Diabetic foot ulcers (DFUs) result in tissue damage or impairment of deeper structures that affect quality of life. The impacts are numerous, and even after a long treatment period, 65% of patients experience recurrence. Among the interventions used to accelerate the healing process of DFUs, photobiomodulation therapy (PBMT) is a painless, noninvasive, and low-cost treatment. To achieve effective therapeutic results optimal PBMT parameters are necessary. The positive effect of PBMT on diabetic cells may be dependent on fluence (J/cm2) and wavelength (nm). This double-blind, randomized clinical trial will be conducted at the University Clinic of Physical Therapy. One hundred patients will be randomly placed in 4 groups. A Laserpulse Ibramed (Helium-Neon, HeNe, 660 nm) with 20 W power will be used (continuous mode), with doses stipulated for each treatment group (GL1, 4 J/cm2; GL2, 8 J/cm2; GL3, 12 J/cm2) and Endophoton KLD GaAs 904 nm (ST, 10 J/cm2) for 2 nonconsecutive days per week for 10 weeks, for a total of 20 sessions. The primary outcomes will be ulcer healing rate and University of Texas classification scores. Patients\' DFUs will be assessed on the 1st day, 5 weeks, and 10 weeks of treatment then 1 month after the end of treatment. This study may aid effective clinical decision-making for the management of DFUs.

UNASSIGNED: Diabetic foot ulcers (DFUs) continue to challenge wound care practitioners. This prospective, multicentre, randomised controlled trial (RCT) evaluated the effectiveness of a dehydrated Amnion Chorion Membrane (dACM) (Organogenesis Inc., US) versus standard of care (SoC) alone in complex DFUs in a challenging patient population.
UNASSIGNED: Subjects with a DFU extending into dermis, subcutaneous tissue, tendon, capsule, bone or joint were enrolled in a 12-week trial. They were allocated equally to two treatment groups: dACM (plus SoC); or SoC alone. The primary endpoint was frequency of wound closure determined by a Cox analysis that adjusted for duration and wound area. Kaplan-Meier analysis was used to determine median time to complete wound closure (CWC).
UNASSIGNED: The cohort comprised 218 patients, and these were split equally between the two treatment groups with 109 patients in each. A Cox analysis showed that the estimated frequency of wound closure for the dACM plus SoC group was statistically superior to the SoC alone group at week 4 (12% versus 8%), week 6 (22% versus 11%), week 8 (31% versus 21%), week 10 (42% versus 27%) and week 12 (50% versus 35%), respectively (p=0.04). The computed hazard ratio (1.48 (confidence interval: 0.95, 2.29) showed a 48% greater probability of wound closure in favour of the dACM group. Median time to wound closure for dACM-treated ulcers was 84 days compared to \'not achieved\' in the SoC-treated group (i.e., ≥50% of SoC-treated DFUs failed to heal by week 12; p=0.04).
UNASSIGNED: In an adequately powered DFU RCT, dACM increased the frequency, decreased the median time, and improved the probability of CWC when compared with SoC alone. dACM demonstrated beneficial effects in DFUs in a complex patient population.
UNASSIGNED: This study was funded by Organogenesis Inc., US. JC serves as a consultant and speaker for Organogenesis. RDD serves as a speaker for Organogenesis. OMA and MLS serve as consultants for Organogenesis. The authors have no other conflicts of interest to declare.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols.
OBJECTIVE: To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol.
METHODS: This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed.
RESULTS: The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients.
CONCLUSIONS: Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

OBJECTIVE: This study aimed to examine the impact of a 904 nm photobiomodulation (PBM) on diabetic ulcers using varying dosages.
METHODS: The study was a randomized, double-blind, placebo-controlled clinical trial that compared treatments using PBM (GaAs 904 nm 30w) with three different energy densities (4 J/cm2; 8 J/cm2; 10 J/cm2) in the healing process of non-infected diabetic foot ulcers. Eighty volunteers (48.75% female; 58.5 ± 11.1 years) were randomized into three intervention groups treated with PBM and one control group (PBM placebo). Volunteers performed up 20 interventions with PBM, either placebo or actual, in conjunction with conventional therapy, which involved dressing the wound with Helianthus annuus vegetable oil. The primary variable was the ulcer size reduction rate.
RESULTS: GaAs 904 nm PBM yielded a clinically and significant ulcer size rate reduction of diabetic foot ulcers, independently of energy density range (p < 0.05). However, 10 J/cm² had 60% of completely healed ulcers and the highest proportion of patients reaching 50% of ulcer reduction rate after 5 weeks of treatment. In addition, only 10 J/cm² showed a significant difference between control group after a 10-week follow-up (p < 0.05).
CONCLUSIONS: GaAs 904 nm PBM was effective in treating diabetic foot ulcers in this study and a dosage of 10 J/cm², after a 10-week follow-up, proved to be the most effective compared to the other groups.
BACKGROUND: NCT04246814.

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.

Background: Impaired angiogenesis is a significant factor contributing to delayed healing in diabetic foot ulcers (DFUs) due to inadequate oxygenation. Objective: This study aimed to investigate the impact of photobiomodulation (PBM) using a Ga-As laser on the release of serum hypoxia-inducible factor 1-α (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2, and nitric oxide (NO) in diabetic patients with DFUs. Materials and methods: In this double-blind RCT, a total of 30 patients with grade II DFUs were enrolled. The patients were randomly divided into two groups: the PBM (n = 15) and the placebo (n = 15). In the PBM group, a Ga-As laser (904 nm, 2 J/cm2, 90 W) was given for 3 days/week for 4 weeks (11 sessions). In the placebo group, the power was turned off. Both groups received similar standard wound care. Before and after interventions, the levels of serum HIF-1α, VEGF, NO, and sVEGFR-2 were measured. In addition, the percentage decrease in the wound surface area (%DWSA) was measured. Results: Following the intervention, the results revealed that the PBM group had significantly lower levels of VEGF than the placebo group (p = 0.005). The %DWSA was significantly higher in the PBM group compared to the placebo group (p = 0.003). Moreover, VEGF showed a significant negative correlation with %DWSA (p < 0.001). Conclusions: The observed decrease in serum levels of VEGF and an increase in %DWSA, compared to the placebo group, suggests that PBM effectively improves angiogenesis. Furthermore, the significant correlation found between VEGF levels and %DWSA emphasizes the importance of evaluating wound surface in patients as a dependable indicator of enhanced wound angiogenesis. Clinical Trial Registration: NCT02452086.

UNASSIGNED: Metabolic dysfunction-related fatty liver disease (MAFLD) is closely related to metabolic disorders. However, the relationship between MAFLD and the prognosis in diabetic foot ulcers (DFUs) remains unclear. This study aimed to explore the association between MAFLD and the risk of major adverse cardiac and cerebral events (MACCEs) in patients with DFUs.
UNASSIGNED: 889 inpatients with DFUs (PEDIS/TEXAS mild and above) were included in this study from 2013 to 2023. All participants were placed into non-MAFLD (n = 643) and MAFLD (n = 246) groups and followed up every 6 months for 10.9 years with a median of 63 months through in-person outpatient interviews and family fixed-line telephone visits. The association between MAFLD and the risk of MACCEs was evaluated through Multivariate Cox regression analyses, Stratified analyses and Kaplan-Meier survival analyses.
UNASSIGNED: Of the 889 subjects, 214 (24.07%) experienced MACCEs. Multivariate Cox regression analysis showed that MAFLD was independently associated with MACCEs (P < 0.001), of which with non-fatal myocardial infarction (P = 0.04), non-fatal stroke (P = 0.047), coronary artery revascularization (P = 0.002), heart failure (P = 0.029), and all-cause mortality (P = 0.021), respectively. The stratified analysis revealed that compared with non-MAFLD (HR=1), DFUs with MAFLD had a 2.64-fold increased risk for MACCEs (P <0.001; P for interaction = 0.001) in peripheral arterial disease (PAD) subgroup. Kaplan-Meier analysis evidenced that the MAFLD group had a higher cumulative incidence of MACCEs (log-rank, all P < 0.05).
UNASSIGNED: MAFLD is a high-risk factor for MACCEs in patients with DFUs. The findings will remind clinicians to pay more attention to MAFLD in patients with DFUs, especially in patients with DFUs combined with PAD as early as possible in clinical practice and adopt timely effective intervention strategies to prevent the occurrence of MACCEs to improve the clinical prognosis in patients with DFUs.

BACKGROUND: The pleiotropic effect of cholecalciferol (vitamin D3) has gained significant momentum and has been explored widely.
OBJECTIVE: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli.
METHODS: An in vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method.
RESULTS: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli.
CONCLUSIONS: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents.

This study aimed to explore the association between metabolic-associated fatty liver disease (MAFLD) and ulcer recurrence risk in patients with diabetic foot ulcers (DFUs) through an ambispective longitudinal cohort. From December 2013 to December 2022, a total of 482 inpatients with DFUs (PEDIS grade 3 and above with a severe infection) were eligible for inclusion in this study. This was an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 36 months. According to whether having MAFLD or not, all subjects were placed into two groups: non-MAFLD (n = 351) and MAFLD (n = 131). The association between MAFLD and ulcer recurrence in patients with DFUs was then evaluated through multivariate Cox regression analysis, stratified analyses and Kaplan-Meier survival analysis. Throughout the follow-up period, out of 482 subjects with DFUs, 68 had ulcer recurrence (14.1%). Three Cox regression models were established for data analyses. In the model I (unadjusted), MAFLD was significantly associated with the ulcer recurrence rate in patients with DFUs (HR = 1.79; 95% CI = 1.097-2.92; p = 0.02). Model II (adjusted model I with gender and age) (HR = 1.781; 95% CI = 1.09-2.912; p = 0.021) and model III (adjusted model II with CVD, duration of diabetes and Cr.) (HR = 1.743; 95% CI = 1.065-2.855; p = 0.027) also showed that MAFLD was significantly related to the ulcer recurrence risk in patients with DFUs, respectively. Stratified analysis indicated that subjects aged ≥60 had a greater risk of ulcer recurrence in MAFLD than in non-MAFLD (HR = 2.31; 95% CI = 1.268-4.206; p = 0.006). Kaplan-Meier survival curve analysis showed that ulcer recurrence rate had a significant association with MAFLD (log-rank, p = 0.018). This study indicated a close association between ulcer recurrence risk and MAFLD in patients with DFUs, especially in the elderly (aged ≥60). Therefore, special attention should be paid to the elderly with both DFUs and MAFLD because they have a higher ulcer recurrence rate than other general populations in routine clinical practice.

Inflammation, being a typical response to vascular tissue alterations, induces variations in tissue oxygen diffusion pressure. Diabetic microangiopathy, an inflammatory process, is characterized by an increase in vascular flow at rest, reduced venous and arteriolar responses, and increased capillary permeability, resulting in oedema development, decreased transcutaneous oxygen pressure, and increased transcutaneous carbon dioxide pressure. This phenomenon potentially hampers ulcer healing. Although the figure-of-eight method has proven to be a reliable, valid, quick, and efficient test for assessing foot and ankle measurements in patients with oedema and compromised skin integrity, it has not been studied in patients with diabetic foot. The aim of this study was to determine and compare the intra- and inter-observer variabilities of the figure-of-eight method in patients with diabetic foot. A prospective observational and cross-sectional study was undertaken, involving sixty-one subjects from a specialized Diabetic Foot Unit. Three investigators with varying levels of experience independently measured the subjects to assess both intra-observer and inter-observer variability. The evaluation was conducted using the Intraclass Correlation Coefficient (ICC). In the statistical analysis, an ICC of 0.93, adjusted using a 95% confidence interval (CI), was obtained for inter-observer reliability ICC, indicating excellent reliability among observers. Furthermore, an ICC of 0.98 with a 95% CI was obtained for the intra-observer reliability analysis, indicating excellent reliability. The results support using this test during the clinical management of oedema in patients with diabetic foot. The absence of an objective, fast, and readily available diagnostic method for oedema in diabetic foot patients in clinical practice might pose a limitation. Subsequent research should tackle this issue and explore the correlation between ankle perimeter measurements and other clinical outcomes in diabetic foot patients, including wound healing and quality of life.