Diabetes-related Foot Ulcers Research Articles

Mortality rates in people presenting with a new diabetes-related foot ulcer: a cohort study with implications for management.

People with diabetes-related foot ulcers (DFUs) have high mortality rates. This analysis assesses the impact of selected risk factors on short-term mortality using a population registered in the National Diabetes Foot Care Audit (NDFA). Mortality rates at 12, 26 and 52 weeks was assessed in people with a new DFU registered by a specialist diabetes footcare service in the NDFA in England and Wales between April 2017 and March 2022. Poisson regression models were created to explore risk factors for mortality. In 71,000 people registered with a new DFU, mortality rates at 12, 26 and 52 weeks was 4.2%, 8.2% and 14.4%, respectively. At 26 weeks, higher mortality rates was associated with older age (rate ratio 2.15; 95% CI 2.03, 2.28, for age ≥80 years vs age 65-79 years), certain ulcer characteristics (area ≥1 cm2 [1.50; 95% CI 1.42, 1.59], deep ulcers [1.26; 95% CI 1.18, 1.35] or hindfoot location [1.53; 95% CI 1.44, 1.62]) and recorded evidence of ischaemia in the lower limb (1.78; 95% CI 1.69, 1.88) and various comorbidities (heart failure [2.13; 95% CI 2.00, 2.26], myocardial infarction [1.45; 95% CI 1.29, 1.63], stroke [1.37; 95% CI 1.22, 1.53], renal replacement therapy [2.34; 95% CI 2.09, 2.61] and chronic kidney disease stage 3 or greater [1.20; 95% CI 1.12, 1.29]). The 26-week mortality rate exceeded 25% for 7.3% of all individuals, rising to 11.5% of those aged 65 years and older, and 22.1% of those aged 80 years and over. Short-term mortality rates in people with a DFU is high. Teams managing people with DFUs should consider modifying the burdensome interventions and care required to heal such ulcers so maximising the quality of residual life, rather than focusing exclusively on healing.

A mouldable fibreglass backslab device as a novel approach to offload chronic plantar foot ulcers: A retrospective observational audit.

Pressure offloading is a critical component of plantar foot ulcer management, including diabetes-related foot ulcers (DFU). Conventional offloading options such as total contact casting and removable knee-high walkers may be unsuitable or unsuccessful in patients with morbid obesity, intermittent lower limb oedema, high exudative wounds or poor mobility. A mouldable fibreglass backslab device (BSD) may be a practical alternative to be considered in these situations. Data were retrospectively collected on 28 patients (29 foot ulcers) with non-healing ulcers who received a BSD to offload their foot ulcer as an extension to standard offloading care. Baseline data included: patient demographics, type of offloading prior to BSD application, date of ulcer onset, days ulcer present prior to BSD application and ulcer size at BSD initiation. Measures of success included ulcer size reduction 12weeks post-BSD application, time to complete ulcer healing in BSD, time to 50% reduction in ulcer size post-BSD application and total number of days ulcer present. The median (IQR) ulcer area and ulcer duration at baseline for 19 patients (20 ulcers) who used the BSD was 1.65 (0.4-3.8) cm2 and 531 (101-635) days. At 12weeks, the median (IQR) ulcer area was 0.3 (0-0.55) cm2 with a median (IQR) reduction of 97 (80-100) %. Nine (45%) ulcers achieved complete wound healing (100% reduction in wound size) at 12weeks post-BSD application, and the remaining 11 (55%) ulcers achieved at least 50% reduction in wound size. The median (IQR) time to complete wound healing and 50% reduction in wound size was 71 (35-134) days and 24 (15-44) days, respectively. Nine patients ceased use of the BSD and reverted to conventional offloading before their wounds had healed. Of these, four patients achieved a 50% reduction in wound size at the 12-week mark with conventional offloading. Our preliminary data suggests that a mouldable fibreglass BSD may be a practical offloading option in the management of DFUs, especially when conventional offloading methods are unsuccessful, unsuitable or unacceptable to patients. Higher level evidence is required to demonstrate suitability or efficacy of the BSD compared to current evidence-based recommended offloading methods.

An overview of diabetes-related foot ulcers.

The escalating prevalence of diabetes mellitus presents concern due to its widespread organ damage, including the heart, kidneys, eyes, and nerves, leading to severe complications such as heart attacks, strokes, blindness, and diabetes-related foot ulcers (DFUs). Management in the community setting should be focused on prevention, assessment and patient-centred care. By understanding the complex aetiology, risk factors, and classification of DFUs, along with utilising evidence-based interventions like the Wound, Infection and Ischemia (WIfI) system, we can streamline care. Neuropathy, peripheral arterial disease and infection are major contributors to DFU development, highlighting the importance of early detection and intervention. Comprehensive care addressing vascular health, infection control, pressure offloading, wound management, metabolic control, and patient education is essential for successful DFU management. Ultimately, proactive prevention strategies and interdisciplinary collaboration are necessary in the management of DFUs and improving patient outcomes.

RETHINKING THE MANAGEMENT OF HEALTH IN PEOPLE WITH DIABETES-RELATED FOOT ULCERS FROM AN AEP PERSPECTIVE: AN UPDATE FROM THE DFUEX STUDY

INTRODUCTION & AIMS Current treatments for people with diabetes-related foot ulcers (DFUs) focus on foot outcomes - potentially at the expense of broader health and wellbeing considerations. There are barriers to exercise for people with DFU and hesitancy in promoting physical activity by clinicians. AEPs may have the clinical skills to help people with DFUs engage in safe and effective exercise. The aim of this study was to examine the impact of AEP supervised exercise intervention on cardiorespiratory fitness, health and wound healing in adults with DFU. METHODS Using a randomised control trial design (ANZTR registration: 12622000885796p) adults aged 18 to 70 years (n=32) with active DFU are being recruited from an interdisciplinary High-Risk Foot Service (iHRFS) at Royal Prince Alfred Hospital Sydney Australia, and randomised to receive 12 weeks of supervised exercise (aerobic and resistance) training (Exercise) with usual care or usual care (Control) Measurements including fitness, metabolic and wound outcomes are acquired at baseline and after 12 weeks. RESULTS Preliminary baseline demographic, fitness and health data will be presented. Consideration for the scope of practice for AEPs in the multidisciplinary management of DFUs will be discussed incorporating observations and guidance on implementing exercise in a high risk DFU population, where there is limited patient and practitioner knowledge about safe and effective exercise options, and historical avoidance of physical activity to lessen the risk of wound deterioration. This will include consideration of aspects around exercise which are unique to people with DFUs, such as working with iHRFS, patient ambulation and transport, wound type and location, diversity of wound offloading devices and individual facilitators and barriers to exercise participation. CONCLUSIONS There is a need for robust evidence concerning the efficacy and safety of exercise intervention, and a need for strategies to engage AEPs into the multidisciplinary care of people with DFUs. Supported by the Exercise and Sports Science Australia Research Grant.

Diabetic foot ulcers, their characteristics, and trends in survival: Real world outcomes at a tertiary care facility in India

AimsCharacteristics of diabetes-related foot ulcers (DFU), association with recurrence and amputation are poorly described in the Asian Indian population. MethodsA prospectively maintained database was reviewed to characterize DFU and its association with amputation and recurrence. ResultsOf 200 patients, 63.5 % were male, the median age was 62 years (Min-Max:40–86), and median BMI was 27.90 kg/m2 (Min-Max:18.5–42.7). Median duration of Diabetes mellitus was 15 years (Min-Max:2–43). Complete healing occurred at a median of three months (Min-Max:0.23–37.62). Amputation for the current ulcer was required in 43.4 % of individuals. Ulcer recurrence was documented in 42.4 % instances, 66.1 % evolving on the ipsilateral side. Previous amputation was associated with the risk of subsequent amputation (Adjusted OR-3.08,p-0.047). Median time to ulcer recurrence was 4.23 years among those with amputation, in contrast to 9.61 years in those with healing. Cardiovascular death was the commonest cause of mortality, followed by sepsis. At a median follow up of 6.08 years, mortality at 1,3,5 and 10 years was 2.5 %,2.5 %,8.2 % and 30.9 % respectively among those who underwent amputation versus 0 %,0 %,10.1 % and 24.5 % respectively for those who achieved healing. ConclusionsPatients with DFU in India incur amputations at rates higher than conventionally described. With previous amputation, subsequent amputation risk triples. Ten-year mortality is 25%–30 %. Underestimates of the burden of recurrence and mortality are consequential of limited follow-up.

Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019).

Diabetes-related foot ulcers (DFU) are a persistent healthcare challenge, impacting both patients and healthcare systems, with adverse effects on quality of life and productivity. Our primary aim was to examine the trends in lifetime prevalence of DFU, as well as other micro- and macrovascular complications in the Trøndelag Health Study (HUNT) in Norway. This study consists of individuals ≥20 years with diabetes participating in the population-based cross-sectional HUNT surveys (1995-2019). Prevalence ratios, comparing the lifetime prevalence of DFU and other relevant micro- and macrovascular complications between the HUNT surveys, were calculated using Poisson regression. The lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 11.0% (9.5-12.7) in HUNT2, 7.5% (6.3-8.8) in HUNT3 and 5.3% (4.4-6.3) in HUNT4. The decrease in DFU prevalence from 1995 to 2019 was observed in both men and women, for all age groups, and for both type 1 and type 2 diabetes. The highest lifetime prevalence of DFU was found among those with type 1 diabetes. The decrease in HbA1c from HUNT2 to HUNT4 did not differ between those with and without a DFU. The prevalence of chronic kidney disease (eGFR <60 mL/min/1.73 m2 (eGFR categories G3-G5)) increased in both individuals with and without a DFU. Results from the HUNT surveys show a substantial decline in the lifetime prevalence of DFU from 1995 to 2019.

Effectiveness of offloading interventions for people with diabetes-related foot ulcers: A systematic review and meta-analysis.

Offloading treatment is crucial to heal diabetes-related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU. We searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight-bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost-effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta-analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed. From 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non-controlled), 35 meta-analyses performed, and 128 evidence statements developed. We found non-removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09-1.41; N=14, n=1083), and may increase adherence, cost-effectiveness and decrease infections, but may increase new lesions. Removable knee-high offloading devices may make little difference to ulcers healed compared to removable ankle-high offloading devices (RR 1.00, 0.86-1.16; N=6, n=439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89-2.18; N=5, n=235) and cost-effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05-5.59; N=1, n=16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97-1.27; N=1, n=64) and sustained healing compared to devices alone, but likely increase new heel ulcers. Non-removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non-surgical offloading interventions to heal most plantar DFU. However, all these interventions have low-to-moderate certainty of evidence supporting their outcomes and more high-quality trials are needed to improve our certainty for the effectiveness of most offloading interventions.

Comparative efficacy of growth factor therapy in healing diabetes-related foot ulcers: A network meta-analysis of randomized controlled trials.

This study examined the relative efficacy of growth factor therapies in healing diabetes-related foot ulcers (DFU). PubMed and Cochrane databases were searched for randomized controlled trials testing growth factor therapies for treating DFU. The primary outcome was complete wound closure. Results were reported as relative risk (RR)±95% credible intervals (CrI). The risk of bias was assessed using Cochrane's RoB-2 tool. A total of 31 RCTs involving 2174 participants were included. Only 13 of the trials (n=924) reported on the aetiology of the ulcers (85.4% neuropathic and 14.6% ischaemic). Epidermal growth factor (RR 3.83; 95% CrI 1.81, 9.10), plasma-rich protein (PRP) (RR 3.36; 95% CrI 1.66, 8.03) and platelet-derived growth factor (PDGF) (RR 2.47; 95% CrI 1.23, 5.17) significantly improved the likelihood of complete ulcer healing compared to control. Sub-analyses suggested that PRP (3 trials - RR 9.69; 95% CrI 1.37, 103.37) and PDGF (6 trials - RR 2.22; 95% CrI 1.12, 5.19) significantly improved the likelihood of wound closure amongst trial mainly recruiting participants with neuropathic ulcers. Eleven trials had a low risk of bias, 9 had some concerns and 11 had a high risk of bias. Sub-analysis of trials with a low risk of bias suggested that none of the growth factors significantly improved ulcer healing compared with control. This network meta-analysis found low-quality evidence that Epidermal growth factor, PRP and PDGF therapy improved DFU healing likelihood compared with control. Larger well-designed trials are needed.

The Validity and Reliability of Self-Reported Adherence to Using Offloading Treatment in People with Diabetes-Related Foot Ulcers.

Adherence to using offloading treatment is crucial to healing diabetes-related foot ulcers (DFUs). Offloading adherence is recommended to be measured using objective monitors. However, self-reported adherence is commonly used and has unknown validity and reliability. This study aimed to assess the validity and reliability of self-reported adherence to using removable cast walker (RCW) offloading treatment among people with DFUs. Fifty-three participants with DFUs using RCWs were included. Each participant self-reported their percentage adherence to using their RCW of total daily steps. Participants also had adherence objectively measured using dual activity monitors. After one week, a subset of 19 participants again self-reported their percentage adherence to investigate test-retest reliability. Validity was tested using Pearson's r and Bland-Altman tests, and reliability using Cohen's kappa. Median (IQR) self-reported adherence was greater than objectively measured adherence (90% (60-100) vs. 35% (19-47), p < 0.01). There was fair agreement (r = 0.46; p < 0.01) and large 95% limits of agreement with significant proportional bias (β = 0.46, p < 0.01) for validity, and minimal agreement for test-retest reliability (K = 0.36; p < 0.01). The validity and reliability of self-reported offloading adherence in people with DFU are fair at best. People with DFU significantly overestimate their offloading adherence. Clinicians and researchers should instead use objective adherence measures.

Do diabetes-related foot ulcer wound fluid measures have clinical utility as biomarkers for healing? A systematic review.

This study aimed to identify potential biomarkers reported in wound fluid of diabetes-related foot ulcers (DRFUs), and their ability to reflect current and prospective wound healing. A systematic search was executed following the PRISMA methodology across five chosen databases: MEDLINE, Embase, Scopus, Cochrane Clinical Trials and Cochrane Systematic Reviews. Using keywords and phrases, it yielded 5022 results. Based on predetermined inclusion and exclusion criteria, 19 papers were included in the final analysis, among which: seven reported serial temporal biomarker changes in wounds; six reported measures from baseline and related them to healing rate and/or final healing outcome; four papers reported both end-points, and two papers reported solely on baseline biomarker levels in a generalised diabetic foot ulcer group. Across the studies, a total of 46 distinct markers were described from the wound fluid of n=1141 participants. Biomarkers examined included proteases, protease inhibitors, growth factors, chemokines and cytokines, with proteases being the largest subcategory making up 16 (34.8%) of the markers investigated (n=7). Matrix metalloproteinase-9 (MMP-9) was the most frequently investigated protease and it currently holds the most biomarker promise (n=5). Wound bacterial profiles variably related to wound healing outcome (n=5). One study reported biophysical markers rather than biomarkers, including measurement of wound fluid pH. Study quality was generally good. Drawing quantitative comparisons between papers was not possible due to variability in experimental design including sampling and assessment methods. These studies collectively indicate several wound fluid measures that could identify DRFU status and outcomes, and that methodological standardisation in the field is needed to determine reliable predictive thresholds for healing.

Self-Monitoring Diabetes-Related Foot Ulcers with the MyFootCare App: A Mixed Methods Study

People with diabetes-related foot ulcers (DFUs) need to perform self-care consistently over many months to promote healing and to mitigate risks of hospitalisation and amputation. However, during that time, improvement in their DFU can be hard to detect. Hence, there is a need for an accessible method to self-monitor DFUs at home. We developed a new mobile phone app, "MyFootCare", to self-monitor DFU healing progression from photos of the foot. The aim of this study is to evaluate the engagement and perceived value of MyFootCare for people with a plantar DFU over 3 months' duration. Data are collected through app log data and semi-structured interviews (weeks 0, 3, and 12) and analysed through descriptive statistics and thematic analysis. Ten out of 12 participants perceive MyFootCare as valuable to monitor progress and to reflect on events that affected self-care, and seven participants see it as potentially valuable to enhance consultations. Three app engagement patterns emerge: continuous, temporary, and failed engagement. These patterns highlight enablers for self-monitoring (such as having MyFootCare installed on the participant's phone) and barriers (such as usability issues and lack of healing progress). We conclude that while many people with DFUs perceive app-based self-monitoring as valuable, actual engagement can be achieved for some but not for all people because of various facilitators and barriers. Further research should target improving usability, accuracy and sharing with healthcare professionals and test clinical outcomes when using the app.

Differences in adherence to using removable cast walker treatment during daytime and nighttime weight-bearing activities in people with diabetes-related foot ulcers.

Patients' adherence to using knee-high offloading treatment is critical to effective healing of diabetes-related foot ulcers (DFUs). Previous studies have found that patients generally have low adherence to using removable knee-high offloading treatments, yet no study has investigated whether their adherence differs during daytime and nighttime. This study aimed to investigate the levels and factors associated with adherence to using knee-high removable cast walker (RCW) treatment during daytime and nighttime weight-bearing activities in people with DFUs. This was a secondary analysis of data collected from a multi-centre cross-sectional study investigating adherence to using knee-high RCWs among 57 participants with DFUs. All participants had multiple socio-demographic, physiological and psychosocial factors collected, before having their adherence to using RCWs during weight-bearing activity monitored over a 1-week period using the dual activity monitor method. Adherence data were categorised into daytime (06:00-18:00) and nighttime (18:00-06:00) periods and calculated separately. Multiple linear regression was used to identify factors associated with daytime and nighttime adherence. Mean adherence to using RCW during weight-bearing activities in people with DFUs was higher during daytime compared with nighttime [39.9% (SD = 18.9) versus 20.4% (SD = 16.7), p < 0.001]. Factors independently associated with lower adherence during daytime were being male, longer diabetes duration, not having peripheral artery disease (PAD), and higher perceived RCW heaviness. Factors associated with lower adherence during nighttime were higher mean daytime steps, not having retinopathy and having dyslipidaemia. Adherence to using RCWs during weight-bearing activities reduced significantly at nighttime compared with daytime among people with DFUs, and this was associated with different factors. Interventions to improve adherence, in research and clinical practice, should incorporate methods to target daytime or nighttime adherence specifically.

Offloading effects of a removable cast walker with and without modification for diabetes-related foot ulceration: a plantar pressure study

BackgroundRemovable cast walkers (RCWs), with or without modifications, are used to offload diabetes-related foot ulcers (DRFUs), however there is limited data relating to their offloading effects. This study aimed to quantify plantar pressure reductions with an RCW with and without modification for DRFUs.MethodsThis within-participant, repeated measures study included 16 participants with plantar neuropathic DRFUs. Walking peak plantar pressures at DRFU sites were measured for four conditions: post-operative boot (control condition), RCW alone, RCW with 20 mm of felt adhered to an orthosis, and RCW with 20 mm of felt adhered to the foot.ResultsCompared to the control condition, the greatest amount of peak plantar pressure reduction occurred with the RCW with felt adhered to the foot (83.1% reduction, p < .001). The RCW with felt adhered to the foot also offered greater peak plantar pressure reduction than the RCW alone (51.3%, p = .021) and the RCW with felt adhered to an orthosis (31.4%, p = .009).ConclusionThe largest offloading effect recorded was with the RCW with felt adhered to the foot. High-quality randomised trials are now needed to evaluate the effectiveness of this device for healing DRFUs.

In vivo observations of biofilm adhering to a dialkylcarbamoyl chloride-coated mesh dressing when applied to diabetes-related foot ulcers: A proof of concept study.

In this proof-of-concept study of twenty participants, we sought to determine if a DACC (Dialkylcarbamoyl chloride)-coated mesh dressing demonstrates an ability to adhere biofilm when placed on Diabetes Related Foot Ulcers (DRFUs) with chronic infection. The study also sought to determine if removal of the DACC-coated mesh dressings contributes to reducing the total number of bacteria in DRFUs, by exploring the total microbial loads, microbial community composition, and diversity. Standard of care was provided in addition to the application of DACC or DACC hydrogel every three days for a total of two weeks. Wound swabs, tissue curettage, and soiled dressings were collected pre and post-treatment. Tissue specimens obtained pre-treatment were analysed with scanning electron microscopy (SEM) and peptide nucleic acid fluorescent in situ hybridisation (PNA-FISH) with confocal laser scanning microscopy and confirmed the presence of biofilm in all DRFUs. SEM confirmed the presence of biofilms readily adhered to soiled DACC-coated mesh dressings pre- and post-treatment in all participants. Real-time quantitative polymerase chain reaction (qPCR) demonstrated the mean total microbial load of DRFUs in 20 participants did not change after two weeks of therapy (pre-treatment=4.31 Log10 16 S copies (±0.8) versus end of treatment=4.32 Log10 16 S copies (±0.9), P=.96, 95% CI -0.56 to 0.5). 16 S sequencing has shown the microbial composition of DACC dressings and wound swabs pre- and post-treatment remained similar (DACC; R=-.047, P=.98, Swab; R=-.04, P=.86), indicating the microbial communities originate from the ulcer. Biofilms adhere to DACC-coated mesh dressings; however, this may not reduce the total microbial load present within DRFU tissue. Wound dressings for use in hard-to-heal wounds should be used as an adjunct to a good standard of care which includes debridement and wound bed preparation.

Cost-effectiveness of guideline-based care provision for patients with diabetes-related foot ulcers: A modelled analysis using discrete event simulation.

The provision of guideline-based care for patients with diabetes-related foot ulcers (DFU) in clinical practice is suboptimal. We estimated the cost-effectiveness of higher rates of guideline-based care, compared with current practice. The costs and quality-adjusted life-years (QALYs) associated with current practice (30% of patients receiving guideline-based care) were compared with seven hypothetical scenarios with increasing proportion of guideline-based care (40%, 50%, 60%, 70%, 80%, 90% and 100%). Comparisons were made using discrete event simulations reflecting the natural history of DFU over a 3-year time horizon from the Australian healthcare perspective. Incremental cost-effectiveness ratios were calculated for each scenario and compared to a willingness-to-pay of AUD 28,000 per QALY. Probabilistic sensitivity analyses were conducted to incorporate joint parameter uncertainty. All seven scenarios with higher rates of guideline-based care were likely cheaper and more effective than current practice. Increased proportions compared with current practice resulted in between AUD 0.28 and 1.84million in cost savings and 11-56 additional QALYs per 1000 patients. Probabilistic sensitivity analyses indicated that the finding is robust to parameter uncertainty. Higher proportions of patients receiving guideline-based care are less costly and improve patient outcomes. Strategies to increase the proportion of patients receiving guideline-based care are warranted.

A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

Cellular mechanisms and/or microbiological interactions which contribute to chronic diabetes related foot ulcers (DRFUs) were explored using serially collected tissue specimens from chronic DRFUs and control healthy foot skin. Total RNA was isolated for next‐generation sequencing. We found differentially expressed genes (DEGs) and enriched hallmark gene ontology biological processes upregulated in chronic DRFUs which primarily functioned in the host immune response including: (i) Inflammatory response; (ii) TNF signalling via NFKB; (iii) IL6 JAK‐STAT3 signalling; (iv) IL2 STAT5 signalling and (v) Reactive oxygen species. A temporal analysis identified RN7SL1 signal recognition protein and IGHG4 immunoglobulin protein coding genes as being the most upregulated genes after the onset of treatment. Testing relative temporal changes between healing and non‐healing DRFUs identified progressive upregulation in healed wounds of CXCR5 and MS4A1 (CD20), both canonical markers of lymphocytes (follicular B cells/follicular T helper cells and B cells, respectively). Collectively, our RNA‐seq data provides insights into chronic DRFU pathogenesis.

Multiple factors predict longer and shorter time-to-ulcer-free in people with diabetes-related foot ulcers: Survival analyses of a large prospective cohort followed-up for 24-months

AimsTo investigate factors independently associated with time-to-(being)-ulcer-free, time-varying effects and predict adjusted ulcer-free probabilities, in a large prospective cohort with diabetes-related foot ulcers (DFU) followed-up for 24 months. MethodsPatients presenting with DFU(s) to 65 Diabetic Foot Services across Queensland, Australia, between July-2011 and December-2017 were included. Demographic, comorbidity, limb, ulcer, and treatment factors were captured at presentation. Patients were followed-up until ulcer-free (all DFU(s) healed), amputation, death or two years. Factors associated with time-to-ulcer-free were investigated using both Cox proportional hazards and flexible parametric survival models to explore time-varying effects and plot predicted adjusted ulcer-free probability graphs. ResultsOf 4,709 included patients (median age 63 years, 69.5% male), median time-to-ulcer-free was 112 days (IQR:40->730), with 68.4% ulcer-free within two years. Factors independently associated with longer time-to-ulcer-free were each year of age younger than 60 years, living in a regional or remote area, smoking, neuropathy, peripheral artery disease (PAD), ulcer size >1 cm2, deep ulcer and mild infection (all p < 0.05). Time-varying effects were found for PAD and ulcer size limiting their association to six months only. Shorter time-to-ulcer-free was associated with recent DFU treatment by a podiatrist and receiving knee-high offloading treatment (both p < 0.05). Predicted adjusted ulcer-free probability graphs reported largest differences in time-to-ulcer-free over 24-months for geographical remoteness and PAD factors. ConclusionsMultiple factors predicted longer and shorter time-to-ulcer-free in people presenting with DFUs. Considering these factors, their time-varying effects and adjusted ulcer-free probability graphs, should aid the prediction of the likely time-to-(being)-ulcer-free for DFU patients.

Factors associated with adherence to using removable cast walker treatment among patients with diabetes-related foot ulcers

IntroductionAdherence to using knee-high offloading treatment is critical for healing diabetes-related foot ulcers (DFUs). However, few studies have investigated patients’ adherence to using knee-high offloading treatment. We aimed to investigate...

Australian guideline on offloading treatment for foot ulcers: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease.

BackgroundPressure offloading treatment is critical for healing diabetes-related foot ulcers (DFU). Yet the 2011 Australian DFU guidelines regarding offloading treatment are outdated. A national expert panel aimed to develop a new Australian guideline on offloading treatment for people with DFU by adapting international guidelines that have been assessed as suitable to adapt to the Australian context.MethodsNational Health and Medical Research Council procedures were used to adapt suitable International Working Group on the Diabetic Foot (IWGDF) guidelines to the Australian context. We systematically screened, assessed and judged all IWGDF offloading recommendations using best practice ADAPTE and GRADE frameworks to decide which recommendations should be adopted, adapted or excluded in the Australian context. For each recommendation, we re-evaluated the wording, quality of evidence, strength of recommendation, and provided rationale, justifications and implementation considerations, including for geographically remote and Aboriginal and Torres Strait Islander peoples. This guideline, along with five accompanying Australian DFU guidelines, underwent public consultation, further revision and approval by ten national peak bodies (professional organisations).ResultsOf the 13 original IWGDF offloading treatment recommendations, we adopted four and adapted nine. The main reasons for adapting the IWGDF recommendations included differences in quality of evidence ratings and clarification of the intervention(s) and control treatment(s) in the recommendations for the Australian context. For Australians with plantar DFU, we recommend a step-down offloading treatment approach based on their contraindications and tolerance. We strongly recommend non-removable knee-high offloading devices as first-line treatment, removable knee-high offloading devices as second-line, removable ankle-high offloading devices third-line, and medical grade footwear as last-line. We recommend considering using felted foam in combination with the chosen offloading device or footwear to further reduce plantar pressure. If offloading device options fail to heal a person with plantar DFU, we recommend considering various surgical offloading procedures. For people with non-plantar DFU, depending on the type and location of the DFU, we recommend using a removable offloading device, felted foam, toe spacers or orthoses, or medical grade footwear. The six new guidelines and the full protocol can be found at: https://diabetesfeetaustralia.org/new-guidelines/.ConclusionsWe have developed a new Australian evidence-based guideline on offloading treatment for people with DFU that has been endorsed by ten key national peak bodies. Health professionals implementing these offloading recommendations in Australia should produce better DFU healing outcomes for their patients, communities, and country.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13047-022-00538-3.

Routine bacterial culture of proximal bone specimens during minor amputation in patients with diabetes-related foot infections has little clinical utility in predicting re-operation or ulcer healing

BackgroundTrans-phalangeal and trans-metatarsal amputation, collectively termed ‘minor amputations’ are important procedures for managing infections of diabetes-related foot ulcers (DFU). Following minor amputation, international guidelines recommend a prolonged course of antibiotics if residual infected bone on intra-operative bone samples are identified, but the quality of the evidence underpinning these guidelines is low. In this study, we examined the concordance of microbiological results from proximal bone cultures compared to results from superficial wound swabs in relation to patient outcomes; with the aim of determining the utility of routinely obtaining marginal bone specimens.MethodsData was retrospectively collected on 144 individuals who underwent minor amputations for infected DFU at a large Australian tertiary hospital. Concordance was identified for patients with both superficial wound swabs and intra-operative bone samples available. Patient outcomes were monitored up to 6 months post-amputation. The primary outcome was complete healing at 6 months; and secondary outcome measures included further surgery and death. Mann Whitney U testing was performed for bivariate analyses of continuous variables, Chi-Squared testing used for categorical variables and a logistic regression was performed with healing as the dependent variable.ResultsA moderate-high degree of concordance was observed between microbiological samples, with 38/111 (35%) of patients having discordant wound swab and bone sample microbiology. Discordant results were not associated with adverse outcomes (67.2% with concordant results achieved complete healing compared with 68.6% patients with discordant results; P = 0.89). Revascularisation during admission (0.37 [0.13–0.96], P = 0.04) and amputation of the 5th ray (0.45 [0.21–0.94], P = 0.03) were independent risk factors for non-healing.ConclusionThere was a moderate-high degree of concordance between superficial wound swab results and intra-operative bone sample microbiology in this patient cohort. Discordance was not associated with adverse outcomes. These results suggest there is little clinical utility in routinely collecting proximal bone as an adjunct to routine wound swabs for culture during minor amputation for an infected DFU.