How Diabetic Foot Ulcer Patients Can Self-Treat Wound Care: An Integrative Literature Review.

Introduction: To improve the capacity of diabetic foot ulcer (DFU) patients for self-management of wound care, there is a renewed need for self-care on their part, as well as an increase in their readiness to deal with issues and heal their wounds. Therefore, this review empirically assessed contemporary evidence on how patients with DFU can perform self-treat wound care. Methods: This integrative literature review assessed how patients with DFU could perform self-treat wound care. Whittemore and Knafl integrative information literature review involved searching four databases (Scopus, PubMed, Web of Science, and Google Scholar), which resulted in 2,595 published articles, between 2010 and 2023. Nineteen articles satisfied the requirements for inclusion and quality assessment, and the PRISMA review checklist was followed. Results: No research has addressed DFU patients' self-treatment of wound care. The integration of evidence from quantitative and qualitative studies was achieved in three categories: (1) motivation, (2) self-wound care strategy, and (3) self-wound care performance by DFU patients. Conclusion: To equip themselves to perform wound care independently, patients with DFU must receive training to clean wounds, apply wound medication, and perform dressings. There is a need for research that develops a self-treat wound care intervention model in patients with DFU.

Conservative surgery in the management of diabetic foot complications (excluding Charcot). The role of the orthopedic surgeon.

Diabetic foot complications (DFC) such as ulcers and infection are the leading cause for non-traumatic non-oncologic amputations worldwide with a 5-year mortality reaching 70 %. Every attempt is warranted to preserve the limb for physical and psychological integrity of these patients. When possible to perform, conservative surgeries could save the foot and its function. This review will focus on those procedures that do not require in-depth surgical or microsurgical skills and that could be performed by general orthopedic surgeons. Along with the technical description and specific indication, a literature search was performed to locate the evidence in relation with the efficacy of these procedures. The procedures could be described in 3 categories: bony surgeries, soft tissue procedures and orthoplastic techniques. The bones surgeries include resection arthroplasty, metatarsal osteotomy, internal pedal amputation, distal Symes amputation, cement augmentation and partial or total calcanectomy. Soft tissue procedures include Achilles tendon lengthening, gastrocnemius recession, toe flexor tenotomy and tendon transfer. The reconstructive/orthoplastic techniques include skin grafting, local flaps, fillet flap and regional flaps, mainly the reverse sural flap. Though most of these conservative surgeries have been shown to yield good to excellent results, the indication for each surgery could be confusing. The role of the orthopedic surgeon is fundamental for the optimal treatment of DFC. Though most procedures are easy to learn and to perform without the need of extra surgical skills, mastering indications is key for successful outcomes. In addition, the knowledge of these limb preserving techniques could be paramount in rural areas or if no foot and ankle surgeons are available.

A multicentre clinical trial evaluating the outcomes of two application regimens of a unique keratin-based graft in the treatment of Wagner grade one non-healing diabetic foot ulcers.

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs.

Screening tools for diabetic foot ulcers: a narrative review.

The prevalence of diabetic foot ulcers (DFUs) is 4 to 10% among people with diabetes mellitus. DFUs are associated with increased morbidity and mortality as well as reduced quality of life and have a significant impact on overall healthcare expenditure. The main predisposing factors for DFU are diabetic neuropathy, peripheral arterial disease, and trauma. The fact that a range of tests can be used to identify patients at risk for DFU often causes confusion among practitioners regarding which screening tests should be implemented in clinical practice. Herein we sought to determine whether tests of somatic nerve function, such as pinprick sensation, thermal (cold/hot) test, ankle reflexes, vibration perception, 10-g monofilament, Ipswich touch test, neuropathy disability score, and nerve conduction studies, predict the development of DFUs. In addition, we examined whether sudomotor function screening tests, such as Neuropad, sympathetic skin response, and other tests, such as elevated plantar pressure or temperature measurements, can be used for DFU screening. If not treated properly, DFUs can have serious consequences, including amputation, early detection and treatment are vital for patient outcomes.

Safety evaluation of bi-layered allogenic keratinocyte and fibroblast skin substitute for diabetic foot ulcers-SAFESKIN-DFU: A Phase 1 clinical trial.

AIM: To assess the safety and efficacy of a local skin substitute product in the treatment of chronic diabetic foot ulcers (DFUs). MATERIALS AND METHODS: Five patients were evaluated over 6 months. Skin substitutes were applied twice at 2-week intervals. Patients were monitored for any possible adverse effects and wound improvement. RESULTS: The results indicated the overall safety of the skin substitute, with only few adverse effects unrelated to this product. Significant reduction in wound size was observed in four patients during the initial 12-week treatment phase, with complete closure in two patients at 24 weeks. CONCLUSIONS: The application of a bi-layered allogeneic keratinocyte and fibroblast skin substitute in patients with chronic DFU was safe and associated with favourable wound healing results. Adherence to standard treatment protocols, including optimal offloading, is essential to maximize the likelihood of successful wound healing.

Evolving Trends in the Management of Diabetic Foot Ulcers: A Narrative Review.

The prevalence of diabetic foot ulcers (DFUs) is projected to increase worldwide, which necessitates a review of the current management principles and the development of new approaches to care. The principles of management involve proper glycemic control, infection control, pressure redistribution, wound care debridement, and revascularization. Other modalities of management, such as hyperbaric oxygen therapy and negative wound pressure therapy, are also being explored. While some aspects of DFU care lack high-quality evidence, a multidisciplinary approach incorporating these evolving trends has the potential to improve outcomes and prevent lower extremity amputations in this challenging condition. This review highlights the need for further research to establish definitive treatment protocols for optimal DFU management.

Trajectories of Remnant Cholesterol are Associated with Diabetic Foot Ulcer in Adult Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Objective: This study aimed to investigate the potential association between long-term variations in remnant cholesterol (RC) levels and the development of diabetic foot ulcers (DFU) in participants with type 2 diabetes (T2D). Methods: This was a retrospective cohort study. Variation in RC was assessed by the following metrics: mean, standard deviation (SD), coefficient of variation (CV) and trajectories pattern of RC. To identify RC trajectories, we employed the latent class mixture model. The primary endpoint was the development of DFU, and the time-to-event data were analyzed using Cox regression. Results: A total of 1874 patients with T2D were included, with a median follow-up duration of 4.7 years. Among them, 129 individuals (6.9%) developed DFU. The proportion of DFU was significantly higher in the U-shaped group compared to the median group (P for trend < 0.001). Upon adjustment for confounding variables, the U-shaped trajectory correlated with a higher risk of DFU, demonstrating a hazard ratio (HR) of 2.57 (95% CI, 1.54-4.27). Subgroup analysis showed the U-shaped trajectory had a higher DFU risk regardless of gender (HR=2.40 and 2.81, respectively), glycemic control (HR=1.89 and 7.41, respectively), smoking (HR=2.36 and 2.93, respectively), or hypertension (HR=2.30 and 2.97, respectively). No association was found between mean, SD and CV of RC and DFU. Conclusion: A U-shape trajectory of RC was independently associated with an elevated risk of DFU among patients with T2D.

Treatment of bacterially contaminated lower extremity ulcers with a fatty acid-containing wound matrix: a case series.

OBJECTIVE: The aim was to evaluate the effectiveness of a marine omega fatty acid-containing multimodal wound matrix (MWM) in reducing bacterial contamination and supporting wound area reduction (WAR) in patients with hard-to-heal wounds of varying aetiologies. METHOD: A prospective, single-site, pilot case series of patients with hard-to-heal wounds. All wounds were considered non-healing prior to inclusion as they had failed to achieve at least 50% WAR after at least four weeks of standard of care (SoC) treatments. Patients were seen once weekly for wound assessments, matrix application and dressing changes. Baseline and weekly fluorescence images, standard wound images and wound measurements were obtained. RESULTS: A total of three patients, two with venous leg ulcers (VLUs) and one with a diabetic foot ulcer (DFU) were enrolled in this pilot study. The mean baseline wound age prior to study enrolment was 24 weeks, with a mean baseline wound size of 8.61cm2. The two VLUs went on to complete closure. The DFU displayed a total WAR of 53% by six weeks, when the patient was lost to follow-up due to a geographical relocation. The mean percentage area reduction of all wounds combined was 82% upon study completion. CONCLUSION: The use of MWM proved to be effective and safe in this patient cohort. The wounds included in this case series failed to enter a healing trajectory with SoC wound therapies. The MWM supported wound closure and reduced bacterial loads in this patient cohort.

Vildagliptin promotes diabetic foot ulcer healing through autophagy modulation.

The study aimed to investigate the molecular mechanisms underlying the effects of Vildagliptin on the healing of diabetic foot ulcers (DFUs). The research compared patients who received 12 weeks of Vildagliptin treatment to those who did not. Various molecular markers associated with wound healing were measured. Wound fluid samples were collected from DFUs using a filter paper absorption technique, and total RNA was extracted for quantitative real-time PCR (qPCR). The results showed that the autophagy marker NUP62 was significantly downregulated in the Vildagliptin group at week 12 compared to baseline (median expression 0.57 vs. 1.28; P = 0.0234). No significant change was observed in the placebo group (median expression 1.61 vs. 1.48; P = 0.9102). Both groups showed substantial downregulation of RIPK3, a necroptosis marker, at week 12 compared to their respective baselines. In addition to its effects on blood sugar levels, Vildagliptin may promote DFU healing by reducing autophagy in patients with diabetes.

Effect of different inner pressures of air insoles and walking durations on plantar pressure time integral.

Air insoles have provided insights for reducing the risk of diabetic foot ulcers (DFU). The pressure time integral (PTI) is an effective assessment that considers the time effect in various physical activities. We investigated the interactions between three different insole inner pressures (80, 160, and 240 mmHg) and two walking durations (10 and 20 min). The big toe (T1), first metatarsal head (M1), and second metatarsal head (M2) were investigated in 13 healthy participants. One-way analysis of variance (ANOVA) showed that the effects of each insole inner pressure significantly differed (P < 0.05) with a 10 min walking duration. The PTI values resulting from 80 mmHg in M2 (38.4 ± 3.8, P = 0.002) and 160 mmHg in M1 (44.3 ± 4.3, P = 0.027) were lower than those from 240 mmHg. Additionally, the paired t test showed that the effects of each walking duration were also considerably different at 160 mmHg. The PTI at 10 min was lower than that at 20 min in M1 (44.31 ± 4.31, P = 0.015) and M2 (47.14 ± 5.27, P = 0.047). Thus, we suggest that walking with a pressure of 160 mmHg for 10 min has a lower risk of DFU.

Predictors of limb saving in diabetic foot ulcer.

Objectives: This study was aimed to determine the various factors which could serve as predictor of saving of lower limb from amputation in patients with diabetic foot ulcer (DFU). Method: This three-year retrospective study was conducted in the Diabetes and Endocrinology Unit of Hayatabad Medical complex Peshawar, Pakistan. Demographic, clinical, laboratory and radiological information of the diabetic patients with DFU admitted between January 2020 to December 2022 was retrieved from the hospital files. Information regarding initial and final decision regarding amputation and the outcome of the ulcer was also recorded. Results: A total of 502 patients of diabetes mellitus (DM) with DFU were included in the study, of whom there were 279 (55.6%) males and 223 (44.4%) females. The mean age of the study population, mean duration of DM and mean HbA1c were 55.2 ± 9.8 years, 13.7 ± 6.7 years and 11.2 ± 2.4 %, respectively. Patients who had an amputation of their lower limbs had an increased age (p= 0.034), raised total leucocyte count (TLC) (p= <0.001), higher HbA1c (p= 0.025), had osteomyelitis (p= <0.001), and had a higher-grade ulcer (p= <0.001). On binary logistic regression analysis, ulcer grade (OR=7.4, p= <0.001), osteomyelitis (OR=11.8, p= <0.001), and initial decision of no amputation at the time of admission (OR=33.6, p=<0.001) were independently associated with the lower limb salvage. Conclusion: DFU which were of grade I to II, had no evidence of osteomyelitis and for which an initial decision was of no amputation were more likely to be salvaged.

Association of vitamin D status and vitamin D receptor polymorphism in diabetic foot ulcer patients: A prospective observational study in a South-Indian tertiary healthcare facility.

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case-control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non-DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real-time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs.

Effects of diabetes-related foot ulcer depth on healing days, cost, and quality of life: A prospective observational study.

The relationship between the depth of the diabetes-related foot ulcers, and the healing days, cost, and QOL was examined.Depth 4 and 5 ulcers, namely beyond the tendons, exhibited significantly longer healing days and higher costs than Depth 2 and 3 ulcers. As for QOL, there were no significant differences in utility values between the depth categories.Results on healing time and cost reiterate the importance of early consultation, especially before the depth becomes deeper than the tendon.

A retrospective cohort study on enhanced recovery after surgery (ERAS) in patients with diabetic foot ulcer.

Enhanced recovery after surgery (ERAS) has been successfully integrated into a diverse array of surgical fields to improve the quality and efficacy of treatment intervention. Nonetheless, the application of the ERAS protocol for patients with diabetic foot ulcer (DFU) subsequent to undergoing surgical procedures has not been previously explored. Therefore, this study aimed to investigate the effect of an enhanced recovery protocol on perioperative outcomes in patients with DFU following surgical procedures. A retrospective analysis was conducted on 112 patients with DFU who underwent surgery between January 2020 and December 2021 at a tertiary referral care center. In total, 57 patients received standard perioperative care (the non-ERAS group), and 55 patients received ERAS care (the ERAS group). The primary outcomes included the length of stay (LOS), wound healing time, patient satisfaction, and costs, serving as the basis for assessing the effectiveness of the two approaches. Secondary outcomes included preoperative anxiety (APAIS score), nutritional status (PG-SGA), pain (NRS score), the incidence of lower-extremity deep vein thrombosis (DVT), the reduction in lower-limb circumference, and the activity of daily living scale (Barthel Index). The ERAS group exhibited significantly shorter LOS (11.36 vs. 26.74 days; P < 0.001) and lower hospital costs (CNY 62,165.27 vs. CNY 118,326.84; P < 0.001), as well as a higher patient satisfaction score and Barthel Index score (P < 0.05). Additionally, we found a lower APAIS score, incidence of DVT, and circumference reduction in lower limbs in the ERAS group compared to the non-ERAS group (P < 0.05). In comparison, the wound healing time, nutritional status, and pain levels of participants in both groups showed no significant difference (P > 0.05). By reducing the LOS and hospital costs, and by minimizing perioperative complications, the ERAS protocol improves the quality and efficacy of treatment intervention in patients with DFU who underwent surgical procedures.Trial registration number: ChiCTR 2200064223 (Registration Date: 30/09/2022).

Effects of vitamin D supplementation on diabetic foot ulcer healing: a meta-analysis.

PURPOSE: To systematically review the effect of vitamin D supplementation on diabetic foot ulcer (DFU) healing. METHODS: The PubMed, Web of Science, Science direct, Ebsco host, CNKI, WanFang, VIP, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the impact of vitamin D supplementation on DFUs from inception to 19 November 2022. Two researchers independently screened the literature, extracted the data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. RESULTS: A total of seven studies involving 580 patients were included. The results of meta-analysis showed that compared with control group, the wound healing efficiency rate (RR = 1.42, 95%CI 1.03 to 1.95, P = 0.03) and wound reduction rate (MD = 13.11, 95%CI 4.65 to 21.56, P < 0.01) of the experimental group were higher; the change values of the wound area (MD = -3.29, 95%CI -4.89 to 1.70, P < 0.01) and 25 (OH) D (MD = 9.63, 95%CI 6.96 to 12.31, P < 0.01) were larger. Supplementation of vitamin D on DFU patients can improve glucose metabolism and insulin indexes: hemoglobin A1c (MD = -0.44, 95%CI -0.62 to -0.26, P < 0.01), fasting insulin (MD = -3.75, 95%CI -5.83 to -1.67, P < 0.01), HOMA - ß (MD = -5.14, 95%CI -8.74 to -1.54, P < 0.01), and quantitative insulin sensitivity check index (MD = 0.02, 95%CI 0.01 to 0.02, P < 0.01). It can also improve inflammation and oxidative stress markers: high sensitivity C-reactive protein (MD = -0.83, 95%CI -1.06 to -0.59, P < 0.01), erythrocyte sedimentation rate (MD = -15.74, 95%CI -21.78 to -9.71, P<0.01), nitric oxide (MD = 1.81, 95%CI 0.07 to 3.55, P = 0.04), and malondialdehyde (MD = -0.43, 95%CI -0.61 to -0.24, P<0.01). There was no statistically significant difference in changes of fasting plasma glucose, homeostasis model of assessment-insulin resistance, total antioxidant capacity, glutathione, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol (P>0.05). CONCLUSION: The current evidence suggests that vitamin D supplementation can significantly promote DFU healing by lowering blood sugar and alleviating inflammation and oxidative stress. Key messages What is already known on this topic  Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, with high morbidity, mortality and resource utilization. Vitamin D has the effect of lowering blood sugar, improving insulin sensitivity, and increasing anti-inflammatory response. Clinical research on vitamin D supplementation for the treatment of DFU is increasing, but due to the lack of combing and integration, the actual efficacy of vitamin D in patients is unclear. What this study adds  This meta-analysis has shown that vitamin D supplementation can significantly promote DFU healing by lowering blood glucose and alleviating inflammation and oxidative stress. How this study might affect research, practice or policy  This study preliminarily found the effectiveness of vitamin D supplementation on the healing of DFU, which can provide a reference for the treatment of DFU by medical staff.

A Case of Recurrent Diabetic Foot Ulcers With Multi-drug Resistant Poly-Microbial Infections.

For people with diabetes, diabetic foot ulcers (DFUs) are a serious condition that can result in amputations, among other dire consequences. This case report details the clinical course and management of a 40-year-old male with type II diabetes mellitus presenting with recurrent DFUs and blackening of the toes. Despite initial surgical intervention and aggressive antimicrobial therapy, the patient experienced persistent infection and graft failure, necessitating multiple treatments and ongoing care. Most of the bacteria that were identified from diabetic foot infections (DFIs) were gram-negative, and they were resistant to common treatments. The intensity of DFI was correlated with polymicrobial illnesses.

Determining the Best Noninvasive Test for Peripheral Arterial Disease Diagnosis to Predict Diabetic Foot Ulcer Healing in Patients Following Endovascular Revascularization.

BACKGROUND/OBJECTIVES: To analyze the best noninvasive tests prognosis marker in patients with diabetic foot ulcer (DFU) who underwent endovascular revascularization based on clinical outcomes, such as healing rate, time to heal, and free amputation survival after at least a six-month follow-up. METHODS: A multicentric prospective observational study was performed with 28 participants with ischemic or neuroischemic DFU who came to the participant centers and underwent endovascular revascularization between January 2022 and March 2023. Toe systolic pressure (TP), ankle systolic pressure (AP), the ankle brachial pressure index (ABPI), the toe brachial pressure index (TBPI), transcutaneous pressure of oxygen (TcPO2), and skin perfusion pressure (SPP) were evaluated using PeriFlux 6000 System, Perimed, Sweden, before (Visit 0) and four weeks after revascularization (Visit 1). The primary clinical outcome was an evaluation of the clinical evolution of noninvasive tests comparing Visit 0 and Visit 1, estimating the sensitivity for predicting wound healing of noninvasive tests at six months following initial recruitment. RESULTS: After six months, 71.43% (n = 20) of DFU healed, four patients (14.3%) received major amputations, and one (3.5%) died. The two tests that best predicted wound healing after revascularization according to the ROC curve were TcPO2 and TP with sensitivities of 0.89 and 0.70 for the cut-off points of 24 mmHg and 46 mmHg, respectively. CONCLUSIONS: TcPO2 and TP were the two tests that best predicted wound healing in patients who underwent endovascular revascularization. Clinicians should consider the importance of the evaluation of microcirculation in the healing prognosis of patients with diabetic foot ulcers.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine.

Diabetic peripheral neuropathy (DPN) is one of the strongest risk factors for diabetic foot ulcers (neuropathic ulcerations) and the existing ulcers may further deteriorate due to the damage to sensory neurons. Moreover, the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time. DPN is associated with gut microbiota dysbiosis. Traditional Chinese medicine (TCM) compounds such as Shenqi Dihuang Decoction, Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota. The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut mic-robiota.

A Case Report: The Effects of Photobiomodulation Therapy and Amniotic Fluid Gel on a Severe Diabetic Foot Ulcer.

Introduction: Diabetic patients frequently experience a serious complication known as impaired wound healing, which increases the likelihood of foot infection and limb amputation. Investigators have been looking for novel methods to treat diabetic foot ulcers (DFUs) recently. Case Report: A 75-year-old woman with type one diabetes mellitus (DM) has been accepted. There was a sizable (40 cm2 full-thickness cutaneous wound) in the plantar part of her right foot (Wagner Ulcer Grade Classification System: grade 3) which had not been treated by the usual treatment for DFUs. In this present case, we used amniotic fluid gel (AF gel) and photobiomodulation therapy (PBMT) (400 mW/cm2; 810 nm, once a week for 16 weeks) to treat and speed up the healing of a harsh DFU. The size of the ulcer area significantly decreased as combination therapy progressed, and within 16 weeks, the wound was healed and the pain was reduced. Conclusion: This revealed contextual analysis demonstrated the useful effect of the mix of PBMT and AF gel on a serious DFU. To confirm the findings, we recommend conducting additional clinical trials in a clinical setting. In addition, it is recommended that additional research using preclinical models uncover the mechanism of action of the combination therapy.