Examining diabetic heel ulcers through an ecological lens: microbial community dynamics associated with healing and infection.

PURPOSE: While some micro-organisms, such as Staphylococcus aureus, are clearly implicated in causing tissue damage in diabetic foot ulcers (DFUs), our knowledge of the contribution of the entire microbiome to clinical outcomes is limited. We profiled the microbiome of a longitudinal sample series of 28 people with diabetes and DFUs of the heel in an attempt to better characterize the relationship between healing, infection and the microbiome. METHODOLOGY: In total, 237 samples were analysed from 28 DFUs, collected at fortnightly intervals for 6 months or until healing. Microbiome profiles were generated by 16S rRNA gene sequence analysis, supplemented by targeted nanopore sequencing.Result/Key findings. DFUs which failed to heal during the study period (20/28, 71.4 %) were more likely to be persistently colonized with a heterogeneous community of micro-organisms including anaerobes and Enterobacteriaceae (log-likelihood ratio 9.56, P=0.008). During clinically apparent infection, a reduction in the diversity of micro-organisms in a DFU was often observed due to expansion of one or two taxa, with recovery in diversity at resolution. Modelling of the predicted species interactions in a single DFU with high diversity indicated that networks of metabolic interactions may exist that contribute to the formation of stable communities. CONCLUSION: Longitudinal profiling is an essential tool for improving our understanding of the microbiology of chronic wounds, as community dynamics associated with clinical events can only be identified by examining changes over multiple time points. The development of complex communities, particularly involving Enterobacteriaceae and strict anaerobes, may be contributing to poor outcomes in DFUs and requires further investigation.

Dressing and Diabetic Foot Ulcers: A Current Review of the Evidence.

BACKGROUND: The outcome of ulcers of the foot in diabetes is generally poor with around 1 in 10 resulting in the loss of a limb. There is an urgent need for the development of interventions to improve the outcome for patients. To date, however, the evidence base to support many of the interventions in common use, including wound dressings, is poor. METHODS: This article summarizes the findings of systematic reviews of the subject published between 2006 and 2014 and covers all relevant articles in any language, as well as comments on certain newer publications. RESULTS: The 3 consecutive systematic reviews selected a total of 207 articles that met the predefined criteria from a total of 5,632 identified. These included articles on a very wide range of interventions designed to be applied to ulcers of the foot in diabetes to promote wound healing. CONCLUSIONS: The available data suggest that although some newer therapies show promise, few published studies were of high quality, and the majority were susceptible to bias. More work is needed to substantiate the role of available dressings and wound care products in day-to-day clinical practice. Future work will require studies to be performed to a higher standard than many of those reviewed here and should establish not just clinical effectiveness but cost-effectiveness. The conclusions drawn from the studies of diabetic foot ulcers (DFUs) might apply to the management of other types of chronic wounds.

Reporting standards of studies and papers on the prevention and management of foot ulcers in diabetes: required details and markers of good quality.

The evidence base for many aspects of the management of foot ulcers in people with diabetes is weak, and good-quality research, especially relating to studies of direct relevance to routine clinical care, is needed. In this paper, we summarise the core details required in the planning and reporting of intervention studies in the prevention and management of diabetic foot ulcers, including studies that focus on off-loading, stimulation of wound healing, peripheral artery disease, and infection. We highlight aspects of trial design, conduct, and reporting that should be taken into account to minimise bias and improve quality. We also provide a 21-point checklist for researchers and for readers who assess the quality of published work.

Evidence for the use of biological therapies in ulcers of the foot in diabetes.

Because the chronic ulcer of the foot in diabetes is often unresponsive to standard care, there has been considerable interest in the potential benefit of so-called "advanced wound therapies"--many of which have a biological basis. This article summarizes the findings of earlier systematic reviews, together with the findings of more recent publications. The available evidence suggests that while some biological therapies offer promise, more work is needed to substantiate their role in clinical practice. This conclusion needs to be placed in the context of very strong observational data demonstrating the major improvements that can accompany changes to the way in which wound care is delivered with, in particular, the introduction of multidisciplinary team work and more rapid referral for expert assessment.

Osteomyelitis in the diabetic foot: diagnosis and management.

Although osteomyelitis of the foot in diabetes remains common in specialist foot clinics across the world, the quality of published work to guide clinicians in the diagnosis and management is generally poor. Diagnosis should be based primarily on clinical signs supported by results of pathologic and radiologic investigations. Although the gold standard comes from the histologic and microbiological examination of bone, clinicians should be aware of the problems of sampling error. This lack of standardization of diagnostic criteria and of consensus on the choice of outcome measures poses further difficulties when seeking evidence to support management decisions. Experts have traditionally recommended surgical removal of infected bone but available evidence suggests that in many cases (excepting those in whom immediate surgery is required to save life or limb) a nonsurgical approach to management of osteomyelitis may be effective for many, if not most, patients with osteomyelitis of the diabetic foot. The benefits and limitations of both approaches need, however, to be established in prospective trials so that appropriate therapy can be offered to appropriate patients at the appropriate time, with the patients' views taken fully into account.

Temporal association between the incidence of foot ulceration and the start of dialysis in diabetes mellitus.

BACKGROUND: The aim of this study was to seek a temporal association between the start of renal replacement therapy (RRT) and the first recorded foot ulcer in diabetes. METHODS: Details of all patients with diabetes who had received RRT were extracted from the renal database and were cross-checked with the database held in the specialist foot clinic. The date of onset of first registered foot ulcer was taken and compared with the date of onset of RRT. The self-controlled case-series method was used to establish any significant temporal association between the start of RRT and first recorded foot ulcer in diabetes. RESULTS: Of 466 patients with diabetes dialysed at our hospital since 1976, 94 (20.2%) were recorded as having at least one foot ulcer, with 15 of these undergoing major amputation. Incidence ratios (IRs) were calculated for 90 patients in whom complete data were available. A close temporal association was observed between the start of RRT and the first recorded foot ulceration: IR (95% CI) in the first and between the second and fifth years of dialysis were 3.35 (95% CI: 1.59-7.04), and 4.56 (2.19-9.50), respectively, relative to the time before dialysis. The IR for major amputation was 31.98 (2.09-490.3) in the first year and 34.01 (1.74-666.2) in the second to fifth years. CONCLUSION: These results reveal a close relationship between the onset of RRT in diabetes and the onset of foot ulceration, and confirm the high incidence of amputation in those on dialysis. Urgent steps should be taken to coordinate all aspects of diabetes foot care before and after the start of RRT.