Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation.

Diabetic foot ulcer (DFU), a common intractable chronic complication of diabetes mellitus (DM), has a prevalence of up to 25%, with more than 17% of the affected patients at risk of amputation or even death. Vascular risk factors, including vascular stenosis or occlusion, dyslipidemia, impaired neurosensory and motor function, and skin infection caused by trauma, all increase the risk of DFU in patients with diabetes. Therefore, diabetic foot is not a single pathogenesis. Preclinical studies have contributed greatly to the pathogenesis determination and efficacy evaluation of DFU. Many therapeutic tools are currently being investigated using DFU animal models for effective clinical translation. However, preclinical animal models that completely mimic the pathogenesis of DFU remain unexplored. Therefore, in this review, the preparation methods and evaluation criteria of DFU animal models with three major pathological mechanisms: neuropathy, angiopathy and DFU infection were discussed in detail. And the advantages and disadvantages of various DFU animal models for clinical sign simulation. Furthermore, the current status of vitro models of DFU and some preclinical studies have been transformed into clinical treatment programs, such as medical dressings, growth factor therapy, 3D bioprinting and pre-vascularization, Traditional Chinese Medicine treatment. However, because of the complexity of the pathological mechanism of DFU, the clinical transformation of DFU model still faces many challenges. We need to further optimize the existing preclinical studies of DFU to provide an effective animal platform for the future study of pathophysiology and clinical treatment of DFU.

Evaluation of the Effectiveness of Remote Foot Temperature Monitoring for Prevention of Amputation in a Large Integrated Health Care System.

OBJECTIVE: We evaluated the effectiveness of remote foot temperature monitoring (RTM) in the Veterans Affairs health care system. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study that included 924 eligible patients enrolled in RTM between 2019 and 2021 who were matched up to 3:1 to 2,757 nonenrolled comparison patients. We used conditional Cox regression to estimate adjusted cause-specific hazard ratios (aHRs) and corresponding 95% CIs for lower-extremity amputation (LEA) as the primary outcome and all-cause hospitalization and death as secondary outcomes. RESULTS: RTM was not associated with LEA incidence (aHR 0.92, 95% CI 0.62-1.37) or all-cause hospitalization (aHR 0.97, 95% CI 0.82-1.14) but was inversely associated (reduced risk) with death (aHR 0.63, 95% CI 0.49-0.82). CONCLUSIONS: This study does not provide support that RTM reduces the risk of LEA or all-cause hospitalization in individuals with a history of diabetic foot ulcer. Randomized controlled trials can overcome important limitations.

The association between micronutrient levels and diabetic foot ulcer: A systematic review with meta-analysis.

Background: Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU. Methods: A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed. Results: Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)]. Conclusion: This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.

Factors influencing diabetes-related foot ulcer healing in Australian adults: A prospective cohort study.

OBJECTIVE: Diabetes-related foot ulceration (DFU) is a common limb-threatening condition, which is complex and subsequently challenging to manage. The aim of this study was to determine the contribution of a range of clinical and social factors to the healing of diabetes-related foot ulceration in an Australian population. RESEARCH DESIGN AND METHODS: This was a prospective cohort study of individuals with diabetes-related foot ulceration (DFU). Age, sex, medical history, medications, dietary supplementation (e.g. vitamin C intake) and smoking history were elicited at baseline. The index of relative socio-economic disadvantage (IRSD) was calculated. The Australian Eating Survey and International Physical Activity Questionnaire-short were administered. Wound history, size, grade, time to healing and infection were captured and monitored over 6 months. Logistic regression was performed to determine the relationship between healing and diet quality, toe systolic pressure, wound size at, IRSD, infection and previous amputation. RESULTS: A total of 117 participants were included. The majority were male n = 96 (82%), socio-economically disadvantaged (mean IRSD 965, SD 60), and obese (BMI 36 kg/m2 , SD 11) with a long history of diabetes (20 years, SD 11). Wounds were predominantly neuropathic (n = 85, 73%) and classified 1A (n = 63, 54%) on the University of Texas wound classification system with few infections (n = 23, 16%). Dietary supplementation was associated with 4.36 increased odds of healing (95% 1.28-14.84, p = 0.02), and greater levels of socio-economic advantage were also associated with increased odds of healing (OR 1.01, 95% CI 1.01-1.02, p = 0.03). CONCLUSIONS: In this cohort study of predominantly neuropathic, non-infected DFU, individuals who had greater levels of socio-economic advantage had significantly greater odds of DFU healing. Diet quality was poor in most participants, with individuals taking supplementation significantly more likely to heal.

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.

Impact of Diabetes Foot Care Education on Amputation Rate in the University of Abuja Teaching Hospital, Nigeria.

Ulceration of the foot is a major problem for people with diabetes. In a developing country like Nigeria, huge challenge is caused by diabetes foot problems. The aim of this study was to determine the impact of diabetic foot care education of patients and health care staff on the outcome of diabetic foot complications in our hospital. This was a pre and post design carried out from April 2013 to March 2014 on 155 diabetes patients. Patient education was carried out by diabetes nurses and doctors, at diagnosis and re-enforced at follow-up clinics. At the end of 1 year, the impact of education was assessed. Descriptive statistics were generated as appropriate. A total of 155 patients, 64 (41%) males and 91 (59%) females, were studied with mean age of 49 ± 3 years and mean duration of diabetes 6 ± 2.6 years. At the onset of the program, 70% of the patients had no knowledge of foot care education. Only 13.5% knew that diabetes mellitus foot ulcer could be related to long duration of diabetes, nerve damage, blood vessel blockage, foot deformity, and uncontrolled blood glucose. Ninety-two percent of the patients preferred home remedies, herbal treatment, or chemist in the event of an ulcer. After the program, 77% would seek hospital care as first option, and amputation rate decreased from 50% in 2009 to 10% by 2017. Our experience has shown that education is the cheaper option for the prevention of lower limb amputation in a resource-poor setting like ours.

Hyperbaric oxygen therapy for chronic diabetic foot ulcers: An overview of systematic reviews.

OBJECTIVES: Hyperbaric oxygen therapy in the treatment of diabetic foot ulcer has been widely used in medical practice, but its clinical effect is not clear. The purpose of this overview of systematic reviews is to evaluate the clinical evidence of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers. METHODS: PubMed, Cochrane Library, Web of Knowledge, Embase, MEDLINE, Chinese National Knowledge Infrastructure Database, the Chongqing VIP Database, Chinese Biomedical Database, and Wanfang Database were searched in 1st December 2020. Systematic reviews (SRs) evaluating the effects of Hyperbaric oxygen therapy in people with diabetic foot ulcer were included. Methodological quality of the included SRs was assessed using the AMSTAR-2 tool. The quality of evidence of the primary studies was assessed using GRADE. The integrity of the included SRs was assessed using PRISMA. The bias risk of each SR was assessed using ROBIS evaluation tool. RESULTS: Eleven SRs/MAs met all inclusion criteria. According to the results of the AMSTAR-2, only 1 included review were rated critically as being of high quality, 6 included review were rated critically as being of medium quality. With PRISMA, the reporting checklist was relatively complete, but some reporting weaknesses remained in the topics of the protocol and registration, search strategy, and additional analyses. Based on the ROBIS tool, only five SRs/MAs had a low risk of bias. With the GRADE system, no high-quality evidence was found, and only 13 outcomes provided moderate-quality evidence. CONCLUSIONS: There is limited clinical evidence to support hyperbaric oxygen therapy in the treatment of diabetic foot ulcers, it is not recommended to routinely apply hyperbaric oxygen therapy to all patients with diabetic foot ulcers, especially those with non-ischemic diabetic foot ulcers. Hyperbaric oxygen therapy has certain potential to promote ulcer healing and reduce amputation rate in patients with ischemic diabetic foot ulcers, but due to the low quality and small quantity of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.

Treatment Strategies Against Diabetic Foot Ulcer: Success so Far and the Road Ahead.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It is associated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. There are four stages of wound healing, namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In the case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Conventional dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer for many years. INTRODUCTION: In this review, the global prevalence as well as etiopathogenesis related to diabetic foot ulcer have been discussed. The potential role of various synthetic and herbal drugs, as well as their conventional dosage forms in the effective management of DFU have been discussed in detail. METHODS: Structured search of bibliographic databases from previously published peer-reviewed research papers was explored and data has been represented in terms of various approaches that are used for the treatment of DFU. RESULTS: About 148 papers, including both research and review articles, were included in this review to produce a comprehensive as well as a readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action. CONCLUSION: DFU has become one of the most common complications in patients having diabetes for more than ten years. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as the judicious selection of drugs as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemic or they have been repositioned. In clinical practice, much focus has been given to dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that combination therapy of herbal and synthetic drugs with multiple treatment pathways could be able to offer better management of DFU.

Does Hyperbaric Oxygen Improve Lower Extremity Ulcer Outcomes?

A person with a diabetic foot ulcer (DFU) requires multidisciplinary care, including moist wound healing, consistent offloading of insensate areas, glycemic control, and adequate circulation. This is especially important during the COVID-19 pandemic, as patients with diabetes are at a higher risk of mortality.1 Reviewed in a 2018 installment of Evidence Corner,2 a double-blind, randomized clinical trial (RCT) reported that topical oxygen continuously diffused to DFU tissue resulted in nonhealing DFUs healing more than 20 days faster than those that were similarly treated with standard therapy and a sham device.3 More than twice the DFUs closed in patients receiving continuously diffused topical oxygen in comparison with the sham arm completely healed in 12 weeks (P = .02). It has been hypothesized that intervals of hyperbaric oxygen (HBO)-breathing 100% oxygen at atmosphere absolute (ATA) greater than the 1.0 normal at sea level-may similarly improve lower extremity ulcer healing outcomes. This month's Evidence Corner summarizes 2 studies regarding patients receiving HBO. The first study focused on patients with a DFU on a non-ischemic limb.4 The second studied the effects of HBO on lower extremity ulcers on ischemic limbs in patients with or without diabetes mellitus (DM).5 Read on to discover how informative and beneficial each of these studies can be in furthering best practice as well as which patients may experience improved lower limb ulcer healing in response to interventions that increase tissue oxygenation.

Association Between Vitamin D Status and Diabetic Complications in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study in Hunan China.

Background: Vitamin D status has been linked to diabetes-related complications due to multiple extraskeletal effects. We aimed to investigate the association between vitamin D deficiency (VDD) and diabetic vascular complications, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic foot ulcers (DFU). Methods: A total of 4,284 Chinese patients with type 2 diabetic mellitus (T2DM) were enrolled into the cross-sectional study. VDD was defined as serum 25-hydroxyvitamin D <50 nmol/L. Demographic data, physical measurements, laboratory measurements, comorbidities, and related medications were collected and analyzed by VDD status. Poisson regression with robust variance estimation and binary logistic regression were performed to explore the relationship between VDD and diabetic complications. Results: The prevalence of VDD, DR, DKD, DFU accounted to 71.7% (95% confidence intervals [CI]: 70.3-73.0%), 28.5% (95% CI: 27.2-29.9%), 28.2% (95% CI: 26.8-29.5%), and 5.7% (95% CI: 5.1-6.5%), respectively. The prevalence ratios (95% CI) for DR and DKD by VDD status, adjusted for demographics, physical measurements, laboratory measurements, related complications, and comorbidities, and medications, were 1.093 (0.983-1.215) and 1.041 (0.937-1.156), respectively. The odds ratio (95% CI) for DFU by VDD status was 1.656 (1.159-2.367) in the final adjusted model. Meanwhile, the prevalence of VDD was significantly higher in patients with DFU compared with patients without DFU. Conclusions: The present study firstly indicated that VDD was significantly associated with a higher prevalence of DFU among Chinese T2DM patients. The association between VDD status and DR or DKD was not significant when adjusting for all potential covariates. Vitamin D screening or supplementation may be beneficial to prevent DFU and improve the prognosis of T2DM patients.

Lower resource utilization for patients with healed diabetic foot ulcers during participation in a prevention program with foot temperature monitoring.

INTRODUCTION: We assessed the impact of a diabetic foot ulcer prevention program incorporating once-daily foot temperature monitoring on hospitalizations, emergency department and outpatient visits, and rates of diabetic foot ulcer recurrence and lower extremity amputations for patients with recently healed foot ulcers. RESEARCH DESIGN AND METHODS: In this retrospective analysis of real-world data, we enrolled 80 participants with a healed diabetic foot ulcer in a year-long foot ulcer recurrence prevention program. Four outpatient centers within a large integrated healthcare system in the USA contributed to enrollment. We evaluated diabetic foot-related outcomes and associated resource utilization for participants during three periods: the 2 years before the program, the year during the program, and after the program ended. We reported unadjusted resource utilization rates during the program and the periods before and after it. We then adjusted rates of outcomes in each phase using an interrupted time series approach, explicitly controlling for overall trends in resource utilization and recurrence during the three periods. RESULTS: Our unadjusted data showed high initial rates of resource utilization and recurrence before enrollment in the program, followed by lower rates during the program, and higher rates of resource utilization and similar rates of recurrence in the period following the end of the program. The adjusted data showed lower rates of hospitalizations (relative risk reduction (RRR)=0.52; number needed to treat (NNT)=3.4), lower extremity amputations (RRR=0.71; NNT=6.4), and outpatient visits (RRR=0.26; absolute risk reduction (ARR)=3.5) during the program. We also found lower rates of foot ulcer recurrence during the program in the adjusted data, particularly for wounds with infection or greater than superficial depth (RRR=0.91; NNT=4.4). CONCLUSIONS: We observed lower rates of healthcare resource utilization for high-risk participants during enrollment in a diabetic foot prevention program incorporating once-daily foot temperature monitoring. TRIAL REGISTRATION NUMBER: NCT04345016.

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.

Is there an association between vitamin D and diabetic foot disease? A meta-analysis.

It has been demonstrated that Vitamin D (25(OH)D) deficiency is associated with diabetes and with diabetic neuropathy. Some reports stated that vitamin D deficiency is also associated with diabetic foot ulcer and/or infection. Knowing the beneficial effect of vitamin D on wound healing, a quantitative evidence synthesis is needed to look for such association. Medline, Embase, Scopus, CINAHL, Cochrane Library, and Google Scholar were searched for from inception. The outcomes were set to be either the serum 25(OH)D level or the prevalence of patients with 25(OH)D with severe deficiency. Ten studies met the inclusion criteria with 1,644 patients; 817 diabetic patients with foot ulcers and 827 patients having diabetes without foot complications. The weighted mean differences was -0.93 (95% CI = -1.684 to -0.174, I2 = 97.8%, p = 0.01). The odds ratio of having severe vitamin D deficiency was 3.6 (95% CI = 2.940 to 4.415, I2 = 40.9%, p < 0.0001), in favor of the foot group. The quality of the included studies was found to be good to excellent. Diabetic foot complications are associated with significantly lower levels of vitamin D. Patients with diabetic ulcers or diabetic infection are at higher risk of bearing severe vitamin D deficiency. Knowing the beneficial effect of vitamin D on wound healing, it is likely that recognizing and supplementing with vitamin D could prevent or improve the outcomes of diabetic foot complications.

Microbiology of diabetic foot infections in three district hospital in Malaysia and comparison with South East Asian Countries.

INTRODUCTION: Diabetic foot infection, a complication that is associated with lower-limb amputation, incurs a huge economic burden to the hospital and health care system of Malaysia. The bacteriological profile of pathogens in diabetic foot infections in Malaysia has been sparsely studied. We investigated the microbiology of diabetic foot infections in patients admitted to the district hospitals on the east coast of Malaysia. METHODS: A retrospective analysis was conducted in three district hospitals (Hospital Kuala Lipis, Hospital Bentong and Hospital Raub) in Malaysia from 1st of January 2016 to 31st December 2016. The clinical specimens were cultured using Clinical and Laboratory Standards Institute (CLSI) guidelines. Antibiotic sensitivity testing to different antibiotics was carried out using the disc diffusion method. RESULT: A total of 188 pathogens were isolated from 173 patients, with an average of 1.09 pathogens per lesion. Majority of the pathogens isolated were gram negative pathogens (73.4%). The most commonly isolated pathogens were Staphylococcus aureus (17.5%). This was followed by Klebsiella spp. (17%), Pseudomonas spp. (15.4%) and Proteus spp. (13.8%). Gram positive pathogens were sensitive to most of the antibiotics tested except penicillin and fusidic acid. Gram negative pathogens were sensitive to all antibiotics tested except ampicillin and amoxicillin/clavulanic acid. Amikacin provide coverage for all gram negative pathogens in DFI. CONCLUSION: For the management of patient with infection in diabetic foot, the choice of antibiotic therapy depends on the sensitivity of the pathogens, the severity of the infection, the patient's allergies history, toxicity and excretion of the antibiotics.

Bacterial isolation and antibiotic susceptibility from diabetic foot ulcers in Kenya using microbiological tests and comparison with RT-PCR in detection of S. aureus and MRSA.

OBJECTIVES: Diabetic foot ulcers (DFUs) often lead to hospital admissions, amputations and deaths; however, there is no up-to-date information on microbial isolates from DFUs and no mention of utilization of molecular techniques in Sub-Saharan Africa. We conducted a cross-sectional study among 83 adult patients at a tertiary hospital in Kenya over 12 months. The study aimed to isolate, identify bacteria, their antibiotic susceptibility patterns in active DFUs, and to compare standard microbiological methods versus a real-time PCR commercial kit in the detection of Staphylococcus aureus DNA and methicillin-resistant S. aureus (MRSA) DNA. RESULTS: Eighty swabs (94%) were culture-positive; 29% were Gram-positive and 65% were Gram-negative. The main organisms isolated were S. aureus (16%), Escherichia coli (15%), Proteus mirabilis (11%), Klebsiella pneumoniae (7%) and Pseudomonas aeruginosa (7%). The bacterial isolates showed resistance to commonly used antibiotics such as ampicillin, amoxicillin, cefepime, ceftazidime, cefuroxime, clindamycin, erythromycin, piperacillin-tazobactam, tetracycline and trimethoprim-sulphamethoxazole (TMPSMX). Thirty-one percent of the S. aureus isolated and 40% of the Gram-negatives were multi-drug resistant organisms (MDROs). There was a high prevalence of nosocomial bacteria. MRSA were not identified using culture methods but were identified using PCR. PCR was more sensitive but less specific than culture-based methods to identify S. aureus.

Efficacy of Maggot Therapy on Staphylococcus aureus and Pseudomonas aeruginosa in Diabetic Foot Ulcers: A Randomized Controlled Trial.

PURPOSE: This study was conducted to evaluate the antimicrobial effects of medicinal maggots of Lucilia sericata on Staphylococcus aureus and Pseudomonas aeruginosa on diabetic foot ulcers (DFUs). DESIGN: Randomized controlled trial. SUBJECTS AND SETTING: The sample comprised 50 adult patients from the clinic of the Academic Center for Education, Culture and Research of Tehran University of Medical Sciences, Iran. All participants who had at least 1 DFU present for at least 12 weeks, an arterial brachial index value of more than 0.6, and a hemoglobin A1c value of less than 8% were included in this study. METHODS: Subjects were randomly selected for the maggot-treated (treatment) or conventional treatment (control) group. Conventional treatments such as antibiotic therapy, debridement, and offloading were done for both groups, but maggot therapy (MT) was added to the protocol of the treatment group. Bacterial burden was monitored and compared for both groups using cultures collected using swab technique. Wound secretions were measured and compared in both groups. RESULTS: The number of infected cases with S aureus in the treatment group was significantly reduced after 48 hours in comparison with the control group (P = .047). The number of infected cases with P aeruginosa was significantly reduced after 96 hours (P = .002). We also found that wound secretions in the treatment group were significantly higher than in the control group (P < .00). CONCLUSIONS: Our findings indicate that MT is a safe and efficacious treatment of DFUs.

Enhanced antibacterial effects of green synthesized ZnO NPs using Aristolochia indica against Multi-drug resistant bacterial pathogens from Diabetic Foot Ulcer.

BACKGROUND: Increased incidence of Multi-drug resistance in microorganisms has become the greatest challenge in the treatment of Diabetic Foot Ulcer (DFU) and urges the need of a new antimicrobial agent. In this study, we determined the bactericidal effects of ZnO nanoparticles (ZnO NPs) green synthesized from Aristolochia indica against Multi-drug Resistant Organisms (MDROs) isolated from pus samples of DFU patients attending in a tertiary care hospital in South India. METHODS: ZnO NPs were characterized by UV-vis-DRS spectroscopy, Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM) and for its zeta potential value. MIC/MBC assays were performed to determine bactericidal or bacteriostatic effects. Time-kill assays, Protein leakage and Flow cytometric analysis evaluated bacterial cell death at 1x MIC and 2x MIC concentrations of ZnO NPs. RESULTS: ZnO NPs of size 22.5nm with a zeta potential of -21.9±1mV exhibited remarkable bactericidal activity with MIC/MBC ranging from 25 to 400µg/ml with a significant reduction in viable count from 2h onwards. Protein leakage and Flow cytometric analysis confirmed bacterial cell death due to ZnO NPs. CONCLUSION: This study concluded that green synthesis protocol offers reliable, eco-friendly approach towards the development of antimicrobial ZnO NPs to combat antibiotic drug resistance.

To Smoke or Not To Smoke: Cigarettes Have a Negative Effect on Wound Healing of Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) have a complex pathophysiology and require an expert multidisciplinary treatment. There are several, both systemic and local, risk factors for DFUs. A recent meta-analysis of 18 studies has now provided robust evidence on the detrimental effect of smoking on healing of DFUs. Indeed, healing rates were consistently lower among smokers than among nonsmokers. Based on this new evidence, it is reasonable to consider the utility of smoking cessation programs. Incorporation of the latter into the holistic therapeutic strategy for DFUs may be anticipated to improve healing rates, but this remains to be shown.