Prevention of surgical site infection in total joint arthroplasty : an international tertiary care center survery

Background Prevention strategies are critical to reduce infection rates in total joint arthroplasty (TJA), but evidence-based consensus guidelines on prevention of surgical site infection (SSI) remain heterogeneous and do not necessarily represent this particular patient population. Questions/Purposes What infection prevention measures are recommended by consensus evidence-based guidelines for prevention of periprosthetic joint infection? How do these recommendations compare to expert consensus on infection prevention strategies from orthopedic surgeons from the largest international tertiary referral centers for TJA? Patients and Methods A review of consensus guidelines was undertaken as described by Merollini et al. Four clinical guidelines met inclusion criteria: Centers for Disease Control and Prevention's, British Orthopedic Association, National Institute of Clinical Excellence's, and National Health and Medical Research Council's (NHMRC). Twenty-eight recommendations from these guidelines were used to create an evidence-based survey of infection prevention strategies that was administered to 28 orthopedic surgeons from members of the International Society of Orthopedic Centers. The results between existing consensus guidelines and expert opinion were then compared. Results Recommended strategies in the guidelines such as prophylactic antibiotics, preoperative skin preparation of patients and staff, and sterile surgical attire were considered critically or significantly important by the surveyed surgeons. Additional strategies such as ultraclean air/laminar flow, antibiotic cement, wound irrigation, and preoperative blood glucose control were also considered highly important by surveyed surgeons, but were not recommended or not uniformly addressed in existing guidelines on SSI prevention. Conclusion Current evidence-based guidelines are incomplete and evidence should be updated specifically to address patient needs undergoing TJA.

Treatment of experimental periodontal disease by a selective inhibitor of cyclooxygenase-2 with scaling and root planing (SRP)

Lumiracoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) approved for the relief of symptoms of chronic inflammatory conditions. The aim of this study was to evaluate the effects of this specific inhibitor of COX-2 as adjunctive treatment on induced periodontitis in rats. Periodontal disease was induced at the first mandibular molar of 60 rats. After 7 days, the ligature was removed and all animals were submitted to scaling and root planing (SRP) along with local irrigation with saline solution and were divided into 2 groups: SRP (n = 30)-received subcutaneous injections of 1 mg/kg of body weight/day of saline solution for 3 days and; SRP + L (n = 30)-received subcutaneous injections of 1 mg/kg of body weight/day of Lumiracoxib for 3 days. Ten animals in each group were killed at 7, 15, and 30 days. The histological description was performed and the histometric values were statistically analyzed. In Group SRP + L, the histometric analysis (0.58 ± 0.08, 0.64 ± 0.06, and 0.56 ± 0.10 mm 2) showed less bone loss (p < 0.05) than Group SRP (1.52 ± 0.08, 1.55 ± 0.09, and 1.49 ± 0.24 mm 2) at 7, 15, and 30 days, respectively. Within the limits of this study it can be concluded that subcutaneous application of specific inhibitor of COX-2 was a beneficial adjunctive treatment for periodontal diseases induced in rats. © 2010 Springer Basel AG.

Realistic irrigation visualization in a surgical wound debridement simulator

Wound debridement refers to the removal of necrotic, devitalized, or contaminated tissue and/or foreign material to promote wound healing. Surgical debridement uses sharp instruments to cut dead tissue from a wound and it is the quickest and most efficient method of debridement. A wound debridement simulator [1,2] can ensure that a medical trainee is competent prior to performing a procedure on a genuine patient. Irrigation is performed at different stages of debridement in order to remove debris and reduce the bacteria count through rinsing the wound. This paper presents a novel approach for realistic irrigation visualization based on texture representations of debris. This approach applies image processing techniques to a series of images, which model the cleanliness of the wound. The active texture is generated and updated dynamically based on the irrigation state, location, and range. Presented results demonstrate that texture mapping and image processing techniques can provide effective and efficient solutions for irrigation visualization in the wound debridement simulator.

The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats

The Copaiba oil has been used as an auxiliary treatment of inflammations, skin disorders and stomach ulcers, however, in dentistry, this alternative medicine has not been investigated yet. The purpose of this study was to evaluate the influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction. Twenty-eight wistar male rats had their lower first molar teeth extracted. Subsequently, they were divided in four groups, according to the treatment performed: (a) alveolar socket irrigation with copaiba oil; (b) alveolar socket irrigation with physiological serum; (c) daily gavage with copaiba oil or (d) daily gavage with physiological serum. After the sacrifice, the mandibles were removed and processed in order to obtain decalcified histological sections. The results demonstrated high level of epithelial migration, small number of inflammatory cells and vascular enhancement in the animals which received systemic administration of copaiba oil. The rats treated with topic administration of copaiba oil presented ulcerations and large number of inflammatory cells. An increased bone neoformation was observed in both groups treated with copaiba oil when compared with placebo group. It could be concluded that topic or systemic administration of copaiba oil leads to a better alveolar bone healing, however the topic application on connective tissue should be carefully considered, regarding the whole socket wound healing. © Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488.

Influence of irrigation and intracanal dressing on the healing process of dogs' teeth with apical periodontitis.

Dogs' teeth with apical periodontitis were treated endodontically, Dakin's solution being used in an experimental group as the irrigation solution, and camphorated paramonochlorophenol as an intracanal dressing. For a second group of teeth, the irrigation solution used was physiologic saline, dry cotton only being placed into the pulpal chamber to take the place of an intracanal dressing. In a second visit, overinstrumentation and a new application of the same kind of dressing were performed, the root canals being then filled with gutta-percha cones and zinc oxide-eugenol cement. Other specimens were treated, in one visit, where physiologic saline or Dakin's solution were the irrigation solutions. The animals were sacrificed 6 months after the obturation of the root canals. Histologic exams showed better results for the experimental group where Dakin's solution and camphorated paramonochlorophenol had been used, with signs of repair characterized by newly formed cementum and bone tissue, as well as a marked reduction in size of the periapical lesions. No differences were seen in the results with physiologic saline or Dakin's solution as irrigants.

Aseptic tissue necrosis and chronic inflammation after irrigation of penetrating hand wounds using Octenisept®

Penetrating hand wounds are common and these are managed by thorough debridement. However, stab wounds without evidence of divided structures are often treated with irrigation using antiseptic substances, antibiotic therapy, and immobilization. Octenisept® (Schülke & Mayr Ltd) is a widely used antiseptic agent for disinfection of acute or chronic wounds. It has a broad spectrum of antiseptic efficacy and has become an antiseptic of first choice in many hospitals. Within a few months, four patients presented to us with chronic inflammation and severe tissue necrosis after irrigation of penetrating hand wounds with Octenisept®. Repeated surgery and debridement was required in all patients. Wound healing was prolonged and patients had persisting oedema. Penetrating hand wounds must not be irrigated with Octenisept®.

Ex vivo investigation of novel wound healing therapies and development of a 3-D human skin equivalent wound model

It has previously been found that complexes comprised of vitronectin and growth factors (VN:GF) enhance keratinocyte protein synthesis and migration. More specifically, these complexes have been shown to significantly enhance the migration of dermal keratinocytes derived from human skin. In view of this, it was thought that these complexes may hold potential as a novel therapy for healing chronic wounds. However, there was no evidence indicating that the VN:GF complexes would retain their effect on keratinocytes in the presence of chronic wound fluid. The studies in this thesis demonstrate for the first time that the VN:GF complexes not only stimulate proliferation and migration of keratinocytes, but also these effects are maintained in the presence of chronic wound fluid in a 2-dimensional (2-D) cell culture model. Whilst the 2-D culture system provided insights into how the cells might respond to the VN:GF complexes, this investigative approach is not ideal as skin is a 3-dimensional (3-D) tissue. In view of this, a 3-D human skin equivalent (HSE) model, which reflects more closely the in vivo environment, was used to test the VN:GF complexes on epidermopoiesis. These studies revealed that the VN:GF complexes enable keratinocytes to migrate, proliferate and differentiate on a de-epidermalised dermis (DED), ultimately forming a fully stratified epidermis. In addition, fibroblasts were seeded on DED and shown to migrate into the DED in the presence of the VN:GF complexes and hyaluronic acid, another important biological factor in the wound healing cascade. This HSE model was then further developed to enable studies examining the potential of the VN:GF complexes in epidermal wound healing. Specifically, a reproducible partial-thickness HSE wound model was created in fully-defined media and monitored as it healed. In this situation, the VN:GF complexes were shown to significantly enhance keratinocyte migration and proliferation, as well as differentiation. This model was also subsequently utilized to assess the wound healing potential of a synthetic fibrin-like gel that had previously been demonstrated to bind growth factors. Of note, keratinocyte re-epitheliasation was shown to be markedly improved in the presence of this 3-D matrix, highlighting its future potential for use as a delivery vehicle for the VN:GF complexes. Furthermore, this synthetic fibrin-like gel was injected into a 4 mm diameter full-thickness wound created in the HSE, both keratinocytes and fibroblasts were shown to migrate into this gel, as revealed by immunofluorescence. Interestingly, keratinocyte migration into this matrix was found to be dependent upon the presence of the fibroblasts. Taken together, these data indicate that reproducible wounds, as created in the HSEs, provide a relevant ex vivo tool to assess potential wound healing therapies. Moreover, the models will decrease our reliance on animals for scientific experimentation. Additionally, it is clear that these models will significantly assist in the development of novel treatments, such as the VN:GF complexes and the synthetic fibrin-like gel described herein, ultimately facilitating their clinical trial in the treatment of chronic wounds.

Distribution of benefits of irrigation induced technological changes and commodity markets : new evidence

A plethora of literature exists on irrigation development. However, only a few studies analyse the distributional issues associated with irrigation induced technological changes (IITC) in the context of commodity markets. Furthermore, these studies deal with only the theoretical arguments and to date no proper investigation has been conducted to examine the long-term benefits of adopting modern irrigation technology. This study investigates the long-term benefit changes of irrigation induced technological changes using data from Sri Lanka with reference to rice farming. The results show that (1) adopting modern technology on irrigation increases the overall social welfare through consumption of a larger quantity at a lower cost (2) the magnitude, sensitivity and distributional gains depend on the price elasticity of demand and supply as well as the size of the marketable surplus (3) non-farm sector gains are larger than farm sector gains (4) the distribution of the benefits among different types of producers depend on the magnitude of the expansion of the irrigated areas as well as the competition faced by traditional farmers (5) selective technological adoption and subsidies have a detrimental effect on the welfare of other producers who do not enjoy the same benefits (6) the short-term distributional effects are more severe than the long-term effects among different groups of farmers.

Recent advances in dermal wound healing : biomedical device approaches

Successful repair of wounds and tissues remains a major healthcare and biomedical challenge in the 21st Century. In particular, chronic wounds often lead to loss of functional ability, increased pain and decreased quality of life, and can be a burden on carers and health-system resources. Advanced healing therapies employing biological dressings, skin substitutes, growth factor-based therapies and synthetic a cellular matrices, all of which aim to correct irregular and dysfunctional cellular pathways present in chronic wounds, are becoming more popular. This review focuses on recent advances in biologically inspired devices for would healing and includes a commentary on the challenges facing the regulatory governance of such products.

A new future for growth factor complexes as wound therapies?

Background: Topical administration of growth factors (GFs) has displayed some potential in wound healing, but variable efficacy, high doses and costs have hampered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple GFs and extracellular matrix (ECM) proteins. The Problem: Deep dermal partial thickness burn (DDPTB) injuries are the most common burn presentation to pediatric hospitals and also represent the most difficult burn injury to manage clinically. DDPTB often repair with a hypertrophic scar. Wounds that close rapidly exhibit reduced scarring. Thus treatments that shorten the time taken to close DDTPB’s may coincidently reduce scarring. Basic/Clinical Science Advances: We have observed that multi-protein complexes comprised of IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes. These responses require activation of both the IGF-1R and the VN-binding αv integrins. We have recently evaluated the wound healing potential of these GF:VN complexes in a porcine model of DDTPB injury. Clinical Care Relevance: This pilot study demonstrates that GF:VN complexes hold promise as a wound healing therapy. Enhanced healing responses were observed after treatment with nanogram doses of the GF:VN complexes in vitro and in vivo. Critically healing was achieved using substantially less GF than studies in which GFs alone have been used. Conclusion: These data suggest that coupling GFs to ECM proteins, such as VN, may ultimately prove to be an improved technique for the delivery of novel GF-based wound therapies.

In vivo evaluation of an ultra-thin polycaprolactone film as a wound dressing

The use of ultra-thin films as dressings for cutaneous wounds could prove advantageous in terms of better conformity to wound topography and improved vapour transmission. For this purpose, ultra-thin poly(epsilon-caprolactone) (PCL) films of 5-15 microm thickness were fabricated via a biaxial stretching technique. To evaluate their in vivo biocompatibility and feasibility as an external wound dressing, PCL films were applied over full and partial-thickness wounds in rat and pig models. Different groups of PCL films were used: untreated, NaOH-treated, untreated with fibrin, NaOH-treated with perforations, and NaOH-treated with fibrin and S-nitrosoglutathione. Wounds with no external dressings were used as controls. Wound contraction rate, histology and biomechanical analyses were carried out. Wounds re-epithelialized completely at a comparable rate. Formation of a neo-dermal layer and re-epithelialization were observed in all the wounds. A lower level of fibrosis was observed when PCL films were used, compared to the control wounds. Ultimate tensile strength of the regenerated tissue in rats reached 50-60% of that in native rat skin. Results indicated that biaxially-stretched PCL films did not induce inflammatory reactions when used in vivo as a wound dressing and supported the normal wound healing process in full and partial-thickness wounds.

A two-compartment mechanochemical model of the roles of transforming growth factor-beta and tissue tension in dermal wound healing

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor-beta (TGF-beta) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF-beta and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF-beta in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF-beta significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures.

Development of a 3-dimensional human skin equivalent wound model for investigating novel wound healing therapies

Numerous difficulties are associated with the conduct of preclinical studies related to skin and wound repair. Use of small animal models such as rodents is not optimal because of their physiological differences to human skin and mode of wound healing. Although pigs have previously been used because of their human-like mode of healing, the expense and logistics related to their use also renders them suboptimal. In view of this, alternatives are urgently required to advance the field. The experiments reported herein were aimed at developing and validating a simple, reproducible, three-dimensional ex vivo de-epidermised dermis human skin equivalent wound model for the preclinical evaluation of novel wound therapies. Having established that the human skin equivalent wound model does in fact “heal," we tested the effect of two novel wound healing therapies. We also examined the utility of the model for studies exploring the mechanisms underpinning these therapies. Taken together the data demonstrate that these new models will have wide-spread application for the generation of fundamental new information on wound healing processes and also hold potential in facilitating preclinical optimization of dosage, duration of therapies, and treatment strategies prior to clinical trials.

Mathematical modelling of chronic wound healing

Chronicwounds fail to proceed through an orderly process to produce anatomic and functional integrity and are a significant socioeconomic problem. There is much debate about the best way to treat these wounds. In this thesis we review earlier mathematical models of angiogenesis and wound healing. Many of these models assume a chemotactic response of endothelial cells, the primary cell type involved in angiogenesis. Modelling this chemotactic response leads to a system of advection-dominated partial differential equations and we review numerical methods to solve these equations and argue that the finite volume method with flux limiting is best-suited to these problems. One treatment of chronic wounds that is shrouded with controversy is hyperbaric oxygen therapy (HBOT). There is currently no conclusive data showing that HBOT can assist chronic wound healing, but there has been some clinical success. In this thesis we use several mathematical models of wound healing to investigate the use of hyperbaric oxygen therapy to assist the healing process - a novel threespecies model and a more complex six-species model. The second model accounts formore of the biological phenomena but does not lend itself tomathematical analysis. Bothmodels are then used tomake predictions about the efficacy of hyperbaric oxygen therapy and the optimal treatment protocol. Based on our modelling, we are able to make several predictions including that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds, treatment should continue until healing is complete and finding the right protocol for an individual patient is crucial if HBOT is to be effective. Analysis of the models allows us to derive constraints for the range of HBOT protocols that will stimulate healing, which enables us to predict which patients are more likely to have a positive response to HBOT and thus has the potential to assist in improving both the success rate and thus the cost-effectiveness of this therapy.