Search

David C Klonoff,1 Brian L Levy,2 Michael J Jaasma,3 Manish Bharara,3 Deborah R Edgar,4 Christian Nasr,5 David L Caraway,3 Erika A Petersen,6 David G Armstrong7 1Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA, USA; 2New York University Grossman School of Medicine, New York, NY, USA; 3Nevro Corp, Redwood City, CA, USA; 4Commexus Ltd, Dunblane, Scotland, UK; 5Division of Endocrinology, Department of Internal Medicine, The University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; 6Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 7Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, USACorrespondence: David C Klonoff, Diabetes Research Institute, Mills-Peninsula Medical Center, 100 South San Mateo Drive, Room 1165, San Mateo, CA, 94401, USA, Tel +1650-218-1142, Email dklonoff@diabetestechnology.orgPurpose: The recent SENZA-PDN study showed that high-frequency (10kHz) spinal cord stimulation (SCS) provided significant, durable pain relief for individuals with painful diabetic neuropathy (PDN), along with secondary benefits, including improved sleep quality and HRQoL. Given that metabolic factors and chronic neuropathic pain are related, we evaluated potential secondary effects of 10kHz SCS on hemoglobin A1c (HbA1c) and weight in SENZA-PDN participants with type 2 diabetes (T2D).Patients and Methods: This analysis included 144 participants with T2D and lower limb pain due to PDN who received 10kHz SCS during the SENZA-PDN study. Changes in HbA1c, weight, pain intensity, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c (> 7% and > 8%) and body mass index (BMI; ≥ 30 and ≥ 35 kg/m2).Results: At 24 months, participants with preimplantation HbA1c > 7% and > 8% achieved clinically meaningful and statistically significant mean reductions in HbA1c of 0.5% (P = 0.031) and 1.1% (P = 0.004), respectively. Additionally, we observed a significant mean weight loss of 3.1 kg (P = 0.003) across all study participants. In subgroups with BMI ≥ 30 and ≥ 35 kg/m2, weight reductions at 24 months were 4.1 kg (P = 0.001) and 5.4 kg (P = 0.005), respectively. These reductions were accompanied by a mean pain reduction of 79.8% and a mean decrease in pain interference with sleep of 65.2% at 24 months across all cohorts.Conclusion: This is the first study of SCS to demonstrate long-term, significant, and clinically meaningful reductions in HbA1c and weight in study participants with PDN and T2D, particularly among those with elevated preimplantation HbA1c and BMI. Although the mechanism for these improvements has yet to be established, the results suggest possible direct and indirect metabolic benefits with 10kHz SCS in addition to durable pain relief.Trial Registration: ClincalTrials.gov Identifier, NCT03228420.Keywords: diabetic peripheral neuropathy, painful diabetic neuropathy, spinal cord stimulation, neuromodulation, neuropathic pain

Jonathan M Hagedorn,1 Jordan Tate,2 Manish Bharara3 1iSpine Pain Physicians, Maple Grove, MN, USA; 2Southern Pain and Spine, Jasper, GA, USA; 3Clinical Affairs Department, Nevro Corp, Redwood City, CA, USACorrespondence: Jonathan M Hagedorn, iSpine Pain Physicians, Maple Grove, MN, USA, Tel +1 763-201-8191, Fax +1 763-201-8192, Email jonhagedornmd@yahoo.comIntroduction: Chronic pain is a common clinical condition and is frequently treated with a variety of medications, but pharmacotherapy is oftentimes not the optimal long-term treatment option. Safe and effective long-term pain relief for trunk and limb pain is available using high-frequency spinal cord stimulation at 10 kHz (10 kHz SCS), which is delivered using a rechargeable implantable pulse generator (IPG). Although rechargeable devices have been shown to reduce patient risk and overall cost by eliminating the need for periodic surgeries to replace depleted non-rechargeable IPGs, there is little published evidence that rechargeable technology is practical and convenient for patients, especially in the context of 10 kHz SCS.Objective: This analysis of real-world patients implanted with 10 kHz SCS devices was undertaken using patient data from an industry-maintained database to investigate whether there was a substantial burden associated with rechargeable SCS and the degree of patient satisfaction or dissatisfaction with 10 kHz SCS.Results: This study included 10,391 men and women who were implanted with 10 kHz SCS devices to treat chronic pain of the trunk and/or limbs. They received stimulation for a median of 361 days (180– 1550 days), and 65.48% had previous spine surgery. In this patient sample, most patients were satisfied with the efficacy of 10 kHz SCS, including 77% who would repeat the procedure and 71% who would recommend it to other patients with similar pain. In regards to IPG recharging, 70% were satisfied or very satisfied and 19% were neutral, and a majority of patients recharged their device daily for 30 to 60 minutes.Conclusion: These results indicate most patients do not find IPG recharging inconvenient or burdensome. In addition, IPG recharging is not a barrier to the majority of patients benefitting from 10 kHz SCS for long-term pain relief.Keywords: SCS, spinal cord stimulation, satisfaction, real-world

There are currently 3 established techniques employed routinely to determine the risk of foot ulceration in the patient with diabetes mellitus. These are the assessment of circulation, neuropathy, and foot [...]

Objective: There is a dearth of long-term data regarding patient and limb survival in patients with diabetic foot ulcers (DFUs). The purpose of our study was therefore to prospectively investigate the limb and person survival of DFU patients during a follow-up period of more than 10 years.Research Design and Methods: Two hundred forty-seven patients with DFUs and without previous major amputation consecutively presenting to a single diabetes center between June 1998 and December 1999 were included in this study and followed up until May 2011. Mean patient age was 68.8 ± 10.9 years, 58.7% were male, and 55.5% had peripheral arterial disease (PAD). Times to first major amputation and to death were analyzed with Kaplan-Meier curves and Cox multiple regression.Results: A first major amputation occurred in 38 patients (15.4%) during follow-up. All but one of these patients had evidence of PAD at inclusion in the study, and 51.4% had severe PAD [ankle-brachial pressure index ≤0.4]). Age (hazard ratio [HR] per year, 1.05 [95% CI, 1.01-1.10]), being on dialysis (3.51 [1.02-12.07]), and PAD (35.34 [4.81-259.79]) were significant predictors for first major amputation. Cumulative mortalities at years 1, 3, 5, and 10 were 15.4, 33.1, 45.8, and 70.4%, respectively. Significant predictors for death were age (HR per year, 1.08 [95% CI, 1.06-1.10]), male sex ([1.18-2.32]), chronic renal insufficiency (1.83 [1.25-2.66]), dialysis (6.43 [3.14-13.16]), and PAD (1.44 [1.05-1.98]).Conclusions: Although long-term limb salvage in this modern series of diabetic foot patients is favorable, long-term survival remains poor, especially among patients with PAD or renal insufficiency. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the accuracy and effective service life of commercially available Semmes-Weinstein monofilaments with repetitive loading. METHODS: We obtained 6 brands of Semmes-Weinstein monofilaments (SWM) from commercial vendors identified from the Internet and the federal registry. Five monofilaments of each brand were subjected to repeat loading cycles, allowed to rest over night and loaded again the next day. First, sets of five monofilaments were loaded 25 times for each of five days. Then sets of five monofilaments were subjected to 200 loading cycles a day for 15 days. A testing jig ensured each SWM was loaded perpendicular to a digital pressure plate. The buckling force was measured via the pressure plate to determine failure loads. Several statistical techniques were used to examine the behavior of the monofilaments over repeated loadings: time series analysis, ANOVA and nonparametric comparisons of load distributions. RESULTS: The monofilaments tested were neither precise nor accurate. The plasticity of filaments increased with repeated loadings resulting in lower bending forces. Individual and average bending forces varied widely both within and between monofilament brands. All monofilaments showed a typical material failure pattern. Initially the bending force was high but rapidly decreased and then leveled out at levels 1-2g lower than the starting values. After resting over night, the initial bending force was again high but usually not as high as the previous day and bending forces decreased and then leveled out. Most monofilaments did not start at the accepted 10-g buckling force but varied by up to 30% (p<0.01). At best, monofilaments starting at the accepted 10±1g buckling force would remain within a usable range (9-11g) for 7-9 days or to evaluate 70-90 patients. CONCLUSION: Commercially available SWM have significant variability within and between devices from different manufacturers. Their actual bending force varies widely from their designated 10g value. When used they have a short service life where the instrument is within 10% of their initial bending force which is not usually the stated 10g of force. [ABSTRACT FROM AUTHOR]

Background: Painful diabetic neuropathy (PDN) can result in the loss of protective sensation, in which people are at twice the likelihood of foot ulceration and three times the risk of lower extremity amputation. Here, we evaluated the long-term effects of high-frequency (10 kHz) paresthesia-independent spinal cord stimulation (SCS) on protective sensation in the feet and the associated risk of foot ulceration for individuals with PDN., Methods: The SENZA-PDN clinical study was a randomized, controlled trial in which 216 participants with PDN were randomized to receive either conventional medical management (CMM) alone or 10 kHz SCS plus CMM, with optional treatment crossover after 6 months. At study visits (baseline through 24 months), 10-g monofilament sensory assessments were conducted at 10 locations per foot. Two published methods were used to evaluate protective sensation via classifying risk of foot ulceration., Results: Participants in the 10 kHz SCS group reported increased numbers of sensate locations as compared to CMM alone ( P < .001) and to preimplantation ( P < .01) and were significantly more likely to be at low risk of foot ulceration using both classification methods. The proportion of low-risk participants approximately doubled from preimplantation to 3 months postimplantation and remained stable through 24 months ( P ≤ .01)., Conclusions: Significant improvements were observed in protective sensation from preimplantation to 24 months postimplantation for the 10 kHz SCS group. With this unique, disease-modifying improvement in sensory function, 10 kHz SCS provides the potential to reduce ulceration, amputation, and other severe sequelae of PDN., Trial Registration: The SENZA-PDN study is registered on ClinicalTrials.gov with identifier NCT03228420., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The objective of this study was to evaluate the 24-month durability of pain relief, function, quality of life, and safety outcomes for patients with nonsurgical refractory back pain (NSRBP) treated with high-frequency spinal cord stimulation (SCS) within a large, national, multicenter randomized controlled trial (RCT)., Methods: Following the completion of an RCT comparing high-frequency SCS plus CMM with CMM alone for the treatment of NSRBP, patients gave additional consent for a follow-up extension to 24 months. Presented is the cohort analysis of all patients treated with high-frequency SCS following the optional crossover at 6 months. The outcomes assessed to 24 months included responder rate of ≥ 50% pain relief measured according to the visual analog scale [VAS]), disability (Oswestry Disability Index [ODI]), quality of life (EQ-5D 5-level [EQ-5D-5L]), opioid reduction., Results: Of the 125 patients who received a permanent implant, 121 completed the 12-month follow-up, 101 gave additional consent for extended follow-up, and 98 completed the 24-month follow-up. At 24 months after implantation, the mean back pain VAS score was reduced by 73% and the responder rate was 82%. ODI and EQ-5D-5L both improved by at least double the minimal clinically important difference for each measure. No unexpected adverse events were observed, and the rates of serious adverse events (3.4%) and device explantations (4.8%) were low., Conclusions: The addition of high-frequency SCS to CMM in patients with NSRBP offers profound improvements at 24 months in pain, function, quality of life, and reduced opioid use. This study provides much-needed evidence to inform current clinical practice for managing patients with NSRBP.

Background: Diabetes is one of the most prevalent chronic health conditions and diabetic neuropathy one of its most prevalent and debilitating complications. While there are treatments available for painful diabetic peripheral neuropathy (pDPN), their effectiveness is limited., Method: This retrospective, multi-center, real-world review assessed pain relief and functional improvements for consecutive patients with diabetic neuropathy aged ≥18 years of age who were permanently implanted with a high-frequency (10 kHz) spinal cord stimulation (SCS) device. Available data were extracted from a commercial database., Results: In total 89 patients consented to being included in the analysis. Sixty-one percent (54/89) of participants were male and the average age was 64.4 years (SD = 9.1). Most patients (78.7%, 70/89) identified pain primarily in their feet or legs bilaterally. At the last assessment, 79.5% (58/73) of patients were treatment responders, defined as having at least 50% patient-reported pain relief from baseline. The average time of follow-up was 21.8 months (range: 4.3 to 46.3 months). A majority of patients reported improvements in sleep and overall function relative to their baseline., Conclusions: This real-world study in typical clinical practices found 10 kHz SCS provided meaningful pain relief for a substantial proportion of patients refractory to current pDPN management, similar to published literature. This patient population has tremendous unmet needs and this study helps demonstrate the potential for 10 kHz SCS to provide an alternative pain management approach.

Objective: The objective was to report patterns of physical activity and their relationship to wound healing success in patients with diabetic foot ulcers protected with removable or irremovable offloading devices., Methods: Forty-nine people with diabetic foot ulcers were randomized to wear either a removable cast walker (RCW) or an irremovable instant total contact cast (iTCC). Primary outcome measures included change in wound size, physical activities including position (ie, sitting, standing, lying) and locomotion (speed, steps, etc). Outcomes parameters were assessed on weekly basis until wound healing or until 12 weeks., Results: A higher proportion of patients healed at 12 weeks in the iTCC group ( P = .038). Significant differences in activity were observed between groups starting at week 4. RCW patients became more active than the iTCC group (75% higher duration of standing, 100% longer duration of walking, and 126% longer unbroken walking bout, P < .05). Overall, there was an inverse association between rate of weekly wound healing and number of steps taken per day ( r < -.33, P < .05) for both groups. RCW patients had a significant inverse correlation between duration of daily standing and weekly rate of healing ( r = -.67, P < .05). Standing duration was the only significant predictor of healing at 12 weeks., Conclusion: The results from this study suggest significant differences in activity patterns between removable and irremovable offloading devices. These patterns appear to start diverging at week 4, which may indicate a decline in adherence to offloading. Results suggest that while walking may delay wound healing, unprotected standing might be an even more unrealized and sinister culprit.

The high mortality and disability of diabetic nonhealing skin ulcers create an urgent need for the development of more efficacious strategies targeting diabetic wound healing. In the current study, using human clinical specimens, we show that perilesional skin tissues from patients with diabetes are under more severe oxidative stress and display higher activation of the nuclear factor-E2-related factor 2 (NRF2)-mediated antioxidant response than perilesional skin tissues from normoglycemic patients. In a streptozotocin-induced diabetes mouse model, Nrf2(-/-) mice have delayed wound closure rates compared with Nrf2(+/+) mice, which is, at least partially, due to greater oxidative DNA damage, low transforming growth factor-β1 (TGF-β1) and high matrix metalloproteinase 9 (MMP9) expression, and increased apoptosis. More importantly, pharmacological activation of the NRF2 pathway significantly improves diabetic wound healing. In vitro experiments in human immortalized keratinocyte cells confirm that NRF2 contributes to wound healing by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis, and increasing the expression of TGF-β1 and lowering MMP9 under high-glucose conditions. This study indicates an essential role for NRF2 in diabetic wound healing and the therapeutic benefits of activating NRF2 in this disease, laying the foundation for future clinical trials using NRF2 activators in treating diabetic skin ulcers., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Individuals with diabetic peripheral neuropathy (DPN) have deficits in sensory and motor skills leading to inadequate proprioceptive feedback, impaired postural balance and higher fall risk., Objective: This study investigated the effect of sensor-based interactive balance training on postural stability and daily physical activity in older adults with diabetes., Methods: Thirty-nine older adults with DPN were enrolled (age 63.7 ± 8.2 years, BMI 30.6 ± 6, 54% females) and randomized to either an intervention (IG) or a control (CG) group. The IG received sensor-based interactive exercise training tailored for people with diabetes (twice a week for 4 weeks). The exercises focused on shifting weight and crossing virtual obstacles. Body-worn sensors were implemented to acquire kinematic data and provide real-time joint visual feedback during the training. Outcome measurements included changes in center of mass (CoM) sway, ankle and hip joint sway measured during a balance test while the eyes were open and closed at baseline and after the intervention. Daily physical activities were also measured during a 48-hour period at baseline and at follow-up. Analysis of covariance was performed for the post-training outcome comparison., Results: Compared with the CG, the patients in the IG showed a significantly reduced CoM sway (58.31%; p = 0.009), ankle sway (62.7%; p = 0.008) and hip joint sway (72.4%; p = 0.017) during the balance test with open eyes. The ankle sway was also significantly reduced in the IG group (58.8%; p = 0.037) during measurements while the eyes were closed. The number of steps walked showed a substantial but nonsignificant increase (+27.68%; p = 0.064) in the IG following training., Conclusion: The results of this randomized controlled trial demonstrate that people with DPN can significantly improve their postural balance with diabetes-specific, tailored, sensor-based exercise training. The results promote the use of wearable technology in exercise training; however, future studies comparing this technology with commercially available systems are required to evaluate the benefit of interactive visual joint movement feedback., (© 2015 S. Karger AG, Basel.)

Background: Individuals with diabetic peripheral neuropathy frequently experience concomitant impaired proprioception and postural instability. Conventional exercise training has been demonstrated to be effective in improving balance but does not incorporate visual feedback targeting joint perception, which is an integral mechanism that helps compensate for impaired proprioception in diabetic peripheral neuropathy., Methods: This prospective cohort study recruited 29 participants (mean ± SD: age, 57 ± 10 years; body mass index [calculated as weight in kilograms divided by height in meters squared], 26.9 ± 3.1). Participants satisfying the inclusion criteria performed predefined ankle exercises through reaching tasks, with visual feedback from the ankle joint projected on a screen. Ankle motion in the mediolateral and anteroposterior directions was captured using wearable sensors attached to the participant's shank. Improvements in postural stability were quantified by measuring center of mass sway area and the reciprocal compensatory index before and after training using validated body-worn sensor technology., Results: Findings revealed a significant reduction in center of mass sway after training (mean, 22%; P = .02). A higher postural stability deficit (high body sway) at baseline was associated with higher training gains in postural balance (reduction in center of mass sway) (r = -0.52, P < .05). In addition, significant improvement was observed in postural coordination between the ankle and hip joints (mean, 10.4%; P = .04)., Conclusions: The present research implemented a novel balance rehabilitation strategy based on virtual reality technology. The method included wearable sensors and an interactive user interface for real-time visual feedback based on ankle joint motion, similar to a video gaming environment, for compensating impaired joint proprioception. These findings support that visual feedback generated from the ankle joint coupled with motor learning may be effective in improving postural stability in patients with diabetic peripheral neuropathy.

Background: Gait-related fall risk is the leading cause of mortality among patients with diabetes, especially those older than 65 years. Deterioration in balance and loss of protective sensation in lower extremities contribute significantly to fall risk in patients with diabetic peripheral neuropathy (DPN). This study aimed to explore the impact of neuropathy and foot ulcer on gait., Methods: We recruited 39 participants (age, 56.9 ± 8.2 years; body mass index, 29.6.3 ± 4.7 kg/m2), including 15 DPN patients without foot ulcers, 16 DPN patients with foot ulcers, and 8 healthy aged-matched controls. Patients with active foot ulcers wore an offloading device during gait examination, including removable cast walker., Results: Results suggest that neuropathy alters gait mainly by increasing gait initiation, gait variability (coefficient of variation of gait velocity), and double support (DS) time, while reducing knee range of motion and center of mass sway (p < .05). Interestingly, the presence of foot ulcer does not impact gait velocity (p > .1) but enhances some of the gait parameters such as gait variability and DS time., Conclusions: This study demonstrates that neuropathy deteriorates gait, but the presence of foot ulcers does not alter gait parameters further than neuropathy. In addition, patients with foot ulcers demonstrated a better gait compared with DPN patients without ulcers. We speculate that offloading footwear may be enhancing the somatosensory feedback from sensate skin, thereby positively affecting gait parameters. A study with a larger sample is required to explore the effect of prescribed footwear in the DPN population in order to validate the findings of this research study., (© 2013 Diabetes Technology Society.)

Objective: This study aimed to quantify the impact of an integrated diabetic foot surgical service on outcomes and changes in surgical volume and focus., Methods: We abstracted registry data from 48 consecutive months at a single institution, evaluating all patients with diabetic foot complications requiring surgery or vascular intervention, and compared outcomes in the 24 months before and after integrating podiatric surgery with vascular surgical limb-salvage service., Results: The service performed 2923 operations; 790 (27.0%) were related to treatment of diabetic foot complications in 374 patients. Of these, 502 were classified as non-vascular diabetic foot surgery and 288 were vascular interventions. Urgent surgery was significantly reduced after team implementation (77.7% vs 48.5%, p < 0.0001; OR = 3.7, 95% CI: 2.4-5.5). The high/low amputation ratio decreased from 0.35 to 0.27 due to an increase in low-level (midfoot) amputations (8.2% vs 26.1%, p < 0.0001; OR = 4.0, 95% CI: 2.0-83.3). A 45.7% reduction in below-knee amputations was realized with a stable above-knee/below-knee amputation ratio (0.73-0.81). One-third of patients required vascular intervention. Vascular reconstructions increased 44.1% following institution of the team. Initial revascularization was endovascular in 70.6% of patients. Repeat endovascular intervention or conversion to open bypass was required in 37.1% of these patients, almost double the reintervention rate of those receiving open bypass first (18.9%)., Conclusions: Interdisciplinary diabetic foot surgery teams may significantly impact surgery type, with greater focus on proactive and preventive, rather than reactive and ablative, procedures. Although endovascular limb-sparing procedures have become increasingly applicable, open bypass remains critical to success., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: While endovascular (ENDO) therapy has increasingly become the initial intervention of choice to treat lower extremity peripheral arterial disease, reported outcomes for ENDO in patients with critical limb ischemia (CLI) and diabetes have been reported to be inferior compared to open bypass surgery (OPEN). Objective data assessing the hemodynamic success of ENDO compared to the established benchmark of OPEN are sparse. We therefore evaluated and compared early hemodynamic outcomes of ENDO and OPEN in patients with diabetes with CLI at a single academic center., Methods: We studied 85 consecutive patients with diabetes and CLI who underwent 109 interventions, either ENDO (n = 78) or OPEN (n = 31). The mean patient age was 69 years; 62% were men. All patients presented with either rest pain and/or ulcer/gangrene. Per protocol, all were assessed using ankle brachial index (ABI) and toe pressure (TP) determinations before and early postintervention., Results: Both ENDO (ΔABI = 0.36 ± 0.24, P < .0001; ΔTP = 35.6 ± 24.1, P < .0001) and OPEN (ΔABI = 0.39 ± 0.17, P < .0001; ΔTP = 34.3 ± 24.0, P < .0001) resulted in significant hemodynamic improvement. There was no statistically significant initial difference between the two types of intervention (ABI, P = .6; TP, P = .6)., Conclusions: These data suggest that with appropriate patient selection, each intervention is similarly efficacious in initially improving hemodynamics. If the intermediate or long-term results of ENDO for CLI in people with diabetes are inferior, the problem is not one of initial hemodynamic response, but more likely due to differing patient characteristics or durability of the intervention., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

The incidence of diabetic foot complications, most notably wounds, is increasing worldwide. Most people who present for care of a foot wound will become infected. Globally, this results in one major amputation every 30 seconds with over 2500 limbs lost per day. Presently, clinicians assess circulation, neuropathy and plantar pressures to identify the risk of foot ulceration. Several studies have suggested prevention of foot ulcers by identifying individuals at high risk and treating for lower extremity complications. Our group has proposed several diagnostics as well as prevention strategies, especially thermography and thermometry for management of patients with diabetic foot complications. These strategies employ non-invasive assessment of inflammation for acute as well as chronic care for the foot, with the intent to prevent ulceration/re-ulceration and subsequent traumatic amputations. The authors' review some important clinical studies and ongoing research in this area, with the long-term goal to further the role of thermography and thermometry in clinical care for the diabetic foot., (Copyright © 2012 John Wiley & Sons, Ltd.)

Preventing amputations in persons with lower extremity complications of diabetes is a complex endeavor, particularly in those with concomitant ischemia and tissue loss. Fluorescence angiography (Novadaq SPY system) may provide a tool for objective evaluations of tissue viability in the diabetic foot, which is an important indicator of the ability of the diabetic ulcer to heal adequately. The SPY system uses a low-power laser coupled with a charge-coupled device camera and indocyanine green (ICG) to sequence perfusion at the surface of the skin. We present an illustrated example of the potential utility of ICG fluorescence angiography (ICGFA) before and after vascular intervention in a high-risk limb. ICGFA appeared to reveal demarcation between viable and nonviable tissue and real-time perfusion, specifically capillary fill. ICGFA clarified the extent of necessary debridement and provided an immediate indication of improvement in regional perfusion status following revascularization. Future studies involving ICGFA may include pre- and postdebridement and closure perfusion, comparison of tissue perfusion pre- and post-endovascular therapy, and lower extremity flap viability. Future works will also address the consistency of results with ICGFA by analyzing a larger cohort of patients being treated by our unit., (© 2012 Diabetes Technology Society.)

Adventitious bursae typically develop in areas of chronic frictional irritation, usually under bony prominences. Although adventitious bursae are generally well understood, there is a paucity of data on effects of bursae underlying chronic wounds in neuropathic patients. This manuscripts reviews 4 clinical cases, each with a neuropathic patient with adventitious bursae underlying chronic nonhealing wound and strategies for treatment.

Diabetic foot complications are increasing in prevalence worldwide. Care and attention to these complications have improved greatly. Many advanced therapies are now being investigated or taken through final stages of clinical studies worldwide. However, the data upon which assumptions regarding morbidity, healing, and mortality have been based are grossly outdated. The purpose of this brief article is to report on current data regarding neuropathic and neuroischemic wounds and to propose that the latter category of advanced-stage diabetic foot wound may now be emerging as the most commonly encountered lesion in the developed world. Unfortunately, it is still systematically excluded from most clinical study criteria. Additionally, just as in the care of cancer, we call for therapy of these advanced-stage diabetic foot ulcers to be managed in similarly interdisciplinary centers where patients may have access to potentially beneficial clinical trials., (© 2011 Diabetes Technology Society.)

Diabetic foot ulcers are the most common lower extremity complications of diabetes. Peripheral neuropathy and peripheral vascular disease are the underlying risk factors for diabetic foot ulcers, subsequently leading to infections and requiring antimicrobial therapy for the management of the disease. Each risk factor is a target for clinical intervention, with the intent to delay or prevent disease progression to amputation. The effective therapy includes interdisciplinary care, which involves optimized pharmacological interventions in concert with other treatments such as debridement strategies and specialized wound dressings. The pharmacological therapy alone cannot lead to successful therapy, and therefore, these supplementary techniques/modalities should not be overlooked. It is therefore the aim of this report to review various pharmacological interventions, specific to the diabetic foot and wound healing, along with incorporation of advanced therapies required to achieve a multifaceted treatment of diabetic foot ulcers and provide basis for superior drugs as well as drug delivery systems.

Diabetic foot disease frequently leads to substantial long-term complications, imposing a huge socioeconomic burden on available resources and health care systems. Peripheral neuropathy, repetitive trauma, and peripheral vascular disease are common underlying pathways that lead to skin breakdown, often setting the stage for limb-threatening infection. Individuals with diabetes presenting with foot infection warrant optimal surgical management to effect limb salvage and prevent amputation; aggressive short-term and meticulous long-term care plans are required. In addition, the initial surgical intervention or series of interventions must be coupled with appropriate systemic metabolic management as part of an integrated, multidisciplinary team. Such teams typically include multiple medical, surgical, and nursing specialties across a variety of public and private health care systems. This article presents a stepwise approach to the diagnosis and treatment of diabetic foot infections with special emphasis on the appropriate use of surgical interventions and includes the following key elements: incision, wound investigation, debridement, wound irrigation and lavage, and definitive wound closure., (Copyright © 2010 Society for Vascular Surgery and the American Podiatric Medical Association. Published by Mosby, Inc. All rights reserved.)

Autologous platelet-rich plasma (PRP) may enhance wound healing through the formation of a platelet plug that provides both hemostasis and the secretion of biologically active proteins, including growth factors such as platelet-derived growth factor, transforming growth factor (TGF)-β, TGF-β2, and epidermal growth factor. The release of these growth factors into the wound may create an environment more conducive to tissue repair and could accelerate postoperative wound healing. To our knowledge, there are no reports of combining the use of PRP with curative diabetic foot surgery. This article provides a summary of the literature regarding PRP and wound healing and presents a case of a 49-year-old man with diabetes and a three-month history of a deep, nonhealing plantar hallux wound in which PRP was combined with a first metatarsophalangeal joint arthroplasty. Through the use of the PRP and bioengineered tissue to supplement curative diabetic foot surgery, the patient healed uneventfully at seven weeks., (© 2010 Diabetes Technology Society.)

Diabetic foot disease frequently leads to substantial long-term complications, imposing a huge socioeconomic burden on available resources and health-care systems. Peripheral neuropathy, repetitive trauma, and peripheral vascular disease are common underlying pathways that lead to skin breakdown, often setting the stage for limb-threatening infection. Individuals with diabetes presenting with foot infection warrant optimal surgical management to affect limb salvage and prevent amputation; aggressive short-term and meticulous long-term care plans are required. In addition, the initial surgical intervention or series of interventions must be coupled with appropriate systemic metabolic management as part of an integrated, multidisciplinary team. Such teams typically include multiple medical, surgical, and nursing specialties across a variety of public and private health-care systems. This article presents a stepwise approach to the diagnosis and treatment of diabetic foot infections with emphasis on the appropriate use of surgical interventions and includes the following key elements: incision, wound investigation, debridement, wound irrigation and lavage, and definitive wound closure.

With the advent of several innovative wound care management tools, the choice of products and treatment modalities available to clinicians continues to expand. High costs associated with wound care, especially diabetic foot wounds, make it important for clinician scientists to research alternative therapies and optimally incorporate them into wound care protocols appropriately. This article reviews using sugar as a treatment option in diabetic foot care and provides a guide to its appropriate use in healing foot ulcers. In addition to a clinical case study, the physiological significance and advantages of sugar are discussed., (© 2010 Diabetes Technology Society.)

Negative-pressure wound therapy (NPWT) is frequently employed in the treatment of complex wounds. The authors present a description of real-time streaming therapy of a variety of wound chemotherapeutic agents through NPWT. Doxycycline, which acts as a competitive inhibitor of matrix metalloproteinases and tumor necrosis factor alpha and further decreases inflammation through the reduction of nitrous oxide production, may prove helpful when delivered in this manner. To the authors' knowledge, this is the first report in the literature describing this method of delivery of doxycycline.

The standard of care for wound coverage is to use an autologous skin graft. However, large or chronic wounds become an exceptionally challenging problem especially when donor sites are limited. It is important that the clinician be aware of various treatment modalities for wound care and incorporate those methods appropriately in the proper clinical context. This report reviews an alternative to traditional meshed skin grafting for wound coverage: micrografting. The physiological concept of micrografting, along with historical context, and the evolution of the technique are discussed, as well as studies needed for micrograft characterization and future applications of the technique., (2010 Diabetes Technology Society.)

Diabetes around the globe results in one major limb amputation every 30 seconds, over 2500 limbs lost per day. The underlying pathophysiology sometimes leads to a chronic inflammatory stage, which may prevent appropriate healing, and therefore, the need for a clear strategy for assessing and classifying wounds and wound healing cannot be overstated. Temperature is a surrogate marker for inflammation. Quantitative thermography using a numerical index provides a useful way to assess wound healing. Advances in technology have afforded the availability of low-cost, high-resolution thermal imaging systems, which can be used to quantify sensitive changes on the skin surface and may be particularly useful to develop monitoring strategies for wounds. This article provides a standardized technique for calculating a thermal index (TI) supported with a case report from assessment of a diabetic foot ulcer. In this single case study, the TI/wound inflammatory index indicates a shift from negative to positive (p < .05) before it reaches zero., (2010 Diabetes Technology Society.)

Negative pressure wound therapy (NPWT) is frequently employed in the treatment of complex wounds. A variety of wound chemotherapeutic agents such as insulin, which acts as a growth factor, may prove helpful in treatment as well. We present a case report in which insulin was used as a chemotherapeutic agent in continuous-instillation NPWT. To our knowledge, this is the first report in the literature describing this method of delivery., (2010 Diabetes Technology Society.)

Reducing and preventing postoperative pain are currently a topic of great interest. There are different modalities for providing analgesia that can provide an alternative or adjunct to opioid therapy. One mode of therapy involves the use of portable pain pump devices that can deliver continuous local anaesthesia directly to the site of interest. A considerable amount of attention in literature has been dedicated to using regional anaesthesia postoperatively for various surgical applications. However, to our knowledge, little or no work has been published concerning the use of infusion of regional anaesthesia in the treatment of painful lower extremity wounds. We present a case report of a 55-year-old gentleman with a complex past medical history, 2-year history of opioid dependency and a 2-week history of intractable pain associated with the combination of debilitating painful diabetic neuropathy and painful lower extremity wounds. After surgical debridement of the lower extremity wounds, substantial analgesia was achieved postoperatively through the implantation of a portable direct infusion pump device. The device supplied 2 ml/hour of 0.25% bupivacaine and resulted in a reduction in pain within the first hour of implantation. Although the device achieved maximal analgesia at 6 hours, we found that this could have been likely reduced through the use of a 5-ml bolus dose of 0.25% bupivacaine at the time of implantation. The device provided sufficient analgesia to the patient without any observed adverse effects, and showed significant potential in avoiding an increase in his requirement for other systemic analgesia including opioids.

Foot wounds are the most common diabetes-related cause of hospitalization and frequently result in amputation. Although generally diagnosed clinically based on signs and symptoms of inflammation, empirical antibiotic treatment should be based on tissue cultures until resolution of infection. Advances in molecular detection over the past decade, including rapid chromogenic agar and real-time polymerase chain reaction, have improved diagnostic capabilities. However, chronic wounds may host biofilm bacteria not adequately detected by current microbiological testing. Enhanced DNA testing is required to identify these pathogens as well as evolving and previously underdiagnosed bacteria. Two options, nucleic acid fluorescent in situ hybridization and rDNA sequencing, are on the horizon for clinical use. Wound biofilms also necessitate more complex clinical management including debridement, augmenting host defenses, suppression of biofilms, and wound closure. Adopting these advances in diagnosis and treatment may help with overall prognosis and reduce health care costs.

This paper discusses the application of Nanoflex powder dressing for management of complex soft tissue wounds. A case report is presented detailing the management of a 43-year-old Native American woman with diabetes mellitus who required serial debridements for necrotising fasciitis. Following debridement, the patient was left with a large dorsal foot wound and was transitioned through multiple advanced wound healing modalities. Negative pressure wound therapy (NPWT) was initially utilised in the early postoperative setting to control drainage and to promote granulation tissue; the patient was subsequently transitioned to a Nanoflex powder dressing on postoperative day 4. She reported a decrease in pain associated with dressing changes when transitioned from NPWT to the use of Nanoflex powder dressing. We hypothesise that this pain reduction is the result of a light cooling effect of the exudate-controlling dressing and subsequent reduction in inflammation as well as the total contact nature of the dressing. Nanoflex powder dressings are a recently developed advanced wound healing modality with promise in the management of complex soft tissue wounds, both as a primary wound dressing as well as a delivery platform for analgesics, antimicrobials and pro-angiogenic compounds.