Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

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Background: Despite a growing consensus that biofilms contribute to a delay in the healing of chronic wounds, conflicting evidence pertaining to their identification and management can lead to uncertainty regarding treatment. This, in part, has been driven by reliance on in vitro data or animal models, which may not directly correlate to clinical evidence on the importance of biofilms. Limited data presented in human studies have further contributed to the uncertainty. Guidelines for care of chronic wounds with a focus on biofilms are needed to help aid the identification and management of biofilms, providing a clinical focus to support clinicians in improving patient care through evidence-based medicine. Methods: A Global Wound Biofilm Expert Panel, comprising 10 clinicians and researchers with expertise in laboratory and clinical aspects of biofilms, was identified and convened. A modified Delphi process, based on published scientific data and expert opinion, was used to develop consensus statements that could help identify and treat biofilms as part of the management of chronic nonhealing wounds. Using an electronic survey, panel members rated their agreement with statements about biofilm identification and treatment, and the management of chronic nonhealing wounds. Final consensus statements were agreed on in a faceto-face meeting. Results: Participants reached consensus on 61 statements in the following topic areas: understanding biofilms and the problems they cause clinicians; current diagnostic options; clinical indicators of biofilms; future options for diagnostic tests; treatment strategies; mechanical debridement; topical antiseptics; screening antibiofilm agents; and levels of evidence when choosing antibiofilm treatments. Conclusion: This consensus document attempts to clarify misunderstandings about the role of biofilms in clinical practice, and provides a basis for clinicians to recognize biofilms in chronic nonhealing wounds and manage patients optimally. A new paradigm for wound care, based on a steppeddown treatment approach, was derived from the consensus statements.

The presence of biofilms in chronic non-healing wounds, has been identified through in vitro model and in vivo animal data. However, human chronic wound studies are under-represented and generally report low sample sizes. For this reason we sought to ascertain the prevalence of biofilms in human chronic wounds by undertaking a systematic review and meta-analysis. Our initial search identified 554 studies from the literature databases (Cochrane Library, Embase, Medline). After removal of duplicates, and those not meeting the requirements of inclusion, nine studies involving 185 chronic wounds met the inclusion criteria. Prevalence of biofilms in chronic wounds was 78.2 % (confidence interval [CI 61.6-89, p<0.002]). The results of our meta-analysis support our clinical assumptions that biofilms are ubiquitous in human chronic non-healing wounds.

Dressings have a part to play in the management of wounds; whether they are sutured or open, usually chronic wounds of many aetiologies which are healing by secondary intention. They traditionally provide a moist wound environment, but this property has been extended through simple to complex, active dressings which can handle excessive exudate, aid in debridement, and promote disorganised, stalled healing. The control of infection remains a major challenge. Inappropriate antibiotic use risks allergy, toxicity and most importantly resistance, which is much reduced by the use of topical antiseptics (such as povidone iodine and chlorhexidine). The definition of what is an antimicrobial and the recognition of infection has proven difficult. Although silver has been recognised for centuries to inhibit infection its use in wound care is relatively recent. Evidence of the efficacy of the growing number of silver dressings in clinical trials, judged by the criteria of the Cochrane Collaboration, is lacking, but there are good indications for the use of silver dressings, to remove or reduce an increasing bioburden in burns and open wounds healing by secondary intention, or to act as a barrier against cross contamination of resistant organisms such as MRSA. More laboratory, and clinical data in particular, are needed to prove the value of the many silver dressings which are now available. Some confusion persists over the measurement of toxicity and antibacterial activity but all dressings provide an antibacterial action, involving several methods of delivery. Nanocrystalline technology appears to give the highest, sustained release of silver to a wound without clear risk of toxicity.

The TIME acronym (tissue, infection/inflammation, moisture balance and edge of wound) was first developed more than 10 years ago, by an international group of wound healing experts, to provide a framework for a structured approach to wound bed preparation; a basis for optimising the management of open chronic wounds healing by secondary intention. However, it should be recognised that the TIME principles are only a part of the systematic and holistic evaluation of each patient at every wound assessment. This review, prepared by the International Wound Infection Institute, examines how new data and evidence generated in the intervening decade affects the original concepts of TIME, and how it is translated into current best practice. Four developments stand out: recognition of the importance of biofilms (and the need for a simple diagnostic), use of negative pressure wound therapy (NPWT), evolution of topical antiseptic therapy as dressings and for wound lavage (notably, silver and polyhexamethylene biguanide) and expanded insight of the role of molecular biological processes in chronic wounds (with emerging diagnostics and theranostics). Tissue: a major advance has been the recognition of the value of repetitive and maintenance debridement and wound cleansing, both in time-honoured and novel methods (notably using NPWT and hydrosurgery). Infection/inflammation: clinical recognition of infection (and non infective causes of persisting inflammation) is critical. The concept of a bacterial continuum through contamination, colonisation and infection is now widely accepted, together with the understanding of biofilm presence. There has been a return to topical antiseptics to control bioburden in wounds, emphasised by the awareness of increasing antibiotic resistance. Moisture: the relevance of excessive or insufficient wound exudate and its molecular components has led to the development and use of a wide range of dressings to regulate moisture balance, and to protect peri-wound skin, and optimise healing. Edge of wound: several treatment modalities are being investigated and introduced to improve epithelial advancement, which can be regarded as the clearest sign of wound healing. The TIME principle remains relevant 10 years on, with continuing important developments that incorporate new evidence for wound care.

SummaryThis paper reports a controlled prospective unselected real-time comparison of human and computer-aided diagnosis in a series of 304 patients suffering from abdominal pain of acute onset.The computing system's overall diagnostic accuracy (91-8%) was significantly higher than that of the most (79 6%). It is suggested as a result of these studies that the provision of such a system to aid the clinician is both feasible in a real-time clinical setting, and likely to be of practical value, albeit in a small percentage of cases.