Search

Complications secondary to diabetes, such as diabetic foot ulcers, continue to be a major worldwide health problem. At the same time, health care systems are changing rapidly, causing concern about the quality of patient care. While the ultimate effect of current changes on health care professionals and patient outcomes remain uncertain, measures commonly used to reduce costs, e.g., disease and multi discliplinary management strategies, have been shown to help prevent the occurrence of diabetic ulcers. In addition, ultilizing a multi discliplinary approach, the principles of off-loading and optimal wound care, the vast majority of diabetic foot ulcers can be expected to heal within 12 weeks of treatment. Education of primary care providers and patients is paramount. [ABSTRACT FROM AUTHOR]

Objective: Our objective is to examine the pathophysiology of oedema in the ischaemic and post-revascularised limb, compare compression stockings to pneumatic compression devices, and summarise compression regimens in patients with severe peripheral artery disease (PAD) without revascularisation, after revascularisation, and in mixed arterial and venous disease., Method: A scoping literature review of the aforementioned topics was carried out using PubMed., Results: Compression therapy has been shown to increase blood flow and aid in wound healing through a variety of mechanisms. Several studies suggest that intermittent pneumatic compression (IPC) devices can be used to treat critical limb ischaemia in patients without surgical options. Additionally, compression stockings may have a role in preventing oedema after peripheral artery bypass surgery, thereby diminishing pain and reducing the risk of surgical wound dehiscence., Conclusion: Oedema may occur in the ischaemic limb after revascularisation surgery, as well as in combination with venous disease. Clinicians should not fear using compression therapy in PAD.

Objective: The goal of this research was to identify a population of diabetic foot ulcer patients who demonstrate a significant response to hyperbaric oxygen therapy (HBOT) using a large sample size to provide guidance for clinicians when treating these complicated patients. Approach: The effect of HBOT on diabetic foot ulcers, Wagner grades 3 and 4, was evaluated using a retrospective observational real-world data set. The study reported on the overall healing rate, (74.2%) at the population level, for >2 million wounds. Results: When a subgroup of patients of only foot ulcers with a Wagner grade 3 or 4 were considered, the healing rate was only 56.04%. The use of HBOT, without filtering for the number of treatments received, improved the healing rate to 60.01% overall. Healing rates for this same subgroup, however, were improved to 75.24% for patients who completed the prescribed number of hyperbaric treatments. Innovation: This observational study discusses the importance of reporting at the population level, specific wound etiology level, a risk-stratified level, and to then overlay the effect of treatment adherence on those outcomes to provide clinicians with a comprehensive understanding of when to prescribe an advanced modality such as hyperbaric oxygen. Conclusion: The authors provide healing outcomes data from several prior HBOT studies as well as other advanced modalities that have been used in diabetic foot ulcer care for comparison and context.

Ischemic tissue damage activates hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM)-generating myeloid cells, and persistent HSPC activity may drive chronic inflammation and impair tissue recovery. Although increased reactive oxygen species in the BM regulate HSPC functions, their roles in myelopoiesis of activated HSPCs and subsequent tissue recovery during ischemic damage are not well understood. In this paper, we report that deletion of Nox2 NADPH oxidase in mice results in persistent elevations in BM HSPC activity and levels of inflammatory monocytes/macrophages in BM and ischemic tissue in a model of hindlimb ischemia. Ischemic tissue damage induces oxidants in BM such as elevations of hydrogen peroxide and oxidized phospholipids, which activate redox-sensitive Lyn kinase in a Nox2-dependent manner. Moreover, during tissue recovery after ischemic injury, this Nox2-ROS-Lyn kinase axis is induced by Nox2 in neutrophils that home to the BM, which inhibits HSPC activity and inflammatory monocyte generation and promotes tissue regeneration after ischemic damage. Thus, oxidant signaling in the BM mediated by Nox2 in neutrophils regulates myelopoiesis of HSPCs to promote regeneration of damaged tissue., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Objective: Sickle cell ulcers affect as many as 15% of patients with sickle cell disease in the United States and severely impact quality of life. An understanding of baseline healing patterns is important to inform study design for future trials that test therapies for this disease. Approach: In this study, an electronic wound management system was leveraged to analyze retrospective data on 133 unique sickle cell patients who were treated across 114 wound healing centers, and to describe their characteristics and healing patterns as compared with those of venous ulcer patients. The data included 198 care episodes for 427 wounds. Results: Patients with sickle cell ulcers were younger and had fewer comorbid diseases than those with venous ulcers. Larger size and longer duration were predictors of poor healing. Between the first and fourth assessments, mean change in area for sickle cell ulcers showed a 58% increase, compared with a 13% decrease for venous ulcers. Kaplan-Meier curves showed poorer healing in sickle cell ulcers than in venous ulcers across all categories of size and duration. Patients with sickle cell ulcers had longer care episodes and were more likely to re-present for care. Innovation: This study reports on the largest data set of sickle cell ulcer patients analyzed to date in the published literature to provide a more detailed understanding of wound healing patterns of this disease. Conclusion: A national network of electronic health records can effectively identify a large number of patients with sickle cell ulcers to support analysis of epidemiology, healing patterns, and health care utilization.

Objective: The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials., Methods: Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm 2 to 12 cm 2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm 2 and ≤36 cm 2 with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure., Results: This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955-0.987])., Conclusions: Factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Chronic wounds are increasing in prevalence and are a costly problem for the US healthcare system and throughout the world. Typically outcomes studies in the field of wound care have been limited to small clinical trials, comparative effectiveness cohorts and attempts to extrapolate results from claims databases. As a result, outcomes in real world clinical settings may differ from these published studies. This study presents a modified intent-to-treat framework for measuring wound outcomes and measures the consistency of population based outcomes across two distinct settings. In this retrospective observational analysis, we describe the largest to date, cohort of patient wound outcomes derived from 626 hospital based clinics and one academic tertiary care clinic. We present the results of a modified intent-to-treat analysis of wound outcomes as well as demographic and descriptive data. After applying the exclusion criteria, the final analytic sample includes the outcomes from 667,291 wounds in the national sample and 1,788 wounds in the academic sample. We found a consistent modified intent to treat healing rate of 74.6% from the 626 clinics and 77.6% in the academic center. We recommend that a standard modified intent to treat healing rate be used to report wound outcomes to allow for consistency and comparability in measurement across providers, payers and healthcare systems., (© 2017 by the Wound Healing Society.)

Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory evaluation., (© 2017 by the Wound Healing Society.)

Sickle cell leg ulcers (SCLUs) are a common complication of sickle cell disease (SCD). Patients who develop ulcers appear to have a more severe haemolysis-associated vasculopathy than individuals who do not develop them, and manifest other complications such as priapism and pulmonary hypertension. SCLUs are slow to heal and often recur, affecting both the emotional and physical well-being of patients. Here we summarise what is known about the pathophysiology of SCLUs, describe available treatment options and propose a treatment algorithm., (© 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Cellular energy is required for the healing cascade to occur. A combination of cells, cytokines, chemokines, tissue perfusion, an extracellular matrix, and local forces are also required to allow for human tissue repair to proceed. Although there are many examples of treatment options, energy-based therapies are the least understood, appreciated, and employed by practicing wound care physicians. The recent growth of tissue engineering has encouraged researchers to employ both electrical stimulation and therapeutic ultrasound (US) to stimulate cells, induce migration, and modify tissue constructs., Methods: The authors have reviewed the literature on electrical stimulation, US, and vibrational therapy and are providing an update to a prior 2007 publication on this topic. The hope was to provide a broad exposure to these treatments but not to create a comprehensive review. A table of evidence was generated from the recent literature to help guide treatment decisions for the clinician., Results: In the current literature, there is much debate over which treatment modality, dosage levels, and timing are optimal. There are numerous in-vitro-based publications that describe mechanism of action and several clinical articles that describe effectiveness of electrical stimulation and US, but few well-controlled and/or randomized trials. The absence of level one evidence has hindered the adoption of these techniques throughout the years. Three energy-based treatment options, electrical stimulation, vibration, and US, will be reviewed along with possible clinical applications, Conclusions: : Although most trials are underpowered with inconsistent treatment settings, physical therapy modality use is increasing in the clinical community. Recent guidelines reference the use of these treatments with increasing evidence level recommendations. At the present time, electrical stimulation carries the greatest level of evidence for clinical use.

A case series of five patients with a total of six chronic non-healing wounds (>30 day duration) were non-randomly selected to evaluate the performance, safety and handling properties of dehydrated human amnion/chorion membrane allograft, an amniotic membrane scaffolding product. The patients had lower extremity wounds that had previously failed standard of care within a university outpatient/inpatient wound healing programme. Five wounds treated with dehydrated amnion/chorion membrane allograft showed a mean 43% area reduction from baseline (51% median) at 3 weeks into treatment and completely healed with a 64-day median time to closure (SD ±27·6 days). One wound worsened at 3 weeks and was found to have a complete central vein obstruction that was treated with long-term mild compression but still eventually healed at 6 months. Removing this outlier, the four responding wounds had a 72% mean and 69% median change in area from baseline, at the 3 week point. All five patients received only one application of dehydrated human amnion/chorion membrane allograft, and there were no adverse events. The product was easy to use, administer and handle. In summary, dehydrated human amnion/chorion membrane allograft appears to be a safe, effective and easy to use therapy for chronic non-healing wounds. This study describes the details of these clinical cases and provides an overview of the current evidence on the use of amniotic tissue in clinical practice., (© 2015 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Chronic wounds are a common complication in patients with diabetes that often lead to amputation. These non-healing wounds are described as being stuck in a persistent inflammatory state characterized by accumulation of pro-inflammatory macrophages, cytokines and proteases. Some medications approved for management of type 2 diabetes have demonstrated anti-inflammatory properties independent of their marketed insulinotropic effects and thus have underappreciated potential to promote wound healing. In this review, the potential for insulin, metformin, specific sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors to promote healing is evaluated by reviewing human and animal studies on inflammation and wound healing. The available evidence indicates that diabetic medications have potential to prevent wounds from becoming arrested in the inflammatory stage of healing and to promote wound healing by downregulating pro-inflammatory cytokines, upregulating growth factors, lowering matrix metalloproteinases, stimulating angiogenesis, and increasing epithelization. However, no clinical recommendations currently exist on the potential for specific diabetic medications to impact healing of chronic wounds. Thus, we encourage further research that may guide physicians on providing personalized diabetes treatments that achieve glycemic goals while promoting healing in patients with chronic wounds., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Macrophages undergo a transition from pro-inflammatory to healing-associated phenotypes that is critical for efficient wound healing. However, the regulation of this transition during normal and impaired healing remains to be elucidated. In our studies, the switch in macrophage phenotypes during skin wound healing was associated with up-regulation of the peroxisome proliferator-activated receptor (PPAR)γ and its downstream targets, along with increased mitochondrial content. In the setting of diabetes, up-regulation of PPARγ activity was impaired by sustained expression of IL-1β in both mouse and human wounds. In addition, experiments with myeloid-specific PPARγ knockout mice indicated that loss of PPARγ in macrophages is sufficient to prolong wound inflammation and delay healing. Furthermore, PPARγ agonists promoted a healing-associated macrophage phenotype both in vitro and in vivo, even in the diabetic wound environment. Importantly, topical administration of PPARγ agonists improved healing in diabetic mice, suggesting an appealing strategy for down-regulating inflammation and improving the healing of chronic wounds., (Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Calcinosis cutis is a poorly understood process in which calcium salts deposit in the skin and subcutaneous tissues. Due to its multifactorial pathogenesis, several subtypes and potential etiologies have been described. Presented here is a case of bilateral pretibial calcinosis cutis in a patient on long-term tyrosine kinase inhibitor therapy for chronic myeloid leukemia. The patient initially presented with a right tibial ulceration treated with multiple surgical debridements, antibiotics, and negative pressure wound therapy. The wound was ultimately closed with a split-thickness skin graft. Relevant literature is examined and several possible mechanisms are discussed.

Patient preferences are statements made or actions taken by consumers that reflect their desirability of a range of health options. The concept occupies an increasingly prominent place at the center of healthcare reform, and is connected to all aspects of healthcare, including discovery, research, delivery, outcome, and payment. Patient preference research has focused on shared decisions, decisional aids, and clinical practice guideline development, with limited study in acute and chronic wound care populations. The wound care community has focused primarily on patient focused symptoms and quality of life measurement. With increasing recognition of wound care as a medical specialty and as a public health concern that consumes extensive resources, attention to the preferences of end-users with wounds is necessary. This article will provide an overview of related patient-centered concepts and begin to establish a framework for consideration of patient preference in wound care.

Chronic wounds represent a significant health problem, especially in diabetic patients. In the current study, we investigated a novel therapeutic approach to wound healing--whole body low-intensity vibration (LIV). LIV is anabolic for bone, by stimulating the release of growth factors, and modulating stem cell proliferation and differentiation. We hypothesized that LIV improves the delayed wound healing in diabetic mice by promoting a pro-healing wound environment. Diabetic db/db mice received excisional cutaneous wounds and were subjected to LIV (0.4 g at 45 Hz) for 30 min/d or a non-vibrated sham treatment (controls). Wound tissue was collected at 7 and 15 d post-wounding and wound healing, angiogenesis, growth factor levels and wound cell phenotypes were assessed. LIV increased angiogenesis and granulation tissue formation at day 7, and accelerated wound closure and re-epithelialization over days 7 and 15. LIV also reduced neutrophil accumulation and increased macrophage accumulation. In addition, LIV increased expression of pro-healing growth factors and chemokines (insulin-like growth factor-1, vascular endothelial growth factor and monocyte chemotactic protein-1) in wounds. Despite no evidence of a change in the phenotype of CD11b+ macrophages in wounds, LIV resulted in trends towards a less inflammatory phenotype in the CD11b- cells. Our findings indicate that LIV may exert beneficial effects on wound healing by enhancing angiogenesis and granulation tissue formation, and these changes are associated with increases in pro-angiogenic growth factors.

The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound-conditioned medium activates caspase-1 and induces release of interleukin (IL)-1β and IL-18 in cultured Mp via a reactive oxygen species-mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from proinflammatory to healing-associated Mp phenotypes, and increased levels of prohealing growth factors. Furthermore, data generated from bone marrow-transfer experiments from NLRP-3 or caspase-1 knockout to db/db mice indicated that blocking inflammasome activity in bone marrow cells is sufficient to improve healing. Our findings indicate that sustained inflammasome activity in wound Mp contributes to impaired early healing responses of diabetic wounds and that the inflammasome may represent a new therapeutic target for improving healing in diabetic individuals.

Objective: To compare the efficacy of wheelchair tilt-in-space and recline on enhancing muscle and skin perfusion over the ischial tuberosities in people with spinal cord injury (SCI)., Design: Repeated-measures and before-after trial design., Setting: University research laboratory., Participants: Power wheelchair users with SCI (N=20)., Interventions: Six combinations of wheelchair tilt-in-space and recline angles were presented to participants in a random order. The testing protocol consisted of a baseline 5 minutes sitting with no tilt/recline and 5 minutes positioned in a tilted and reclined position at each of 6 conditions, including: (1) 15° tilt-in-space and 100° recline, (2) 25° tilt-in-space and 100° recline, (3) 35° tilt-in-space and 100° recline, (4) 15° tilt-in-space and 120° recline, (5) 25° tilt-in-space and 120° recline, and (6) 35° tilt-in-space and 120° recline., Main Outcome Measures: Muscle and skin perfusion were assessed by near-infrared spectroscopy and laser Doppler flowmetry, respectively., Results: Muscle perfusion was significantly increased at 25° and 35° tilt-in-space when combined with 120° recline, and skin perfusion was significantly increased at 3 tilt-in-space angles (15°, 25°, 35°) when combined with 120° recline and at 35° tilt-in-space when combined with 100° recline (P<.05). Even in the positions of increased muscle perfusion and skin perfusion (25° and 35° of tilt-in-space combined with 120° of recline), the amount of muscle perfusion change was significantly lower than the amount of skin perfusion change (P<.05)., Conclusions: Our results indicate that a larger angle of tilt-in-space and recline is needed to improve muscle perfusion compared with skin perfusion. A position of 25° tilt-in-space combined with 120° recline is effective in enhancing muscle and skin perfusion of weight-bearing soft tissues at the ischial tuberosities., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Diabetic foot ulcers are one of the most common complications in diabetics, causing significant disabilities and decreasing the quality of life. Impaired microvascular reactivity contributes to the development of diabetic foot ulcers. However, underlying physiological mechanisms responsible for the impaired microvascular reactivity in response to extrinsic causative factors of foot ulcers such as mechanical and thermal stresses have not been well investigated. A total of 26 participants were recruited into this study, including 18 type 2 diabetics with peripheral neuropathy and 8 healthy controls. Laser Doppler flowmetry was used to measure skin blood flow at the first metatarsal head in response to a mechanical stress at 300mmHg and a fast thermal stress at 42°C. Wavelet analysis of skin blood flow oscillations was used to assess metabolic, neurogenic and myogenic controls. Our results indicated that diabetics have significantly decreased metabolic, neurogenic and myogenic responses to thermal stress, especially in the neurogenic and myogenic controls during the first vasodilatory response and in the metabolic control during the second vasodilatory response. Diabetics have a significantly decreased myogenic response to mechanical stress during reactive hyperemia. Our findings demonstrate that locally applied mechanical and thermal stresses can be used to assess microvascular reactivity and risk of diabetic foot ulcers., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Diabetes is associated with persistent inflammation and defective tissue repair responses. The hypothesis of this study was that interleukin (IL)-1β is part of a proinflammatory positive feedback loop that sustains a persistent proinflammatory wound macrophage phenotype that contributes to impaired healing in diabetes. Macrophages isolated from wounds in diabetic humans and mice exhibited a proinflammatory phenotype, including expression and secretion of IL-1β. The diabetic wound environment appears to be sufficient to induce these inflammatory phenomena because in vitro studies demonstrated that conditioned medium of both mouse and human wounds upregulates expression of proinflammatory genes and downregulates expression of prohealing factors in cultured macrophages. Furthermore, inhibiting the IL-1β pathway using a neutralizing antibody and macrophages from IL-1 receptor knockout mice blocked the conditioned medium-induced upregulation of proinflammatory genes and downregulation of prohealing factors. Importantly, inhibiting the IL-1β pathway in wounds of diabetic mice using a neutralizing antibody induced a switch from proinflammatory to healing-associated macrophage phenotypes, increased levels of wound growth factors, and improved healing of these wounds. Our findings indicate that targeting the IL-1β pathway represents a new therapeutic approach for improving the healing of diabetic wounds.

Wound healing is a complex pathway that requires cells, an appropriate biochemical environment (i.e., cytokines, chemokines), an extracellular matrix, perfusion, and the application of both macrostrain and microstrain. The process is both biochemically complex and energy dependent. Healing can be assisted in difficult cases through the use of physical modalities. In the current literature, there is much debate over which treatment modality, dosage level, and timing is optimal. The mechanism of action for both electrical stimulation and ultrasound are reviewed along with possible clinical applications for the plastic surgeon.

Triage is the process of prioritizing patient care based on need and available resources. Clinicians in wound clinics triage daily because time and resources never seem to be sufficient. The triage concept is taken to an extreme when a disaster strikes--the clinical goal of patient care transforms from the individual patient to providing the greatest good for the greatest number of patients. Situational awareness of system resources is of paramount importance in a disaster. Planning for surge capacity while simultaneously attending to patients who require immediate attention is a must. The recent earthquake in Haiti provided an opportunity to test those skill sets. Scores of clinicians volunteered their time and expertise, elevating wound care to the status of a clinical division. The experience of providing quality wound care despite a myriad of situational limitations suggests that busy wound clinics can learn valuable lessons from the realm of disaster management. The rate of under- and over-triage in wound clinics can be reduced by utilizing commonly collected outcomes and operational data. Patient safety improves when the hierarchy is flattened, communication is open, checklists are used, debriefings are held, and teamwork is encouraged. Reflecting on the working conditions in Haiti, it is clear that patients and clinicians benefit when success is measured by patient outcomes instead of individual accomplishments.

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Wound healing has evolved from gauze therapy to the use of proteomics, gene therapy, and cellular-based therapies in the short time span of 45 years. Education for health care providers has not kept pace with the logarithmic acceleration in technology development and treatment options. A patient with a non-healing wound requires a comprehensive work-up, including a focus on six primary points of interest. These points include the status of tissue perfusion, role of bacterial contamination, pressure applied to the tissue, the immune status of the host, co-morbid medical conditions including the patient's psychosocial status, and lastly, the status of the wound itself. Even after re-establishing macrovascular flow, many wounds either fail to improve or paradoxically worsen. Potential mechanisms for these unexpected findings include reperfusion injury, no-reflow, and the presence of stunned/hibernating tissue. Using the concept of mechanotransduction, the clinician can simulate normal pulsatile blood flow and re-establish adequate microvascular perfusion. Treatment regimens may include negative pressure therapy, electrical stimulation, ultrasound therapy, and other energy-based modalities.

Introduction: Maintenance debridement has been proposed as a therapeutic intervention to address the problem of chronic wounds characterized by an adequate wound bed but absent or slow healing. A panel of experts convened to address the rationale and method of maintenance debridement., Purpose: The goals of the panel were to summarize the scientific rationale for maintenance debridement, discuss the biochemical and cellular abnormalities in the wound bed, and provide a working algorithm for how maintenance debridement should be used., Methods: A multidisciplinary panel of wound healing and wound care experts comprising the fields of nursing, dermatology, internal medicine, and surgery was assembled to address maintenance debridement from different points of view and offer a unified approach., Findings: The chronic wound contains a number of microbial, biochemical, and cellular features and abnormalities that prevent or slow its progression to healing despite a seemingly adequate wound bed. Under these circumstances, maintenance debridement is proposed as a way to remove tissues that are colonized with an excessive bacterial burden and diminish what can be described as a biochemical and cellular burden that impairs healing. A working clinical algorithm is proposed., Conclusion: Maintenance debridement is a proactive way to "jump-start" the wound and keep it in a healing mode, even when traditional debridement may not appear necessary because of a seemingly "healthy" wound bed.

Unlabelled:  As healthcare providers prepare for pay for performance (P4P) and outcomes-based reimbursement strategies, it is increasingly important to document clinical results. Historically, healing rates have been reported from hospital-based, outpatient wound clinics. Time-to-healing curves from one site of care may not accurately reflect the entire healing "episode of care." Few outpatients from a wound clinic require hospitalization and even fewer are admitted to sub-acute care. Care setting and population risk strata must be clearly identified before comparing wound outcomes data., Aim: Primary objectives were to determine comparability of complete healing and 50% wound volume reduction of current and prior sub-acute care programs. Predictive value of Minimum Data Set (MDS 2.0) items on admission was also explored in discriminating healing versus nonhealing patients., Methods: Wound outcomes were analyzed for all patients (N = 101) treated at a dedicated sub-acute wound unit from January 2006 through April 2007 in a prospective, longitudinal, intent-to-treat, cohort study. Results were compared to prior sub-acute care wound outcomes reported by a similarly composed team using similar protocols., Results: Of 101 evaluable patients with 209 wounds, 41.6% healed in a median of 7.9 weeks while 31.6% achieved > 50% volume reduction. Outcomes were similar to prior sub-acute results, but less than the 72%-74% healing rate reported by a similar team in hospital outpatient clinic programs. Minimum Data Set comorbidities analyzed did not significantly predict nonhealing., Conclusion: To allow risk-adjusted P4P and reimbursement metrics, wound outcome reports should include clinical team involved, protocol utilization, care setting, and case mix severity to control for variables associated with different settings.

The history of surgery is rich with accomplishments in wound care, a legacy that recently has been abandoned by many surgeons only to be taken up by nonsurgical providers. When dealing with advanced wounds at the end of life, such as pressure ulcers or venous stasis ulcers, goals of treatment are relief of pain, elimination of odor, and control of wound exudates and infection. Benefits and risks of surgical intervention must be discussed with the patient and family in terms of the patient's perceived prognosis, extent of tissue necrosis and infection, the rate of deterioration, and the underlying wound pathogenesis. When appropriate, the role of surgery looms large in the treatment of chronic, advanced wounds, especially when minimally invasive surgical techniques are used.

Wound healing is a complex pathway that is energy dependent. Nonhealing wounds frequently require the use of physical modalities to achieve healing. There is much debate over which treatment modality to use, with varying clinical results in the literature. This review paper describes a common biochemical pathway that helps the clinician understand, at a molecular level, how the transference of energy to a wound can result in positive clinical results. The mechanisms of action for ultraviolet light, electrical stimulation, and ultrasound are reviewed along with a proposed biochemical roadmap. An emphasis on protein biochemistry is supported with an extensive review of the literature.

An estimated 15% of patients with diabetes will develop a foot ulcer sometime in their life, making them 30 to 40 times more likely to undergo amputation due to a non-healing foot ulcer than the non-diabetic population. To determine the safety and efficacy of a new, non-contact, kilohertz ultrasound therapy for the healing of recalcitrant diabetic foot ulcers - as well as to evaluate the impact on total closure and quantitative bacterial cultures and the effect on healing of various levels of sharp/surgical debridement - a randomized, double-blinded, sham-controlled, multicenter study was conducted in hospital-based and private wound care clinics. Patients (55 met criteria for efficacy analysis) received standard of care, which included products that provide a moist environment, offloading diabetic shoes and socks, debridement, wound evaluation, and measurement. The "therapy" was either active 40 KHz ultrasound delivered by a saline mist or a "sham device" which delivered a saline mist without the use of ultrasound. After 12 weeks of care, the proportion of wounds healed (defined as complete epithelialization without drainage) in the active ultrasound therapy device group was significantly higher than that in the sham control group (40.7% versus 14.3%, P = 0.0366, Fisher's exact test). The ultrasound treatment was easy to use and no difference in the number and type of adverse events between the two treatment groups was noted. Of interest, wounds were debrided at baseline followed by a quantitative culture biopsy. The results of these cultures demonstrated a significant bioburden (greater than 10(5)) in the majority of cases, despite a lack of clinical signs of infection. Compared to control, this therapeutic modality was found to increase the healing rate of recalcitrant, diabetic foot ulcers.

This article represents a process paper describing the development, at our facility, of a wound care fellowship that was scheduled to begin in July of 2003. The proposed program is in no way a finished product or our statement of how the program must be. This article is presented as a call to wound care professionals for input, criticism, guidance, and--we hope--adoption and acceptance of wound care fellowships in some format in the future. After many years of work in this field, it has become apparent that without medical specialization wound care will never rise from its current status of part-time avocation to full-time occupation. After a brief background and description of the present status of wound care education, an initial curriculum, program objectives, and clinical rotation schedule are presented. We look forward to the day when this program will have been replaced with a fully accredited, readily accepted, board-certifiable fellowship program with all the rights and responsibilities afforded the other medical specialties.

Many factors can negatively impact the wound-healing process leading to recalcitrant wounds. Biochemical and cellular commonalties can be identified across a number of wound etiologies. Healing data for various wound etiologies are presented, but these outcomes fail to show significant differences. Tissue perfusion, debridement, and wound fluid management can all impact healing. This review article discusses these topics and introduces a theoretical concept, the "stunned wound."

Integration is being discussed at all levels today in healthcare. The term is confusing and the literature provides numerous definitions and explanations. In general, integration refers to the coordination and reorganization of various healthcare units (such as home health care, acute care hospitals, and skilled nursing facilities) either horizontally, vertically, or via a combination of both. To discuss integration, a healthy understanding of managed care and healthcare trends are essential. With current and projected future trends serving as a backdrop, this article will attempt to describe various integration delivery models. The application of the above to wound care as a specific disease state serves as the closing message.

Background/aims: Phospholipids are the most important component of the plasma membrane in skin cells. Until recently, skin phospholipids have only been studied by chromatography and those results need confirmation by other methods such as (31) PNMR spectroscopy., Methods: Phospholipid profiles were analyzed from human skin and granulation tissue using (31) PNMR spectroscopy. Skin samples were taken from lower extremity amputation specimens and from one healthy volunteer. The granulation tissue was obtained from the wound bed of venous stasis ulcers, pressure ulcers and post-op non-healing surgical wounds. Phospholipid extractions were performed on full thickness skin samples (excluding the subcutaneous layer), epidermis, dermis, and granulation tissue biopsies., Results: Twelve phospholipid species were detected in each of the groups studied: PA, CL, DHSM, Eplas, PE, PS, SM, LPC, PI, AAPC, and PC. Statistically significant differences were found between epidermis and full thickness skin in relation to the quantity of PA, CL, DHSM, LPC, AAPC, and PC. The phospholipid ratio [(PE+Eplas+PI+PA)/PC] was calculated for each group: the epidermis value was 1.30, the dermis value was 0.62 and full thickness skin value was 0.49., Conclusions: These phospholipid profiles present a very unique distribution, which correlates with the physiological activity of the individual layer. The study of the phospholipid profile of granulation tissue opens a new line of research, evaluating changes in these profiles during the various phases of wound healing.

Pressure ulcers are an example of chronic medical problem that has a larger public health impact on our health care resources. An integrated health care delivery system is needed to attack the problem. A theoretical model recently put into place to address this issue is described.

Transforming the current event-driven reimbursement system into a quality powered marketplace will require clinical evaluation of how care is delivered. The managed care marketplace is evolving in three stages, from an event-driven, cost-avoidance model, to which the concepts of "value" and "quality" are added, with the final addition of a more "public health" focus. Clinical evaluation is a scientific process of outcomes assessment, clinical guidelines, and benchmarking. This process was applied to a hospital-based outpatient wound clinic, leading to a determination that the overall clinic Kaplan-Meier median time to healing could be improved. Two groups of patients were studied, 141 retrospectively from 1993 to 1994 and 57 prospectively in 1995. While there was no significant difference in the percentage healed between the groups, a significant difference in the median times to healing was revealed, which was linked to antibiotic use. Even when antibiotics were used prophylactically, the median times for healing were elevated from those without infections. Introspection led to fewer patients receiving preventive antibiotics. The overall lower median time to healing curve in 1995 can be explained by this change in clinical practice. This quality improvement demonstrates the utility of the clinical evaluation process as the healthcare marketplace evolves.

With the advent of managed care, wound care professionals have limited time to heal chronic wounds. They need to know whether the repair process is progressing or stagnating in response to treatments. Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopic measurements of chronic wound biochemistry yields rapid knowledge of whether a wound is generating, storing, or using energy. We used 31P NMR analysis on biopsy samples to explore the energy status of two chronic non-healing leg ulcers, before and after the first week of treatment with two low-pH hydrocolloid materials. Energy generation (i.e., energy "charge") was initially low in both wounds and was significantly elevated after 1 week of treatment. Earlier work has shown that leg ulcer pathophysiology is altered during the first week of hydrocolloid treatment. This work traces the origins of such effects deeper into the cellular biochemistry and correlates the measures with the final healing outcome. 31P NMR spectroscopy may provide a real-time biochemical "fingerprint" that shows clinicians the healing status of a questionable wound. Further study is needed to confirm the reliability and validity of 31P NMR spectroscopy as a predictor of healing outcomes in other wound environments.

The present trend in healthcare delivery is away from classic fee-for-service practices toward providing tightly controlled "products" in the form of Health Maintenance Organizations (HMO's). To thrive in this changing marketplace, wound clinic practitioners must understand the background of managed care and its terms, and be familiar with the concepts of capitation and incentives. Part of managed care's impact upon the specialty of wound care is that practitioners must define outcomes, healing rates and standards of care. Patient referral will depend on the cost effective delivery of care from all specialists in addition to the primary care physician. To meet these needs the authors created a hospital based wound care clinic with multiple interrelated areas of influence and have gathered statistical data. Managed care is here to stay and wound care practitioners must learn how to prepare for it and deal with it effectively.

Wound care has become a complicated science and specialty field of its own; however, all patients are initially seen by the primary care provider, and it is here that the greatest impact on wound healing and limb salvage can be made. Clinicians frequently treat chronic leg ulcers with a variety of products at various costs to the patients and third party payors based on experience not scientific literature, making the interpretation of outcomes difficult. With the problem of leg ulcers being so common, this paper sets out to review the basics of wound healing common to all wounds and to describe the current concepts of management of the three most common leg ulcers seen in a typical outpatient wound clinic setting: venous stasis ulcers, ischemic ulcers, and diabetic foot ulcers.

Purpose: To compare the usefulness of transluminal angioplasty coupled with thrombectomy versus surgical revision coupled with thrombectomy in the restoration and maintenance of flow in thrombosed dialysis access grafts., Materials and Methods: Twenty-four patients undergoing 28 angioplasty procedures were retrospectively compared to 24 patients who underwent 33 surgical revisions with a minimum 12-month follow-up period. All patients had thrombosed upper-arm expanded polytetrafluoroethylene (ePTFE) grafts., Results: Initial success rates were 88% for angioplasty and 87% for surgery. Mean primary patency for angioplasty and surgery was 4.6 and 3.3 months, respectively. Mean secondary patency for angioplasty and surgery was 5.4 and 4.5 months, respectively. These differences were not statistically significant. A significantly shorter hospital stay and lower anesthesia requirement were noted in the angioplasty group., Conclusion: Transluminal angioplasty coupled with Fogarty thrombectomy is an effective alternative to surgical revision for thrombosed dialysis access grafts. Angioplasty extends graft life, thereby preserving proximal venous outflow sites for future use.

Epidural anesthesia may be performed as a single injection or by staged doses. Thirty patients undergoing primary total hip replacement were randomly assigned to have epidural anesthesia using a single injection or a staged technique with 25 mL of 0.75% bupivacaine. Arterial plasma bupivacaine concentrations were significantly higher in the single injection group for the first 15 min but were not significantly different thereafter. Peak bupivacaine concentrations did not differ significantly between groups, but the time to achieve the peak concentration was delayed by staging injections (P = 0.001). Hemodynamic effects were similar between groups. Resolution of thoracic sensory block through T12 and duration of motor block measured by Bromage scale were both significantly longer in the staged injection group (P < 0.01). The method of epidural injection may affect resolution of neural block and the time to reach peak arterial plasma concentration of local anesthetic.