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1.  Clinical effectiveness of hemoglobin spray (Granulox®) as adjunctive therapy in the treatment of chronic diabetic foot ulcers 
Diabetic Foot & Ankle  2016;7:10.3402/dfa.v7.33101.
Introduction
Hemoglobin spray (Granulox®) comprises purified hemoglobin and is a novel approach for increasing oxygen availability in the wound bed in diabetic foot ulcer patients. Its mode of action is to bind oxygen from the atmosphere and diffuse it into the wound bed to accelerate wound healing in slow-healing wounds.
Patients and methods
Wound healing outcomes, that is, wound size, pain, percentage of slough, and exudate levels, were compared retrospectively to a similar cohort of patients treated over the same period the previous year. The same inclusion and exclusion criteria applied to both groups.
Results
All 20 (100%) hemoglobin spray-treated patients and 15 (75%) control patients experienced some wound healing by week 4, with 5 (25%) and 1 (5%), respectively, achieving complete wound closure. At week 4, mean wound size reduction was 63% in the hemoglobin spray group versus 26% for controls, increasing to 95% reduction at week 28 in the hemoglobin spray group versus 63% for controls (p<0.05 at all timepoints). Hemoglobin spray was associated with substantially lower pain scores using a 10-cm visual analogue scale, with 19/19 patients (100%) being pain-free from week 12 onwards, compared to 6/18 patients (33%) in the control group. At week 28, 2/18 patients (11%) in the control group still had pain. Both groups had similar baseline slough levels, but hemoglobin spray-treated wounds had slough completely eliminated after 4 weeks versus 10% mean reduction in the control group (p<0.001). Hemoglobin spray was associated with markedly reduced exudate levels; within 4 weeks, no patients had high exudate levels in the hemoglobin spray group versus 5 in the control group.
Conclusion
Standard wound care plus hemoglobin spray results in improvements in wound closure, wound size reduction, pain, slough, and exudate levels compared to control patients for chronic diabetic foot ulcer treatment.
doi:10.3402/dfa.v7.33101
PMCID: PMC5102129  PMID: 27829487
diabetes-related complications; diabetic foot ulcer; hemoglobin; topical oxygen therapy; wound healing
2.  Conventional deep pressure algometry is not suitable for clinical assessment of nociception in painless diabetic neuropathy 
Diabetic Foot & Ankle  2016;7:10.3402/dfa.v7.31922.
Background
In diabetic persons with painless neuropathic foot ulceration, foot skin was found to be insensate to noxious pinprick stimulation (stimulation area less than 0.05 mm2), while compression of deep subcutaneous foot tissues by Algometer II® (stimulation area 1 cm2) could evoke a deep dull aching. To elucidate this discrepancy, the Algometer II stimulation technique was critically reviewed by varying probe sizes and anatomical sites in the same study population 3 years later.
Methods
Ten control subjects without neuropathy and 11 persons with painless diabetic neuropathy (PLDN, seven of whom with diabetic foot syndrome, i.e., past painless foot ulcer, or inactive Charcot arthropathy) were re-examined using Algometer II. Deep pressure pain perception threshold (DPPPT) was measured in random sequence with stimulation areas of 0.5 cm2, 1 cm2, and 2 cm2 (separated by 5 min intervals), at the plantar forefoot, the instep, and the hindfoot of both legs.
Results
In the control and PLDN groups, median DPPPTs differed significantly between stimulation areas (highest with 0.5 cm2, intermediate with 1 cm2, lowest with 2 cm2; p<0.001), and varied moderately by anatomical site. Between-group differences were relatively small. Results of the 1 cm2 assessments repeated 3 years apart were similar.
Conclusions
Algometer II readings represent spatial summation of low-threshold pressure-receptor rather than of high-threshold nociceptor stimulation and are, thus, unhelpful for assessing PLDN. Reproducibility of the measurements is good.
doi:10.3402/dfa.v7.31922
PMCID: PMC5045473  PMID: 27702429
diabetic neuropathy; nociception; algometry; diabetes mellitus
3.  Consensus on surgical aspects of managing osteomyelitis in the diabetic foot 
Diabetic Foot & Ankle  2016;7:10.3402/dfa.v7.30079.
Background
The aim of this study was to develop consensus statements that may help share or even establish ‘best practices’ in the surgical aspects of managing diabetic foot osteomyelitis (DFO) that can be applied in appropriate clinical situations pending the publication of more high-quality data.
Methods
We asked 14 panelists with expertise in DFO management to participate. Delphi methodology was used to develop consensus statements. First, a questionnaire elicited practices and beliefs concerning various aspects of the surgical management of DFO. Thereafter, we constructed 63 statements for analysis and, using a nine-point Likert scale, asked the panelists to indicate the extent to which they agreed or disagreed with the statements. We defined consensus as a mean score of greater than 7.0.
Results
The panelists reached consensus on 38 items after three rounds. Among these, seven provide guidance on initial diagnosis of DFO and selection of patients for surgical management. Another 15 statements provide guidance on specific aspects of operative management, including the timing of operations and the type of specimens to be obtained. Ten statements provide guidance on postoperative management, including wound closure and offloading, and six statements summarize the panelists’ agreement on general principles for surgical management of DFO.
Conclusions
Consensus statement on the perioperative management of DFO were formed with an expert panel comprised of a variety of surgical specialties. We believe these statements may serve as ‘best practice’ guidelines until properly performed studies provide more robust evidence to support or refute specific surgical management steps in DFO.
doi:10.3402/dfa.v7.30079
PMCID: PMC4944594  PMID: 27414481
osteomyelitis; foot infection; foot ulcer; forefoot; diabetic foot; diabetes; consensus; Delphi methodology; consensus
4.  Does obtaining an initial magnetic resonance imaging decrease the reamputation rates in the diabetic foot? 
Diabetic Foot & Ankle  2016;7:10.3402/dfa.v7.31240.
Objective
Diabetes mellitus (DM) through its over glycosylation of neurovascular structures and resultant peripheral neuropathy continues to be the major risk factor for pedal amputation. Repetitive trauma to the insensate foot results in diabetic foot ulcers, which are at high risk to develop osteomyelitis. Many patients who present with diabetic foot complications will undergo one or more pedal amputations during the course of their disease. The purpose of this study was to determine if obtaining an initial magnetic resonance imaging (MRI), prior to the first amputation, is associated with a decreased rate of reamputation in the diabetic foot. Our hypothesis was that the rate of reamputation may be associated with underutilization of obtaining an initial MRI, useful in presurgical planning. This study was designed to determine whether there was an association between the reamputation rate in diabetic patients and utilization of MRI in the presurgical planning and prior to initial forefoot amputations.
Methods
Following approval by our institutional review board, our study design consisted of a retrospective cohort analysis of 413 patients at Staten Island University Hospital, a 700-bed tertiary referral center between 2008 and 2013 who underwent an initial great toe (hallux) amputation. Of the 413 patients with a hallux amputation, there were 368 eligible patients who had a history of DM with documented hemoglobin A1c (HbA1c) within 3 months of the initial first ray (hallux and first metatarsal) amputation and available radiographic data. Statistical analysis compared the incidence rates of reamputation between patients who underwent initial MRI and those who did not obtain an initial MRI prior to their first amputation. The reamputation rate was compared after adjustment for age, gender, ethnicity, HbA1c, cardiovascular disease, hypoalbuminemia, smoking, body mass index, and prior antibiotic treatment.
Results
The results of our statistical analysis failed to reveal a significant association between obtaining an initial MRI and the reamputation rate. We did, however, find a statistical association between obtaining an early MRI and decreased mortality rates.
Discussion
Obtaining an early MRI was not associated with the reamputation rate incidence in the treatment of the diabetic foot. It did, however, have a statistically significant association with the mortality rate as demonstrated by the increased survival rate in patients undergoing MRI prior to initial amputation.
doi:10.3402/dfa.v7.31240
PMCID: PMC4912603  PMID: 27316920
diabetic foot; osteomyelitis; diabetic foot infections; foot ulcer; amputations; magnetic resonance imaging
5.  Stepwise surgical approach to diabetic partial foot amputations with autogenous split thickness skin grafting 
Diabetic Foot & Ankle  2016;7:10.3402/dfa.v7.27751.
In the surgical treatment of severe diabetic foot infections, substantial soft tissue loss often accompanies partial foot amputations. These sizeable soft tissue defects require extensive care with the goal of expedited closure to inhibit further infection and to provide resilient surfaces capable of withstanding long-term ambulation. Definitive wound closure management in the diabetic population is dependent on multiple factors and can have a major impact on the risk of future diabetic foot complications. In this article, the authors provide an overview of autogenous skin grafting, including anatomical considerations, clinical conditions, surgical approach, and adjunctive treatments, for diabetic partial foot amputations.
doi:10.3402/dfa.v7.27751
PMCID: PMC4901508  PMID: 27283728
diabetic foot infections; amputations; osteomyelitis; wounds; skin grafting
6.  Risk factors for occurrence and recurrence of diabetic foot ulcers among Iraqi diabetic patients 
Diabetic Foot & Ankle  2016;7:10.3402/dfa.v7.29605.
There are a few studies that discuss the medical causes for diabetic foot (DF) ulcerations in Iraq, one of them in Wasit province. The aim of our study was to analyze the medical, therapeutic, and patient risk factors for developing DF ulcerations among diabetic patients in Baghdad, Iraq.
doi:10.3402/dfa.v7.29605
PMCID: PMC4794731  PMID: 26983600
diabetes mellitus; risk factors; diabetic foot ulcerations
7.  Type 2 diabetes–related foot care knowledge and foot self-care practice interventions in the United States: a systematic review of the literature 
Diabetic Foot & Ankle  2016;7:10.3402/dfa.v7.29758.
Introduction
The purpose of this systematic literature review is to review published studies on foot care knowledge and foot care practice interventions as part of diabetic foot care self-management interventions.
Methods
Medline, CINAHL, CENTRAL, and Cochrane Central Register of Controlled Trials databases were searched. References from the included studies were reviewed to identify any missing studies that could be included. Only foot care knowledge and foot care practice intervention studies that focused on the person living with type 2 diabetes were included in this review. Author, study design, sample, intervention, and results were extracted.
Results
Thirty studies met the inclusion criteria and were classified according to randomized controlled trial (n=9), survey design (n=13), cohort studies (n=4), cross-sectional studies (n=2), qualitative studies (n=2), and case series (n=1). Improving lower extremity complications associated with type 2 diabetes can be done through effective foot care interventions that include foot care knowledge and foot care practices.
Conclusion
Preventing these complications, understanding the risk factors, and having the ability to manage complications outside of the clinical encounter is an important part of a diabetes foot self-care management program. Interventions and research studies that aim to reduce lower extremity complications are still lacking. Further research is needed to test foot care interventions across multiple populations and geographic locations.
doi:10.3402/dfa.v7.29758
PMCID: PMC4761684  PMID: 26899439
diabetes; foot care; foot care knowledge; diabetic foot disease; self-care management
8.  Risk factors for lower extremity amputation in patients with diabetic foot ulcers: a hospital-based case–control study 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.29629.
Background
Diabetic foot ulcers (DFU) may cause significant morbidity and lower extremity amputation (LEA) due to diabetic foot problems can occur more often compared to the general population. The purpose of the present study was to use an epidemiological design to determine and to quantify the risk factors of subsequent amputation in hospitalized DFU patients.
Methods
We performed a hospital-based, case–control study of 47 DFU patients with LEA and 47 control DFU patients without LEA. The control subjects were matched to cases in respect to age (±5 years), sex, and nutritional status, with ratio of 1:1. This study was conducted in Dr. Kariadi General Hospital Semarang between January 2012 and December 2014. Patients’ demographical data and all risk factors-related information were collected from clinical records using a short structural chart. Using LEA as the outcome variable, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression. Univariate and stepwise logistic regression analyses were used to assess the independent effect of selected risk factors associated with LEA. The data were analyzed in SPSS version 21.
Results
There were 47 case–control pairs, all of which were diagnosed with type 2 diabetes mellitus. Seven potential independent variables show a promise of influence, the latter being defined as p≤0.15 upon univariate analysis. Multivariable logistic regression identified levels of HbA1c ≥8% (OR 20.47, 95% CI 3.12–134.31; p=0.002), presence of peripheral arterial disease (PAD) (OR 12.97, 95% CI 3.44–48.88; p<0.001), hypertriglyceridemia (OR 5.58, 95% CI 1.74–17.91; p=0.004), and hypertension (OR 3.67, 95% CI 1.14–11.79; p=0.028) as the independent risk factors associated with subsequent LEA in DFU.
Conclusions
Several risk factors for LEA were identified. We found that HbA1c ≥8%, PAD, hypertriglyceridemia, and hypertension have been recognized as the predictors of LEA in this study. Good glycemic control, active investigation against PAD, and management of comorbidities such as hypertriglyceridemia and hypertension are considered important to reduce amputation risk.
doi:10.3402/dfa.v6.29629
PMCID: PMC4673055  PMID: 26651032
diabetic foot ulcers; hospitalized patients; risk factors; amputation
9.  Intralesional epidermal growth factor for diabetic foot wounds: the first cases in Turkey 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.28419.
Background
Intralesional recombinant epidermal growth factor (EGF) was produced in the Centre for Genetic Engineering and Biotechnology (CIGB), Cuba, in 1988 and licensed in 2006. Because it may accelerate wound healing, it is a potential new treatment option in patients with a diabetic foot wound (whether infected or not) as an adjunct to standard treatment (i.e. debridement, antibiotics). We conducted the initial evaluation of EGF for diabetic foot wounds in Turkey.
Methods
We enrolled 17 patients who were hospitalized in various medical centers for a foot ulcer and/or infection and for whom below the knee amputation was suggested to all except one. All patients received 75 μg intralesional EGF three times per week on alternate days.
Results
The appearance of new granulation tissue on the wound site (≥75%) was observed in 13 patients (76%), and complete wound closure was observed in 3 patients (18%), yielding a ‘complete recovery’ rate of 94%. The most common side effects were tremor (n=10, 59%) and nausea (n=6, 35%). In only one case,a serious side effect requiring cessation of EGF treatment was noted. That patient experienced severe hypotension at the 16th application session, and treatment was discontinued. At baseline, a total of 21 causative bacteria were isolated from 15 patients, whereascultures were sterile in two patients. The most frequently isolated species was Pseudomonas aeruginosa.
Conclusion
Thus, this preliminary study suggests that EGF seems to be a potential adjunctive treatment option in patients with limb-threatening diabetic foot wounds.
doi:10.3402/dfa.v6.28419
PMCID: PMC4534624  PMID: 26268583
diabetic foot; intralesional epidermal growth factor; treatment
10.  Retrograde pedal access with a 20-gauge intravenous cannula after failed antegrade recanalization of a tibialis anterior artery in a diabetic patient: a case report 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.28504.
Retrograde tibiopedal approach is being used frequently in below-the-knee vascular interventions. In patients with diabetic foot pathology, complex anatomy often requires a retrograde technique when the distal vascular anatomy and puncture site is suitable. The dorsalis pedis and posterior tibial arteries can be punctured because of their relatively superficial position. We report a retrograde puncturing technique in patients with chronic total occlusions. After failed antegrade recanalization, puncturing and cannulation of a tiny dorsalis pedis artery with a narrow bore [20-gauge (0.8 mm)] intravenous cannula is described.
doi:10.3402/dfa.v6.28504
PMCID: PMC4530141  PMID: 26257023
intravenous cannula; retrograde access; diabetic foot; critical limb ischemia
11.  Negative-pressure wound therapy for management of diabetic foot wounds: a review of the mechanism of action, clinical applications, and recent developments 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.27618.
Negative-pressure wound therapy (NPWT) plays an important role in the treatment of complex wounds. Its effect on limb salvage in the management of the diabetic foot is well described in the literature. However, a successful outcome in this subgroup of diabetic patients requires a multidisciplinary approach with careful patient selection, appropriate surgical debridement, targeted antibiotic therapy, and optimization of healing markers. Evolving NPWT technology including instillation therapy, nanocrystalline adjuncts, and portable systems can further improve results if used with correct indications. This review article summarizes current knowledge about the role of NPWT in the management of the diabetic foot and its mode of action, clinical applications, and recent developments.
doi:10.3402/dfa.v6.27618
PMCID: PMC4490797  PMID: 26140663
vacuum therapy; subatmospheric pressure dressing; topical negative-pressure therapy; diabetic ulcers; wound bed preparation; amputation
12.  Foot deformities, function in the lower extremities, and plantar pressure in patients with diabetes at high risk to develop foot ulcers 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.27593.
Objective
Foot deformities, neuropathy, and dysfunction in the lower extremities are known risk factors that increase plantar peak pressure (PP) and, as a result, the risk of developing foot ulcers in patients with diabetes. However, knowledge about the prevalence of these factors is still limited. The aim of the present study was to describe the prevalence of risk factors observed in patients with diabetes without foot ulcers and to explore possible connections between the risk factors and high plantar pressure.
Patients and methods
Patients diagnosed with type 1 (n=27) or type 2 (n=47) diabetes (mean age 60.0±15.0 years) were included in this cross-sectional study. Assessments included the registration of foot deformities; test of gross function at the hip, knee, and ankle joints; a stratification of the risk of developing foot ulcers according to the Swedish National Diabetes Register; a walking test; and self-reported questionnaires including the SF-36 health survey. In-shoe PP was measured in seven regions of interests on the sole of the foot using F-Scan®. An exploratory analysis of the association of risk factors with PP was performed.
Results
Neuropathy was present in 28 (38%), and 39 (53%) had callosities in the heel region. Low forefoot arch was present in 57 (77%). Gait-related parameters, such as the ability to walk on the forefoot or heel, were normal in all patients. Eighty percent had normal function at the hip and ankle joints. Gait velocity was 1.2±0.2 m/s. All patients were stratified to risk group 3. Hallux valgus and hallux rigidus were associated with an increase in the PP in the medial forefoot. A higher body mass index (BMI) was found to increase the PP at metatarsal heads 4 and 5. Pes planus was associated with a decrease in PP at metatarsal head 1. Neuropathy did not have a high association with PP.
Conclusions
This study identified several potential risk factors for the onset of diabetic foot ulcers (DFU). Hallux valgus and hallux rigidus appeared to increase the PP under the medial forefoot and a high BMI appeared to increase the PP under the lateral forefoot. There is a need to construct a simple, valid, and reliable assessment routine to detect potential risk factors for the onset of DFU.
doi:10.3402/dfa.v6.27593
PMCID: PMC4472554  PMID: 26087865
diabetic foot; foot deformities; neuropathy; prevention; foot anthropometrics; plantar pressure; risk factors
13.  A prospective audit of the impact of additional staff on the care of diabetic patients in a community podiatry service 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.25508.
Objective
The purpose of this study was to evaluate the impact of the employment of additional podiatry staff on patients with diabetes attending a community-based podiatry service.
Methods
An audit was conducted to evaluate the intervention of two additional podiatry staff. All patients with diabetes referred to and attending community podiatry services in a specified area in the Republic of Ireland between June 2011 and June 2012 were included. The service was benchmarked against the UK gold standard outlined in the ‘Guidelines on prevention & management of foot problems in Type 2 Diabetes’ by the National Institute of Clinical Excellence (NICE). Process of care measures addressed were the number of patients with diabetes receiving treatment and the waiting times of patients with diabetes from referral to initial review.
Results
An increase in the number of patients with diabetes receiving treatment was seen in all risk categories (ranging from low risk to the emergency foot). Waiting times for patients with diabetes decreased post-intervention but did not reach the targets outlined in the NICE guidelines. The average time from referral to initial review of patients with an emergency diabetic foot was 37 weeks post-intervention. NICE guidelines recommend that these patients are seen within 24 hours.
Discussion
During the life cycle of this audit, increased numbers of patients were treated and waiting times for patients with diabetes were reduced. An internal re-organisation of the services coincided with the commencement of the additional staff. The improvements observed were due to the effects of a combination of additional staff and service re-organisation. Efficient organisation of services is key to optimal performance. Continued efforts to improve services are required to reach the standards outlined in the NICE guidelines.
doi:10.3402/dfa.v6.25508
PMCID: PMC4457780  PMID: 26048860
podiatry; audit; waiting times; diabetic foot
14.  A literature-based guide to the conservative and surgical management of the acute Charcot foot and ankle 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.26627.
Acute Charcot neuroarthropathy of the foot and ankle presents with the insidious onset of a unilateral acutely edematous, erythematous, and warm lower extremity. The acute stages are typically defined as Eichenholtz Stage 1, or Stage 0, which was first described by Shibata et al. in 1990. The ultimate goal of treatment is maintenance of a stable, plantigrade foot which can be easily shod, minimizing the risk of callus, ulceration, infection, and amputation. The gold standard of treatment is non-weight-bearing immobilization in a total contact cast. Surgical intervention remains controversial. A review of the literature was performed to provide an evidenced-based approach to the conservative and surgical management of acute Charcot neuroarthropathy of the foot and ankle.
doi:10.3402/dfa.v6.26627
PMCID: PMC4368713  PMID: 25795102
foot collapse; neuroarthropathy; peripheral neuropathy; swollen foot; total contact cast
15.  Staphylococcus aureus small colony variants in diabetic foot infections 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.26431.
Background
Staphylococcus aureus (S. aureus) is one of the major pathogens causing chronic infections. The ability of S. aureus to acquire resistance to a diverse range of antimicrobial compounds results in limited treatment options, particularly in methicillin-resistant S. aureus (MRSA). A mechanism by which S. aureus develops reduced susceptibility to antimicrobials is through the formation of small colony variants (SCVs). Infections by SCVs of S. aureus are an upcoming problem due to difficulties in laboratory diagnosis and resistance to antimicrobial therapy.
Methods
A prospective study was performed on 120 patients diagnosed with both type 2 diabetes mellitus and infected diabetic foot ulcers. The study was carried out from July 2012 to December 2013 in Hospital General de Mexico. The samples were cultured in blood agar, mannitol salt agar, and MacConkey agar media, and incubated at 37°C in aerobic conditions.
Results
We describe the first known cases of diabetic foot infections caused by MRSA-SCVs in patients diagnosed with type 2 diabetes mellitus and infected diabetic foot ulcers. In all of our cases, the patients had not received any form of gentamicin therapy.
Conclusions
The antibiotic therapy commonly used in diabetic patients with infected diabetic foot ulcers fails in the case of MRSA-SCVs because the intracellular location protects S. aureus-SCVs from the host's defenses and also helps them resist antibiotics. The cases studied in this article add to the spectrum of persistent and relapsing infections attributed to MRSA-SCVs and emphasizes that these variants may also play a relevant role in diabetic foot infections.
doi:10.3402/dfa.v6.26431
PMCID: PMC4365137  PMID: 25787018
diabetic foot; infection; ulcer; small colony variants; methicillin-resistant Staphylococcus aureus
16.  Use of collagenase ointment in conjunction with negative pressure wound therapy in the care of diabetic wounds: a case series of six patients 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.24999.
Background
Diabetic wounds with additional comorbidities are costly, time intensive, and difficult to heal. Often, multiple modalities may be necessary to achieve wound resolution, relying on the synergistic advantage of each therapy to affect wound healing. The selectivity of Clostridium collagenase is physiologically effective at degrading non-viable collagen fibers while preserving living collagen tissue. Additionally, negative pressure wound therapy (NPWT) has long been used to aid wound healing while concurrently depreciating biological wound burden time.
Methods
Six patients were selected from those appearing to our university based limb salvage service. Inclusion criteria included patients with a recurrent mixed fibrotic and granular wound base, in which NPWT was indicated, without exclusion criteria. Patients enrolled were administered clostridial collagenase ointment at each regularly scheduled NPWT dressing change. Patients were followed until healing, with visual representations of wound progression and time to full healing recorded.
Results
Tandem application of these therapies appeared to expedite wound healing by clearing degenerative fibrous tissue and expediting wound granulation without additional complication. Unfortunately, not all patients were able to reach full healing; with two patients experiencing ulcer recurrence, likely a result of their significant comorbid nature.
Conclusion
In our experience, we have noticed a specific subgroup of patients who benefit greatly when collagenase enzymatic debridement therapy is combined with NPWT. It is our belief that this combination therapy combines the molecular clearing of non-viable collagen with the wound granulation necessary to advance complex wounds to the next step in healing despite the current paucity in literature discussing this specific pairing.
doi:10.3402/dfa.v6.24999
PMCID: PMC4309834  PMID: 25630362
diabetes; ulcers; wound healing; negative pressure wound therapy; collagenase
17.  Reduction of pain via platelet-rich plasma in split-thickness skin graft donor sites: a series of matched pairs 
Diabetic Foot & Ankle  2015;6:10.3402/dfa.v6.24972.
In the past decade, autologous platelet-rich plasma (PRP) therapy has seen increasingly widespread integration into medical specialties. PRP application is known to accelerate wound epithelialization rates, and may also reduce postoperative wound site pain. Recently, we observed an increase in patient satisfaction following PRP gel (Angel, Cytomedix, Rockville, MD) application to split-thickness skin graft (STSG) donor sites. We assessed all patients known to our university-based hospital service who underwent multiple STSGs up to the year 2014, with at least one treated with topical PRP. Based on these criteria, five patients aged 48.4±17.6 (80% male) were identified who could serve as their own control, with mean time of 4.4±5.1 years between operations. In both therapies, initial dressing changes occurred on postoperative day (POD) 7, with donor site pain measured by Likert visual pain scale. Paired t-tests compared the size and thickness of harvested skin graft and patient pain level, and STSG thickness and surface area were comparable between control and PRP interventions (p>0.05 for all). Donor site pain was reduced from an average of 7.2 (±2.6) to 3 (±3.7), an average reduction in pain of 4.2 (standard error 1.1, p=0.0098) following PRP use. Based on these results, the authors suggest PRP as a beneficial adjunct for reducing donor site pain following STSG harvest.
doi:10.3402/dfa.v6.24972
PMCID: PMC4306752  PMID: 25623477
skin grafts; platelet-rich plasma; diabetic foot; pain reduction
18.  The lateral lesser toe fillet flap for diabetic foot soft tissue closure: surgical technique and case report 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.25732.
Wound closure for the diabetic foot can be challenging and often involves amputation or reconstruction. The authors describe a surgical technique and a case report of lateral lesser toe fillet flap in the management of a diabetic foot wound. The lateral lesser toe fillet flap reconstruction is a reproducible technique that incurs comparatively minimal technical complexity and provides a favorable option in the management of diabetic foot wounds where soft tissue coverage is required.
doi:10.3402/dfa.v5.25732
PMCID: PMC4272413  PMID: 25527137
diabetes mellitus; diabetic foot; toe fillet flap; amputation
19.  The role of Renasys-GO™ in the treatment of diabetic lower limb ulcers: a case series 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.24718.
Introduction
This case series aims to study the effectiveness of Renasys-GO™ negative pressure wound therapy system in the healing of diabetic lower limb ulcers.
Materials and methods
An electronic vacuum pump (Renasys-GO™, Smith & Nephew GmbH) was used to apply negative pressure wound therapy on wounds, with pressure settings determined according to clinical indication. Changes in wound dimension, infection status and duration of treatment were recorded over the course of Renasys-GO™ therapy in 10 patients with diabetic lower limb ulcers.
Results
Healing was achieved in all wounds, three by secondary closure and seven by split-thickness skin grafting. Eight wounds showed a reduction in wound size. The average duration of treatment with Renasys-GO™ therapy was 15.9 days, and all wounds showed sufficient granulation and were cleared of bacterial infection at the end of therapy.
Conclusions
Renasys-GO™ therapy may be beneficial in the treatment of diabetic lower limb ulcers and wounds. In this study, which included wounds presenting as post-surgery ray amputation, metatarsal excision wounds, post-debridement abscesses and ulcers, the Renasys-GO™ therapy prepared all wounds for closure via split-thickness skin grafting or secondary healing by promoting granulation tissue and reducing bacterial infection in approximately 2 weeks.
doi:10.3402/dfa.v5.24718
PMCID: PMC4236639  PMID: 25406680
diabetic lower limb wounds; negative pressure wound therapy; wound healing
20.  Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.24926.
Introduction and objective
Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy).
Design and methods
A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®).
Results
In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively.
Conclusion
Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.
doi:10.3402/dfa.v5.24926
PMCID: PMC4224703  PMID: 25397867
quantitative sensory testing; allodynia; neuropathy; neuropathic ulcer; neuropathic arthropathy; nociception
21.  An overview of factors maximizing successful split-thickness skin grafting in diabetic wounds 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.24769.
Open wounds, from ulcerations or slow healing, are one of the comorbidities in diabetic patients that can lead to amputation. Therefore, an optimal way to close and heal wounds quickly in diabetic patients is required. Split-thickness skin grafts (STSG) offer a quick method of wound closure for diabetic patients. This article review will look at causes of failure in STSG, and ways to optimize success.
doi:10.3402/dfa.v5.24769
PMCID: PMC4216388
biofilm; chronic; bioengineered alternative tissue; debridement; closure
22.  Osteomyelitis in the diabetic foot 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.24445.
Osteomyelitis (OM) is a common complication of diabetic foot ulcers and/or diabetic foot infections. This review article discusses the clinical presentation, diagnosis, and treatment of OM in the diabetic foot. Clinical features that point to the possibility of OM include the presence of exposed bone in the depth of a diabetic foot ulcer. Medical imaging studies include plain radiographs, magnetic resonance imaging, and bone scintigraphy. A high index of suspicion is also required to make the diagnosis of OM in the diabetic foot combined with clinical and radiological studies.
doi:10.3402/dfa.v5.24445
PMCID: PMC4119293  PMID: 25147627
osteomyelitis; diabetic foot; ulcer; infection; antibiotics; amputation
23.  Complication rates in diabetics with first metatarsophalangeal joint arthrodesis 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.24649.
Background
First metatarsophalangeal joint (MTPJ) arthrodesis has been an effective surgical entity when indicated, but a range of severe to mild complications can occur from this procedure. Patients with diabetes mellitus have an increased risk in surgical complications, most commonly associated with soft tissue and bone healing, when compared to non-diabetic patients. The purpose of this study was to evaluate the complication rates of first MTPJ arthrodesis in diabetic patients and compare them to the existing complication rates for the procedure.
Methods
A retrospective chart review was done on 76 diabetic patients, from June 2002 to August 2012. Thirty-two males and 44 females were included in the study. The authors evaluated many variables that could impact postoperative complications, including age, gender, bone graft incorporation, hemoglobin A1c, tobacco use, body mass index, peripheral neuropathy, hallux extensus, hallux interphalangeal arthritis, and rheumatoid arthritis, and compared them with the complication findings. Patient follow-up was no less than 24 months.
Results
Overall, approximately two-thirds of the patients had no complications and 35.5% of patients had at least one mild or moderate complication. Of the non-union and mal-union complications, 80 and 70% had peripheral neuropathy, respectively. One hundred percent of the patients that had mal-positions or hardware failure also had peripheral neuropathy. No severe complications were seen during follow-up. Only two of the moderate complications needed revisions, and the rest of those with moderate complications were asymptomatic.
Conclusion
In conclusion, first MTPJ arthrodesis is overall an effective and beneficial procedure in patients with diabetes mellitus. Diabetic patients with peripheral neuropathy have an increased risk for mild and moderate complications.
doi:10.3402/dfa.v5.24649
PMCID: PMC4074606  PMID: 24987496
diabetes mellitus; complications; peripheral neuropathy; first metatarsophalangeal arthrodesis
24.  Risk factors for methicillin-resistant Staphylococcus aureus in diabetic foot infections 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.23575.
Objective
The purpose of this study was to evaluate risk factors for methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized for diabetic foot infections.
Methods
We reviewed hospital admissions for foot infections in patients with diabetes which had nasal swabs, and anaerobic and aerobic tissue cultures at the time of admission. Data collected included patient characteristics and medical history to determine risk factors for developing an MRSA infection in the foot.
Results
The prevalence of MRSA in these infections was 29.8%. Risk factors for MRSA diabetic foot infections were history of MRSA foot infection, MRSA nasal colonization, and multidrug-resistant organisms (p<0.05). Positive predictive value (PPV) and negative predictive value (NPV) of nasal colonization with MRSA to identify MRSA diabetic foot infections were 66.7% and 80.0% (sensitivity 41%, specificity 90%). Admission from a nursing home was not a significant risk factor.
Conclusion
Positive nasal swabs are not predictive of the infecting agent; however, a negative nasal swab rules out MRSA as the infecting agent in foot wounds with 90% accuracy.
doi:10.3402/dfa.v5.23575
PMCID: PMC3984406  PMID: 24765246
MRSA; infection; diabetic foot; ulcer
25.  Vacuum-assisted closure versus conventional dressings in the management of diabetic foot ulcers: a prospective case–control study 
Diabetic Foot & Ankle  2014;5:10.3402/dfa.v5.23345.
Objective
To compare the effectiveness of vacuum-assisted closure (VAC) versus conventional dressings in the healing of diabetic foot ulcerations (DFUs) in terms of healing rate (time to prepare the wound for closure either spontaneously or by surgery), safety, and patient satisfaction.
Methods
Randomized case–control study enrolling 56 patients, divided into two groups. Group A (patients treated with VAC) and Group B (patients treated with conventional dressings), with an equal number of patients in each group. DFUs were treated until wound closure, either spontaneously, surgically, or until completion of the 8-week period.
Results
Granulation tissue appeared in 26 (92.85%) patients by the end of Week 2 in Group A, while it appeared in 15 (53.57%) patients by that time in Group B. 100% granulation was achieved in 21 (77.78%) patients by the end of Week 5 in Group A as compared to only 10 (40%) patients by that time in Group B. Patients in Group A had fewer number of positive blood cultures, secondary amputations and were satisfied with treatment as compared to Group B.
Conclusion
VAC appears to be more effective, safe, and patient satisfactory compared to conventional dressings for the treatment of DFUs.
doi:10.3402/dfa.v5.23345
PMCID: PMC3982118  PMID: 24765245
diabetic foot ulcer; infections; conventional dressings; vacuum-assisted closure; wound closure

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