU related adverse events. We analyzed 502 patients, with 328 in healing group and 174 in non-healing/recurrent group. The general clinical data and laboratory indicators of patients were compared through Spearman correlation analysis, ROC analysis and logistic regression analysis. Finally, the independent risk factors for adverse prognosis in DFU patients were confirmed. Spearman analysis reveals a positive correlation between the DFU healing rate and ABI, VEGF in wound tissue, and positive rate of VEGF expression, and a negative correlation with DM duration, FPG, HbA1c, TC, Scr, BUN, and serum VEGF. Further logistic regression analysis finds that the DM duration, FPG, HbA1c, ABI, serum VEGF, VEGF in wound tissue, and positive rate of VEGF expression are the independent risk factors for adverse prognosis in DFU (p < 0.05). DM duration, FPG, HbA1c, ABI, serum VEGF, VEGF in wound tissue, and positive rate of VEGF expression are the independent risk factors for prognosis in DFU patients. Patients with these risk factors should be screened in time, which is of great significance to prevent DFU related adverse events and improve outcomes.