Comprehensible evaluation of prognostic factors and prediction of wound healing

We analyzed the data of a controlled clinical study of the chronic wound healing acceleration as a result of electrical stimulation. The study involved a conventional conservative treatment, sham treatment, biphasic pulsed current, and direct current electrical stimulation. Data was collected over 10 years and suffices for an analysis with machine learning methods. So far, only a limited number of studies have investigated the wound and patient attributes which affect the chronic wound healing. There is none to our knowledge to include treatment attributes. The aims of our study are to determine effects of the wound, patient and treatment attributes on the wound healing process and to propose a system for prediction of the wound healing rate. First we analyzed which wound and patient attributes play a predominant role in the wound healing process and investigated a possibility to predict the wound healing rate at the beginning of the treatment based on the initial wound, patient and treatment attributes. Later we tried to enhance the wound healing rate prediction accuracy by predicting it after a few weeks of the wound healing follow-up. Using the attribute estimation algorithms ReliefF and RReliefF we obtained a ranking of the prognostic factors which was comprehensible to experts. We used regression and classification trees to build models for prediction of the wound healing rate. The obtained results are encouraging and may form a basis for an expert system for the chronic wound healing rate prediction. If the wound healing rate is known, then the provided information can help to formulate the appropriate treatment decisions and orient resources towards individuals with poor prognosis.     

慷舒灵治疗糖尿病足及下肢慢性创面疗效观察

目的探讨慷舒灵敷料治疗糖尿病足及下肢慢性创面的疗效。方法选择常规治疗四周以上无效的糖尿病足及下肢慢性创面患者16例，使用慷舒灵敷料治疗，视创面渗出的情况每3～5d换药1次，1周为一观察周期。结果5周愈合1例、6周愈合5例、7周愈合6例、10周愈合1例，11周愈合2例，有1例于12周行需要行自体皮片移植后创面愈合。慷舒灵全组总有效率为100％，8周愈合率为75％。结论慷舒灵敷料可有效治疗糖尿病足及下肢慢性创面，提高慢性创面愈合率，并可减少患者创面处理的痛苦。     

Modelling of chronic wound healing dynamics

Following chronic wound area over time can give a general overview of wound healing dynamics. Decrease or increase in wound area over time has been modelled using either exponential or linear models, which are two-parameter mathematical models. In many cases of chronic wound healing, a delay of healing process was noticed. Such dynamics cannot be described solely with two parameters. The reported study deals with two-, three-, and four-parameter models. Assessment of the models was based on weekly measurements of 226 chronic wounds of various aetiologies. Several quantitative fitting criteria, i.e. goodness of fit, handling missing data and prediction capability, and qualitative criteria, i.e. number of parameters and their biophysical meaning were considered. The median of goodness of fit of three- and four-parameter models was between 0.937 and 0.958, and the median of two-parameter moels was 0.821 to 0.883. Two-parameter models fitted wound area over time significantly (p=0.001) worse than three- and four-parameter models. The criterion handling missing data provided similar results, with no significant difference between three- and four-parameter models. Median prediction error of two-parameter models was between 111 and 746; three-parameter models resulted in an error of 64 to 128, and finally four-parameter models resulted in the highest prediction error of 407 and 238. Based on the values of quantitative fitting criteria obtained, three parameters were chosen as the most appropriate. Based on qualitative criteria, the delayed exponential model was selected as the most general three-parameter model. It was found to have good prediction capability and in this capacity it could be used to help physicians choose the most appropriate treatment for patients with chronic wounds after an initial three-week observation period, when the median error increase of fitting is 74%.     

A reliable method of determining wound healing rate

Several wound healing rate measures have been introduced with the main goal of enabling quantification of the effects of various therapeutic modalities on the healing of open wounds. Different definitions of wound healing rate render comparison of clinical results difficult. The goal of the present study was to propose a measure of wound healing rate that is independent of initial wound extent and to present a method of wound healing rate prediction. Comparisons were made of wound healing rate defined as absolute area healed per day, percentage of initial area healed per day and advance of the wound margin towards the wound centre per day. Analysis was performed on 300 wound cases. A disadvantage of wound healing measures that either use absolute area healed per day or percentage of initial area healed per day is their very limited use for comparing healing rates of wounds with different initial sizes. This disadvantage was overcome by incorporating a wound perimeter; thus obtaining a measure of the advance of the wound margin towards the wound centre. A definition of healing rate expressed as the greatest average wound margin distance from the wound centre divided by the time to complete wound closure is proposed. Because not all wounds are closed in the observation period, the time to complete wound closure has to be predicted. A method of wound healing rate prediction is presented based on a delayed exponential model the parameters of which are obtained from at least five weekly wound area measurements. Paired t-tests between actual time needed to complete wound closure and the predicted time resulted in p=0.062 after four, 0.484 after five and 0.900 after six weeks of observation.     

认知行为疗法在合并焦虑的慢性难愈合创面患者中的临床研究

目的探讨认知行为疗法对合并焦虑的慢性难愈合创面患者创面治疗效果的影响。 方法选取2018年2月至9月于临沂市中心医院烧伤整形科住院治疗的符合入选标准的40例合并焦虑的慢性难愈合创面患者,将所有患者随机编号,编号为奇数的设为干预组,编号为偶数的设为对照组,每组各20例。2组患者均接受常规慢性难愈合创面的治疗和护理,干预组患者在此基础上给予认知行为疗法干预,包括会谈治疗、音乐治疗及腹式呼吸放松治疗,共4周,对照组未予任何心理干预治疗。分别于入院时、治疗2周、治疗4周采用焦虑自评量表(SAS)、汉密尔顿焦虑量表(HAMA)对2组患者进行焦虑程度评分;应用毫米网格纸法测量患者入院时、治疗2周、治疗4周创面面积并计算创面愈合率。数据比较采用t检验。 结果入院时,干预组患者SAS评分(67.1±2.4) 分,对照组(65.9±2.2) 分,2组比较差异无统计学意义(t＝0.49, P＝0.65);认知行为疗法干预治疗2、4周后,干预组患者SAS评分分别为(55.6±1.9)、(49.3±2.6) 分,低于同期对照组(59.8±2.1)、(53.5±2.7) 分,差异均有统计学意义(t＝2.17、2.54,P＝0.04、0.02);入院时,干预组患者HAMA评分(23.8±3.3) 分,对照组(24.1±3.6) 分,2组比较差异无统计学意义(t＝0.96, P＝0.34);干预2、4周后,干预组患者HAMA评分分别为(17.2±2.7)、(11.9±2.1) 分,低于同期对照组(20.8±3.4)、(15.3±3.0) 分,差异均有统计学意义(t＝2.23、2.86,P＝0.03、0.01)。治疗2、4周后,干预组患者创面愈合率分别为(26.2±2.4)%、(80.5±4.2)%,均高于同期对照组(22.3±2.1)%、(59.2±3.9)%,2组比较差异均有统计学意义(t＝2.54、2.86,P＝0.02、0.01)。 结论认知行为疗法干预有助于缓解慢性难愈合创面患者的焦虑情绪,提高慢性难愈合创面的愈合速度。     

超声清创系统结合负压创面疗法在骨外露创面中的应用

目的 研究超声清创系统结合负压创面疗法治疗骨外露创面的临床效果.方法 采用超声手术系统结合负压创面疗法治疗17例患者,共18个骨外露创面,骨外露创面面积平均（10.5±6.6）cm^2.观察坏死骨组织清除速度、清除效果,清创术后3周创面愈合率,植皮成活率,创面完全愈合时间.结果 超声清创系统可以快速而有效地清除坏死骨组织以及磨除骨皮质.清创术后3周创面愈合（62.3±25.1）%,未愈合创面肉芽组织长满创面,色鲜红.植皮全部成活率88.9%,从第一次清创至创面完全愈合时间为（28.1±9.1）d.结论 超声清创系统结合负压创面疗法治疗骨外露创面可有效清除坏死骨组织,促进肉芽组织迅速生长,缩小创面面积,从而加速创面愈合,是治疗骨外露创面的一种行之有效的方法.     

改性甲壳素联合重组人碱性成纤维细胞生长因子治疗浅Ⅱ度烧伤创面的临床观察

目的观察改性甲壳素联合重组人碱性成纤维细胞生长因子(rh-bFGF)在治疗浅Ⅱ度烧伤创面的治疗效果。 方法将石家庄市第一医院烧伤整形科2015年11月至2017年8月收治的80例浅Ⅱ度烧伤患者按随机数字表法分为治疗组和对照组,每组40例。治疗组患者创面先外用rh-bFGF喷洒,再用改性甲壳素生物修复膜覆盖,常规预防感染治疗,每天换药1次,直至创面愈合;对照组清理创面后,外用改性甲壳素生物修复膜覆盖创面,每日换药1次。观察两组患者平均创面愈合时间、患者伤后7、10、13 d创面愈合率、创面感染情况、瘢痕情况、患者换药疼痛指数及其他不良反应。患者创面平均愈合时间及不同时间点烧伤创面愈合率、患者换药疼痛指数比较均采用t检验。 结果治疗组患者创面平均愈合时间(11.55±2.02) d,较对照组[(12.63±1.96) d]明显缩短,差异均有统计学意义(t＝2.41,P＝0.02);治疗组伤后7、10、13 d创面愈合率分别为(86.00±4.28)%、(95.53±3.65)%和(99.55±0.68)%,明显高于对照组[(84.23±3.38)%、(93.50±3.21)%和(99.10±1.06)%],差异均有统计学意义(t＝2.06、2.63、2.27,P＝0.04、0.01、0.03);治疗组患者换药疼痛数字评分法(NRS)评分为(3.46±0.51)分,对照组患者换药疼痛NRS评分为(3.50±0.50)分,两组比较差异无统计学意义(t＝0.27,P＝0.78)。治疗过程两组均未出现感染患者,随访3个月均未出现瘢痕增生;未发现其他不良反应。 结论应用改性甲壳素联合rh-bFGF能明显缩短浅Ⅱ度烧伤患者创面愈合时间,提高创面愈合率,未见其他不良反应。     

糖尿病足伤口处理中的护理风险及其相关性研究

目的 探讨影响糖尿病足伤口处理中护理风险的相关因素,为降低护理风险所采取的护理措施提供理论依据。方法 采用自行设计的一般资料调查表、护理风险表对在本院门诊就诊的79例2型糖尿病足患者进行问卷调查,并分析影响糖尿病足伤口处理中护理风险的相关因素。结果 护理差错缺陷率为0.62%,愈合率为88.61%,满意度为93.67%。患者年龄、文化程度、糖尿病治疗情况、对糖尿病足认识程度、就诊情况及伤口治疗情况与护理差错缺陷率、伤口愈合情况和满意度有相关性（P＜0.05）;吸烟与伤口愈合情况有相关性（P＜0.05）;并发糖尿病其它并发症与护理差错缺陷率有相关性（P＜0.05）。结论 年龄越大、文化程度越低、不坚持糖尿病治疗、对糖尿病足认识模糊、有伤口不及时就诊和不坚持伤口治疗、吸烟及并发糖尿病其它并发症的糖尿病足患者护理风险高,在制定护理风险管理措施时,应根据患者具体情况,规避不利因素,以降低护理差错缺陷率、提高治愈率及患者的满意度。     

Effects of granulocyte-macrophage colony-stimulating factor on wound contraction

The effect of topical recombinant murine and human GM-CSF, 1 or 10 µg/cm² for one to ten days, on the contraction and healing of acute and chronic granulating wounds infected withEscherichia coli was studied in Sprague-Dawley rats. Bacterial contamination of wounds produced significant inhibition of wound contraction. Application of GM-CSF at either dose level to infected wounds markedly increased the rate of wound closure compared to the rate in infected untreated controls. Ten days treatment was found to be more effective than a single application. An advanced stage of wound healing was observed at ten days in the GM-CSF-treated rats compared with controls. Bacterial counts decreased in the GM-CSF-treated wounds which may suggest bactericidal activity. Topical treatment with GM-CSF was shown to effectively inhibit the retardation of wound closure produced by bacterial contamination and may therefore be useful in the management of patients with infected wounds.     

Effects of granulocyte-macrophage colony-stimulating factor on wound contraction

The effect of topical recombinant murine and human GM-CSF, 1 or 10 µg/cm² for one to ten days, on the contraction and healing of acute and chronic granulating wounds infected withEscherichia coli was studied in Sprague-Dawley rats. Bacterial contamination of wounds produced significant inhibition of wound contraction. Application of GM-CSF at either dose level to infected wounds markedly increased the rate of wound closure compared to the rate in infected untreated controls. Ten days treatment was found to be more effective than a single application. An advanced stage of wound healing was observed at ten days in the GM-CSF-treated rats compared with controls. Bacterial counts decreased in the GM-CSF-treated wounds which may suggest bactericidal activity. Topical treatment with GM-CSF was shown to effectively inhibit the retardation of wound closure produced by bacterial contamination and may therefore be useful in the management of patients with infected wounds.     

Cell Therapy for Wound Healing

In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin grafts and local flaps, the cell therapy technique is simple, less time-consuming, and reduces the surgical burden for patients in the repair of acute wounds. Cell therapy has also been developed for chronic wound healing. By transplanting cells with an excellent wound healing capacity profile to chronic wounds, in which wound healing cannot be achieved successfully, attempts are made to convert the wound bed into the environment where maximum wound healing can be achieved. Fibroblasts, keratinocytes, adipose-derived stromal vascular fraction cells, bone marrow stem cells, and platelets have been used for wound healing in clinical practice. Some formulations are commercially available. To establish the cell therapy as a standard treatment, however, further research is needed.

Graphical Abstract

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光交联壳聚糖水凝胶膜治疗深Ⅱ度烧伤创面的临床研究

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循环纤维细胞与慢性创面愈合

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Low-Level Laser Therapy Facilitates Superficial Wound Healing in Humans: A Triple-Blind, Sham-Controlled Study

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Higher numbers of autologous fibroblasts in an artificial dermal substitute improve tissue regeneration and modulate scar tissue formation

Cultured skin substitutes are increasingly important for the treatment of burns and chronic wounds. The role of fibroblast numbers present in a living-skin equivalent is at present unknown. The quality of dermal tissue regeneration was therefore investigated in relation to the number of autologous fibroblasts seeded in dermal substitutes, transplanted instantaneously or precultured for 10 days in the substitute. A full-thickness porcine wound model was used to compare acellular dermal substitutes (ADS) with dermal substitutes seeded with fibroblasts at two densities, 1x10(5) (0-DS10) and 5x10(5) cells/cm(2) (0-DS50), and with dermal substitutes seeded 10 days before operation at the same densities (10-DS10 and 10-DS50) (n=7 for each group, five pigs). After transplantation of the dermal substitutes, split-skin mesh grafts were applied on top. Wound healing was evaluated blind for 6 weeks. Cosmetic appearance was evaluated and wound contraction was measured by planimetry. The wound biopsies taken after 3 weeks were stained for myofibroblasts (alpha-smooth muscle actin), and after 6 weeks for scar tissue formation (collagen bundles organized in parallel and the absence of elastin staining). Collagen maturation was investigated with polarized light. For wound cosmetic parameters, the 10-DS50 and 0-DS50 treatments scored significantly better than the ADS treatment, as did the 10-DS50 treatment for wound contraction (p<0.05, paired t-test). Three weeks after wounding, the area with myofibroblasts in the granulation tissue, determined by image analysis, was significantly smaller for 0-DS50, 10-DS10, and 10-DS50 than for the ADS treatment (p<0.04, paired t-test). After 6 weeks, the wounds treated with 0-DS50, 0-DS10, and 10-DS50 had significantly less scar tissue and significantly more mature collagen bundles in the regenerated dermis. This improvement of wound healing was correlated with the higher numbers of fibroblasts present in the dermal substitute at the moment of transplantation. In conclusion, dermal regeneration of experimental full-skin defects was significantly improved by treatment with dermal substitutes containing high numbers of (precultured) autologous fibroblasts.     

“创面床准备”理论实施的系统评价

目的 评价“创面床准备”理论的实施对慢性创面的治疗效果,从而得出一个系统、规范、科学的慢性创面治疗原则.方法 采用Cochrane系统评价方法,检索万方,中国期刊网(CNKI)、中国生物医学文献光盘数据库(CBM)和PubMed等电子数据库,对国内外公开发表的有关“创面床准备”理论实施的研究文献进行荟萃分析.结果 共纳入65个研究、3989例各种慢性创面疾病患者.干预措施包括不同时期选择合适新型敷料、各种生长因子,清创及封闭式负压引流.按测量指标和干预措施进行亚组分析,得出结果:实施“创面床准备”理论,其创面的愈合率[0R=2.12,95％ CI( 1.79,2.52)]、愈合时间[WMD =-12.38,95％ CI(-15.14,-9.62)]、换药次数[WMD=-15.56,95％CI(-20.57,-10.56)]、需要植皮手术的例数[ 0R=0.26,95％ CI (0.10,0.66)]、缩小创面面积[WMD=8.97, 95％ CI( 1.04,16.91)]、植皮手术成功率[0R=5.69,95％CI(2.19,14.82)]均优于对照组,治疗费用[WMD=- 1.53,95％CI(-10.38,7.33)]与对照组差异无统计学意义.结论 实施“创面床准备”理论指导治疗,可以提高创面的愈合率,减少创面愈合时间,加速缩小创面面积,减少换药次数,减少需要植皮手术率,提高植皮手术成功率,并且不增加治疗费用.     

Microvascular transfer of free tissue for closure of bone wounds of the distal lower extremity

Extensive compound fractures of the distal lower extremity may result in chronic infection of the deep tissues and bone if primary healing does not occur. Treatment may require several operations and prolonged hospitalization. In an attempt to improve the management of such problems, 18 patients who had chronic bone-exposure wounds and four patients who had extensive compound fracture wounds of the distal lower extremity were treated with radical debridement, intravenous antibiotics, and microvascular transfer of vascularized tissues for immediate wound closure. All wounds healed, and there was no evidence of recurrent infection during a mean follow-up period of 19.3 months in the patients with chronic wounds and 16.3 months in those with acute wounds. In selected patients this free-tissue-transfer method of wound closure appears to have considerable advantages over conventional methods of management.     

Synergistic effect of bismuth subgallate and borneol,the major components of Sulbogin,on the healing of skin wound

Most skin lesions heal delay and even heal efficiently within 1-2 weeks, the healed tissue is neither aesthetically nor functionally perfect. Therefore, facilitating skin healing rate and controlling healed skin quality are major aims of drug treatment for a wound event. Bismuth subgallate (BS) and Borneol (BO) are the two components of Sulbogin, a new Vaseline-based wound healing ointment, one for treating skin wounds. Although BO has antibiotic function, while BS is widely used clinically, neither has been used specifically for wound healing.The experiment described here aimed to study the effect of BS and BO on the healing of skin wounds. This study also compared the effects of BS and BO with Flamazine cream, which is currently the most popular drug for wound healing in hospitals. Full-thickness wounds (3 cm x 3 cm x 0.2 cm) were created on the back of adult male Sprague-Dawley rats. BS, BO, BS+BO, and Flamazine were then evenly applied to cheesecloth and placed over the lesion areas. The drug patches were replaced every 2-3 days until the wound areas were completely covered by epidermis in any kinds of drug treatment. The combined BS and BO treatment had the best effect on healing by decreasing lesion area, while increasing granulation tissue formation, re-epithelialization, eating behavior and reconstitution of skin appendages. This investigation showed that BS and BO have a synergistic effect on the skin wound restoration.     

Interpenetrating polymer networks containing gelatin modified with PEGylated RGD and soluble KGF: synthesis, characterization, and application in in vivo critical dermal wound

The purpose of this study was to evaluate the biocompatibility and the efficacy in wound healing of a gelatin-based interpenetrating polymer network (IPN) containing poly(ethylene glycol) (PEG)-ylated RGD and soluble KGF-1 (RGD-IPN+KGF). IPNs were applied to full-thickness wounds on a rat model. Wound healing was assessed through histological grading of the host response and percent area contraction at 2 days, 1 week, 2 weeks, and 3 weeks. A control IPN containing unmodified gelatin (unmod-IPN) and a conventional clinical bandage were applied to similar wounds and also evaluated. During the first week of healing, the unmod-IPN and conventional dressing wound showed a greater amount of contraction than that of RGD-IPN+KGF. However, by 3 weeks the extent of wound contraction was comparable between treatments. The RGD-IPN+KGF treated wound demonstrated lower macrophage and fibroblast densities at 3 weeks as compared to unmod-IPN treated wounds. RGD-IPN+KGF acted as a tissue scaffold while preventing the entry of foreign bodies, advantages not seen with the conventional dressing. The extent of cellularity and extracellular matrix organization was higher for wounds healed with RGD-IPN+KGF than those healed with unmod-IPN. These results indicate that both soluble and immobilized bioactive factors can be incorporated into our IPN platform to enhance the rate and the quality of dermal wound healing.