EUROPEAN TISSUE REPAIR SOCIETY
ETRS ANNUAL MEETING, PISA, 2007 |
EUROPEAN TISSUE REPAIR SOCIETY ETRS ANNUAL MEETING, PISA, 2007 |
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SELECTED ABSTRACTS Abstracts
from 15 September (Pisa meeting) LOCAL AND SYSTEMIC WARMING, SURGICAL SITE INFECTION AND MICROBIOLOGY Professor David Leaper, Emeritus Professor of Surgery, University of Newcastle upon Tyne, UK The value of prophylactic antibiotics in the prevention of surgical site infection (SSI) after clean and clean-contaminated surgery is supported by level I evidence based medicine. Their value in clean surgery is controversial but a Cochrane review concluded that, although there is no statistically significant advantage to giving antibiotic prophylaxis, it cannot be firmly discarded. The definition of SSIs is difficult with no universal agreements. The reported rates of postoperative clean wound surgery are as high as 10- 18%. With the increase of day case surgery most of these infections are being transferred to primary health care where they be unrecognised and inappropriately treated. There is increasing recognition that optimal attention to perfusion, oxygenation and maintenance of normothermia and normoglycaemia are associated with low postoperative infection rates. Value of systemic warming The addition of peri-operative warming using a conductive carbon polymer mattress and overblanket (Inditherm, UK) to intra-operative warming with the Bair-Hugger (Arizant, USA) was studied in patients undergoing major, elective abdominal surgery. A statistically significant reduction in morbidity and mortality, particularly infectious complications, was found in the Inditherm group (n = 47, 15%) compared to the controls (n = 56, 34%). There was also a statistically significant reduction in operative blood loss, POSSUM physiological score and improvement in core temperature. In a more limited study of systemic warming, using the carbon polymer mattress, patients presenting with severe secondary peritonitis (n = 33) were randomised to standard care or warming during resuscitation. In the warmed group there was a reduction in their APACHE score and their predicted mortality. Value of local warming In an RCT of clean-wound surgery it was found that local warming with non-contact radiant heat (Warm-Up, Arizant, USA) was as good as systemic warming. Close post-discharge surveillance by a trained, blinded observer for 6 weeks showed an SSI rate of 15% in controls with 4- 6% in the local and systemically warmed groups (p < 0.001). Warmed patients had less antibiotics prescribed in primary care for wound complications (6% and 16% respectively, p < 0.002). Methicillin resistant Staphylococcus aureus (MRSA) is an increasing cause of Healthcare Associated Infection. In 33 community-based patients with stage III-IV pressure sores MRSA was cultured from 14. When their pressure sores were randomised to standard care or local warming using there was a statistically significant eradication of MRSA colonisation in the warmed group (5/8 vs 0/6; p < 0.03). UPDATE ON 3D WOUND ASSESSMENT Tommaso Bianchi, Dept of Clinical and Experimental Medicine, Division of Dermatology, University of Bologna; and Valentina Dini, Maria Stefania Bertone and Marco Romanelli, Dept of Dermatology, University of Pisa, Italy Venous leg ulcers, which may take months to heal, account for 40 to 70% of all lower extremity chronic wounds. Predicting the prognosis of a venous ulcer is an important task. Clinical evaluation of wound size is normally limited to measuring length, width, and depth, and comparing those figures to previously obtained values. Wound measuring systems can be divided in contact and non-contact types. The first group includes bidimensional techniques such as simple measurement of length and width, manual or digital planimetrics and 3D techniques such as molds/wound filling, kundin gauge and ultrasonic measurement tools. Non-contact systems include 2D techniques like use of scaled photographs or enhanced digital photography and volume analyzers such as computerized stereophotogrammetry devices. Non-contact three-dimensional devices provide accurate results which can be used for wound care research. So far, prognostic indicators for healing in venous leg ulcer have been based upon 2D wound measurements. In this study a Minolta VL 900 3D laser scanner was used to measure wound area and volume. This device is able to acquire data of surface with a SEM (standard error of measurement) < 3% for surface and < 5% for volume. Our purpose was to compare measurements of depth, area and volume obtained by threedimensional laser scanner acquisition in subjects affected by venous leg ulcers during 24 weeks of standard wound care and to assess feasibility of these indicators for prediction of healing or non-healing. DESIGNING A WOUND MEASUREMENT SYSTEM FOR APPLICATION IN CLINICAL TRIALS AND ROUTINE CLINICAL PRACTICE Dr W Richard Fright, Dr Bruce LK Davey, Dr Bruce C McCallum, Dr Mark A Nixon and James TG Preddey. ARANZ Medical Ltd, Christchurch, New Zealand Aim Develop a portable measurement and documentation system to accurately record wound image, surface area and depth, that is compact, inexpensive and easy to use for clinical trials and routine clinical practice. Method An imaging system consisting of lasers and high-resolution camera has been developed for measuring wound image, surface area and depth. The lasers define three-dimensional surface data, allowing the skin surface to be modelled, enabling accurate surface area and depth measurement. Software running on an attached Personal Digital Assistant (PDA), enables user analysis of scanned images, creation of reports, and local storage and remote archiving of data. The resulting system is the ARANZ Medical SilhouetteTM. To assess accuracy, patches of known surface area were placed on a mannequin leg. Each patch was measured five times with Silhouette, and five times by transparent film wound tracing. Next, three wound models of known depths were constructed and their depth measured five times with Silhouette. The mean error, standard deviation and maximum error were calculated for each patch and model measured. Results Silhouette is compact and portable, weighing and measuring less than 300 grams and 17 x 11 x 3cm respectively. It is quick to use with scanning taking less than 2 minutes. For Silhouette accuracy tests, the largest mean error and largest standard deviation of the five patches measured was 1.5% and 0.5% respectively. The largest error of any single measurement was 1.9%. By comparison, for transparent film tracings, the largest mean error and largest standard deviation was 1.6% and 1.2% respectively. The largest error of any single measurement was 3.0%. For Silhouette depth measurements, the largest mean error and largest standard deviation was 0.8% and 0.4% respectively. The largest error of any single measurement was 1.3%. Conclusion Silhouette is a compact and portable imaging device that measures surface area and depth of wound models more accurately and repeatably than existing methods. PLACENTA GROWTH FACTOR IN SKIN REPAIR Teresa Odorisio, IDI-IRCCS, Rome, Italy Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family promoting adult pathophysiological neovascularization. In adult skin, PlGF expression is barely detectable, and it is upregulated in association with both physiological and pathological neoangiogenesis. During wound healing, PlGF expression is induced in migrating keratinocytes and endothelial cells of small blood vessels, acting in a paracrine and autocrine way on VEGFR-1-expressing endothelium. Knockout mice for PlGF show delayed wound closure associated with reduced number of mature vessels within the granulation tissue, indicating that PlGF contributes to skin repair by inducing angiogenesis. Since reduced dermal microcirculation and diminished expression of growth factors contribute to ulcer formation in diabetes, we investigated whether PlGF may be involved in the healing impairment of diabetic cutaneous wounds and tested the activity of adenovirus-mediated PlGF gene transfer in promoting diabetic skin repair. By using streptozotocin-induced diabetic mice, we found that PlGF induction is greatly reduced in the diabetic wounds compared to non diabetic controls, both at the mRNA and protein level. Moreover, diabetic transgenic mice overexpressing PlGF in the skin under the control of a keratin 14 promoter (K14-PlGF mice) have an accelerated wound closure with respect to diabetic wildtype littermates. Local treatment with an adenoviral vector carrying the human PlGF gene (AdCMV.PlGF) in diabetic mice significantly improves the healing process and accelerates wound closure compared to the control vector (AdCMV.LacZ) or saline. The histological analysis of wound specimens revealed that granulation tissue formation is increased and accelerated in AdCMV.PlGF-treated mice, compared to AdCMV.LacZ- or saline-treated mice. Immunohistochemical PECAM/CD31 staining demonstrated that granulation tissue vascularization is significantly augmented in AdCMV.PlGF-treated mice as compared to controls, and smooth muscle ß-actin staining revealed an increased number of mature vessels in the granulation tissue following PlGF transduction. Immunohistochemistry with an antibody detecting monocytes/macrophages (Mac-3) indicated that AdCMV.PlGF treatment is associated with inflammatory cell local recruitment. On the contrary, colony forming assay of myeloid precursors in the peripheral blood did not show any increase in progenitor stem cell mobilization from the bone marrow in AdCMV.PlGF-treated mice with respect to controls, suggesting a local effect of transduced PlGF. PDGF, FGF-2 and VEGF mRNA levels, analyzed by real time RT-PCR, are increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated effects. Finally, we found that cultured dermal fibroblasts express the PlGF receptor VEGFR-1 and respond to PlGF treatment by enhancing their migration. Such effect is inhibited by an anti-PlGF or an anti-VEGFR1 antibody, pointing to a possible direct role of PlGF in promoting granulation tissue maturation. In conclusion, our data show that reduced PlGF expression contributes to impaired wound healing in diabetes. They also indicate that PlGF has therapeutic potential for diabetic ulcer treatment. PlGF gene transfer exerts its beneficial effect by enhancing different aspects of the repair process suggesting a wider spectrum of action for this factor in the wound healing process, not limited to its capacity to induce angiogenesis. A VIEW OF THE CLINICAL ASPECTS OF KELOIDS AND THEIR MANAGEMENT WITH STEROIDS. Dr E Anthony, Vaiude PN, Syed M, Davies K, Moir GC, Shibu MM and Navsaria HN. Barts and The London School of Medicine and Dentistry, London, UK 256 keloids were classified on the basis of the type of previous treatment, previous history of keloids, site of keloids, surface area, different combinations of steroid therapy and the number of keloids that recurred. Keloids in the nonbearded area of the face had a mean dose of 9.67mg by the end of treatment with no recurrence. Likewise the bearded area had a mean dose of 20.3mg with a 33% chance of recurrence, the upper limbs 21.9mg with 20% recurrence, the earlobes 16.4mg with 10% recurrence, occipital area of the head 18.3mg with 0% recurrence. After treatment in our keloid clinic we found that 42% were discharged with no recurrence, 9% returned for further injections, 3% went on to have excision surgery, 7% went on to have camouflage treatment, 29% were partially treated and declined further treatment following steroid therapy, 3 % were discharged fully treated with pressure earrings and 1% refused steroid therapy and went for surgery. The mean dose that the patients received who had recurrence post treatment was 34.62mg, 29.96mg in those who had no recurrence and in those who had persistence it was 24.12mg. Of those who had 10mg/ml of Triamcinolone 22% had recurrence, those on 40mg/ml had a 25% recurrence. Those who had 10mg/ml followed by 40 mg/ml had a 10% recurrence, those on 40mg/ml then 10mg/ml had a 50% possibility of recurrence and then those who had 10mg then 40mg/ml and then 10mg/ml had a 24% recurrence. Previous treatment had no bearing on the possibility of recurrence. AUTOLOGOUS CONDITIONED SERUM (ACS) COMPARED TO HYALURONAN- AND SALINE-INJECTIONS FOR REGENERATIVE TREATMENT OF KNEE OSTEOARTHRITIS Carsten Moser and Julio Reinecke, Orthogen Objective Non-surgical treatments for OA are underdeveloped. A therapy based on intra-articular injection of autologous conditioned serum (ACS), has shown clinical benefit in animal and human studies. In the present controlled, clinical study, clinical efficacy and safety of intra-articular injections of ACS were compared to intra-articular hyaluronan (HA), and saline in patients with confirmed knee OA. Methods ACS was generated by incubating venous blood with medical grade glass beads. PBMC produce endogenous antiinflammatory cytokines such as interleukin-1 receptor antagonist (IL-1Ra)(1). In a prospective, randomized, double blind, controlled trial with three parallel groups, 399 patients with knee OA were included in an intention to treat (ITT-) analysis. Efficacy was assessed by WOMAC, VAS, SF-8, GPA after 7, 13 and 26 weeks. Frequency and severity of adverse events wee recorded. Results In all treatment groups, intra-articular injections produced significant improvement (WOMAC-scores and weightbearing pain (VAS)). Health-related quality of life improved. ACS was statistically significant superior to the other groups for all outcome measures and all time points. Mean improvement for patients treated with HA and saline was half that in the ACS-group (p < 0.001). No significant differences between HA- and saline-group were recorded. Frequency of adverse advents (AE) was comparable in the ACS- and saline-group (p > 0.05). Significantly more AE occured in the HA-group (p < 0.05 for the comparison with ACS and saline). Conclusion Patients with OA of the knee treated by intra-articular injection of ACS showed significant clinical improvement during 26 weeks observation compared to patients injected with HA or saline. Results demonstrate that ACS is effective and well tolerated in the management of chronic, idiopathic knee OA. So far, efficacy of ACS is defined through improvement in clinical symptoms, particularly pain. It remains to be determined whether there are disease-modifying, tissue protective, or even tissue regenerative, sequelae. EVALUATION
OF THE CLINICAL EFFECTIVENESS OF A COLLAGEN-ORC ANTIMICROBIAL MATRIX IN
VENOUS LEG ULCERATIONS POLYACRYLATE-SUPERABSORBER INHIBITS EXCESSIVE METALLOPROTEASE ACTIVITY IN WOUND FLUID FROM NON-HEALING WOUNDS Hans Smola3, Sabine Eming1, Sigrun Smola-Hess2 and Thomas Krieg1 1) Department of Dermatology, University of Cologne; 2) Institute of Virology, University of Cologne, Germany; 3) Paul Hartmann AG, Heidenheim, Germany. Introduction: Impaired wound healing such as in leg ulcers, diabetic foot ulcers and pressure sores is associated with excessive protease levels most of all metalloproteases (MMP)which degrade newly formed extracellular matrix and thus perturb granulation tissue formation. Polyacrylate-superabsorbers consist of acrylic acid polymers and have been introduced into wound dressings such as in TenderWet® for more than ten years. Their physico-chemical properties make these polymers exquisite candidates for inhibiting MMPs. Aim: We tested whether polyacrylate-superabsorber can inactivate MMP activity in wound fluid and thus reduce the excessive MMP burden in chronic non-healing skin ulcers. Methods: Wound fluid from non-healing venous leg ulcers, was incubated with ringer’s solution pre-activated polyacrylatesuperabsorber. MMP activity was measured with specific peptide substrates as well as gelatine zymography after incubation with the pre-activated polyacrylate-superabsorber. Results: Our data reveal that pre-activated polyacrylate-superabsorber inhibits 90% of MMP-2, -9 activity in wound fluid from non-healing venous leg ulcers. Detailed analysis showed that inhibition was due to compartmentalization of MMPs on the pre-activated polyacrylate-superabsorber as well as by long ranging diffusible mechanisms. Conclusion: Polyacrylate-superabsorber have been employed to balance wound moisture for more than ten years now. They can provide moisture to dry wounds as well as absorb copious amounts of exudates. The current finding of MMP inhibition provides a novel rationale for use of these polymers to actively influence the non-healing wound environment and promote granulation tissue formation at attractive costs.
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