Aging influences wound healing in patients with chronic lower extremity wounds treated in a specialized wound care center

With the dramatic increase in the aging population, the study and care of wounds in the elderly have become priority topics for both researchers and clinicians. The effects of aging on wound healing in humans have remained controversial. The study was a 5-year epidemiological evaluation of standardized data collected regularly during patients' visits at a specialized Wound Care Center with the aim to determine the key factors influencing the healing of chronic lower extremity wounds. In this analysis of 1,158 chronic wounds, the frequency of wound closure was statistically significantly lower in older patients compared with younger patients. The share of closed wounds decreased by nearly 25% in the elderly patients (≥70 years). The relationship between the patient's age and the proportion of wound closure was nonlinear. The effect of aging on the frequency of wound closure of chronic wounds became clinically apparent after age 60. The chronicity of the wounds was illustrated by their recurrent nature, their long duration, the presence of multiple wounds, and the frequency of concurrent infection. Comorbidity was documented by the coprevalence of up to three underlying diseases related to impaired wound healing. The present study clearly showed that aging affects chronic wound healing negatively.     

The extracellular matrix in wound healing: a closer look at therapeutics for chronic wounds

Disappointing results with the use of exogenous recombinant growth factors in chronic wounds have redirected the focus to the extracellular matrix (ECM). Newer research has clearly changed our view on the role of the ECM in tissue repair and dismissed the dogma that the sole function of ECM is a passive physical support for cells. It is now clear that intact or fragmented ECM molecules are capable of transducing signals pivotal for cell processes in wound healing primarily via integrin interactions in concert with growth factor activation. In addition, our knowledge about ECM molecules in minute concentrations with biological activity, but devoid of significant structural influence, is increasing. This article reviews the multifaceted molecular roles of ECM in the normal wound-healing process and some molecular abnormalities in chronic wounds, and touches on potential therapies based on the developments of tissue biology.     

Prevalence of immune disease in patients with wounds presenting to a tertiary wound healing centre

Chronic leg ulcers are a significant cause of morbidity and mortality and account for considerable healthcare and socioeconomic costs. Leg ulcers are a recognised complication of immune disease, and the purpose of this study was to establish the prevalence of immune disease in a cohort of patients with chronic wounds, and to compare wound outcomes in the subjects with and without immune disease. Retrospective chart review was completed on consecutive patients scheduled with the plastic surgeon in the Georgetown University Center for Wound Healing between 1 January 2009 and 31 March 2009. Of the 520 patients scheduled for appointments, 340 were eligible for inclusion. The prevalence of immune disease was higher than expected with 78 of 340 patients (23%) having associated immune disease. At presentation, wounds in patients with immune disease had a significantly larger mean surface area [33·4 cm(2) (69·05) compared to 22·5 cm(2) (63·65), P = 0·02]. Split thickness skin graft (STSG) and bioengineered alternative tissue (BAT) graft data was available on 177 grafts from 55 subjects. There was a significantly lower response rate to STSG in subjects with immune disease (50% compared to 97%, P = 0·0002), but response rates to BAT were not different. The association between immune diseases and chronic wounds may provide unique insights into pathways of wound healing, and warrants further study.     

Effectiveness of biofilm‐based wound care system on wound healing in chronic wounds

A biofilm plays a crucial role in delaying wound healing. Sharp debridement, a possible effective method for eliminating biofilms, can only be applied to the wound with visible necrotic tissue; thus, no option has been available for eliminating biofilms that are not accompanied by necrotic tissue. Wound blotting was recently developed to visualize biofilm noninvasively and quickly, and ultrasonic debridement is available for biofilm removal. Therefore, the purpose of this study was to investigate the efficacy of “biofilm‐based wound care system (BWCS),” a combination of wound blotting as a point‐of‐care testing and ultrasonic debridement, for promoting wound healing. Firstly, the cross‐sectional study was conducted to examine the proportion of biofilm removal by ultrasonic debridement in pressure ulcers [Study 1]. Subsequently, the retrospective cohort study was conducted to examine the effectiveness of BWCS for healing of chronic wounds [Study 2]. The proportions of wound healing between wounds treated with BWCS and those with standard care in the home‐visiting clinic were compared by Kaplan–Meier curve, and the Cox proportional hazard modeling was used to assess the effect of BWCS on wound healing. In Study 1, the median of biofilm removal proportion was 38.9% (interquartile range, 12.9–68.0%) for pressure ulcers treated with standard care and 65.2% (41.1–78.8%) for those treated with ultrasonic debridement (p = 0.009). In Study 2, the proportion of wound healing within 90 days was significantly higher in wounds treated with BWCS than in those treated with standard care (p = 0.001). The adjusted hazard ratio of BWCS for wound healing was 4.5 (95% confidence interval, 1.3–15.0; p = 0.015). In conclusion, we demonstrated that our novel approach, BWCS, can be a promising therapeutic strategy for visualizing biofilms that are not accompanied by necrotic tissue and promoting healing in chronic wounds.     

Negative pressure wound therapy as an adjunct in healing of chronic wounds

Negative pressure wound therapy (NPWT) has emerged as a cutting‐edge technology and provides an alternative solution to the problem of wounds. This study was undertaken to assess the efficacy of this technique in the treatment of chronic wounds. A prospective clinical study was used to evaluate our experience in use of NPWT in the healing of pressure ulcers and chronic wounds over 2 years. The primary end point of the study group was the time taken for appearance of healthy granulation tissue and full reepithelialisation without drainage. All patients with sepsis were excluded from the study. The statistical analysis of the data was carried out. Of the 60 patients studied, 41 had associated comorbidities including diabetes mellitus. The commonest site of occurrence was the lower limb. Coverage in the form of a flap was required at presentation in 63·33% of patients. However, after initiation of NPWT, none of them required the procedure and they healed spontaneously either by secondary intention or by skin grafting. The time taken for appearance of healthy granulation tissue was 14·36 ± 4·24 days. Complete healing of wounds occurred by 33·1 ± 10·22 days. There was a statistically significant difference in the volume of the wounds before and after the intervention (P = 0·000). Complications resulting from NPWT were minimal. This technique is an excellent adjunct to surgical debridement.     

Protease activity as a prognostic factor for wound healing in complex wounds

Healing mechanisms are disrupted in complex wounds. Proteases may persist longer in nonhealing wounds. We sought to investigate whether protease activity, protease inhibitor activity, or their combinations are independent prognostic factors for healing of complex wounds. We searched MEDLINE, EMBASE, CINAHL, and The Cochrane Library to March 2019. Study selection comprised longitudinal studies assessing the independent effect of proteases, their inhibitors or ratios of the two, on healing of complex wounds, while controlling for confounding factors. Two reviewers independently extracted data and assessed risk of bias. We conducted meta‐analyses separately for proteases, inhibitors, and ratios. We graded the evidence certainty (quality). We identified eight eligible studies in 10 cohorts involving 343 participants. Risk of bias was moderate or high. Elevated protease activity may be associated with less wound healing (standardized mean difference [SMD]: ?0.41, 95% CI ?0.72 to ?0.11; nine cohorts); and elevated protease inhibitor activity with more healing (SMD: 0.37, 95% CI 0.06‐0.68; five cohorts), this is low certainty evidence. Increased protease: inhibitor ratios may be associated with less healing (SMD ?0.47, 95% CI ?0.94 to ?0.01; four cohorts), but this evidence is of very low certainty. Heterogeneity in protease activity was unexplained by prespecified subgroup analyses for wound type or protease activity status, but partially explained by protease class. Posthoc analysis suggested elevated levels of a particular protease, MMP‐1, may be associated with more healing and other proteases with less healing. This is low/very low certainty evidence. Limitations were small included studies at moderate or high risk of bias, and the use of posthoc analyses. Elevated protease activity and protease: inhibitor ratios may be associated with less healing, and elevated inhibitor levels with more healing. There may be important differences between MMP‐1 and other proteases. High quality research is needed to explore these new findings further.     

Electrochemical detection of Pseudomonas in wound exudate samples from patients with chronic wounds

In clinical practice, point‐of‐care diagnostic testing has progressed rapidly in the last decade. For the field of wound care, there is a compelling need to develop rapid alternatives for bacterial identification in the clinical setting, where it generally takes over 24 hours to receive a positive identification. Even new molecular and biochemical identification methods require an initial incubation period of several hours to obtain a sufficient number of cells prior to performing the analysis. Here we report the use of an inexpensive, disposable electrochemical sensor to detect pyocyanin, a unique, redox‐active quorum sensing molecule released by Pseudomonas aeruginosa, in wound fluid from patients with chronic wounds enrolled in the WE‐HEAL Study. By measuring the metabolite excreted by the cells, this electrochemical detection strategy eliminates sample preparation, takes less than a minute to complete, and requires only 7.5 μL of sample to complete the analysis. The electrochemical results were compared against 16S rRNA profiling using 454 pyrosequencing. Blind identification yielded 9 correct matches, 2 false negatives, and 3 false positives giving a sensitivity of 71% and specificity of 57% for detection of Pseudomonas. Ongoing enhancement and development of this approach with a view to develop a rapid point‐of‐care diagnostic tool is planned.     

A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report

Previous studies have suggested that topically applied platelet-derived wound healing factors (PDWHF) accelerate wound healing by stimulating angiogenesis, fibroblast proliferation, and collagen synthesis. To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a randomized, prospective, double-blind, placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy. Wounds were present for at least 8 weeks (mean, 5.5 +/- 4.3 months). They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks. Eight patients with nine wounds were treated with placebo solution (controls), and 10 patients with 17 wounds were treated with PDWHF (treatment group). Seventy-eight percent of patients had diabetes mellitus, 72% had occlusive peripheral vascular disease, and 28% had venous disease; distribution of these disorders was equivalent in both groups. Ankle-brachial indexes, which were often spuriously elevated, averaged 0.93 +/- 0.54 in controls and 1.04 +/- 0.56 in patients treated with PDWHF (p greater than 0.5). Mean transcutaneous oxygen tension was 37.8 +/- 11.9 mmHg in controls and 37.1 +/- 9.1 mmHg in patients treated with PDWHF. Initial wound area was larger in controls than in the patients treated with PDWHF (28.9 +/- 45.2 cm2 vs 13.0 +/- 4.4 cm2), but this difference was not statistically significant (p = 0.19). Three (33%) wounds (in two patients) healed in controls, and four (24%) wounds (in three patients) healed in the PDWHF group (p greater than 0.5). The rate of healing in controls was 1.9 +/- 2.7 cm2/week.(ABSTRACT TRUNCATED AT 250 WORDS)     

急性创面无干扰伤口愈合的护理研究进展

介绍无干扰伤口愈合的概念及其在急性创面处理中的应用现状,分析无干扰伤口愈合在急性创面愈合中的促进因素及效果评价,以期为医护人员在临床实践中重视将急性创面处于无干扰愈合环境,结合患者情况,制定最佳的创面处理方案提供参考。     

Effects of negative pressure wound therapy on wound infection and healing in patients with open fracture wounds: A meta-analysis

A meta-analysis was conducted to comprehensively evaluate the impact of negative pressure wound therapy (NPWT) on wound infection and healing in patients with open fracture wounds. Computer searches were performed in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) on the application of NPWT in open fracture wounds, with the search period covering the databases inception to September 2023. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 17 RCTs involving 1814 patients with open fracture wounds were included. The analysis revealed that compared with other treatment methods, NPWT significantly shortened the wound healing time (standardized mean difference [SMD] = −2.86, 95% confidence intervals [CI]: −3.51 to −2.20, p < 0.001) and fracture healing time (SMD = −3.14, 95% CI: −4.49 to −1.79, p < 0.001) in patients with open fracture wounds. It also significantly reduced the incidence of wound infection (odds ratio [OR] = 0.36, 95% CI: 0.23–0.56, p < 0.001) and complications (OR = 0.29, 95% CI: 0.20–0.40, p < 0.001). This study indicates that in the treatment of open fracture wounds, NPWT, compared with conventional treatment methods, can accelerate the healing of wounds and fractures, effectively control infections and reduce the occurrence of complications, demonstrating high safety.     

Molecular and mechanistic validation of delayed healing rat wounds as a model for human chronic wounds

The purpose of this study was to provide molecular and mechanistic evaluation of an ischemic wound model in rats to determine if it is a valid model for human chronic wounds. Compared to acute wounds, human chronic wounds contain markedly elevated levels of proinflammatory cytokines and matrix metalloproteinases, while matrix metalloproteinase inhibitors and growth factor activity are diminished. Accordingly, tissue from ischemic and normal rat wounds were analyzed for cytokine, proteases and growth factor levels. Dorsal full thickness punch wounds were created in rats using a reproducible template. The ischemic wound group (n = 10) had six uniformly placed wounds within a bipedicled dorsal flap. The control group (n = 10) had the same wounds created without elevation of a flap. On postwound days 3, 6 and 13 wounds were excised and analyzed. Protein levels for tumor necrosis factor-alpha were determined with a rat-specific enzyme-linked immunosorbent assay, while mRNA was determined by RNase protection assay. Matrix metalloproteinases and serine protease detection was done using gelatin and casein zymography, respectively. Significant delay in healing was achieved in the ischemic group: 50% healing for control wounds was at 7 days and 11 days for ischemic wounds (p < 0.001). No significant differences between wound groups were found for interleukin-1beta, and mRNA for tumor necrosis factor-alpha and interleukin-1beta. However, at day 13 ischemic wounds contained significantly more tumor necrosis factor-alpha than controls and normal skin (586 +/- 106 pg/biopsy vs. 79 +/- 7 pg/biopsy vs. 52 +/- 2 pg/biopsy; p < 0. 001). Zymography showed substantially greater quantities of matrix metalloproteinase-2, matrix metalloproteinase-9, and serine proteases in ischemic wounds. This model of delayed healing in rats shares many of the key biochemical, molecular and mechanistic characteristics found in human chronic wounds, namely elevated tumor necrosis factor-alpha and protease levels. As such, this model will likely prove to be useful in chronic wound research, particularly in developing novel therapeutics.     

Outcome predictors for wound healing in patients with a diabetic foot ulcer

The aim of this study was to identify diabetic foot ulcer (DFU) patients at risk for the development of a hard‐to‐heal wound. This is a post‐hoc analysis of a prospective cohort study including a total of 208 patients with a DFU. The primary endpoints were time to healing and the development of a hard‐to‐heal‐wound. Univariable and multivariable logistic and Cox regression analysis were used to study the associations of patient characteristics with the primary endpoints. The number of previous DFUs [odds ratio (OR): 1.42, 95% confidence interval (CI): 1.01‐1.99, P = .04], University of Texas (UT) classification grade 2 (OR: 2.93, 95% CI: 1.27‐6.72, P = .01), UT classification grade 3 (OR: 2.80, 95% CI: 1.17‐6.71, P = .02), and a diagnosis of foot stand deformation (OR: 1.54, 95% CI: 0.77‐3.08, P = .05) were significantly associated with the development of a hard‐to‐heal wound. Only UT classification grade 3 (HR: 0.61, 95% CI: 0.41‐0.90, P = .01) was associated with time to healing. The number of previous DFUs, UT classification grade, and a diagnosis of foot deformation are significantly associated with development of a hard‐to‐heal wound in patients with a DFU. The only predictor significantly associated with time to healing was UT classification grade 3. These patient characteristics can be used to identify patients at risk for the development of hard‐to‐heal wounds, who might need an early intervention to prevent wound problems.