Keith Harding

Cardiff University | CU · School of Medicine

Chronic wounds are characterized by their inability to heal within an expected time frame and have emerged as an increasingly important clinical problem over the past several decades, owing to their increasing incidence and greater recognition of associated morbidity and socio-economic burden. Even up to a few years ago, the management of chronic w...

Introduction: WounD14 (WD14) gene signature is a recently developed tool derived from genetic interrogation of wound edge biopsies of chronic venous leg ulcers to identify heard-to-heal wounds and enable clinicians to target aggressive therapies to promote wound healing. This study aimed to evaluate if changes in wound clinical healing status were...

The invention relates to medical treatment patch, ideally for applying topically, that permits the targeted, sustained and controlled release of potassium KMnO4; For the treatment of overly exuding wound and as a broad spectrum antimicrobial. The intention is for use in chronic or hard to heal wounds. Patent Granted 28-Sep-2021

Chronic wounds have a debilitating effect on the quality of life of many individuals, and the large economic impact on health system budgets warrants greater attention in policy making and condition management than is currently evident. The aim of this narrative review is to summarize the nature and extent of the chronic wound problem that confront...

Complete healing is problematic as an endpoint for evaluating interventions for wound healing. The great heterogeneity of wounds makes it difficult to match groups, and this is only possible with multivariate stratification and/or very large numbers of subjects. The substantial time taken for wounds to heal necessitates a very lengthy study. Conseq...

This study uses a scientific realist methodology to explain how social outcomes of community care interventions are produced, sustained and contextually dependent. We evaluate an organization dedicated to wound care and leg health known as the Lindsay Leg Club network, so far studied mostly from a phenomenological perspective, to demonstrate the ge...

The coronavirus disease (COVID-19) outbreak has presented enormous challenges for healthcare, societal, and economic systems worldwide. There is an urgent global need for a universal vaccine to cover all SARS-CoV-2 mutant strains to stop the current COVID-19 pandemic and the threat of an inevitable second wave of coronavirus. Carbon dioxide is safe...

The aim of this study was to estimate costs associated with the management of patients with venous leg ulcers (VLUs) from the perspective of the UK National Health Service (NHS). The analysis was undertaken through the Secure Anonymised Information Linkage Databank which brings together and anonymously links a wide range of person‐based data from a...

Background: Pressure ulcers are associated with significant morbidity and mortality as well as high cost to the health service. Although often linked with inadequate care, in some patients, they may be unavoidable. Aim: This systematic review aims to quantify the prevalence and incidence of pressure ulcers in patients receiving palliative care a...

This was a prospective observational pilot study of a unique intermittent pneumatic compression (IPC) device designed to be applied in the thigh region of the affected limb in patients with lower limb ulceration of both venous and mixed (venous and arterial) aetiologies. This compression system consists of a circumferential three‐chamber thigh garm...

Background The aim of this paper was to create an updated Australian guideline on footwear for people with diabetes. Methods We reviewed new footwear publications, (inter)national guidelines, and consensus expert opinion alongside the 2013 Australian footwear guideline to formulate updated recommendations. ResultWe recommend health professionals ma...

The ideal treatment for patients who suffer from pilonidal sinus disease should lead to a cure with a rapid recovery period allowing a return to normal daily activities, with a low level of associated morbidity. A variety of different surgical techniques have been described for the primary treatment of pilonidal sinus disease and current practice r...

Background Venous leg ulcers (VLUs) are the most common cause of leg ulceration, affecting 1 in 100 adults. VLUs may take many months to heal (25% fail to heal). Estimated prevalence is between 1% and 3% of the elderly population. Compression is the mainstay of treatment and few additional therapies exist to improve healing. Two previous trials hav...

Wounds affect large numbers of patients and produce a considerable socioeconomic burden. In 2012/2013, about 2.2 million patients were treated by the NHS in the UK for an acute or chronic wound at a cost of £4.5–5.1 billion (Guest et al, 2015). Timely healing of wounds can help to minimise impact on patients and contain costs. Wound infection or in...

Pigment epithelial derived factor (PEDF) is a secreted glycoprotein that is a non-inhibitory member of the serine protease inhibitor (serpin) family. PEDF exhibits multiple biological properties including neuroprotective, anti-angiogenic, and immunemodulating. Interestingly, PEDF exerts the inhibitory effects in cancers derived from certain tissues...

Allergic contact dermatitis commonly affects patients with chronic venous leg ulcers and can contribute to impaired wound healing. Many allergens have been identified, and despite the use of advanced dressings, the incidence of allergy has remained high. We discuss an unusual presentation of allergic contact dermatitis in a patient with a chronic w...

Abstract Infection is a very common cause for complications and delayed healing of both acute and chronic wounds. Currently, clinicians depend on clinical signs and symptoms to diagnose infection within wounds. When infection is suspected most practitioners will send a microbiological culture specimen from the wound site to elucidate the type of mi...

Gurudutt Naik, Keith G Harding Welsh Wound Innovation Centre, Cardiff University, Cardiff, UK Abstract: Chronic wounds remain a challenge to most healthcare systems worldwide despite the technological advances we have seen to date. Many chronic non-healing wounds require alternative approaches, in addition to standard conventional therapies. Maggot...

Maintaining a moist environment plays an important role in promoting wound healing, however, achieving the right moisture balance in moderate to highly exuding wounds can be a clinical challenge. Complications arising from poor exudate management can often lead to delayed wound healing and subsequent trauma to the surrounding skin (White, 2009)...

Wound healing and the management of chronic wounds represent a significant burden on the NHS. Members of the suppressor of cytokine signalling (SOCS) family have been implicated in the regulation of a range of cellular processes. The current study aims to explore the importance of SOCS-3 and SOCS-4 in regulating cellular traits associated with woun...

Psoriasin, which is also known as S100A7, is a member of the S100 protein family, a group of calcium-responsive signalling proteins. Psoriasin expression remains high in patients with psoriasis, whereas it is downregulated in patients with invasive breast carcinoma. This observation suggests that this protein may be a notable marker of keratinocyte...

Chronic wounds are relatively common and have huge financial implications. The etiology of chronic wounds can be diverse, and the healing process is affected by patients' comorbidities, as well as local wound factors. There is an urgent need for improved treatment options for the management of chronic wounds. There has been the recent development o...

Diabetes-related foot disease remains a common problem. For wounds, classic teaching recommends the treatment of any infection, offloading the wound and ensuring a good blood supply, as well as ensuring that the other modifiable risk factors are addressed and optimized. There remain, however, several questions about these and other aspects of the c...

Há indicações em publicações específicas que a implementação de estratégias de prevenção da lesão por pressão (LP) pode resultar em redução da ocorrência da lesão por pressão em cenários agudos e de longo prazo3-8. Entretanto, as lesões por pressão continuam ocorrendo e resultando em considerável morbidade e mortalidade e encargos sociais e económi...

While the overwhelming majority of wounds heal rapidly, a significant proportion fail to progress through the wound-healing process. These resultant chronic wounds cause considerable morbidity and are costly to treat. Wound bed preparation, summarised by the TIME (Tissue, Inflammation/infection, Moisture imbalance, Epithelial edge advancement) conc...

Abstract. Cytokines play important roles in the wound healing process through various signalling pathways. The JAK-STAT pathway is utilised by most cytokines for signal transduction and is regulated by a variety of molecules, including suppressor of cytokine signalling (SOCS) proteins. SOCS are associated with inflammatory diseases and have an impa...

Background Split-thickness skin grafting (SSG) is an important modality for wound closure. However, the donor site becomes a second, often painful wound, which may take more time to heal than the graft site itself and holds the risk of infection and scarring. Epidermal grafting (EG) is an alternative method of autologous skin grafting that harvests...

The under-utilisation of compression for venous leg ulcer (VLU) management translates into lost opportunities to heal wounds, improve patients' quality of life and maximise health care system efficiency. Although compression therapy is considered gold standard according to clinical guidelines, lack of clinician knowledge, unclear referral pathways,...

Methods of identifying chronic wounds that will heal in a timely, coordinated fashion and those that will not, together with novel therapeutic strategies, are vital for progression in the field of wound healing. Interleukin (IL)-7 has been associated with various biological and pathological processes. The present study explored the potential role o...

Current wound management through the use of a split-thickness skin graft often requires hospital admission, a period of immobility, attentive donor site wound care and pain management. This study evaluates the feasibility of using a novel epidermal graft-harvesting device (CelluTome) that allows pain-free epidermal skin grafting in the outpatient c...

Wound healing is a dynamic process comprising three overlapping, highly orchestrated stages known as inflammation, proliferation and re-epithelialization, and tissue remodeling. This complex process is regulated by numerous cytokines, with dysregulation of cytokine-induced signaling leading to impaired wound healing. Suppressor of cytokine signalin...

Managing wound infection is a complex situation requiring thorough diagnostic skills on the part of the clinician but also a good understanding of the realities of clinical practice. Patients live in the real world and it is frequently the environment in which care is practised as well as the complexities of individual patients that makes tailoring...

Background: Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs – it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is oft...

For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor...

Movie S1. Time-Lapse Imaging of Control (top) and Ephrin-B1/B2 KD (bottom) HaCaT Cells following Scratch Wounding over 15 hr (5 min/frame), Related to Figure 5

Movie S2. Time-Lapse Imaging of Control (top) and Ephrin-B1/B2 KD (bottom) HaCaT Cell Lamellipodia 15 hr after Wounding (2 min/frame), Related to Figure 5

Movie S4. Time-Lapse Imaging of a Confluent HaCaT Cell Monolayer with One efnB1-GFP-Overexpressing Cell (green; 1 min/frame) in View, Related to Figure 7

Movie S3. Time-Lapse Imaging of Ephrin-B1/B2 KD HaCaT Cells before and after the Addition of Y27632, Related to Figure 6

Introduction Pigment epithelium-derived factor (PEDF) is a 50kDa, secreted glycoprotein that has been identified as a member of the serpin gene family and has been shown to exhibit neurotrophic, neuroprotective, anti-angiogenic and anti-tumourigenic effects. The aims of our study were to determine the expression profile of PEDF in a range of colore...

The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound - defined as a barrier defect that has not healed in 3 months - has become...

Motility is a requirement for a number of biological processes, including embryonic development, neuronal development, immune responses, cancer progression and wound healing. Specific to wound healing is the migration of endothelial cells, fibroblasts and other key cellular players into the wound space. Aberrations in wound healing can result in ei...

Multiple factors affect the likelihood of a wound healing. One of these factors, wound duration, is well known to be related to healing rates, with numerous publications showing that older wounds are less likely to heal. However, disentangling the effect of this factor on wound healing rates is complex. Is this simply an observation of the obvious;...

Within chronic wounds, the relationship between the clinical diagnosis of infection and bacterial/immuno-inflammatory responses is imprecise. This study prospectively examined the interrelationship between clinical, microbiological, and proinflammatory biomarker levels between chronic venous leg ulcers (CVLUs) and diabetic foot ulcers (DFUs). Wound...

It has been known for centuries that the application of larvae is useful to heal certain wounds by facilitating debridement of necrotic tissue,(1) yet the efficacy of larval therapy continues to be debatable. This study compared the clinical effectiveness of a larval therapy dressing (BioFOAM) with a standard debridement technique (Purilon gel; hyd...

This case report describes a patient with Charcot neuroarthropathy, which has developed as a complication of his type 2 diabetes. The case is further complicated by a persistent neuropathic plantar foot ulcer. Charcot deformity significantly increases the chance of ulcers developing. In cases of ulceration, prompt treatment from a specialist multid...

Hard-to-heal leg ulcers are a major cause of morbidity in the elderly population. Despite improvements in wound care, some wounds will not heal and they present a significant challenge for patients and health care providers. A multi-centre cohort study was conducted to evaluate the effectiveness and safety of a synthetic, extracellular matrix prote...

Background: Multiple factors have been shown to delay dermal wound healing. These resultant wounds pose a significant problem in terms of morbidity and healthcare spend. Recently, an increasing volume of research has focused on the molecular perturbations underlying non-healing wounds. Objectives: This study investigates the effect of a novel ca...

Background: Wound chronicity can be due to a range of intrinsic and extrinsic factors, some of which can be controlled. Aim: The main aim of this pilot study was to explore how medications, smoking, and alcohol affect healing rates in a sample of patients at three tertiary wound care clinics. Methods: Seventy-three patients, each with an open wound...

Interleukin (IL)-24, also known as melanoma differentiation-associated gene-7, is a cytokine initially identified from cancerous cells and expressed in a range of cell types. It is a regulator of cell differentiation, growth, and apoptosis, and a promising anticancer agent. IL-24 acts via its heterodimic receptors: the IL-20R1 and IL-20R2 complex a...

Carcinomas, cancers of epithelial tissues, are the commonest malignancies and cause the greatest cancer mortality worldwide. Among these, the incidence of keratinocyte-derived non-melanoma skin cancers (NMSC), by far the greatest, is increasing rapidly. Yet despite access to tumor tissue, acceptance of human NMSC as a model carcinoma has been hinde...

Introduction: Aurora-A, Aurora-B and Aurora-C are a family of protein kinases which have been identified as key regulators of the mitotic cell division process. Members of this group have been linked with pro-tumorigenic effects and have been reported as being up-regulated in certain cancers. Our current study examines the expression profile of the...

Interleukin (IL)-8 is a pro-inflammatory cytokine that has a direct effect on immune cells, including polymorphonuclear cells. Keratinocytes are a rich source of IL-8. However, there is little knowledge on the role of IL-8 in clinical wound healing and the direct biological effect of IL-8 on keratinocytes. In this study, the effect of recombinant h...

Evaluation of keratinocyte adhesion and migration using ECIS, as will be shown below, is predominantly used to study the effects of various genes, proteins and molecules on wound healing. Keratinocytes undertake epithelialisation during the process of wound healing, and understanding their function, and their regulating factors, is important in und...

Human antigen R (HuR) is a post-translational modifier of mRNAs rich in AU- and U-rich elements. These mRNAs typically code for proteins involved in cell growth and differentiation, signal transduction, transcriptional and translational control, apoptosis, nutrient transport and metabolism. Thus, HuR affects a variety of biological functions and pr...

The aim of this study was to evaluate the cytotoxic effect of octenidine dihydrochloride/phenoxyethanol (OHP) found in vitro by conducting a randomized, double-blind controlled clinical study focusing on its safe and effective use in chronic venous leg ulcers. In total, 126 male and female patients were treated with either OHP (n = 60) or Ringer so...

This study compared wound healing efficacy of two silver dressings, AQUACEL(®) Ag and Urgotul(®) Silver, against venous ulcers at risk of infection, over 8 weeks of treatment. The primary objective was to show non inferiority of AQUACEL(®) Ag to Urgotul(®) Silver. Patients (281) were randomised into two groups. The AQUACEL(®) Ag group had 145 patie...

The incidence of tetanus in patients with wounds is unknown; however, recently concern has been raised over the proportion of tetanus cases in which a chronic wound is the portal of entry for Clostridium tetani. Varicose ulcers, dermatosis and necrosed tumours are estimated to be the point of entry for C. tetani spores in 11-14% of three cases. Of...

Combining silver-based dressings with negative pressure therapy after radical excision of chronically infected breast disease is a novel application of two technologies. One patient with complex, chronic, infected breast disease underwent radical excision of the affected area and was treated early with a combination of silver-based dressings and to...

Activated leukocyte cell adhesion molecule (ALCAM) is a glycoprotein of the immunoglobulin superfamily that has been implicated in the processes of cell adhesion and migration. The current study examines the importance of ALCAM in regulating HaCaT cell growth and migration and its potential to impact on wound healing. ALCAM levels were examined in...