Nous avons effectué une étude bibliographique intitulée “The diabetic foot microbiota: A review”. Cette revue a permis une réactualisation des données connues sur le microbiote du pied diabétique. Nous avons discuté le rôle des bactéries dans la pathogénèse de l’ulcère du pied diabétique et la différenciation entre l’infection et la colonisation bactérienne au niveau de la plaie ainsi que la superposition de l’approche moléculaire et la culture. Nous avons étudié le microbiote du pied diabétique infecté par culturomic. Il s’agit de varier les conditions de culture, puis identifier les colonies par MALDI-TOF ou par amplification et séquençage ARNr 16S. Cette technique s’est montrée efficace dans l’élargissement de l’éventail des bactéries identifiées. 53 espèces bactériennes différentes ont été identifiées à partir des échantillons de 43 patients. L’hétérogénéité et la richesse des plaies se sont montrées importantes. Staphylococcus aureus était l’espèce dominante. Nous nous sommes servis de tests statistiques pour évaluer l’influence que les facteurs cliniques chez les patients pourraient avoir sur la composition de cette flore et l’évolution de la plaie. On s’est orienté vers des souches spéciales « ExPEC » isolées des pieds diabétiques reconnues par leur virulence et impliquées dans des infections extra intestinales sévères. Nous avons disposé d’une collection de souches d’E Coli isolées des pieds diabétiques afin de mener une étude génétique. Nous sommes parvenus à amplifier les gènes de virulence, classer les souches par phylogroupes et les assembler dans des clones. En plus, nous avons réalisé un typage des souches ainsi qu’une exploitation des gènes de résistance. / We conducted a bibliographic study entitled "The Diabetic Foot Microbiota: a review". This review has offered an update of the data concerning the diabetic foot microbiota. We discussed the role of bacteria in the pathogenesis of diabetic foot ulcer, the differentiation between infection and bacterial colonization of the wound and the importance of superposing culture and molecular Tools.We studied the diabetic foot microbiota using the culturomics. It consists in varying the culture conditions and then to identify the colonies by MALDI-TOF or 16s rRNA amplification and sequencing. We decided to practice this technique on the diabetic foot microbiota because it has proven to be effective in broadening the range of identified bacteria. 53 different bacterial species were identified from the samples of 43 patients. The heterogeneity and richness of the wounds were elevated. Staphylococcus aureus was the dominant species. We used statistical tests to evaluate the influence that clinical factors in patients might have on the composition of this flora and the evolution of the wound. We targeted special strains « ExPEC »isolated from diabetic feet known to their virulance and involved in severe extra intestinal infections. We disposed of a collection of E Coli strains isolated from diabetic wounds to conduct a genetic study. We have managed to amplify the virulence genes, classify the strains by phylogroupes and assemble them in clones. In addition, we performed a strain typing as well as an exploitation of the resistance genes.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diabetic foot ulcers (DFUs) impart a large burden on patients and the healthcare system in Canada. Health utility estimates are an integral part of determining the cost-effectiveness of treatments for DFUs. The objective of this thesis was to identify health utility estimates for patients with non-healing DFUs. A systematic review of studies reporting health utility estimates for non-healing DFUs was conducted and included nine studies. The quality of the studies, as it related to the health utility estimates for non-healing DFUs, was difficult to determine due to a lack of reporting of study and patient characteristics. The health utility estimates ranged from 0.44 to 0.89. None of the studies investigated for factors associated with the health utility of patients with non-healing DFUs. In addition, an exploratory regression analysis of data from a randomized controlled trial (RCT) of hyperbaric oxygen therapy (HBOT) in patients with chronic, non-healing DFUs was conducted. No factors were identified that were associated with health utility; however, the sample size was small and the analysis exploratory. Further research is required to identify such factors. Finally, a descriptive regression model, including several baseline factors, was created which provided a heath utility estimate of 0.647 for Canadian patients with non-healing DFUs; however, the results should be interpreted with caution, especially as some subgroups had very small numbers of patients (e.g., Wagner Grade of 4; patients with 4 or more wounds). In summary, guidance is lacking on the best methodology to conduct and analyze studies that provide estimates of the health utility of patients with non-healing DFUs, or any other health state, that are to be used to inform economic evaluations. Additionally, a tool is needed to aid analysts in critically appraising studies so that they can select the best estimate of health utility value to include in economic evaluations. / Thesis / Master of Health Sciences (MSc) / Diabetic foot ulcers (DFUs) impart a large burden on patients and the healthcare system in Canada. The objective of this thesis was to identify health utility estimates for patients with non-healing DFUs. A systematic review was conducted and included nine studies, for which health utility estimates ranged from 0.44 to 0.89. An exploratory regression analysis of data from an Ontario-based study in patients with non-healing DFUs was conducted. No factors associated with health utility were identified but further research is required. A descriptive regression model, adjusting for several baseline factors, provides a health utility of 0.647 for Canadian patients, but should be interpreted with caution. Guidance is needed on the best methodology to conduct studies to estimate the health utilities for use in economic evaluations and for a tool to critically appraise studies to help select the best estimate of health utility for inclusion in economic evaluations.

No description available.

Class of 2010 Abstract / OBJECTIVES:The main purpose of this study was to review recent and good quality studies of the antimicrobial therapy of for moderate to severe (“limb threatening”) DFI. The analysis of these studies was to conclude with one or two “standard” approach to the routine management of this clinical entity. METHODS: This literature review study consisted of an evaluation of clinical trials that compare two or more active systemic antimicrobial regimens for the treatment of moderate to severe (i.e., “limb-threatening”) diabetic foot infections in human patients. Literature sources were identified primarily from OVID MEDLINE, but also included additional tertiary sources. The primary criteria for the clinical studies were: prospective, controlled, randomized and investigator blinded. Studies had to be published after the year 2003, and be available in full-text in English. RESULTS: Ultimately, only four studies were found that met the criteria for consideration. Trials differed in numerous features. All four studies were sponsored by the manufacturer of one of the comparator drugs. Three of the four were non-inferiority design. Evidence is lacking that any of the suggested regimens are superior. CONCLUSIONS: Instead of meeting our original goal of concluding that one or two regimens could be the “standard” management of DFI, we were limited to commentary on the quality and applicability of the current literature on this clinical entity. Numerous suggestions for improvement in the clinical information provided by DFI studies were offered. We eagerly anticipate the publication of the updated IDSA guideline document on DFI.

Diabetic foot ulcers (DFUs) are a common and severe adverse event associated with diabetes, as 25% of diabetic patients will experience DFUs. The lack of effective DFU therapies results in 20% of diabetic patients requiring amputation. We first developed an algorithm to account for polydispersity when calculating nanoparticle concentration, which will reduce variability between batches and treatments. We also developed a novel 2-layer biomaterial, which combines anti-microbial properties of CLKRS peptide coated silver nanoparticles (CLKRS- AgNPs) with a pro-regenerative collagen matrix embedded with microscopic skin tissue columns (MSTC), to promote DFU wound healing. The collagen hydrogel formulation was optimized, and the physical properties, biocompatibility, and wound healing properties were assessed. Our results indicate that the CLKRS-AgNPs prevent bacterial growth and the collagen matrix provides a regenerative environment. Last, we developed and tested antimicrobial fabrics which can also be applied to chronic wounds, such as DFUs, to prevent and treat infections.

Introduction: Diabetic foot (DF) is a common complication in patients with diabetes mellitus. Due to arterial abnormalities and diabetic neuropathy, as well as a tendency to delayed wound healing, infection or gangrene of the foot is relatively common. Early study indicated Si-Miao-Yong-An (SMYA) decoction is the most chosen Chinese herbal formulae in the treatment of DF. The aim of this study is to assess the quality of current evidence, and systematic review the effectiveness and safety of SMYA decoction for the treatment of DF. Method: (1) Search strategy: a special protocol was designed, and electronic databases and hand-search materials were used for screening eligible trials. (2) Inclusive criteria: randomized controlled trials (RCTs) to examine the efficacy and/or safety of SMYA decoction in DF treatments were valid. (3)Data analysis: the Jadad’s scale was used to assess the quality of eligible trials. Result: Total 23 RCTs met the inclusion criteria. Among those, 1341 patients are involved, 702 patients were treated by SYMA decoction. 22 trails using SMYA decoction combined WM claimed that they showed a statistically significant advantages over the treatments using WM alone in reducing DF symptoms. Only 1 RCT reported adverse events related to SMYA decoction, but less than WM treatment. Conclusion: All available evidence points to the fact that SMYA decoction may benefit to those diabetes patients with foot problem. However, due to the poor quality of included trials, more high-quality trials are required to substantiate or refute these early findings.

Tetracycline molecules including doxycycline (DOX), consist of a group of broad-spectrum antibiotics. In addition, tetracyclines inhibit matrix metalloproteinase (MMPs) that contribute to tissue remodeling, inflammation, angiogenesis and are over-expressed in certain pathologies - such as Alzheimer’s disease, metastasis and diabetic foot ulcers (DFUs). Tetracyclines are hypothesized to inhibit MMPs through the chelation and sequestration of catalytic divalent ions such zinc and calcium. This inhibitory duality may be beneficial in pathologies that are characterized by MMP over-expression and prone to infection, such as DFUs. Compared to oral administration, topical DOX is an attractive route of administration for chronic wound healing as it may minimize the risks: associated antibiotic resistance; is being targeted directly to the wound bed. However, DOX is notoriously unstable in aqueous solution and common topical formulations. Liquid chromatography and mass spectrometry (LCMS) were employed to monitor stability using an in vitro MMP assay and an applicable E. coli anti-bacterial assay was assessed to quantify drug activity. 2 % (w/w) topical DOX demonstrated an acceptable stability 30 day when stored at 4 ºC. DOX inhibited MMP9 activity with an IC50 value of 48.27 μM. With respect to anti-bacterial activity, using cultured BL21 E.Coli and quantification of drug activity as an expression of colony forming units (CFUs) successfully reproduced the antimicrobial IC50 of doxycycline as 4.3 µM. Transdermal DOX has the potential to improve standard of care for DFUs, quality of life for the patient and reduce costs to the healthcare system. / Thesis / Master of Science (MSc) / Tetracyclines comprise of a group of broad-spectrum antibiotics; whose primary mechanism of action is inhibition of protein synthesis through binding of the bacterial ribosome. In addition, tetracyclines inhibit matrix metalloprotease (MMPs), zinc-dependent proteases that contribute to tissue remodeling, angiogenesis and are over-expressed in certain pathophysiologies such as diabetic foot ulcers (DFUs). The antibacterial mechanism of DOX on MMPs is reported and understood, however the inhibition is hypothesized to involve cation chelation. Thus, investigating this interaction is warranted to assist in developing a therapeutic for DFUs. A more logical product would involve direct topical application, such as a stable transdermal formulation of DOX.

No / Bullosis diabeticorum is considered a rare skin manifestation of diabetes mellitus. Tense blisters appear rapidly, mostly on the feet, the cause of which is unclear, with multiple pathophysiologies hypothesised. This is a retrospective review of 4 diabetic patients who presented over six months with diabetic bullae; the condition may therefore not be as rare as commonly believed. All the patients had early surgical debridement followed by topical negative pressure wound dressings. A multidisciplinary team that included vascular surgeons, diabetologists, diabetic foot care team, wound care team, physiotherapists and occupational therapists managed the patients and none of them required amputations. We propose an alternative way of managing these patients with early surgical debridement followed by topical negative pressure wound dressing.

No / The establishment of a correct diagnosis links care to established guidelines and underpins all subsequent therapeutic activity. Problems can arise when definitions of disease overlap, as is the case with diabetic foot ulceration and pressure ulcers on the foot occurring in people with diabetes. In such cases, clinicians must ensure that patients receive a care bundle that recognises both the wound causation (pressure and shear) and the underlying pathology (diabetic neuropathy, potential foot architecture disruption and ischaemia). All patients with diabetes that have foot ulceration, irrespective of wound aetiology should, therefore, be seen by the multidisciplinary diabetic foot team. Care can then be optimised to include appropriate assessments, including assessment of peripheral perfusion, correct offloading, appropriate diabetic management, and general foot and skin care.