Skin Pigmentation Impacts the Clinical Diagnosis of Wound Infection: Imaging of Bacterial Burden to Overcome Diagnostic Limitations.

Underrepresentation of diverse skin tones in medical education and providers' implicit racial bias drives inequities in wound care, such as disproportionally poor outcomes for Black patients. Diagnostic indicators (e.g., erythema) can present differently depending on skin pigmentation. This post hoc analysis of 350 chronic wounds from a prospective 14-site clinical trial aimed to determine how the perception of clinical signs and symptoms of infection (CSS) differs by patient skin tone and if fluorescence-imaging can offer a more objective diagnostic solution. Participants were grouped by skin tone (low, medium, high) as measured by the Fitzpatrick Skin Phototype Classification (FSPC) scale. CSS and total bacterial load (TBL) were compared across FSPC groups, along with sensitivity to detect TBL >104 CFU/g using CSS alone and combined with fluorescence-imaging. Erythema was reported less often with increasing FSPC score (p = 0.05), from 13.4% (low), to 7.2% (medium), to 2.3% (high), despite comparable bacterial loads (median = 1.8 × 106 CFU/g). CSS sensitivity in the high group (2.9%) was 4.8-fold to 8.4-fold lower than the low (p = 0.003) and medium groups (p = 0.04). Fluorescence-imaging significantly improved the detection of high bacterial load in each group, peaking in the high group at 12-fold over CSS alone. These findings underscore the threat of pervasive racialized health inequities in wound care, where missed diagnosis of pathogenic bacteria and infection could delay treatment, increasing the risk of complications and poor outcomes. Fluorescence-imaging is poised to fill this gap, at least in part, serving as a more objective and equitable indicator of wound bacteria. Clinicaltrials.gov #NCT03540004 registered 16-05-2018.

Reliance on Clinical Signs and Symptoms Assessment Leads to Misuse of Antimicrobials: Post hoc Analysis of 350 Chronic Wounds.

Objectives: Bacteria frequently impede wound healing and cause infection. Clinicians rely on clinical signs and symptoms (CSS) to assess for bacteria at the point of care, and inform prescription of antibiotics and other antimicrobials. Yet, robust evidence suggests that CSS has poor sensitivity for detection of problematic bacterial burden and infection, hindering antimicrobial stewardship efforts. This study evaluated CSS-based antimicrobial prescribing practices across 14 wound care centers. Approach: Data were analyzed from the fluorescence assessment and guidance (FLAAG) trial, a study of 350 chronic wounds across 20 clinicians. Clinicians reviewed patient history and assessed for CSS using the International Wound Infection Institute infection checklist. Wounds with >3 criteria or any overwhelming symptom were considered CSS+. Bacterial levels were confirmed with quantitative tissue culture of wound biopsies. Results: Antimicrobials (including dressings, topicals, and systemic antibiotics) were prescribed at a similar rate for wounds identified as CSS+ (75.0%) and CSS- (72.8%, p = 0.76). Antimicrobial dressings, the most frequently prescribed antimicrobial, were prescribed at a similar rate for CSS+ (83.3%) and CSS- (89.5%, p = 0.27) wounds. In 33.3% of patients prescribed systemic antibiotics, no CSS were present. Prescribing patterns did not correlate with bacterial load. Innovation: This study is the first to evaluate antimicrobial prescribing trends in a large, multisite cohort of chronic wound patients. Conclusions: Reliance on CSS to diagnose clinically significant bacterial burden in chronic wounds leads to the haphazard use of antimicrobials. Improved methods of identifying bacterial burden and infection are needed to enhance antimicrobial stewardship efforts in wound care. Clinicaltrials.gov ID. NCT03540004.

Diagnostic Accuracy of Point-of-Care Fluorescence Imaging for the Detection of Bacterial Burden in Wounds: Results from the 350-Patient Fluorescence Imaging Assessment and Guidance Trial.

Objective: High bacterial load contributes to chronicity of wounds and is diagnosed based on assessment of clinical signs and symptoms (CSS) of infection, but these characteristics are poor predictors of bacterial burden. Point-of-care fluorescence imaging (FL) MolecuLight i:X can improve identification of wounds with high bacterial burden (>104 colony-forming unit [CFU]/g). FL detects bacteria, whether planktonic or in biofilm, but does not distinguish between the two. In this study, diagnostic accuracy of FL was compared to CSS during routine wound assessment. Postassessment, clinicians were surveyed to assess impact of FL on treatment plan. Approach: A prospective multicenter controlled study was conducted by 20 study clinicians from 14 outpatient advanced wound care centers across the United States. Wounds underwent assessment for CSS followed by FL. Biopsies were collected to confirm total bacterial load. Three hundred fifty patients completed the study (138 diabetic foot ulcers, 106 venous leg ulcers, 60 surgical sites, 22 pressure ulcers, and 24 others). Results: Around 287/350 wounds (82%) had bacterial loads >104 CFU/g, and CSS missed detection of 85% of these wounds. FL significantly increased detection of bacteria (>104 CFU/g) by fourfold, and this was consistent across wound types (p < 0.001). Specificity of CSS+FL remained comparably high to CSS (p = 1.0). FL information modified treatment plans (69% of wounds), influenced wound bed preparation (85%), and improved overall patient care (90%) as reported by study clinicians. Innovation: This novel noncontact, handheld FL device provides immediate, objective information on presence, location, and load of bacteria at point of care. Conclusion: Use of FL facilitates adherence to clinical guidelines recommending prompt detection and removal of bacterial burden to reduce wound infection and facilitate healing.

A Post-marketing Surveillance Study of Chronic Wounds Treated With a Native Collagen Calcium Alginate Dressing.

Chronic wounds (ie, wounds that fail to progress through a normal, orderly, timely sequence of repair) continue to pose significant clinical and economic burdens. A prospective, descriptive, 3-week post-marketing surveillance study was conducted across 3 wound care centers in the United States to evaluate the effectiveness of a collagen calcium alginate dressing on chronic wounds in conjunction with standard care (SC) practices (eg, offloading, debridement, compression) to support healing. Eligible participants had to be >18 years of age, have at least 1 chronic wound, and no known sensitivity to collagen. Demographic characteristics were recorded at the screening visit on case report forms. At each visit, wound-related pain was assessed using the Visual Analog Scale along with wound characteristics including size (using digital planimetry), wound exudate (minimal, moderate, heavy), and odor (none, mild). Participants were monitored for adverse events as well as infection based on signs and symptoms in and around the local wound bed, the deeper structures, and the surrounding skin. An intention-to-treat approach was used for all analyses. If an observation was missing, the last observation carried forward principle was used. For wounds that healed, pain and exudate were set to 0 (no pain/exudate) at visit 4. Descriptive, paired t tests and the Wilcoxon signed rank test were used to analyze the data. Of the 31 participants (15 men, 16 women, mean age 66.6 years), most (13, 42%) had a diabetic foot ulcer or venous leg ulcer (10, 32%); median duration of all wounds was 148 days. Thirty (30) patients completed the study. The mean number of comorbidities was 10.6 ± 6.3, and patients used a mean of 9.3 ± 5.64 prescription or over-the-counter medications. For all wounds combined, mean wound area was 4.8 ± 8.38 cm2 at baseline. At week 3, a decrease in wound area of 38.1% was noted (median: 45% ± 42.54; P = .006); 3 wounds healed completely. The change in wound exudate level from visit 1 to visit 4 was statistically significant (P = .006). No adverse events or infections occurred. In this population, the use of etiology-appropriate SC and a collagen calcium alginate dressing resulted in a decrease in wound area after 3 weeks of care. Longer-term studies to confirm these observations and controlled clinical studies to compare the effects of this dressing to other nongauze dressing treatments are needed.

A new approach to clinical research: Integrating clinical care, quality reporting, and research using a wound care network-based learning healthcare system.

The disparity between ideal evidence from randomized controlled trials and real-world evidence in medical research has prompted the United States Food and Drug Administration to consider the use of real-world data to better understand safety and effectiveness of new devices for a broader patient population and to prioritize real-world data in regulatory decision making. As the healthcare system transitions from volume- to value-based care, there is a growing need to harness the power of real-world data to change the paradigm for wound care clinical research and enable more generalizable clinical trials. This paper describes the implementation of a network-based learning healthcare system by a for-profit consortium of wound care clinics that integrates wound care management, quality improvement, and comparative effectiveness research, by harnessing structured real-world data within a purpose-built electronic health record at the point of care. Centers participating in the consortium submit their clinical data and quality measures to a qualified clinical data registry for wound care, enabling benchmarking of their data across this national network. The common definitional framework of the purpose-built electronic health record and the 21 wound-specific quality measures help to standardize the potential sources of bias in real-world data, making the consortium data useful for comparative effectiveness research. This consortium can transform wound care clinical research and raise the standards of care, while helping physicians achieve success with the Merit-Based Incentive Payment System.

Human Reticular Acellular Dermal Matrix in the Healing of Chronic Diabetic Foot Ulcerations that Failed Standard Conservative Treatment: A Retrospective Crossover Study.

BACKGROUND: Acellular matrices have been successfully used to heal indolent diabetic foot ulcers (DFUs). These tissues include allogenic dermis as well as xenograft dermis, pericardium, and small intestine submucosa. While all of these tissues show promise for healing DFUs, dermal-derived matrices have shown considerable potential. MATERIALS AND METHODS: The authors retrospectively reviewed healing in patients with DFUs that failed the standard of care (SOC) treatment from a previous prospective randomized, controlled trial (RCT). That trial compared the efficacy of human reticular acellular dermal matrices (HR-ADMs) with the SOC. Of the 16 out of 20 patients who did not heal in the SOC group, 12 were eligible for crossover treatment with the HR-ADM. The authors studied the rate of complete healing in that specific cohort after 12 weeks of crossover treatment. RESULTS: Of the 12 patients who were eligible for the HR-ADM, 10 (83%) achieved complete wound healing, with a mean healing time of 21 days to closure. The corresponding wound area reduction was from 1.7 cm2 to 0.6 cm2. The mean product cost to closure was $800/patient. CONCLUSION: This study further demonstrates the effectiveness of the HR-ADM in facilitating the closure of nonhealing DFUs refractory to SOC.

Defining a new diagnostic assessment parameter for wound care: Elevated protease activity, an indicator of nonhealing, for targeted protease-modulating treatment.

It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil-derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2-4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies.

Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective, randomised, controlled, multi-centre comparative study examining clinical efficacy and cost.

Advanced therapies such as bioengineered skin substitutes (BSS) and dehydrated human amnion/chorion membrane (dHACM) have been shown to promote healing of chronic diabetic ulcers. An interim analysis of data from 60 patients enrolled in a prospective, randomised, controlled, parallel group, multi-centre clinical trial showed that dHACM (EpiFix, MiMedx Group Inc., Marietta, GA) is superior to standard wound care (SWC) and BSS (Apligraf, Organogenesis, Inc., Canton, MA) in achieving complete wound closure within 4-6 weeks. Rates and time to closure at a longer time interval and factors influencing outcomes remained unassessed; therefore, the study was continued in order to achieve at least 100 patients. With the larger cohort, we compare clinical outcomes at 12 weeks in 100 patients with chronic lower extremity diabetic ulcers treated with weekly applications of Apligraf (n = 33), EpiFix (n = 32) or SWC (n = 35) with collagen-alginate dressing as controls. A Cox regression was performed to analyse the time to heal within 12 weeks, adjusting for all significant covariates. A Kaplan-Meier analysis was conducted to compare time-to-heal within 12 weeks for the three treatment groups. Clinical characteristics were well matched across study groups. The proportion of wounds achieving complete closure within the 12-week study period were 73% (24/33), 97% (31/32), and 51% (18/35) for Apligraf, EpiFix and SWC, respectively (adjusted P = 0·00019). Subjects treated with EpiFix had a very significant higher probability of their wounds healing [hazard ratio (HR: 5·66; adjusted P: 1·3 x 10(-7) ] compared to SWC alone. No difference in probability of healing was observed for the Apligraf and SWC groups. Patients treated with Apligraf were less likely to heal than those treated with EpiFix [HR: 0·30; 95% confidence interval (CI): 0·17-0·54; unadjusted P: 5·8 x 10(-5) ]. Increased wound size and presence of hypertension were significant factors that influenced healing. Mean time-to-heal within 12 weeks was 47·9 days (95% CI: 38·2-57·7) with Apligraf, 23·6 days (95% CI: 17·0-30·2) with EpiFix group and 57·4 days (95%CI: 48·2-66·6) with the SWC alone group (adjusted P = 3·2 x 10(-7) ). Median number of grafts used per healed wound were six (range 1-13) and 2·5 (range 1-12) for the Apligraf and EpiFix groups, respectively. Median graft cost was $8918 (range $1,486-19,323) per healed wound for the Apligraf group and $1,517 (range $434-25,710) per healed wound in the EpiFix group (P < 0·0001). These results provide further evidence of the clinical and resource utilisation superiority of EpiFix compared to Apligraf for the treatment of lower extremity diabetic wounds.

Use of a fluorescence angiography system in assessment of lower extremity ulcers in patients with peripheral arterial disease: A review and a look forward.

The prevalence of chronic wounds is sharply rising throughout the world due to an aging population and increases in the incidence of obesity, diabetes, and cardiovascular diseases. People with diabetes, hypertension, and hyperlipidemia are at increased risk for developing peripheral arterial disease (PAD). PAD affects 8 to 12 million people over the age of 40 years in the United States and it is a major contributing factor to the development of lower extremity ulcers. Although a number of noninvasive diagnostic tests are available to detect PAD in lower extremities, they have several clinical limitations. In this review, current understanding of the pathophysiology of commonly seen lower extremity ulcers is described and vascular assessments typically used in practice are evaluated. In addition, application of the LUNA Fluorescence Angiography System (Novadaq, Bonita Springs, FL) for the screening and treatment of complex nonhealing wounds in patients with PAD is discussed.