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Synergistic in vitro effects of indocyanine green and ethylenediamine tetraacetate-mediated photodynamic antimicrobial chemotherapy combined with antibiotics for resistant bacterial biofilms in diabetic foot infection
摘要： Background: Antibiotic resistance has emerged as one of the most important determinants in diabetic foot infections outcomes. Photodynamic antimicrobial chemotherapy (PACT) has been proposed as an alternative approach for inactivating bacteria, especially resistant bacterial biofilms. This research investigated the synergistic effects of PACT mediated by the photosensitizer indocyanine green (ICG) and ethylenediamine tetraacetate (EDTA) combined with antibiotics against common pathogens of diabetic foot ulcer infection, including Staphylococcus aureus and Pseudomonas aeruginosa, in vitro. Methods: Planktonic bacteria and biofilms of S. aureus and P. aeruginosa were incubated with ICG and EDTA, and then exposed to laser treatment. Quantitative viable counting estimates the phototoxic effects on S. aureus and P. aeruginosa. The susceptibility of methicillin-resistant S. aureus (MRSA) and multidrug-resistant P. aeruginosa (MRPA) to PACT treatment was detected by disk diffusion and micro-broth dilution methods. Confocal microscopy was used to detect the morphology of biofilms treated with PACT and antibiotics. The resazurin assay was used to quantify the metabolic activity of bacteria in biofilms. Results: PACT mediated by ICG and EDTA led to a more pronounced antibacterial effect in S. aureus and P. aeruginosa compared with ICG alone-mediated PACT. P. aeruginosa was more sensitive to ICG and EDTA-mediated PACT than S. aureus. After PACT treatment, the susceptibility of MRSA and MRPA to antibiotics increased. Furthermore, PACT combined with antibiotic treatment significantly contributed to killing bacteria in the biofilm and disrupting biofilm structure. Conclusions: ICG and EDTA-mediated PACT combined with antibiotics synergistically enhanced the effects of sterilization and biofilm destruction.
关键词： photodynamic antimicrobial chemotherapy,antibacterial effect,diabetic foot infection,bacterial biofilm,EDTA,indocyanine green
更新于2025-09-23 15:23:52
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A Systematic Review and Meta-Analysis of the Effects of Low-Level Laser Therapy in the Treatment of Diabetic Foot Ulcers
摘要： Diabetic foot ulcers (DFUs) are considered one of the most aggressive and expensive complications of diabetes. Low-level laser therapy (LLLT) has been highlighted as a potential modality of treatment to accelerate the healing of ulcers. This systematic review and meta-analysis aimed to investigate the efficacy of LLLT in the treatment of DFU and identify the LLLT application parameters recommended for the treatment of DFU over the past 10 years. A systematic search was conducted in PubMed, BVS, PEDro, Scopus, Web of Science, and CINAHL up to March 31, 2019. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, randomized controlled trials (RCTs) that assessed the effect of LLLT on the treatment of DFU were included. Thirteen RCTs with a total of 361 participants were included in this review. Three RCTs reported a reduction in the percentage size of the ulcers and were included in the meta-analysis. The meta-analysis of the percentage size difference demonstrated a significant reduction in ulcer size in the LLLT group compared with controls (22.96 [95% confidence interval = 18.22-27.69; z = 9.51, P < .0001]). Treatment with 632.8 to 685 nm, 50 mW/cm2, 3 to 6 J/cm2, and irradiation for 30 to 80 seconds, 3 times weekly for a month is of benefit to patients with DFU. LLLT is effective and safe for the treatment of DFU. Additionally, well-designed, high-quality studies are needed to allow its ideal parameterization for clinical practice.
关键词： diabetic foot ulcer,meta-analysis,low-level laser therapy,systematic review
更新于2025-09-23 15:21:01
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Evaluation of fluorescence biomodulation in the real-life management of chronic wounds: the EUREKA trial
摘要： Objective: Fluorescence biomodulation (FB), a form of photobiomodulation (PBM) that is also known as low energy level light (LELL), has become an increasingly used clinical tool to induce wound healing in wounds that remain recalcitrant to treatment. In a real-life clinical setting, the aim of the EUREKA (EvalUation of Real-lifE use of Klox biophotonic system in chronic wound mAnagement) study was to confirm the efficacy and safety of LumiHeal, a system based on FB, in the treatment of chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs) and pressure ulcers (PUs). The effects of this FB system on the modulation of wound healing in chronic ulcers through FB induction were previously examined in an interim analysis of this study. Method: A multicenter, prospective, observational, uncontrolled trial in 12 clinical sites in Italy. The wound was cleansed with saline and a 2mm thick layer of a chromophore gel was applied to the affected area in a biweekly regimen. The area was then illuminated with the LED activator for five minutes at a distance of 5cm. Treatment was used in combination with standard of care specific to each type of chronic wound (VLU, DFU, PU). Wound area evaluation was assessed using the Silhouette Imaging System and quality of life (QoL) with the Cardiff Wound Impact Schedule (CWIS). A seven-point evaluation of the clinicans’ view was also examined. Results: We enrolled 100 subjects, with the final analysis including 99 patients/ulcers consisting of 52 VLUs, 32 DFUs and 15 PUs. Total wound closure at the end of the study was achieved in 47 patients by aetiology: 26 VLUs (50% of VLUs); 16 DFUs (50% of DFUs); and five PUs (33.3% of PUs). The mean wound area regression at last study assessment was significant for VLUs (41.0%; p<0.001) and DFUs (52.4%; p<0.001). After four weeks of treatment, it was possible to significantly predict if the ulcer would respond (defined as a decrease of wound size) to the study treatment. Adherence was high (95.2%) and no related serious adverse events were reported during the study. QoL significantly improved, with an increase of 15.4% of the total score, using the CWIS (p<0.001). Conclusion: The study confirmed a positive efficacy profile of the FB system in inducing the wound healing process in three different types of hard-to-heal chronic wounds. The treatment was shown to be safe and well tolerated by the patients, with a significant improvement in patient QoL. This approach offers an effective modality for the treatment of hard-to-heal chronic ulcers.
关键词： pressure ulcers,phototherapy,photobiomodulation,diabetic foot ulcers,biophotonics,fluorescence biomodulation,venous leg ulcers
更新于2025-09-23 15:21:01
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Validation of low-cost smartphone-based thermal camera for diabetic foot assessment
摘要： Infrared thermal imaging (IR) is not yet routinely implemented for early detection of diabetic foot ulcers (DFU), despite proven clinical effectiveness. Low-cost, smartphone-based IR-cameras are now available and may lower the threshold for implementation, but the quality of these cameras is unknown. We aim to validate a smartphone-based IR-camera against a high-end IR-camera for diabetic foot assessment. Methods: We acquired plantar IR images of feet of 32 participants with a current or recently healed DFU with the smartphone-based FLIR-One and the high-end FLIR-SC305. Contralateral temperature differences of the entire plantar foot and nine pre-specified regions were compared for validation. Intra-class correlations coefficient (ICC(3,1)) and Bland-Altman plots were used to test agreement. Clinical validity was assessed by calculating statistical measures of diagnostic performance. Results: Almost perfect agreement was found for temperature measurements in both the entire plantar foot and the combined pre-specified regions, respectively, with ICC values of 0.987 and 0.981, Bland-Altman plots’ mean Δ=-0.14 and Δ=-0.06. Diagnostic accuracy showed 94% and 93% sensitivity, and 86% and 91% specificity. Conclusions: The smartphone-based IR-camera shows excellent validity for diabetic foot assessment.
关键词： Smartphone,Thermal Infrared,Diabetes Mellitus,Diabetic Foot,Foot Ulcer,Temperature
更新于2025-09-19 17:15:36
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Quantitative Analysis of Heel Skin Microcirculation Using Laser Doppler Flowmetry and Tissue Spectrophotometry
摘要： OBJECTIVE: To examine perfusion changes in the heel skin of individuals with and without diabetes mellitus to understand how skin is pathologically affected by diabetes mellitus. METHODS: This case-control study was conducted at an academic hospital in Tuebingen, Germany. A total of 30 subjects were enrolled in the study: 15 with known type 2 diabetes mellitus and 15 without. Each subject was asked to lie in a supine position on a hard lateral transfer mat for 10 minutes. MAIN OUTCOME MEASURES: Heel perfusion was quantitatively assessed directly after relief of pressure and after 3 and 6 minutes after relief of pressure using laser Doppler flowmetry and tissue spectrophotometry. MAIN RESULTS: Directly after relief of pressure, blood flow increased in the superficial skin layers (2 mm below the surface of the skin) in both groups. However, in deep skin layers (8 mm below the surface of the skin), blood flow increased in patients with diabetes mellitus and decreased in healthy patients. Oxygen saturation (SO2) was higher in healthy subjects directly after pressure relief. CONCLUSIONS: The increase in blood flow in superficial skin layers indicates reactive hyperemia after exposure in both groups. The prolonged hyperemia in deep skin layers in patients with diabetes indicates increased tissue vulnerability. Despite the increase in blood flow in deep skin layers, the SO2 and thus supply of tissue in patients with diabetes were reduced.
关键词： diabetes mellitus,pressure injury,oxygen saturation,blood flow,perfusion,diabetic foot ulcers,laser Doppler flowmetry,pressure ulcer,microcirculation
更新于2025-09-12 10:27:22
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Infrared thermography and ulcer prevention in the high‐risk diabetic foot: data from a single‐blind multicentre controlled clinical trial
摘要： Aim To assess the usefulness of monthly thermography and standard foot care to reduce diabetic foot ulcer recurrence. Methods People with diabetes (n=110), neuropathy and history of ≥1 foot ulcer participated in a single-blind multicentre clinical trial. Feet were imaged with a novel thermal imaging device (Diabetic Foot Ulcer Prevention System). Participants were randomized to intervention (active thermography + standard foot care) or control (blinded thermography + standard foot care) and were followed up monthly until ulcer recurrence or for 12 months. Foot thermograms of participants from the intervention group were assessed for hot spots (areas with temperature ≥2.2°C higher than the corresponding contralateral site) and acted upon as per local standards. Results After 12 months, 62% of participants were ulcer-free in the intervention group and 56% in the control group. The odds ratios of ulcer recurrence (intervention vs control) were 0.82 (95% CI 0.38, 1.8; P=0.62) and 0.55 (95% CI 0.21, 1.4; P=0.22) in univariate and multivariate logistic regression analyses, respectively. The hazard ratios for the time to ulcer recurrence (intervention vs control) were 0.84 (95% CI 0.45, 1.6; P=0.58) and 0.67 (95% CI 0.34, 1.3; P=0.24) in univariate and multivariate Cox regression analyses, respectively. Conclusions Monthly intervention with thermal imaging did not result in a significant reduction in ulcer recurrence rate or increased ulcer-free survival in this cohort at high risk of foot ulcers. This trial has, however, informed the design of a refined study with longer follow-up and group stratification, further aiming to assess the efficacy of thermography to reduce ulcer recurrence.
关键词： ulcer prevention,diabetic foot ulcer,thermal imaging,neuropathy,thermography
更新于2025-09-11 14:15:04
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Efficacy of negative pressure wound therapy using vacuum-assisted closure combined with photon therapy for management of diabetic foot ulcers
摘要： Background: Diabetes mellitus, one of the most prevalent chronic metabolic diseases, causes many complications. Among the complications, one of the most common chronic complications is diabetic foot ulcers (DFUs). Objective: This study was conducted to investigate the efficacy of negative pressure wound therapy using vacuum-assisted closure (VAC) combined with photon therapy for the management of DFUs. Patients and methods: The study included a total of 69 patients with DFUs during the period from January 2014 to December 2015. All patients were diagnosed with DFUs with Wagner’s stage 2 or 3 and were divided into two groups – the VAC group in which patients received only VAC and the combined group in which patients received both VAC and photon therapy. Data on duration of the treatment, pre- and postoperative wound surface areas, dressing changing times, pain conditions assessed using visual analog scale scores, recurrence rate and amputation rate were collected. Results: Among all patients, 35 patients were divided into the VAC group and 34 patients into the combined group. Areas of foot ulcers for all patients ranged from 5 to 100 cm2. The treatment duration, dressing changing times and the peak value of visual analog scale scores were all significantly lower in the combined group compared with the VAC group (P,0.05). However, the reduced area for wound surface showed no significant difference between the two groups. Both recurrence and amputation rates showed no significant difference between the two groups of patients. Conclusion: Both VAC and VAC combined with photon therapy were effective and safe in the treatment of DFUs, while the combined therapy might have accelerated wound healing, but did not influence the long-term efficacy.
关键词： diabetic foot ulcer,photon therapy,vacuum-assisted closure
更新于2025-09-10 09:29:36
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[IEEE 2018 International Conference on Communication and Signal Processing (ICCSP) - Chennai, India (2018.4.3-2018.4.5)] 2018 International Conference on Communication and Signal Processing (ICCSP) - Statistical Analysis of Surface Temperature Distribution Pattern in Plantar Foot of Healthy and Diabetic Subjects Using Thermography
摘要： Diabetic foot complications are a major cause of concern for diabetic patients as it affects mobility and quality of life. Any computer aided diagnosis system would be very useful in the early detection and hence treatment and cure. For such a system, the surface temperature distribution patterns in the plantar region of the foot of both healthy and diabetic subjects have to be analyzed to detect any abnormality. In this paper we have analyzed the infrared thermal images of 62 diabetic and 20 healthy subjects to identify the temperature distribution patterns capable of detecting diabetic foot complications. The images were taken using Fluke TiX560 thermal imager. Image processing and analysis was done in MATLAB.
关键词： Infrared Thermography,Statistical Analysis,Mean Temperature Difference,Surface temperature distribution,Diabetic Foot Complications,Correlation
更新于2025-09-09 09:28:46
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Improvement in infected wound healing in type 1 diabetic rat by the synergistic effect of photobiomodulation therapy and conditioned medium
摘要： We investigated the effects of photobiomodulation therapy (PBMT) and conditioned medium (CM) of human bone marrow mesenchymal stem cells (hBM‐MSC) individually and/or in combination on the stereological parameters and the expression of basic fibroblast growth factor (bFGF), hypoxia‐inducible factor (HIF‐1α), and stromal cell–derived factor‐1α (SDF‐1α) in a wound model infected with methicillin‐resistant Staphylococcus aureus (MRSA) in diabetic rats. CM was provided by culturing hBM‐MSCs. Type 1 diabetes mellitus (T1DM) was induced in 72 rats, divided into four groups, harboring 18 rats each: group 1 served as a control group, group 2 received PBMT, group 3 received CM, and group 4 received CM + PBMT. On days 4, 7, and 15, six animals from each group were euthanized and the skin samples were separated for stereology examination and gene expression analysis by real‐time polymerase chain reaction. In the CM + PBMT, CM, and PBMT groups, significant decreases were induced in the number of neutrophils (1460 ± 93, 1854 ± 138, 1719 ± 248) and macrophages (539 ± 69, 804 ± 63, 912 ± 41), and significant increases in the number of fibroblasts (1073 ± 116, 836 ± 75, 912 ± 41) and angiogenesis (15 230 ± 516, 13 318 ± 1116, 14 041 ± 867), compared with those of the control group (2690 ± 371, 1139 ± 145, 566 ± 90, 12 585 ± 1219). Interestingly, the findings of the stereological examination in the CM + PBMT group were statistically more significant than those in the other groups. In the PBMT group, in most cases, the expression of bFGF, HIF‐1α, and SDF‐1α, on day 4 (27.7 ± 0.14, 28.8 ± 0.52, 27.5 ± 0.54) and day 7 (26.8 ± 1.4, 29.6 ± 1.4, 28.3 ± 1.2) were more significant than those in the control (day 4, 19.3 ± 0.42, 25.5 ± 0.08, 22.6 ± 0.04; day 7, 22.3 ± 0.22, 28.3 ± 0.59, 24.3 ± 0.19) and other treatment groups. The application of PBMT + CM induced anti-inflammatory and angiogenic activities, and hastened wound healing process in a T1 DM model of MRSA infected wound.
关键词： stereology,diabetes mellitus,diabetic foot ulcer,methicillin‐resistant staphylococcal aureus,low‐level laser therapy,phobiomodulation therapy,human bone marrow mesenchymal stem cell‐conditioned medium,real‐time PCR,rat
更新于2025-09-04 15:30:14