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Rothschild Hospital Paris and the Elancourt Excellence Center

Two and a half day focus on new and advanced technologies

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Diabetic foot Ulcers

Jan Apelqvist

85% of diabetes-related amputations are preceded by a foot ulcer.
50% to 70% of all lower extremity amputations are related to diabetes.
3% to 8% of people with diabetes have a foot ulcer.

It takes on average 11-14 weeks to heal a diabetes foot ulcer. There is a 15% amputation rate in people with diabetes foot ulcer. 20% of total expenditure on diabetes can be attributable to the diabetic foot.

The diabetic foot can be defined as infection, ulceration and/or destruction of deep tissues associated with neurological abnormalities and various degree of peripheral vascular disease in the lower limb.

Foot complications in diabetes present a particularly troubling and it has been claimed that every 30 seconds, a lower limb is amputated due to diabetes. The complexity of diabetes foot ulcers necessitates an intrinsic knowledge of underlying patophysiology and a multifactorial approach in which aggressive management of infection is of major importance. The negative consequences of foot ulcers in people with diabetes on quality of life include not only morbidity but also disability and premature mortality

A multidisciplinary approach including preventive strategy, patient and staff education and multifactorial treatment of foot ulcers has been reported to reduce amputation rate by more than 50%.

Evolution of signs of clinical infection and biofilms

Keith Cutting

The clinical signs of wound infection have yet to be universally agreed and accepted as these are often a personal interpretation. Publications in 1994 and more recently in 2005 have provided greater insight into how infection may manifest especially in chronic wounds.

However, it remains unclear as to whether there is any association of these clinical signs with infections that are primarily of biofilm generated. This presentation will explore this situation.

Maggot Debridement

Finn Gottrup

Introduction

The maggots of Lucilia sericata provide effective treatment for debridement of problem wounds. Maggot’s debridement has been suggested to work by a mechanical and biochemical mode. The mechanical mode is based on use of the mandibles or “mouth hooks” of the maggots and their rough body, while biochemical mode is caused by the maggot excretions and secretion, which possess proteolytic enzymes that can dissolve the dead and/or infected matrix on the wound bed. Recent research shows that the biochemical mechanisms may be of most importance for the debridement of wounds by maggots.

Methods

Maggot provides a more selective debridement than a surgeon. This is especially important in areas where exposed bone is critical (e.g. the heel area).

Two modes of application are available, the free range and captured method. Both methods are effective, but in undermined cavity wounds free maggots may be preferred.

Maggot therapy has been suggested for treatment of biofilms in wounds, and it has been shown that maggot excretion/secretions breakdown biofilms of both Gram-positive and Gram-negative bacteria.

Conclusion

Even though evidence on the highest level of the effect of MDT is lacking, the clinical experience strongly suggests that the technique is an effective and safe method of debridement of wounds. Maggot treatment could also provide a new treatment of biofilm formation in patients suffering of problem wounds.

Topical Negative Pressure Instillation Therapy with polyhexanid solution as treatment for posttraumatic osteomyelitis and biofilm formation

Gerrolt Jukema

Posttraumatic osteomeyelits is a hard to heal complication in orthopaedic and trauma surgery. This complication is often associated with biofilm formation on implants.

Bacterial specimens who are often associated with biofilm formation are S.aureus, S.epidermidis and P. aeruginosa.

Surgical debridement in combination with lavage is still the corner stone for treatment.

A new mode of negative pressure therapy, so called instillation negative pressure therapy with polyhesanid solution seems to be very promising as adjunct therapy for treatment of posttraumatic osteomyelitis

Biofilm characterization

Véronique Larreta-Garde

A biofilm is a complex supramolecular and supracellular assembly. Its characterization consists in focusing on its different constituents on a one hand and on its global properties on the other hand.

First, the general aspect of the biofilm may be observed through microscopic studies; scanning electron microscopy and laser confocal microscopy give the best result. Second, bacteria involved in the biofilm may be characterized by classical microscopic observations or bacterial analysis. Cell-attachment may be observed with crystal violet or biofilm ring test. DNA staining permits to determine the organization of bacterial cells such as dispersed bacteria oraggregated cells. Specific DNA fluorescent probes even allow the recognizing of the variousstrains in a bacterial mixture.

Then, the matrix part of the biofilm may be investigated. The polysaccharide part may be characterized qualitatively and quantitatively with the use of florescent lectins. Proteins may be quantified and analyzed mainly with 2D electrophoresis or Western blot. Proteomics has been extensively used for this fine characterization.

Finally, the mechanical properties of the biofilm may be examined with physicochemical methods such as rheology.

Vascular evaluation in wound management: effectiveness and value

Raj Mani

Some 80% of chronic wounds are lower extremity wounds of which the majority result from hypertension and or diabetes. It is essential to seek exclusion of vascular disease when treating such wounds.

Measures such as ABPI (ankle-brachial pressure index) are well understood and widely available. Its limitations are also understood. In the current climate where there is an increase in the prevalence of peripheral vascular disease in the diabetic population, early Duplex examination to image and to derive haemodynamic profiles offer incredible value to clinicians.

Transcutaneous oxygen sensors permit reliable measurement of tissue viability in diabetic skin that is subject to insults from ischaemia as well as infection.

Other techniques with potential to assess the microcirculation must be examined carefully so clinical management of chronic wounds may be co-ordinated at all levels of care.

Venous Leg Ulcers Presenting Inflammatory Signs Suggesting Heavy Bacterial Colonization: Results of a Randomized Controlled Study

Sylvie Meaume

Objective

Clinical interest of silver in the management of chronic wounds is not fully established. The main objective of this clinical study was to assess the ability of a new silver releasing lipido-colloid contact layer to promote the healing process of venous leg ulcers (VLU) presenting inflammatory signs suggesting a heavy bacteria colonization and then a delayed healing, in comparison to the same wound dressing not impregnated with silver salts.

Methods

This was an open-labeled, randomized, controlled trial. VLU presenting at least 3 out of 5 clinical signs suggesting heavy bacterial colonization were recruited. Patients were treated with contact layer silver dressing ([CLS], Restore® Contact Layer, Silver* (Hollister Wound Care, Libertyville, Ill) or contact layer dressing ([CL] Restore® Contact Layer**, Hollister Wound Care, Libertyville, Ill) for 4 weeks, then all treated ulcers were treated with CL for the 4 additional weeks. Wound evaluation and area measurements were conducted weekly during the first 4 weeks and then at week 6 and 8. Main efficacy criterion was absolute wound area decrease (AD) at week 4 and week 8

Results

Patients (N = 102) were randomized and treated. Ulcers were present for nearly 11 months on average; 65% were recurrent and mean area was 20.0 ± 17.8 cm2. Almost 80% of the treated VLU were stagnating/ aggravating with their previous treatment. By week 4, mean surface area decreased by 6.5 ± 13.4 cm2 (median: 4.2 cm2) and 1.3 ± 9.0 cm2 (median: 1.1 cm2) in CLS and CL groups, respectively (P = 0.023). At week 8, median decrease was 5.9 cm2 versus 0.8 cm2 (P = 0.002) with a wound percentage decrease of 47.9% and 5.6% (P = 0.036). Median closure rate was 0.145 versus 0.044 cm2/day (P = 0.009) at week 4 and remained higher in the CLS group up to week 8 even after switching to CL dressing in these patients (P = 0.001). Odds ratio (multinomial logistic regression) of the chance to reach a ? 40% wound area reduction was 2.7 (95% CI: 1.1 to 6.7; P = 0.038) for silver treated ulcers. Dressing tolerance was good in both groups.

Conclusion

A 4-week treatment with silver releasing lipido-colloid contact layer promotes a sustained increase of closure rate of venous leg ulcers presenting inflammatory signs suggesting a high bacterial load. Also marketed as *Urgotul® Silver and **Urgotul®, Laboratoires Urgo, (France).

Molecular aspects of wound healing: growth factors and stem cells

Antonio Montalvo

Wound healing, from a molecular viewpoint, is a complex process involving blood clotting, inflammation, new tissue formation, and tissue remodeling. Underlying this healing process, it is involved a cascade and a finely tuned interplay between several Cell types, molecular Factors, such as Growth Factors, Bone Morphogenetic Proteins, Cytokines, low-molecular weight compounds and their downstream effectors and pathways.

The dysregulation of these factors may lead to wound healing disorders resulting in chronic wounds, as well as abnormal scars.

Experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors are still unclear.

Functional data have being obtained by applying neutralizing antibodies to wounds.

A rising number of stem cell therapies for cutaneous wounds are currently under development. These have been encouraged by promising preliminary findings in both animal models and human studies. However, we still lack an in-depth understanding of the underlying mechanisms through which stem cells contribute to cutaneous wound healing.

Wound Assessment

Marco Romanelli

Assessment of cutaneous wounds in order to detect the progression of a disease is a routine part of medical practice. Although measurement technology has evolved continuously over the years in all fields of medicine, its direct application to cutaneous disorders has increased only in recent years. In fact, only over the past decade has significant research been undertaken to further develop techniques for specifically examining the skin.

Advances in both the technology of imaging and computer systems have greatly supported this process and brought it closer to the clinical area. Assessment of any wound should begin with the determination of the extent of the area involved.

Because the extent of a wound is a dynamic process, it requires repeated systematic assess-ment. The total wound extent is based on the wound dimensions and the tissue level involved. The clinical evaluation of the extent of tissue involvement due to a skin lesion and, moreover, the way a lesion evolves over time are often assessed according to the common sense and memory of the clinician.

Evaluations are in general performed on the basis of clinical experience, using very basic, low-tech equipment to make objective measurements. The determination of the extent of a wound may also be accomplished by non-invasive and invasive technologies. Non-invasive wound assessment includes the measurement of perimeter, maximum dimensions of length and width, surface area, volume and determination of tissue viability.

A wound can be further described through the use of various parameters, which include the following: duration, blood flow, oxygen, hardness, inflammation, pain, and coexisting systemic factors. These parameters are clues to the definition of the cause, pathophysiology, and status of the wound, but we believe that a complete and detailed history and physical examination are also fundamental.

Translational research

Sergio Roman Roman

The goal of Translational Research is to transform the scientific discoveries from laboratory, clinical and population studies into clinical applications in the benefit of patients.

Success in Translational Research depends on basic scientists and clinical and epidemiological researchers working together to solve problems focused on patient care. A number of barriers prevent efficient integration of scientists and clinicians to carry out successful translational research.

Some of these barriers are:
a lack of significant financial support for translational research, difficulty of hospitals in recruiting and retaining top clinical scientists, a gap in finding clinicians skilled in research and able to devote time to translational projects, and the current career system in most academic institutions/hospitals, which does not favor translational research topics.

Recent major advances in cancer translational research will be taken as examples to illustrate how these barriers could be circumvented.

Cultured keratinocytes in the closure of chronic wounds

Xavier Santos

Long-standing chronic wounds are a challenge for any specialist dealing with wounds. Although different new approaches and therapies have been developed in recent years, some cases are really refractory and impair the quality of life of the patients.
Cultured keratinocytes (CK) is a proven technique since its development by Green and Rheinwald in 1975. It has been used for burns as unique coverage technique and more recently combined with dermal substitutes in massive burns. Although is a multiple layer skin substitute, its take rate is very high. For this reason we used CK to close long standing chronic wounds when other therapies proved non-efficient.
Cultured fibroblast in a fibrin transport media have been used to close 48 long standing chronic ulcer (more than 6 months) in lower limbs. The etiology, previous treatments, culture technique and results are presented.

Planktonic bacteria and antimicrobial solutions, prospects and research in wound care

Vincent Semetey

The development of any infection involves a portal of entry, a susceptible host and virulence of the microorganisms. In this context, any break in the skin generates the loss of the skin’s protective function and constitutes a portal of entry for planktonic bacteria, through the endogenous or exogenous route, leading to the colonization of the wound and sometimes infections.

This underscores the importance of research to find antimicrobial solution to prevent infections in wound care.

Biofilm formation and biofilm in vitro

Damien Seyer

In nature, biofilms are structured communities of microorganisms surrounded by a polysaccharide matrix found with a wide range of surfaces (biotic or abiotic). These surface-attached communities are found in hospitals and are responsible for numerous infections.

The main clinical problem of biofilm-associated infections is the treatment failure due to the remarkable resistance to antibiotics of biofilm-growing bacteria. Many studies have examined the ability of bacteria to colonize different environments in order to understand their mechanism of development.

The first step of biofilm formation corresponds to the adhesion of planktonic bacteria to the surface. When bacteria are definitely attached, they increase in numbers and cells produce polysaccharides to build a mature biofilm. Single cells or heaps of cells are detached from the biofilm and brought to new surfaces.

Antibiofilm strategies

Pascal Thebault

It is now accepted that microbial populations use cell attachment to solid supports to survive forming structured communities called biofilms. Biofilms are defined as biopolymer matrix-enclosed microbial population adhering to each other and/or surfaces. Bacterial biofilm infections are particularly problematic because sessile bacteria can withstand host immune responses and are drastically more resistant to antibiotics (up to 1000-fold), biocides and hydrodynamic shear forces than their planktonic counterparts. In humans, individuals with implanted medical devices, e.g., prosthesis or catheters, and those with compromised immune systems are considered to be most at risk for biofilm infections although humans with competent immune defences often fail to resolve these infections independently.

Due to the high resistance of sessile microorganisms to inhibitors, eradication of biofilms needs high concentrations of disinfectants or antibiotics, causing severe environmental damages and multiresistance emergence. In this context, some new strategies have appeared using for example inhibitors of the quorum sensing. However, prevention of biofilm formation is clearly preferable to any treatment. A strategy to prevent bacterial attachment and proliferation on materials is to kill micro-organisms when they come into contact with the surface. To this aim, antibacterial coatings have been developed, receiving continued attention in the recent years.

Impact of abdominal Wounds complications on Stoma Management

Rosine van den Bulck

Stomas are not wounds but peristomal skin disorders may require a specific assessment prior to appliances and dressings selection.
In spite of a wide range of stoma appliances and ET nurse’s counselling, skin disorders around the stoma are still a significant:problem affecting 30% of colostomy patients, 60% of urostomates and ileostomates (CAREY PD et al, Surgery 1993).

The peristomal skin is not only exposed to feces, urine and intestinal mucus, it is also exposed to adhesive materials used in ostomy appliances which also causes disorders at times. Therefore, we must have a good understanding of wound management and constantly monitor the condition of stoma and skin in which appliances are applied for long term.

The common causes of complications abdominal wounds are poor surgical conditions, abdominal distension, pre operative radiotherapy, recurrence of primary disease inappropriate skin care …Most of these above complications will impair pouch adhesion and consequently cause leakage and skin disorders due to contact of effluents on to the skin.

Skin disorders may also be due to internal causes. In order to identify the cause, it is essential to look for changes in the patient’s condition when skin disorders occur.

The first steps in the management of peristomal skin are to assess the skin damages, to identify the cause and if this can be done, efforts should be made to eliminate it.

If these basic rules are not observed and if care just relies on treatment of symptoms the problem will become more complex
Actually, a clear understanding of healing mechanisms and a knowledge of dressings characteristics are very helpful to assess and manage peristomal skin disorders and surgical wounds when the skin is traumatized or when the wound is left to heal by secondary intention.

The healing process may be improved by the appropriate use of modern dressings such as hydrofibers, alginates or T.N.P.

Modern Dressings are commonly used on wounds but it is known from experience that such dressings, in comparison of skin barriers, cream, powders will promote better healing.when used to manage peristomal skin disorders.

However, at the present time, there is no ideal dressing to manage wounds or peristomal skin disorders.

It is thus important;

to have a good knowledge of dressings mechanisms
– to assess the patient, the wound, the stoma and the peristomal skin disorders
– to identify and eliminate the cause of skin problems or wound dehiscence
– to select the most appropriate dressing and appliances
– to decide which is the best procedure to be applied.

Effectiveness and tissue compatibility of a 12 weeks treatment of chronic venous leg ulcers with an octenidine based antiseptic – A randomized, double-blind controlled study

Wolfgang Vanscheidt

Objective

The aim of this study was to evaluate the cytotoxic effect of octenidine dihydrochloride/phenoxyethanol found in vitro by conducting a randomized, double-blind controlled clinical study focusing on its safe and effective use in chronic venous leg ulcers.

Study design

In total, 126 male and female patients were treated either with octenidine dihydrochloride/phenoxyethanol (n = 60) or Ringer solution (n = 66). The treatment lasted over a period of maximum 12 weeks. For the assessment of the wound healing process, clinical outcome parameters were applied, i. e. time span until 100% epithelization, wound status and the wound surface area were analyzed. Side effects were recorded during the study period.

Results

The median time to complete ulcer healing was comparable between the octenidine dihydrochloride/phenoxyethanol and Ringer solution group (92 vs. 87 days; p = 0.952), without being influenced by wound size or duration of the target ulcer (p-values: 0.947 / 0.978). In patients treated with octenidine dihydrochloride/phenoxyethanol, fewer adverse events were observed compared to the Ringer group (17% vs. 29% of patients reported 20 vs. 38 adverse events).

Conclusions

Octenidine dihydrochloride/phenoxyethanol is well suitable for the treatment of chronic wounds without cytotoxic effects. Furthermore, octenidine dihydrochloride/phenoxyethanol does not impair the wound healing in chronic venous ulcers.

Diabetic foot Ulcers
(Jan Apelqvist)

Evolution of signs of clinical infection and biofilms
(Keith Cutting)

Maggot Debridement
(Finn Gottrup)

Topical Negative Pressure Instillation Therapy with polyhexanid solution as treatment for posttraumatic osteomyelitis and biofilm formation
(Gerrolt Jukema)

Biofilm characterization
(Véronique Larreta-Garde)

Vascular evaluation in wound management: effectiveness and value
(Raj Mani)

Venous Leg Ulcers Presenting Inflammatory Signs Suggesting Heavy Bacterial Colonization: Results of a Randomized Controlled Study
(Sylvie Meaume)

Molecular aspects of wound healing: growth factors and stem cells
(Antonio Montalvo)

Wound Assessment
(Marco Romanelli)

Translational research
(Sergio Roman Roman)

Cultured keratinocytes in the closure of chronic wounds
(Xavier Santos)

Planktonic bacteria and antimicrobial solutions, prospects and research in wound care
(Vincent Semetey)

Biofilm formation and biofilm in vitro
(Damien Seyer)

Antibiofilm strategies
(Pascal Thebault)

Impact of abdominal Wounds complications on Stoma Management
(Rosine van den Bulck)

Effectiveness and tissue compatibility of a 12 weeks treatment of chronic venous leg ulcers with an octenidine based antiseptic – A randomized, double-blind controlled study
(Wolfgang Vanscheidt)