L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model.

Diabetic foot ulcers (DFUs) are the most common complications of diabetes resulting from hyperglycemia leading to ischemic hypoxic tissue and nerve damage. Staphylococcus aureus is the most frequently isolated bacteria from DFUs and causes severe necrotic infections leading to amputations with a poor 5-year survival rate. However, very little is known about the mechanisms by which S. aureus dominantly colonizes and causes severe disease in DFUs. Herein, we utilized a pressure wound model in diabetic TALLYHO/JngJ mice to reproduce ischemic hypoxic tissue damage seen in DFUs and demonstrated that anaerobic fermentative growth of S. aureus significantly increased the virulence and the severity of disease by activating two-component regulatory systems leading to expression of virulence factors. Our in vitro studies showed that supplementation of nitrate as a terminal electron acceptor promotes anaerobic respiration and suppresses the expression of S. aureus virulence factors through inactivation of two-component regulatory systems, suggesting potential therapeutic benefits by promoting anaerobic nitrate respiration. Our in vivo studies revealed that dietary supplementation of L-arginine (L-Arg) significantly attenuated the severity of disease caused by S. aureus in the pressure wound model by providing nitrate. Collectively, these findings highlight the importance of anaerobic fermentative growth in S. aureus pathogenesis and the potential of dietary L-Arg supplementation as a therapeutic to prevent severe S. aureus infection in DFUs.IMPORTANCES. aureus is the most common cause of infection in DFUs, often resulting in lower-extremity amputation with a distressingly poor 5-year survival rate. Treatment for S. aureus infections has largely remained unchanged for decades and involves tissue debridement with antibiotic therapy. With high levels of conservative treatment failure, recurrence of ulcers, and antibiotic resistance, a new approach is necessary to prevent lower-extremity amputations. Nutritional aspects of DFU treatment have largely been overlooked as there has been contradictory clinical trial evidence, but very few in vitro and in vivo modelings of nutritional treatment studies have been performed. Here we demonstrate that dietary supplementation of L-Arg in a diabetic mouse model significantly reduced duration and severity of disease caused by S. aureus. These findings suggest that L-Arg supplementation could be useful as a potential preventive measure against severe S. aureus infections in DFUs.

Efficacy of Chinese and Western Medical Techniques in Treating Diabetic Foot Ulcers With Necrotizing Fasciitis of the Lower Leg.

To analyze and evaluate the clinical efficacy of Chinese and Western medical techniques in the treatment of severe diabetic foot ulcers complicated with necrotizing fasciitis of the lower leg and summarize the treatment experience of such patients to identify a new method of limb salvage treatment. A total of 46 patients with severe diabetic foot ulcers and necrotizing fasciitis of the lower leg were treated with such techniques as surgical debridement, bone drilling, open joint fusion, and microskin implantation. Wounds were treated with moisture-exposed burn therapy (a regenerative medical treatment for burns, wounds, and ulcers) and moisture-exposed burn ointment (a traditional Chinese medicine); underlying diseases were also treated effectively. The wound healing time, rate of high amputation, and mortality of these patients were summarized, and the clinical efficacy of such treatments was evaluated. Of the 46 patients enrolled, 38 patients were cured, with a cure rate of 82.61%. The average wound healing time was 130 ± 74.37 days. Two patients underwent high amputations, with an amputation rate of 4.35%, and 4 deaths occurred, with a mortality rate of 8.70%. The combination of Chinese and Western medical techniques in the treatment of severe diabetic foot ulcers complicated with necrotizing fasciitis of the lower leg not only effectively saved patients' lives and promoted wound healing but also greatly reduced the rates of high amputation and disability.

The efficacy of electroacupuncture in among early diabetic patients with lower limb arteriosclerotic wounds.

Diabetic foot ulcers are the prevalent complication of diabetes mellitus, frequently culminating in arteriosclerosis of the lower extremities and consequent development of chronic wounds. The effectiveness of electroacupuncture (EA) as therapeutic intervention for promoting wound healing in this particular group of patients has been comprehensively assessed in this study. A randomized controlled trial involving 380 early diabetic patients with arteriosclerotic lesions of the lower limbs was conducted. Standard wound care plus EA was administered to the treatment group, while standard wound care alone was administered to the control group. The principal outcome assessed was the reduction in lesion size following the 8-week treatment period. Pain scores, recuperation time, and quality of life (QoL) evaluations constituted secondary outcomes. In comparison to the control group, the treatment group exhibited a significantly greater reduction in wound size (p < 0.05). The treatment group exhibited significantly reduced pain scores and significantly higher QoL scores (p < 0.05). The duration of recovery did not vary substantially among the groups (p > 0.05). Electroacupuncture thus appeared to be an effective adjunctive treatment for early diabetic patients with lower limb arteriosclerotic lesions, promoting pain relief and quality of life. Additional investigation is necessary to validate these results and delve into the underlying mechanisms of action.

Association Between Atrial Fibrillation and Diabetes-Related Complications: A Nationwide Cohort Study.

OBJECTIVE: This study aimed to investigate the associations between concurrent atrial fibrillation and diabetes-related complications among patients with diabetes. RESEARCH DESIGN AND METHODS: This nationwide observational cohort study used the health checkup database from the Korean National Health Insurance Service. Patients diagnosed with diabetes who underwent health checkups between 2009 and 2012 were investigated. The patients with atrial fibrillation were matched in a 1:5 ratio with those without atrial fibrillation using propensity scores. Study outcomes included macrovascular, microvascular (diabetic retinopathy and diabetic nephropathy), and diabetic foot complications. The risks of clinical outcomes were measured using hazard ratios (HRs) with 95% CIs. RESULTS: A total of 65,760 patients with diabetes were analyzed (54,800 without atrial fibrillation and 10,960 with atrial fibrillation). After well-balanced propensity score matching, atrial fibrillation was associated with significantly higher risks of macrovascular complications (HR 1.12, 95% CI 1.09-1.16), diabetic nephropathy (HR 1.23, 95% CI 1.16-1.30), and diabetic foot complications (HR 1.13, 95% CI 1.09-1.17) compared with no atrial fibrillation, while the risk of diabetic retinopathy was comparable (HR 0.99, 95% CI 0.96-1.03). Patients with atrial fibrillation had a significantly higher risk of diabetic foot amputation (HR 4.12, 95% CI 1.98-8.56). CONCLUSIONS: Among patients with diabetes, concurrent atrial fibrillation was associated with increased risks for diabetes-related macrovascular complications, diabetic nephropathy, and diabetic foot. Such patients require holistic management to reduce the risk of adverse outcomes.

Combination of Shengji ointment and bromelain in the treatment of exposed tendons in diabetic foot ulcers: study protocol for a non-blind, randomized, positive control clinical trial.

BACKGROUND: Diabetic foot ulcers often affect tendon tissue. Consequently, the infection may spread proximally along the tendon, leading to amputation or even the death of patients. Exposed, degenerated, and necrotic tendons are key factors affecting the healing of diabetic foot ulcers. The effective treatment of the tendon involvement may positively affect the prognosis. In clinical practice, treatment with Shengji ointment and bromelain induces islands of granulation tissue on the denatured tendon surface, which gradually grows and merges. Ideally, the exposed tendon is covered entirely by granulation tissue. This trial aims to assess the effect of a combined treatment regime of Shengji ointment, which has been shown to regenerate muscle tissue and pineapple protease in preventing the loss of function and amputation caused by tendon necrosis. This trial will provide high-quality evidence for the effectiveness of this combination in healing diabetic ulcers with tendon necrosis. METHODS: The sample size will be 180 patients who will be randomly assigned 1:1 to a treatment group (90 patients) using Shengji ointment combined with bromelain and a control group (90 patients) using hydrocolloid dressing. Both groups will continue their conventional treatments, such as blood glucose and blood pressure medication, lipid regulation, antiplatelets, and others. The primary outcome will be the wound coverage with granulation tissue. Secondary outcomes will be the wound healing rate, amputation extent (where needed), time to granulation, and the Maryland Foot Score. Other efficacy outcomes will be the time to debridement of necrotic tendon tissue and granulation tissue score. DISCUSSION: This study will treat patients with diabetic foot ulcers with exposed, degenerated, and necrotic tendons with Shengji ointment and bromelain. The trial aims to promote regeneration and healing, to preserve the limb and its function, and to develop a comprehensive and effective protocol that can be applied to promote the healing of exposed tendons in diabetic foot wounds. TRIAL REGISTRATION: ChiCTR2000039327 ; date of registration: 2020-10-23.

DIONYSIUS trial: "Does increasing oxygen nurture your symptomatic ischaemic ulcer sufficiently?" Study protocol for an international multicentre randomised trial.

INTRODUCTION: Diabetic foot ulcers (DFUs) are a major complication of diabetes and often associated with peripheral arterial occlusive disease. Current available evidence shows hyperbaric oxygen therapy (HBOT) can reduce the risk of major amputation, but clinicians remain sceptical about the (cost-)effectiveness and feasibility of HBOT for ischaemic DFUs in clinical practice. Therefore, vascular surgeons and HBOT physicians worldwide feel a strong need for a sufficiently powered clinical trial to determine whether and how many HBOT sessions may be a (cost-)effective adjunctive treatment to ischaemic DFUs. METHODS: An international, multicentre, multi-arm multi-stage design is chosen to conduct an efficient randomised clinical trial. Patients will be randomised to receive standard care (wound treatment and surgical interventions following international guidelines) with either 0, 20, 30 or at least 40 sessions of HBOT. These sessions will comprise 90-120 min of HBOT at a pressure of 2.2-2.5 atmospheres absolute according to international standards. Based on a planned interim analysis, the best performing study arm(s) will continue. Primary end point is major amputation (ie, above ankle) rate after 12 months. Secondary end points are amputation-free survival, wound healing, health-related quality of life and cost-effectiveness. ETHICS AND DISSEMINATION: All patients enrolled in this trial will receive maximum vascular, endovascular or conservative treatment and local wound care according to best practice and (inter)national guidelines. HBOT therapy is added to the standard treatment and is regarded as a low-risk to moderate-risk therapy. The study is approved by the medical ethics committee of the Amsterdam University Medical Centers, location University of Amsterdam. TRIAL REGISTRATION NUMBER: 2020-000449-15, NL9152, NCT05804097.

Evaluation of Vitamin D Levels in Patients With Diabetic Foot Ulcers.

Low vitamin D levels have been associated with several diseases as its receptors are expressed in almost all tissues of the human body. Literature data have shown delayed diabetic foot ulcer (DFU) healing in patients with low vitamin D; however, data on the association between vitamin D levels and DFU in Mediterranean countries are scarce. In this cross-sectional study we examined for differences in serum vitamin D levels between patients with DFU, people with diabetes mellitus (DM) without DFU and healthy individuals in a Southern European country. A total of 96 subjects (33 patients with DFU, 35 patients without DFU and 28 healthy controls) were recruited. Medical and dietary history was obtained and total serum 25-hydroxyvitamin D [25(OH)D] levels were determined. Serum vitamin D levels differed significantly among the three groups of participants; sub-analysis showed that healthy individuals had higher vitamin D levels when compared with patients with and without DFU, while vitamin D levels did not differ between patients with and without DFU (17.9 ± 6.7 vs. 19.8 ± 8.7 ng/mL, P = 0.329, respectively). More than half of patients with DM with or without DFU had vitamin D levels <20 ng/ml. A positive correlation was found between vitamin D and sun exposure duration in participants without DFU. In conclusion, although serum vitamin D levels did not differ between people with and without DFU, the prevalence of deficiency and insufficiency was high in both groups in a Mediterranean country. This finding highlights the need for screening and supplementation with vitamin D in individuals with DM.

Association of vitamin D status with all-cause mortality and outcomes among Chinese individuals with diabetic foot ulcers.

AIMS/INTRODUCTION: The aim of this study was to examine the correlation between serum vitamin D concentrations and prognosis among Chinese individuals with diabetic foot ulcers (DFUs). MATERIALS AND METHODS: We retrospectively recruited 488 adults with DFUs in West China Hospital from 1 January 2012 to 31 December 2019. After telephone follow up, 275 patients were finally included. We compared serum vitamin D concentrations among DFUs patients with different prognostic status, and examined the association of vitamin D status with prognostic variables by Kaplan-Meier analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for all-cause mortality. RESULTS: The median concentration of serum vitamin D of patients with DFUs was 37.78 nmol/L (interquartile range 27.91-50.66 nmol/L), with 31.6% having vitamin D deficiency (<30 nmol/L) and 42.2% having insufficient vitamin D (<50 nmol/L). During a median follow-up period of 52 months, 65 patients died, with an all-cause mortality of 23.64%. Vitamin D deficiency was independently linked to increased all-cause mortality after multivariable adjustments (hazard ratio 0.565, 95% confidence interval 0.338-0.946, P = 0.030). There were no significant differences between vitamin D concentrations and other outcomes of DFUs. Patients who suffered amputations had a tendency of lower vitamin D concentrations (34.00 [interquartile range 26.90-41.81] vs 40.21 [interquartile range 29.60-53.96] nmol/L, P = 0.053). CONCLUSIONS: Vitamin D deficiency was significantly associated with increased all-cause mortality in Chinese individuals with DFUs. Vitamin D supplementation might be a potential therapy for DFUs to prevent premature death and improve outcomes.

Evaluation of the healing potential of short-term ozone therapy for the treatment of diabetic foot ulcers.

Background: The availability of research on short-term ozone therapy for diabetic foot ulcers (DFUs) is limited, and even when it is accessible, it mainly comprises of basic analysis conducted during long-term ozone therapy. This study was to evaluate the efficacy of short-term ozone therapy in promoting wound healing in DFUs. Methods: A retrospective analysis was conducted on 89 patients with type 2 diabetes complicated by DFUs. The patients were divided into two groups: ozone therapy group (n=41) and control group (n=48). Wound condition, change of bacterial types, changes in inflammatory indicators (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and procalcitonin [PCT]), vascular endothelial growth factor (VEGF), cytokines [Interleukin 6 (IL-6) and tumor necrosis factor-α(TNF-α)], and oxidative stress levels (superoxide dismutase [SOD], malondialdehyde [MDA], and total antioxidant capacity [T-AOC]) were observed pre-treatment and after 1 week. After a 12-week of follow-up, wound healing rate, amputation rate, inpatient day, duration of antibiotics, reinfection rate, incidence of new ulcers, readmission rate, and reoperation rate, and cumulative wound healing rate using Kaplan-Meier curves were assessed. Results: After 1 week of treatment, the ozone therapy group showed higher VEGF, SOD, and T-AOC levels compared to the control group (P<0.05), while CRP, PCT, ESR, IL-6, TNF-α, MDA levels and bacterial types were lower (P<0.05). The ozone therapy group had a higher wound healing rate after a 12-week follow-up (P<0.05). Kaplan-Meier curves indicated a higher cumulative wound healing rate in the ozone therapy group (P<0.05). Additionally, the ozone therapy group had lower inpatient day, duration of antibiotics, reinfection rate, and readmission rate compared to the control group (P<0.05). Conclusion: Short-term ozone therapy is effective in promoting wound healing in DFUs by reducing inflammation, increasing growth factor levels, improving oxidative stress status, shortening healing time, and improving long-term prognosis. These findings suggest the potential of short-term ozone therapy as a valuable treatment modality for DFUs.

Investigation of the relationship between the use of complementary alternative medicine and illness perception and illness cognition in patients with diabetic foot ulcer.

OBJECTIVE: to examine the relationship between illness perception, illness cognition, and other sociodemographic characteristics of individuals with diabetic foot ulcer (DFU) and their complementary alternative therapies (CAM) use within the framework of self-regulation model (SRM). MATERIAL AND METHODS: This cross-sectional descriptive study was carried out with 220 individuals with DFU in the Endocrinology and Metabolic Diseases outpatient clinic of two training and research hospitals between December 5, 2020, and June 5, 2021. Research data were collected by using the Patient Information Form, Brief Illness Perception Scale (BIPS), and Illness Cognition Questionnaire (ICQ). Descriptive statistical methods and the Mann-Whitney U test were used to were used in the evaluation of the data. The determinants of the CAM use status of the patients were evaluated by logistic regression analysis. RESULTS: It was determined that 136 (61.81%) patients who used CAM mostly preferred herbal methods. Patients' mean scores were 42.23 ± 5.66 on the total BIPS, 39.65 ± 16.01 on the total ICQ. Increasing age, female gender, increased disease perception (BIPS) and disease cognition (ICQ) increased the use of CAM (Nagelkerke R2:0.552; Model: x2 = 168.579 p = 0.00) CONCLUSIONS: It was determined that our patients frequently preferred CAM. Predictors of CAM use were identified as female gender, advanced age, illness perception, and illness cognition. Accordingly, for effective management of DFU, besides the comprehensive evaluation of individuals with DFU and the provision of wound care by health care professionals, illness perceptions, illness cognition, and CAM use should be considered carefully.

Hyperbaric oxygen therapy as an adjunct to the standard wound care for the treatment of diabetic foot ulcers in Indian patients: a cost utility analysis.

BACKGROUND: Diabetic foot ulcer (DFU) is a common complication of diabetes. Hyperbaric oxygen therapy (HBOT) is an adjunct treatment that expedites the healing of DFU. AIM: To evaluate the cost-utility of using standard wound care (SWC) plus HBOT as compared to SWC alone for the treatment of DFU from a societal perspective in the Indian context. METHOD: A Markov decision analysis model comparing SWC with and without HBOT was developed. Data for the model were derived from relevant literature and secondary data from India. The main outcome measures were minor and major lower extremity amputations (LEA) averted, incremental quality-adjusted-life-years (QALY) gained, incremental costs, incremental cost-effectiveness ratio (ICER) per amputation averted and ICER per QALY gained. Sensitivity and threshold analyses were also done. RESULT: HBOT, when added to SWC, lowered the proportion of minor LEA and major LEA among patients with DFU by 6.1% and 4.2%, respectively. The discounted ICER was INR 193,939 [95% CI: 186,745-203,753] or US$ 2,621 [95% CI: 2,524-2,753] per QALY gained. CONCLUSION: SWC plus HBOT is not cost-effective in India. Additional information is required on patient experiences with adjunctive HBOT, if it were to be adopted as the standard of care in India.

Hyperbaric oxygen therapy: when pressure is good for diabetic foot ulcers.

The diabetic foot ulcer (DFU) as a common complication of diabetes. Even with adequate treatment, up to 35% of these ulcers do not heal. This is due to the effect of aging, repeated ischemia-reperfusion (IR) injury, bacterial colonisation of the wound and chronic hypoxia. All wound-healing processes are highly dependent on oxygen, so hyperbaric oxygen therapy (HBOT) can be employed to improve wound healing and correct the four pathophysiological factors for chronic wounds. It is, in fact, internationally recognised as a treatment option for non-healing DFUs. Several trials and systematic reviews have been performed on its efficacy, which show a positive trend towards increased wound healing and reduced amputation risk. Some controversy exists due to contradictory results in these studies, which may be due to grouping patients with and without peripheral arterial occlusive disease (PAOD) together. Side effects are usually mild and transient, and the treatment is considered safe.

Efficacy of moxibustion in diabetes peripheral neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. The main clinical manifestations of DPN include pain, numbness, paraesthesia, and weakness of the lower limbs which often leads to diabetic foot ulceration, eventually resulting in amputation. Based on Traditional Chinese Medicine theory, moxibustion has a great effect on treating and preventing DPN. However, randomized clinical trials done to evaluate the efficacy of this treatment are still lacking. Hence, this study is carried out to evaluate the effectiveness and safety of moxibustion therapy on diabetic peripheral neuropathy. METHODS: This study will be a pilot, interventional, randomized, 2-armed, parallel, singled-masked, controlled trial. A total of 40 diabetes mellitus patients with peripheral neuropathy will be recruited and assigned randomly into 2 groups (moxibustion group and waiting group) at a 1:1 ratio. This trial consists of an 8-week intervention period and a 4-week follow-up period. During the intervention period, the moxibustion group will take 3 moxibustion sessions per week, whereas no intervention will be done on the waiting group to act as the control group. The outcome will be assessed by an outcome assessor who is unaware of the group assignment. The primary outcome will be pain assessment measured with algometry, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, visual analogue scale, and neuropathy pain scale. The secondary outcome will be an evaluation of functional performance capacity with 6 minutes walking test, evaluation of the Foot and Ankle Ability Measure, and serum HbA1c and albumin levels. DISCUSSION: We hope that this trial will provide valuable insights on the efficacy of moxibustion in the management of diabetic peripheral neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov Registry No.: NCT04894461 (URL: https://clinicaltrials.gov/ct2/show/NCT04894461?term=NCT04894461&draw=2&rank=1) Registered on May 20, 2021.

Associations between Nutrients and Foot Ulceration in Diabetes: A Systematic Review.

We reviewed the literature to evaluate potential associations between vitamins, nutrients, nutritional status or nutritional interventions and presence or healing of foot ulceration in diabetes. Embase, Medline, PubMed, and the Cochrane Library were searched for studies published prior to September 2020. We assessed eligible studies for the association between nutritional status or interventions and foot ulcers. Fifteen studies met the inclusion criteria and were included in this review. Overall, there is a correlation between poor nutritional status and the presence of foot ulceration or a delay in healing. However, there is not enough data to reach conclusions about whether the relationships are causal or only association. Further research is required to test whether any forms of nutritional supplementation improve foot ulcer healing.

[Nutrition in the prevention and healing of chronic wounds. Importance in improving the diabetic foot]. / La nutrición en la prevención y curación de heridas crónicas. Importancia en la mejora del pie diabético.

INTRODUCTION: Nutrition plays an essential role in chronic wound healing as extra nutrients are needed for tissue repair and to restore losses through wound exudate. Insufficient intake of energy, protein, antioxidants (vitamin C, A, and zinc) and vitamin D are common in patients with chronic wounds and have been linked to delayed wound healing and dehiscence. Other risk factors such as obesity, diabetes, advanced age, corticosteroid use, and dehydration can also reduce or impede the healing process, and nutritional screening is important to identify patients with malnutrition. Proteins, amino acids (arginine, glutamine and methionine), vitamins C and A, and zinc have been used as pharmacological nutrients in pressure ulcer healing; however, omega-3 fatty acids, although they appear to slow progression, do not show improved healing rates. In patients with diabetic foot, supplementation with vitamins D, C, A, and E, magnesium, zinc, omega-3 fatty acids, and probiotics reduces ulcer size and improves glycemic control, although they have not been associated with complete healing; however, supplementation with arginine, glutamine, and ß-hydroxy-ß-methylbutyrate does show wound healing, although further evidence is needed to confirm these results.

INTRODUCCIÓN: La nutrición tiene un papel esencial en la cicatrización de las heridas crónicas ya que se necesita un aporte extra de nutrientes en la reparación tisular y para restablecer las pérdidas originadas a través del exudado de la herida. El aporte insuficiente de energía, proteínas, antioxidantes (vitamina C, vitamina A y zinc) y vitamina D es frecuente en los pacientes con heridas crónicas y se ha relacionado con retrasos en la curación y dehiscencia de la herida. También otros factores de riesgo como la obesidad, la diabetes, la edad avanzada, el consumo de glucocorticoides y la deshidratación pueden disminuir o impedir el proceso de la cicatrización, siendo importante la realización de un cribado nutricional para identificar a los pacientes con desnutrición. Las proteínas, los aminoácidos (arginina, glutamina y metionina), las vitaminas C y A, y el zinc se han utilizado como nutrientes farmacológicos para la cicatrización de las úlceras por presión; sin embargo, los ácidos grasos omega-3, aunque parecen disminuir su progresión, no muestran mejores tasas de curación. En los pacientes con pie diabético, la suplementación con vitaminas D, C, A y E, magnesio, zinc y ácidos grasos omega-3, así como la administración de probióticos, reduce el tamaño de la úlcera y mejora el control glucémico, aunque no se han relacionado con una cicatrización completa; sin embargo, la suplementación con arginina, glutamina y ß-hidroxi-ß-metilbutirato logra la curación de la herida, aunque es necesaria una mayor evidencia que confirme estos resultados.

[Management of a foot ulcer in a patient with diabetes]. / Ulcère du pied chez un patient avec un diabète : quelle prise en charge médico-chirurgicale ?

Despite a benign appearance, any foot injury occurring in a patient with diabetes requires multidisciplinary management if dreaded complications such as amputation are to be avoided. From a pathophysiological point of view, foot ulcer generally results from the combination of lower extremity neuropathy, mechanical overload, immunopathy and vascular insufficiency. The treatment associates in all cases an offloading and one or more debridements. Depending on the grade of the ulcer, adjuvant treatments, such as antibiotic therapy, revascularization, and hyperbaric oxygen therapy may be indicated.

En dépit d'un aspect bénin, toute plaie au niveau d'un pied survenant chez un patient avec un diabète nécessite une prise en charge multidisciplinaire si l'on veut éviter des complications redoutables comme une amputation. D'un point de vue physiopathologique, l'ulcère du pied résulte généralement de la combinaison entre une neuropathie des membres inférieurs, une surcharge mécanique, une immunopathie et une insuffisance vasculaire. La prise en charge associe dans tous les cas une décharge et un ou plusieurs débridements. Selon la gravité de l'ulcère, des traitements adjuvants sont indiqués, tels qu'une antibiothérapie, une revascularisation et une oxygénothérapie hyperbare.

Long-term effects of hyperbaric oxygen therapy on visual acuity and retinopathy.

Hyperbaric oxygen (HBO2) therapy is an adjunct treatment for diabetic foot ulcers. Since plausible mechanisms of action for this treatment include increased angiogenesis and high tissue oxygen concentrations, concerns about deterioration of retinopathy have been raised. The aim of this study was to evaluate the effects of HBO2 on visual acuity (VA) and retinopathy in patients with chronic diabetic foot ulcers during a two-year follow-up period. This is a randomized, single-center, double-blinded and placebo-controlled clinical trial evaluating the effects of HBO2 in patients with diabetes mellitus and chronic foot ulcers. All study participants underwent an ophthalmological examination before the first study treatment and then at three, six, 12 and 24 months. Fifty patients with a median age of 67 years were included. Visual acuity was similar between groups and did not change during the two-year observation period. No differences in retinopathy were seen between groups; neither were any differences found in numbers or areas of bleedings, hard exudates, microaneurysms or edemas, nor between groups or visits. New clinically significant macular edema was identified in four eyes in the HBO2 group and in three eyes in the placebo group. In this population of diabetic foot ulcer patients HBO2 seems to be neutral in an ophthalmological perspective. From a retinal point of view, we could not identify any indication of harmful effects of HBO2 on the microvascular bed in the placebo group.

[Complex treatment of patients with pyo-necrotic complications of the neuropathic form of diabetic foot syndrome]. / Kompleksnoe lechenie bol'nykh s gnoino-nekroticheskimi oslozhneniyami pri neiropaticheskoi forme sindroma diabeticheskoi stopy.

OBJECTIVE: Of study is improving the results of treatment of patients with pyo-necrotic complications of diabetic foot syndrome by including the method of negative pressure wound treatment in the complex treatment program in combination with using of the combined antibacterial drug Cifran ST and immunocorrective therapy. MATERIAL AND METHODS: The results of examination and treatment of 184 patients with pyo-necrotic complications of the neuropathic form of diabetic foot syndrome were analyzed. According to choice of treatment methods in the postoperative period all patients were divided into two groups. In 95 patients (group I), iodine-containing ointments based on polyethylene glycol were used for local treatment of purulent foot wounds and standard systemic antibacterial therapy was performed. In 89 patients (group II), negative pressure wound treatment (NPWT) was used to treat wounds in the postoperative period. In addition to standard parenteral antimicrobial therapy, these patients also received an oral combined antibacterial drug Cifran ST and immunocorrective cytokine therapy (Leukinferon). The analysis of the dynamics of the wound process was carried out based on the clinical picture and the results of cytological, bacteriological and immunological studies of the wound exudate. RESULTS: The presented strategy of complex treatment of pyo-necrotic complications of the neuropathic form of diabetic foot syndrome allowed group II patients to significantly reduce the degree of microbial contamination of wounds, to achieve a faster regression of the content of proinflammatory and inflammatory cytokines in the wound exudate, as well as to reduce the time of wound cleansing and the transition of the pyo-necrotic process to the reparative stage in comparison with group I patients. This allowed group II patients to reduce the time of plastic closure of the wound from 24.3±0.5 to 15.6±1.7 days, to avoid generalization of infection, death and high level amputation of the limb. At the same time, 11.6% of patients in group I had high level limb amputation due to generalization of infection. The mortality rate in group I was 5.3%. CONCLUSIONS: Adding of vacuum therapy of wounds, systemic antimicrobial therapy using the combined antibacterial drug Cifran ST and immunocorrective cytokine therapy in the complex treatment program for patients with neuropathic form of diabetic foot syndrome after radical surgical treatment of the pyo-necrotic lesion allows reducing the time of wound cleansing and the transition of the pyo-necrotic process to the reparative stage. On the other hand, this makes it possible for this category of patients to perform plastic closure of the wound at an earlier date, avoid generalization of infection and high level amputation of the limb.

Acupuncture as adjuvant therapy for diabetic foot: A protocol for systematic review.

BACKGROUND: Diabetic foot (DF) problems are common throughout the world, about one-fourth of them develop a foot ulcer and serious cases would suffer from amputation, which seriously affects the patient's work and life. Previous studies indicated that acupuncture as adjuvant therapy would be effective in treating DF. However, these studies have no consistent results. Therefore, the aim of our study was to explore the efficacy and safety of acupuncture as adjuvant therapy for DF. METHODS: The randomized controlled trials associated with acupuncture therapy (or as adjuvant therapy) for DF will be included. We will search 6 electronic databases relevant to health sciences, including PubMed, Embase, the Cochrane Library, the Chinese databases Sino-Med, CNKI, and WANFANG database. All searches were from databases inception to March 30, 2019. The primary outcomes are the total curative effective rate, and the hemodynamic parameter and adverse events will be deemed as secondary outcomes. The Stata15.1 software and Review Manager (RevMan 5.3; Cochrane Collaboration, Copenhagen, Denmark) will be used for analysis, to assess the bias risk, subgroup analysis, and data synthesis. RESULTS: In this systematic review and meta-analysis, we will synthesize the studies to assess the safety and efficacy of acupuncture as adjuvant therapy for DF. CONCLUSION: The summary of our study will clarify whether acupuncture as adjuvant therapy could be an efficient method for DF.

A systematic review and meta-analysis of hyperbaric oxygen therapy for diabetic foot ulcers with arterial insufficiency.

BACKGROUND: Diabetic foot ulcers (DFUs) are frequently associated with peripheral arterial occlusive disease (PAOD) and may ultimately lead to amputations of the lower extremity. Adjuvant hyperbaric oxygen treatment (HBOT) might foster better wound healing and lower amputation rates in patients with DFU and PAOD. A systematic review was conducted to assess the effects of HBOT as an adjunctive therapy to standard treatment for patients with DFUs with PAOD. METHODS: Systematic review using the MEDLINE, EMBASE, and Cochrane CENTRAL databases (from inception to October 2018). All original, comparative studies on the effect of HBOT on DFUs with PAOD were eligible. The primary outcome measures were amputation rate, amputation-free survival, complete ulcer healing, and mortality. RESULTS: Eleven studies, totaling 729 patients, were included for analysis, including 7 randomized clinical trials, 2 controlled clinical trials, and 2 retrospective cohorts. Four were used for quantitative synthesis. Meta-analysis showed a significantly fewer major amputations in the HBOT group (10.7% vs 26.0%; risk difference, -15%; 95% confidence interval [CI], -25 to -6; P = .002; number needed to treat, 7; 95% CI, 4-20). No difference was found for minor amputations (risk difference, 8%; 95% CI, -13 to 30; P = .46). Three studies reporting on complete wound healing showed contrasting results. No significant difference was found for mortality or amputation-free survival. CONCLUSIONS: Current evidence shows that adjuvant HBOT improves major amputation rate, but not wound healing, in patients with DFUs and PAOD. Given the wide range of patients included in the trials, better patient selection may help define which patients with DFUs and PAOD benefit most from HBOT as standard adjunctive treatment.