Molecular characterization of chronic cutaneous wounds reveals subregion- and wound type-specific differential gene expression.

A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.

The impact of the SARS-CoV-2 pandemic on the management of chronic limb-threatening ischemia and wound care.

In the wake of the coronavirus pandemic, the critical limb ischemia (CLI) Global Society aims to develop improved clinical guidance that will inform better care standards to reduce tissue loss and amputations during and following the new SARS-CoV-2 era. This will include developing standards of practice, improve gaps in care, and design improved research protocols to study new chronic limb-threatening ischemia treatment and diagnostic options. Following a round table discussion that identified hypotheses and suppositions the wound care community had during the SARS-CoV-2 pandemic, the CLI Global Society undertook a critical review of literature using PubMed to confirm or rebut these hypotheses, identify knowledge gaps, and analyse the findings in terms of what in wound care has changed due to the pandemic and what wound care providers need to do differently as a result of these changes. Evidence was graded using the Oxford Centre for Evidence-Based Medicine scheme. The majority of hypotheses and related suppositions were confirmed, but there is noticeable heterogeneity, so the experiences reported herein are not universal for wound care providers and centres. Moreover, the effects of the dynamic pandemic vary over time in geographic areas. Wound care will unlikely return to prepandemic practices. Importantly, Levels 2-5 evidence reveals a paradigm shift in wound care towards a hybrid telemedicine and home healthcare model to keep patients at home to minimize the number of in-person visits at clinics and hospitalizations, with the exception of severe cases such as chronic limb-threatening ischemia. The use of telemedicine and home care will likely continue and improve in the postpandemic era.

Modern multidisciplinary team approach is crucial in treatment for critical limb threatening ischemia.

The aim of this study was to provide a brief overview of the history the multidisciplinary team approach, highlighting the benefit to the patient with critical limb threatening ischemia in relation to health care economics. Furthermore, we provided a description of the requisites and key components, showing how to build a multidisciplinary team.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 3: The Patient Survey.

The 2006 U.S. Food and Drug Administration Guidance for Industry emphasizes wound closure as the primary outcome for clinical trials in wound healing. Wound care professionals understand that complete wound healing is not always achievable when evaluating new treatments. FDA, Association for the Advancement of Wound Care, and Wound Healing Society are working collaboratively to identify scientifically achievable, clinically relevant, and patient-centered endpoints with sufficient support to serve as primary outcomes for clinical trials. The Opinion Survey from People with Wounds presented here addresses an important but understudied issue: the gap between clinician, healthcare insurance companies, government agencies, and patient perspectives regarding clinically meaningful and scientifically achievable primary endpoints for wound care. The survey, adapted from the clinician survey with adjustment for health literacy, was pilot tested and revised based on a limited number of patients in a single clinic. After central IRB approval, the on-line survey was administered in English and Spanish and submitted anonymously to a server with the cooperation of multiple wound clinics and societies. Four hundred and thirty-eight patients and caregivers from across the United States responded over a 10-month period. Based on this survey, the most valuable clinical endpoints were reduced infection, recurrence, and amputation. The most valuable quality of life outcomes were increased independence, reduced social isolation, and pain. The top five endpoints in terms of usefulness for measuring clinical trial success were time to heal, wound size, infection, recurrence, and pain. Narrative responses from wound patients emphasized the inability to perform activities of daily living and pain as major factors that impacted their daily lives. Engagement of patients in clinical trials and evaluation of potential treatments is critical to improving wound care. This survey provides insight into the needs of patients with wounds and provides a roadmap for structuring future clinical trials to better meet those needs.

Digital Subtraction Angiography Prior to an Amputation for Critical Limb Ischemia (CLI): An Expert Recommendation Statement From the CLI Global Society to Optimize Limb Salvage.

Despite recent guideline updates on peripheral artery disease (PAD) and critical limb ischemia (CLI) treatment, the optimal treatment for CLI is still being debated. As a result, care is inconsistent, with many CLI patients undergoing an amputation prior to what many consider to be mandatory: consultation with an interdisciplinary specialty care team and a comprehensive imaging assessment. More importantly, quality imaging is critical in CLI patients with below-the-knee disease. Therefore, the CLI Global Society has put forth an interdisciplinary expert recommendation for superselective digital subtraction angiography (DSA) that includes the ankle and foot in properly indicated CLI patients to optimize limb salvage. A recommended imaging algorithm for CLI patients is included.

One-Year Outcomes of Peripheral Endovascular Device Intervention in Critical Limb Ischemia Patients: Sub-Analysis of the LIBERTY 360 Study.

BACKGROUND: High-risk patients with advanced peripheral artery disease (PAD), including critical limb ischemia (CLI), are often excluded from peripheral endovascular device intervention clinical trials, leading to difficulty in translating trial results into real-world practice. There is a need for prospectively assessed studies to evaluate peripheral endovascular device intervention outcomes in CLI patients. METHODS: LIBERTY 360 is a prospective, observational, multi-center study designed to evaluate the procedural and long-term clinical outcomes of peripheral endovascular device intervention in real-world patients with symptomatic lower-extremity PAD. One thousand two hundred and four patients were enrolled and stratified based on Rutherford Classification (RC): RC2-3 (N=501), RC4-5 (N=603), and RC6 (N=100). For this sub-analysis, RC5 and RC6 patients (RC5-6; N=404) were pooled and 1-year outcomes were assessed. RESULTS: Procedural complications rarely (1.7%) resulted in post-procedural hospitalization and 89.1% of RC5-6 patients were discharged to home. Considering the advanced disease state in RC5-6 patients, there was a high freedom from 1-year major adverse event rate of 65.5% (defined as target vessel revascularization, death to 30 days, and major target limb amputation). At 1 year, freedom from major amputation was 89.6%. Wounds identified at baseline on the target limb had completely healed in 172/243 (70.8%) of the RC5-6 subjects by 1 year. Additionally, the overall quality of life, as measured by VascuQoL, improved from baseline to 1 year. CONCLUSION: LIBERTY investigated real-world PAD patients with independent oversight of outcomes. This analysis of LIBERTY RC5-6 patients demonstrates that peripheral endovascular device intervention can be successful in CLI patients, with low rates of major amputation and improvement in wound healing and quality of life through 1-year follow-up.LIBERTY 360, https://clinicaltrials.gov/ct2/show/NCT01855412, ClinicalTrials.gov Identifier: NCT01855412.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 2. Literature survey.

Patients with wounds bear significant clinical, personal, and economic burdens yet complete wound healing is the only United States Food and Drug Administration (FDA) recognized primary clinical trial end point. The overall goal of this project is to work with FDA to expand the list of acceptable primary end points, recognizing that new and innovative treatments, devices, and drugs may not have complete healing as the focus. Part 1 of the project surveyed 628 wound care experts who identified and content-validated 15 end points most relevant to clinical practice and benefitting patients' lives as primary outcomes in clinical trials. Part 2 is focused on critical appraisal of the evidence in the wound care literature supporting FDA criteria to qualify these 15 end points as primary end points in clinical trials. Further research involved systematic review of the literature regarding the most promising end points. Forty volunteer, interdisciplinary, wound healing experts in fields related to the end points compiled evidence from systematic MEDLINE searches and society databases supporting the FDA criteria of reliability, clinical construct validity, capacity to detect concurrent or longitudinal change, and responder analysis. The search revealed 485 references involving over 462,000 subjects supporting FDA-required parameters for all 15 end points More than 50 references supported FDA-required parameters qualifying the following outcomes for use in clinical trials supporting interventions for FDA clearance: Pain reduction, Physical function and ambulation, Infection reduction, Time to heal, and Percent wound area reduction in 4-8 weeks. Among these, only Time to heal is currently recognized by the FDA as a primary wound outcome in clinical trials. These results suggest that wound science is already serving patients and professionals by improving these content-validated outcomes that merit regulatory consideration.

Does noncontact low-frequency ultrasound therapy contribute to wound healing at the molecular level?

Noncontact low-frequency ultrasound (NLFU) is used to treat various types of chronic wounds including venous, diabetic, and pressure ulcers. The objective for this substudy of the IN BALANCE RCT VLU trial was to characterize and compare the NLFU treatment group and patients receiving standard of care (SOC) with respect to the effect of the assigned study treatment on content/quantity of inflammatory cytokines and fibrinogen as well as bacteria. Higher mean wound area reduction was observed in the NLFU treatment group (67.0%) compared to the SOC group (41.6%, p < 0.05). Hypertension, diabetes type II, coronary artery disease, and anemia were identified as the most common comorbidities of the Chronic venous leg ulcer (CVLU) patients included in the study. Pseudomonas, Corynebacterium, and unclassified Enterobacteriaceae were dominant in the highest number of samples. Anaerococcus, Peptoniphilus, and Finegoldia, had the highest median proportion in the samples overall. Peptoniphilus abundance decreased more in the NLFU treatment group relative to SOC; similar trends were observed for Anaerococcus and Finegoldia. Progression of mediators like TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 as well as PF4, TGF-beta, and fibrinogen was monitored and trends for several of the mediators were identified. Fibrinogen amounts were significantly reduced over time in the NLFU treatment group (p < 0.05). IL-8 levels declined in wound fluid from NLFU responders as well as SOC responders. Bacterial load (total bacterial abundance) determined local parameters of ulcer inflammation. If a bioburden of ≥ 10E5 was found compared to < 10E5 , levels of IL-1beta, IL-8, and TNF-alpha were significantly higher. In conclusion, NLFU treatment is an effective adjuvant tool for CVLU therapy. This study demonstrates that it improves wound healing by equally inhibiting abundant levels of pro-inflammatory cytokines as well as by reducing the overall bacterial burden.

A Prospective, Randomized, Blinded, Controlled Trial Comparing Transdermal Continuous Oxygen Delivery to Moist Wound Therapy for the Treatment of Diabetic Foot Ulcers.

Worldwide, diabetic foot ulcers (DFUs) continue to exact a major burden on patients and health care providers. Although hyperbaric oxygen therapy is well-known as an adjunct option, less is known about the efficacy of transdermal continuous oxygen therapy (TCOT). A prospective, randomized, blinded, multicenter, parallel study was conducted from October 2009 to November 2012 to evaluate healing time and the proportion of DFUs healed after 12 weeks of moist wound therapy (MWT) with or without TCOT. Study participants (persons with type 1 or type 2 diabetes and a nonhealing [>1-month but <1-year duration], 1 cm² to 10 cm² in area, infection-free DFU) were randomized to TCOT or a sham device (control) in addition to receiving MWT. TCOT treatment consisted of continuous administration of 98+% oxygen to the wound site using a 15-day device with dressings changed every 3 to 7 days per care plan or more often when clinically required. Potential participants completed demographic and clinical screening and wound and laboratory evaluations at baseline, and wound evaluations, evaluation of adverse events, debridement, and treatment once weekly until the wound healed or up to 12 weeks. The primary endpoint was defined as complete wound closure by week 12. Wound measurements were made utilizing acetate tracings. Original tracings were collected at approximately 6-week intervals and analyzed upon study closure. Data were collected via paper Case Report Forms and entered into an electronic database after the patient's final visit. Statistical analysis was performed on datasets exported from the electronic database. Wound measurement data were analyzed using chi-squared. Time to complete closure was analyzed using Kaplan-Meier analysis in conjunction with the log-rank test. Of the 130 potential participants, 8 with protocol violations were excluded from analysis. In the intent-to-treat (ITT) population (N = 122, average age 59 years [range 28-85 years]), the majority were male (74%), Caucasian (81%), and had a plantar ulcer (76%). Mean baseline wound area was 2.3 ± 1.7 cm² (range 0.4-8.9 cm2) and 2.0 ± 1.7 cm² (range 0.6-8.7 cm²) in the control and TCOT groups, respectively. HbA1c (%) was 7.9 ± 1.7 in the control and 8.0 ± 1.7 in the treatment group. In the TCOT group, 35 of 65 (54%) wounds healed compared to 31 of 63 (49%) in the control arm (P = .4167). In the per-protocol population (PP) (ie, patients without protocol violations), 34 of 61 wounds (56%) in the TCOT group and 31 of 61 (49%) in the control group healed. In the ≥65 years PP subgroup, 14 of 17 (82%) in the TCOT and 8 of 16 (50%) in the control arm healed (P = .049). Median time to complete closure in the PP group was 63 days for the TCOT and 77 days for the control group (P >.05). No device-related serious adverse events occurred in either group. Wound outcomes of patients in both groups were good, but the TCOT device did not appear to offer added benefit over moist wound healing treatment and offloading to facilitate the healing of small, nonsevere diabetic foot ulcers of relatively healthy patients. The data suggest the device may offer a greater benefit to older patients. Studies including a more diverse and larger sample patient population are warranted.

Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

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.

Cost-effectiveness of negative pressure wound therapy in patients with many comorbidities and severe wounds of various etiology.

This study analyzed a cross-section of patients with severe chronic wounds and multiple comorbidities at an outpatient wound clinic, with regard to the cost-effectiveness and cost-benefit of negative pressure wound therapy (intervention) vs. no negative pressure wound therapy (control) at 1 and 2 years. Medicare reimbursement charges for wound care were used to calculate costs. Amputation charges were assessed using diagnosis-related groups. Cost-benefit analysis was based on ulcer-free months and cost-effectiveness on quality-adjusted life-years. Undiscounted costs, benefits, quality-adjusted life-years, undiscounted and discounted incremental net health benefits, and incremental cost-effectiveness ratios were calculated for unmatched and matched cohorts. There were 150 subjects in the intervention group and 154 controls before matching and 103 subjects in each of the matched cohorts. Time to heal for the intervention cohort was significantly shorter compared to the controls (270 vs. 635 days, p = 1.0 × 10-7 , matched cohorts). The intervention cohort had higher benefits and quality-adjusted life-year gains compared to the control cohort at years 1 and 2; by year 2, the gains were 68-73% higher. In the unmatched cohorts, the incremental net health benefit was $9,933 per ulcer-free month at year 2 for the intervention; the incremental cost-effectiveness ratio was -825,271 per quality-adjusted life-year gained (undiscounted costs and benefits). For the matched cohorts, the incremental net health benefits was only $1,371 per ulcer-free month for the intervention, but the incremental cost-effectiveness ratio was $366,683 per quality-adjusted life-year gained for year 2 (discounted costs and benefits). In a patient population with severe chronic wounds and serious comorbidities, negative pressure wound therapy resulted in faster healing wounds and was more cost-effective with greater cost-benefits than not using negative pressure wound therapy. Regarding overall cost-effectiveness, the intervention was still expensive, but that is the reality amidst limited treatment options for such serious cases of chronic wounds.

Clinical interventions for venous leg ulcers: Proposals to improve the quality of clinical leg ulcer research.

The present status of clinical leg ulcer healing research was reviewed by 25 experts over 2 days on September 28 and 29, 2015. Multiple clinical effectiveness reviews were presented suggesting that published clinical wound healing research often does not meet present (2015) evidence based standards. Specific areas requiring remediation were highlighted and approaches to overcoming existing challenges were proposed. Participants using anonymous voting technology developed an action plan to resolve perceived deficiencies. Statements were accepted if 75% of participants agreed. Older patients with a high frequency of comorbid conditions posed particular difficulties in designing clinical research protocols and better diagnostic categorization is necessary A standardized model template for collecting information about diagnosis and evaluation of the effect of interventions on healing of all types of leg ulcers was considered a high priority. Such a model template could be modified depending on the specific etiology of the leg ulcers. Generally agreed on quantifiable standards to establish degree of morbidity was considered a high priority. There was universal agreement that sources of funding and conflicts of interest needed to be disclosed in presentations and all publications. All clinical research studies should be registered with appropriate authorities. There was substantial enthusiasm for a clinical research network with quality standards for membership and an advisory research core available to investigators. Such a network should be funded and actively managed to insure long-term viability. The governance of such an entity needs to be established by the wound care community. The present trend to integrate patients into the clinical research process was endorsed and there was enthusiasm to develop patient advocacy for wound healing research.

Treatment of a High-Risk Diabetic Patient with Peripheral Vascular Disease and Osteomyelitis.

We report a case of calcaneal osteomyelitis that was surgically resected from a patient with diabetes and peripheral vascular disease. A 91-year-old male with history of type 2 diabetes, peripheral vascular disease, balloon angioplasty, and recent (2 months ago) stent of the superficial femoral artery presented to the emergency department with a left heel wound infection probed to bone. The patient reported having been on intravenous Zosyn for several months via an outside infectious disease provider for clinical suspicion of osteomyelitis, but noted no improvement. This report includes information regarding the clinical examination and imaging findings, which were used to assess this high-risk patient. Our patient underwent a partial calcanectomy and completed a 6-week course of intravenous antibiotics. The purpose of this case report is to illustrate limb preservation in a high-risk patient with compromised vascular supply who underwent a partial calcanectomy for treatment of calcaneal osteomyelitis. The patient underwent surgical resection of the calcaneus without complications and healed unremarkably with the ability to ambulate while wearing an ankle foot orthosis with a custom shoe. This report was authorized for publication as an educational report to contribute to generalizable knowledge and does not include any patient health information.

The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine.

BACKGROUND: Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline. METHODS: The committee made specific practice recommendations using the Grades of Recommendation Assessment, Development, and Evaluation system. This was based on five systematic reviews of the literature. Specific areas of focus included (1) prevention of diabetic foot ulceration, (2) off-loading, (3) diagnosis of osteomyelitis, (4) wound care, and (5) peripheral arterial disease. RESULTS: Although we identified only limited high-quality evidence for many of the critical questions, we used the best available evidence and considered the patients' values and preferences and the clinical context to develop these guidelines. We include preventive recommendations such as those for adequate glycemic control, periodic foot inspection, and patient and family education. We recommend using custom therapeutic footwear in high-risk diabetic patients, including those with significant neuropathy, foot deformities, or previous amputation. In patients with plantar diabetic foot ulcer (DFU), we recommend off-loading with a total contact cast or irremovable fixed ankle walking boot. In patients with a new DFU, we recommend probe to bone test and plain films to be followed by magnetic resonance imaging if a soft tissue abscess or osteomyelitis is suspected. We provide recommendations on comprehensive wound care and various débridement methods. For DFUs that fail to improve (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, we recommend adjunctive wound therapy options. In patients with DFU who have peripheral arterial disease, we recommend revascularization by either surgical bypass or endovascular therapy. CONCLUSIONS: Whereas these guidelines have addressed five key areas in the care of DFUs, they do not cover all the aspects of this complex condition. Going forward as future evidence accumulates, we plan to update our recommendations accordingly.

A clinical trial of Integra Template for diabetic foot ulcer treatment.

Individuals with diabetes mellitus are at an increased risk of developing a diabetic foot ulcer (DFU). This study evaluated the safety and efficacy of Integra Dermal Regeneration Template (IDRT) for the treatment of nonhealing DFUs. The Foot Ulcer New Dermal Replacement Study was a multicenter, randomized, controlled, parallel group clinical trial conducted under an Investigational Device Exemption. Thirty-two sites enrolled and randomized 307 subjects with at least one DFU. Consented patients were entered into the 14-day run-in phase where they were treated with the standard of care (0.9% sodium chloride gel) plus a secondary dressing and an offloading/protective device. Patients with less than 30% reepithelialization of the study ulcer after the run-in phase were randomized into the treatment phase. The subjects were randomized to the control treatment group (0.9% sodium chloride gel; n = 153) or the active treatment group (IDRT, n = 154). The treatment phase was 16 weeks or until confirmation of complete wound closure (100% reepithelialization of the wound surface), whichever occurred first. Following the treatment phase, all subjects were followed for 12 weeks. Complete DFU closure during the treatment phase was significantly greater with IDRT treatment (51%) than control treatment (32%; p = 0.001) at sixteen weeks. The median time to complete DFU closure was 43 days for IDRT subjects and 78 days for control subjects in wounds that healed. The rate of wound size reduction was 7.2% per week for IDRT subjects vs. 4.8% per week for control subjects (p = 0.012). For the treatment of chronic DFUs, IDRT treatment decreased the time to complete wound closure, increased the rate of wound closure, improved components of quality of life and had less adverse events compared with the standard of care treatment. IDRT could greatly enhance the treatment of nonhealing DFUs.

Case studies evaluating transdermal continuous oxygen for the treatment of chronic sickle cell ulcers.

OBJECTIVE: Refractory leg ulcerations are common in homozygous sickle cell anemia. In this case series, patients were treated with transdermal continuous oxygen therapy (TCOT), based on the hypothesis that oxygen deprivation caused by arteriovenous shunting may be remedied by providing oxygen directly to the wound bed. The authors believe this is the first attempt to treat sickle cell ulcers with TCOT. CASE PRESENTATION: Five patients with long histories of recurring sickle cell disease ulcers that would not heal with various conventional and/or other adjunctive wound healing modalities were treated with TCOT. The patients had recurring nonhealing wounds for 30, 21, 20, 20, and 15 years, respectively. All 5 patients healed or showed substantial improvement in the treatment periods of 3 to 36 weeks. CONCLUSION: The authors conclude that TCOT may be a novel, effective, and inexpensive modality in treating patients with sickle cell disease ulcers. Improvement was typically noticeable within 2 weeks. Further clinical trials may be considered to evaluate the efficacy of TCOT in sickle cell ulcers.

A prospective, randomized, controlled trial comparing the effects of noncontact, low-frequency ultrasound to standard care in healing venous leg ulcers.

Current scientific evidence suggests venous leg ulcers (VLUs) that do not respond to guideline-defined care may have a wound microenvironment that is out of physiological balance. A prospective, randomized, controlled, multicenter trial was conducted to compare percent wound size reduction, proportions healed, pain, and quality-of-life (QOL) outcomes in patients randomized to standard care (SC) alone or SC and 40 kHz noncontact, low-frequency ultrasound (NLFU) treatments 3 times per week for 4 weeks. One hundred, twelve (112) eligible participants with documented venous stasis, a VLU >30 days' duration, measuring 4 cm2 to 50 cm2, and demonstrated arterial flow were enrolled. Of these, 81 reduced <30% in size during the 2-week run-in study phase and were randomized (SC, n = 40; NLFU+SC, n = 41). Median age of participants was 59 years; 83% had multiple complex comorbidities. Index ulcers were 56% recurrent, with a median duration of 10.3 months (range 1 month to 204.5 months) and median ulcer area of 11.0 cm2 (range 3.7 cm2-41.3 cm2). All participants received protocol-defined SC compression (30-40 mm Hg), dressings to promote a moist wound environment, and sharp debridement at the bedside for a minimum of 1 time per week. Ulcer measurements were obtained weekly using digital planimetry. Pain and QOL scores were assessed at baseline and after 4 weeks of treatment using the Visual Analog Scale and the Short Form-36 Health Survey. After 4 weeks of treatment, average wound size reduction was 61.6% ± 28.9 in the NLFU+SC compared to 45% ± 32.5 in the SC group (P = 0.02). Reductions in median (65.7% versus 44.4%, P = 0.02) and absolute wound area (9.0 cm2 versus 4.1 cm2, P = 0.003) as well as pain scores (from 3.0 to 0.6 versus 3.0 to 2.4, P = 0.01) were also significant. NLFU therapy with guideline-defined standard VLU care should be considered for healing VLUs not responding to SC alone. The results of this study warrant further research on barriers to healing and the changes occurring in the tissue of the wound to explore theories that the microenvironment impacts wounds that do not heal despite provision of guideline-defined care.

Human acellular dermal wound matrix: evidence and experience.

A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM.

Evaluation of wound care and health-care use costs in patients with diabetic foot ulcers treated with negative pressure wound therapy versus advanced moist wound therapy.

BACKGROUND: We conducted a post-hoc retrospective analysis of patients enrolled in a randomized controlled trial to evaluate overall costs of negative pressure wound therapy (NPWT; V.A.C. Therapy; KCI USA, Inc, San Antonio, Texas) versus advanced moist wound therapy (AMWT) in treating grade 2 and 3 diabetic foot wounds during a 12-week therapy course. METHODS: Data from two study arms (NPWT [n = 169] or AMWT [n = 166]) originating from Protocol VAC2001-08 were collected from patient records and used as the basis of the calculations performed in our cost analysis. RESULTS: A total of 324 patient records (NPWT = 162; AMWT = 162) were analyzed. There was a median wound area reduction of 85.0% from baseline in patients treated with NPWT compared to a 61.8% reduction in those treated with AMWT. The total cost for all patients, regardless of closure, was $1,941,472.07 in the NPWT group compared to $2,196,315.86 in the AMWT group. In patients who achieved complete wound closure, the mean cost per patient in the NPWT group was $10,172 compared to $9,505 in the AMWT group; the median cost per 1 cm(2) of closure was $1,227 with NPWT and $1,695 with AMWT. In patients who did not achieve complete wound closure, the mean total wound care cost per patient in the NPWT group was $13,262, compared to $15,069 in the AMWT group. The median cost to close 1 cm(2) in wounds that didn't heal using NPWT was $1,633, compared to $2,927 with AMWT. CONCLUSIONS: Our results show greater cost effectiveness with NPWT versus AMWT in recalcitrant wounds that didn't close during a 12-week period, due to lower expenditures on procedures and use of health-care resources.