Diabetic foot infections (DFIs) caused by are notoriously difficult to treat due to multidrug resistance, biofilm formation, and impaired tissue perfusion. This narrative review summarises emerging non-antibiotic and adjunctive therapies beyond conventional antimicrobial regimens. We highlight the potential of bacteriophage therapy, antimicrobial peptides, quorum sensing inhibitors, biofilm-disrupting enzymes, nanotechnology-based delivery systems, monoclonal antibodies, iron metabolism inhibitors, and photodynamic therapy. Each of these offers unique mechanisms to disrupt biofilms, neutralise virulence, or enhance immune clearance. In addition, we review advanced localized delivery platforms and diagnostic-guided personalized regimens optimizing intra-wound efficacy. Most of these novel interventions remain investigational, based on preclinical models, early-phase trials, or case reports. Nevertheless, they appear promising in managing chronic, refractory DFIs. Integration of these strategies into clinical practice will depend on robust clinical trials, regulatory clarity, and precision diagnostics. By moving beyond antibiotics, this evolving therapeutic landscape offers hope for improved outcomes in a population at high risk for limb loss and systemic complications.

Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, leading to significant morbidity, amputation risk, and healthcare burden. This systematic review and meta-analysis aimed to evaluate the association between circulating ischemia-modified albumin (IMA) levels and DFU. A comprehensive search of PubMed, Scopus, Cochrane Central and Google Scholar databases was conducted to identify eligible observational studies reporting IMA concentrations in DFU patients, diabetics without foot ulcers, and healthy controls. Meta-analyses were performed using both frequentist random-effects models and Bayesian approaches. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to express continuous outcomes. PET-PEESE regression analyses assessed publication bias and small-study effects. A total of six studies were included, with five eligible for meta-analysis. Compared to healthy controls, DFU patients exhibited significantly higher IMA levels [pooled SMD = 3.21 (95% CI: 1.40, 5.03)]. Similarly, DFU patients had higher IMA levels than diabetics without foot ulcers [pooled SMD = 1.21 (95% CI: 0.23, 2.20)]. Both frequentist and Bayesian analyses consistently supported these findings despite notable heterogeneity. Adjusted analyses of IMA for serum albumin further confirmed its discriminative value in DFU. PET-PEESE analyses did not detect significant publication bias. This meta-analysis highlights the potential of IMA as a biomarker for diagnosis, risk stratification, and monitoring in DFU management. Despite significant associations, high inter-study heterogeneity and the limited number of studies restrict generalizability. Future research should focus on standardizing measurement protocols, validating clinical cut-offs, and conducting large-scale prospective studies to confirm its utility.

Aims/hypothesisDiabetic foot ulcers are a common and serious complication of diabetes, frequently resulting in infection, amputation, and increased mortality. Cold atmospheric plasma (CAP) is a new treatment modality that combines antimicrobial activity with promotion of tissue regeneration. We aimed to systematically review and meta-analyse randomized controlled trials to determine whether cold atmospheric plasma therapy, when added to standard wound care, improves healing outcomes and safety in patients with diabetic foot ulcers (DFUs).MethodsFollowing PRISMA 2020 guidelines, we included randomized controlled trials in adults with DFUs comparing adjunctive CAP plus standard care versus standard care. Non-RCTs, non-CAP energy modalities, CAP without concomitant standard care, and studies without a concurrent control were excluded. The primary outcome was final fractional wound area (final/baseline; unitless proportion, 0-1). Secondary outcomes were ≥50% wound-size reduction by week 3, bacterial load, and adverse events.ResultsThree RCTs (107 participants; 126 ulcers) showed that CAP reduced final fractional wound area (mean difference -0.29 proportion units, 95% CI -0.47 to -0.11;  = 0.002;  = 22%). The proportion achieving ≥50% wound-size reduction by week 3 was higher with CAP (RR 2.39, 95% CI 1.46-3.91;  < 0.001;  = 0%). Bacterial load declined over time in both groups with no sustained between-group difference; immediate post-application reductions were observed with CAP within sessions. No serious treatment-related adverse events were reported.Conclusions/interpretationAdjunctive cold atmospheric plasma improved early healing of diabetic foot ulcers and showed a favourable short-term safety profile, with no sustained advantage in infection control over standard care. Larger, longer randomized trials are warranted to assess complete closure and recurrence outcomes and to define optimal treatment parameters.RegistrationPROSPERO registration ID CRD4201113940.

Diabetic foot ulcers (DFUs) and diabetic peripheral neuropathy (DPN) are severe complications in type 2 diabetes mellitus (T2DM). Selenium (Se) is an important element with antioxidant properties, which is crucial for human homeostasis. In this narrative mini review, we summarise the evidence on the potential association of Se with DPN and DFUs. Generally, in most of the limited number of studies, serum Se levels were significantly lower in subjects with DPN or DFUs. In addition, one study demonstrated that urinary Se levels were lower in the DPN group. Nevertheless, further investigations are needed to confirm these preliminary findings.

BackgroundChronic wounds represent a pathological state characterized by failure to heal within the normal timeframe, often accompanied by infection, high recurrence rates, and treatment challenges. Nicotine, the primary component of both electronic cigarettes and traditional tobacco, is known not only for its addictive properties but also for its potential to interfere with wound healing through multiple mechanisms. However, its toxicological mechanisms at the multi-target and multi-pathway levels remain unclear.MethodsThis study employed network toxicology and molecular docking techniques. Targets of nicotine and chronic wound-related genes were obtained from databases such as PubChem, GeneCards, and OMIM. Common targets were screened, and a protein-protein interaction (PPI) network was constructed. The CytoHubba plugin was used to identify core targets, while GO and KEGG enrichment analyses were performed to elucidate their biological functions and pathways. Molecular docking was subsequently conducted to validate the binding affinity between nicotine and the core targets.ResultsNicotine exhibited significant skin sensitization, neurotoxicity, and respiratory toxicity. A total of 160 common targets of nicotine and chronic wounds were identified, with TNF, IL6, and IL1B recognized as core targets. Enrichment analysis revealed significant involvement in inflammatory responses, the PI3K-AKT signaling pathway, the AGE-RAGE signaling pathway, and others. Molecular docking demonstrated strong binding affinity between nicotine and TNF (-5.6 kcal/mol) as well as IL6 (-5.0 kcal/mol).ConclusionNicotine disrupts the homeostasis of the wound microenvironment by regulating core inflammatory factors such as TNF and IL6, inhibiting the PI3K-AKT repair pathway, and activating the AGE-RAGE metabolic toxicity pathway, thereby impeding the healing of chronic wounds. This study provides a multi-target network perspective on the toxic mechanisms of nicotine in wound healing and offers a theoretical foundation for clinical smoking cessation to promote wound recovery.

ObjectiveTo investigate the association between frailty and diabetic foot ulcer (DFU) risk among patients with diabetes and to evaluate the frailty index as a potential predictive tool.MethodsThis cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES). Participants were categorized into frailty Z-score quartiles. Survey-weighted generalized linear models (SWGLMs) were used to evaluate the association between Frailty and DFU, with restricted cubic spline (RCS) analysis to examine non-linear relationships. Subgroup and interaction analyses were also conducted.ResultsAmong 831 adults with diabetes (mean age 59.2 years; 49.6% female), higher frailty scores were significantly associated with increased DFU risk. After multivariate adjustment, each standard deviation increase in frailty Z-score was linked to a 92% higher DFU risk (OR = 1.92, 95% CI: 1.34-2.73, P < 0.001). Participants in the highest frailty quartile had a nearly 5-fold increased risk compared to the lowest (OR = 5.95, 95% CI: 0.44-30.0, P = 0.033), with a significant dose-response trend (P for trend=0.023). RCS analysis supported a significant overall association (P < 0.001), showing a primarily linear relationship (P for nonlinearity=0.207). Subgroup analyses revealed consistent associations without significant interactions.ConclusionsFrailty is independently associated with elevated DFU risk among patients with diabetes. The frailty index may serve as a useful adjunct to conventional risk factors for early identification of high-risk individuals.

AimsThe goal was to gather and assess information about the features of patients suffering from Diabetic Foot Syndrome with active ulcers. This data was compared to findings gathered by a designated researcher for evaluation.Materials and MethodsThis cross-sectional observational study was designed using data from a validated survey.ResultsWe conducted 102 surveys, revealing positive data on the respondents' knowledge, awareness, attitudes, and practices. However, discrepancies appeared between the participants' self-assessments, the researcher's evaluations and the actual implementation of recommendations, such as wearing inappropriate footwear, not moisturizing the feet or avoiding walking more than an hour while there is an active ulcer.ConclusionDespite participants showing positive knowledge, awareness, attitudes, and practices, it is crucial to enhance educational measures in regular clinical practice. This would further reinforce patients' preventative actions against DFU in everyday life.Practice ImplicationsThis study highlights the need to enhance patient education and preventative measures in clinical practice, ensuring patients consistently apply knowledge to prevent diabetic foot ulcers daily.

BackgroundThis study aimed to analyze the global epidemiological trends of pressure injuries (PIs) from 1990 to 2021, focusing on mortality, prevalence and disability-adjusted life years (DALYs). By leveraging the Global Burden of Disease (GBD) 2021 data-set, we sought to identify sex- and age-specific patterns, temporal trends, and future trend prediction to inform targeted public health interventions.MethodsWe extracted data from the GBD 2021 database, including prevalence, mortality and DALYs, stratified by age, sex, and location. Statistical analyses included joinpoint regression to identify temporal trends, age-period-cohort modeling to disentangle age, period, and cohort effects, frontier analysis to assess efficiency gaps relative to sociodemographic development, and ARIMA modeling to forecast future trends.ResultsGlobally, crude mortality increased from 0.31 (0.26-0.37) per 100,000 in 1990 to 0.47 (0.36-0.54) in 2021, with prevalence rising from 5.63 (5.08-6.25) to 8.18 (7.38-9.03). Disability burden also escalated, with DALYs increasing from 408,886.98 (329 846.87-490 564.17) in 1990 to 803 747.40 (612 264.19-903 732.23) in 2021. However, age-standardized rates declined: ASMR decreased from 0.53 (0.44-0.63) to 0.46 (0.35-0.51), ASPR from 8.24 (7.15-9.40) to 7.92 (7.10-8.80), and ASDR from 10.74 (8.86-12.74) to 9.70 (7.41-10.88) per 100 000. Sex-specific analyses revealed higher mortality number in females, peaking at 85-89 years, while males exhibited earlier peaks in disability burden at 70 years. Joinpoint regression identified an overall decreasing trend of ASMR (AAPC = -0.47%), while ASPR (AAPC = -0.13%) and ASDR (AAPC = -0.31%) showed intermittent rises amid overall declines. Age-period-cohort analysis confirmed net declines in age-standardized rates, with 2004 marking a turning point for mortality reductions. Frontier analysis revealed persistent efficiency gaps, particularly in high-SDI countries like the U.S. and Singapore. ARIMA models projected continued but marginal declines by 2031 for both ASMR (0.45per 100 000) and ASDR (9.23 per 100 000), with similar trends for both sexes.ConclusionsDespite progress in age-standardized metrics, the absolute burden of PIs is escalating due to demographic aging. Targeted interventions must address geriatric populations, sex-specific vulnerabilities, and regional disparities. Policy priorities include scaling cost-effective prevention technologies, integrating PIs into universal health coverage, and optimizing resource allocation to bridge efficiency gaps.

Diabetic foot complications often escalate and lead to devastating consequences, particularly lower limb amputations. This study recorded the microorganisms isolated from Major and Minor diabetic lower limb amputations over a period of four years. This retrospective observational study analysed data obtained from a tertiary care centre for diabetes in Chennai, India, from 1st January 2021 to 31st December 2024. A predominance of Gram negative microorganisms for both Major and Minor amputations were observed. Most infections were monomicrobial. and were most frequently isolated from Major and Minor amputations respectively. The difference between dominant pathogens isolated from Major and Minor amputations suggest complex infection dynamics within the site of infection. This study also reinforces the importance of routine microbiological surveillance. Cumulatively, these findings indicate the need for further investigation.

BackgroundThe use of vancomycin-loaded polymethylmethacrylate cement (vPMMA) has been widely implemented in the treatment of infected diabetes-related foot ulcers (IDFUs). However, its clinical efficacy remains controversial due to limited sample sizes and significant biases in existing studies.MethodsA total of 66 patients diagnosed with IDFUs were retrospectively analyzed and assigned to four groups based on the sensitivity of the isolated pathogens to vancomycin and whether vPMMA was administered. Each group was further stratified into two subgroups according to the presence of osteomyelitis or simple soft tissue infection (STI). Clinical outcomes, including wound healing duration, number of debridement procedures, and pathogen-positive duration, were collected to evaluate the therapeutic effect of vPMMA.ResultsAfter verifying statistical comparability using the WIfI (Wound, Ischemia, and foot Infection) classification system, the statistically significant improvement in wound healing duration was observed in the subgroup A + (with osteomyelitis caused by vancomycin-sensitive pathogens, treated with vPMMA) (69.0 ± 29.6 days, P < 0.05). While, no significant differences were observed among the four groups (A, B, C, D) with respect to wound healing duration (71.5 ± 25.2, 93.5 ± 26.5, 91.0 ± 41.9, 97.1 ± 43.2 days, P > 0.05), debridement numbers (P > 0.05), or pathogen-positive duration (P > 0.05).ConclusionsContrary to previous reports, our findings do not support the use of vPMMA as a universally effective treatment for IDFUs. The therapy demonstrated superior efficacy compared to simple debridement only in cases where osteomyelitis was present and complete surgical clearance of the lesion was not feasible.

Aims/IntroductionVitamin D deficiency is prevalent among individuals with diabetic foot infections (DFIs) and can influence a range of patient-related parameters. Hence, we aimed to find the association of serum vitamin D levels with various clinical, biochemical, and inflammatory parameters, as well as the microbial environment in the wounds of DFI patients.Materials and MethodsFrom September 2022 to March 2024, 169 DFI patients participated in cross-sectional research at the hospital. Utilising an electrochemiluminescence immunoassay, vitamin D levels were determined. Vitamin D receptor (VDR) and Cathelicidin (LL-37) were estimated using ELISA Kits. The tissue culture plate technique was used to analyze biofilm formation. Patient-related parameters were obtained from medical records.ResultsThe vitamin D status of DFI patients indicated that 70.4% were deficient, 19.5% were insufficient, and 10.1% were sufficient. The median vitamin D, VDR protein, and LL-37 values were 15.3 ng/mL, 0.832 ng/mL, and 1.54 ng/mL, respectively. Biofilm formation was seen in 84.36% of bacteria from vitamin D-deficient DFI patients ( < .001). Vitamin D levels were negatively correlated with ulcer duration, hospital stay, white blood cell count, neutrophil-lymphocyte ratio, C-reactive protein, and systemic inflammation index (r = -0.787, -0.849, -0.6, -0.475, -0.402, and -0.521, respectively;  < .001). However, vitamin D levels were positively correlated with VDR and LL-37 levels (r = 0.988 and 0.944, respectively;  < .001).ConclusionsThe majority of DFI patients exhibited vitamin D deficiency, which was significantly associated with most of the clinical, biochemical, and inflammatory parameters, in addition to the microbial environment within the wound.

BackgroundChronic ulcers cause persistent pain and impaired healing, often showing resistance to standard therapies. Topical sevoflurane has emerged as a potential agent for both pain relief and wound healing; however, current evidence remains limited. This review assesses the safety and efficacy of topical sevoflurane in managing painful chronic ulcers and promoting a reduction in ulcer size.ObjectiveTo assess the safety and efficacy of topical sevoflurane as a promising drug compared with standard care.MethodsWe searched PubMed, Web of Science, Cochrane Library, and Scopus up to March 2025 for studies on topical sevoflurane in chronic ulcers. Meta-analysis was based on the Cochrane Handbook for Systematic Reviews of Intervention.ResultsOur meta-analysis showed that three studies (n = 127) demonstrated a significant reduction in pain with topical sevoflurane treatment, with a pooled Standardized Mean Difference (SMD) of -1.88 (95% CI: -2.31 to -1.44,  < .0001), and low heterogeneity (I² = 18.9%). Ulcer size reduction was also statistically significant in two studies (n = 79), with a pooled mean difference of -4.77 cm² (95% CI: -7.30 to -2.23,  = .0002), and moderate heterogeneity (I² = 30.0%). Effects were more pronounced at earlier assessment time points.ConclusionTopical sevoflurane shows promise for pain management in chronic ulcers, with potential benefits for healing and reducing opioid use. However, stronger evidence from high-quality studies is needed to support a definitive recommendation.

BackgroundA variety of dressings are used for burn patients in the clinic, and the difference in efficacy between different dressings is controversial Therefore, we used Bayesian net meta-analysis to evaluate the clinical efficacy of 14 dressings in patients with second-degree burns.MethodsPubMed, Cochrane Library, Web of Science, Embase, and China Knowledge Network databases were searched to collect randomised controlled trials on different dressings used in the treatment of second-degree burns that met the inclusion criteria from 2010-01 to 2024-12 in each database. Literature was screened by 2 investigators, who independently collected and organised the data for extraction, assessed the quality of the included studies using the Cochrane Risk of Bias tool and Review Manager 5.4, and scored the evidence using GRADEPro. Network meta-analysis (NMA) was performed using R Studio, and SUCRA was used to rank the included dressings for each outcome indicator.ResultsA total of 28 studies containing 2072 patients with second-degree burns and 14 different interventions were included, and the results of the network meta-analysis showed that:1) the top 3 results of the ranked probability of wound healing rate within 2 weeks were: human amniotic membrane (85.3%)>Recombinant human granulocyte macrophage colony stimulating factor(81.7%)>Recombinant Human Erythropoietin(78.1%); ②The top three results in terms of wound healing time were: Recombinant Human Erythropoietin(1.6%)ConclusionBased on the SUCRA values and NMA results, we found that Human amniotic membrane can significantly increase the wound healing rate of patients with second-degree burns, Recombinant Human Erythropoietin can significantly shorten the wound healing time, and Heparin has a better effect on reducing the pain of burn patients.However, limited by the quality of the included literature, further high-quality clinical studies are needed to confirm this.

AimsDiabetes-related foot disease (DFD) is a prevalent and costly complication of diabetes in Latin America (LATAM). Our bibliometric study aims to identify emerging research output from LATAM countries, knowledge gaps, and future opportunities in research.MethodsA bibliometric analysis between 2000 and 2025 was done using PubMed and Scopus databases. English-language articles with corresponding authors affiliated with LATAM institutions were included. A total of 1423 records were screened, with 435 meeting inclusion criteria. Data on authorship, country, study type, citations, journal impact, and collaboration type were extracted and analyzed.ResultsOverall, Brazil contributed to 51.5% publications, followed by Mexico (18.6%) and Cuba (7.8%). Citation analysis revealed a total of 9397 citations, with a median of seven citations per publication. Venezuela and Barbados had the highest median citations per article, despite low output. Collaboration analyses showed that only 1.6% involved intra-LATAM collaborations. International collaborations outside the region were associated with higher median citations. Observational studies (n = 198) were most prevalent, with experimental, trial, and review studies showing significant growth over time.ConclusionDespite the recent growth of DFD research in Latin America, structural barriers such as research equity, international visibility, and regional collaboration persist. Addressing these by strengthening intra-regional collaboration, improving funding equity, and investing in research infrastructure may enhance scientific visibility and improve healthcare outcomes for DFD in the region.

The current study aimed to evaluate the outcomes of heel diabetic foot osteomyelitis (DFO) managed in a specialized diabetic foot service. The research is a single-center retrospective observational study including a population of patients with diabetic foot ulcers (DFUs) complicated by DFO and requiring hospitalization, managed between 2019 and 2022 in a tertiary level diabetic foot service. According to the location of bone infection, patients were divided into two groups: those with heel DFO and those with forefoot/midfoot DFO. After one year of follow-up, the following outcomes were evaluated and compared between groups: healing, healing time, major amputation, and mortality.Overall, 114 patients were included. The mean age was 67.9 ± 12, most of them were male (72.8%) and had type 2 diabetes (91.2%); 84 (73.7%) of patients reported forefoot/midfoot DFO, while 30 (26.3%) reported heel DFO. Patients with heel DFO showed greater rates of soft tissue infection (80 vs 68.7%, p = 0.04), ulcer size >5 cm (93.3 vs 34.3%, p = <0.0001), gangrene (63.3 vs 22.9%, p = <0.0001), higher C-reactive protein values (67.6 ± 25 vs 24 ± 16 mg/dl, p = 0.0002) and concomitant peripheral arterial disease (PAD) (83.3 vs 52.4%, p = 0.0002).Outcomes for heel DFO and forefoot/midfoot DFO were: wound healing (66.7 vs 97%, p = <0.0001), healing time (14 ± 6 vs 6.8 ± 5 weeks, p=<0.0001), major amputation (10 vs 0%, p = 0.0002), and mortality (6.6 vs 4.8%, p = 0.3) respectively. At the multivariate logistic regression analysis, heel DFO [OR 8.4, CI95% (2.1-14.8), p=<0.0001] and PAD [OR 3.5, CI95% (1.1-4.2), p = 0.001] were independent predictors of major amputation, while heel DFO [OR 6.8, CI95% (1.9-10.5), p=<0.0001], PAD [OR 4.8, CI95% (1.4-7.6), p = 0.0001], and ulcer size [OR 1.5, CI95% (1.2-2.6), p=<0.0001] were independent predictors of non-healing.Heel DFO resulted associated with a higher risk of major amputation and reduced chance of healing.

Diabetic foot ulcers are a significant complication of diabetes mellitus, contributing to high morbidity, prolonged hospitalisations, and increased healthcare costs. Early detection through diabetic foot screening (DFS) and preventive management strategies are therefore crucial in reducing the incidence of diabetic foot ulcers and improving patient outcomes. Hence, this study aims to review and summarise the current practices in DFS and risk stratification to aid subsequent clinical management. A systematic search of PubMed and Embase was conducted to identify articles relevant to DFS guidelines and questionnaire-based screening tools. Of 1761 studies screened, 15 met the inclusion criteria. While national and international guidelines provide comprehensive protocols for DFS with similarities in screening components, differences exist in risk stratification approaches, frequency of assessments, and integration of questionnaire-based tools such as Q-DFD, Thai Q-DFD, DFSQ-UMA and MNSI. Analysis of DFS guidelines identified three key components: neuropathy assessment, vascular assessment, and visual inspection. The screening methods include monofilament testing, vibration perception, and pedal pulse palpation with additional tools such as ankle-brachial index being used in some of the guidelines. These can be performed by various healthcare providers, including general practitioners, diabetes nurses, and podiatrists, ensuring accessibility across different healthcare settings. Risk stratification models classify patients into low-, moderate-, or high-risk categories, guiding screening frequency which varies from annual to quarterly assessments depending on risk level. Effective DFS, based on standardised guidelines and risk stratification models, is essential for preventing diabetic foot ulcers. The integration of DFS into routine clinical practice, supported by tools such as validated questionnaires, can significantly improve outcomes for diabetic patients.

BackgroundWound complications are a significant concern globally. Artificial dermal (AD) scaffolds, a novel material used in wound repair, hold promise for enhancing wound repair. However, it is limited by challenges such as prolonged vascularization time. This study aimed to investigate the effects of AD scaffold composites with recombinant human epidermal growth factor (Rh-EGF) on wound repair in ratsMethodsRh-EGF absorption and release from the artificial dermis were evaluated using an enzyme-linked immunosorbent assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. Cell adhesion was examined via electron microscopy and confocal microscopy. Rats were divided into four groups: (1) AD/Rh-EGF composite scaffolds, (2) AD scaffolds alone, (3) Rh-EGF alone, and (4) untreated control. Wound healing was assessed over 21 days via histological analysis and wound closure rates.ResultsAbsorption and release experiments confirmed that the artificial dermis can retain and release Rh-EGF. In cell co-culture experiments, the Rh-EGF-combined AD scaffolds enhanced L929 cell proliferation and adhesion. The Rh-EGF composite artificial dermis promoted wound healing . Histological and immunohistochemical analyses revealed that the Rh-EGF composite artificial dermis stimulated epithelial tissue regeneration, collagen production, cell proliferation, and angiogenesis while showing a potential trend toward reduced scar formation based on molecular markers.ConclusionThe AD/Rh-EGF composite scaffold accelerates wound repair while minimizing scar formation, providing a theoretical basis for its potential clinical applications.

This letter critically appraises the study by Juttada et al, (doi: 10.1177/15347346251332708) which explored ischemia-modified albumin (IMA) as a marker of healing in diabetic foot ulcers (DFUs). We acknowledge the study's novel contribution through its serial IMA monitoring during treatment and compare it with a growing body of evidence. While the study demonstrates promising clinical applicability, there are important limitations regarding its predictive strength, albumin adjustment, and the influence of oxidative therapies. We suggest that future studies adopt a multi-biomarker approach and address variability in oxidative stress conditions such as those encountered during hyperbaric oxygen therapy.