BACKGROUND: This study aimed to determine the relationship between HbA1c variability and foot ulcer healing at 12 weeks and 12 months.
METHODS: Using National Diabetic Foot Care Audit (NDFA) and hospital records, demographics, baseline ulcer characteristics and healing outcomes for subjects presenting with a foot ulcer between 2017-2022 were collected at 12 weeks and 12 months. Subjects had diabetes duration > 3 years and ≥ 3 HbA1c recordings in the 5 years prior to presentation.
RESULTS: At 12 weeks, factors associated with an active ulcer were presence on hind foot (adjusted odds ratios) (2.1 [95% CI 1.3-3.7]), ischaemia (2.1 [95% CI:1.4-3.2]), area > 1 cm2 (2.7 [95% CI:1.7-4.2]) and diabetes duration > 24 years vs 3-10 (AOR 2.0 [95% CI 1.2-3.5]). After adjustment, HbA1c variability 6-10 mmol/mol and > 14.5 mmol/mol had AOR of 1.76 (95% CI 1.1-2.8; p = 0.0192) and 1.5 (95% CI 0.9-2.6; p = 0.1148) of an active ulcer at 12 weeks vs variability < 6 mmol/mol. At 12 months, ischaemia (AOR 2.4 [95% CI 1.5-3.8]) and diabetes duration > 24 years vs 3-10 years (AOR 3.3 [95% CI 1.7-6.4] were significant factors. HbA1c variability was not significant at 12 months.
CONCLUSIONS: In keeping with the national NDFA data, in our cohort ulcer characteristics, but not HbA1c variability, were the key factors associated with ulcer healing at 12 weeks and 12 months.
Diabetes complications occur more frequently when glucose control is not as good as it could be. For a long time, HbA1c, or glycated haemoglobin, has been used as a measure of how well someone’s diabetes has been controlled. However, another way of looking at diabetes control is to look at the changes of HbA1c over time—this is called glycaemic variability. Diabetes-related foot disease is one of the most feared complications of the condition, and our group has previously shown in a small study that glycaemic variability was associated with ulcer healing at 12 weeks—with lower variability leading to better healing. However, it did not consider other variables known to be associated with not being alive and ulcer free at 12 months. In the UK, data are collected as part of the National Diabetes Footcare Audit (NDFA). This dataset collects a lot of information on new foot ulcers and their outcomes 12 weeks later. We have used our centre’s data to look at factors not included in the NDFA dataset—in particular glycaemic variability—to determine whether this influences ulcer outcomes at 12 weeks, but also at 12 months. We found that low glycaemic variability is associated with greater chances of healing but that the greatest association is the presence of poor blood flow and diabetes duration.

BACKGROUND: To analyze the learning curve of novices in mastering short-term Spinal Cord Stimulation (st-SCS) for diabetic foot, evaluating the efficacy, safety, and difficulty of this technique.
METHODS: A retrospective review of diabetic foot patients treated with st-SCS at our hospital was conducted. All procedures were performed by the same physician and patients were sequentially numbered according to the order of surgery. Learning curves were plotted using segmented linear regression and cumulative sum curves based on surgery duration. Patients were divided into two groups according to the inflection points on the learning curve: the learning group and the mastery group. Pre- and post-operative efficacy indicators were recorded and compared, along with general patient data, perioperative parameters, and incidence of complications.
RESULTS: A total of 36 patients were included. Significant improvements were observed post-st-SCS in ulcer size (from 7.00 cm2 to 4.00 cm2), visual analog scale (from 7.00 to 3.00), foot temperature (from 30.06°C to 32.37°C), and pittsburgh sleep quality index (from 14.42 to 8.36) (P<0.05). The physician could proficiently perform st-SCS after 9 cases. Surgery time was significantly shorter in the mastery group (1-9 cases) compared to the learning group (10-36 cases) (28.04 vs 43.56 min, P<0.05). There were no significant differences between the two groups in baseline data, improvement in efficacy indicators, or complications (P>0.05).
CONCLUSIONS: St-SCS is beneficial for wound healing, pain relief, improving peripheral circulation, and improving sleep quality. Surgeons can master this simple and safe technique in about nine cases.

OBJECTIVE: To evaluate the efficacy of stem cell therapy from different sources on the ankle-brachial index, wound closure percentage, and wound closure time in the treatment of diabetic foot ulcers (DFUs).
METHODS: A literature search was conducted in PubMed, Embase, Cochrane Library\'s Central Register of Controlled Trials, and Web of Science, extending through June 29, 2023. Quality evaluation was done using the Cochrane\'s bias risk assessment tool (RoB 2.0). Employing a Bayesian approach, the statistical computations was executed with the JAGS software, leveraging the gemtc 0.8-2 and rjags 4-10 libraries, within the R environment 4.1.2. The included interventions came from peripheral blood, bone marrow, placenta, umbilical cord blood, adipose tissue, or others.
RESULTS: A preliminary search identified 2286 articles, of which 23 randomized controlled trials met the inclusion criteria and were ultimately included. The analysis findings indicated that mesenchymal stem cells derived from the umbilical cord (HUCMSCs) led to a notable enhanced the ankle-brachial index in patients with DFUs compared to standard treatment (MD: 0.2; 95% CI [0.01, 0.36]). HUCMSCs were found to be the optimal therapeutic approach for enhancing the ankle-brachial index (SUCRA = 82.7%). Research on the wound closure percentage revealed that compared to platelet-rich plasma (PRP), processed microvascular tissue (PMVT), peripheral blood stem cells (PBSCs), microfragmented adipose tissue (MFAT), autologous bone marrow-derived stem cell therapy (ABMSCT), adipose-derived stem cells (ASCs), and dehydrated human umbilical cord allograft (EpiCord), Huoxue Shengji Decoction (HXSJD) + ABMSCT (H_Group_hematopoietic) significantly increased the wound closure percentage in DFU patients (P < 0.05). According to the SUCRA ranking, HXSJD + ABMSCT was the best therapeutic method to increase the percentage of wound closure (SUCRA = 93.8%).
CONCLUSIONS: This study employed a network meta-analysis method, combining direct and indirect comparisons, to analyze the latest clinical data and concluded that umbilical cord mesenchymal stem cells and the combination of HXSJD + autologous bone marrow hematopoietic stem cell treatment as adjunctive therapies for DFUs may have beneficial effects. Future research needs to focus on this.

BACKGROUND: Diabetic foot disease is the major cause of nontraumatic limb amputations worldwide causing a high socioeconomic and psychological toll and a huge burden to the healthcare system. Currently, standard treatment of diabetic foot ulcer is through multidisciplinary therapy. Foot exercises have been shown to improve healing in diabetic ulcers although evidence is limited and applicability is non-uniform. Our study aimed to generate more evidence regarding the benefit of addition of protocolized foot exercises so that it can be instituted as a standard of care.
METHODS: It was an open label Randomized controlled trial with seventy-two patients and study duration of one and half years Patients with diabetic foot ulcers were randomized into two groups. Both groups received standard therapy for diabetic foot ulcer. The intervention group in addition received three months of protocolized foot exercises. At the end of three months ulcer healing and quality of life were m compared among both the groups.
RESULTS: Regular exercises for three months caused significant reduction in ulcer area compared to the non-intervention group [100% versus 45.22%, 95% CI =36.30(16.04-56.56), P-value = 0.001]. Quality of life analyzed by SF-36 score showed significant improvement in components like physical function [69.4 ± 8.9 versus 63.7 ± 11.0, 95% CI = 5.73 (0.97-10.48), P-value = 0.01], emotional well-being [65.2 ± 7.6 versus 60.8 ± 7.9, 95% CI = 4.44 (0.79-8.10), P-value = 0.01], and pain components [55.4 ± 18.5 versus 47.5 ± 14.5, 95% CI = 7.99 (0.16-15.81), P-value = 0.04) at 3 months although change in social functioning, physical health limitation, health change, energy and general health improvement were not significant.
CONCLUSIONS: Addition of protocolized foot exercises are beneficial for patients of diabetic foot ulcers in terms of ulcer healing as well as improvement of quality of life provided compliance to exercises can be ensured.

OBJECTIVE: Recombinant human hepatocyte growth factor (HGF) plasmids are novel alternatives to salvage limbs in patients with chronic limb threatening ischaemia (CLTI). A systematic review and meta-analysis of data were conducted to assess the therapeutic efficacy of HGF plasmids in patients with CLTI.
METHODS: Randomised controlled studies evaluating HGF plasmid efficacy in patients with CLTI were identified using Medline, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases.
METHODS: Meta-analyses of the reported relative risks (RR) or mean differences (MD) were conducted. Subgroup analyses determined the efficacy of HGF plasmids in cohorts excluding Buerger\'s disease. Certainty of evidence for each outcome was assessed.
RESULTS: Seven studies (n = 655) were included. Based on low certainty evidence, patients treated with HGF had a significantly higher complete ulcer healing rate (RR 1.99, 95% CI 1.30 - 3.04; p = .015) than patients treated with placebo. The HGF treatment was associated with reduced visual analogue scale (VAS) scores of pain severity (MD -1.56, 95% CI -2.12 - -1.00; p < .001) vs. placebo in patients with CLTI assessed at the 3 month follow up (low certainty evidence); no significant differences were observed in major amputation (RR 0.91, 95% CI 0.48 - 1.73; p = .77) (low certainty evidence), or all-cause mortality (RR 0.93, 95% CI 0.38 - 2.27; p = .87) (low certainty evidence) between patients treated with HGF and placebo. Low certainty evidence suggested no significant differences in change in ankle-brachial index at 6 months (MD 0.00, 95% CI -0.09 - 0.09; p = 1.0) between patients treated with HGF and placebo. The complete ulcer healing rate and improved 3 month VAS scores of pain severity benefits persisted in subgroup analyses (low certainty evidence).
CONCLUSIONS: Hepatocyte growth factor treatment is associated with an increased complete ulcer healing rate and reduced ischaemic pain in patients with CLTI.

BACKGROUND: Chronic nonhealing ulcers present significant challenges in diabetic, dermatological, and surgical patients. Platelet-rich plasma (PRP), enriched with bioactive factors, offers promise for wound healing enhancement. This study evaluates PRP\'s efficacy, prepared via single and double spin methods in nonhealing chronic ulcers.
METHODS:  Twenty-two patients aged 18-65 years participated and 100 mL of blood was drawn into citrate phosphate dextrose adenine (CPDA) bags with all aseptic precautions. PRP was prepared by single and double spin methods. Patient serum and 10% calcium gluconate were added to fibrin gel. PRP was injected around the ulcer and then dressed. Dressings were changed on the fifth, 15th, and 20th days with PRP. Evaluation occurred on day 30 using surface area and volume assessments by both methods.
RESULTS: The single spin PRP group and double spin PRP group had 11 patients each with hemoglobin range of 10.79±1.88 to 12.63±2.22 g/dL. Initial lesions (16.27 cm²) significantly reduced to 14.76 cm² after double spin PRP sessions (p=0.005) and Initial lesions (9.87 cm²) significantly reduced to 7.65 cm² after single spin PRP sessions (p=0.005). Platelet count differences between whole blood and PRP were significant (p<0.05).
CONCLUSIONS: The single spin PRP method exhibited considerable improvements in healing parameters, showcasing its potential for chronic ulcer management.

OBJECTIVE: to assess the effects of advanced wound dressings (AWD) commonly used in the treatment of predominantly neuropathic diabetic foot ulcers (DFU) The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS).
METHODS: A Medline and Embase search were performed up to April 1st, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AWD with placebo/standard of care (SoC), with a duration of at least 12 weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, frequency of dressings change, major and minor amputation, pain, and all-cause mortality. AWD assessed were: alginates; foam, hydrocolloids, hydrogels, hyaluronic acid, hemoglobin spray, silver-impregnated, sucrose octasulfate-impregnated, honey-impregnated, micro-organism-binding, and protease-modulating matrix dressings. Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences (WMD) and 95% CIs were calculated for continuous variables.
RESULTS: Fifteen studies fulfilled all inclusion criteria. Participants treated with AWD had a significantly higher ulcer healing rate and shorter time-to-healing in comparison with SoC/placebo (MH-OR 1.50 [0.80, 2.79], p = 0.20 and WMD:: - 24.38 [- 42.90, - 5.86] days, p = 0.010). No other significant effect on the above reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as \"moderate\".
CONCLUSIONS: In conclusion, AWD, particularly sucrose-octasulfate, hydrogels, hyaluronic acid, and honey dressings, can actively promote wound healing and shortening time-to-healing in patients with DFU.

BACKGROUND: Diabetic foot ulcers (DFUs) are a challenging complication of diabetes mellitus, often leading to poor clinical outcomes and significant socioeconomic burdens. We evaluated the effectiveness of a definitive single-stage protocolized surgical management pathway, including the use of local antibiotic bone graft substitute, for the treatment of infected DFUs with associated osteomyelitis.
METHODS: A retrospective cohort study was conducted. Medical records were extracted (from January 2017 to December 2020) to establish a database consisting of patients who underwent surgical intervention for the treatment of an infected DFU with osteomyelitis. Patients were divided into conventional (control) and protocolized (intervention) surgical groups depending on the treatment received. Clinical outcomes were assessed over a 12-month follow-up period.
RESULTS: A total of 136 consecutive patients were included (conventional = 33, protocolized = 103). The protocolized group demonstrated a statistically significant reduction in the mean number of operations performed per patient (1.2 vs. 3.5) (P < 0.001) and a shorter accumulative hospital length of stay (12.6 vs. 25.1 days) (P < 0.001) compared to the conventional group. Major amputation rates were significantly lower in the protocolized group (2% vs. 18%) (P < 0.001). Within 12 months of surgical intervention, the protocolized group exhibited an ulcer healing rate of 89%, with a low rate of recurrence (3%).
CONCLUSIONS: The protocolized surgical pathway, including local antibiotic bone graft substitute use, demonstrated superior outcomes compared to conventional management for the treatment of infected DFUs with osteomyelitis. Further research is needed to evaluate the cost-effectiveness and generalizability of this approach.

Smoking may increase the risk of diabetic foot disease and ulceration. It does so by impairing glycaemic control and promoting the formation of advanced glycated end-products. Additionally, smoking is known to delay surgical wound healing and accelerate peripheral arterial disease. We aimed to determine whether toe pressures differed in smokers with a foot ulcer, when compared to non-smokers and ex-smokers, as well as ulcer outcomes at 12 months, among patients attending Blacktown Hospital High Risk Foot Service (HRFS). This study is a retrospective analysis of our prospectively collected clinic database. Eligible participants were adults attending the HRFS between June 2020 and April 2022. Participants were included if they had an ulcer, at least one systolic toe pressure reading completed at their initial visit and attended at least one follow-up visit. Participants were followed until healing, loss to follow-up or a minimum of 12 months. A total of 195 participants were included; 36 smokers, 82 ex-smokers, and 77 controls who had never smoked. Smoking status was by self-report. Current smokers were significantly younger at initial presentation (p = .002) and tended towards lower socioeconomic status (p = .067). Current smokers were significantly more likely to have ischaemic grade 3 toe pressures (< 30 mmHg) of their left foot (p = .027), suggestive of reduced perfusion. At the end of follow up period, smokers had the numerically highest rates of minor amputations. In conclusion, smokers ulcerate younger and are more likely to have grade 3 ischaemia. Collecting information about the brachial artery pressures and the time since the last cigarette may clarify any relationship between smoking and toe pressures.Trial registration: WSLHD HREC ethics approval 2111-02 and ANZCTR registration 382470. Registered on 15/09/2021.

Chronic stress often triggers gastrointestinal complications, including gastric injury and ulcers. Understanding the role of heat shock protein 27 (HSP27) in stress-induced gastric ulcers could unveil novel therapeutic targets. Here, we established a stress-induced gastric ulcer rat model using water immersion restraint stress and administered adenovirus-packaged HSP27 overexpression vector. Gastric ulcer severity was scored, and mucosal changes were assessed. Gastric epithelial and endothelial cells were treated with lipopolysaccharide and transfected with HSP27 overexpression vectors to evaluate cell viability, migration and angiogenesis. Expression levels of HSP27, C-X-C motif chemokine ligand 12 (CXCL12) and C-X-C motif chemokine receptor 4 (CXCR4) were measured in tissues and cells. HSP27 expression was initially low during stress-induced gastric ulceration but increased during ulcer healing. HSP27 overexpression accelerated ulcer healing in rats, promoting gastric epithelial cell proliferation and migration and gastric endothelial cell angiogenesis through the CXCL12/CXCR4 axis. Inhibitor IT1t reversed the effects of HSP27 overexpression on cell proliferation, migration and angiogenesis. In summary, HSP27 overexpression facilitated ulcer healing, which was partially mediated by the CXCL12/CXCR4 axis.