The international journal of lower extremity wounds最新文献

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; p = 0.002; I² = 22%). The proportion achieving ≥50% wound-size reduction by week 3 was higher with CAP (RR 2.39, 95% CI 1.46-3.91; p < 0.001; I² = 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.

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.

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.

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.

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. Proteus mirabilis and Enterococcus spp. 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.

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 (P < .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; P < .001). However, vitamin D levels were positively correlated with VDR and LL-37 levels (r = 0.988 and 0.944, respectively; P < .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, P < .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, P = .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.

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.

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.