Search

Objective: Unusual clinical course Background: Diabetes mellitus is a significant global health issue, affecting millions and costing billions annually in management. A major complication of diabetes is foot ulcers, which heal slowly due to nerve damage (neuropathy) and poor circulation. These ulcers have a high risk of infection and, if untreated, can lead to amputation. The rise of antibiotic-resistant bacteria further complicates treatment, making traditional methods like wound cleaning, dressings, and antibiotics less effective. Cold atmospheric plasma (CAP) therapy is a noninvasive, innovative treatment showing promise in addressing these wounds. CAP generates reactive oxygen and nitrogen species that stimulate cell growth, migration, and proliferation, which are critical for wound healing. It also kills bacteria, including antibiotic-resistant strains, preventing infection and promoting tissue regeneration. Additionally, CAP encourages release of growth factors and cytokines, helping tissue repair and reducing inflammation. Unlike traditional treatments, CAP targets harmful bacteria without harming healthy tissue, making it safer and more effective for treating non-healing wounds. This case highlights a 69-year-old man with a chronic diabetic foot ulcer, previously unresponsive to standard treatments, who experienced successful healing with CAP therapy. Case Report: A 69-year-old man with a chronic non-healing diabetic foot ulcer on the plantar surface of his left foot underwent multiple failed treatments over 60 weeks, including traditional wound care and advanced clinical trials, before being treated with CAP, leading to significant wound closure over the course of 15 weeks. Conclusions: This report has highlighted the challenges of managing chronic diabetic foot ulcers and has shown that CAP can promote wound healing. [ABSTRACT FROM AUTHOR]

Phase transition materials have the potential to be utilized as high‐resolution temperature‐sensitive materials. However, it is a challenge to develop them into temperature sensors with good stability and repeatability. In this work, inspired by phase transition theory and the electrical double‐layer capacitance principle, a novel high‐resolution flexible capacitive temperature sensor based on Polyethylene oxide(PEO)/Poly(vinylidene fluoride‐co‐hexafluoropropylene)/H3PO4 is proposed for the first time. By blending high and low molecular weight PEO and adding ionic solution, the proposed sensor exhibits high resolution (0.05 °C) and response speed (<12 s) within 35–43 °C. The novel introduction of a mesh structure aids the material in achieving microdomain control of PEO crystallization and improves the repeatability (Ex < 2.2%) of the sensor. The sensor is used for monitoring human body temperature and diabetic foot ulcers, and the results show that the sensor can achieve continuous and comfortable body temperature monitoring and early‐stage diabetic foot ulcer diagnosis, offering broad applications in health monitoring and rehabilitation medicine. [ABSTRACT FROM AUTHOR]

Chronic limb-threatening ischemia (CLTI), the most advanced form of peripheral arterial disease (PAD), is the comorbidity primarily responsible for major lower-limb amputations, particularly for diabetic patients. Autologous cell therapy has been the focus of efforts over the past 20 years to create non-interventional therapeutic options for no-option CLTI to improve limb perfusion and wound healing. Among the different available techniques, peripheral blood mononuclear cells (PBMNC) appear to be the most promising autologous cell therapy due to physio-pathological considerations and clinical evidence, which will be discussed in this review. A meta-analysis of six clinical studies, including 256 diabetic patients treated with naive, fresh PBMNC produced via a selective filtration point-of-care device, was conducted. PBMNC was associated with a mean yearly amputation rate of 15.7%, a mean healing rate of 62%, and a time to healing of 208.6 ± 136.5 days. Moreover, an increase in TcPO2 and a reduction in pain were observed. All-cause mortality, with a mean rate of 22.2% and a yearly mortality rate of 18.8%, was reported. No serious adverse events were reported. Finally, some practical and financial considerations are provided, which point to the therapy's recommendation as the first line of treatment for this particular and crucial patient group. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the differences in pathogen survival between single and revision amputations in diabetic foot infections. Current research lacks data on the postoperative pathogen profiles, particularly in cases involving repeated surgeries, making this study essential for targeted infection management. Materials and Methods: The medical records of 168 diabetic foot ulcer patients treated at a single center, divided into single (n=113) and revision amputation groups (n=55) were analyzed retrospectively. Preoperative deep tissue samples and postoperative wound swab samples were collected to analyze the pathogens. The C-reactive protein (CRP) levels were measured as an inflammation marker. The pathogen diversity, frequency, and survival rate were compared. The 'survival rate' was defined as the frequency of postoperative persistence of pathogens relative to the preoperative detection frequency. Results: Revision amputation cases showed a higher diversity (p=0.0029) and persistence of pathogens, with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, and most other detected pathogens displaying higher survival rates. The CRP levels generally decreased postoperatively, but the variability was more pronounced in the revision group, suggesting that CRP may not consistently correlate with infection control in complex cases. Conclusion: These findings revealed significant differences in the pathogen profiles between single and revision amputations, with revision cases facing more significant infection challenges because of the higher resistant pathogen persistence. [ABSTRACT FROM AUTHOR]

Purpose: Forefoot ulcers have been implicated as a causative factor in diabetic foot amputation. The treatment of a bunionette deformity with an ulcer is not well established. This study examined the outcomes of a S.E.R.I. (simple, effective, rapid, and inexpensive) operation for bunionette deformity with ulcers in diabetic neuropathy. Materials and Methods: Between January 2014 and June 2022, 20 patients (20 feet) treated for the bunionette deformity with a S.E.R.I. operation were reviewed retrospectively. All patients had diabetic neuropathy. Eleven patients were female, and the mean age at the time of surgery was 62 years. The mean follow-up time was 16 months. Radiologically, the 4th, 5th intermetatarsal angle (4, 5 IMA), lateral deviation angle (LDA), and the length of the 5th metatarsal bone were analyzed preoperatively and after a 1-year follow-up, and the clinical healing time of the ulcer was also reviewed. Results: The 4, 5 IMA and LDA were reduced from the mean preoperative values of 11.4° and 7.9° to 4.8° and 3.8°, respectively (p<0.05). The mean 5th metatarsal length was reduced from 64.3 mm to 61.2 mm (p<0.05). All ulcers were healed at 3 months with no recurrence at the final follow-up. Four patients showed delayed union, and nine patients had developed hard corn around the previous lesion. Conclusion: The S.E.R.I. operation can be an acceptable treatment modality for bunionette deformity with an ulcer who has diabetic neuropathy by offloading the bunionette so that ulcer healing can occur. [ABSTRACT FROM AUTHOR]

Hypoxic diabetic foot ulcers (HDFUs) pose a challenging chronic condition characterized by oxidative stress damage, bacterial infection, and persistent inflammation. This study introduces a novel therapeutic approach combining ergothioneine (EGT), luteolin (LUT), and quaternized chitosan oxidized dextran (QCOD) to address these challenges and facilitate wound healing in hypoxic DFUs. In vitro, assessments have validated the biosafety, antioxidant, and antimicrobial properties of the ergothioneine‐luteolin‐chitin (QCOD@EGT‐LUT) hydrogel. Furthermore, near‐infrared II (NIR‐II) fluorescence image‐guided the application of QCOD@EGT‐LUT hydrogel in simulated HDFUs. Mechanistically, QCOD@EGT‐LUT hydrogel modulates the diabetic wound microenvironment by reducing reactive oxygen species (ROS). In vivo studies demonstrated increased expression of angiogenic factors mannose receptor (CD206) and latelet endothelial cell adhesion molecule‐1 (PECAM‐1/CD31), coupled with decreased inflammatory factors tumor necrosis factor‐α (TNF‐α) and Interleukin‐6 (IL‐6), thereby promoting diabetic wound healing through up‐regulation of transforming growth factor β‐1 (TGF‐β1). [ABSTRACT FROM AUTHOR]

Aim: to assess the effects of advanced wound dressings (AWD) commonly used in the treatment of predominantly neuropathic diabetic foot ulcers (DFU) The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS). Methods: A Medline and Embase search were performed up to April 1st, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AWD with placebo/standard of care (SoC), with a duration of at least 12 weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, frequency of dressings change, major and minor amputation, pain, and all-cause mortality. AWD assessed were: alginates; foam, hydrocolloids, hydrogels, hyaluronic acid, hemoglobin spray, silver-impregnated, sucrose octasulfate-impregnated, honey-impregnated, micro-organism-binding, and protease-modulating matrix dressings. Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences (WMD) and 95% CIs were calculated for continuous variables. Results: Fifteen studies fulfilled all inclusion criteria. Participants treated with AWD had a significantly higher ulcer healing rate and shorter time-to-healing in comparison with SoC/placebo (MH-OR 1.50 [0.80, 2.79], p = 0.20 and WMD:: − 24.38 [− 42.90, − 5.86] days, p = 0.010). No other significant effect on the above reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as "moderate". Conclusions: In conclusion, AWD, particularly sucrose-octasulfate, hydrogels, hyaluronic acid, and honey dressings, can actively promote wound healing and shortening time-to-healing in patients with DFU. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the molecular mechanism of homeodomain-interacting protein kinase 2 (HIPK2) in diabetic foot ulcers (DFU). Methods: High glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were used to construct DFU cell models. Cell functions were determined using CCK8 assay, EdU assay, flow cytometry, transwell assay, wound healing assay and tube formation assay. Quantitative real-time PCR and western blot were applied to measure the gene expression. Results: HG treatment suppressed HUVECs proliferation, invasion, migration, and angiogenesis, while enhanced apoptosis. HIPK2 was overexpressed in DFU patients, and its knockdown alleviated HG-induced HUVECs dysfunctions. USP7 stabilised HIPK2 protein by reducing its ubiquitination. USP7 overexpression promoted HG-induced HUVECs dysfunctions, and HIPK2 upregulation also reversed the regulation of USP7 knockdown on HG-induced HUVECs dysfunctions. USP7/HIPK2 axis inhibited the activity of PI3K/AKT pathway. Conclusion: Our study revealed that USP7-stabilised HIPK2 contributed to HG-induced HUVECs dysfunctions, thus accelerating DFU process. [ABSTRACT FROM AUTHOR]

• Tagetes erecta flowers were collected and extracted. • Diabetic foot ulcers were induced to diabetic rats and wound healing potential of flower extract was studied. • There is decrease in wound size when test compound was administered through oral route to animals. Diabetes mellitus is a prevalent endocrine disorder characterized by inadequate insulin production by the pancreas or improper utilization of insulin by the body, which imposes severe health complications, including cardiovascular, kidney, and neurological disorders with a high potential of foot ulcers. Globally, diabetes is responsible for over 70 % of limb amputations. Alloxan was used to induce diabetes in rats while foot ulcers were induced by the excision method in diabetic rats. Diabetes was confirmed by measuring the parameters like blood glucose, body weight changes, urine excretion, and other biomarker levels after oral administration of Tagetes erecta L. flower extract (TEFE) at different doses. During the work, it was observed that TEFE demonstrated a dose-dependent effect on blood sugar level from 370.2 mg/dl to 113.00 mg/dl and healing of diabetic foot ulcers in a 13 days animal model (p < 0.01). There is significant decline in SGOT, SPGT and ALP levels when compared with diseased group animals. Decrease in wound size was observed when TEFE was administered to diabetic foot ulcer rats. These exciting results steered to enumerate the possible role of TEFE in Diabetes mellitus through a panel of mechanisms of action like inhibition of free radical generation, modulation of liver enzymes and metabolism of glucose etc. The above findings support the hypoglycaemic and diabetic foot ulcer healing potential of TEFE. Moreover, further investigation is required to completely understand the possible mechanism of TEFE. [ABSTRACT FROM AUTHOR]

Objectives: Digital infrared thermography is a noninvasive tool used for assessing diseases, including the diabetic foot. This study aims to analyze thermal patterns of the foot sole in patients with type 2 diabetes mellitus using thermography and explore correlations with clinical variables. Additionally, a machine learning approach was developed for classification. Methods: A total of 23 diabetic patients and 27 age- and sex-matched controls were included. Thermograms of the plantar foot surface were acquired and segmented into regions of interest. Mean foot temperature and temperature change index were calculated from predefined regions of interest. Pearson's correlation analysis was conducted for temperature measures, glycated hemoglobin, and body mass index. A two-layered cross-validation model using principal component analysis and support vector machines were employed for classification. Results: Significant positive correlations were found between mean foot temperature and glycated hemoglobin (ρ = 0.44, p = 0.0015), as well as between mean foot temperature and body mass index (ρ = 0.35, p = 0.013). Temperature change index did not show significant correlations with clinical variables. The machine learning model achieved high overall accuracy (90%) and specificity (100%) with a moderate sensitivity (78.3%) for classifying diabetic and control groups based on thermal data. Conclusions: Thermography combined with machine learning shows potential for assessing diabetic foot complications. Correlations between mean foot temperature and clinical variables suggest foot temperature changes as potential indicators. The machine learning model demonstrates promising accuracy for classification, suitable for screening purposes. Further research is needed to understand underlying mechanisms and establish clinical utility in diagnosing and managing diabetic foot complications. [ABSTRACT FROM AUTHOR]

Aim: To describe the trends of hospitalisation for infections in people with diabetes and in the general population. Methods: People with diabetes were identified from the Australian National Diabetes Services Scheme linked to hospitalisation datasets from 2010/11 to 2018/19. Data on hospitalisations in the general population were obtained from the Australian Institute of Health and Welfare. Joinpoint regression software was used to calculate the annual percentage change (APC) of rates. Results: The rate of hospitalisation for total infections increased with an APC of 2.6% (95% CI: 1.5, 3.7) among people with type 1 diabetes, 3.6% (2.6, 4.6) among people with type 2 diabetes, and 2.5% (1.3, 3.9) in the general population. Increasing rates were observed for sepsis, influenza, kidney infections, osteomyelitis, cellulitis, and foot infections in all groups. The rate of hospitalisation for urinary tract infection declined among people with type 2 diabetes though it was stable in other groups. The rate of hospitalisation for respiratory tract infections was stable among people with type 1 diabetes but increased in other groups. The rate of hospitalisation for gastrointestinal infection was stable in all cohorts. Conclusion: Hospitalisation rates for infection have increased more rapidly over time in people with diabetes than in the general population. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot is one of the most serious complications of type 2 diabetes mellitus (T2DM), and its incidence is increasing in China. Early detection of abnormal microcirculation in the foot is very important for the prevention and treatment of diabetic foot. Objective: To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosing microcirculatory alterations in the dorsum of the foot for patients with type 2 diabetes mellitus (T2DM). Methods: Eighty-eight T2DM patients were included, among them 30 patients sustained diabetes mellitus without complications (group A), 28 with lesions in the dorsum of the foot (no acute infection) that can be classified as Wagner grade 0 ~ 1 (group B), and 30 with lesions in the dorsum of the foot that can be classified as Wagner grade 2–5 (group C). Another 30 healthy adults were included as the control group. All subjects underwent CEUS to examine the dorsalis pedis arteries and blood perfusion to the underlying soft tissues. Parameters of the time-intensity curve (TIC), including rise time (RT), ascending slope (AS), time to peak (TTP), peak intensity (PI), area under the curve (AUC), and half of drop time (DT/2) were analyzed. Results: The analysis of TIC data of the dorsalis pedis arteries showed that group C had decreased AS, PI, and AUC and increased TTP, RT, and DT/2 compared with groups A, B, and the control group; the differences were statistically significant (p < 0.05). The analysis of TIC data of the perfusion to the underlying soft tissues showed that AS, PI, and AUC decreased from the control group through group A, B, and then C; the differences were all statistically significant (p < 0.05). The TIC data were correlated with the severity of microcirculatory impairment in the dorsum of the foot and among them the AUC, PI, and AS had higher predictive value. Conclusions: Microcirculatory impairment in the dorsum of the foot in T2DM patients presents itself as "delayed wash-in, delayed wash-out, and weak enhancement" on CEUS images. CEUS can provide quantification of the microcirculatory changes in the soft tissues in the dorsum of the foot and reflect the differences of microcirculatory perfusion across different grades of lesions. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that diabetes-related lower-extremity complications (DRLECs) may be associated with cognitive changes in people with diabetes. However, existing literature has produced inconsistent findings, and no systematic reviews have been conducted to investigate whether DRLECs impact the cognition of people with diabetes. This systematic review evaluated existing studies that investigated cognition in people with diabetes with DRLECs and without DRLECs. Method: Seven databases; MEDLINE, PubMed, CINAHL, EMBASE, Cochrane, PsycINFO and Web of Science were searched from inception until 22/8/2022 for studies that compared cognition in people with diabetes with and without DRLECs. Results were independently screened for eligibility and assessed for methodological quality by two authors, with key data extracted. Studies were eligible for meta-analysis if the studies reported similar cases, controls, and outcome measures. Results: Thirteen studies were included in the review, with eleven of medium methodological quality, one of high quality, and one of low quality. Four studies found significant differences in cognition between those with and without DRLECs, four found significant associations between diabetes-related lower-extremity complications and cognition, and five found no differences or associations. One small meta-analysis of eligible studies found that there was no statistically significant difference in cognition in people without, compared to with, peripheral neuropathy (Mean difference = -0.49; 95%CI: -1.59–0.61; N = 3; n = 215). Leave-one-out sensitivity analyses further confirmed that there was no significant difference in cognition among people with and without peripheral neuropathy (p > 0.05). Conclusion: DRLECs may be related to cognition in people with diabetes, however, existing evidence is unclear due to variability in used methodologies that may challenge concluding the findings. Future high-quality studies investigating cognition among people with and without DRLECs are needed. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic condition characterized by impaired insulin production or utilization, leading to serious complications such as diabetic foot ulcers (DFUs). DFUs are chronic wounds with high levels of inflammatory cytokines, arterial occlusion, and persistent infection, often resulting in significant morbidity. Traditional treatment methods, including debridement, offloading, and infection control, have shown limited success, prompting the exploration of novel therapeutic strategies. Insulin, known for its role in glucose metabolism, also possesses wound‐healing properties by promoting cell proliferation, protein synthesis, and modulating inflammation. However, systemic insulin administration is not ideal due to hypoglycemia risks and difficulties in achieving therapeutic concentrations at wound sites. This review focuses on advanced drug delivery systems for the topical application of insulin in wound dressings. Various delivery platforms, including hydrogels, nanoparticles, liposomes, and microemulsions have been developed to optimize insulin bioavailability, protect it from degradation, and ensure controlled release. These systems aim to enhance the management of diabetic wounds by addressing the multifactorial nature of wound healing complications in diabetic patients. The review provides a comprehensive overview of current advancements, evaluates the efficacy of these systems in preclinical and clinical studies, and discusses the challenges and future perspectives in this field. By highlighting the potential of these innovative approaches, this review underscores the promise of advanced topical insulin delivery systems in improving diabetic wound management and patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the significance of monitoring temperature change trends at various wound sites in the healing process of diabetic foot ulcers after microcirculation reconstruction surgery. Methods: A retrospective analysis was conducted on individuals with diabetic foot ulcers who had been admitted to the Department of Orthopedics at the Second Hospital of Shanxi Medical University between July 2020 and February 2022. Temperature changes were regularly monitored at the center of the wound and the distal tibia of the ipsilateral lower leg to assess microcirculatory blood perfusion. Wound, ischemia, and foot infection (WIFi) grading was performed at admission and the final follow-up was to determine the value of temperature monitoring at various sites. Additionally, the formation of collateral microarterial vessels was monitored to determine their consistency with the observed trends in temperature differences. Follow-up assessments included the recurrence of ulcers, development of ulcers at different locations, re-amputation of the toe or limb, and diabetes-related mortality. Results: A total of 29 patients were included in the follow-up, with an average age of 57.14 ± 14.75 years and a follow-up period of 9.79 ± 4.13 months. Following microcirculation reconstruction surgery, as the microvascular network formed, the temperature difference between the center of the wound and the distal tibia on the same side gradually decreased, with no statistical difference observed at 4 weeks postoperatively. At both admission and the final follow-up, there was a significant reduction in the wound (W) and ischemia (I) grades within the WIFi classification. The temperature at the wound center showed progressive improvement as collateral microarterial vessels developed. During the follow-up period, there were 2 cases of ulcer recurrence, 1 case of an ulcer appearing at a different location, no cases of re-amputation of the toe or limb, and 2 diabetes-related fatalities. Conclusion: Skin temperature monitoring offers a direct and reliable indication of microcirculatory blood perfusion. Its simplicity and cost-effectiveness make it a valuable tool for widespread use in evaluating wound healing following microcirculation reconstruction surgery. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFU) are notoriously challenging to heal due to severe infection, excessive inflammation, and difficulty in angiogenesis. In response to these problems, first, a pH/glucose dual‐responsive hydrogel dressing (HPC) is constructed using dual dynamic crosslinking through Schiff base and phenylboronate ester between m‐aminophenylboronic acid and adipic dihydrazide bifunctionalized hyaluronic acid (AHP) and oxidized chondroitin sulfate (OCS). Then, polydopamine‐reduced graphene oxide compounded glycine‐modified fullerene (GPC) with photothermal/photodynamic synergistic antibacterial properties and the drug pirfenidone (PFD) with pro‐angiogenesis and suppress inflammatory are loaded into the above HPC hydrogel. Based on the response of Schiff base/phenylboronate ester to pH/glucose, the HPC/GPC/PFD (HPCG/PFD) hydrogel can accelerate the release of PFD, thereby improving excessive inflammation and angiogenesis in DFU. In addition, dual dynamic crosslinking provided the hydrogel with good on‐demand removal and self‐healing performance, while GPC brought good tissue adhesion, antioxidation, and electrical conductivity to the hydrogel. The rheology, morphology, mechanical properties, swelling, degradation, and biocompatibility of the hydrogel have been well verified. Finally, in the DFU model of rats, this hydrogel can promote wound repair by reducing infection and inflammation, accelerating wound closure, and enhancing epidermal regeneration, collagen deposition, and angiogenesis, showing promoting effect on diabetic wound healing. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFUs), a prevalent chronic disease caused by various factors, significantly impact patients' quality of life due to prolonged healing times and increased infection risks. Current treatment modalities, including pharmacological, physical, and surgical interventions, often yield limited efficacy and adverse effects, highlighting the urgent need for novel therapeutic strategies. The objective of this research is to create SIKVAV-modified chitosan hydrogels with the intention of improving the process of skin wound healing in diabetic mice. We synthesized the hydrogels and established a diabetic mice model with skin wounding to evaluate its healing effects and underlying mechanisms. The results of our study indicate that the SIKVAV-modified chitosan hydrogels markedly enhance the wound healing process in diabetic mice. This effect may be attributed to several mechanisms, including differentiation of fibroblasts, proliferation of keratinocytes, the promotion of angiogenesis, stimulation of collagen synthesis, upregulation of growth factor expression, and possible involvement of the TGF-β1/Smad3 signaling pathway. This research not only provides a new biomaterial for the treatment of diabetic wounds but also elucidates the related molecular mechanisms involved in wound healing of DFUs, offering valuable insights for future clinical applications. [ABSTRACT FROM AUTHOR]

The treatment of diabetic wounds is impaired by the intricate nature of diabetes and its associated complications, necessitating novel strategies. The utilization of mesenchymal stem/stromal cells (MSCs) as a therapeutic modality for chronic and recalcitrant wounds in diabetic patients is an active area of investigation aimed at enhancing its therapeutic potential covering tissue regeneration. The threat posed to the patient and their environment by the presence of a diabetic foot ulcer (DFU) is so significant that any additional therapeutic approach that opens new pathways to halt the progression of local changes, which subsequently lead to a generalized inflammatory process, offers a chance to reduce the risk of amputation or even death. This article explores the potential of MSCs in diabetic foot ulcer treatment, examining their mechanisms of action, clinical application challenges, and future directions for research and therapy. [ABSTRACT FROM AUTHOR]

Highlights: 1. This is the first report identifying SCUBE1 and RNF103-CHMP3 as therapeutic targets for diabetic foot ulcers (DFU). 2. Our study found that SCUBE1 and RNF103-CHMP3 were significantly downregulated in patients who were cured of DFU. 3. This study discovered that SCUBE1 and RNF103-CHMP3 are associated with extracellular interactions. 4. Our findings indicate that SCUBE1 and RNF103-CHMP3 are related to immune cell infiltration. 5. This study provides new theoretical foundations and molecular targets for the diagnosis and treatment of DFU. Background: To utilize machine learning for identifying treatment response genes in diabetic foot ulcers (DFU). Methods: Transcriptome data from patients with DFU were collected and subjected to comprehensive analysis. Initially, differential expression analysis was conducted to identify genes with significant changes in expression levels between DFU patients and healthy controls. Following this, enrichment analyses were performed to uncover biological pathways and processes associated with these differentially expressed genes. Machine learning algorithms, including feature selection and classification techniques, were then applied to the data to pinpoint key genes that play crucial roles in the pathogenesis of DFU. An independent transcriptome dataset was used to validate the key genes identified in our study. Further analysis of single-cell datasets was conducted to investigate changes in key genes at the single-cell level. Results: Through this integrated approach, SCUBE1 and RNF103-CHMP3 were identified as key genes significantly associated with DFU. SCUBE1 was found to be involved in immune regulation, playing a role in the body's response to inflammation and infection, which are common in DFU. RNF103-CHMP3 was linked to extracellular interactions, suggesting its involvement in cellular communication and tissue repair mechanisms essential for wound healing. The reliability of our analysis results was confirmed in the independent transcriptome dataset. Additionally, the expression of SCUBE1 and RNF103-CHMP3 was examined in single-cell transcriptome data, showing that these genes were significantly downregulated in the cured DFU patient group, particularly in NK cells and macrophages. Conclusion: The identification of SCUBE1 and RNF103-CHMP3 as potential biomarkers for DFU marks a significant step forward in understanding the molecular basis of the disease. These genes offer new directions for both diagnosis and treatment, with the potential for developing targeted therapies that could enhance patient outcomes. This study underscores the value of integrating computational methods with biological data to uncover novel insights into complex diseases like DFU. Future research should focus on validating these findings in larger cohorts and exploring the therapeutic potential of targeting SCUBE1 and RNF103-CHMP3 in clinical settings. [ABSTRACT FROM AUTHOR]

AbstractDiabetic foot ulcers (DFUs) are a severe microvascular complication. Platelet-rich plasma (PRP) pitches in DFU treatment. This study explored the mechanism of PRP facilitating wound repair in DFU mice via vascular endothelial growth factor A (VEGFA)/VEGF receptor 2 (VEGFR2)/extracellular signal-regulated kinase (ERK) pathway. The DFU mouse model was established, with wound skin injected with PRP, followed by the detections of wound area, histopathological changes, and CD31-positive cells. IL-6/TNF-α/VEGFA/VEGFR2/p-VEGFR2/(ERK1/2)/(p-ERK1/2) levels in wound tissue homogenates were assessed. VEGFA-VEGFR2 interaction was evaluated. PRP-treated DFU mice were simultaneously treated with fruquintinib/PD98059. PRP reduced wound area, IL-6 and TNF-α levels, elevated epidermal dermal thickness, CD31-positive cell number, and aligned tissue structure, which were mitigated by fruquintinib/PD98059. PRP promoted VEGFR2 phosphorylation. PRP and fruquintinib/PD98059 abated p-VEGFR2/VEGFR2 or p-ERK1/2/ERK1/2 levels in DFU mice. PRP activated the ERK pathway through VEGFA/VEGFR2. Collectively, PRP promoted VEGFR2 phosphorylation and activated the ERK pathway, thereby facilitating wound repair in DFU mice. [ABSTRACT FROM AUTHOR]

Background: Participant non-response is a source of bias in all research, especially in randomised controlled trials. Participants followed up remotely can have high non-response rates. Four such trials have been conducted of a cover letter with content informed by behaviour change theory to overcome hypothesised barriers to responding to a mailed questionnaire. Pooled results to date have suggested further research to be worthwhile. We conducted an embedded randomised study within a trial of such cover letters in the hope that we would improve response rates to our postal quality of life questionnaires. Methods: One hundred forty-eight participants in the CODIFI2 diabetic foot ulcer sampling trial were randomised 1:1 to receive one of two different cover letters at follow-up timepoints: either a standard cover letter accompanying their postal follow-up questionnaires or to an 'enhanced' (theory-informed) cover letter. Questionnaires were mailed at 39, 52 and (for some participants) 104 weeks post randomisation. Outcome measures were response to mailing at each timepoint. Analysis was restricted to those for whom a questionnaire and letter was issued. Owing to limited recruitment, a reduced analysis plan, comprising solely observed response rates and 95% confidence intervals for difference in response rates was followed. Post hoc, we added our week 52 results to an already-published meta-analysis. Results: Sixty-seven out of 74 enhanced cover letter group (Enhanced) and 67/74 standard cover letter group (Standard) participants who had not already died or withdrawn were sent their first mailing at 39 weeks. The 39-week response rates were 47/67 (70.1%) and 39/67 (58.2%) for Enhanced and Standard participants, respectively. At week 52, the response rates were 45/64 (70.3%) and 35/63 (55.6%) for Enhanced and Standard participants, respectively. At week 104, the response rates were 24/33 (72.7%) and 19/33 (57.6%) for the Enhanced and Standard participants, respectively. Adding our week 52 results to a published meta-analysis increased the pooled estimate of differences in response rates to 0.04 (− 0.01 to 0.09) favouring enhanced letters. Conclusion: While this embedded randomised controlled trial observed greater response rates at all times among those randomised to the enhanced letter, the reduced sample size meant that these results are imprecise. Trial registration: ISRCTN registry ISRCTN74929588. Registered on 5 March 2019. [ABSTRACT FROM AUTHOR]

To assess the accuracy of a nomogram for predicting the risk of lower-extremity amputation (LEA) in individuals with diabetic foot ulcers (DFUs). We retrospectively analyzed data from 144 patients with DFUs at the Department of Orthopedics of the First Affiliated Hospital of Nanchang University, collected between January 2020 and December 2023. Univariate analysis determined primary predictive factors for amputation, followed by single and multifactor logistic regression analyses to indentify independent factors. These were utilized to develop a prediction model using R4.3.3, and a nomogram was created. Its performance was verified using receiver operating characteristic (ROC), corrected calibration, and clinical decision curves. Twelve primary predictive factors were identified from 20 variables, including age, Wagner grades, peripheral angiopathy of diabetes (PAD), chronic kidney disease(CKD), C-reactive protein(CRP) and the number of blood sugar abnormalities(BSA) etc. Multivariate logical regression analysis illustrated that Wagner grades, PAD, CRP, CKD, and the number of BSA were independent risk factors. The area under the curve (AUC) of the ROC curve was 0.967, and the revised calibration curve of the nomogram demonstrated strong fitting ability. This prediction model is a valuable tool for screening LEA risk and preventing DFU from progressing into amputation. [ABSTRACT FROM AUTHOR]

Background: The diabetic foot (DF) ulcer is the severe complication of type 2 diabetes mellitus (T2DM). Sarcopenia is characterized as the loss of muscle mass and strength, resulting in the increased risk of fracture and physical disability. Sarcopenia may affect the foot-ankle function in DF ulcer patients, compromise the quality of life. Objective: The aim was to clarify the effect of sarcopenia on foot-ankle function in patients with DF ulcer. Methods: In total of 108 T2DM patients with DF ulcer were enrolled. Based on the examination of muscle mass by dual energy X-ray absorptiometry (DXA) and grip strength and 5x sit-to-stand test, the DF patients were divided into sarcopenia and non-sarcopenia groups. The severity of DF ulcer was evaluated by Wagner classification. The foot-ankle function was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score. Results: DF patients with sarcopenia showed advanced age, lower BMI, longer duration of T2DM, and more severe Wagner classification, reduced appendicular skeletal muscle mass index (ASMI), grip strength, transcutaneous oxygenpressure (TcPO2) and prolonged time of 5X sit-to-stand test. The stratified comparison analysis indicated that severity of sarcopenia and DF ulcer, reduced TcPO2, and grip strength were aggravated with the impaired foot-ankle function (P < 0.05). Multivariate Logistic analysis showed that age, TcPO2, and severe sarcopenia were risk factors deteriorating the foot-ankle function. Conclusion: The sarcopenia is a key risk factor of decreasing foot-ankle function in patients with DF ulcer. Thus, the prevention of muscle mass and strength loss could be considered as part of comprehensive therapy for DF ulcer. [ABSTRACT FROM AUTHOR]

Background: Digital solutions in healthcare can facilitate and improve care. However, the experiences and the usefulness of using either digital foot examinations or traditional foot examinations need to be evaluated. The aims of the study were to evaluate: 1) The differences in patient experiences, having their foot examined supported by the Clinical Decision Support System as compared with having their foot examined in traditional practice, 2) How healthcare professionals, by using the digital tool, experienced the routine compared with performing the foot examination as in traditional practice. Methods: Of a total of 141 patients, 100 patients with diabetes were single-blind digitally randomised to one of two parallel arms: having their foot examined by a healthcare professional using a digital tool (n = 47) or having their foot examined as in traditional practice (n = 53) at the Department of Prosthetics and Orthotics at Sahlgrenska University Hospital, Gothenburg, Sweden. Patients filled in a modified version of the National Patient Survey and the Orthotics and Prosthetics Users' Survey at study end. Two healthcare professionals, working at a Department of Prosthetics and Orthotics, answered surveys regarding the interaction between the patient and the certified prosthetist and orthotist. Results: Patients, aged 66 ± 13 years, perceived a high level of satisfaction with the service at the department, regardless of the method used. No significant differences between groups were found when evaluated by 27 questions in the National Patient Survey or by the Orthotics and Prosthetics Users' Survey, with scores of 67.17 ± 12.18 vs. 66.35 ± 16.52 (p = 0.78) for the intervention and control group respectively. For the same patient that healthcare professionals foot examined, the risk class was fully obtained when the risk to develop foot ulcers was assessed by using the digital tool, whereas only 2% of the patients were classified when foot assessed in traditional practice. Conclusions: Regardless of the method used for the foot examination, patients perceived a high level of satisfaction with the services at the Department of Prosthetics and Orthotics. All the patients were risk classified in the intervention group. The healthcare professionals found that, by using the Clinical Decision Support System, the foot examination was structured and followed clinical guidelines. Furthermore, the documentation in the electronic health record was thorough, even though further improvements, such as integration with co-existing health record systems, were requested. Trial registration: Clinical Trials NCT03088566, Registered 23 March 2017. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Diabetic foot ulcers (DFU) are one of the most destructive complications of diabetes mellitus. The aim of this study was to link miR‐155 and SOX2 with DFU to explore the regulation of wound healing by DFU and its potential mechanism.Human keratinocytes (HaCaT) were induced with advanced glycation end products (AGEs) to construct DFU models in vitro. AGE‐induced HaCaT cells were subjected to CCK‐8 assays, flow cytometry, and wound healing assays to evaluate cell proliferation, apoptosis, and migration capacity, respectively. RT–qPCR and Western blotting were used to determine gene and protein expression levels, respectively. N6‐methyladenosine (M6A) levels in total RNA were assessed using an M6A methylation quantification kit.Our results suggested that the inhibition of miR‐155 promoted wound healing in an in vitro DFU model, while the knockdown of HIF‐1α reversed this process, and that HIF‐1α was a target protein of miR‐155. In addition, knockdown of HIF‐1α promoted the m6A level of SOX2 mRNA, inhibited the expression of SOX2, and inhibited the activation of the EGFR/MEK/ERK signaling pathway, thus inhibiting the proliferation and migration of HaCaT cells and promoting the apoptosis of HaCaT cells, while overexpression of SOX2 reversed this effect. We also found that METTL3 knockdown had the opposite effect of HIF‐1α knockdown.Inhibition of miR‐155 promoted the expression of HIF‐1α and attenuated the m6A modification of SOX2 mRNA, thereby promoting the expression of SOX2 and activating the downstream EGFR/MEK/ERK signaling pathway to promote wound healing in an in vitro DFU model. [ABSTRACT FROM AUTHOR]

Background: A cross-sectional study was conducted to investigate the prevalence of onychomycosis (ONM) and its causative pathogens in populations with and without diabetes in Spain. The association between the presence of ONM, different risk factors, and comorbidities was also examined. Methodology: A total of 160 patients with diabetes and 160 individuals without diabetes were recruited consecutively. A single investigator recorded the relative data of each patient and sampled nail dust and detritus for microbiological culture and polymerase chain reaction (PCR) analyses of patients who showed clinical signs of fungal infection. Results: The prevalence of ONM was 36.88% (59/160) in the population with diabetes, 17.5% (28/160) in the population without diabetes, and 34.35% (45/131) in the population with diabetic foot. Dermatophyte fungi were most frequently identified, although the proportion was higher among those without diabetes than those with diabetes (19/28 and 28/59, respectively). However, the rate of mixed infections was higher in the population with diabetes compared to those without diabetes (13/59 and 2/28, respectively). A statistically significant association was found between the presence of diabetes and the risk of ONM (p < 0.001; odds ratio (OR) = 2.754; 95% confidence interval (CI) 1.652–4.679). The risk factors associated with ONM among the patients with diabetes were a history of minor amputation, revascularisation, or cardiovascular disease, a low educational level, HbA1c values > 7%, hyperkeratosis, and subungual detritus. Among the patients without diabetes, nail thickening and chromonychia were associated with ONM. Conclusion: The results of this study suggest that the early diagnosis of ONM and knowledge of risk factors among patients with diabetes could enable the prevention of ONM, complications, and serious injuries through education for professionals and patients. [ABSTRACT FROM AUTHOR]

Introduction: Globally, the health and quality of life of millions of people are negatively affected by diabetic foot ulcers (DFUs). To treat these chronic wounds, a novel injectable drug for closing DFUs composed of micronized amniotic membrane was developed. This new therapeutic drug for wound repair expands on traditional allograft therapies by allowing extracellular matrix proteins, growth factors, and cytokines to reach wound anatomies in DFUs that are difficult to treat. The aim of this study was to evaluate the components of the injectable drug. Methods: Liquid chromatography with tandem mass spectrometry and a Quantibody® human cytokine array were conducted to identify and characterize growth factors and proteins known to contribute to wound healing. In addition, hyaluronic acid was quantified and compared between the injectable and human amniotic fluid using a hyaluronan enzyme-linked immunosorbent assay. Cell proliferation, migration, angiogenesis, and viability were evaluated to assess the performance of the novel injectable in vitro. The rheometric properties of the product were evaluated by assessing it pre- and post-injection through a 22-gauge needle to measure the viscosity using a shear- and temperature-dependent viscosity protocol. Results: Liquid chromatography with tandem mass spectrometry and Quantibody® human cytokine array revealed growth factors and proteins imperative for wound healing. The quantified hyaluronic acid was compared between the injectable and human amniotic fluid, resulting in a statistically significant difference, with higher protein concentrations found in the injectable. In vitro qualitative and quantitative analysis confirmed an increase in cell viability, proliferation, and migration when treated with the drug. An evaluation of the rheometric properties of the injectable drug after passing through a 22-gauge cannula presented no alterations to the biologic drug. Conclusions: Collectively, these data present the potential of a novel injectable drug for the treatment of DFUs. [ABSTRACT FROM AUTHOR]

Despite growing numbers of scientific publications on the optimal antibiotic treatment for diabetic foot infections, the data on the adult population with non-diabetic (postsurgical) foot infections is limited. Therefore, one of the largest single-center databases at the Balgrist University Hospital in Zurich, Switzerland, was established between January 2014 and August 2022. Using a case–control study design, we retrospectively investigated failures of combined surgical and antibiotic therapy for surgical site foot infections (SSIs). Overall, 17.4% of the episodes experienced therapeutic failures, particularly in patients with infected ankle prostheses. However, age, biological sex, pathogens, the duration of post-debridement antibiotic treatment, the number of surgical debridements, or the use of negative-pressure wound care altered the failure risk. In the multivariate logistic regression analyses, the duration of postsurgical antibiotic use was completely indifferent (as a continuous variable with an odds ratio of 1.0 and a 95% confidence interval ranging from 0.96 to 1.03) when stratified into inter-tertiary groups. Our findings suggest that shorter courses of systemic antibiotics may be appropriate in non-diabetic adults, supporting better antibiotic stewardship. Ongoing randomized controlled trials are under way to investigate which patients might safely receive shorter antibiotic treatments for surgical site infections following elective foot and ankle procedures. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers and infections are complications that can result in significant morbidity such as the need for amputations, especially in uncontrolled diabetes, thereby profoundly impacting quality of life. While traditional treatments like wound care and antibiotics are effective, there is growing interest in the role of micronutrients (such as vitamins C, D, E, zinc and magnesium) in improving outcomes. This study aims to evaluate how these micronutrients affect diabetic foot infections and the need for amputation, offering insights to enhance overall prognosis. Patients who were hospitalised with a diagnosis of diabetic foot infection in the Infectious Diseases Department of Ege University Faculty of Medicine Hospital between 1 April 2022, and 31 January 2023 were included in the study. The patients' socio‐demographic information, characteristics of diabetic wounds, operation history, as well as their levels of micronutrients recorded on the case report form. A total of 202 patients were included in the study. The most common micronutrient deficiencies were vitamin D (69%), vitamin C (64%) and zinc (49%). The amputation rates were significantly higher in patients with deficiencies vitamin C, vitamin A and vitamin D (p < 0.005). Our research revealed a significant prevalence of vitamin deficiencies among the participants, and we observed a noteworthy correlation between amputation rates and these deficiencies. Although these findings show promise, it is essential to emphasise that micronutrient supplements should not replace traditional treatments but should rather be considered as a warning sign for preventing complications, particularly amputation or extremity loss. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcer (DFU) is a chronic and serious complication of diabetes mellitus. It is mainly caused by hyperglycaemia, diabetic peripheral vasculopathy and diabetic peripheral neuropathy. These conditions result in ulceration of foot tissues and chronic wounds. If left untreated, DFU can lead to amputation or even endanger the patient's life. Single‐cell RNA sequencing (scRNA‐seq) is a technique used to identify and characterise transcriptional subpopulations at the single‐cell level. It provides insight into cellular function and the molecular drivers of disease. The objective of this paper is to examine the subpopulations, genes and molecules of cells associated with chronic wounds of diabetic foot by using scRNA‐seq. The paper aims to explore the wound‐healing mechanism of DFU from three aspects: inflammation, angiogenesis and extracellular matrix remodelling. The goal is to gain a better understanding of the mechanism of DFU wound healing and identify possible DFU therapeutic targets, providing new insights for the application of DFU personalised therapy. [ABSTRACT FROM AUTHOR]

The aim of this meta‐analysis is to compare the clinical outcomes in patients with and without residual osteomyelitis (ROM) after surgical bone resection for diabetic foot osteomyelitis (DFO). We completed a systematic literature search using PubMed, Scopus, and Embase using keywords DFO, Residual OM (ROM), and positive bone margins. The study outcomes included wound healing, antibiotic duration, amputation, and re‐infection. Five hundred and thirty patients were included in the analysis; 319 had no residual osteomyelitis (NROM), and 211 had ROM. There was not a significant difference in the proportion of wounds that healed 0.6 (p = 0.1, 95% confidence intervals [95% CI] 0.3–1.3). The risk of infection was 2.0 times higher (OR = 2.0, p = 0.02, 95% CI 1.1–3.4), and the risk of amputation was 4.3 times higher (OR = 4.3, p = 0.0001, 95% CI 2.4–7.6) in patients with ROM. Patients with ROM received antibiotics significantly longer. The mean difference was 16.3 days (p = 0.02, 95% CI 11.1–21.1). [ABSTRACT FROM AUTHOR]

Slough is a well‐known feature of non‐healing wounds. This pilot study aims to determine the proteomic and microbiologic components of slough as well as interrogate the associations between wound slough components and wound healing. Ten subjects with slow‐to‐heal wounds and visible slough were enrolled. Aetiologies included venous stasis ulcers, post‐surgical site infections and pressure ulcers. Patient co‐morbidities and wound healing outcome at 3‐months post‐sample collection was recorded. Debrided slough was analysed microscopically, through untargeted proteomics, and high‐throughput bacterial 16S‐ribosomal gene sequencing. Microscopic imaging revealed wound slough to be amorphous in structure and highly variable. 16S‐profiling found slough microbial communities to associate with wound aetiology and location on the body. Across all subjects, slough largely consisted of proteins involved in skin structure and formation, blood‐clot formation and immune processes. To predict variables associated with wound healing, protein, microbial and clinical datasets were integrated into a supervised discriminant analysis. This analysis revealed that healing wounds were enriched for proteins involved in skin barrier development and negative regulation of immune responses. While wounds that deteriorated over time started off with a higher baseline Bates‐Jensen Wound Assessment Score and were enriched for anaerobic bacterial taxa and chronic inflammatory proteins. To our knowledge, this is the first study to integrate clinical, microbiome, and proteomic data to systematically characterise wound slough and integrate it into a single assessment to predict wound healing outcome. Collectively, our findings underscore how slough components can help identify wounds at risk of continued impaired healing and serves as an underutilised biomarker. [ABSTRACT FROM AUTHOR]

Introduction. Diabetes mellitus is a significant global health issue, particularly due to its chronic complications, such as neuropathy and peripheral arterial disease (PAD), which can lead to debilitating outcomes like diabetic foot, ulcers, and amputations. These complications not only afflict the patient’s quality of life, but also present significant social and healthcare challenges. Traditional therapeutic approaches often provide only partial symptoms’ relief, prompting the exploration of alternative therapies to enhance disease management and patient’s quality of life. Ozone therapy has emerged as a promising adjuvant treatment for patients with diabetes. In clinical practice, ozone therapy has demonstrated encouraging results in reducing neuropathic and vascular symptoms and in improving overall quality of life. The therapeutic versatility of ozone is attributed to its ability to generate a cascade of biologically active compounds that target multiple pathological processes. These include cardiovascular, peripheral vascular, neurologic, and skin conditions, as well as enhanced wound healing, making it particularly beneficial for the complex and multifactorial nature of diabetes-related complications. Conclusions. Ozone therapy has demonstrated potential as a therapeutic option for managing neurovascular complications in diabetic patients. Clinical evidence shows an improvement in symptoms, as verified by specific diagnostic tests, suggesting that ozone therapy may serve as a valuable addition to the conventional treatment of diabetic neuropathy and peripheral arterial disease. [ABSTRACT FROM AUTHOR]

Objective • This study aims to evaluate the effect of rehabilitation interventions based on the motive behavioral conversion concept on diabetic foot ulcer patients after artificial dermal transplantation. The focus is on enhancing self-management and quality of life by integrating intrinsic motivation and behavioral changes in postoperative care. It also aims to introduce and clarify this concept for readers less familiar with this approach in diabetic foot ulcer rehabilitation. Methods • The study involved 102 diabetic foot ulcer patients who had undergone artificial dermal transplantation, randomly divided into a control and an observation group. Both groups received standard postsurgical care including antimicrobial agents with alginate supplements and closed negative pressure drainage therapy. The control group underwent conventional rehabilitation, while the observation group received rehabilitation based on motivational behavior transformation. Key evaluation metrics included Visual Analog Scale (VAS) scores, frequency/time of dressing changes, wound healing time, incidence of adverse events, self-care ability scores, and Diabetes-Specific Quality of Life (DSQL) scores, allowing for a comprehensive comparison of outcomes between the two groups. Results • Before the intervention, there was no significant difference in the VAS pain scores between the groups. However, after 7, 10, and 14 days of intervention, the observation group showed a greater reduction in VAS pain scores. The observation group also had shorter dressing change times (12.77 ± 2.18 minutes) and wound healing times (25.77 ± 2.94 days) compared to the control group (16.56 ± 3.25 minutes for dressing change, 27.85 ± 3.26 days for wound healing). There were no significant differences in the frequency of dressing changes or the cumulative incidence of adverse events between the groups. After 6 months, the observation group demonstrated higher self-care ability scores in several domains and lower total DSQL scores, indicating better outcomes in quality of life dimensions. Conclusion • Rehabilitation interventions based on the motive behavioral conversion concept significantly enhanced postoperative recovery, demonstrating potential implications for clinical practices and future research. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFUs) present a substantial health risk across diverse age groups, creating challenges for healthcare professionals in the accurate classification and grading. DFU plays a crucial role in automated health monitoring and diagnosis systems, where the integration of medical imaging, computer vision, statistical analysis, and gait information is essential for comprehensive understanding and effective management. Diagnosing DFU is imperative, as it plays a major role in the processes of diagnosis, treatment planning, and neuropathy research within automated health monitoring and diagnosis systems. To address this, various machine learning and deep learning‐based methodologies have emerged in the literature to support healthcare practitioners in achieving improved diagnostic analyses for DFU. This survey paper investigates various diagnostic methodologies for DFU, spanning traditional statistical approaches to cutting‐edge deep learning techniques. It systematically reviews key stages involved in diabetic foot ulcer classification (DFUC) methods, including preprocessing, feature extraction, and classification, explaining their benefits and drawbacks. The investigation extends to exploring state‐of‐the‐art convolutional neural network models tailored for DFUC, involving extensive experiments with data augmentation and transfer learning methods. The overview also outlines datasets commonly employed for evaluating DFUC methodologies. Recognizing that neuropathy and reduced blood flow in the lower limbs might be caused by atherosclerotic blood vessels, this paper provides recommendations to researchers and practitioners involved in routine medical therapy to prevent substantial complications. Apart from reviewing prior literature, this survey aims to influence the future of DFU diagnostics by outlining prospective research directions, particularly in the domains of personalized and intelligent healthcare. Finally, this overview is to contribute to the continual evolution of DFU diagnosis in order to provide more effective and customized medical care. This article is categorized under:Application Areas > Health CareTechnologies > Machine LearningTechnologies > Artificial Intelligence [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a leading cause of disability with adverse effects on the quality of life. It also affects occupational health by impacting several work-related parameters. This review discusses the relationship between diabetes and absenteeism, presenteeism, work impairment and unemployment. The association between work and diabetic complications such as neuropathic pain, diabetic foot, psychological issues and hypoglycemia due to treatment is also examined. Evidence points to a relationship between diabetes and absenteeism, reduced work productivity, and, thus, overall work impairment. A stronger negative impact on work performance is mediated by painful diabetic neuropathy and diabetic foot. In addition, psychological distress has been positively correlated with total workdays lost and frequency of absence. Depression in the diabetic population has also been linked with increased absenteeism, presenteeism, and work disability. Moreover, hypoglycaemia induced by antidiabetic medication may affect work attendance and performance. Finally, diabetes has been associated with inequality in the work environment, lower job satisfaction and higher unemployment rates, mainly because of its complications. [ABSTRACT FROM AUTHOR]

Objectives: Levonadifloxacin (IV) and alalevonadifloxacin (oral) are novel broad-spectrum anti-methicillin-resistant Staphylococcus aureus (S. aureus) agents based on novel benzoquinolizine core. Both are recently approved in India for the treatment of acute bacterial skin and skin structure infections, including diabetic foot infections and concurrent bacteremia. The present investigation reports the findings from preclinical pharmacokinetic (PK) studies that support the development of levonadifloxacin as a treatment option for bone and joint infections (BJIs). Methods: PK profiles of levonadifloxacin were obtained in serum, and/or various anatomical segments of femoral bone such as whole bone (WB), hard bone (HB), and bone marrow (BM) following subcutaneous administration of levonadifloxacin single doses at 50, 100, 200, and 400 mg/kg, as well as multiple doses at 200 mg/kg (BID (two times a day), 6 hours apart) for 5 days in Wistar rats. Results: The distribution of levonadifloxacin in bone was rapid, and the extent of distribution (B/S ratio; bone-to-serum area under the concentration–time curve ratio) was nearly comparable across bone segments. In single-dosage PK studies, the mean B/S ratio in WB, HB, and BM was 0.40, 0.33, and 0.34, respectively; however, in 5 days' repeated dose studies, it increased to 1.01, 1.14, and 0.61, respectively. Conclusions: On the basis of bone PK data in Wistar rat and ever-growing clinical experience in terms of safety and efficacy, levonadifloxacin has the potential to offer a well-differentiated therapy for the treatment of BJIs. [ABSTRACT FROM AUTHOR]

The prevention of diabetic foot ulcers remains a critical challenge. This study evaluates a smart compression sock designed to address this issue by integrating temperature, plantar pressure, and blood oxygen sensors and monitoring data recorded by these sensors. The smart sock, developed with input from a certified Pedorthist, was tested on 20 healthy adult participants aged 16 to 53. It includes four temperature sensors and pressure sensors at common ulcer sites (first and fifth metatarsal heads, calcaneus, and hallux), and a blood oxygen sensor on the hallux. The sensors are monitored, and their transduced data are collected and stored through an app installed on a personal cell phone. The mobile app interface is user-friendly, providing intuitive navigation and easy access to the sensors' data. Using repeated measures ANOVA and post hoc tests, we analyzed the impact of various physical activities on physiological changes in the foot. The device effectively detected significant variations in blood oxygen, temperature, and pressure across six activities. Statistical analyses revealed significant differences based on activity type and sensor location. These results highlight the smart sock's sensitivity and accuracy, suggesting its potential to prevent diabetic foot ulcers. Further clinical trials are needed to evaluate its efficacy in a larger, more diverse population. [ABSTRACT FROM AUTHOR]

Background and Aims: The COVID‐19 pandemic significantly disrupted lower limb diabetes care. We aimed to map trends in diabetes‐related lower limb amputation and hospitalisation rates through the COVID‐19 pandemic. Methods: We performed a retrospective cohort study of all individuals who underwent a lower limb amputation for a diabetes‐related foot complication from 2018 to 2021 at the Royal Melbourne Hospital, a quaternary hospital in Australia. Hospitalisation rates with a diabetes‐related foot complication were collected for comparison. The start of the COVID‐19 epoch was defined as 16 March 2020, when a state of emergency was declared in Melbourne. Results: During the study period, 360 lower limb amputations for diabetes‐related foot complications were performed in 247 individuals. The median monthly number of amputations remained stable prior to and during the COVID‐19 epoch; there was a median of 8.0 amputations per month (interquartile range (IQR) = 6.5–11) before COVID‐19, compared to 6.5 amputations (IQR = 5.0–8.3) during the COVID‐19 epoch (P = 0.23). Hospitalisation with a diabetes‐related foot complication significantly increased from a median monthly rate of 11 individuals (IQR = 9.0–14) before COVID‐19 to 19 individuals (IQR = 14–22) during the COVID‐19 epoch (p < 0.001). Conclusions: Despite increased hospitalisations for diabetes‐related foot complications during COVID‐19, there was not a corresponding increase in amputation rates. Face‐to‐face care of diabetes‐related foot complications was prioritised at this centre and may have contributed to stable amputation rates during the pandemic. [ABSTRACT FROM AUTHOR]

Aim: To compare the effectiveness of preventive interventions in reducing reccurrent diabetic foot ulcers. Meta-analysis (MA) was conducted to address clinical questions on this topic of the Italian guidelines on diabetic foot. Methods: This MA includes randomized controlled trials evaluating the effectiveness of various preventive interventions, namely: treatment of pre-ulcerative foot lesions, structured educational programs, psychological interventions and the use of therapeutic footwear to relieve plantar pressure in people with diabetes mellitus and a history of previous ulcers. Results: A total of 731 studies were identified and 14 were considered eligible for the analysis. We found that treatments of pre-ulcerative foot lesions did not provide any statistically significant effects (MH-OR: 0.84 [0.31, 2.33], p = 0.74, I2 = 38%). Conversely, structured educational programs were associated with a trend toward reduction of ulcer recurrence risk (MH-OR: 0.13 [0.01, 1.64], p = 0.10, I2 = 88%). No randomized controlled studies assessing the efficacy of psychological interventions have been retrieved. The use of therapeutic footwears can effectively reduce the risk of reulceration in diabetic patients with an history of previous DFU, in particular prefabricated rigid-soled therapeutic footwears showed a significant reduction of the risk of ulcer recurrence in comparison with semirigid soles (MH-OR: 0.17 [0.05, 0.57], p = 0.004). Conclusions: The study provides low-certainty evidence that, among preventive strategies in patients with previous DFU, rigid-sole therapeutic footwear and structured education programs are capable of reducing the risk of foot re-ulceration. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE), for diagnosing osteomyelitis in the diabetic foot. A thorough search was carried out to identify suitable studies published up to September 2023. The quality of the studies involved was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The diagnostic sensitivity and specificity of each imaging modality/method for each specific cut point were summarized. The summary receiver operating characteristic (SROC) curve was calculated using bivariate mixed effects models. Five studies investigating 187 patients and 234 bone lesions with 110 diagnosed osteomyelitis were enrolled. Four studies used DWI (172 lesions), three studies used DCE techniques (140 lesions) and two studies presented results of conventional MRI (66 lesions). The sensitivity ranges using conventional MRI, DWI and DCE were 65%-100%, 65%-100% and 64%-100%, respectively. The specificity ranges were 50%-61%, 56%-95%, and 66%-93%, respectively. The SROC curve of DWI and DCE was 0.89 (95% CI, 0.86–0.92) and 0.90 (95% CI, 0.87–0.92), respectively. Combining DWI and DCE methods, alongside conventional MRI, can improve the reliability and accuracy of diabetic foot osteomyelitis diagnosis. However, the study recognizes result variability due to varying protocols and emphasizes the need for well-designed studies with standardized approaches. To optimize diagnostic performance, the study recommends considering low ADC values, Ktrans or rapid wash-in rate from DCE such as iAUC60, along with using large ROIs that cover the entire lesion while excluding normal bone marrow. [ABSTRACT FROM AUTHOR]

Aim: To assess the safety and efficacy of a local skin substitute product in the treatment of chronic diabetic foot ulcers (DFUs). Materials and Methods: Five patients were evaluated over 6 months. Skin substitutes were applied twice at 2‐week intervals. Patients were monitored for any possible adverse effects and wound improvement. Results: The results indicated the overall safety of the skin substitute, with only few adverse effects unrelated to this product. Significant reduction in wound size was observed in four patients during the initial 12‐week treatment phase, with complete closure in two patients at 24 weeks. Conclusions: The application of a bi‐layered allogeneic keratinocyte and fibroblast skin substitute in patients with chronic DFU was safe and associated with favourable wound healing results. Adherence to standard treatment protocols, including optimal offloading, is essential to maximize the likelihood of successful wound healing. [ABSTRACT FROM AUTHOR]

Background: Research on the relationship between dietary phytochemical intake and the anthropometric indices as well as the diabetic foot ulcers (DFUs) remains inconsistent. We aimed to investigate the associations of dietary phytochemical index (DPI) with the novel anthropometric indices and the severity of DFUs. Methods: This cross-sectional study was conducted on 339 adults with type 2 diabetes. Dietary intake was assessed using three 24-hour dietary recalls. To quantify the phytochemical content of the diet, the DPI estimation was done through an equation proposed by McCarty. The International Working Group on the Diabetic Foot (IWGDF) criteria and Wagner classification system were applied to assess DFUs. New anthropometric indices including a body shape index (ABSI), body roundness index (BRI) and abdominal volume index (AVI) were calculated based on formulas. We employed analysis of variance (ANOVA), analysis of covariance (ANCOVA) and logistic regression to explore associations between DPI and the anthropometric indices and DFU variables. Results: Our results revealed no significant association between DPI and the foot ulcer indices, following adjusting for the possible covariates. Furthermore, we also examined the relationship between diabetic neuropathy, as measured by monofilament score, and the DPI. Similarly, we did not find any substantial relationship between the DPI and monofilament score (OR: 1.18; 95% CI: 0.66–2.09; Ptrend = 0.56), as well as biochemical indices. Our analysis did not reveal any significant associations between the DPI and ABSI (OR: 0.70; 95% CI: 0.35–1.38; Ptrend = 0.30), BRI (OR: 0.80; 95% CI: 0.33–1.95; Ptrend = 0.59), and AVI (OR: 1.99; 95% CI: 0.92–4.33; Ptrend = 0.08). Conclusions: Our study revealed no significant links between the DPI and foot ulcer indices, neuropathy measures, and anthropometric indices. These findings imply that factors beyond dietary phytochemical intake may exert greater influence on the development of foot ulcers in diabetes. [ABSTRACT FROM AUTHOR]

Dermal fibroblasts play a crucial role in the formation of granulation tissue in skin wounds. Consequently, the differentiation, migration, and proliferation of dermal fibroblasts are considered key factors in the skin wound healing process. However, in patients with diabetic foot ulcers, the proliferation and migration of fibroblasts are impaired by reactive oxygen species and inflammatory factors impair. Therefore, a novel magnetic gelatin-hesperidin microrobots drug delivery system was developed using microfluidics. The morphology, motility characteristics, and drug release of the microrobot were assessed, along with its impact on the proliferation and migration of human dermal fibroblasts under high-glucose conditions. Subjected to a rotating magnetic field, the microrobots exhibit precise, controllable, and flexible autonomous motion, achieving a maximum speed of 9.237 µm/s. In vitro drug release experiments revealed that approximately 78% of the drug was released within 30 min. It was demonstrated through cellular experiments that the proliferation of human dermal fibroblasts was actively promoted by the nanorobot, the migration ability of fibroblasts in a high-glucose state was enhanced, and good biocompatibility was exhibited. Hence, our study may provide a novel drug delivery system with significant potential for promoting the healing of diabetic foot wounds. [ABSTRACT FROM AUTHOR]

AbstractDiabetic foot wounds associated with oxidative stress are treated with hyperbaric oxygen (HBO), but that may also induce the stress itself; therefore, we studied the effect of HBO treatments on the oxidant–antioxidant balance in the venous blood of patients with diabetic foot syndrome. In addition, blood counts were also examined. 14 male patients (24–74 years), at risk of lower limb amputation were treated with 30 HBO procedures (60 min of the inhalation of pure oxygen at a pressure of 2.5 atm per day, 5 days a week). The control group consisted of 29 healthy male volunteers aged 25–69 years. No members of the group had been subjected to HBO therapy previously (ClinicalTrials.gov, no. NCT06401941). The analyzed redox parameters did not change during the experiment in the patients (p > 0.05). The concentration of thiobarbituric acid reactive substances (TBARS) in the plasma was higher in the patients before the first and after the thirtieth HBO treatments when compared to the control group. In contrast, the TBARS concentration in erythrocytes was lower in the patients after the first treatment vs. the controls. Moreover, the higher activity of catalase in the patients’ erythrocytes was noted before the therapy and after the first and last treatments compared to the controls. HBO therapy increased the percentage of monocytes and platelet volume, but it decreased the volume of platelets in the patients’ blood. HBO therapy does not affect the oxidant–antioxidant balance disturbed in diabetic foot patients. [ABSTRACT FROM AUTHOR]

The early expectations about growth factors' (GFs') discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes' and fibroblasts' physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs' clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts' epigenetic core, mitigating the consequences of metabolic memory imprinting. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is the predominant pathogen isolated in diabetic foot infections. Recently, the skin commensal bacterium, Helcococcus kunzii, was found to modulate the virulence of this pathogen in an in vivo model. This study aims to elucidate the molecular mechanisms underlying the interaction between these two bacterial species, using a proteomic approach. Results: Our results reveal that H. kunzii can coexist and proliferate alongside S. aureus in a Chronic Wound Media (CWM), thereby mimicking an in vitro chronic wound environment. We noted that the secreted proteome of H. kunzii induced a transcriptional effect on S. aureus virulence, resulting in a decrease in the expression level of agrA, a gene involved in quorum sensing. The observed effect could be ascribed to specific proteins secreted by H. kunzii including polysaccharide deacetylase, peptidoglycan DD-metalloendopeptidase, glyceraldehyde-3-phosphate dehydrogenase, trypsin-like peptidase, and an extracellular solute-binding protein. These proteins potentially interact with the agr system, influencing S. aureus virulence. Additionally, the virulence of S. aureus was notably affected by modifications in iron-related pathways and components of cell wall architecture in the presence of H. kunzii. Furthermore, the overall metabolism of S. aureus was reduced when cocultured with H. kunzii. Conclusion: Future research will focus on elucidating the role of these excreted factors in modulating virulence. [ABSTRACT FROM AUTHOR]

Assessing the responses to the application of photobiomodulation using red and infrared spectrum light-emitting diodes (LED) on diabetic foot ulcers. Diabetic volunteers, of both genders, aged between 30 and 65 years, with grade I or II ulcers, were randomized into the groups: red LED, infrared LED, LED associated, and control. Home-based interventions took place on a daily basis for 12 weeks. Assessments of sample characterization were performed on day 1 and 90, and the variables wound healing index, mean skin temperature, sensitivity and pain in the wound area were measured at the pre-intervention time on days 1, 30, 60 and 90, with subsequent follow-up 30 days after the end of treatment. For statistical analysis, the software SPSS, version 17.0, intention-to-treat analysis, data normality was tested, and the linear mixed effects model, with a significance level of 5%. Magnitudes of clinical effect by Cohen's d. At the pre vs post intervention time of 90 days, we found a large clinical effect of G-LED V (d=1.7) and G -LED IV (d=1.6) in relation to G-C, where these intervention groups showed a tendency for faster wound healing compared to G-C. We also observed small clinical effect of G-LED IV, which showed greater reduction in the area in relation to G-LED V (d=0.4) and G-LED A (d=0.3). Conclusion: The use of individually applied red and infrared LED phototherapy clinically tended to be more effective for the reduction of diabetic foot ulcer areas, and infrared LED was the most effective. Trial registration: NCT03250533 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: The repair of diabetic foot defects (DFD) is a major challenge in clinical practice. The purpose of this study was to investigate the difference in clinical efficacy of different flap techniques in repairing DFD wounds, and to compare the difference in clinical efficacy of anterolateral thigh perforator flap (ALTP) in repairing DFD and non-DFD. Methods: This study is a retrospective clinical study of different types of flap reconstruction in patients with DFD admitted to our hospital from January 2010 to December 2021. A total of 40 patients with DFD and 43 patients with non-DFD were included in this study. Detailed preoperative basic information, intraoperative details, postoperative complications and long-term follow-up results were collected. Result: The comorbidities, wound infection and wound duration of DFD group were more serious than those of non-DFD group. In addition, the incidence of complications was higher in DFD group, the wound healing time was longer, the aesthetic evaluation, the functional recovery rate of ankle joint and the sensory recovery effect of flaps were worse. Conclusion: In this study, it is concluded that different flap techniques can obtain better clinical efficacy in repairing DFD wounds. Compared with non-DFD wounds, the postoperative risk of DFD wounds using free ALTP flaps is higher, but the risk can be reduced by reasonable preoperative vascular examination. Free flap can deal with various irregular wounds and provide more options for clinical repair. Level of evidence: III, Case–control study. [ABSTRACT FROM AUTHOR]

Wound healing is a dynamic and intricate biological process crucial for tissue repair and regeneration. This study explores the potential therapeutic impact of non-thermal plasma generated by a hand-held cold atmospheric pressure plasma jet (C-APPJ) source on fibroblast cells (NIH/3T3) in vitro. The sequential phases of wound healing—inflammation, cell proliferation, and tissue remodelling, were assessed in the context of cell migration and oxidative stress dynamics. Typically, plasma generates a mixture of several reactive oxygen/nitrogen (ROS/RNS) species. The present study investigates the safety and efficacy of C-APPJ under distinct operating conditions (argon (GI) and argon + nitrogen (GII)) and exposure times (1 min and 3 min). Cell viability assays confirmed the non-cytotoxic nature of the cold plasma conditioned medium. The levels of ROS/RNS and malondialdehyde (biomarker of oxidative stress) in the plasma-treated samples remained comparable with the control fibroblast cells grown in normal media, suggesting the favourable modulation of ROS by the cellular antioxidant mechanisms. Accelerated wound-closure rates from 6th hour to 24th hour in all the treated groups ranged from 38.76% to 45.66%, when compared to 34.25% in the control cells. Substantial cell migration leading to 51.59% of wound closure was recorded in the argon + nitrogen (GII) group exposed for 3 min. Taken together, the potential of cold plasma to effectively heal wounds without causing prolonged oxidative stress and chronic inflammation is implicated. These outcomes suggest scope for clinical application of C-APPJ as safe and cost-effective treatment of wounds (ulcers, burns, diabetic foot) and wound disinfection. [ABSTRACT FROM AUTHOR]