Diabetic Foot Disease: Emerging Technologies: Reconsidering Nerve Decompression: An Overlooked Opportunity to Limit Diabetic Foot Ulcer Recurrence and Amputation

Nerve decompression for relief of subjective diabetic sensorimotor polyneuropathy pain and numbness has been labeled of “unknown” benefit. Objective outcomes in treatment and prevention of diabetic foot complications are reviewed. There is growing evidence that plantar foot ulceration and recurrence in high-risk feet are minimized with this operation. Avoiding neuropathic and neuroischemic ulcer wounds should theoretically reduce amputations and perhaps mortality risk. Protective effects are hypothesized to act via relief of neuro-vascular entrapment, thereby improving neurally modulated tissue homeostasis factors. Nerve decompression deserves considerable research attention to understand its role in limiting foot complications. Its apparent benefits challenge the paradigm that diabetic neuropathy is a purely length-dependent axonopathy and may necessitate appreciation of superimposed nerve entrapment as an significant operant factor.     

Guidelines on the classification of diabetic foot ulcers (IWGDF 2019)

The International Working Group on the Diabetic Foot (IWGDF) has been publishing evidence‐based guidelines on the prevention and management of diabetic foot disease since 1999. This publication represents a new guideline addressing the use of classifications of diabetic foot ulcers in routine clinical practice and reviews those which have been published. We only consider systems of classification used for active diabetic foot ulcers and do not include those that might be used to define risk of future ulceration. The guidelines are based on a review of the available literature and on expert opinion leading to the identification of eight key factors judged to contribute most to clinical outcomes. Classifications are graded on the number of key factors included as well as on internal and external validation and the use for which a classification is intended. Key factors judged to contribute to the scoring of classifications are of three types: patient related (end‐stage renal failure), limb‐related (peripheral artery disease and loss of protective sensation), and ulcer‐related (area, depth, site, single, or multiple and infection). Particular systems considered for each of the following five clinical situations: (a) communication among health professionals, (b) predicting the outcome of an individual ulcer, (c) as an aid to clinical decision‐making for an individual case, (d) assessment of a wound, with/without infection, and peripheral artery disease (assessment of perfusion and potential benefit from revascularisation), and (d) audit of outcome in local, regional, or national populations. We recommend: (a) for communication among health professionals the use of the SINBAD system (that includes Site, Ischaemia, Neuropathy, Bacterial Infection and Depth); (b) no existing classification for predicting outcome of an individual ulcer; (c) the Infectious Diseases Society of America/IWGDF (IDSA/IWGDF) classification for assessment of infection; (d) the WIfI (Wound, Ischemia, and foot Infection) system for the assessment of perfusion and the likely benefit of revascularisation; and (e) the SINBAD classification for the audit of outcome of populations.     

Portugal meets Eurodiale: Better late than never

Understanding the quality of diabetic foot care delivery is essential. The Eurodiale consortium addressed subjects’ characteristics, diabetic foot ulcer prognostic predictors and clinical outcomes, in 10 European countries. We analyzed the results of a specialized Portuguese diabetic foot clinic at the light of the ones from Eurodiale.     

Digital imaging: an accurate and easy method of measuring foot ulcers.

AIMS: A progressive reduction in the area of foot ulcer on serial measurement is traditionally done by tracing the margin of the ulcer on a transparent film and counting the number of squares on a graph paper underneath. We set out to use and validate the measurement of foot ulcers using a digital imaging technique and compare this with the traditional method. METHODS: Thirty diabetic foot ulcers (18 patients) were studied over 10 weeks. Each ulcer was traced by three independent observers with a pen over a flexigrid Opsite film and digital photographs were taken. Each observer calculated the area of an ulcer first using a 1-mm2 graph paper and then with the computer software. For each ulcer we calculated the mean area using measurements from all the observers. We then calculated the deviation from this mean for each observer. RESULTS: There was significantly less interobserver variation using the digital image than the traditional method with mean coefficient of variation (CV) 16% vs. 27%; P = 0.05. CONCLUSIONS: The digital imaging method was faster and easier to use and the patients preferred it, as it was a noncontact method. In addition it also provides a photographic record for comparison.     

A study to identify bacteriological profile and other risk factors among diabetic and non-diabetic foot ulcer patients in a Guyanese hospital setting

Diabetic foot infection is a global epidemic and a major public health concern. Development of microbial resistance to many antimicrobial agents in foot ulcer leads to serious complications. Therefore, the study aims to identify the microbiological profile and the potential risk factors among diabetic and non-diabetic foot ulcer patients.A prospective cross sectional study was carried out among 183 ulcer patients from diabetic foot clinic and wound dressing clinic at the public health hospital, Guyana.A total of 254 bacteria were isolated from the study with an average of 1.4 organism per lesion. Gram negative bacteria (63.0%) were prevalent than gram positive bacteria (37.0%) in this study. Among DF patients, Pseudomonas aeruginosa (18.8%) was the most common isolate followed by Escherichia coli (13.9%) among gram negative group. Were as MRSA (12.1%) followed by MSSA (7.9%) dominated among gram positive group in diabetic foot patients. Almost 42.1% (95% CI 34.8–49.6) of the infections were caused by poly-microbial. Interestingly, a stepwise logistic regression model determined increasing age and lack of health education as independent risk factor identified for acquiring an MDR wound infection (OR = 1.1; p ≥ 0.05; 95% CI 1.0–1.1). Mild, moderate and severe infection among MDR and NMDR patients were recorded as 45.3% (95% CI 32.8–58.3), 26.5% (95% CI 16.3–39.1), 28.1% (95% CI 17.6–40.8) and 51.3% (95% CI 41.9–60.5), 32.8% (95% CI 24.4–42.0), 16.0% (95% CI 9.9–23.8). Therefore, it is concluded that there's an urgent need for surveillance of resistant bacteria in diabetic foot infections to reduce the risk of major complications.     

Illustration of Cost Saving Implications of Lower Extremity Nerve Decompression to Prevent Recurrence of Diabetic Foot Ulceration

The US diabetic foot ulcer (DFU) incidence is 3-4% of 22.3 million diagnosed diabetes cases plus 6.3 million undiagnosed, 858 000 cases total. Risk of recurrence after healing is 30% annually. Lower extremity multiple nerve decompression (ND) surgery reduces neuropathic DFU (nDFU) recurrence risk by >80%. Cost effectiveness of hypothetical ND implementation to minimize nDFU recurrence is compared to the current $6.171 billion annual nDFU expense. A literature review identified best estimates of annual incidence, recurrence risk, medical management expense, and noneconomic costs for DFU. Illustrative cost/benefit calculations were performed assuming widespread application of bilateral ND after wound healing to the nDFU problem, using Center for Medicare Services mean expense data of $1143/case for unilateral lower extremity ND. Calculations use conservative, evidence-based cost figures, which are contemporary (2012) or adjusted for inflation. Widespread adoption of ND after nDFU healing could reduce annual DFU occurrences by at least 21% in the third year and 24% by year 5, representing calculated cost savings of $1.296 billion (year 3) to $1.481 billion (year 5). This scenario proffers significant expense reduction and societal benefit, and represents a minimum 1.9× return on the investment cost for surgical treatment. Further large cost savings would require reductions in initial DFU incidence, which ND might achieve by selective application to advanced diabetic sensorimotor polyneuropathy (DSPN). By minimizing the contribution of recurrences to yearly nDFU incidence, ND has potential to reduce by nearly $1 billion the annual cost of DFU treatment in the United States.     

Standards for the development and methodology of the 2019 International Working Group on the Diabetic Foot guidelines

Diabetic foot disease is a source of major patient suffering and societal costs. Investing in evidence‐based international guidelines on diabetic foot disease is likely among the most cost‐effective forms of health care expenditure, provided the guidelines are outcome focused, evidence based, and properly implemented. The International Working Group on the Diabetic Foot (IWGDF) has published and updated international guidelines since 1999. The 2019 updates are based on formulating relevant clinical questions and outcomes, rigorous systematic reviews of the literature, and recommendations that are specific, and unambiguous along with their transparent rationale, all using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework. We herein describe the development of the 2019 IWGDF guidelines on the prevention and management of diabetic foot disease, which consists of six chapters, each prepared by a separate working group of international experts. These documents provide guidelines related to diabetic foot disease on prevention; offloading; peripheral artery disease; infection; wound healing interventions; and classification of diabetic foot ulcers. Based on these six chapters, the IWGDF Editorial Board also produced a set of practical guidelines. Each guideline underwent extensive review by the members of the IWGDF Editorial Board as well as independent international experts in each field. We believe that adoption and implementation of the 2019 IWGDF guidelines by health care providers, public health agencies, and policymakers will result in improved prevention and management of diabetic foot disease and a subsequent worldwide reduction in the patient and societal burden this disease causes.     

糖尿病足溃疡危险因素分析

观察23例糖尿病足溃疡患者的年龄、糖尿病病程、空腹血糖、血清总蛋白、血清白蛋白、血清肌酐、血清尿素氮及溃疡发生的位置,并与20例无溃疡糖尿病患者进行对比分析。结果显示：两组患者糖尿病病程、空腹血糖、血清总蛋白、血清白蛋白有显著性差异,年龄,血清肌酐、尿素氮、无显著性差异,糖尿病足溃疡患者右足溃疡发生率（86％）显著高于左足（39％）,双母趾溃疡发生率（65％）高于部位（35％）,但无显著性差异,结果提示：糖尿病程、高血糖、低蛋白血症及足部受力过多和压迫是糖尿病足溃疡发生的危险因素。     

The future for diabetic foot ulcer prevention: A paradigm shift from stratified healthcare towards personalized medicine

Prevention of diabetic foot ulcers is important to reduce the burden of diabetic foot disease. However, we found that ulcer prevention is underexposed in research and clinical practice. Barriers to explain this are seen in patient's goal‐setting; in the lack of interdisciplinary teams for ulcer prevention; in sample sizes and funding for research; in industrial engagement; and in limited understanding of ulcer development. Rather than separately solving these barriers, we propose a paradigm shift from stratified healthcare towards personalized medicine for diabetic foot disease. Personalized medicine aims to deliver the right treatment to the right patient at the right time, based on individual diagnostics. Different treatment strategies should be available for different patients, delivered in an integrated, objective, quantitative and evidence‐based approach. More than on the classical risk factors of peripheral neuropathy and peripheral artery disease, individual diagnostics should focus on modifiable risk factors for ulceration. This includes structured biomechanical and behavioral profiling, while new research with (big) data science may identify additional risk factors, such as geographical or temporal patterns in ulceration. Industry involvement can drive the development of wearable instruments and assessment tools, to facilitate large‐scale individual diagnostics. For a paradigm shift towards personalized medicine in prevention, large‐scale collaborations between stakeholders are needed. As each ulcer episode not prevented costs about €10,000 in medical costs alone, such investments can be cost‐effective. We hope to see more discussions around this paradigm shift, and increasing investments of energy and money in diabetic foot ulcer prevention in research and clinical practice.     

Diabetic foot ulcer and multidrug‐resistant organisms: risk factors and impact

Aims The primary objective was to characterize factors allowing the colonization of diabetic foot wounds by multidrug‐resistant organisms (MDRO), and the secondary objective was to evaluate the influence of MDRO colonization/infection on wound healing. Methods In 180 patients admitted to a specialized diabetic foot unit, microbiological specimens were taken on admission. Potential risk factors for MDRO‐positive specimens were examined using univariate and multivariate analyses. Prospective follow‐up data from 75 patients were used to evaluate the influence of MDRO colonization/infection on time to healing. Results Eighteen per cent of admission specimens were positive for MDRO. MDRO‐positive status was not associated with patient characteristics (age, sex, type of diabetes, complications of diabetes), wound duration, or wound type (neuropathic or ischaemic). In the multivariate analysis, the only factors significantly associated with positive MDRO status on admission were a history of previous hospitalization for the same wound (21/32 compared with 48/148; P = 0.0008) or the presence of osteomyelitis (22/32 compared with 71/148; P = 0.025). In the longitudinal study of 75 wounds, MDRO‐positive status on admission or during follow‐up (6 months at least or until healing, mean 9 ± 7 months) was not associated with time to healing (P = 0.71). Conclusion MDROs are often present in severe diabetic foot wounds. About one‐third of patients with a history of previous hospitalization for the same wound, and 25% of patients with osteomyelitis, had MDRO‐positive specimens. This suggests that hygiene measures, or isolation precautions in the case of admission of patients presenting with these characteristics, should be aggressively implemented to prevent cross‐transmission. Positive MDRO status is not associated with a longer time to healing.     

Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing

Aims Matrix metalloproteinases (MMPs) play a major role in wound healing: they can degrade all components of the extracellular matrix. In diabetic foot ulcers there is an excess of MMPs and a decrease of the tissue inhibitors of MMPs (TIMPs). This imbalance is probably one cause of impaired healing. However, little is known about changes in MMPs during wound healing. Methods Sixteen patients with neuropathic diabetic foot ulcers participated. Wound fluid was collected regularly during the 12-week follow-up period, for measurement of MMP-1, MMP-2, MMP-8, MMP-9 and TIMP-1. Results were analysed by the degree of wound healing: good healers (defined by a reduction of at least 82% in initial wound surface at 4 weeks) and poor healers (reduction of less than 82% in wound surface at 4 weeks). Results In good healers, levels of MMP-8 and -9 secreted by inflammatory cells decreased earlier. The initial levels of MMP-1 were similar in good and poor healers (P = 0.1) but rose significantly at week 2 in good healers (P = 0.039). There was a significant correlation between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, P = 0.008). Receiver Operator Curve (ROC) analysis showed that an MMP-1/TIMP-1 ratio of 0.39 best predicted wound healing (sensitivity = 71%, specificity = 87.5%). Conclusions A high level of MMP-1 seems essential to wound healing, while an excess of MMP-8 and -9 is deleterious, and could be a target for new topical treatments. The MMP-1/TIMP-1 ratio is a predictor of wound healing in diabetic foot ulcers.     

Treatment of diabetic foot ulcers: a comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy

Objective

This study compared the effectiveness of extracorporeal shockwave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) in chronic diabetic foot ulcers.

Patients and methods

The ESWT group (39 patients/44 feet) received shockwave therapy twice per week for total six treatments. The HBOT group (38 patients/40 feet) received hyperbaric oxygen therapy daily for total 20 treatments. Evaluations included clinical assessment, blood flow perfusion scan and histopathological examination.

Results

The overall clinical results showed completely healed ulcers in 57% and 25% (P = 0.003); ≥50% improved ulcers in 32% and 15% (P = 0.071); unchanged ulcers in 11% and 60% (P < 0.001) and none worsened for the ESWT and the HBOT group respectively. The blood flow perfusion rates were comparable between the two groups before treatment (P = 0.245), however, significant differences were noted after treatment favoring the ESWT group (P = 0.002). Histopathological examination revealed considerable increases in cell proliferation and decreases in cell apoptosis in the ESWT group as compared to the HBOT group.

Conclusion

ESWT is more effective than HBOT in chronic diabetic foot ulcers. ESWT-treated ulcers showed significant improvement in blood flow perfusion rate and cell activity leading to better healing of the ulcers relative to HBOT in chronic diabetic foot ulcers.     

Screening of Diabetic Foot in Surgical Inpatients: A Hospital-Based Study in Saudi Arabia

Previous reports found that identification of diabetic patients at high risk of foot ulcers, and managing the risk factors early, lower extremity amputations could be prevented. The aim of this study is to determine the value of screening diabetics in estimating the risk of foot ulceration among surgical inpatients. This is a prospective study on all diabetic patients admitted to the surgical department, King Fahd Hospital of the University, Saudi Arabia, during the year 2011. Patients were screened for the presence of diabetic foot. They were classified according to the international working group on the diabetic foot into four grades [0 (lowest risk patients), 1, 2, 3 (highest risk patients)]. During the study period, 391 patients had diabetes mellitus (DM), of these 73 (19%) had active ulcer and were excluded from the study and the rest were screened. Grade 0 was in 174 (54.5%) patients, the rest were grades 1, 2, and 3. There was significant difference between low-risk groups (grades 0, 1) and high-risk groups (grades 2, 3) as regards age, smoking and duration of DM. This study indicates that prevalence of diabetic patients with risk of foot ulceration in surgical inpatients was high. Routine screening of diabetic foot is recommended specially in old patients.     

The steel ball-bearing test: a new test for evaluating protective sensation in the diabetic foot

Aims/hypothesis The aim of the study was to assess a new steel ball-bearing test as a means of evaluating protective sensation in the diabetic foot. Methods Subjects were enrolled for this study as follows: (1) 39 patients (mean age 61.3±9.7 years) with neuropathy and prior neuropathic ulcer (Group A); (2) 36 patients (mean age 63.7±10.1 years) with neuropathy without neuropathic ulcer (Group B); (3) 34 patients (mean age 52.1±10.4 years) without neuropathy (Group C); and (4) 21 healthy volunteers (mean age 46.7±8.7 years) (Group D). Neuropathy was diagnosed by means of neuropathy disability score (NDS). The plantar area over the second metatarsal head of each foot was examined with steel ball-bearings of varying diameters. The smallest diameter that the patient could feel was used to define the ball-bearing score (range 1–6). Results A high ball-bearing score was significantly more frequent in patients with neuropathic ulceration than in neuropathic patients without ulceration and in diabetic patients without neuropathy (p<0.001). A high score was also more frequent in neuropathic patients without ulceration, than in patients without neuropathy (p<0.001). The ball-bearing score was significantly (p=0.01) correlated with the NDS, the monofilament test, the vibration perception threshold and the thermal perception threshold. The ball-bearing test had a sensitivity of 84% and a specificity of 100% for impaired protective sensation due to neuropathy, and a sensitivity of 84.6% and a specificity of 86.1% for detection of patients with prior neuropathic ulceration. Conclusions/interpretation The steel ball-bearing test has a high sensitivity and specificity both for the evaluation of protective sensation and for detection of patients with prior neuropathic ulceration.