Implementation of health-related quality of life in the German TraumaRegister DGU® - first results of a pilot study.

BACKGROUND: Approximately 30,000 people are affected by severe injuries in Germany each year. Continuous progress in prehospital and hospital care has significantly reduced the mortality of polytrauma patients. With increasing survival rates, the functional outcome, health-related quality (hrQoL) of life and ability to work are now gaining importance. Aim of the study is, the presentation of the response behavior of seriously injured patients on the one hand and the examination of the factors influencing the quality of life and ability to work 12 months after major trauma on the other hand. Building on these initial results, a standard outcome tool shall be integrated in the established TraumaRegister DGU® in the future. METHODS: In 2018, patients [Injury Severity Score (ISS) ≥ 16; age:18-75 years] underwent multicenter one-year posttraumatic follow-up in six study hospitals. In addition to assessing hrQoL by using the Short-Form Health Survey (SF-12), five additional questions (treatment satisfaction; ability to work; trauma-related medical treatment; relevant physical disability, hrQoL as compared with the prior to injury status) were applied. RESULTS: Of the 1,162 patients contacted, 594 responded and were included in the analysis. The post-injury hrQoL does not show statistically significant differences between the sexes. Regarding age, however, the younger the patient at injury, the better the SF-12 physical sum score. Furthermore, the physically perceived quality of life decreases statistically significantly in relation to the severity of the trauma as measured by the ISS, whereas the mentally perceived quality of life shows no differences in terms of injury severity. A large proportion of severely injured patients were very satisfied (42.2%) or satisfied (39.9%) with the treatment outcome. It should be emphasized that patients with a high injury severity (ISS > 50) were on average more often very satisfied with the treatment outcome (46.7%). A total of 429 patients provided information on their ability to work 12 months post-injury. Here, 194 (45.2%) patients had a full employment, and 58 (13.5%) patients were had a restricted employment. CONCLUSION: The present results show the importance of a structured assessment of the postinjury hrQoL and the ability to work after polytrauma. Further studies on the detection of influenceable risk factors on hrQoL and ability to work in the intersectoral course of treatment should follow to enable the best possible outcome of polytrauma survivors.

Application of the PANELVIEW instrument to evaluate the guideline development process of the German polytrauma guideline.

BACKGROUND: PANELVIEW is an instrument for evaluating the appropriateness of the process, methods, and outcome of guideline development and the satisfaction of the guideline group with these steps. OBJECTIVE: To evaluate the guideline development process of the German guideline on the treatment of patients with severe/multiple injuries ('German polytrauma guideline') from the perspective of the guideline group, and to identify areas where this process may be improved in the future. METHODS: We administered PANELVIEW to the participants of the 2022 update of the German polytrauma guideline. All guideline group members, including delegates of participating medical societies, steering group members, authors of guideline chapters, the chair, and methodological lead, were invited to participate. Responses were analysed using descriptive statistics. Comments received were categorised by domains/items of the tool. RESULTS: After the first, second, and last consensus conference, the guideline group was invited via email to participate in a web-based survey. Response rates were 36% (n/N = 13/36), 40% (12/30), and 37% (20/54), respectively. The mean scores for items ranged between 5.1 and 6.9 on a scale from 1 (fully disagree) to 7 (fully agree). Items with mean scores below 6.0 were related to (1) administration, (2) consideration of patients' views, perspectives, values, and preferences, and (3) the discussion of research gaps and needs for future research. CONCLUSION: The PANELVIEW tool showed that the guideline group was satisfied with most aspects of the guideline development process. Areas for improvement of the process were identified. Strategies to improve response rates should be explored.

An adapted 'Ottawa' method allowed assessing the need to update topic areas within clinical practice guidelines.

OBJECTIVES: To adapt and evaluate a method for assessing the need to update guideline topic areas involving multiple recommendations. STUDY DESIGN AND SETTING: The 'Ottawa method' uses literature signals to determine changes in evidence that trigger a need to update individual guideline questions. We adapted the Ottawa method to include a process for aggregating updating signals by topic area (e.g., resuscitation) and tested this method using the German guideline on the treatment of patients with severe/multiple injuries. This involved a focused systematic evaluation of current evidence to identify updating signals and classifying the need to update for each topic area. Then, we surveyed the guideline group online about the modified method. RESULTS: We conducted focused literature searches for 37 topic areas and screened a mean of 97 abstracts per topic area in 2021. The need to update was high for eight (21.6%), intermediate for eight (21.6%), and low for 21 topic areas (56.8%) based on updating signals. The survey response rate was 56% (24/43). Most guideline group members (94%, 16/17 responders) would use the Ottawa method again but their comments identified some weaknesses. CONCLUSION: The modified Ottawa method is a suitable, efficient tool to generate evidence-based updating signals for guideline topic areas involving multiple recommendations. Further fine-tuning is recommended.

Evaluation of a Diagnostic-Therapeutic Algorithm for Finger Epiphyseal Growth Plate Stress Injuries in Adolescent Climbers.

BACKGROUND: Finger epiphyseal growth plate stress injuries are the most frequent sport-specific injuries in adolescent climbers. Definitive diagnostic and therapeutic guidelines are pending. PURPOSE: To evaluate a diagnostic-therapeutic algorithm for finger epiphyseal growth plate stress injuries in adolescent climbers. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: On the basis of previous work on diagnostics and treatment of finger epiphyseal growth plate stress injuries (EGPIs) in adolescent climbers, we developed a new algorithm for management of these injuries, which was implemented into our clinical work. During a 4-year period, we performed a prospective multicentered analysis of our patients treated according to the algorithm. Climbing-specific background was evaluated (training years, climbing level, training methods, etc); injuries were analyzed (Salter-Harris classification and UIAA MedCom score [Union Internationale des Associations d'Alpinisme]); and treatments and outcomes were recorded: union, time to return to climbing, VAS (visual analog scale), QuickDASH (shortened version of the Disabilities of the Arm, Shoulder, and Hand), and a climbing-specific outcome score. RESULTS: Within the observation period, 27 patients with 37 independent EGPIs of the fingers were recorded (mean ± SD age, 14.7 ± 1.5 years; 19 male, 8 female; 66.7% competitive athletes). Regarding maturity at time of injury, the mean age at injury did not differ by sex. Average UIAA climbing level was 9.5 ± 0.8, with 6 ± 4.6 years of climbing or bouldering and 14 ± 9.1 hours of weekly climbing-specific training volume. Among the 37 injuries there were 7 epiphyseal strains, 2 Salter-Harris I fractures, and 28 Salter-Harris III fractures (UIAA 1, n = 7; UIAA 2, n = 30). Thirty-six injuries developed through repetitive stress, while 1 had an acute onset. Twenty-eight injuries were treated nonoperatively and 9 surgically. Osseous union was achieved in all cases, and there were no recurrences. The time between the start of treatment and the return to sport was 40.1 ± 65.2 days. The climbing-specific outcome score was excellent in 34 patients and good in 3. VAS decreased from 2.3 ± 0.6 to 0.1 ± 0.4 after treatment and QuickDASH from 48.1 ± 7.9 to 28.5 ± 3.3. CONCLUSION: The proposed management algorithm led to osseous union in all cases. Effective treatment of EGPIs of the fingers may include nonsurgical or surgical intervention, depending on the time course and severity of the injury. Further awareness of EGPI is important to help prevent these injuries in the future.

Assessment of patient-reported outcomes after polytrauma - instruments and methods: a systematic review.

OBJECTIVES: We (1) collected instruments that assess health-related quality of life (HRQoL), activities of daily living (ADL) and social participation during follow-up after polytrauma, (2) described their use and (3) investigated other relevant patient-reported outcomes (PROs) assessed in the studies. DESIGN: Systematic Review using the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. DATA SOURCES: MEDLINE, Embase, CINAHL, PsycINFO, CENTRAL, as well as the trials registers ClinicalTrials.gov and WHO ICTRP were searched from January 2005 to April 2018. ELIGIBILITY CRITERIA: All original empirical research published in English or German including PROs of patients aged 18-75 years with an Injury Severity Score≥16 and/or an Abbreviated Injury Scale≥3. Studies with defined injuries or diseases (e.g. low-energy injuries) and some text types (e.g. grey literature and books) were excluded. Systematic reviews and meta-analyses were excluded, but references screened for appropriate studies. DATA EXTRACTION AND SYNTHESIS: Data extraction, narrative content analysis and a critical appraisal (e.g. UK National Institute for Health and Care Excellence) were performed by two reviewers independently. RESULTS: The search yielded 3496 hits; 54 publications were included. Predominantly, HRQoL was assessed, with Short Form-36 Health Survey applied most frequently. ADL and (social) participation were rarely assessed. The methods most used were postal surveys and single assessments of PROs, with a follow-up period of one to one and a half years. Other relevant PRO areas reported were function, mental disorders and pain. CONCLUSIONS: There is a large variation in the assessment of PROs after polytrauma, impairing comparability of outcomes. First efforts to standardise the collection of PROs have been initiated, but require further harmonisation between central players. Additional knowledge on rarely reported PRO areas (e.g. (social) participation, social networks) may lead to their consideration in health services provision. PROSPERO REGISTRATION NUMBER: CRD42017060825.

Polytrauma outcome: implementation of health-related quality of life assessment into the German Trauma Registry.

INTRODUCTION: As a result of improvement in polytrauma management within the last years, more patients survive a significant trauma. Trauma registers, such as the TraumaRegister DGU®, played a role in identifying risk factors of poor outcomes which led to an improvement of survival rates. In recent years the health-related quality of life (HRQoL) after trauma got into the focus of trauma studies. MATERIALS AND METHODS: Under the sponsorship of the German Society of Trauma Surgery (DGU) the members of the Committee on Emergency Medicine, Intensive Care and Trauma Management (Sektion NIS) convened intending to identify an assessment tool for implementation into the TraumaRegister DGU®. RESULTS: After the conduct of a systematic literature review, the working group decided to choose the 12-item Short-Form Health Survey (SF-12) and five more questions, capturing the satisfaction of treatment, work capacity and trauma-related medical treatment. CONCLUSION: The data collection of HRQoL and the additional variables started in 2017 in participating clinics as a part of the regular data collection of the TraumaRegister DGU®.

[Surgery during the SARS-CoV-2 pandemic : Recommendations on operative procedures]. / Chirurgie in der SARS-CoV-2-Pandemie : Empfehlungen zum operativen Vorgehen.

BACKGROUND: In February 2020 Germany was also hit by the SARS-CoV­2 pandemic. Even patients infected by SARS-CoV­2 or COVID-19 may need operative procedures. Currently, no uniform recommendations exist on precautions to be taken when operating on these patients. Furthermore, they may differ from one hospital to another. METHODS: The task force COVID-19 of the emergency, intensive and severely injured section of the German Trauma Society (DGU e. V.) has developed consensus-based recommendations on surgical treatment of patients with SARS-CoV­2 infections. Great importance is placed on the implementation in hospitals at all levels of care. RESULTS: The indications for surgical interventions in patients with COVID-19 infections require an extremely critical evaluation. When indicated these surgical intervention should ideally be performed in a separate operating theater. All personnel involved should wear personal protective equipment with FFP2 masks, face shields and double gloves. The emergency team in the resuscitation bay should generally wear the same personal protective equipment. Special training is mandatory and the exposure of team members should be minimized. CONCLUSION: The recommendations are principally used for all kinds of surgery and comply with the currently available knowledge. Nevertheless, all recommendations represent a compromise between maximum safety of all medical staff and practicability in the routine hospital workflow.

Circulating growth/differentiation factor 15 is associated with human CD56bright natural killer cell dysfunction and nosocomial infection in severe systemic inflammation.

BACKGROUND: Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation. METHODS: NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis. FINDINGS: During systemic inflammation, the expression of the IL-12 receptor ß2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus. The profound suppression of NK cells developed within 24 h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor ß receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor ß2 expression on NK cells and was enhanced in patients who later acquired septic complications. INTERPRETATION: GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections. FUND: The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen.

Development of trauma systems in Europe-reports from England, Germany, the Netherlands, and Spain.

Major trauma systems have evolved in many European countries and have resulted in improved care in terms of mortality and morbidity. Many of the systems have similar history, with reports of either poor services, or a single disaster, driving change of policy and set up. We report on 4 European systems, looking at the background, set up and some of the results. Similar issues are identified including the importance of triage, the concentration of specialist skills which require patients to bypass hospitals, and the standardization of treatment protocols. The issues of rehabilitation and the increasing importance of measuring outcome with patient reported metrics are discussed.

Assessment of patient-reported outcomes after polytrauma: protocol for a systematic review.

INTRODUCTION: Survivors of polytrauma experience long-term and short-term burden that influences their lives. The patients' view of relevant short-term and long-term outcomes should be captured in instruments that measure quality of life and other patient-reported outcomes (PROs) after a polytrauma. The aim of this systematic review is to (1) collect instruments that assess PROs (quality of life, social participation and activities of daily living) during follow-up after polytrauma, (2) describe the instruments' application (eg, duration of period of follow-up) and (3) investigate other relevant PROs that are also assessed in the included studies (pain, depression, anxiety and cognitive function). METHODS AND ANALYSIS: The systematic review protocol is developed in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Cochrane Central Register of Controlled Trials and the trials registers ClinicalTrials.gov and WHO International Clinical Trials Registry Platform will be searched. Keywords, for example, 'polytrauma', 'multiple trauma', 'quality of life', 'activities of daily living' or 'pain' will be used. Publications published between January 2005 and the most recent date (currently: August 2016) will be included. In order to present the latest possible results, an update of the search is conducted before publication. The data extraction and a content analysis will be carried out systematically. A critical appraisal will be performed. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. The results will be published in a peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42017060825.

Surgical Management of Proximal Interphalangeal Joint Repetitive Stress Epiphyseal Fracture Nonunion in Elite Sport Climbers.

Repetitive stress fracture of the middle phalanx epiphysis is an injury specific to elite adolescent sport climbers. As sport climbing becomes increasingly popular in younger age groups, an increased number of these injuries have been reported in recent years. To date, treatment of these fractures has been nonsurgical, with strict rest and physiotherapy prescribed until fracture union. However, when these patients present in a delayed fashion with an established nonunion, nonsurgical treatment may fail, leading to disabling chronic pain and/or digital deformity in some cases. In this article, we present 2 cases of surgical treatment for finger middle phalanx repetitive stress epiphyseal fracture nonunion, using a percutaneous spot drilling epiphysiodesis technique.

Dendritic Cell-Like Cells Accumulate in Regenerating Murine Skeletal Muscle after Injury and Boost Adaptive Immune Responses Only upon a Microbial Challenge.

Skeletal muscle injury causes a local sterile inflammatory response. In parallel, a state of immunosuppression develops distal to the site of tissue damage. Granulocytes and monocytes that are rapidly recruited to the site of injury contribute to tissue regeneration. In this study we used a mouse model of traumatic skeletal muscle injury to investigate the previously unknown role of dendritic cells (DCs) that accumulate in injured tissue. We injected the model antigen ovalbumin (OVA) into the skeletal muscle of injured or sham-treated mice to address the ability of these DCs in antigen uptake, migration, and specific T cell activation in the draining popliteal lymph node (pLN). Immature DC-like cells appeared in the skeletal muscle by 4 days after injury and subsequently acquired a mature phenotype, as indicated by increased expression of the costimulatory molecules CD40 and CD86. After the injection of OVA into the muscle, OVA-loaded DCs migrated into the pLN. The migration of DC-like cells from the injured muscle was enhanced in the presence of the microbial stimulus lipopolysaccharide at the site of antigen uptake and triggered an increased OVA-specific T helper cell type 1 (Th1) response in the pLN. Naïve OVA-loaded DCs were superior in Th1-like priming in the pLN when adoptively transferred into the skeletal muscle of injured mice, a finding indicating the relevance of the microenvironment in the regenerating skeletal muscle for increased Th1-like priming. These findings suggest that DC-like cells that accumulate in the regenerating muscle initiate a protective immune response upon microbial challenge and thereby overcome injury-induced immunosuppression.

Induced Hypothermia Preserves the Functional Enterocyte Mass in A Porcine Multiple Trauma Model: Retracted.

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) and the resulting multiple organ failure (MOF) following severe trauma are associated with increased morbidity and mortality. Due to intestinal mucosal lesions and gut barrier disorders, the intestine contributes decisively to how post-traumatic MOF develops. As mild therapeutic hypothermia has been found to have protective effects on post-traumatic organ injuries, we analysed its effects on the intestine. METHODS: In a porcine model, Forty pigs were assigned to four groups: sham or trauma groups each with two sub-groups receiving either hypothermia or normothermia. The trauma was a combined trauma of blunt chest trauma, liver laceration and haemorrhagic shock. Functional enterocyte mass and enterocyte necrosis were evaluated by measuring plasma citrulline and iFABP. Mucosal lesions were assessed using a semi-quantitative histological scoring system. RESULTS: In normothermic trauma animals, citrulline decreased significantly compared to both sham groups and to the hypothermic trauma group. However, citrulline levels did not differ significantly between the hypothermic trauma group and the hypothermic sham group. Although histological analysis demonstrated subepithelial lifting and mucosal oedema in the ileal mucosa of all trauma animals, the semi-quantitative score of the group treated with hypothermia was comparable to that of the hypothermic sham group. However, the score was significantly elevated in normothermic trauma animals in comparison to sham and hypothermic trauma animals. CONCLUSION: Induced hypothermia preserves the functional enterocyte mass after severe trauma. Therefore induced hypothermia might represent a therapeutic strategy to avoid posttraumatic organ dysfunction, although further studies regarding the safety and long-term effects are required. LEVEL OF EVIDENCE: Level III; therapeutic study.

Staurosporine resistance in inflammatory neutrophils is associated with the inhibition of caspase- and proteasome-mediated Mcl-1 degradation.

Apoptosis resistance in activated neutrophils is known to be associated with collateral damage of surrounding tissue, as well as immune and organ dysfunction. Thus, the safe removal of neutrophils by apoptosis induction represents a prerequisite for the resolution of inflammation. Here, we report that intrinsic apoptosis resistance in human neutrophils, isolated from severely injured patients, is based on enhanced stabilization of antiapoptotic myeloid cell leukemia 1 and subsequent impairment of downstream apoptotic pathways. Whereas extrinsic apoptosis induction by the activation of Fas death receptor on inflammatory neutrophils was accompanied by caspase- and proteasome-mediated myeloid cell leukemia 1 degradation, intrinsic apoptosis induction by staurosporine led to a significant stabilization of myeloid cell leukemia 1 protein, which impeded on truncated forms of B cell lymphoma 2-associated X protein and B cell lymphoma 2 homology domain 3-interacting domain death translocation and subsequent cytochrome c release from the mitochondria. We show further that profound inhibition of myeloid cell leukemia 1 degradation is based on the inhibition of caspases and sustained activation of kinases involved in cell survival, such as Akt. Accordingly, impeded myeloid cell leukemia 1 phosphorylation on Ser159 by glycogen synthase kinase 3 and protein ubiquitination has been demonstrated. Inhibition of myeloid cell leukemia 1 activity markedly increased sensitivity to staurosporine-induced cell death. Altogether, these results provide new insights into the mechanisms underlying myeloid cell leukemia 1-mediated apoptosis resistance to staurosporine under inflammatory situations and should be considered for the development of novel therapeutic strategies.

Reconstruction of septic diaphyseal bone defects with the induced membrane technique.

Septic segmental bone voids of the diaphysis are difficult to manage. The induced membrane technique by Masquelet has been successfully used to reconstruct segmental defects more than 20 cm. Our article describes a series of 13 cases with extensive posttraumatic bone loss of the metatarsal, tibial, femoral and radial bones after septic injuries followed by multiple surgical interventions. Antibiotic-impregnated polymethyl methacrylate (PMMA) cement spacers were implanted after successful eradication of bacterial infections of soft tissue and bones. After a mean of 9.8 weeks, body-induced membranes were established and the cements spacers removed. To fill up the bone void, cancellous bone autografts were implanted into the membranes. The follow-up examination after 24 months revealed bony union in all cases and favorable functional results. The induced membrane technique has shown to be effective in treating bone defects of upper and lower extremity bone defects.

Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model.

BACKGROUND: The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. METHODS: We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. RESULTS: Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. CONCLUSIONS: Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia.

Level of Evidence Analysis for the Latest German National Guideline on Treatment of Patients with Severe and Multiple Injuries and ATLS.

PURPOSE: Advanced Trauma Life Support (ATLS®) is one of the world's best-known training programs for medical providers. Revisions of the ATLS manual have been evidence based for a number of years. In 2011, a level 3 (S3) evidence- and consensus-based guideline on the treatment of patients with severe and multiple injuries was published in Germany. The scope of this study was the systematic comparison of the educational content of the ATLS concept and the interdisciplinary "S3 polytrauma guideline." METHODS: A total of 123 key recommendations of the guideline were compared with the content of the ATLS manual (9th edition). Depending on the level of agreement, the recommendations were classed in the following categories: (1) Agreement. (2) Minor variation. (3) Major variation. RESULTS: An overall 86% conformity was found between the key recommendations of the guideline and the ATLS® manual. The ATLS® primary survey (ABCDE) showed an 85% conformity. The degree of conformity for the individual priorities was as follows: A (Airway) 79%, B (Breathing) 79%, C (Circulation) 86%, D (Disability) 93%, E (Exposure) 100%. The ATLS® secondary survey showed a 94% conformity. The main differences were in the areas of anesthetic induction, fluid administration, and coagulation therapy. CONCLUSIONS: According to our comparison, the educational content and manual of the ATLS are largely compatible with a high level of evidence S3 guideline. However, subsequent editions of both the ATLS® and the S3 guideline should re-examine and reassess a number of aspects.

Lysostaphin-coated titan-implants preventing localized osteitis by Staphylococcus aureus in a mouse model.

The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures.

How to define severely injured patients? -- an Injury Severity Score (ISS) based approach alone is not sufficient.

INTRODUCTION: Multiple injured patients, polytrauma or severely injured patients are terms used as synonyms in international literature describing injured patients with a high risk of mortality and cost consuming therapeutic demands. In order to advance the definition of these terms, we analysed a large trauma registry. In detail, we compared critically ill trauma patients first specified on a pure anatomical base according to the ISS or NISS, second in the original "polytrauma definition" with two body regions affected and finally all of them combined with a physiological component. PATIENTS AND METHODS: Records that were collected in the TraumaRegister DGU(®) of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie, DGU) between 1993 and 2011 (92,479 patients) were considered for this study. All patients with primary admission from scene with a minimum hospital stay of 48 h and an Injury Severity Score (ISS)≥ 16 were included. Pre-hospital and early admission data were used to determine physiological risk factors and calculate individual risk of death using the Revised Injury Severity Classification (RISC). RESULTS: 45,350 patients met inclusion criteria. The overall hospital mortality rate was 20.4%. The predicted mortality according to the RISC-Score was 21.6%. 36,897 patients (81.4%) had injuries in several body regions. The prevalence of the five physiological risk factors varied between 17% (high age) and 34% (unconsciousness). There were 17,617 patients (38.8%) without any risk factor present on admission, while 30.6% (n=13,890) of the patients had one and 30.5% (n=13,843) had two or more factors present. Patients with ISS ≥ 16 but no physiological risk factor present had a very low mortality rate of 3.1% (542 of 17,617). With an increasing number of physiological factors there was an almost linear increase in mortality up to an 86% rate in patients with all five factors present. The 'polytrauma' definition of Butcher and colleagues with AIS ≥ 3 in at least two different body regions would apply to only 56.2% of patients in the present group with ISS ≥ 16. The mortality in this subgroup is only marginally higher (21.8%; 5559 of 25,494) than in the group of patients with only one severely affected body region (18.5%; 3675 of 19,875). CONCLUSIONS: In our opinion the principle of sharpening an anatomically based definition by a defined physiological problem will help to specify the really critically ill trauma patients.