Healing Of Diabetic Foot Ulcers Research Articles

Effectiveness of Percutaneous Flexor Tenotomies for the Prevention and Management of Toe-Related Diabetic Foot Ulcers: A Systematic Review.

There is a high prevalence of digital deformities in diabetic patients, particularly claw toe, which can result in ulceration, often located at the tip of the toe. These lesions are challenging to off-load with conventional devices and frequently lead to infection and high amputation rates. Recent guidelines recommend considering flexor tenotomies to manage these ulcerations and prevent complications. This review, which analyzed 11 studies, aimed to assess the effect of flexor tenotomies on the healing and prevention of diabetic foot ulcers (DFUs) at the toe tip. Satisfactory results were found, with a healing rate of 92% to 100% and a mean healing time of 2-4 weeks. Few mild complications were observed, and the recurrence rate was very low. Transfer lesions were the most prevalent, but simultaneous tenotomy of all toes can eliminate this risk. Flexor tenotomies are a simple, effective, and safe procedure for the treatment and management of DFUs located at the apex of the toes and should be considered part of the standard of care for diabetic feet.

Bone marrow stromal cell-derived exosomal circular RNA improves diabetic foot ulcer wound healing by activating the nuclear factor erythroid 2-related factor 2 pathway and inhibiting ferroptosis.

Diabetic foot ulcer (DFU) remains a serious chronic diabetic complication that can lead to disability. CircRNA-itchy E3 ubiquitin protein ligase (circ-ITCH) was observed to be down-regulated in diabetic retinopathy and diabetic nephropathy, and overexpression of circ-ITCH could inhibit the processes of these diseases. However, the detailed physiological and pathological functions of circ-ITCH in wound healing of DFU remain undetermined. Exosomes derived from bone marrow stromal cells (BMSCs) were isolated and identified. Cell viability and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit-8 (CCK-8) and tube formation assays, respectively. The interplays of circ-ITCH, TATA-Box-binding protein associated factor 15 (TAF15) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA were analysed by RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) combined immunofluorescent staining and RNA pull-down assays. qRT-PCR, western blot or immunohistochemistry (IHC) were used to measure the expression of circ-ITCH, TAF15, Nrf2, vascular endothelial growth factor (VEGFR) and ferroptosis-related makers. The mice DFU model was established to verify the in vitro results. Circ-ITCH was down-regulated in in vitro and in vivo models of DFU. Deferoxamine (DFO), an iron chelating agent, improved the viability and angiogenic ability of high glucose (HG)-treated HUVECs. Overexpression of circ-ITCH or co-cultured with exosomal circ-ITCH from BMSCs could alleviate HG-induced ferroptosis and improve the angiogenesis ability of HUVECs. Circ-ITCH in HUVECs recruited TAF15 protein to stabilize Nrf2 mRNA, thus activating the Nrf2 signalling pathway and suppressing ferroptosis. Exosomal circ-ITCH from BMSCs also accelerated the wound healing process by inhibiting ferroptosis in the DFU mice in a time-dependent manner. Exosomal circ-ITCH from BMSCs inhibited ferroptosis and improved the angiogenesis of HUVECs through activation of the Nrf2 signalling pathway by recruiting TAF15 protein, ultimately accelerating the wound healing process in DFU.

The short-term impact of non-removable offloading devices on quality of life in people with recurrent diabetic foot ulcers

Recurrent diabetic foot ulcers (DFUs) are associated with poor health-related quality of life and reduced mobility. Current guidelines recommend application of non-removable offloading devices (NROLDs) as they may improve the healing of DFUs, but there is a lack of information on the wider effects of wearing these devices. Few studies have examined the impact of NROLDs on holistic wellbeing or physical activity. We aimed to investigate the short-term impact of NROLDs on physical activity and DFU-related quality of life (DFU-QoL) in a small sample of community-dwelling people with recurrent DFUs. We measured DFU-QoL and physical activity (GPAQ) in people with DFUs, recruited from a single clinic before NROLD application, and at three and six weeks after device fitting. Participants were aged from 39-81 years (mean 58.4±10.1 years) with an equal number of male and female participants. The study cohort comprised 18 participants, of whom 14 (78%) completed six-week questionnaires. Although there was some interim decline observed within individual domains of the DFU-QoL (financial: mean difference (MD) 16.2 (95% confidence interval (CI) 2.1, 30.2); p=0.03); non-compliance: MD 12.5 (95% CI-0.2, 25.2); p=0.05), no differences were observed over six weeks. Levels of physical activity declined over time, with over half (56%) of participants classified as having low levels of physical activity at baseline, rising to two-thirds (67%) at follow-up. Future studies should explore the longer-term holistic impact of NROLDs and develop more personalised approaches to care at the point of prescription, during and post-device use.

Keeping feet in remission after healing of diabetic foot ulcers: a qualitative study of patients’ experiences

Keeping feet in remission after healing of diabetic foot ulcers: a qualitative study of patients’ experiences

Workshop Pencucian Luka Kaki Diabetik Menggunakan Bahan Alam bagi Perawat di Puskesmas Mapane, Kabupaten Poso, Provinsi Sulawesi Tengah

Wound care of diabetic foot ulcer by Public Health Center nurses still use povidone iodine and rivanol which are toxic to tissues. Innovations in wound care including the use of natural materials have been proven to be effective in accelerating the healing of diabetic foot ulcers. This community service activity aims to increase the knowledge and skills of Public Health Center nurses in wound care using natural materials. The implementation method, namely workshops and wound care practices using natural materials, was held for 1 day on July 11 2022 at the Mapane Health Center. The target was Public Health Center nurses, totaling 28 participant. The form of evaluation is measuring the knowledge and skills of nurses before and after the activity. The results showed that the participants knowledge increased from 60.7% to 89.3% and the average skill score increased from 9.04 to 16.14. The conclusion is that after the workshop activities there was an increase in the knowledge and skills of Public Health Center nurses for wound care using natural materials. Suggestions for Public Health Center nurses to be able to utilize natural materials in the diabetic foot wound care.

Multidisciplinary approach in the treatment of patients with diabetic foot syndrome. Experience of Almazov National Medical Research Centrе

Objective Evaluate the effectiveness of the multidisciplinary specialists team in Almazov National Medical Research Centrе to the treatment of patients with the neuroischemic form of diabetic foot syndrome in a multi-field hospital.Materials and methods We made retrospective analysis of the multidisciplinary approach to the treatment of patients with a neuroischemic form of diabetic foot syndrome who were hospitalized to Almazov National Medical Research Centrе during the period from January 2018 to July 2020 (inclusively). The patients were treated in the clinic of the Almazov National Medical Research Centrе during one hospitalization period. The investigation includes patients over 18 years old with a diabetes mellitus who were performed revascularization at the vascular surgery clinic Almazov National Medical Research Centrе. Patients with a secondary diabetes mellitus, immunosuppressive therapy were excluded from the study. 51 patients with neuroischemic form of diabetic foot syndrome were specifically selected for analysis. We gathered all information about them till August 2022. So, the period of observation was from 2 years 8 months (32 months) to 4 years 8 months (56 months). The mediana time was 44 months (3.67 years). All inclusive patients had a diabetic ulcer on the foot. The outcomes of this study were the healing or non-healing of diabetic foot ulcers, major amputation or death (from all causes).Results Successful healing of ulcers or postoperative wounds at the time of contact with the patient or his relatives, was with 45 patients (88.3 %). In more than half of the patients (56.86 %) healing of ulcers and wounds was occurred in the 3 months after operation.70.59 % (n = 36) patients were performed orthopedic organ-preserving reconstructions on the feet in the hospital. 6 patients (11.7 %) were performed initially revascularization according to the “less affected pathway” principle which didn’t heal the ulcers in the postoperative period and leaded to repeated surgery to restore blood flow according to the angiosomal principle. For 9 patients (17.64 %) it was required to perform repeated orthopedic intervention on the foot during the current hospitalization. The causes of complications were: stent thrombosis (n=3), intimal dissections (n = 2) and distal embolism (n = 1). The reasons for repeated orthopedic surgery were marginal necrosis in the postoperative wounds. Optimal revascularization wasn’t achieved with 10 (19.6 %) patients. Despite this in 4 (7.84 %) cases ulcers was healed. In two cases, 3.92 % (n = 2) suboptimal revascularization was associated with the lack of technical possibility in revascularization of the lower leg arteries with satisfactory revascularization of the femoral-popliteal segment. Indirect revascularization with no effect was performed in 4 cases (7.84 %). 6 major amputations (11.7 %) were performed during the observation period, 1 major amputation during the current hospitalization and 5 in the long-term period. The Kaplan-Mayer three-year survival rate was 80 %.Conclusion The analysis of the results of a multidisciplinary approach to the treatment of patients with diabetic foot syndrome demonstrated an improvement in the preservation of the limbs, reduced of bone-plastic reconstructions, reduсtion of hospitalization time and improving the lives of patients.

MALAT1 participates in the role of platelet-rich plasma exosomes in promoting wound healing of diabetic foot ulcer

Exosomes isolated from platelet-rich plasma (PRP-exos) have been recently deemed as an optimized therapeutic strategy in diabetic foot ulcer (DFU) treatment. Herein, we aimed to explore whether MALAT1 participates in DFU wound healing by PRP-exos treatment and the related preliminary mechanism. Fibroblasts were isolated from healthy donors and DFU patients, and the expression of MALAT1, miR-374a-3p and DNMT3A were detected by RT-PCR. The effect of MALAT1 and miR-374a-3p on DFU fibroblast function was verified by gain/loss of function experiment. The targeted binding of MALAT and miRNA was verified by double luciferase reporter gene assay. PRP-exos were isolated from normal human blood and characterized, and then co-cultured with DFU fibroblasts. The MALAT1 expression was donwregulated while the miR-374a-5p expression was upregulated in DFU fibroblasts. Double luciferase reporter gene assay demonstrated the targeted binding of MALAT and miR-374a-5p. Overexpression of MALAT1 or knockdown of miR-374a-5p could increase viability and inhibit apoptosis and pyroptosis of DFU fibroblast. And overexpression of miR-374a-5p reversed the effect of PRR-exos or MALAT1 overexpression on cell viability, apoptosis and pyroptosis. Collectively, MALAT1 mediated signal axis participates in the role of PRP-exos in promoting DFU wound healing, which may help identify optimal targets and effective therapies for DFU treatment.

Determinants of healing of diabetic foot ulcer comparing two offloading modalities: A randomized prospective study

IntroductionHealing of Diabetic Foot ulcer is crucial to prevent amputation. Offloading is key treatment of diabetic foot ulcers, but choosing which offloading modality is still not clear. Besides, other factors that control ulcer healing, is a question that needs to be determined. Objective: to assess factors that affect ulcer healing, comparing two commonly used offloading devices, removable walker and cast-shoe. MethodsThis is a Randomized Clinical Trial which recruited 87 patients with active diabetic foot ulcers randomly assigned to either a removable walker (W-arm) or a cast-shoe (C-arm) at 3:2 ratio. Both groups received the routine ulcer care, and were followed-up for 24 weeks. Different possible factors related to healing were assessed, and a regression model was built for the most predictive factors. ResultsThe 24-week healing rate was 81% for the walker group and 62 % for the cast-shoe group. The mean adherence was 55 % ± 26 % and 46 % ± 29 for the walker and cast shoe groups respectively. Ulcer healing was significantly positively associated with: better adherence, device type (walker), less SINBAD score (2 or less), absence of ischemia, absence of infection, smaller ulcer area, superficial ulcer, better 4-week area reduction, and better blood glucose control. The most important predictors were adherence, total SINBAD score and 4-week area reduction. ConclusionSINBAD score at initial presentation and the degree of adherence to offloading device, are two major determinants of ulcer healing. Ulcer area reduction at 4 weeks represents an important clinical parameter to predict and guide the success of ulcer management.

Mechanisms of diabetic foot ulceration: A review.

Diabetic foot ulcers (DFUs) are associated with complex pathogenic factors and are considered a serious complication of diabetes. The potential mechanisms underlying DFUs have been increasingly investigated. Previous studies have focused on the three aspects of diabetic peripheral vascular disease, neuropathy, and wound infections. With advances in technology, researchers have been gradually conducting studies using immune cells, endothelial cells, keratinocytes, and fibroblasts, as they are involved in wound healing. It has been reported that the upregulation or downregulation of molecular signaling pathways is essential for the healing of DFUs. With a recent increase in the awareness of epigenetics, its regulatory role in wound healing has become a much sought-after trend in the treatment of DFUs. This review focuses on four aspects involved in the pathogenesis of DFUs: physiological and pathological mechanisms, cellular mechanisms, molecular signaling pathway mechanisms, and epigenetics. Given the challenge in the treatment of DFUs, we are hopeful that our review will provide new ideas for peers.

Development and evaluation of Resveratrol-loaded liposomes in hydrogel-based wound dressing for diabetic foot ulcer.

Diabetic foot wounds (DFUs) are counted as one of the most common microvascular complications associated with poorly controlled and chronic diabetes mellitus. It confers a serious challenge to clinical practice, surmounting hyperglycemia-induced disturbance in angiogenesis and endothelial dysfunction, with limited fruitful intervention to control the manifestations of DFUs. Resveratrol (RV) can improve endothelial function and has strong pro-angiogenic properties for the treatment of diabetic foot wounds. The present study aims to design an RV-loaded liposome-in-hydrogel system to effectively heal diabetic foot ulcers. A thin-film hydration method was used to prepare RV-loaded liposomes. Liposomal vesicles were assessed, for various characteristics such as particle size, zeta potential, and entrapment efficiency. The best-prepared liposomal vesicle was then incorporated into 1% carbopol 940 gel to develop a hydrogel system. The RV-loaded liposomal gel showed improved skin penetration. To assess the efficacy of the developed formulation, a diabetic foot ulcer animal model was used. The topical application of the developed formulation significantly reduced blood glucose and increased glycosaminoglycans (GAGs) to improve ulcer healing as well as wound closure on day 9. Faster re-epithelization, proliferation of fibroblast, formation of collagen, and reduced inflammatory cell infiltration at the wound site were also noted. Results indicate that RV-loaded liposomes in hydrogel-based wound dressing significantly accelerate wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetics.

Extracorporeal shockwave therapy for diabetic foot ulcers: a feasibility study

The purpose of this study was to assess the feasibility of delivering extracorporeal shockwave therapy (ESWT) to patients with diabetic foot ulcers (DFUs). It also aimed to explore any potential clinical effect of ESWT on wound healing and investigate whether ESWT offers any patient-reported benefits. In this single-centre, mixed methods feasibility study, patients with a DFU who met the eligibility criteria underwent ESWT three times over a seven-day period. Primary outcome was feasibility of delivering the intervention. Secondary outcomes included wound size, number of DFUs healed at 12 weeks and quality of life (QoL). Semi-structured interviews explored participants' experience of undergoing ESWT. Of 106 patients screened, 24 (22.6%) were recruited. Following recruitment, two patients were withdrawn from the study with 22 patients included in the final analysis. The mean attendance at clinic was 90.9% and 65.1% for follow-up. The mean score for acceptability and tolerability was 9.86±0.48 (95% confidence interval (CI): 9.62-10.01) and 9.15±2.57 (95% CI: 7.87-10.42), respectively. There were no serious adverse events or side-effects. Of the DFUs, 45.5% healed during follow-up and QoL scores improved until eight weeks. Key themes identified from the qualitative interviews were: desire for fast healing; improved QoL; flexibility of new treatments; and accessibility of transport. This study has shown that it is possible to recruit and retain patents into a single-arm study of ESWT for DFUs. This study supports development of a large randomised control trial to determine the clinical and cost-effectiveness of ESWT for DFU healing.

E2F2 Promotes Wound Healing of Diabetic Foot Ulcer by Regulating CDCA7L Transcription.

The E2F2 transcription factor can accelerate cell proliferation and wound healing. However, its mechanism of action in a diabetic foot ulcer (DFU) remains unclear. Therefore, this study explores the influence of E2F2 on wound healing in DFU by examining cell division cycle-associated 7-like (CDCA7L) expression. CDCA7L and E2F2 expression in DFU tissues were analyzed with databases. CDCA7L and E2F2 expression were altered in human umbilical vein endothelial cells (HUVECs) and spontaneously transformed human keratinocyte cell culture (HaCaT) cells. Cell viability, migration, colony formation, and angiogenesis were evaluated. Binding of E2F2 to the CDCA7L promoter was examined. Subsequently, a diabetes mellitus (DM) mouse model was established and treated with full-thickness excision followed by CDCA7L overexpression. Wound healing in these mice was observed and recorded, and vascular endothelial growth factor receptor 2 (VEGFR2) and hematopoietic progenitor cell antigen CD34 (CD34) expression were determined. E2F2 and CDCA7L expression levels in cells and mice were evaluated. The expression of growth factors was tested. CDCA7L expression was downregulated in DFU tissues and wound tissues from DM mice. Mechanistically, E2F2 bound to the CDCA7L promoter to upregulate CDCA7L expression. E2F2 overexpression enhanced viability, migration, and growth factor expression in HaCaT cells and HUVECs, and augmented HUVEC angiogenesis and HaCaT cell proliferation, which was nullified by silencing CDCA7L. In DM mice, CDCA7L overexpression facilitated wound healing and elevated the expression level of growth factors. E2F2 facilitated cell proliferation and migration and fostered wound healing in DFU cells through binding to the CDCA7L promoter.

A COMPARATIVE STUDY BETWEEN EFFICACY OF TOPICAL INSULIN AND NORMAL SALINE DRESSINGS IN DIABETIC FOOT ULCERS.

Introduction: One of the most prevalent problems a surgeon encounters is chronic wounds, especially those that do not heal. The development of agents for wound healing is the subject of ongoing study. Insulin is one such substance that stimulates connective tissue. Objective: To evaluate the effectiveness of topical insulin dressings with traditional saline dressings in the healing of chronic diabetic foot ulcers (DFUs), in terms of the size of the ulcer, the amount of time spent in the hospital, and any side effects. In this prospective longitudinal study,the Materials and Methods: patient's willingness to receive topical insulin therapy was used to separate the study population (n=100) into study group (insulin group, n=50) and Control group (saline group, n=50). Using paired and unpaired Student's t-tests, the variables of ulcer surface area, granulation tissue formation and length of hospital staywere compared. A p-value of < 0.05 was deemed signicant. In t Results: he study group, the mean ulcer surface area was 40.4 cm2, compared to 37.6 cm2 in the control group (p-value = 0.012). After dressings, the mean area of granulation tissue formation in the study group was 39.63 cm2+2.6 , while it was 36.07 cm2+ 5.7 in the control group (p-value=0.001*). The control group's average hospital stay was 31.3 + 4.2 days whereas in the study group it was 27.8 ± 2.4 days (p-value=0.001*). Insulin is a chea Conclusion: p and superior alternative dressing agent for diabetic foot ulcer care

Wound pH and Surface Temperature as a Predictive Biomarker of Healing in Diabetic Foot Ulcers.

To monitor wound pH and surface temperature as predictors of wound healing in diabetic foot ulcers (DFU). Prospective, observational, time-bound study of 18 months, enrolling patients aged 18 to 60 years with uninfected DFU. The wound was assessed at baseline and after that, every week for 4 weeks according to the leg ulcer measurement tool (LUMT). Concurrently, wound surface pH and temperature were measured. The data were analyzed using descriptive statistics, and a P-value < .05 was considered statistically significant. Fifty-four patients with DFU were included in the study with a mean age of 55 years and a male to female ratio of 1.57. The wound showed progressive improvement, a maximum mean LUMT score of 48.89 (± 2.81) at the initial evaluation and decreased progressively to the mean of 19.80 at week 4 (± 3.43), both of which were statistically significant (P-value < .001). Similarly, the median wound pH progressively reduced from 7.7 at baseline to 7.20 in the fourth week, and median wound temperature decreased from 90°F (32.22 °C) at baseline to 85°F (29.44 °C) in the fourth week, both of which were statistically significant (P-value < .001). Progressive and significant change in wound pH to acidic and drop in wound surface temperature, both corresponding to improvement in the status of DFU, maximum at 4 weeks, make them valuable predictors of wound healing. However, further, more extensive studies are required to establish a concrete relationship.

THE EFFECT OF SUCRALFATE DRESSING IN DIABETIC FOOT ULCER PATIENTS

Introduction-Diabetic foot ulcers are most commonly occurring complication in patients of diabetes mellitus who have poor glycaemic control. It's also the common cause for osteomyelitis of foot, amputation of lower extremities. About 60% of patients develop neuropathy eventually leads to formation of foot ulcers. Staphylococcus is common infective organism which cause ulcers over the foot. Objective-To study efcacy of topical Sucralfate in healing of diabetic ulcer, in terms of number of days needed for healing, rate of reduction in mean ulcer surface area. Also, to assess the bacterial load by culture &amp; sensitivity of wound swabs before and after application of Sucralfate and conventional dressing. Methodology-The present prospective study was conducted at Dr. D.Y. Patil Medical College Hospital Research Institute, Kolhapur. Atotal of 30 patients from OPD &amp; IPD with diabetic foot ulcers of Wagner grade- I&amp;II having size less than 15x15cm were included in study. All patients were evaluated and investigated by a standard protocol for the management of the ulcer. The dressings were changed everyday morning in both groups for 6-weeks and appearance of the healthy granulation tissue is observed daily. The nal area is measured on 43rd day by planimetry using a transparent graph sheet and subjected to statistical analysis. Result-Sucralfate on daily application to wounds increases thickness of granulation tissue and promotes rapid epithelialization of second-degree burns. An ideal dressing that promotes chronic ulcer healing without any complications. Conclusions-The results of the study showed signicant effect in area of reduction, negative culture rate and weeks for recovery are seen in study group, suggesting that topical Sucralfate dressing can effectively increase the wound healing in diabetic foot ulcer compared to conventional dressing.

Use of hyperspectral imaging to predict healing of diabetic foot ulceration.

Our main objective was to validate that hyperspectral imaging via a new portable camera carries the potential to provide a reliable clinical biomarker that can predict DFU healing. We recruited patients with diabetic foot ulceration (DFU) without peripheral arterial disease, infection or other serious illness. Using an hyperspectral imaging (HSI) apparatus, post-debridement hyperspectral images were taken evaluating the ulcer size, periwound oxyhemoglobin (OxyHb), deoxyhemoglobin level (DeoxyHb) and oxygen saturation (O2 Sat) for four consecutive visits. Twenty-seven patients were followed, out of whom seven healed their DFU while the remaining 20 failed to heal their DFU. The average time between each visit was 3 weeks. Binary logistic regression of healers versus non-healers on Visit 1 oxyHb and on Visit 2 showed a significant inverse association, OR=0.85 (95% CI: 0.73-0.98, p < 0.001). An inverse correlation was observed between the Visit 1 oxyHb and the percentage of ulcer size reduction between Visit 1 and Visit 4 (r=-0.46, p=0.02) and between the Visit 2 oxyHb and the percentage of ulcer size reduction between Visits 2 and 4 (r=-0.65, p=0.001). Using oxyHb 50 as the cut-off point to predict DFU complete healing, Visit 1 oxyHb measurement provided 85% sensitivity, 70% specificity, 50% positive predictive value and 93% negative predictive value. For Visit 2, oxyHb had 85% sensitivity, 85% specificity, 66% positive predictive value and 94% negative predictive value. We conclude that this preliminary study, which involved a relatively small number of patients, indicates that hyperspectral imaging is a simple exam that can easily be added to daily clinical practice and has the potential to provide useful information regarding the healing potential of DFU over a short period of time.

Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach

Diabetic Foot Ulcer (DFU) is a combination of neuropathy and ischaemia on diabetic patient's lower limbs. It has a high burden of limb amputation rate, mortality rate, disability, economic burden, and lower quality of life on diabetic patients. It took mostly 3-6 months and up to 1 year for DFU to heal. DFU patients also have an increased risk of vitamin D deficiency. Meanwhile vitamin D has effects on immune response, insulin secretion, and sensitivity. The long duration of DFU healing is a problem for the patient's health, job, income, quality of life, economy and healthcare. Therefore, we aim to conduct a meta-analysis to assess reliability of vitamin D supplementation on diabetic foot ulcer clinical outcome. We conducted systematic literature search according to PRISMA guideline on Cochrane Library, PubMed, Google Scholar, ProQuest, EBSCO and ScienceDirect from 16 until 24 June 2022. Effect of vitamin D supplementation on diabetic foot ulcer patients was analyzed with a comprehensive meta-analysis tool. Pooled ulcer area, total cholesterol, triglyceride, C-reactive protein, HbA1c, and fasting plasma glucose assessed with 95% confidence intervals were estimated using fixed-effects or random-effects models. We included 4 papers with 197 people as sample reporting vitamin D capability as treatment for DFU patients. The pooled analysis showed significant differences in ulcer area, serum Vitamin D, Total Cholesterol, Fasting Plasma Glucose, Triglyceride, C-Reactive Protein, and HbA1c. Insignificant results on Erythrocyte Sedimentation Rate and High Density Lipoprotein levels. Vitamin D supplementation is beneficial to be given as adjuvant treatment for diabetic foot ulcer. It may fasten the wound healing and decrease the burden caused by diabetic foot ulcers.

Current scenario of traditional medicines in management of diabetic foot ulcers: A review.

Diabetic foot infections and diabetic foot ulcers (DFU) cause significant suffering and are often recurring. DFU have three important pathogenic factors, namely, microangiopathy causing local tissue anoxia, neuropathy making the foot prone to injuries from trivial trauma, and local tissue hyperglycaemia favouring infection and delaying the wound healing. DFU have been the leading cause for non-traumatic amputations of part or whole of the limb. Western medicines focus mainly on euglycaemia, antimicrobials, debridement and wound cover with grafts, and off-loading techniques. Advances in euglycaemic control, foot care and footwear, systemic antimicrobial therapy, and overall health care access and delivery, have resulted in an overall decrease in amputations. However, the process of wound care after adequate debridement remains a major cost burden globally, especially in developing nations. This process revolves around two basic concerns regarding control/eradication of local infection and promotion of faster healing in a chronic DFU without recurrence. Wound modulation with various dressings and techniques are often a costly affair. Some aspects of the topical therapy with modern/Western medicines are frequently not addressed. Cost of and compliance to these therapies are important as both the wounds and their treatment are "chronic." Naturally occurring agents/medications from traditional medicine systems have been used frequently in different cultures and nations, though without adequate clinical base/relevance. Traditional Chinese medicine involves restoring yin-yang balance, regulating the 'chi', and promoting local blood circulation. Traditional medicines from India have been emphasizing on 'naturally' available products to control wound infection and promote all the aspects of wound healing. There is one more group of chemicals which are not pharmaceutical agents but can create acidic milieu in the wound to satisfy the above-mentioned basic concerns. Various natural and plant derived products (e.g., honey, aloe vera, oils, and calendula) and maggots are also used for wound healing purposes. We believe that patients with a chronic wound are so tired physically, emotionally, and financially that they usually accept native traditional medicine which has the same cultural base, belief, and faith. Many of these products have never been tested in accordance to "evidence-based medicine." There are usually case reports and experience-based reports about these products. Recently, there have been some trials (in vitro and in vivo) to verify the claims of usage of traditional medicines in management of DFU. Such studies show that these natural products enhance the healing process by controlling infection, stimulating granulation tissue, antimicrobial action, promoting fibroblastic activity and collagen deposition, etc. In this review, we attempt to study and analyse the available literature on results of topical traditional medicines, which are usually advocated in the management of DFU. An integrated and 'holistic' approach of both modern and traditional medicine may be more acceptable to the patient, cost effective, and easy to administer and monitor. This may also nevertheless lead to further improvement in quality of life and decrease in the rates of amputations for DFU.

Emerging Antimicrobial and Immunomodulatory Fiber-Based Scaffolding Systems for Treating Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are one of the main complications of diabetes and are characterized by their complexity and severity, which are frequently aggravated by overexpressed inflammatory factors and polymicrobial infections. Most dressing systems offer a passive action in the treatment of DFUs, being frequently combined with antibiotic or immunomodulatory therapies. However, in many instances due to these combined therapies' inability to properly fight microbial presence, and provide a suitable, breathable and moist environment that is also capable of protecting the site from secondary microbial invasions or further harm, aggravation of the wound state is unavoidable and lower limb amputations are necessary. Considering these limitations and knowing of the urgent demand for new and more effective therapeutic systems for DFU care that will guarantee the quality of life for patients, research in this field has boomed in the last few years. In this review, the emerging innovations in DFU dressing systems via fiber-based scaffolds modified with bioactive compounds have been compiled; data focused on the innovations introduced in the last five years (2017-2022). A generalized overview of the classifications and constraints associated with DFUs healing and the bioactive agents, both antimicrobial and immunomodulatory, that can contribute actively to surpass such issues, has also been provided.

The Effect of Vibration on the Acceleration of Wound Healing of Diabetic Neuropathic Foot Ulcer: A Prospective Experimental Study on Human Patients.

Diabetic foot ulcers are a common complication that occurs in approximately 15 percent of patients with diabetes mellitus. Over 60% of diabetic foot ulcers are caused by underlying neuropathy. Former studies on diabetic animals with foot wounds found that vibration platforms significantly accelerate wound healing by catalyzing epithelization, promoting angiogenesis, and enhancing muscle bulk. This result suggests that there is evidence that vibrations may accelerate diabetic neuropathic ulcer healing in human patients. However, to the best of our knowledge, the effect of vibration on the enhancements of diabetic foot ulcer healing in human patients is rarely investigated. Hence, in this work, we conducted an experimental study with human subjects to investigate whether vibration therapy, as a complement to the standard wound treatment, can accelerate the wound healing rate of diabetic neuropathic foot ulcers. In this prospective experimental study, 80 participants diagnosed with Wagner grades I−III diabetic neuropathic foot ulcers were randomly distributed to experimental (n = 40) and control groups (n = 40). Patients in the intervention group received standard wound treatment and vibration wound therapy (VWT), whereas patients in the control group retrieved only standard wound treatment. The results (p = 0.024, α = 0.05) show notable differences in the median healing rate between the intervention group (25 days, 95% CI: 20.3−29.7) and control group (33 days, 95% CI: 25.6−40.4), with the effect-size r, Cohen’s d, Glass’s Δ, and Hedges’ g, respectively, being 0.810, 2.764, 2.311, and 2.772. Moreover, the nitric oxide (NO) level, wound closure area, and wound healing score after intervention significantly differed between the two groups (p < 0.05), putting the intervention group on a higher level than the control group. Furthermore, positive associations were found between the NO level and wound healing closure rates. These findings suggested that VWT enhances diabetic neuropathic foot ulcer healing in terms of healing rate, wound closure area, healing score, and elevated NO level. Considering that no clinically adverse effects were found in the patients induced with vibration intervention, VWT can be regarded as a complementary therapy to the existing ones to accelerate the healing of DFUs.