Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition. Diabetic peripheral neuropathy, a common complication of diabetes, is characterized by nerve damage due to high blood sugar levels that lead to symptoms, such as pain, tingling, and numbness, primarily in the hands and feet. The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy, while also examining recent developments in this domain. The investigation encompassed an array of neuromodulation methods, including frequency rhythmic electrical modulated systems, dorsal root ganglion stimulation, and spinal cord stimulation. This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy. Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments. Through these efforts, we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

: Diabetic foot ulcer (DFU) is one of the main health challenges of diabetes complications worldwide. A wide range of factors may increase the risk of DFU. This study aimed to investigate the risk factors of DFU among diabetic patients.

This case-control study was conducted on 800 diabetic patients at the Tehran diabetes clinic of the Endocrinology and Metabolism Research Institute in Iran. The case group included 400 diabetic patients diagnosed with DFU, while the control group included 400 diabetic patients without DFU. Data were collected through medical records, validated questionnaires, and clinical examinations. The association between factors and the risk of DFU was analyzed using both crude and adjusted logistic regression models, adjusting for confounders based on a directed acyclic graphs.

The final adjusted model demonstrated significant direct associations between the risk of DFU with a longer duration of diabetes, a history of previous DFU, peripheral neuropathy, retinopathy, high blood pressure, severe kidney function loss, and good foot self-care. However, there were significant inverse associations between DFU risk with female gender, higher education levels, being married, use of oral diabetes drugs, higher hemoglobin levels, and high physical activity.

The risk of DFU was significantly associated with the following factors: diabetes duration, previous DFU history, peripheral neuropathy, retinopathy, blood pressure, kidney function, foot self-care, gender, education levels, marital status, diabetes drugs, hemoglobin levels, and physical activity. Further studies, especially ones in multicenter cohorts with a special focus on novel risk factors, are warranted to expand on our findings.

The online version contains supplementary material available at 10.1007/s40200-025-01582-z.

ObjectivesTotal contact casting (TCC) is used to promote wound closure in diabetic foot ulcers (DFUs); however, this technique is underused today. This study aims to further evaluate the efficacy of TCC in a large cohort, including patients with peripheral artery disease (PAD).MethodsThis was a retrospective analysis of patients with DFUs who underwent TCC from 2017 to 2021. PAD was defined as absence of pedal pulse or ABI <0.9. Demographic data, DFU characteristics, and peripheral arterial intervention were evaluated. Outcomes included complete healing, healing time, and rate of major amputation. Subgroup analysis was performed on patients undergoing peripheral intervention.Results152 patients underwent TCC. Mean age was 58.8 ± 12.1 years, 79.6% were male, and 26.3% had PAD. Mean DFU size was 8.27 ± 9.9 cm2, with mean depth 0.61 ± 0.49 cm. 112 patients had palpable pedal pulses on the affected extremity (73.7%). Average ABI was 1.12 ± 0.22 (n = 90). Complete healing was observed in 122 (80.3%) patients, with average healing time of 81.5 ± 57.1 days. Thirteen (8.6%) patients eventually required amputation (3 major). When compared to patients with healed DFUs, those without healing had higher rates of amputation (39.1% vs 3.1%, P < .001), intervention (43.4% vs 17.8%, P = .006), and noncompliance (39.1% vs 20.2%, P = .046). Thirty-three patients underwent revascularization, undergoing angioplasty (81.8%), atherectomy (63.6%), stent (15.2%), and/or bypass (9.1%). Interventions were performed in aortoiliac (3.0%), femoropopliteal (45.5%), and tibial (72.7%) segments. Twenty-two (66.7%) patients who underwent revascularization completely healed. Patients requiring revascularization were more likely to have previous intervention (57.6% vs 13.4%, P < .0001) and incompressible vessels (36.4% vs 7.6%, P < .00001), with lower ABIs (0.94 ± 0.25 vs 1.17 ± 0.18, P = .0008) compared to patients without intervention.ConclusionsTCC remains an effective option for treatment of DFUs, as most were completely healed. Patients with PAD may benefit from TCC and revascularization, however, healing rates are lower in this cohort, necessitating the need for close observation.

Diabetic or diabetic infectious wounds pose a global challenge, marked by delayed healing and high amputation/mortality rates. This study of participating transcriptomes and their regulators unveils critical alterations.

Transcriptome data from GEO analyzed DEGs in diabetic foot ulcers vs. controls using RNA-Seq, limma, STRINGdb, Cytoscape, and clusterProfiler for PPI networks and functional enrichment. TRRUST database was used to predict transcriptional factors (TFs). Adverse molecular pathology in different models of wounds (non-diabetic, acute diabetic, diabetic infectious wounds) was validated by RT-PCR, Western blotting, oxidative stress markers, cytokines, and histological analysis.

RNA-Seq dataset 'GSE199939' was analyzed after normalization to identify DEGs (total 47 DEG, 31 upregulated, 16 downregulated) in diabetic wound healing using limma. PPI networks revealed seven hub genes which were further processed for functional enrichment and highlighted oxidative stress, ECM remodeling, AGE-RAGE, and IL-17 signaling in diabetic wound pathology. Additionally, 17 key TFs were identified as hub gene regulators. The healing rate was significantly impaired in diabetic wounds, with delayed contraction, elevated pro-inflammatory cytokines, oxidative stress, reduced anti-inflammatory cytokines, antioxidants, angiogenesis, collagen deposition, and re-epithelialization. Further, RT-PCR and Western blot analysis validated the expression of target genes including the overexpression of HSPA1B, FOS, and down-expression of SOD2, COL1A1, and CCL2, whereas TFs including upregulation of RELA, NFKB1, STAT3, and downregulation of SP1 and JUN in diabetic and diabetic infectious wounds.

Molecular analyses reveal disrupted oxidative stress, ECM remodeling, and inflammatory signaling in diabetic and diabetic infectious, emphasizing impaired healing dynamics and identifying therapeutic targets.

Bone marrow mesenchymal stem cell (BM-MSC) dysfunction and poor viability are prominent in diabetes and limit their therapeutic efficacy. A proteomic investigation was performed to assess disease associated alterations and the efficacy of antioxidants to rescue cellular function. BM-MSCs were isolated from obese diabetic mice (B6.Cg-Lepob/J) cultured in the presence or absence of N-acetylcysteine (NAC) and ascorbic acid-2phosphate (AAP). Label free Liquid Chromatography and Mass Spectrometry (LC-MS) analysis detected 5079 proteins with 251 being differentially expressed between treatment groups. NAC/AAP improved cellular growth/viability post isolation by up-regulating proteins involved in redox status, ATP synthesis, Rho-GTPase signaling and modulated the immunophenotype of BM-MSCs. Despite a single application of the secretome not providing any advantage for wound bed regeneration in full thickness excisional diabetic wounds, the intracellular proteome illustrated the potential mechanisms of action by which NAC/AAP targeted the respiratory chain and modulated the immune phenotype of BM-MSCs. Given these observations, antioxidant supplementation might be more effective as prophylactic strategy to protect MSCs against functional decline instead of using it as a restorative agent and warrants further investigation.

Diabetic foot ulcers (DFUs) are a prevalent and severe complication of diabetes, leading to significant morbidity, impaired health-related quality of life (HRQoL) and economic burden on healthcare systems. The complexity of DFUs often results in prolonged healing and high recurrence rates. Effective management strategies are crucial for improving outcomes and reducing complications.

This study aimed to review the efficacy of antiseptic solutions in the treatment and care of DFUs.

A literature analysis was conducted to review clinical studies and guidelines on the use and efficacy of antiseptic solutions, particularly Octenisept® (0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol). The review focused on the antimicrobial properties, biofilm-disruption capabilities and wound healing outcomes associated with the use of antiseptic solutions in DFU management.

Antiseptic solutions have potential to reduce bioburden, disrupt biofilm and modulate healing. There is a need to balance antimicrobial clinical efficacy with tolerability and cytotoxicity. The use and choice of adjunctive antiseptic solutions must be tailored to the patient, as antimicrobial efficacy can vary for antiseptic solutions, particularly for hypochlorous solutions. It is important to use products according to their instructions, with consideration of minimum contact time to maximise clinical efficacy. Low-pressure irrigation is adjunctive, and concurrent wound-bed preparation, including debridement, frequent inspection, infection and moisture control, remain important.

The therapeutic application of antiseptic solutions in DFU care presents a promising approach to enhancing wound healing and reducing infection risks. Integrating these solutions into standard wound care protocols could lower the incidence of complications, improve HRQoL and decrease the economic burden associated with diabetic foot disease. Further large-scale studies are recommended to validate these findings and refine guidelines for antiseptic use in DFU management.

The chronic diabetic wounds represented by diabetes foot ulcers (DFUs) are a worldwide challenge. Excessive production of reactive oxygen species (ROS) and persistent inflammation caused by the impaired phenotype switch of macrophages from M1 to M2 during wound healing are the main culprits of non-healing diabetic wounds. Therefore, an injectable DMM/GelMA hydrogel as a promising wound dressing was designed to regulate the mitochondrial metabolism of macrophages via inhibiting succinate dehydrogenase (SDH) activity and to promote macrophage repolarization towards M2 type. DMM/GelMA hydrogel exhibited good biocompatibility, injectability and water absorption and retention capacity. In vitro studies showed that DMM/GelMA hydrogel inhibited SDH activity, recovered the decrease in mitochondrial membrane potential, and significantly reduced the production of ROS and inflammatory cytokines in the LPS-evoked macrophages. In vivo evaluations and RNA sequencing analysis demonstrated that DMM/GelMA hydrogel downregulated ROS generation, the ratio of M1/M2 macrophages and pro-inflammatory cytokine production in the full-thickness skin wound model in the diabetic mice. Additionally, DMM/GelMA hydrogel improved the wound-healing quality with thicker epidermis, more collagen deposition and higher ratio of collagen I/III by sustained release of DMM. These findings indicate this hydrogel has a great potential to be a biocompatible, injectable and anti-inflammatory dressing for better diabetic wound healing.

The Western Pacific Region hosts the largest proportion of people with diabetes. Despite being a key diabetes-related complication, diabetic foot ulcer has been neglected in both prevention and treatment efforts. This narrative review highlights available data on the burden (either prevalence or incidence), as well as microbial profiles of diabetic foot ulcers in the Western Pacific Region, identifies data gaps, and discusses strategies to address these gaps. There are substantial gaps in epidemiological data and microbial profiles for many countries in the Western Pacific Region. Addressing these gaps require developing and strengthening data collection systems for effective surveillance and benchmarking of diabetes care.

The present study aimed to investigate the effects and underling mechanisms of cardiomyocyte-specific STING knockout on cardiac function and wound healing in diabetes.

In this study, type 2 diabetes was induced in cardiomyocyte-specific STING knockout mice using a combination of a high-fat diet and streptozotocin. Cardiac function and remodeling were assessed by echocardiography and histopathological analysis. Glucose homeostasis was evaluated through insulin sensitivity tests and intraperitoneal glucose tolerance tests. Wound healing was quantified by measuring the wound area in diabetic mice.

The results demonstrated that STING deletion in cardiomyocytes improved cardiac function in diabetic mice, which was accompanied by enhanced insulin sensitivity and improved glucose tolerance. Furthermore, the deletion of STING partially mitigated mitochondrial dysfunction in the myocardium. STING knockout in cardiomyocytes also facilitated angiogenesis and wound healing in diabetic mice.

Our findings suggest that cardiomyocyte-specific STING deletion enhances cardiac function, glucose homeostasis, and wound healing, indicating that targeting STING in the heart may serve as a promising therapeutic strategy for managing diabetes mellitus.

This study examines the relationship between the TyG index and the risk of sudden cardiac death (SCD) in the patients with diabetic foot ulcer (DFU).

688 type 2 diabetes mellitus (T2DM) inpatients with DFU between January 2010 and December 2023 was included in this retrospective study. The 1:1 propensity score matching (PSM) method was applied. The relationship between TyG index and SCD risk was analyzed using the Kaplan-Meier (K-M) survival curve analysis, multivariate Cox proportional hazard regression model, Restricted cubic spline (RCS) model analysis and subgroup analyses.

Over a median follow-up period of 61 months, 38 cases of SCD were recorded. After PSM, 71 pairs of score-matched patients according to TyG index were generated. K-M survival curves revealed higher SCD rates in patients with TyG index ≥9.65. The Cox proportional hazard model, independently associated with the risk of SCD (HR: 75.98; 95 % CI: 9.16 ∼ 630.40; P < 0.001). RCS model showed that SCD risk was non-linearly correlated with gradual increases in TyG index levels. Stratified analyses indicated a consistent relationship between increasing TyG index and SCD risk across all subgroups.

Elevated TyG index independently confers an increased risk for SCD in individuals with DFU.

Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot.

Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness.

In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm).

S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.

Shengji-Huayu (SJHY) formula has been used clinically for diabetic ulcer (DU) treatment. The transcriptional profiles analysis revealed the PI3K/Akt signaling pathway plays a critical role for diabetic wound healing. However, the effects and underlying mechanisms of SJHY are often challenging in diabetic wound treatment.

To explore the novel monomers recipe and mechanism of SJHY treated diabetic wound via the in vivo and in vitro experiments.

The diabetic wound mice model was established to evaluate the therapeutic efficacy of SJHY treated diabetic ulcer. The transcriptional profile was implemented to identify the differentially expressed genes (DEGs) of SJHY treated diabetic wound mice. The constructed PPI network and KEGG-target network were used to identify the core pathway and related targets. The HPLC-MS method was used to identify the ingredients of SJHY formula. The molecular docking and in vitro experiment was used to screen which monomers regulated core pathway in diabetic wound. Finally, a novel monomers recipe was performed for diabetic wound healing.

The in vivo experiment demonstrated SJHY formula significantly promoted diabetic wound healing. Transcriptomic and network analysis revealed the existence of PI3K/Akt signaling pathway was high correlated with SJHY treated diabetic wound. The HPLC-MS and molecular docking revealed that Calycosin (Cal) and Dehydromiltirone (DHT) were strongly targeting Itga6 and Thbs1. The mRNA and protein levels suggested that Itga6 and Thbs1 acted as important upstream regulators of PI3K/Akt signaling pathway in diabetic wound, and the in vitro experiments revealed Cal, DHT and their recipe were significantly increased the levels of Itga6, Thbs1, PI3K and Akt in MGO induced HaCaT cells.

SJHY formula has therapeutic efficiency for diabetic wound healing, and Cal and DHT may be a part of the important monomers that alleviate inflammation via activating the PI3K/Akt signaling pathway by regulated Itga6 and Thbs1. Our study demonstrated Cal and DHT formed a novel monomers recipe, which may be one of the critical strategies of SJHY formula promote diabetic wound healing.

Hydrogels are three-dimensional structures that replicate natural tissues' extracellular matrix (ECM). They are essential for transporting exudates, gases, and moisture and facilitating cellular interactions in tissue engineering and wound healing. The choice of primary material in designing the scaffold is necessary to be paid more attention rather than common sources, including plant fibres like cotton, bamboo, and algae, as well as bacterial and marine-derived materials. Among them, cellulose-based polymers are especially valued for their biocompatibility and ability to promote wound healing. Chronic diabetic wounds pose unique treatment challenges, such as necrosis and infection risks. Consequently, a growing interest is in incorporating bioactive molecules into cellulose-based hydrogels. This article investigates how these infused hydrogels enhance the healing process in chronic diabetic wounds, examining various loading and crosslinking techniques alongside their clinical applications. It also discusses the benefits and limitations of bioactive molecules and their interactions with hydrogels to improve treatment strategies.

This review examines the role of fibrates and the selective PPAR-alpha modulators (SPPARM-α), pemafibrate, in diabetic microvascular disease. It reviews their potential to mitigate residual risk in retinopathy, nephropathy, neuropathy and peripheral vascular disease.

These pharmacotherapies, beyond their lipid-lowering effects, may exert anti-inflammatory, antioxidant, and endothelial-protective actions. Secondary analyses of large clinical trials supports their efficacy in slowing retinopathy progression, reducing albuminuria, and preventing minor amputations. Recent analyses suggest that pemafibrate offers an enhanced efficacy and safety profile compared to conventional fibrate and may lower the incidence of diabetic foot ulcers and gangrene. Fibrates and SPPARM-α agonists represent promising therapies to prevent diabetic microvascular complications. Their benefits in reducing microvascular damage support their broader adoption in clinical practice. However, additional dedicated randomized trials are essential to validate the efficacy of those agents in contemporary diabetes care era and to address the growing burden of diabetes-related microvascular complications.

Significance: Diabetic foot ulcer (DFU) is a common complication of diabetes, characterized by chronic, hard-to-heal wounds that can lead to serious infections and amputations. Effective self-management is crucial for treatment and prevention. Recent Advances: A comprehensive literature search was conducted across academic databases, clinical practice guideline (CPG) databases, and the websites of diabetes societies. The characteristics, recommendations, and evaluation criteria of the CPGs were extracted and organized using Excel. Four researchers independently assessed the methodological and reporting quality of the CPGs using the Appraisal of Guidelines Research and Evaluation II instrument and the Reporting Items for practice Guidelines in HealThcare checklist. Data were synthesized and visualized through evidence mapping to provide an overview of current guideline coverage and key recommendations. Critical Issues: This study included 13 CPGs and synthesized 46 recommendations. Self-management strategies for patients with DFU mainly involve health education, foot self-care, lifestyle change, comorbidity/symptom management, as well as follow-up and medical help-seeking. The identified CPGs were of mixed quality, with four classified as high quality. With respect to methodology, the CPGs performed well in scope and purpose (82.6%±10.9%) and clarity (80.77%±9.19%), but showed deficiencies in stakeholder involvement (52.8%; interquartile range [IQR]: 17.3%) and editorial independence (58.3%; IQR: 82.3%). For reporting quality, limitations were noted in transparency regarding review and quality assurance (18.75%; IQR: 100%), as well as funding and declaration of interests (12.5%; IQR: 32.82%). Future Directions: The evidence provided by CPGs for DFU self-management varied in strength, and some recommendations were inconsistent. The results adds to our knowledge and promotes the development of trustworthy CPGs on DFU. Further research is necessary to propose more evidence-based and high-quality recommendations.

With the increase in the incidence of diabetes mellitus (DM) in recent years, diabetic foot ulcers (DFU), which are common and serious chronic complications of diabetes, have also become widespread. DFU is highly associated with a significant deterioration in quality of life as well as increased morbidity and mortality. Meteorin is a potent neurotrophic growth factor and shows antiangiogenic, antihyperalgesic, antinociceptive and neuroprotective effects. This study aimed to determine the possible relationship between meteorin, diabetes and diabetic foot ulcer by comparing the serum meteorin levels of healthy control group, DM patients and patients with diabetic foot ulcers.

Our study included a total of 62 diabetic patients, 31 of whom had DFU, and 29 healthy individuals as a control group. Meteorin levels of the participants were measured using ELISA method in serum samples. Other laboratory and epidemiological data of the patients were obtained from the hospital database.

In the wound cultures taken from patients with DFU, the most commonly isolated bacteria were Staphylococcus aureus and Pseudomonas aeruginosa. Serum meteorin levels were found to be statistically significantly higher in diabetic patients as compared to the healthy control group, and among diabetic patients, those with DFU had significantly higher levels compared to those without DFU. A positive significant correlation was found between meteorin level and age, HbA1c, WBC, urea, sedimentation, CRP and ferritin.

The results of our study, aimed at better understanding the biological functions and potential clinical applications of meteorin, suggest that meteorin could potentially be used as a biomarker for the development of DFU.

The human-centered design approach has gained prominence in the development of mobile health solutions. However, its application to support foot self-care for persons with diabetes has not been extensively explored. This study aims to develop a mobile application prototype using a human-centered design approach to support foot self-care for persons with type 2 diabetes. The project used mixed methods, including a scoping review, patient interviews, a Delphi panel, and an acceptability and usability study of an educational booklet. This three-phase approach encompassed defining the context of use, specifying user requirements, and developing design solutions. This article specifically details the third phase of the project: the development of the low-fidelity prototype. Functionalities such as daily reminders for foot care, notifications for medical appointments, communication features with healthcare professionals and peers, and repositories of videos and educational content were integrated into the design. These features were tailored to address user needs, emphasizing knowledge enhancement in self-care practices. The human-centered design approach enabled the creation of a comprehensive prototype with essential functionalities and robust educational content, filling gaps in the digital health market and empowering persons to better manage their foot health.

Diabetic wounds are blocked in the inflammatory stage, growth factors are degraded, and blood vessels are difficult to regenerate, leading to continuous necrosis and nonhealing of the wound. Hydrogen sulfide (H2S) plays an important role in the pathophysiological process of wound healing and has a long history of treating skin diseases. Although the sulfide salt solution is the preferred donor of exogenous H2S, its rapid release rate, excess production, and difficulty in accurately controlling the dose limit its use. Herein, we developed H2S sustained-release nanospheres NaHS@MS@LP for the treatment of diabetic wounds. NaHS@MS@LP nanosphere was composed of a NaHS-loaded mesoporous silicon core and a DSPE-PEG liposome outer membrane. When NaHS@MS@LP nanospheres were used to treat the wound of diabetic rats, mesoporous silicon was delivered into the cells and the loaded NaHS slowly released H2S through hydrolysis, participating in all stages of wound healing. In conclusion, NaHS@MS@LP nanospheres regulated the inflammatory microenvironment of wound skin by inducing the transformation of macrophages into M2 type and promoted angiogenesis and collagen deposition to accelerate wound healing in diabetic rats. Our findings provide strategies for the treatment of chronic wounds, including but not limited to diabetic wounds.

Diabetic foot ulcers (DFUs) are a major complication of diabetes, leading to high morbidity, mortality, and healthcare costs. Current DFU risk stratification relies on clinical examination, which can be subjective. Electrochemical Skin Conductance (ESC), measured via Sudoscan, offers an objective assessment of small fiber dysfunction. This study evaluates the association between ESC and DFU risk stratification.

A retrospective analysis of 2,157 diabetic patients from four tertiary centers in France was conducted. DFU risk was classified using the 2016 International Working Group on Diabetic Foot (IWGDF) grading system. ESC measurements were analyzed alongside age, sex, diabetes type, and monofilament test results. Regression and ROC analyses assessed predictive performance.

ESC values correlated with DFU grades (p<0.001), with lower foot ESC (FESC) in higher-risk patients. ROC analysis showed strong predictive value for severe DFUs (AUC = 0.82 for grade 3) but limited performance for early stages. Notably, ESC identified at-risk patients within grade 0, undetected by standard classification.

ESC provides a reproducible, operator-independent tool for DFU risk assessment, improving early detection beyond monofilament testing. These findings support its potential role in DFU prevention, reducing amputations and enhancing patient outcomes. Further studies are needed to validate its prognostic value and integration into clinical care.

Diabetic foot (DF) is a major public health concern. As evident from numerous previous studies, supervision of DF ulcer (DFU) is crucial, and a specific quality check-up is needed. Patients should be educated about glycaemic management, DFUs, foot lesions, proper care for injuries, diet, and surgery. Certain reasonably priced treatments, such as hyperbaric oxygen and vacuum-assisted closure therapy, are also available for DFUs, along with modern wound care products and techniques. Nonetheless, DF care (cleaning, applying antimicrobial cream when wounded, and foot reflexology), blood glucose monitoring to control diabetes, and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs. Between 50% and 80% of DF infections are preventable. Regardless of the intensity of the lesion, it needs to be treated carefully and checked daily during infection. Tissue regeneration can be aided by cleaning, dressing, and application of topical medicines. The choice of shoes is also important because it affects blood circulation and nerve impulses. In general, regular check-ups, monitoring of the patient's condition, measuring blood glucose levels, and providing frequent guidance regarding DFU care are crucial. Finally, this important clinical problem requires involvement of multiple professionals to properly manage it.

The risk factors and prediction models for diabetic foot (DF) remain incompletely understood, with several potential factors still requiring in-depth investigations.

To identify risk factors for new-onset DF and develop a robust prediction model for hospitalized patients with type 2 diabetes.

We included 6301 hospitalized patients with type 2 diabetes from January 2016 to December 2021. A univariate Cox model and least absolute shrinkage and selection operator analyses were applied to select the appropriate predictors. Nonlinear associations between continuous variables and the risk of DF were explored using restricted cubic spline functions. The Cox model was further employed to evaluate the impact of risk factors on DF. The area under the curve (AUC) was measured to evaluate the accuracy of the prediction model.

Seventy-five diabetic inpatients experienced DF. The incidence density of DF was 4.5/1000 person-years. A long duration of diabetes, lower extremity arterial disease, lower serum albumin, fasting plasma glucose (FPG), and diabetic nephropathy were independently associated with DF. Among these risk factors, the serum albumin concentration was inversely associated with DF, with a hazard ratio (HR) and 95% confidence interval (CI) of 0.91 (0.88-0.95) (P < 0.001). Additionally, a U-shaped nonlinear relationship was observed between the FPG level and DF. After adjusting for other variables, the HRs and 95%CI for FPG < 4.4 mmol/L and ≥ 7.0 mmol/L were 3.99 (1.55-10.25) (P = 0.004) and 3.12 (1.66-5.87) (P < 0.001), respectively, which was greater than the mid-range level (4.4-6.9 mmol/L). The AUC for predicting DF over 3 years was 0.797.

FPG demonstrated a U-shaped relationship with DF. Serum albumin levels were negatively associated with DF. The prediction nomogram model of DF showed good discrimination ability using diabetes duration, lower extremity arterial disease, serum albumin, FPG, and diabetic nephropathy (Clinicaltrial.gov NCT05519163).

The poor prognosis of diabetic foot ulcers (DFUs) often leads to amputation and high mortality rates, becoming a heavy economic burden on the healthcare system. Several clinical studies have been conducted to investigate the risk factors for DFU mortality and to provide clinical guidance for better prevention and control of DFU mortality.

We used R to organize the mortality data of patients with DFU, collected from the NHANES database during the 1994-2004 period, along with three kidney function indicators including Albumin-to-Creatinine Ratio (ACR), estimated Glomerular Filtration Rate (eGFR) and cystatin C, used to assess chronic kidney disease (CKD). We explored the relationship between CKD and the risk of death in DFU patients through multiple kidney function indicators. Baseline characteristics of the surviving group and the mortality group of patients with DFU were analyzed using the 'svyby' function in the 'survey' package. We used Kaplan-Meier curves, multivariable logistic regression models, Cox proportional risk regression models, and time-dependent ROC curves to analyze the relationship between CKD and the risk of death in patients with DFU.

This study included a total of 112 patients with DFU. The overall sample had an average age of 65 years, with 43 females (38.39%) and 69 males (61.61%). During the follow-up time, 29 survived and 89 died. All-cause mortality in DFU patients was analyzed based on clinical classifications of ACR, eGFR, and cystatin C, with Kaplan-Meier curves illustrating survival variability. Multivariable logistic regression analysis showed no significant correlation between the risk of death in patients with DFU and CKD. However, analysis of Cox proportional risk regression model that accounted for time effects found a significant association between all-cause mortality and cystatin C levels in patients with DFU. Time-dependent ROC curve analysis demonstrated that cystatin C had superior diagnostic accuracy and stability for predicting all-cause mortality in DFU patients.

In this study, we found that cystatin C demonstrated greater stability and accuracy in assessing the risk of death and predicting mortality in patients with DFU.

Despite being a major cause of hospitalisations, there is limited literature on the trends in diabetes-related foot disease (DFD) in Victoria, Australia. The aim of this study was to assess the incidence of DFD admissions and outcomes in inpatients with DM at a major Victorian health service.

Inpatients aged >18 years with DM and DFD between 2013 and 2022 were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes. Admission, demographic and mortality data were extracted from the hospital electronic database. Prevalence and incidence of DM, DFD and amputations were analysed. Independent t tests, Mann-Whitney U tests and χ2 tests were used to compare groups. Linear regression models were used to explore trends, with logistic and Poisson regression for analysis of 5-year mortality and length of stay.

Over 10 years, 37 561 patients with DM required 110 736 admissions at Western Health. DFD prevalence was 17% (n = 6397). An increasing burden of annual DM admissions was observed (6855 to 12 182), with increased rates of DFD admissions (β = 0.480, P < 0.001). Minor amputation rates increased (β = 0.028, P = 0.001), whilst major amputation rates remained stable. DFD cohorts experienced longer admissions (median 4.11 (interquartile range 1.74-9.06) vs 1.83 (interquartile range 0.28-4.50) days, P < 0.001), higher re-admissions (76% vs 47%, P < 0.001) and 5-year mortality (23.4% vs 12.7%, P < 0.001).

This large retrospective audit demonstrated an increasing burden of inpatient DM and DFD at Western Health, Victoria in Australia, with greater morbidity and mortality in DFD patients. Health networks need to be prepared for greater health service utilisation required by DFD cohorts, and further funding to prevent DFD is of particular importance to avoid overwhelming health services.

Diabetic foot ulcers (DFUs) are a severe complication of diabetes, often leading to amputation. Hyperglycemia induced nerve and vascular damage significantly increases DFU risk. The advent of 3D printing technology presents a revolutionary concurrently address glycemic control and wound management, potentially improving patient adherence and offering a more holistic treatment strategy.

This article reviews current oral antidiabetic medications and explores the potential of innovative 3D printing technology to develop extended release tablets in two distinct release profiles. Additionally, it investigates the application of this technology in creating novel wound dressing solutions aimed at facilitating DFU healing. .

The integration of 3D printing technology enables the production of customized, extended-release oral medications that optimize glycemic control while minimizing fluctuations in blood sugar levels. Furthermore, 3D-printed wound dressings demonstrate promising potentialfor enhancing wound healing by providing personalized structural support and controlled drug delivery.

A multidisciplinary approach that integrates advanced wound care and diabetes management is crucial to address the escalating challenges posed by DFUs. Leveraging3D printing technology to develop sustained-release medications and innovative wound dressingsmay significantly improve DFU outcomes and improve the quality of life for individuals with diabetes.

Diabetic foot ulcer (DFU) represents a common and severe complication of diabetes mellitus. Effective and safe treatments need to be developed. Mesenchymal stem cells (MSCs) have demonstrated crucial roles in tissue regeneration, wound repair and inflammation regulation. However, the function is limited. The safety and efficacy of gene-modified MSCs is unknown. Therefore, this study aimed to investigate whether genetically modified MSCs with highly efficient expression of anti-inflammatory factors promote diabetic wound repair by regulating macrophage phenotype transition. This may provide a new approach to treating diabetic wound healing.

In this study, human umbilical cord-derived MSCs (hUMSCs) were genetically modified using recombinant lentiviral vectors to simultaneously overexpress three anti-inflammatory factors, interleukin (IL)-4, IL-10, IL-13 (MSCs-3IL). Cell counting kit-8, flow cytometry and differentiation assay were used to detect the criteria of MSCs. Overexpression efficiency was evaluated using flow cytometry, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, and cell scratch assay. We also assessed MSCs-3IL's ability to modulate Raw264.7 macrophage phenotype using flow cytometry and quantitative real-time PCR. In addition, we evaluated diabetic wound healing through healing rate calculation, HE staining, Masson staining, and immunohistochemical analysis of PCNA, F4/80, CD31, CD86, CD206, IL-4, IL-10 and IL-13. In addition, we evaluated the safety of the MSCs-3IL cells and the effect of the cells on several other models of inflammation.

MSCs-3IL efficiently expressed high levels of IL-4 and IL-10 (mRNA transcription increased by 15,000-fold and 800,000-fold, protein secretion 400 and 200 ng/mL), and IL-13 (mRNA transcription increased by 950,000-fold, protein secretion 6 ng/mL). MSCs-3IL effectively induced phenotypic polarization of pro-inflammatory M1-like macrophages (M1) towards anti-inflammatory M2-like macrophages (M2). The enhancement of function does not change the cell phenotype. The dynamic distribution in vivo was normal and no karyotype variation and tumor risk was observed. In a mouse diabetic wound model, MSCs-3IL promoted diabetic wound healing with a wound closure rate exceeding 96% after 14 days of cell treatment. The healing process was aided by altering macrophage phenotype (reduced CD86 and increased CD206 expression) and accelerating re-epithelialization.

In summary, our study demonstrates that genetically modified hUMSCs effectively overexpressed three key anti-inflammatory factors (IL-4, IL-10, IL-13). MSCs-3IL-based therapy enhances diabetic wound healing with high efficiency and safety. This suggests that genetically modified hUMSCs could be used as a novel therapeutic approach for DFU repair.

Small extracellular vesicles (sEVs) mediate intercellular signaling to coordinate the proliferation of cell types that promote re-epithelialization of skin following injury. Cyclin-dependent kinase 1 (CDK1) drives cell division and is a key regulator of entry to the cell cycle. To understand the potential of sEV-mediated delivery of CDK1 to reverse impaired wound healing, we generated CDK1-loaded sEVs (CDK1-sEVs) and evaluated their ability to mediate cell proliferation, re-epithelialization, and downstream signaling responses in the wound bed. We found that treatment of human keratinocytes with CDK1-sEVs increased phosphorylation of the CDK1 target, eukaryotic translation inhibition factor 4E-binding protein 1 (4E-BP1), and histone H3 within 24 h via AKT and ERK phosphorylation, driving increased proliferation and cell migration. Treatment of the wound bed of diabetic obese mice, a model of delayed wound healing, with a single dose of CDK1-sEVs accelerated wound closure, increased re-epithelialization, and promoted the proliferation of keratinocytes. These studies show that delivery of CDK1 by sEVs can stimulate selective and transient proliferation of cell types that increase re-epithelialization and promote proliferation of keratinocytes to accelerate wound healing.

Diabetic foot infections (DFIs) and diabetic foot osteomyelitis (DFO) are common and serious complications in patients with diabetes, often leading to severe morbidity (including amputation) and even mortality. Professional footcare, prompt diagnosis and appropriate treatment are crucial to preventing limb loss and improving outcomes in infections.

This narrative review addresses the management of all DFIs, including the approach to clinical evaluation, appropriate diagnostic methods, and optimal therapeutic strategies. We specifically address key areas in antibiotic therapy, and surgical interventions and techniques. Based on our literature review and extensive, multidisciplinary experience, we developed a novel treatment flowchart specifically for the management of DFO.

Managing DFIs, including DFO, requires a multidisciplinary approach tailored to each patient's clinical presentation. While antibiotics, surgery, and wound care each play a crucial role, the decision-making process should always consider the infection's severity and chronicity. Our proposed flowchart for DFO management emphasizes the importance of logically-sequenced, easy to apply and tailored interventions to prevent unnecessary amputations and improve outcomes. Further research is needed to further refine this flowchart in clinical practice and demonstrate its effectiveness.

Patients with diabetic foot ulcers (DFUs) often face significant challenges in receiving optimal care in the community. This condition can lead to serious complications if not addressed, including infection, delayed healing, amputation, decreased quality of life, financial burdens and mobility impairments. Community nurses are uniquely positioned to support DFU management, as they serve as the first point of contact for individuals managing this condition. They offer essential education on foot care and emphasise the importance of early intervention. In this context, using Salmon White's model can empower nurses to prevent these complexities effectively. However, there is a lack of nursing review studies in the literature that integrate Salmon White's model with a focus on community care for DFUs. This article, based on three case studies, proposes a paradigm of DFU care that community nurses can adopt to provide comprehensive support within the community.

There is a significant care burden on wound care patients in the acute care space. During hospitalization, additional risk factors can cause wounds to develop, particularly in the emergency room, operating room, and intensive care units. This article will highlight common wound types, their potential complications in the acute care setting, and implications for practice.

Skin wound healing is a dynamic process consisting of multiple cellular and molecular events that must be tightly coordinated to repair the injured tissue efficiently. The healing pace is decided by the type of injuries, the depth and size of the wounds, and whether wound infections occur. However, aging, comorbidities, genetic factors, hormones, and nutrition also impact healing outcomes. During wound healing, cells undergo robust processes of synthesizing new proteins and degrading multifunctional proteins. This imposes an increasing burden on the endoplasmic reticulum (ER), causing ER stress. Unfolded protein response (UPR) represents a collection of highly conserved stress signaling pathways originated from the ER to maintain protein homeostasis and modulate cell physiology. UPR is known to be beneficial for tissue healing. However, when excessive ER stress exceeds ER's folding potential, UPR pathways trigger cell apoptosis, interrupting tissue regeneration. Understanding how UPR pathways modulate the skin's response to injuries is critical for new interventions toward the control of acute and chronic wounds. Herein, in this review, we focus on the participation of the canonical and noncanonical UPR pathways during different stages of wound healing, summarize the available evidence demonstrating UPR's unique position in balancing homeostasis and pathophysiology of healing tissues, and highlight the understudied areas where therapeutic opportunities may arise.

This study focused on the potential of Gliricidia sepium (Jacq.) Kunth. ex. Walp. leaves zinc oxide nanoparticles hydrogel (GSL ZnONPs HG) for diabetic wound healing. The major components identified through HPLC analysis in Gliricidia sepium (Jacq.) Kunth. ex. Walp. leaves ethanolic extract (GSL) were apigenin-7-O-glucoside, kaempferol, and protocatechuic acid. These compounds exhibited anti-inflammatory properties. The hydrogel loaded with GSL ethanolic extract and Gliricidia sepium (Jacq.) Kunth. ex. Walp. leaves ethanolic extract zinc oxide nanoparticles (GSL ZnONPs) displayed controlled release and favorable swelling behavior. GSL ZnONPs HG enhanced tissue regeneration, reduced apoptosis, and modulated inflammation in diabetic wounds as demonstrated by wound morphology and closure measurements, as well as histopathological and immunohistochemical evaluations. It is important to highlight the dose-dependent behavior of GSL ZnONPs, demonstrating their effectiveness in promoting diabetic wound healing even at lower concentrations. This was supported by their response to various biomarkers through a significant reduction in vascular cell adhesion molecule-1 (VCAM-1) and advanced glycation end products levels (AGEs), and a notable increase in interleukin-10 (IL-10) and platelet-derived growth factor concentrations (PDGF). Collectively, the study highlights the potential of GSL ZnONPs HG as a promising approach to enhance diabetic wound healing.

The formation of lower limb arterial plaques, exacerbated by type 2 diabetes (T2D), represents an early stage of lower limb peripheral artery disease (PAD). Second near-infrared region (NIR-II) imaging is an emerging technique with high sensitivity for detecting perfusion levels. This study explores the value of NIR-II imaging in identifying perfusion changes due to lower extremity arterial plaques in T2D patients without PAD.

NIR-II imaging with indocyanine green (ICG) was conducted on 120 T2D patients, who were categorized into two groups: plaque and non-plaque. NIR-II parameters and clinical characteristics were analyzed between the two groups to identify significant predictors of lower extremity arterial plaques.

Six NIR-II imaging parameters (T start, T 1/2, Tmax, Ingress rate, Egress, and Egress rate) showed significant differences and diagnostic efficacy between the two groups. Three NIR-II parameters (T start, Egress, and Egress rate) and two clinical characteristics (age and sex) were identified as independent predictors of lower limb artery plaques. The nomogram showed that a combined model with NIR-II parameters and clinical characteristics exhibited higher diagnostic efficacy.

NIR-II imaging can effectively detect early perfusion changes in T2D patients, showing great potential for pre-diagnosis of individuals at high risk for PAD.

The high incidence and prevalence of diabetic foot ulcers (DFUs) present a substantial clinical and economic burden, necessitating innovative therapeutic approaches. Fibroblasts, characterized by their intrinsic cellular plasticity and multifunctional capabilities, play key roles in the pathophysiological processes underlying DFUs. Hyperglycemic conditions lead to a cascade of biochemical alterations that culminate in the dysregulation of fibroblast phenotype and function, which is the primary cause of impaired wound healing in DFUs. Biomaterials, particularly those engineered at the nanoscale, hold significant promise for enhancing DFU treatment outcomes. Electrospun nanofiber scaffolds, with their structural and compositional similarities to the natural extracellular matrix, serve as an effective substrate for fibroblast adhesion, proliferation, and migration. This review comprehensively summarizes the biological behavior of fibroblasts in DFUs and the mechanism mediating wound healing. At the same time, the mechanism of biological materials, especially electrospun nanofiber scaffolds, to improve the therapeutic effect by regulating the activity of fibroblasts was also discussed. By highlighting the latest advancements and clinical applications, we aim to provide a clear perspective on the future direction of DFU treatment strategies centered on fibroblast-targeted therapies.

Pseudomonas aeruginosa has gained attention in diabetic foot infections, which complicate treatment. Further research is essential to understand the prevalence and clinical impact of P. aeruginosa in diabetic foot ulcers (DFU) and to develop effective management strategies.

Samples were collected from 66 patients with DFU. The prevalence of P. aeruginosa, its antimicrobial profile, and biofilm formation were assessed by disk diffusion and crystal violet assays. The prevalence of resistance and virulence genes, including bla TEM, bla SHV, toxA, alg44, and mucA, was assessed using polymerase chain reaction. Finally, the clonality of the isolates was assessed by repetitive element polymerase chain reaction.

The highest levels of resistance were seen against ciprofloxacin, tobramycin, and imipenem, with 58.6%, 57.1%, and 55.1%, respectively. A total of 41.3% and 62.5% of the isolates were strong biofilm-producers and multidrug-resistant, respectively. The prevalence of toxA, alg44, and mucA, were reported to be 82%,93.1%, and 75.8%, respectively, and for β-lactamase genes, such as bla TEM and bla SHV, were 65.5% and 0%. Among the 28 isolates, 14 GTG types showed clonal relationships with certain strains.

These findings suggest that all clonal types were associated with the same hospital, emphasizing the need for epidemiologic surveillance of hygiene practices within healthcare facilities to mitigate strain dissemination.

Non-healing or chronic wounds in extremities that lead to amputations in patients with Type II diabetes (hyperglycemia) are among the most serious and common health problems in the modern world. Over the past decade, more efficient solutions for diabetic ulcers have been developed. Nanofibers and/or composite materials capable of drug delivery, moisture control, and antibacterial effectiveness are increasingly utilized in the formulation of wound dressings, with a particular focus on the biofunctionalization of polymeric and hydrogel materials. Natural products, including plant extracts, honey, antibacterial agents, nanozymes, and metal nanoparticles, are now commonly and effectively implemented to enhance the functionality of wound dressings. Due to the complicated and dysfunctional physiological structure of the chronic wound sites in the extremities of diabetic patients, formulated nanoscaffold or hydrogel components are becoming more intricate and versatile. This study aimed to investigate the development of wound dressing materials over the years while demonstrating their progressively enhanced complexity in effectively targeting, treating, and managing chronic wounds. The mechanisms of action and bio-functionality of wound dressing technologies were elucidated based on findings from 290 studies conducted over the last decade. A notable observation that emerged from these studies is the evolution of wound dressing development technology, which has led to significant advancements in the operational range of smart systems. These include, but are not limited to, self-healing, self-oxygenation, and adaptable mimicry of human tissue.

Diabetes is an extremely costly disease, one-third of which are attributed to the management of diabetic foot disease including chronic, non-healing, diabetic foot ulcers (DFUs). Therefore, much effort is needed to understand the pathogenesis of DFUs and novel therapeutics. We utilized exosome staining to confirm the interaction between fibroblast-derived exosomes and macrophages. Subsequently, we employed public data and qPCR to screen for upregulated miRNAs in fibroblast-derived exosomes in DFUs. The relationship between was validate miR-93-5 and ATG16L1 through data prediction and dual-luciferase reporter assays. A variety of molecular biology experiments were used for subsequent pathway validation. Additionally, we established Atg16l1MKI and Nlrp3MKO mice for further validation. We identified that miR-93-5p derived from fibroblasts played an important role in M1 macrophages polarization. Predicted by database, we found that miR-93-5p can bind to ATG16L1 mRNA, thereby influencing macrophage autophagy mediated by ATG16L1 in the clearance of ROS, thus activating the NLRP3 signaling pathway. In vivo, miR-93-5p antagomir treatment accelerated diabetic wound healing and induced M2 macrophage polarization. Fibroblasts and macrophages show cell crosstalk during the development of DFUs by miR-93-5p, and that antagomir treatment may be a promising and technically advantageous alternative to DFUs therapies.

The aim of this study was to identify and analyze the incidence rate of amputations and their risk factors in people with Diabetes Mellitus (DM) in two specialized outpatient clinics in Brazil. This is an epidemiological, retrospective cohort study using data collected from electronic health records of 281 adult diabetic patient types 1 or 2; attended in specialized outpatient service between 2015 and 2020. Statistical analyses were performed using the 2 sample t-test or Wilcoxon-Mann-Whitney test, for quantitative variables, and the Pearson's χ2 test or Fisher's exact test for categorical variables. The investigation of the risk factors for amputation was carried out through logistic regression. The study was approved by ethical committee. The sample mean age was 65.6 years (SD 13.05), predominating male gender n = 211 (75%), type 2 DM n = 223 (86.7%), with cardiovascular disease n = 143 (63.2%), and about 68.7% (n = 156) with peripheral arterial disease (PAD). Seventy-seven had lower limb amputation (LLA), with a rate incidence of 31.9% during five years. Logistic regression analysis showed the following associations with amputation: Diabetic peripheral neuropathy increased the rate of amputation by 3.6 times (OR = 3.631, 95% CI = 1.214-11.353; P = .022), and peripheral arterial disease increased by 10 times (OR = 10.631; 95% CI = 2.969-57.029; P = .001). The LLA in individuals with DM in two specialized outpatient services was higher compared to international literature; DPN and PAD were confirmed as risk factors for amputation, according to literature. This finding suggests that the study population faces an increased risk of amputation, highlighting the urgent need for targeted interventions and implementing robust preventive strategies to transform the current scenario and mitigate these severe outcomes. A comprehensive approach is essential to proactively address the underlying issues and reduce the prevalence and impact of amputations in Brazil.

Wound care patients often have a variety of chronic medical conditions that result in poor outcomes, such as delayed healing and nontraumatic limb loss. Many of these suboptimal patient outcomes result from healthcare disparities linked to social determinants of health (SDOH). Race and ethnicity influence SDOH by impacting patients' access to consistent quality healthcare. Understanding and addressing why and how ethnic and cultural factors influence SDOH is crucial for making substantial changes.

Diabetic foot infection can lead to limb amputation in approximately 17% of affected patients. Given the complex pathophysiology associated with diabetic foot infection, the goal of limb preservation is best achieved with a multidisciplinary approach and a team of providers including infectious disease consultants. However, these infections often affect populations living in nonmetropolitan areas, where access to an infectious disease physician may be limited. It may fall on the surgeons and primary care providers to not only diagnose infections early, including osteomyelitis, but also facilitate prompt, appropriate antibiotic management. The decision to treat with antibiotics alone versus surgery, choice of antibiotic, route of administration, and duration of treatment are complicated concepts that require a patient-specific approach. In addition, use of oral antibiotics and long-acting lipoglycopeptides has gained prominence and offers an alternate solution to the tedious, resource-intense process of outpatient intravenous antibiotic treatment. The goal of this article is to outline and address diagnostic and management questions that would be posed to an infectious disease consultant. The responses would include a literature review of current management concepts and highlights from the 2023 Infectious Disease Society of America and International Working Group on the Diabetic Foot guidelines.

The out-of-hospital care pathways of people with DFU have been little studied. We used the French National Health Data System (SNDS) to collect refund and care pathway data for all French residents. The aim of this study was to determine the incidence of major lower limb amputation (MA) and associated risk factors in a population with an incident DFU.

We included any person living with diabetes and incident DFU. The primary endpoint was the occurrence of MA within one year. We considered the course and consumption of care one year before and one year after the initial event.

In 2018, 133,791 people were included, and during the follow-up, MA was performed in 4,733 (3.5 %). Among these people with MAs, 16.4 % were included via the out-of-hospital part of the protocol, and their first contact with the hospital led to MA. Factors associated (hazard ratio, HR [95 % confidence interval, CI]) with MA were: being male (1.92 [1.78;2.08]), arteriopathy of the lower limb (10.16 [9.36;11.03]), psychiatric disease (1.10 [1.01;1.20]) and end-stage renal disease (2.12 [1.93;2.33]). Regarding the care pathway, associations (HR [95 %CI]) were observed between lower MA rates and people with more general practitioner (0.83 [0.75-0.91]), private nurse (0.88 [0.81-0.95]) and diabetologist (0.88 [0.81-0.95]) visits. Living in the most disadvantaged municipalities was associated (HR [95 %CI]) with a higher MA rate (1.17[1.06-1.29]).

This is the first national study of the care pathways followed by people with DFU. Failures in the care pathway, precariousness and several comorbidities were identified, with an impact on the MA risk.

Diabetic foot ulcer is a critical complication of diabetes, but the wound microenvironment and its healing process are not completely understood. In this study, we optimized single-cell profiling from sharp debrided ulcers. Our findings demonstrate that healing diabetic foot ulcers were significantly enriched with distinct fibroblasts-expressing genes related to inflammation (CHI3L1, IL6) and extracellular matrix remodeling (ASPN), validating our previous studies on surgically resected ulcers. The race-focused analysis depicted lower expression of key healing-associated genes such as CHIL3L1, matrix metalloproteinase 11 gene MMP11, and SFRP4 in fibroblasts of non-Hispanic Black patients than in those of White patients. In cellular communication analysis, healing-enriched fibroblasts of non-Hispanic Black patients exhibited upregulation of signaling pathways such as WNT, whereas those of White patients showed insulin-like GF and Midkine pathways upregulation. Our findings advocate race as a risk marker of diabetic foot ulcer outcomes, likely reflecting underlying disparities in environmental exposures and access to care that profoundly influence healing markers. Using sharp debrided tissues for single-cell assays, this study highlights the need for in-depth investigations into dysregulated wound healing microenvironments of under-represented racial groups.