Growth factors for treating chronic venous leg ulcers: A systematic review and meta-analysis.

Chronic venous leg ulcers (VLU) are wounds that commonly occur due to venous insufficiency. Many growth factors have been introduced over the past two decades to treat VLU. This systematic review and meta-analysis evaluates the impact of growth factor treatments of VLU in comparison to control for complete wound healing, percent reduction in wound area, time to wound healing, and adverse events. A systematic review and meta-analysis of randomised trials was conducted. MEDLINE and EMBASE were searched up to December 2020. Studies were included if they compared a growth factor versus placebo or standard care in patients with VLU. From 1645 articles, 13 trials were included (n = 991). There was a significant difference between any growth factor and placebo in complete wound healing (P = 0.04). Any growth factor compared to placebo significantly increased the likelihood of percent wound reduction by 48.80% (P = <0.00001). There was no difference in overall adverse event rate. Most comparisons have low certainty of evidence according to Grading of Recommendations, Assessment, Development, and Evaluation. This meta-analysis suggests that growth factors have a beneficial effect in complete wound healing of VLU. Growth factors may also increase percent reduction in wound area. The suggestion of benefit for growth factors identified in this review is not a strong one based on the low quality of evidence.

Evaluation of wound fluid biomarkers to determine healing in adults with venous leg ulcers: A prospective study.

Clinical practice guidelines recommend using repeated wound surface area measurements to determine if a chronic ulcer is healing. This results in delays in determining the healing status. This study aimed to evaluate whether any of a panel of biomarkers can determine the healing status of chronic venous leg ulcers. Forty-two patients with chronic venous leg ulcers had their wound measured and wound fluid collected at weekly time points for 13 weeks. Wound fluid was analyzed using multiplex enzyme-linked immunosorbent assay to determine the concentration of biomarkers in the wound fluid at each weekly time point. Healing status was determined by examining the change in wound size at the previous and subsequent weeks. Predictive accuracy with 95% confidence intervals (CI) is reported. Of 42 patients, 105 evaluable weekly time points were obtained, with 32 classified as healing, 27 as nonhealing, and 46 as indeterminate. Thirteen biomarkers significantly differed between healing and nonhealing wounds (p < 0.1) and were included in a multivariate logistic regression model. Granulocyte macrophage-colony stimulating factor (p < 0.001) and matrix metalloprotease-13 (p = 0.004) were the best predictors of wound healing. Receiver operating characteristic curves indicated 92% accuracy (95% CI: 85%,100%) for granulocyte macrophage-colony stimulating factor, and 78% accuracy (95% CI: 65%,90%) for matrix metalloprotease-13 in discriminating between healing and nonhealing wounds. This study found that two biomarkers from wound fluid can predict healing status in chronic venous leg ulcers. These findings may lead to the ability to determine the future trajectory of a wound and the ability to modify treatment accordingly.

Reliability and measurement error of digital planimetry for the measurement of chronic venous leg ulcers.

Area measurements of a chronic wound are the gold standard outcome measure to determine if a wound is on a healing or nonhealing trajectory. The use of digital planimetry can provide increased accuracy in measuring wound area however it is important to know the reliability and measurement error of these devices when used by multiple assessors. The aim of this study is to determine the within rater, between rater, and standard error of measurement of a digital planimetry device. Wound area in 42 patients was measured weekly for 12 weeks by two different raters, with each rater measuring the wound 10 times per visit. Intraclass correlation coefficients (ICC 1,k) and standard error of measurement were calculated for both within and between raters using 10 and the first three repeated measures to determine if using less measurements was as reliable. The true change in wound area was calculated by dividing stander error of measurements by mean wound areas. Within rater reliability for raters 1 and 2 were 0.995 and 0.992 for 10 measurements, and 0.996 and 0.992 for 3 measurements per time point. Between rater reliability was 0.979 for 10 measurements and 0.996 for 3 measurements per time point. The within rater standard error of measurement for raters 1 and 2 was 0.98 cm2 and 1.28 cm2 for 10 measurements and 0.895 cm2 and 1.29 cm2 for 3 measurements at each time point. The standard error of measurement for between raters was 2.07 cm2 for 10 measurements and 2.25 cm2 for 3 measurements per time point. The true change in wound size varied from 6.4% for within one rater to 15.7% for across different raters. This study found that both within and between rater reliability of the digital planimetry device was very high for three measurements per time point.