Prophylactic closed incisional negative pressure wound therapy (NPWT) has emerged as a promising strategy to reduce postoperative wound complications following lower extremity amputation in patients with peripheral arterial disease (PAD). We conducted a meta-analysis to evaluate whether closed incisional NPWT reduces wound complications compared with standard wound care (SWC) in this high-risk vasculopathic population. A systematic search was performed to identify studies comparing closed incisional NPWT and SWC among patients with PAD undergoing lower extremity amputation. PubMed, Embase, Web of Science, and CINAHL were searched from inception to January 2025 using predefined search strings. Six studies met eligibility criteria and were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random-effects models as the primary analysis to account for anticipated clinical and methodological heterogeneity across studies. Leave-one-out analyses and an analysis excluding the study in which NPWT was delivered as part of a multifaceted care bundle were performed to assess robustness. A total of 893 patients were included, including 408 in the closed incisional NPWT group and 485 in the SWC group. Closed incisional NPWT was associated with lower odds of postoperative surgical site infection (SSI) (OR = 0.370; 95% CI = 0.143-0.957; P = .044) and wound dehiscence (OR = 0.224; 95% CI = 0.125-0.401; P = .008). Closed incisional NPWT was associated with lower odds of postoperative SSI and wound dehiscence following lower extremity amputation in patients with PAD. Because the evidence is predominantly observational and prediction intervals included the null value, these findings should be interpreted cautiously and confirmed in adequately powered randomized trials.

To evaluate the effectiveness of a specialist-led structured preventive educational intervention on diabetic foot outcomes in adults at risk of diabetic foot complications.Study designParallel-group randomized controlled trial with an embedded qualitative component.SettingSpecialised diabetic foot unit within a public healthcare setting.ParticipantsAdults with diabetes classified at any ulceration risk level according to the International Working Group on the Diabetic Foot were randomly assigned to the intervention or control group. Forty-two participants completed the 6-month follow-up.InterventionsThe intervention group received a specialist-led structured preventive educational programme comprising two structured group sessions in addition to standard podiatric care. The control group received standard podiatric care alone.ResultsForty-two participants completed the study. No diabetic foot ulceration occurred during the 6-month follow-up. Participants receiving the educational intervention improved disease-related knowledge, preventive self-care behaviours, and foot skin quality. Qualitative findings indicated greater confidence, emotional support, and engagement in preventive self-care.ConclusionsA specialist-led structured preventive educational intervention improved disease-related knowledge, preventive self-care behaviours, and foot skin quality in adults at risk of diabetic foot complications. These findings support the integration of structured education into routine preventive diabetic foot care.

AimThis study aimed to evaluate and quantify the mechanical offloading methodological robustness of RCTs cited in the 2023 IWGDF interventions to enhance healing recommendations.MethodsA meta-research audit was conducted on 43 RCTs referenced in IWGDF guideline. A predefined framework assessed study characteristics, offloading system, adherence and activity monitoring, protocol implementation and symmetry, and mechanical offloading confounding risks. Trials were evaluated using a 10-point Offloading Quality Score (OQS), scale. Descriptive analyses and exploratory statistical tests) were performed.ResultsThe mean OQS was 2.07 (SD ± 2.83), with a median of 0 (IQR 0-4). Twenty-seven trials (62.79%) scored ≤2/10, while only three (7%) achieved scores ≥8/10. Offloading strategies were insufficiently described in 81.4% of studies, and adherence monitoring was absent in 88.4% of trials. Non-removable offloading devices were used in 7% of studies and were positively associated with higher OQS in regression analysis (β = 0.82, p < 0.001).ConclusionsMost RCTs underpinning the 2023 IWGDF recommendations demonstrate limited reporting and standardization of mechanical offloading. This may introduce unmeasured variability in mechanical exposure and could affect the interpretation of treatment effects. Future trials should standardize offloading protocols to improve internal validity and DFU research interpretation.

Diabetic foot ulcers (DFUs) complicated by chronic limb threatening ischemia (CLTI) is one of the most severe pattern of diabetic foot disease (DFD). Although significant improvements in the management of CLTI by the availability of advanced devices and the use of extreme revascularization techniques, there is still a group of patients with unreconstructable vascular disease. These patients have a high risk of major amputation and are commonly defined as no-option CLTI subjects. Nonetheless, by the recent availability of autologous cell therapy (ACT), mainly mononuclear cell therapy, the natural history of no-option CLTI seems to change by a significant improvement in the rate of wound healing and limb salvage. Therefore, authors suggest that the term "no-option CLTI" may no longer be appropriate, as these patients could still have a second chance to achieve limb salvage even after failed revascularization procedures. This editorial highlights the practical implications of ACT for diabetic foot patients with unreconstructable vascular disease, suggesting a new definition and future perspectives.

BackgroundLimited studies to date have yielded inconsistent results regarding the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and diabetic foot complications. We conducted a comprehensive analysis of the FDA Adverse Event Reporting System (FAERS) database and performed drug target Mendelian randomization (MR) studies to explore the association between GLP-1RAs and diabetic foot complications.MethodsWe mined the FAERS database from 2005q2 to 2024q2 using AERSMine. Additionally, a two-sample MR analysis was conducted to investigate the causal relationship between GLP-1R agonism and diabetic foot complications.ResultsA total of 1819 adverse event reports were recorded for GLP-1RAs, compared to 17,206 reports for other ATC-A10 class drugs. The frequency of diabetic foot reports in the GLP-1RA group was significantly lower than in the control group (6.38 vs 11.31/1000 reports), with a proportional reporting ratio (PRR) of 0.56 (95% confidence interval [CI], 0.54 to 0.59; P < 0.001). This trend was consistently observed across individual GLP-1RA molecules, including semaglutide (PRR, 0.45; 95% CI, 0.39 to 0.51), dulaglutide (PRR, 0.49; 95% CI, 0.45 to 0.54), and liraglutide (PRR, 0.30; 95% CI, 0.26 to 0.35). These results remained robust after conducting secondary and sensitivity analyses, further supporting their consistency and reliability. MR results generally corroborated the findings from the retrospective analyses of the AE records in the FAERS database.ConclusionsPharmacovigilance and drug target MR suggested a potential association between GLP-1RA use and diabetic foot complications, but the evidence is preliminary and requires further real-world prospective validation.

BackgroundPeripheral artery disease (PAD) is common in maintenance hemodialysis patients, and ankle-brachial index (ABI) may underestimate disease because arterial calcification can yield falsely normal or elevated values. Toe-brachial index (TBI) may better detect distal ischemia. This study compared PAD detection by ABI and TBI and identified factors associated with TBI-defined PAD.MethodsIn this multicenter cross-sectional study, 211 maintenance hemodialysis patients underwent ABI and TBI assessment. PAD was defined separately as ABI <0.90 and TBI <0.70 using guideline-supported thresholds. Intermittent claudication, chronic wounds and burning toe pain were recorded. Detection rates were compared using McNemar's test, and associated factors were evaluated using multivariable Poisson regression with robust variance.ResultsPAD prevalence was 13.3% by ABI and 76.3% by TBI. TBI identified more patients with PAD than ABI (p < 0.001), with 133 patients (63.0%) showing normal ABI but abnormal TBI. Among these, 9.2% had at least one clinical ischemic feature. Diabetes mellitus, older age, and longer renal replacement therapy duration were independently associated with TBI-defined PAD.ConclusionTBI identified substantially more PAD than ABI and may provide complementary information when ABI alone could miss clinically relevant ischemia. Diabetes mellitus, older age, and longer RRT duration were independent correlates of TBI-defined PAD.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus. Statins are widely used for treatment of dyslipidaemia and prevention of cardiovascular events. They also exert multiple pleiotropic effects, including improvement of endothelial function, and promotion of angiogenesis and tissue repair. Accumulating evidence suggests that these properties may be beneficial in diabetic wound healing. The aim of this comprehensive review was to summarise preclinical and clinical data regarding the potential role of statins in DFUs management. Experimental studies consistently demonstrated that statins promote wound healing through several mechanisms, including increased nitric oxide bioavailability, vascular endothelial growth factor (VEGF)-mediated angiogenesis, improved endothelial function, and increased collagen synthesis and deposition. Emerging drug-delivery strategies, including topical formulations and tissue-engineered scaffolds, further improved therapeutic efficacy. Clinical evidence remains limited but encouraging. Observational studies have reported inconsistent findings, whereas randomised controlled trials suggest that statins may reduce ulcer recurrence and accelerate wound healing without significant safety concerns. Overall, the evidence supports a strong biological rationale for the use of statins as adjunctive therapy in DFUs. However, further research is required to establish their clinical efficacy, dosage, route of administration and treatment duration.

ObjectiveTo evaluate the clinical severity and microbiological characteristics of participants with type 2 diabetes and foot ulcers (DFUs) screened for eligibility into a bacteriophage therapy pilot study.Research Design And MethodsAdults aged (≥18 years) with type 2 diabetes mellitus (T2DM) and active DFUs presenting to a tertiary care centre were screened using predefined eligibility criteria. Ulcers were graded according to the University of Texas Diabetic Foot Classification System. Microbiological analysis included standard culture techniques and biochemical tests for identification of microorganism. Descriptive statistics were used to summarize ulcer severity, microbial patterns, and eligibility outcomes.ResultsA total of 595 individuals were screened. Grade 3 ulcers accounted for 51.1% of cases, followed by Grade 2 (29.1%) and Grade 1 (19.8%). Monomicrobial infections were identified in 63.7% of individuals, polymicrobial infections in 17.6%, and no growth in 18.7%. Gram-negative organisms predominated, including Pseudomonas spp. (n = 74), Escherichia spp. (n = 60), Klebsiella spp. (n = 50), Proteus spp. (n = 43), and Acinetobacter spp. (n = 25). Among Gram-positive organisms, Staphylococcus spp. (n = 81) and Enterococcus spp. (n = 43) were common.ConclusionsThe screened population demonstrated a high burden of advanced Grade 3B DFUs, predominantly associated with Gram-negative pathogens amenable to bacteriophage targeting. But this pilot study intentionally focused on Grade 1B and Grade 2B ulcers to assess the feasibility and safety of bacteriophage therapy in predefined, less severe DFUs. This pre-screening process supported the feasibility and enrollment of eligible participants for the subsequent bacteriophage therapy pilot study.

AimTo measure serum levels of Pentraxin-3 (PTX-3) and Netrin-1 in diabetic patients with and without foot ulcers and determine how these levels relate to clinical features, glycemic control, and ulcer status.MethodsIn this cross-sectional study, 80 patients were divided into three groups: infected diabetic foot ulcer (IDFU, n = 27), non-infected diabetic foot ulcer (NIDFU, n = 27), and diabetes control (n = 26). Biochemical, demographic, and clinical data were gathered. PTX-3 and Netrin-1 levels in serum were measured using ELISA. ANOVA, regression, and correlation analyses were used to assess biomarker relationships and group comparisons.ResultsAcross all groups, there was a significant increase in fasting blood glucose, HbA1c, and diabetes duration. There was no significant difference in PTX-3 levels. Netrin-1 levels were linked with HbA1c (r = 0.37) and fasting blood glucose (r = 0.41) and were higher in both ulcer groups (p < 0.001). While PTX3 performed poorly (AUC = 0.518-0.576), Netrin-1 exhibited good diagnostic accuracy for differentiating IDFU and NIDFU from DM (AUC = 0.891 and 0.855, respectively). Netrin-1 did not, however, distinguish infected from non-infected ulcers (AUC = 0.510).ConclusionElevated serum Netrin-1 levels and their positive association with glycemic indices suggest a potential role for Netrin-1 in diabetic foot ulceration, whereas PTX-3 showed no significant associations.

AimsCharcot neuro-osteoarthropathy (CN) is a rare but severe diabetes-related complication characterized by neuropathy, inflammation, and progressive bone and joint destruction. Advanced glycation end products (AGEs) may contribute to diabetes complications through protein glycation and activation of AGE-receptor for AGE (RAGE)-associated inflammatory and oxidative-stress pathways. This cross-sectional case-control study compared AGEs, soluble RAGE (sRAGE), and oxidative-stress markers among individuals with diabetes and CN (DM/CN), individuals with diabetes without CN (DM/noCN), and healthy controls.Research Design and MethodsThis was a case-control study on 15 people with active or chronic DM/CN, 33 individuals with DM/noCN and 26 age-matched healthy controls. Subjects underwent thorough clinical evaluation; AGEs were measured in lens via autofluorescence and in serum samples. Serum levels of sRAGE and reactive oxygen markers were also determined.ResultsParticipants with DM/CN had higher lens and serum AGE levels and oxidative stress than those with DM/noCN. Both diabetes groups had higher AGEs, sRAGE, and oxidative-stress levels than healthy controls. AGEs, sRAGE, and oxidative stress were associated with peripheral neuropathy, and CN was independently associated with higher circulating AGE concentrations after adjustment for HbA1c and BMI.ConclusionsIndividuals with diabetes and CN exhibit increased AGE accumulation and oxidative stress compared with individuals with diabetes without CN. These findings support a potential role for AGE-associated inflammatory and oxidative-stress pathways in the pathophysiology of CN. Larger prospective studies are needed to determine the clinical and prognostic value of AGEs, sRAGE, and oxidative-stress markers in CN.

Diabetic foot ulcers frequently lead to amputation, and early risk identification remains challenging. Although the neutrophil-to-lymphocyte ratio (NLR) may predict amputation risk, supporting evidence remains limited. This study evaluated the association between NLR and amputation risk in patients with diabetic foot (DF). We systematically searched PubMed, Embase, Scopus, Cochrane Library, and Web of Science up to May 31, 2026. Studies reporting NLR value in DF patients with and without amputation were included. The primary outcome was the pooled mean difference (MD) in NLR between groups. Additionally, We performed a diagnostic accuracy analysis extracting sensitivity and specificity. Odds ratios (ORs) for amputation based on NLR were summarized descriptively. Study quality was assessed with the Newcastle-Ottawa Scale (NOS). Fifteen studies comprising 2757 patients were included. The amputation group had significantly higher NLR than the non-amputation group (pooled MD 3.66, 95% CI 2.60-4.71; I[2] = 81%). For major versus minor amputation, the pooled MD was 4.00 (95% CI 1.81-6.19; I[2] = 96%). Diagnostic analysis showed moderate discriminatory ability (area under the curve [AUC] 0.798), with a pooled sensitivity of 0.71 (95% CI 0.66-0.75), specificity of 0.71 (95% CI 0.66-0.75), and a diagnostic odds ratio of 6.85 (95% CI 3.54-13.27). Furthermore, studies reporting ORs indicated a positive association between elevated NLR and amputation risk. In conclusion, elevated NLR is significantly associated with amputation risk in DF patients, including major versus minor amputation. Diagnostic analysis suggests moderate discriminatory ability. However, substantial heterogeneity was observed across studies, which warrants caution in interpreting the pooled estimates. Despite this limitation, NLR remains a valuable, cost-effective biomarker for identifying high-risk patients, particularly in resource-limited settings.