Enzymatic Debridement With Nexobrid®Reduces Surgery in Laser Doppler Imaging-Confirmed Deep Burns.

In contrast to tangential excision, enzymatic debridement with NexoBrid® selectively removes non-viable tissue, allowing some deep dermal burn wounds to still heal conservatively. In this retrospective study, we investigated the reduction in surgery and associated scarring following enzymatic debridement in definitely deep burns as proven by laser Doppler imaging. One hundred two exclusively laser Doppler imaging-blue regions of interest where there was no doubt at all about the surgical indication, were selected for analysis in 32 patients treated with NexoBrid®. The total surface area of the 102 exclusively blue regions of interest was 5,086.4cm2. NexoBrid® resulted in a substantial reduction in the need for autografts as 1,986.9cm2 (39%) healed with conservative treatment. This corresponded with a significant reduction in patients (56.3%) requiring surgery. Exclusively laser Doppler imaging-blue regions of interest treated surgically with split thickness skin grafts required significantly more time to heal compared to conservative treatment (37.8±17.5 vs. 27.0±10.5 days). A very limited rate of hypertrophic scarring (16.7%) was observed. This is the first paper demonstrating a proven and significant reduction in the extent of autografting as well as in the number of surgical procedures after selective enzymatic debridement in objectively laser Doppler imaging-defined and therefore proven deep burns. Even after extended conservative treatment with prolonged healing times following NexoBrid®, hypertrophic scar formation was limited (5/54 regions of interest, 9.3%). Also in operated patients, the incidence of hypertrophic scarring following a strict regimen of aftercare was low (12/48 regions of interest, 25%).

À la différence de l'excision chirurgicale tangentielle, le débridement enzymatique au Nexobrid® ne s'intéresse qu'au tissu nécrosé ce qui permet la cicatrisation spontanée de certaines brûlures intermédiaires. Dans cette étude rétrospective, nous avons évalué la diminution des interventions chirurgicales (et des séquelles y afférant) en cas d'utilisation de l'excision enzymatique sur des brûlures affirmées comme profondes par Imagerie Laser- Doppler (ILD). Nous avons analysé 102 régions d'intérêt, apparaissant bleues à l'ILD chez 32 patients traités par Nexobrid®, représentant une surface totale de 5 086,4 cm2. Ceci a permis une cicatrisation spontanée de 1 986,9 cm2 (39% de l'ensemble et 56,3% chez les patients ayant dû être opérés). Les patients traités par excision- greffe sont restés significativement plus longtemps que ceux ayant cicatrisé spontanément (37,8 +/- 17,5 j VS 27 +/- 10,5). L'incidence globale des cicatrices hypertrophiques était basse (16,7%). Ceci est la première publication montrant une diminution significative de la surface greffée et du nombre d'interventions chirurgicales après l'utilisation d'une excision enzymatique chez des patients souffrant de brûlures définies comme profondes par ILD. Même après une cicatrisation spontanée longue après Nexobrid®, l'incidence des cicatrices hypertrophiques reste faible (5/54 régions d'intérêt - 9,3%) quand elle s'élève à 25% après excision- greffe (12/48).

Development of a dermal matrix from glycerol preserved allogeneic skin.

Dermal substitutes can be used to improve the wound healing of deep burns when placed underneath expanded, thin autologous skin grafts. Such dermal matrix material can be derived from xenogeneic or human tissue. Antigenic structures, such as cells and hairs must be removed to avoid adverse inflammatory response after implantation. In this study, a cost-effective method using low concentrations of NaOH for the de-cellularization of human donor skin preserved in 85% glycerol is described. The donor skin was incubated into NaOH for different time periods; 2, 4, 6 or 8 weeks. These dermal matrix prototypes were analyzed using standard histology techniques. Functional tests were performed in a rat subcutaneous implant model and in a porcine transplantation model; the prototypes were placed in full thickness excision wounds covered with autologous skin grafts.An incubation period of 6 weeks was most optimal, longer periods caused damage to the collagen fibers. Elastin fibers were well preserved. All prototypes showed intact biocompatibility in the rat model by the presence of ingrowing blood vessels and fibroblasts at 4 weeks after implantation. An inflammatory response was observed in the prototypes that were treated for only 2 or 4 weeks with NaOH. The prototypes treated with 6 or 8 weeks NaOH were capable to reduce wound contraction in the porcine model. In neo-dermis of these wounds, elastin fibers derived from the prototype could be observed at 8 weeks after operation, surrounded by more random orientated collagen fibers. Thus, using this effective low cost method, a dermal matrix can be obtained from human donor skin. Further clinical studies will be performed to test this material for dermal substitution in deep (burn) wounds.

The efficacy of a polyhydrated ionogen impregnated dressing in the treatment of recalcitrant diabetic foot ulcers: a multi-centre pilot study.

OBJECTIVE: Assessing the efficacy of a polyhydrated ionogen impregnated dressing in the treatment of recalcitrant diabetic foot ulcers. SUMMARY BACKGROUND DATA: Diabetic Foot Ulcers (DFU) continue to present a formidable challenge in terms of morbidity and health care costs. Increasing evidence ascertains the important role of Matrix MetalloProteinases (MMPs) and their tissue inhibitors, TIMPs, in wound healing. Imbalance of MMPs in the DFU microenvironment has been associated with poor wound healing. Current research is directed towards therapeutic agents that could redress the imbalance of MMPs/TIMPs. Poly Hydrated Ionogen (PHI) formulation is based on metallic ions and citric acid. PHI application aims to positively restore MMP ratios within chronic wounds. This initial multi-centre pilot study aimed to investigate the efficacy of the PHI formulation in achieving stable wound closure in recalcitrant DFUs. MATERIAL AND METHODS: Twenty patients with therapy resistant DFUs of at least 1 cm2 and 3 months duration were treated with PHI formulation in an acetate carrier dressing. Wound debridement, digital imaging and wound perimeter tracing was performed weekly. Off-loading was performed by the use of appropriate shoe-wear (cut-out sandals) and crutches. Patient satisfaction was assessed with a questionnaire. A detailed evaluation sheet was kept for every patient and updated at each visit. RESULTS: Stable wound closure with high patient satisfaction was achieved in 16 (80%) DFUs. The mean time to full closure was 18 weeks. A stable wound epithelization was seen in all full closure patients up to latest follow-up of one year. CONCLUSIONS: Encouraging results of this pilot study prompt us to further investigate the PHI efficacy in DFU treatment in a multi-centre, randomized controlled trial.

The role of silver sulphadiazine in the conservative treatment of partial thickness burn wounds: A systematic review.

BACKGROUND: For more than 40 years, silver sulphadiazine 1% (SSD) is considered as standard therapy for the conservative treatment of burn wounds. However, in the last 10 years, substantial disadvantages of SSD have been reported in the literature and probably as a result of this, several new dressings for burn wounds have been developed and put on the market. The objective of this systematic review is to evaluate the available evidence on SSD in the conservative treatment of burns, specifically in comparison with the newer burn dressings that are increasingly being used nowadays. MATERIALS AND METHODS: A search filter was composed to select randomized controlled trials (RCTs) from the MEDLINE database. Only RCTs studying the effect of conservative treatment on burns were selected. At least one of the two comparative groups was treated with SSD. Each included article was analysed and relevant data (baseline parameters, interventions, outcomes and methodological parameters) were registered using Microsoft Office Excel 2007. RESULTS: Many dressings showed superior healing properties compared to SSD, but no dressing was able to show a clear benefit over SSD regarding infection. The number of dressing changes, pain and patient's satisfaction are more favourable in the newer dressings, especially with solid and biological dressings. CONCLUSIONS: The results of this systematic review clearly demonstrate that a faster wound healing is obtained with the newly developed burn dressings. Additionally, these new dressings tend to be more comfortable for the patients and easier to use for care givers. The minor differences in antibacterial activity between SSD and the new products did not seem to have any influence on the rate of wound healing. Since rapid wound closure is essential to obtain an optimal functional and aesthetic outcome, it can be concluded from the results of this systemic review that the standard use of SSD in the conservative treatment of burn wounds can no longer be supported.

A new metabolite from Streptomyces hygroscopicus II. Identification as 1-deoxy-D-threo-pentulose.

Mass spectrometric studies show this metabolite to be a 1-deoxy-pentulose. The sterochemistry was established by reduction to the corresponding 1-deoxy-D-pentitols.

Biomodification of albocycline by Streptomyces venezuelae.

The macrolide antibiotic albocycline, when added to the fermentations of Streptomyces venezuelae UC-2560 (WC-3627) underwent a gradual loss of antimicrobial activity. The inactive product of this biotransformation was isolated from the fermentations and was shown to be 2,3-dihydroalbocycline.

Reduction products of spectinomycin.

The two epimers of dihydrospectinomycin have been separated and identified structurally. Four tetrahydrospectinomycins have also been prepared.

Kalafungin. II. Chemical transformations and the absolute configuration.

The properties of number of kalafungin derivatives and analogues are consistent with the proposed structure. The absolute stereochemistry of the three active centers was determined to be RRR by optical rotatory dispersion comparisons.

The chemistry of the rubradirins. I. The structures of rubransarols A and B.

The antibiotic rubradirin, C48H46N4O20 was cleaved at an ester function by aqueous methylamine into rubransarol A, C23H23NO8, and a methyl amide, C26H28N4O12. Rubradirin B, C40H33N3O15, was similarly cleaved in methanolic ammonia into rubransarol B, C23H23NO8, and the primary amide, C17H13N3O7. The rubransarols are shown to be unique ansamycins which are isomeric at a double bond in the large ring.

Isolation and characterization of a new antibiotic U-62162.

A new antibiotic U-62162 has been isolated from the fermentations of Streptomyces verdensis Dietz, sp. n. (UC-8157). The compound has been characterized and its gross structure has been elucidated. The antibiotic inhibited the growth of Gram-positive bacteria (particularly Staphylococcus aureus) but was inactive in experimentally infected animals.

The isolation and characterization of rubradirin B.

Rubradirin B, C40H33N3O15, was separated from other components of the rubradirin complex by chromatographic and crystallization procedures. The spectrum of antibacterial activity is similar to that of rubradirin, but the antibiotic is less active.

[Research proposals submitted to the Dutch Investigative Medicine Fund; evaluation of the scientific quality by the Council for Scientific Research (NWO)]. / Aanvragen Ontwikkelingsgeneeskunde: de beoordeling van de wetenschappelijke kwaliteit door de Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO).

The Council for Medical and Health Research (MW-NWO) assessed the scientific quality of research proposals submitted to the Dutch Investigative Medicine Fund, and analysed if there had been changes over time in the proportion of proposals which the MW-NWO advised to reject, the role of reports of external reviewers and the most important methodological flaws. In the period 1995-1999 'reject' had been advised for an average of 50% of the proposals, with a tendency to a smaller proportion in recent years. In nearly half of the proposals the judgements of external reviewers were not in agreement with each other. There was only a weak correlation between the judgements of the reviewers and the final advice of NWO. Among the most important flaws mentioned in the NWO advice were: efficacy not proven (a prerequisite for the Fund), proposed study not needed to solve the policy problem and methodological flaws, e.g. design and power calculation not adequate, deficiencies of inclusion and exclusion criteria.

The value of laboratory tests for the screening and recognition of alcohol abuse in primary care patients.

BACKGROUND: Although alcohol abuse is prevalent in family practice, the diagnosis is not easily established. Laboratory tests are usually heavily relied on in the diagnostic process. METHODS: The value of laboratory tests for the screening and recognition of problem drinking in family practice is summarized, based on a review of the literature. A distinction is made between studies in selected populations of drinkers and studies in nonselected populations, ie, family practice. RESULTS: The most sensitive laboratory tests associated with excessive alcohol intake include gamma-glutamyl transferase (GGT), mean corpuscular volume, and the ratio of alanine aminotransferase to aspartate aminotransferase. No single laboratory test or combination of tests is shown to be appropriate for screening. The positive predictive value for GGT is only about 25% in a population that has a 10% prevalence of problem drinking and increases to about 55% in a population that has a 30% prevalence of problem drinking. CONCLUSIONS: Guidelines for the recognition of problem drinking in family practice should include elevated laboratory test values as one of the "alerting factors" for problem drinking, and not as a confirmation of a suspicion of problem drinking. In monitoring treatment response, GGT may be a powerful patient-motivating factor.

[A national prospective trial register for randomised controlled trials: ethical and practical necessity]. / Een nationaal prospectief trialregister voor gerandomiseerde en gecontroleerde trials; ethisch en praktisch noodzakelijk.

The decision to treat a patient is often based on the results of randomised controlled trials (RCTs). These important investigations inform physicians and patients with regard to the chance of favourable results of treatment and the risks of adverse reactions. However, research has shown that especially the smaller RCTs in which no or even an adverse effect of new interventions is found run a relatively high risk of remaining unpublished, which leads to publication bias and an overestimate of the efficacy of an intervention. This is undesirable. The best way to identify possible publication bias and reduce its negative effects is to register RCTs from their starting date onwards in a prospective and publicly accessible register. Other motives for such a register are the prevention of duplication of research work and its financial support, and informing patients. Currently, a prospective Dutch national trial register is being developed by the Dutch Cochrane Centre. This is not only of importance to researchers and patients, but also to grant-providing bodies and the editors of medical scientific journals.

[A case of fraud in a neurological pharmaceutical clinical trial]. / Een geval van fraude bij farmaceutisch onderzoek in de neurologie.

This paper describes the laborious and lengthy path to clarification and disclosure in a case of fraud in a neurological pharmaceutical clinical trial in the Netherlands. A Dutch neurologist was suspected of irregularities within the context of the 'European stroke prevention study 2' (ESPS-2), a multicentre study into medicinal prophylaxis in patients who had suffered a stroke. The Netherlands Society of Neurology (NVN) established an independent inquiry committee for further investigation of the case. The identity of 425 of the 438 patients (97%) included in the trial by the neurologist could be retrieved. The majority of these patients were known to the neurologist with cerebral infarct. For a sample of 115 patients, the general practitioners (GPs) were contacted by means of a questionnaire. Ninety percent of the responding GPs were unaware of their patients' participation in the pharmaceutical clinical trial. A total of forty patients were asked by their GP about participation: 36 (90%; 95%-CI: 76-97) indicated that they had not participated in the trial, and 4 could not remember. The committee concluded that the neurologist had committed fraud, in the sense that he had used the names of existing patients without these patients actually being enrolled in the study. The report of the independent committee was not made public; the committee and the NVN board differed in opinion on the interpretation and implications of the agreements regarding this subject. Following prolonged legal action, the regional Disciplinary Board suspended the neurologist from practice for one year and the court of law sentenced him to 180 days imprisonment or a fee of 130,000 Euro. Based on the experience gained from this case, recommendations in case of suspicion of fraud are discussed, such as the timely appointment of an independent inquiry committee and the establishment of unambiguous agreements regarding the disclosure of the results of the investigation. Possible legal implications should be considered in advance by the organisations involved; statutes should provide regulations for procedural rules. In the Netherlands there now exists a National Body for Scientific Integrity and a committee for the Scientific Integrity of Healthcare Research to prevent scientific misconduct and to stimulate reporting and appropriate handling of this problem.

Honey in modern wound care: a systematic review.

Honey, known for centuries as a topical treatment for a wide range of wounds, has recently known a revival in modern wound care. The objective of this systematic review is to evaluate the available evidence and the role of honey in contemporary wound care. The search strategy was developed in the databases PubMed and ISI Web of Science. Fifty-five studies of any design, evaluating the use of honey in human burns, ulcers and other wounds, written in English, French, German or Dutch were eligible for inclusion. In all three wound categories honey seems to be a dressing with wound healing stimulating properties. In burns there is also evidence for its antibacterial capacity. In general, honey is also been mentioned to have deodorizing, debridement, anti-inflammatory and wound pain reducing properties, although the evidence for these properties is rather limited. Many of the included studies have methodological problems, and the quality of certain studies is low, making it difficult to formulate conclusive guidelines. This review reveals several gaps in the research of honey in modern wound care, and recommendations are suggested for future research.

The use of platelet-rich plasma in plastic surgery: a systematic review.

OBJECTIVE: The study's aim was to evaluate the available evidence regarding the use of platelet-rich plasma in plastic and reconstructive surgery, through implementation of a systematic review of the literature. DATA SOURCES: PubMed and The Cochrane Library were searched using MeSH terms: 'platelet rich plasma' and 'plastic surgery' for all publications up to July 2011. All English, German, French and Dutch papers were included. In addition, the reference lists of relevant articles were searched for potentially appropriate publications. STUDY SELECTION: Included studies needed to report on topics related to plastic and reconstructive surgery, mentioning at least one clinical end point. Both in vivo and in vitro comparative studies, performed in humans or animals, were included. A total of 82 publications were found, of which 40 studies met the inclusion criteria and were relevant to be used in this systematic review. DATA EXTRACTION: Data from retrieved studies were reviewed and tabulated according to year of publication, study design, human or animal studies, characteristics of the population, mode of application, outcomes and preparation method. DATA SYNTHESIS: A total of 15 randomised controlled trials and 25 case-control studies were found. Thirty-six publications demonstrated favourable outcomes with the use of platelet-rich plasma. The included articles were divided into three topics related to plastic surgery: wound healing, fat grafting and bone grafting. CONCLUSIONS: This systematic review describes a substantially beneficial effect of platelet-rich plasma for several indications, including a better wound healing rate, an increased survival rate of fat grafts and an enhancement of bone graft regeneration.

Burn wound healing time assessed by laser Doppler imaging (LDI). Part 1: Derivation of a dedicated colour code for image interpretation.

INTRODUCTION: Laser Doppler imaging produces a colour-coded image of dermal blood flow, which can be used to quantify the inflammatory response in a burn. The original colour palette had arbitrary boundaries, which inexperienced clinicians found difficult to interpret. The aim of this study was to define clinically useful boundaries that would assist in the prediction of burn healing potential. METHOD: We conducted a prospective, multi-centre study of burns in adults and children. LDI scans were performed between 48 h and 5 days after injury. The burns were assessed clinically and photographed on day of scan, day 14 and day 21 post-injury. Areas healed at day 14, healed between day 14 and 21 and unhealed at day 21 were identified on the LDI scan. The flow values for the pixels in these regions were analysed to calculate boundaries between the three healing categories. RESULTS: We recruited 137 patients (ages 1-88 years, 65% male); 392 LDI scans contained 433 different burn sites; 109 regions of interest were studied. Analysis allowed us to define ranges for the three healing categories: HP14 colour coded red, >600 PU; HP14-21, yellow, 260-440 PU; HP>21, blue, <200 PU; separated by two overlap regions pink, 440-600 PU and green, 200-260 PU. Blue was subdivided to show the very high association between LDI<140 PU and non-healing at day 21. CONCLUSION: We have devised a new colour palette for LDI burn imaging based on healing times of a series of burns. Validation of this palette is described separately, in Part 2.

Reprint of: Burn wound healing time assessed by laser Doppler imaging. Part 2: Validation of a dedicated colour code for image interpretation.

INTRODUCTION: Laser Doppler imaging (LDI) has been investigated and used since 1993 for the assessment of burn wounds. Here we describe tests that validate use of the dedicated colour palette, derived in Part 1, for a standardised interpretation of LDI images for prediction of healing time (<14 days, 14-21 days or >21 days). We also describe clinical and technical factors to be taken into account during LDI imaging and during image interpretation. METHODS: (1) A cohort of images, selected at random, were assessed, according to strict rules of interpretation, by 6 clinicians against photographs of healing, for accuracy of healing time prediction and clinical usefulness using five-point scales. (2) All images were assessed technically in a similar way for accuracy and the accuracy was further studied by analysing the data by ordinal logistic regression to predict the dependence of burn injury healing time on demographic variables (age, sex, race, %TBSA, burn injury cause and site). (3) Where average LDI blood flow could be determined, regression analysis was used to assess the potential accuracy of the technique. RESULTS: (1) Clinical accuracy was found to be 93% and usefulness was 89%; (2) technical accuracy was found to be 96%; (3) regression analysis found that a potential accuracy of 90.9% could be achieved using LDI results alone, increasing to 92% if gender was also considered; no other parameters had an influence on healing time prediction. CONCLUSION: LDI can be used in a standardised way as a valid tool for improving on clinical assessment of burn wounds. This can enable earlier appropriate management.

Burn wound healing time assessed by laser Doppler imaging. Part 2: validation of a dedicated colour code for image interpretation.

INTRODUCTION: Laser Doppler imaging (LDI) has been investigated and used since 1993 for the assessment of burn wounds. Here we describe tests that validate use of the dedicated colour palette, derived in Part 1, for a standardised interpretation of LDI images for prediction of healing time (<14 days, 14-21 days or >21 days). We also describe clinical and technical factors to be taken into account during LDI imaging and during image interpretation. METHODS: (1) A cohort of images, selected at random, were assessed, according to strict rules of interpretation, by 6 clinicians against photographs of healing, for accuracy of healing time prediction and clinical usefulness using five-point scales. (2) All images were assessed technically in a similar way for accuracy and the accuracy was further studied by analysing the data by ordinal logistic regression to predict the dependence of burn healing time on demographic variables (age, sex, race, %TBSA, burn cause and site). (3) Where average LDI blood flow could be determined, regression analysis was used to assess the potential accuracy of the technique. RESULTS: (1) Clinical accuracy was found to be 93% and usefulness was 89%; (2) technical accuracy was found to be 96%; (3) regression analysis found that a potential accuracy of 90.9% could be achieved using LDI results alone, increasing to 92% if gender was also considered; no other parameters had an influence on healing time prediction. CONCLUSION: LDI can be used in a standardised way as a valid tool for improving on clinical assessment of burn wounds. This can enable earlier appropriate management.