Healing Of Foot Ulcers Research Articles

High glucose activates ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic foot ulcers

Increased matrix metalloproteinase 9 (MMP9) expression is involved in delayed wound healing in diabetic foot ulcers. We created skin wounds in normal SD rats and STZ-induced diabetic SD rats, then we found protein levels of activator protein-1 (AP1), a crucial transcription factor to increase MMP9 transcription, as well as MMP9 was up-regulated in epithelium of diabetic skin tissues. Then, we evaluated the mRNA and protein stability of AP1 subunits C-FOS/C-Jun in HaCaT cells after high glucose treatment. Results showed that high glucose could increase protein stability of C-FOS and C-Jun. Additionally, high glucose also activated extracellular signaling-related kinase 1/2 (ERK1/2). ERK1/2 inhibitor could rescue phosphorylation of C-FOS and C-Jun, increased protein stability of C-Jun, and increased MMP9 expressions. Thus, our study demonstrated that high glucose could activate ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic skin and HaCaT cells.

Efficacy of Dehydrated Human Amnion Chorion Membrane in the Treatment of Diabetic Foot Ulcers: A Review

Studies have been conducted to evaluate the efficacy of dehydrated human amnion chorion membrane (dHACM) in treating recalcitrant diabetic foot ulcers. A literature search was performed to review the data collected from the use of dHACM allografts. Two products were explicitly named in these publications, EpiFix and AmnioBand Membrane. Relevant results included the healing rate, number of wounds healed, and number of grafts used. Data had supported the potential of lowering the overall cost to manage a wound despite a relatively higher cost per dressing. However, discrepancy was observed in the rate of healing between several of the studies. Nonetheless, dHACM had demonstrated improvement in healing of recalcitrant diabetic foot ulcers compared to standard of care alone. These results provide grounds for more inclusive research on dHACM in the future.

Evaluation of the efficacy of platelet-rich plasma on healing of clean diabetic foot ulcers: A randomized clinical trial in Tehran, Iran

Background and aimsDiabetic foot ulcers (DFUs) are among challenging hurdles both for the patient and the physician. There is a recent trend toward finding novel and clinically efficient modalities to treat this potentially hazardous complication of diabetes mellitus in a timely manner. Herein, we aim to appraise the efficacy of platelet-rich plasma (PRP) in healing of clean DFUs. Methods90 patients with clean DFUs consisting of 56 (62.2%) males and 34 (37.8%) females with mean age (±standard deviation) of 56.52 (±7.14) years were enrolled in this study between June 2017 and December 2018. They were randomly allocated into control group (47 patients who received conventional dressing along with silver sulfadiazine ointment twice daily), and case group (43 patients who received PRP gel twice weekly for 3 weeks). All the patients were followed up for 6 months. ResultsOur study showed that PRP significantly increased the healing rate of DFUs regardless of the age (p-value: 0.0), gender (p-value: 0.0), or smoking (p-value: 0.0) and blood pressure (p-value: 0.0) status of patients, but it did not have a significant impact on the need for amputation (p-value: 0.11), level of amputation (p-value: 0.16), or the need for further treatments such as graft or angioplasty (p-value: 0.52). ConclusionRegardless of the age, gender, or smoking and blood pressure status of patients, PRP can be efficiently used in diabetic patients to accelerate the healing rate of foot ulcers.

A REVIEW ON DETERMINING FACTORS FOR WOUND HEALING IN DIABETIC FOOT ULCERS

Diabetic Foot Ulcers (DFU) are significant complications of diabetes mellitus. DFU will often heal in a shorter period if factors that inhibit wound healing are identified and managed. This review was to identify determining factors that are associated with wound healing in DFU patients. Glycaemic control, adequate nutrition, presence of infection, the use of modern dressing approach, provide sufficient offloading and avoid unhealthy lifestyle like smoking are the highlighted determining factors discussed in this review and found to have an association towards a timely manner of wound healing in diabetic foot ulcers.

The effectiveness of a new dried human amnion derived membrane in addition to standard care in treating diabetic foot ulcers: A patient and assessor blind, randomised controlled pilot study.

Recent reviews suggest that amniotic membrane products may accelerate healing of diabetic foot ulcers. A new dried human amniotic membrane (dHAM) has been used for ocular ulcers but not for diabetic foot ulcers. This was a multi‐centre, prospective, patient and observer blind, randomised controlled pilot trial, to investigate whether 2 weekly addition of the dHAM to standard care versus standard care alone increased the proportion of healed participants' index foot ulcers within 12 weeks. Thirty‐one people (mean age 59.8 years, 81% male, 87% type 2 diabetes) were randomised (15 dHAM, 16 usual care). Within 12 weeks, healing occurred in 4 (27%) ulcers in the dHAM group versus 1 (6.3%) usual care group (P = .1). Percentage wound area reduction was higher in the dHAM versus control group. (P = .0057). There was no difference in AEs between the two groups. Six participants allocated to dHAM correctly identified their treatment group, although 5 in usual care incorrectly thought they were in the intervention arm. This pilot trial result is encouraging showing that this dHAM preparation is safe and promising treatment. These results will be used to design a statistically powered, definitive double blind randomised controlled trial.

Bacteria and bioburden and healing in complex wounds: A prognostic systematic review.

The wound microbiome may play an important role in the wound healing process. We conducted the first systematic prognosis review investigating whether aspects of the wound microbiome are independent prognostic factors for the healing of complex wounds. We searched Medline, Embase, CINAHL and the Cochrane Library to February 2019. We included longitudinal studies which assessed the independent association of aspects of wound microbiome with healing of complex wounds while controlling for confounding factors. Two reviewers extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. We synthesised studies narratively due to the clinical and methodological heterogeneity of included studies and sparse data. We identified 28 cohorts from 21 studies with a total of 38,604 participants, including people with diabetes and foot ulcers, open surgical wounds, venous leg ulcers and pressure ulcers. Risk of bias varied from low (2 cohorts) to high (17 cohorts); the great majority of participants were in cohorts at high risk of bias. Most evidence related to the association of baseline clinical wound infection with healing. Clinical infection at baseline may be associated with less likelihood of wound healing in foot ulcers in diabetes (HR from cohort with moderate risk of bias 0.53, 95% CI 0.33 to 0.83) or slower healing in open surgical wounds (HR 0.65, 95% CI 0.51 to 0.83); evidence in other wounds is more limited. Most other associations assessed showed no clear relationship with wound healing; evidence was limited and often sparse; and we documented gaps in the evidence. There is low certainty evidence that a diagnosis of wound infection may be prognostic of poorer healing in foot ulcers in diabetes, and some moderate certainty evidence for this in open surgical wounds. Low certainty evidence means that more research could change these findings.

Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers.

Delayed healing of diabetes-related foot ulcers (DRFUs) is associated with increased macrophage and matrix metalloproteinases (MMPs) at the wound site. Whether circulating monocyte phenotype and/or MMPs are altered in association with wound healing outcome is unknown, and was investigated in this study. Blood was obtained from 21 participants with DRFU, at initial visit (V1), week-4 (V2), and week-8 (V3) for measurement of monocyte number (CD14+), phenotype (CD16, CD163) and chemokine receptors (CCRs) by flow cytometry, and circulating MMPs and TIMP-1 by ELISA. Six wounds healed during the study. At V1, non-classical CD16++ monocytes and MMP-3 were higher in healed vs unhealed (both p < 0.05). At V3, the increased %CD16++ persisted and %CCR2+ was decreased in healed, but no other monocyte markers nor MMP/TIMP differed between groups. Increased wound closure rate (WCR) at V3 correlated with increased %CD16++ monocytes and decreased MMP-2 at V1 or V1 + V2. Receiver operating characteristic (ROC) curves yielded an area-under-the-curve of %CD16++ at V1 of 0.78 to predict ulcer healing at V3. These results indicate that circulating monocyte phenotype and MMPs alter as DRFUs heal. The relationship of %CD16++ monocytes with WCR and ROC curve suggest a predictive role of %CD16++ monocytes for ulcer healing.

Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials

Studies have suggested that hyperbaric oxygen therapy (HBOT) is effective in the healing of diabetic foot ulcer (DFU); however, there is a lack of consensus. Therefore, to assess the efficacy of HBOT on diabetic foot ulcer among diabetic patients, controlled clinical trials were searched through PubMed, EMBASE, Clinical key, Ovid Discovery, ERMED, Clinical Trials.gov databases for randomized controlled trials (RCTs) and other sources until 15 September 2020. Studies that evaluated the effect of HBOT on diabetic foot ulcer, complete healing, amputation, adverse events, ulcer reduction area, and mortality rate were included. Of 1984 study records screened, 14 studies (768 participants) including twelve RCTs, and two CCTs were included as per inclusion criteria. The results with pooled analysis have shown that HBOT was significantly effective in complete healing of diabetic foot ulcer (OR = 0.29; 95% CI 0.14–0.61; I2 = 62%) and reduction of major amputation (RR = 0.60; 95% CI 0.39–0.92; I2 = 24%). Although, it was not effective for minor amputations (RR = 0.82; 95% CI 0.34–1.97; I2 = 79%); however, less adverse events were reported in standard treatment group (RR = 1.68; 95% CI 1.07–2.65; I2 = 0%). Nevertheless, reduction in mean percentage of ulcer area and mortality rate did not differ in HBOT and control groups. This review provides an evidence that hyperbaric oxygen therapy is effective as an adjunct treatment measure for the diabetes foot ulcers. These findings could be generalized cautiously by considering methodological flaws within all studies.

Low-level laser therapy (photobiomodulation) versus hyperbaric oxygen therapy on healing of chronic diabetic foot ulcers: a controlled randomized trial

Background and purpose Diabetic foot ulcers (DFU) and concurrent infections are the most frequent complications in patients with diabetes mellitus. Both low-level laser therapy (LLLT), photobiomodulation (PBM), and hyperbaric oxygen therapy (HBOT) promote the healing of wounds. The purpose of this study was to compare the effectiveness of LLLT versus HBOT on the healing of chronic DFU. Patients and methods: Seventy-five patients with chronic diabetic ulcers aged ranging from 40–65 years were recruited and assigned randomly into three groups. HBOT group received 100% pure oxygen 2.5 ATA delivered for 60 min per session for 30 sessions (5 sessions per week for 6 successive weeks). LLLT group received GaAlAs diode laser producing a total power output of 1440 mW with following wavelengths: 5 × 850 nm (200 mW), 12 × 670 nm (10 mW),8 × 880 nm (25 mW), and 8 × 950 nm (15 mW); the energy density (fluency) was adjusted for 4 J/cm2 with a pulse frequency of 10 kHz. Each session lasted 8 min every two days. The control group received conventional wound care only (wound cleansing twice daily using saline or similar dressing). Both LLLT and HBOT groups received conventional wound care in addition to their program. Measurements for ulcer surface area (USA; transparency method) and ulcer volume (volumetric method) were performed before starting the study and in the second, fourth, and sixth-weeks post-treatment. Results: Within group comparisons demonstrated a statistically significant decrease in USA and ulcer volume in both HBOT and LLLT groups (p-value = 0.0001 in all measurements). The multiple comparisons between groups for USA, there was insignificant difference between HBOT and LLLT groups after 2-, 4-, and 6-weeks (p-value = 0.48, 0.813, and 0.629, respectively), while for ulcer volume, there was a statistically significant difference in favor of the LLLT group only after 2- and 4-weeks (p = 0.037 and 0.042, respectively) while an insignificant difference after 6-weeks (p-value = 0.911). Conclusion: Both LLLT and HBOT accelerate healing in chronic DFU, but the LLLT is more favorable in decreasing ulcer volume after during the first 4-weeks.

Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer\u2014study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II

BackgroundDiabetes and its sequelae such as diabetic foot ulcer are rising health hazards not only in western countries but all over the world. Effective, yet safe treatments are desperately sought for by physicians, healthcare providers, and of course patients.Methods/designAPOSEC, a novel, innovative drug, is tested in the phase I/II study MARSYAS II, where its efficacy to promote healing of diabetic foot ulcers will be determined. To this end, the cell-free secretome of peripheral blood mononuclear cells (APOSEC) blended with a hydrogel will be applied topically three times weekly for 4 weeks. APOSEC is predominantly effective in hypoxia-induced tissue damages by modulating the immune system and enhancing angiogenesis, whereby its anti-microbial ability and neuro-regenerative capacity will exert further positive effects. In total, 132 patients will be enrolled in the multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-ranging phase I/II study and treated with APOSEC at three dose levels or placebo for 4 weeks, followed by an 8-week follow-up period to evaluate safety and efficacy of the drug. Wound area reduction after 4 weeks of treatment will serve as the primary endpoint.ConclusionWe consider our study protocol to be suitable to test topically administered APOSEC in patients suffering from diabetic foot ulcers in a clinical phase I/II trial.Trial registrationEudraCT 2018-001653-27. Registered on 30 July 2019. ClinicalTrials.gov NCT04277598. Registered on 20 February 2020. Title: “A randomized, placebo-controlled, double-blind study to evaluate safety and dose-dependent clinical efficacy of APO-2 at three different doses in patients with diabetic foot ulcer (MARSYAS II)”

A Study Assessing Healing of Diabetic Foot Ulcer Before and After Infrared Lamp Therapy Among Patients with Diabetic Foot Ulcer at Gopi Hospital, Salem.

The study was conducted to evaluate the efficacy of infrared lamp therapy for healing of diabetic foot ulcers among patients presenting with diabetic foot ulcer at Gopi Hospital Salem. A pre-experimental research design one group pretest and posttest was adopted for the present study. The tool used for the present study was an interviewobservational schedule. The ulcer healing status was measured by using modified pressure sore status tool developed by Bates Jenes. Convenient sampling technique was used and a sample size of 30 patients with diabetic foot ulcer was studied. Prediabetic ulcer status was observed for all 30 patients and data were collected using the interviewobservational schedule. The study group was exposed to infrared lamp therapy for 5 days by the investigator. Afterwards the posttest diabetic foot ulcer status was observed and evaluated for the experimental group. The study results revealed that infrared lamp therapy was effective in diabetic foot ulcer healing.

Managing Diabetic Foot Ulcers: Pharmacotherapy for Wound Healing.

Historically, there has been a scarcity of evidence-based topical therapy to hasten the healing of diabetic foot ulcers. But recently new evidence-based treatments have emerged from multicentre, randomised, controlled trials. This article highlights those trials, and describes the current pharmacological management of the diabetic foot ulcer and the advances that have been made in wound therapy to date. It provides an overview of topical and systemic pharmacotherapies in current use and those in development for future use in managing the diabetic foot. For each treatment, proposed mechanisms of action and evidence available to support their clinical use are presented. There is supporting randomised, controlled evidence for sucrose octasulfate in the treatment of neuro-ischaemic ulcers, and multi-layered patch of autologous leucocytes, platelets and fibrin in ulcers with or without ischaemia. There is also evidence for placentally derived products and for topical and systemic oxygen therapy in the healing of diabetic foot ulcers. Growth factors, bio-engineered tissues, stem cell therapy, gene therapy and peptide therapy also have some supporting evidence in the healing of diabetic foot ulcers. Nonsurgical debriding agents may be useful when the optimum approach of sharp debridement is not possible, and immunomodulators may be helpful for their antimicrobial effects, but robust data is still required to strengthen the case for general use. The review does not cover antimicrobials as their primary role are as anti-infectives and not in wound healing. The development of nanotechnology has created a means of prolonging the bioavailability of target molecules at the wound site, with the use of glass/hydrogel nanoparticles, polyethylene glycol and hyaluronic acid. Looking forward, novel therapies, including traction force-activated payloads, local delivery of short-interfering RNA and finally hydrogels incorporating bioactive agents or cells may provide possibilities for pharmacotherapy in the future.

糖尿病足潰瘍治癒過程モニタリングスケール（DMIST）の適用

糖尿病足潰瘍治癒過程モニタリングスケール（DMIST）の適用

Effectiveness of Topical Insulin Dressing in Healing of Diabetic Foot Ulcer among Diabetic Patients

Diabetes is previously known as the disease of the rich people, but now there is no partiality between the rich and poor and it has become the third leading cause of death. Diabetic Mellitus (DM) is a metabolic issue that is characteristics by chronic hyperglycemia; it is a typical and conceivably persistent disease. The aims of the present study to assess the effectiveness of insulin dressing of the diabetic foot ulcer among diabetic patients. A quasi-experimental research design with purposive sampling technique was adopted to conduct a study among 30 diabetic foot ulcer patients. Demography data was collected and wound was measured and insulin dressing was done. After one week the wound was measured. Confidentiality was maintained throughout the procedure. The collected data were analyzed by using descriptive and inferential statistics. Among 30 samples pretest mean score of wound healing among patients with diabetic foot ulcer in the topical insulin dressing was 2.67±0.66 and the post test mean score was 1.43±0.57. The calculated paired ‘t’ test value of t = 15.703 was found to be statistically highly significant at p&lt;0.001 level. The above finding clearly infers that topical insulin dressing to patients with diabetic foot ulcer had significant effect which resulted in the improvement in the level of wound healing among patients with diabetic foot ulcer.

A comparative study to assess the effectiveness of Topical Insulin Dressing vs Normal Saline Dressing on wound healing of Diabetic Foot Ulcer

Diabetic foot ulcer (diabetic foot ulcer) is an injury entering through the profound vascular and collagenous (dermis) layers of the skin in diabetic patients. Helpless information by walking care and helpless foot care rehearses were distinguish as significant danger factors for foot issues in diabetes. The principle target of the investigation was to survey the effectiveness of topical insulin dressing versus saline dressing and analyze the degree of diabetic injury healing. Quasi-experimental with comparative research design was embraced for the investigation. Convenience sampling technique was utilized to choose 60 examples. Structured interview was used to collect background variable and Wagner diabetic wound assessment scale for assessing diabetic wound. The diabetic wound was dressed with topical insulin dressing and normal saline dressing for 6 days. The calculated paired 't' test value of t = 15.703 was found to be statistically highly significant at p&lt;0.001 level whereas the calculated paired 't' test value of t = 3.247 was found to be statistically highly significant at p&lt;0.01 level. There was significant that the topical insulin dressing is the more effective and improving the level of wound healing than normal saline dressing.

Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats.

BackgroundDiabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition.MethodsSesamol-PLGA (SM-PLGA) nanosuspension was developed using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson’s trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections.ResultsThe optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels’ development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed.ConclusionResults indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.

Efficacy of low-level light therapy for improving healing of diabetic foot ulcers: A systematic review and meta-analysis of randomized controlled trials.

Diabetic foot ulcers are prevalent among patients with diabetes and negatively affect mortality and life expectancy. This study aimed to synthesize and systematically review the best evidence to assess the efficacy of low-level light therapy in improving healing of diabetic foot ulcers. We search CINAHL, Cochrane Library, EMBASE, ProQuest, PubMed, Scopus, and Web of Science from inception until September 30, 2019. Meta-analysis was performed using the Comprehensive Meta-analysis 3.0 software. Overall effect was measured using Hedges' g and determined using the Z-statistic at a significance level of P < .05. Heterogeneity was assessed using χ2 and I2 statistics. Twelve randomized controlled trials were included. Meta-analysis revealed that 30.90% of the ulcer area was significantly reduced in the therapy group compared with the control group (Z = 3.95, P < .001) with a very large effect (g = 2.81). A 4.2 cm2 reduction of the ulcer area was observed in the therapy group compared with the control group (Z = 2.17, P = .03) with a very large effect (g = 1.37). In addition, diabetic foot ulcers in the therapy group was 4.65 times more likely to heal completely than those in the control group (Z = 3.02, P = .003). Low-level light therapy accelerates wound healing and reduces the size of diabetic foot ulcers. However, our review does not allow any recommendation for the best treatment parameters required to achieve improved healing. Future trials need to include a good design and large sample size in defining the optimal treatment parameters for ulcers of different sizes.

Utilization of smartphone and tablet camera photographs to predict healing of diabetes-related foot ulcers

The objective of this study was to build a machine learning model that can predict healing of diabetes-related foot ulcers, using both clinical attributes extracted from electronic health records (EHR) and image features extracted from photographs. The clinical information and photographs were collected at an academic podiatry wound clinic over a three-year period. Both hand-crafted color and texture features and deep learning-based features from the global average pooling layer of ResNet-50 were extracted from the wound photographs. Random Forest (RF) and Support Vector Machine (SVM) models were then trained for prediction. For prediction of eventual wound healing, the models built with hand-crafted imaging features alone outperformed models built with clinical or deep-learning features alone. Models trained with all features performed comparatively against models trained with hand-crafted imaging features. Utilization of smartphone and tablet photographs taken outside of research settings hold promise for predicting prognosis of diabetes-related foot ulcers.

Randomized controlled clinical trial evaluating the efficacy of hyperbaric oxygen therapy in facilitating the healing of chronic foot ulcers in diabetic patients: the study protocol

BackgroundDiabetic limb ulcers are highly prevalent and contribute to a significant increase in cost for the treatment of these patients in health services. However, healing of these wounds is a major health problem and may even lead to amputation. The primary aim of the current study is to evaluate the efficacy of hyperbaric oxygen therapy (HBOT) in facilitating the healing of diabetic foot ulcers, in addition to secondarily evaluating whether it reduces the number of amputations and improves the quality of life in these patients.MethodsA non-blind randomized clinical study will be conducted in the city of Imperatriz, Maranhão state, Brazil, from 2019 to 2020, in diabetic patients with chronic foot ulcers (classified as Wagner grades 2, 3 and 4, persisting for more than 1 month). The outpatient follow-up for diabetic foot patients will be done at the Unified Health System, with a sample size of 120 patients (the randomization allocation will be 1:1, being 60 patients for each arm). Half of the patients will receive standard treatment, i.e. dressings, debridement, antibiotics and load relief, along with HBOT (HBOT group), and the other half will receive only standard treatment (control group). The patients of the HBOT group will be evaluated upon admission, after 10, 20, 30 and 35 HBOT sessions, and after 6 months and 1 year. The patients of the control group will also be evaluated at equivalent periods (upon admission, after 2, 4, 6 and 7 weeks, 6 months and 1 year). The SF-36 quality of life questionnaire will be filled upon admission and after 3 months of follow-up in both groups. The primary and secondary endpoints will be assessed with 1 year of follow-up.DiscussionDiabetic foot ulcers are a highly prevalent complication of diabetes with serious consequences. A study to assess the efficacy of HBOT in healing the ulcers and reducing the rate of amputations in diabetic patients is justified, which will eventually aid in the development of guidelines for treating these ulcers.Trial registrationRegistration number RBR-7bd3xy. Registered on 17 July 2019—Retrospectively registered.

Vitamin C improves healing of foot ulcers: a randomised, double-blind, placebo-controlled trial.

Chronic foot ulcers are associated with a high risk of osteomyelitis, poor quality of life, amputations and disability. Few strategies improve their healing, and amputation rates in high-risk foot services are usually over 30 %. We conducted a randomised, inactive-placebo controlled, double-blind trial of 500 mg of slow-release vitamin C in sixteen people with foot ulcers in the Foot Wound Clinic at Westmead Hospital. Nine were randomised to control and seven to vitamin C. When serum vitamin C results become available at 4 weeks, all people with deficiency were offered both vitamin C and glucosamine tablets for the next 4 weeks. Patients without baseline deficiency continued their original assigned treatment. The primary outcome was percentage ulcer healing (reduction in ulcer size) at 8 weeks. Fifty percentage of subjects had baseline vitamin C deficiency, half having undetectable levels. Healing at 8 weeks was significantly better in the vitamin C group (median 100 v. -14 %, P = 0·041). Healing without amputation occurred in all patients in the vitamin C group. In contrast, 44 % of controls had not healed their ulcer at the end of the study period. Vitamin C improved healing of foot ulcers. Further studies are needed to determine whether there is a threshold effect for serum vitamin C above which therapy is ineffective and whether there are better or lesser responding subgroups. Because of its low cost and ease of access and administration, we recommend offering vitamin C therapy to all people who have chronic foot ulcers and potentially suboptimal vitamin C intake. Trial registration number: ACTRN12617001142325.