Anaerobic cocci populating the deep tissues of chronic wounds impair cellular wound healing responses in vitro

BACKGROUND: Anaerobic cocci are estimated to be present in the deep tissues of over 50% of chronic skin wounds. While the part they play in the chronicity of these wounds is uninvestigated, anaerobic cocci have previously been shown to be involved in other chronic inflammatory human conditions. METHODS: In this study the anaerobic microflora of the deep tissues of 18 patients with refractory chronic venous leg ulcers (mean age 80.3 years; mean duration > 24 months) was characterized using strict anaerobic culture conditions. The effect of the anaerobic organisms isolated from these tissues on extracellular matrix (ECM) proteolysis and cellular wound healing responses was studied using in vitro models. RESULTS: Anaerobic organisms were present in the deep tissues of 14 of 18 wounds and were principally Peptostreptococcus spp. The effects of three Peptostreptococcus spp. isolated from these wounds (P. magnus, P. vaginalis and P. asaccharolyticus) on cellular wound healing responses were compared with those of two pathogenic organisms also isolated from these wounds (Pseudomonas aeruginosa and Citrobacter diversus). While the direct ECM proteolytic activity exhibited by the Peptostreptococcus spp. was limited, they did significantly inhibit both fibroblast and keratinocyte proliferation, but only at high concentrations. However, at lower concentrations peptostreptococcal supernatants profoundly inhibited keratinocyte wound repopulation and endothelial tubule formation. The magnitude of these effects varied between strains and they were distinct from those demonstrated by Pseudomonas aeruginosa and Citrobacter diversus. CONCLUSIONS: These studies confirm the importance of anaerobic organisms in chronic wounds and demonstrate an indirect, strain-specific mechanism by which these microorganisms may play a part in mediating the chronicity of these wounds.     

A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients

Background Bacterial colonization of chronic wounds slows healing. Cold atmospheric plasma has been shown in vitro to kill a wide range of pathogenic bacteria. Objectives To examine the safety and efficiency of cold atmospheric argon plasma to decrease bacterial load as a new medical treatment for chronic wounds. Patients and methods Thirty‐eight chronic infected wounds in 36 patients were treated in a prospective randomized controlled phase II study with 5 min daily cold atmospheric argon plasma in addition to standard wound care. The patient acted as his or her own control. Bacterial species were detected by standard bacterial swabs and semiquantitative changes by nitrocellulose filters. Plasma setting and safety had been determined in a preceding phase I study. Results Analysis of 291 treatments in 38 wounds found a highly significant (34%, P < 10^?6) reduction of bacterial load in treated wounds, regardless of the type of bacteria. No side‐effects occurred and the treatment was well tolerated. Conclusions Cold atmospheric argon plasma treatment is potentially a safe and painless new technique to decrease bacterial load of chronic wounds and promote healing.     

Novel systemic antibiotics in dermatology

The treatment of bacterial skin infections has become challenging with the evolution of resistant species. As common antibiotics are losing efficacy, there is a pressing need for the discovery of new antibacterial agents. Only several systemic antibiotics have been approved for the treatment of skin infections in recent years. The expanding repertoire includes novel compounds structurally based on existing antibiotic classes, such as the glycopeptides, cephalosporins, and glycylcyclines. Antibiotics with completely unique mechanisms of action are being developed as members of the lipoprotein, oxazolidonone, and streptogramin classes. Most of these drugs require intravenous administration that limits their use. Future development should focus on more accessible routes of antibiotic administration, including oral, inhaled, or transdermal formulations.     

A review of animal models from 2015 to 2020 for preclinical chronic wounds relevant to human health

SignificanceChronic wounds fail to heal in a timely manner and exhibit sustained inflammation with slow tissue repair and remodelling. They decrease mobility and quality of life, and remain a major clinical challenge in the long-term care of many patients, affecting 6.5 million individuals annually in the U.S., decreasing mobility and quality of life. Treatment costs are a major burden on the U.S. healthcare system, totalling between $25 and $100 billion annually. Chronic wound severity depends upon several factors such as comorbidities, severity of tissue damage, infection and presence of necrosis and vary greatly in their healing mechanisms. In vivo animal models are critical for studying healing pathways of chronic wounds and seek to replicate clinical factors for trials of topical, systemic, and device-based therapeutics. This comprehensive review discusses murine, rat, lapine, canine, feline and porcine models of chronic wounds.Recent advancesFoundational chronic wound models for several species are discussed together with refinements and advances in the time period between 2015 and 2020 which have the potential for broad utility in investigating biological and device-based wound treatment therapies for human health.Critical issuesChronic wounds fail to heal in a timely manner and have differing aetiologies, rendering no single in vivo animal model universally applicable.Future directionsFurther studies are required to develop clinically relevant chronic wound animal model which reflect the clinical reality of the various influences of age, disease, comorbidities and gender on delayed healing and enhance understanding of the biological processes of human wound healing.     

Ultrasound imaging of the leg in patients with chronic wounds

A non-invasive method of studying the extent of tissue changes may be of use in evaluating healing therapies for chronic wounds. The aim of this study was to investigate the use of ultrasound imaging to study the appearance of tissue in the vicinity of lesions in the lower limb.

Method:

An ATL Apogee 800 Plus ultrasound system using a broadband 11 MHz linear array scanhead was used. The system was adjusted to allow discrimination in the appearance of dermal, adipose and muscle tissue on two healthy volunteers. For four patients with leg ulcers, scans were taken of the wound and areas around the wound, using an aseptic technique.

Results:

Differences on ultrasound images could be seen between wound and areas around the wound. In a patient with a unilateral wound, differences were seen on ultrasound imaging of the wound with respect to the contralateral unaffected limb.

Conclusion:

This preliminary study suggests that broadband ultrasound imaging may be of use in detecting tissue differences in lower limbs and thus may be of value in the study of wound healing.     

Differential expression of antimicrobial peptides in margins of chronic wounds

Please cite this paper as: Differential expression of antimicrobial peptides in margins of chronic wounds. Experimental Dermatology 2010; 19: 628–632. Abstract: Skin wounds usually heal without major infections, although the loss of the mechanical epithelial barrier exposes the tissue to various bacteria. One reason may be the expression of antimicrobial peptides (AMP) of which some [human β‐defensins (hBD) and LL‐37] were recently shown to support additionally certain steps of wound healing. There are no studies which have compared expression patterns of different classes of AMP in chronic wounds. The aim of our study was therefore to analyse the expression profile of hBD‐2, hBD‐3, LL‐37, psoriasin and RNase 7 by immunohistochemistry from defined wound margins of chronic venous ulcers. We detected a strong induction of psoriasin and hBD‐2 in chronic wounds in comparison with healthy skin. Except for stratum corneum, no expression of RNase 7 and LL‐37 was detected in the epidermis while expression of hBD‐3 was heterogeneous. Bacterial swabs identified Staphylococcus aureus and additional bacterial populations, but no association between colonization and AMP expression was found. The differential expression of AMP is noteworthy considering the high bacterial load of chronic ulcers. Clinically, supplementation of AMP with the capability to enhance wound healing besides restricting bacterial overgrowth could present a physiological support for treatment of disturbed wound healing.     

Non‐interventional study to investigate the efficacy and safety of Tegaderm™ Matrix in the treatment of patients with therapy‐refractory chronic wounds

Background: Despite a variety of therapeutic approaches, many patients with chronic wounds remain refractory to treatment. Products such as Tegaderm? Matrix were developed especially for such patients to alter the wound environment and reactivate the stagnant wound healing process. Patients and Methods: In this prospective post‐authorization observational product study, a total of 314 patients with therapy‐refractory chronic wounds of various origins were evaluated. Beside to the wound area reduction and healing rate, the occurrence of adverse events was documented. Results: On average the wounds were 10 months old. The average wound size was 17.3 cm² (median 6.3 cm²) at the initial visit. In the course of treatment the wound size decreased to 13.0 cm² (median 3.5 cm²) and was finally reduced to 9.3 cm² (median 0.9 cm²) at end of the study. Taking the criteria of the European Wound Management Association for improving the quality of clinical studies into consideration, a wound size reduction of at least 50 % is the parameter for successful treatment of chronic wounds. This study demonstrated a wound size reduction of at least 50 % for 72.9 % of the patients with therapy‐refractory chronic wounds when treated with Tegaderm? Matrix. The safety profile was evaluated; only 4.7 % of the patients experienced a treatment‐related adverse event such as a burning sensation. Conclusions: The results of the study demonstrate that Tegaderm? Matrix along with treatment of underlying causes is a well tolerated wound dressing promoting wound size reduction up to healing for the majority of patients with previously therapy‐refractory chronic wounds.     

Cutaneous and systemic adverse reactions to antibiotics

Antibiotics cause a variety of cutaneous and systemic reactions. Reactions can range from mild exanthems to life-threatening toxic epidermal necrolysis. For this reason, it is important for dermatologists to recognize common cutaneous adverse reactions caused by specific antibiotics. This review highlights the clinical features and management of common adverse reactions to antibiotics.     

Do systemic antibiotics increase the survival of a full thickness graft on the nose?

BACKGROUND: Full thickness grafts on the nose do not always heal without problems. Partial or entire necrosis of the graft is likely to lead to less favourable cosmetic results and prolonged wound care. No consensus exists as to the use of systemic antibiotics to increase the success rate of survival of a full thickness skin graft on the nose after non-melanoma skin cancer surgery. OBJECTIVE: The objective of the study was to evaluate the effect of systemic antibiotics on the survival of full thickness grafts on the nose. METHODS: We performed a randomized, controlled trial in which we compared azithromycin with standard treatment in 30 patients, who underwent a full thickness graft reconstruction of a surgical defect on the nose after surgery for non-melanoma skin cancer. Percentage survival of the graft was the main outcome measure. RESULTS: A statistically significant difference in favour of the grafts treated with azithromycin was seen (P=0.002). Of all the variables analysed, only smoking had a significant negative effect on the survival of the graft. CONCLUSIONS: Systemic antibiotics with an accurate bacterial spectrum should be advised in full thickness skin graft reconstruction after surgery for non-melanoma skin cancer of the nose. Smoking should be strongly discouraged.     

Optimizing use of oral antibiotics in acne vulgaris

Oral antibiotics are commonly used to treat acne vulgaris, primarily in patients presenting with moderate to severe facial or truncal disease severity. These agents are most appropriately used in combination with a topical regimen containing benzoyl peroxide and a topical retinoid. The most common oral antibiotics for treating acne vulgaris are the tetracycline derivatives, although macrolide agents such as erythromycin have also been used extensively. Over the past 4 decades, as the sensitivity of Propionibacterium acnes to several oral and topical antibiotics has decreased, the efficacy of oral tetracycline and erythromycin has markedly diminished, leading to increased use of doxycycline, minocycline, and other agents, such as trimethoprim/sulfamethoxazole.     

Ultrasound evaluation of acute experimental and chronic clinical wounds

Background/aims: An ultrasonic pulse echo Imaging technique was used to visualise various characteristics of experimentally induced acute full-thickness wounds. These characteristics were monitored over time as wound healing progressed. Data obtained from this work have been extrapolated to allow monitoring of healing and non-healing wounds in a human clinical environment.
Methods: Acute experimental full-thickness wounds were monitored using pulsed ultrasound (20 MHz) over a period of 21 days. The scans were interpreted in the light of data obtained from previous studies, clinical observations and current knowledge of wound healing. Similarly, ultrasound scans of healing and nonhealing clinical wounds were evaluated over a 6-week period. Ultrasound scans of amputated tissue were compared with the same site of histology to support scan evaluations of anatomical changes in ulcerated and adjacent tissue.
Results: The serial ultrasound scans of acute experimental full-thickness wounds demonstrated that changes in wounds could be observed and that specific events occurring during wound healing could be monitored, e.g., granulation tissue formation, reepithelialisation and wound contraction/fill. Specifically, these events were related to clinical observations of accumulation/synthesis of fibrotic (collageneous) tissue within the wound. Reepithelialisation of the wound could be monitored but was more problematic in quantitative evaluations.
Conclusions: Ultrasound can be used to monitor non-invasively and sequentially events that occur during acute wound healing. This information may be useful in extrapolating to healing and non-healing clinical wounds and may provide a diagnostic tool to identify early signs of tissue breakdown prior to ulceration.     

A systematic review of antistreptococcal interventions for guttate and chronic plaque psoriasis

BACKGROUND: Guttate psoriasis is closely associated with preceding or concurrent streptococcal infection. Some authorities have claimed that chronic plaque psoriasis may also be made worse by infection. In view of this many dermatologists have recommended using antibiotics for psoriasis, particularly guttate type. Some dermatologists have also recommended tonsillectomy for psoriasis in patients with recurrent streptococcal pharyngitis. OBJECTIVES: This review aims to assess the evidence for the effectiveness of antistreptococcal interventions, including antibiotics and tonsillectomy in the management of acute guttate and chronic plaque psoriasis. METHODS: Studies were identified by searching the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966-September 1999), Embase (1988-September 1999), the Salford Database of Psoriasis Trials (to November 1999) and the European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms (STREPTOCOCC* or ANTIBIOTIC* or TONSIL*) and PSORIASIS using the Cochrane Skin Group search strategy. RESULTS: Only one trial met the selection criteria. This compared the use of two oral antibiotic schedules in 20 psoriasis patients, predominantly of guttate type, who had evidence of beta-haemolytic streptococcal colonization. Either rifampicin or placebo was added to the end of a standard course of phenoxymethylpenicillin or erythromycin. No patient in either arm of the study improved during the observation period. No randomized trials of tonsillectomy for psoriasis were identified. CONCLUSIONS: Although both antibiotics and tonsillectomy have frequently been advocated both for patients with guttate psoriasis and for selected patients with chronic plaque psoriasis, there is to date no good evidence that either intervention is beneficial.     

三氧化二砷在系统性红斑狼疮治疗中的应用

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种由遗传、环境、免疫等多种因素参与引起的多器官、多系统损害的自身免疫性疾病,其发病机制复杂,临床表现多样,病情多呈进行性发展。对于SLE的治疗,传统上主要以糖皮质激素联合免疫抑制剂为主,严重者辅以细胞毒药物或生物调节剂,但总体疗效欠佳,且不良反应较大。近年来,大量的基础研究和临床试验表明,免疫因素在SLE发病机制中起主要作用,三氧化二砷(ATO)能有效缓解、控制SLE的症状,并且对ATO治疗SLE的作用机制也进行了许多深入的研究。该文拟从ATO的药效特性、临床应用、作用机制等方面对ATO治疗SLE的研究现况做一概述。     

三金片、金匮肾气丸联合抗生素治疗老年慢性前列腺炎临床观察

目的：观察三金片、金匮肾气丸联合抗生素治疗老年慢性前列腺炎临床疗效。方法：门诊慢性前列腺炎患者随机分为两组：抗生素治疗组（52例）,给予左氧氟沙星片与罗红霉素片口服;联合治疗组（56例）,给予三金片、金匮肾气丸与左氧氟沙星、罗红霉素同时口服治疗。连续治疗30d观察疗效和NIH—CPSI积分。结果：两组临床疗效总有效率、愈显率比较P〈0．05;两组治疗后NIH—CPSI积分均较治疗前有不同程度的改善P〈0．01,联合治疗组改善更明显P〈0．05。结论：三金片、金匮肾气丸联合抗生素治疗老年慢性前列腺炎安全有效。     

Systematic review of topical interventions for the management of odour in patients with chronic or malignant fungating wounds

Chronic wounds adversely affect the quality of life of individuals and odour is a well-recognised associated factor. Odour can affect sleep, well-being, social interactions, diet and potentially wound healing. This systematic review aims to examine the effectiveness of topical interventions in the management of odour associated with chronic and malignant fungating wounds. A systematic review guided by PRISMA recommendations of randomised controlled trials where odour intensity/odour is the primary outcome was undertaken. Inclusion criteria were adults (18 years and over) with chronic venous, arterial, diabetic or pressure ulcers or with malignant fungating wounds where odour has been managed through topical application of pharmacological/non-pharmacological agents. Searches were conducted in CENTRAL, CINAHL, EMBASE, MEDLINE, Scopus, and Web of Science. Eligibility screening, risk of bias assessment and data extraction was completed by authors working independently. Searches retrieved 171 titles and abstracts (157 post de-duplication). Thirteen studies were retained for full text review of which five (n = 137 individuals) examining the following treatments remained: metronidazole (n = 4), silver (n = 1). Meta-analysis was not possible but individual studies suggest improved outcomes (i.e., reduced odour) using metronidazole. Treatment options to manage wound odour are limited and hampered by lack of clinical trials, small sample sizes, and absence of standardised outcomes and consistent measurement. Whereas metronidazole and silver may have a role in controlling wound odour, robust and well-designed interventions with rigorous procedures and standardised odour outcomes are necessary to evaluate their contribution.     

Current therapeutic options of chronic leg ulcers

Wound treatment is continually becoming more complex and difficult. In the following review, we focus on the different options of wound debridement, stimulation of granulation tissue, different wound dressings, and therapeutic strategies in hard‐to‐heal‐wounds. We also present some future treatment options for chronic wounds.