The anterior transmuscular intrapelvic approach for the treatment of acetabular fractures-a new anterior surgical strategy.

The anterior ilioinguinal and the posterior Kocher-Langenbeck approach have long been the standard surgical approaches to the acetabulum. The last decade has witnessed the development of so-called intrapelvic approaches for anterior pathologies because they provide better exposure of the quadrilateral plate. Currently, the modified Stoppa approach and the pararectus approach are frequently used by surgeons for the treatment of acetabular fractures. We investigated an even more direct access to the entire anterior column and the quadrilateral plate via the abdominal wall muscles, between the incisions for the ilioinguinal and the pararectus approach.After intensive study of anatomic specimens, a cadaver dissection was performed prior to clinical application. The approach was then used in 20 patients who were assessed retrospectively.Postoperative CT scans showed that, according to the Matta scoring system, the quality of fracture reduction was "anatomical" (≤ 1 mm) in 12 (60%), "imperfect" (2-3 mm) in four (20%), and "poor" (> 3 mm) in four (20%) patients. Numerous minor complications were observed; the majority of these had resolved at the time of discharge.In conclusion, the anterior transmuscular intrapelvic approach (ATI) is a safe and effective alternative to the ilioinguinal and pararectal approaches, and may be regarded as an evolutionary advancement of traditional procedures.

Label-free multiplex sensing from buffer and immunoglobulin G sensing from whole blood with photonic crystal slabs using angle-tuning of an optical interference filter.

Direct detection of biomarkers from unpurified whole blood has been a challenge for label-free detection platforms, such as photonic crystal slabs (PCS). A wide range of measurement concepts for PCS exist, but exhibit technical limitations, which render them unsuitable for label-free biosensing with unfiltered whole blood. In this work, we single out the requirements for a label-free point-of-care setup based on PCS and present a wavelength selecting concept by angle tuning of an optical interference filter, which fulfills these requirements. We investigate the limit of detection (LOD) for bulk refractive index changes and obtain a value of 3.4 E-4 refractive index units (RIU). We demonstrate label-free multiplex detection for different types of immobilization entities, including aptamers, antigens, and simple proteins. For this multiplex setup we detect thrombin at a concentration of 6.3 µg/ml, antibodies of glutathione S-transferase (GST) diluted by a factor of 250, and streptavidin at a concentration of 33 µg/ml. In a first proof of principle experiment, we demonstrate the ability to detect immunoglobulins G (IgG) from unfiltered whole blood. These experiments are conducted directly in the hospital without temperature control of the photonic crystal transducer surface or the blood sample. We set the detected concentration levels into a medical frame of reference and point out possible applications.

Alveolar-Capillary Barrier Protection In Vitro: Lung Cell Type-Specific Effects and Molecular Mechanisms Induced by 1α, 25-Dihydroxyvitamin D3.

Low serum levels of 1α, 25-dihydroxyvitamin D3 (VD3) are associated with a higher mortality in trauma patients with sepsis or ARDS. However, the molecular mechanisms behind this observation are not yet understood. VD3 is known to stimulate lung maturity, alveolar type II cell differentiation, or pulmonary surfactant synthesis and guides epithelial defense during infection. In this study, we investigated the impact of VD3 on the alveolar-capillary barrier in a co-culture model of alveolar epithelial cells and microvascular endothelial cells respectively in the individual cell types. After stimulation with bacterial LPS (lipopolysaccharide), gene expression of inflammatory cytokines, surfactant proteins, transport proteins, antimicrobial peptide, and doublecortin-like kinase 1 (DCLK1) were analyzed by real-time PCR, while corresponding proteins were evaluated by ELISA, immune-fluorescence, or Western blot. The effect of VD3 on the intracellular protein composition in H441 cells was analyzed by quantitative liquid chromatography-mass spectrometry-based proteomics. VD3 effectively protected the alveolar-capillary barrier against LPS treatment, as indicated by TEER measurement and morphological assessment. VD3 did not inhibit the IL-6 secretion by H441 and OEC but restricted the diffusion of IL-6 to the epithelial compartment. Further, VD3 could significantly suppress the surfactant protein A expression induced in the co-culture system by LPS treatment. VD3 induced high levels of the antimicrobial peptide LL-37, which counteracted effects by LPS and strengthened the barrier. Quantitative proteomics identified VD3-dependent protein abundance changes ranging from constitutional extracellular matrix components and surfactant-associated proteins to immune-regulatory molecules. DCLK1, as a newly described target molecule for VD3, was prominently stimulated by VD3 (10 nM) and seems to influence the alveolar-epithelial cell barrier and regeneration.

Effectiveness of autonomous home hazard reduction on fear of falling in community-dwelling older women.

BACKGROUND: Many falls in older people occur at home, and home hazards (HOHA) are often involved. Fear of falling (FOF) is a frequent and serious consequence of falls. This study aimed to analyze the effectiveness of an autonomous reduction of HOHA on FOF. METHODS: In this single-blinded, prospective cohort study design, the inclusion criteria were female sex, age ≥60 years, no known dementia, community-dwelling, and written informed consent. Using a 54-item room-by-room checklist, the participants identified and autonomously reduced as many HOHA as possible, within 14 days. The FOF was measured using a dichotomous scale (D-FOF) and the Falls Efficacy Scale International (FES-I). Logistic regression models were used to identify the predictors of a substantial reduction of HOHA (≥50%) and FOF (≥25%). RESULTS: A total of 782 women fulfilled the inclusion criteria, and 431 (60.5%) returned the complete checklist on time. The mean age was 72.5 [SD 7.1] years. 43.8% of participants reduced ≥50% of the HOHA. The D-FOF (odds ratio 22.4 [95% confidence interval 11.0-45.3]), age ≥ 75 years (14.1 [7.5-26.4]), polypharmacy (3.0 [1.4-6.5]), and assumed improvability of housing conditions (2.4 [1.3-4.3]) were identified as predictors for substantially reducing HOHA with an area under the curve of 0.91. The initial FES-I score decreased from 24.5 to 19.5. Prior to the intervention, 53.1% showed a high FOF (>22 FES-I scores). Of these, 70.7% participants reduced their high FOF to low FOF. 29.2% of all participants reduced FOF ≥25% postinterventionally, associated with a substantial reduction in HOHA (3.5 [2.2-5.7]) as the strongest independent factor in the multiple logistic regression analysis. CONCLUSION: The use of a self-administered checklist led to a substantial reduction of HOHA and subsequently to a clinically relevant reduction of FOF in older community-dwelling women. Autonomous competence of older people should be considered when developing fall prevention strategies.

Does the time of the day affect multiple trauma care in hospitals? A retrospective analysis of data from the TraumaRegister DGU®.

BACKGROUND: Optimal multiple trauma care should be continuously provided during the day and night. Several studies have demonstrated worse outcomes and higher mortality in patients admitted at night. This study involved the analysis of a population of multiple trauma patients admitted at night and a comparison of various indicators of the quality of care at different admission times. METHODS: Data from 58,939 multiple trauma patients from 2007 to 2017 were analyzed retrospectively. All data were obtained from TraumaRegister DGU®. Patients were grouped by the time of their admission to the trauma center (6.00 am-11.59 am (morning), 12.00 pm-5.59 pm (afternoon), 6.00 pm-11.59 pm (evening), 0.00 am-5.59 am (night)). Incidences, patient demographics, injury patterns, trauma center levels and trauma care times and outcomes were evaluated. RESULTS: Fewer patients were admitted during the night (6.00 pm-11.59 pm: 18.8% of the patients, 0.00-5.59 am: 4.6% of the patients) than during the day. Patients who arrived between 0.00 am-5.59 am were younger (49.4 ± 22.8 years) and had a higher injury severity score (ISS) (21.4 ± 11.5) and lower Glasgow Coma Scale (GCS) score (11.6 ± 4.4) than those admitted during the day (12.00 pm-05.59 pm; age: 55.3 ± 21.6 years, ISS: 20.6 ± 11.4, GCS: 12.6 ± 4.0). Time in the trauma department and time to an emergency operation were only marginally different. Time to imaging was slightly prolonged during the night (0.00 am-5.59 am: X-ray 16.2 ± 19.8 min; CT scan 24.3 ± 18.1 min versus 12.00 pm- 5.59 pm: X-ray 15.4 ± 19.7 min; CT scan 22.5 ± 17.8 min), but the delay did not affect the outcome. The outcome was also not affected by level of the trauma center. There was no relevant difference in the Revised Injury Severity Classification II (RISC II) score or mortality rate between patients admitted during the day and at night. There were no differences in RISC II scores or mortality rates according to time period. Admission at night was not a predictor of a higher mortality rate. CONCLUSION: The patient population and injury severity vary between the day and night with regard to age, injury pattern and trauma mechanism. Despite the differences in these factors, arrival at night did not have a negative effect on the outcome.

Missed hand and forearm injuries in multiple trauma patients: An analysis from the TraumaRegister DGU®.

PURPOSE: Multiple trauma patients have a high risk of missed injuries. The main point of our study was to provide new epidemiological data on hand and forearm injuries in multiple trauma with a focus on those that were missed. Therefore, we used the database of the TraumaRegister DGU®. METHODS: In this study, we evaluated anonymous data from 139931 patients aged 1-100 years with multiple trauma in the TraumaRegister DGU® of the German Society for Trauma Surgery from 2007 to 2017. Patients with hand and forearm injuries documented during hospital stay were identified and analyzed. We included fractures, dislocations, tendon injuries, nerve injuries and vessel injuries. Patients with missed hand and forearm injuries were compared with patients with primary diagnosed injuries in view of gender, age, ISS, Abbreviated Injury Score (AIS), Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), trauma mechanism type of injury, hospital stay, RISC II and mortality rate. Missed injuries were defined as injuries that were recently diagnosed and documented in the intensive care unit (ICU). RESULTS: A total of 50459 multiple trauma patients (36.1%) had hand or forearm injuries, and 89472 patients (63.9%) had neither. Patients with hand injuries were younger and were more often involved in car and motorcycle accidents. Severe head trauma was evaluated less frequently, and severe thorax trauma was evaluated more often in patients with hand injuries. The times of diagnosis of hand injuries were documented in 10971 cases. A total of 727 patients (6.6%) with missed hand injuries were registered. The most commonly missed injuries in multiple trauma were 104 carpal fractures/dislocations (11.2%), 195 nerve injuries (25.4%) and 54 tendon injuries (11.4%). Predisposing factors for missing injuries were multiple diagnoses, primary care in the first hospital and direct from emergency room transfer to the ICU. CONCLUSION: In contrast to previous findings, severely injured patients, especially those with head injuries and GCS of ≤8, were not predisposed to have missed hand injuries compared to patients without severe head trauma. Special attention should be paid to younger patients after traffic accidents with multiple diagnoses and direct transfer to the ICU.

Missed foot fractures in multiple trauma patients.

BACKGROUND: Missed or underestimated injuries are one of the central problems in trauma care. Foot injuries can easily be missed because they lay beyond the regularly screened field of a trauma computer tomography scan (CT scan). During primary and secondary survey a careful examination of the extremities often becomes of secondary interest in the severely injured patient. METHODS: Thirty-four thousand ninety-one multiple trauma patients of the TraumaRegister DGU® were evaluated from 2002 to 2014. We differentiated between patients with foot injuries, patients with missed foot injuries and patients without foot injuries. Included were ankle fractures, calcaneus fractures, talus fractures, metatarsal fractures, toe fractures, amputation, soft tissue injuries and/or ligamentous injuries. RESULTS: Summarized evaluation of 34,091 trauma patients showed a share of 2532 patients with foot injuries. Time of diagnosis was documented in 2199 cases. 2055 patients had early diagnosed foot injuries and 144 patients had initially missed foot injuries. Missed foot injuries were especially found in patients with car accidents or fall from ≥3 m. Patients with higher Abbreviated Injury Scale (AIS) or lower Glasgow Coma Scale (GCS) were not significantly more affected by missed foot injuries. Missing foot injuries was also not caused by injury severity or higher age. CONCLUSIONS: Our data highlights the need of careful evaluation of the feet during primary and secondary survey particularly when a tibia or femur fracture is diagnosed. Special attention should be turned to patients after car accidents or fall from great height. Suicide victims also need major attention. Patients with early operations also need careful examination and tertiary survey is highly recommended.

A new multiple trauma model of the mouse.

BACKGROUND: Blunt trauma is the most frequent mechanism of injury in multiple trauma, commonly resulting from road traffic collisions or falls. Two of the most frequent injuries in patients with multiple trauma are chest trauma and extremity fracture. Several trauma mouse models combine chest trauma and head injury, but no trauma mouse model to date includes the combination of long bone fractures and chest trauma. Outcome is essentially determined by the combination of these injuries. In this study, we attempted to establish a reproducible novel multiple trauma model in mice that combines blunt trauma, major injuries and simple practicability. METHODS: Ninety-six male C57BL/6 N mice (n = 8/group) were subjected to trauma for isolated femur fracture and a combination of femur fracture and chest injury. Serum samples of mice were obtained by heart puncture at defined time points of 0 h (hour), 6 h, 12 h, 24 h, 3 d (days), and 7 d. RESULTS: A tendency toward reduced weight and temperature was observed at 24 h after chest trauma and femur fracture. Blood analyses revealed a decrease in hemoglobin during the first 24 h after trauma. Some animals were killed by heart puncture immediately after chest contusion; these animals showed the most severe lung contusion and hemorrhage. The extent of structural lung injury varied in different mice but was evident in all animals. Representative H&E-stained (Haematoxylin and Eosin-stained) paraffin lung sections of mice with multiple trauma revealed hemorrhage and an inflammatory immune response. Plasma samples of mice with chest trauma and femur fracture showed an up-regulation of IL-1ß (Interleukin-1ß), IL-6, IL-10, IL-12p70 and TNF-α (Tumor necrosis factor- α) compared with the control group. Mice with femur fracture and chest trauma showed a significant up-regulation of IL-6 compared to group with isolated femur fracture. CONCLUSIONS: The multiple trauma mouse model comprising chest trauma and femur fracture enables many analogies to clinical cases of multiple trauma in humans and demonstrates associated characteristic clinical and pathophysiological changes. This model is easy to perform, is economical and can be used for further research examining specific immunological questions.

Hepatocytes express the antimicrobial peptide HBD-2 after multiple trauma: an experimental study in human and mice.

BACKGROUND: Human-beta defensins (HBD) belong to the family of acute phase peptides and hold a broad antimicrobial spectrum that includes gram-positive and gram-negative bacteria. HBD are up-regulated after severe injuries but the source of posttraumatic HBD expression has not been focused on before. In the current study we analysed the role of liver tissue in expression of HBD after multiple trauma in human and mice. METHODS: HBD-2 expression has been detected in plasma samples of 32 multiple trauma patients (ISS > 16) over 14 days after trauma by ELISA. To investigate major sources of HBD-2, its expression and regulation in plasma samples, polymorphonuclear neutrophils (PMN) and human tissue samples of liver and skin were analysed by ELISA. As liver samples of trauma patients are hard to obtain we tried to review findings in an established trauma model. Plasma samples and liver samples of 56 male C57BL/6 N-mice with a thorax trauma and a femur fracture were analysed by ELISA, real-time PCR and immunohistochemistry for murine beta defensin 4 (MBD-4) and compared with the expression of control group without trauma. The induction of HBD-2 expression in cultured hepatocytes (Hep G2) was analysed after incubation with IL-6, supernatant of Staphylococcus aureus (SA) and Lipopolysaccharides (LPS). One possible signalling pathway was tested by blocking toll-like receptor 2 (TLR2) in hepatocytes. RESULTS: Compared to healthy control group, plasma of multiple traumatized patients and mice showed significantly higher defensin levels after trauma. Compared to skin cells, which are known for high beta defensin expression, liver tissue showed less HBD-2 expression, but higher HBD-2 expression compared to PMN. Immunhistochemical staining demonstrated upregulated MBD-4 in hepatocytes of traumatised mice. In HepG2 cells HBD-2 expression could be increased by stimulation with IL-6 and SA. Neutralization of HepG2 cells with αTLR2 showed reduced HBD-2 expression after stimulation with SA. CONCLUSION: Plasma samples of multiple traumatized patients showed high expression of HBD-2, which may protect the severely injured patient from overwhelming bacterial infection. Our data support the hypothesis that liver is one possible source for HBD-2 in plasma while posttraumatic inflammatory response.

Epidemiology of accidental hypothermia in polytrauma patients: An analysis of 15,230 patients of the TraumaRegister DGU.

BACKGROUND: Accidental hypothermia (AH) endangers the patient after polytrauma. Past studies have emphasized this entity as a major risk factor. The aim of this study was to describe the epidemiology of AH in major trauma considering the preclinical and clinical course. Predictors should be elucidated. METHODS: This is a retrospective investigation from the TraumaRegister DGU. Patients were documented in the period between 2002 and 2012. The study compared multiple-injured patients with or without hypothermic temperatures. Different groups of body core temperature were analyzed. Preclinical and clinical parameters were documented. RESULTS: Fifteen thousand two hundred thirty patients could be included. In 5,078 patients, temperature was below 36.0°C. Blunt trauma mechanisms surpassed penetrating injuries. The majority of patients sustained car accidents, accidents involving pedestrians, and falls from heights of greater than 3 m. Preclinical rescue procedures were extensively long in patients with low body temperature. Female gender, Glasgow Coma Scale score of 8 or less, nighttime, winter, motorcycle/bicycle accidents, Injury Severity Score 9 or greater, shock on site and in the emergency room, preclinical volume therapy, and time until admission to emergency room are significant risk factors to develop AH of 33°C. Volume management ranged between 1,453 ± 1,051 mL (33°C) and 1,058 ± 768 mL (36°C). Treatment in emergency room was extensively long. In further clinical course, severe AH advanced the clinical development of sepsis and multiple organ failure. The overall mortality inclined with decreasing body temperatures. CONCLUSIONS: Accidental hypothermia regularly occurred in polytrauma patients. Certain predictors exist, that is, female gender, which facilitate a body core temperature of 33°C. Preclinical and clinical courses match with other polytrauma studies. High incidence rates of sepsis, multiple organ failure, and mortality in hypothermic patients (33°C) demonstrate the severity of injury. Unfortunately, documentation of body core temperature remains challenging as the number of recorded hypothermic patients appears to be too small. We favor a strict focus on body core temperature on arrival in the emergency room. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

Local pamidronate influences fracture healing in a rodent femur fracture model: an experimental study.

BACKGROUND: Bisphosphonates are a main component in the therapy of osteoporosis and other bone resorptive diseases. Previous studies have shown a positive effect of systemically applied bisphosphonates on fracture healing. Nevertheless high doses are related to side effects like osteonecrosis of the jaw, nephrotoxis and gastrointestinal symptoms. In this study we investigated the effect of locally applied pamidronate on fracture healing. METHODS: In a rodent model a simple femur fracture was set in female Wistar rats. We performed intramedullary fixation of the fracture and placed a collagen matrix around the fracture area. One group was treated with pamidronate, the other group with placebo via the matrix. To investigate the volume and quality of the callus we used micro-CT (µCT) and histology after 14 and 28 days. RESULTS: Our results show a positive influence of local applied pamidronate on callus volume. After 14 days an insignificant increase of callus volume in the treated animals was seen. 28 days after trauma the increase of callus volume in the treatment group was significantly higher in comparison to the control group. Osteonecrosis was not seen. CONCLUSIONS: Locally applied bisphosphonates increase the callus volume in fracture healing.

Reduction and retention of thoracolumbar fractures by minimally invasive stabilisation versus open posterior instrumentation.

PURPOSE: The purpose of this study was in thoracolumbar fractures to assess the effectiveness of minimal invasive stabilisation compared to the open technique with regards to the change in kyphosis angle, the loss of reduction and length of hospital stay. METHODS: The retrospective study consisted of 104 patients who received minimally invasive stabilisation or open stabilisation. Patients were between 15 and 86 years of age, had a thoracolumbar fracture and no neurological deficits. Kyphotic angle (Cobb angle) and loss of reduction was compared after minimal invasive and open stabilisation. The Cobb angle was evaluated directly post operatively, at 6 weeks, 3 months, 6 months and 12 months after surgery. RESULTS: Evaluated patients who received the minimally invasive technique had a shorter surgical intervention time and a shorter hospital stay compared to patients who received the open technique. Kyphosis angle and loss of reduction showed no significant difference compared to open technique. There was also no significant difference between minimally invasive poly-axial and mono-axial stabilisation. CONCLUSION: In this study we provide evidence that MIS instrumentation in selected thoracolumbar fractures can effectively be used without significant differences in loss of reduction compared to open stabilisation. MIS can also sufficiently retain reduction as compared to traditional open techniques. The main advantages are reduced operation time and shorter hospital stay.

Rivaroxaban does not impair fracture healing in a rat femur fracture model: an experimental study.

BACKGROUND: The prescription of the oral anticoagulant rivaroxaban to prevent thromboembolic episodes associated with orthopaedic surgery has dramatically increased since it was introduced. Rivaroxaban is beeing prescribed although recent in-vitro studies revealed that it impaired osteoblast metabolism. In this study we analysed the effect of rivaroxaban on fracture healing in a rat femur fracture model. METHODS: Femur fractures were created by a 3-point-bending device in 48 Wistar rats and subsequently stabilized by intramedullary nailing. After the surgical procedure animals were randomised into four groups. Two groups were fed with 3 mg rivaroxaban per kg body weight per day and two control groups were fed with chow only. Animals were euthanized 28 or 49 days after surgical procedure. Femurs underwent undecalcified histologic staining micro CT scanning and biomechanical testing. The statistical significance was evaluated using one-way Anova with Bonferroni correction. RESULTS: Micro CT-scans revealed significantly increased volume of bone tissue in the fracture zone between day 28 and 49. During the same time callus volume decreased significantly. Comparing the fracture zone of the rivaroxaban group to the control group the treated group revealed a larger callus and a marginal increase of the tissue mineral density. The torsional rigidity was not influenced by the treatment of rivaroxaban. CONCLUSION: In the present study we were able to demonstrate that rivaroxaban does not impair fracture healing in a rat femur fracture model. Considering the fact that low molecular weight heparins delay fracture healing significantly, rivaroxaban might be an improved alternative.

The antimicrobial peptide lysozyme is induced after multiple trauma.

The antimicrobial peptide lysozyme is an important factor of innate immunity and exerts high potential of antibacterial activity. In the present study we evaluated the lysozyme expression in serum of multiple injured patients and subsequently analyzed their possible sources and signaling pathways. Expression of lysozyme was examined in blood samples of multiple trauma patients from the day of trauma until 14 days after trauma by ELISA. To investigate major sources of lysozyme, its expression and regulation in serum samples, different blood cells, and tissue samples were analysed by ELISA and real-time PCR. Neutrophils and hepatocytes were stimulated with cytokines and supernatant of Staphylococcus aureus. The present study demonstrates the induction and release of lysozyme in serum of multiple injured patients. The highest lysozyme expression of all tested cells and tissues was detected in neutrophils. Stimulation with trauma-related factors such as interleukin-6 and S. aureus induced lysozyme expression. Liver tissue samples of patients without trauma show little lysozyme expression compared to neutrophils. After stimulation with bacterial fragments, lysozyme expression of hepatocytes is upregulated significantly. Toll-like receptor 2, a classic receptor of Gram-positive bacterial protein, was detected as a possible target for lysozyme induction.

Cytokine productive capacity of alveolar macrophages and Kupffer cells after femoral fracture and blunt chest trauma in a murine trauma model.

INTRODUCTION: Specific cellular and inflammatory factors that contribute to the severity of pulmonary dysfunction after blunt chest trauma and osteosynthesis of femoral fractures are yet not fully understood. Therefore, we investigated alterations of the cytokine productive capacity of alveolar macrophages (AM) and Kupffer cells (KC) after femoral fracture stabilized with intramedullary pin with or without blunt chest trauma. MATERIALS AND METHODS: In male C57BL/6N mice an intramedullary pin was implanted in an intact femur as the sham procedure. In trauma groups mice either received an isolated femoral fracture with subsequent fracture stabilization with an intramedullary pin (group Fx) or a combined trauma of blunt chest trauma and femur fracture also stabilized by an intramedullary pin (group TTFx). Animals were sacrificed 0h, 6h, 12h, 24h and 3d after trauma induction. Cytokine concentrations were measured in plasma and supernatant of cultivated AM and KC by FACS analysis. Pulmonary and hepatic infiltration of polymorphonuclear leukocytes (PMN) was determined by Ly6G-staining. RESULTS: At 6h, isolated femoral fracture with intramedullary stabilization resulted in a significantly increased productive capacity of KC (IL-6, TNF-α, CCL2, CCL3, CCL5 and CCL7) compared to sham animals. Combined trauma additionally resulted in an increased productive capacity of AM (IL-6, TNF-α, CCL2, CCL3, CCL4, CCL5 and CCL7) at 6h and the effect was prolonged up to 3d compared to controls. Combined trauma also led to a significant higher amount of plasma CCL2 at 3d and plasma CCL7 at 6h after the insult compared to group Fx. Compared to shams, pulmonary and hepatic infiltrations of PMNs were increased in group Fx and TTFx after 6h, but in the combined trauma model the effect was prolonged up to 3d. CONCLUSION: An intramedullary stabilized femur fracture alone results in a significant activation of the immune response. The combination of femoral fracture and blunt chest trauma however, results in an increased and prolonged activation of the inflammatory response. Transferred to the clinical setting, these results emphasize the critical role of severe chest trauma for treatment strategies of femoral fractures in multiple trauma patients.

Expression and function of psoriasin (S100A7) and koebnerisin (S100A15) in the brain.

The expression and function of psoriasin in the brain have been insufficiently characterized. Here, we show the induction of psoriasin expression in the central nervous system (CNS) after bacterial and viral stimulation. We used a pneumococcal meningitis in vivo model that revealed S100A15 expression in astrocytes and meningeal cells. These results were confirmed by a cell-based in vivo assay using primary rat glial and meningeal cell cultures. We investigated psoriasin expression in glial and meningeal cells using polyinosinic-polycytidylic acid, a synthetic analog of double-stranded RNA that mimics viral infection. Furthermore, previous results showed that antimicrobial peptides have not only bactericidal but also immunomodulatory functions. To test this statement, we used recombinant psoriasin as a stimulus. Glial and meningeal cells were treated with recombinant psoriasin at concentrations from 25 to 500 ng/ml. Treated microglia and meningeal cells showed phosphorylation of the extracellular signal-regulated kinase 1 (ERK1)/ERK2 (ERK1/2) signal transduction pathway. We demonstrated that this activation of ERK depends on RAGE, the receptor for advanced glycation end products. Furthermore, microglia cells treated with recombinant psoriasin change their phenotype to an enlarged shape. In conclusion, our results indicate an occurrence of psoriasin in the brain. An involvement of psoriasin as an antimicrobial protein that modulates the innate immune system after bacterial or viral stimulation is possible.

Multiple trauma induces serum production of host defence peptides.

Today multiple trauma still is associated with a high mortality. Although severe open fractures and wounds can give rise to local infections and sepsis, the overall infection rate of multiply injured patients is surprisingly low. We have investigated serum of multiply injured patients with respect to antibacterial properties and screened for host defence peptides (HDP) that constitute a class of fast acting and rapidly available molecules preventing bacterial infection. Serum specimens were obtained from multiply injured patients. Radial diffusion assays were performed to investigate antimicrobial properties. Ultrafiltration and heat-inactivation were used to rule out antimicrobial activity of large proteins i.e. complement factors. ELISA was performed to analyse serum concentrations of the human beta-defensins 2 and 3 (hBD-2 and hBD-3), LL-37 and the proinflammatory cytokines interferon-gamma (IFN-γ) and interleukin-6 (IL-6). Serum of multiply injured patients showed greater zones of inhibition in antimicrobial testing against Gram negative und positive bacteria. This effect was mediated by proteins smaller than 10 kDa, inactivation of the complement system does not significantly reduce antibacterial action. hBD-2, hBD-3 and LL-37 concentrations were significantly elevated after trauma and followed different characteristic concentration curves. Similar patterns of concentration profiles were recorded for hBD-2/IL-6 and hBD-3/IFN-γ suggesting a stimulatory influence within their induction process. With this study we provide evidence, that serum of multiply injured patients has by far higher antibacterial capacity than that of healthy donors. As possible mediators we have detected the HDP hBD-2, hBD-3 and LL-37 and their inducers in serum of multiply injured patients.

The treatment of intra-articular calcaneus fractures with severe soft tissue damage with a hinged external fixator or internal stabilization: long-term results.

We developed a hinged external fixator for the treatment of dislocated intra-articular calcaneus fractures with severe soft tissue damage. The external fixation was performed with a known external fixator system. The screw insertion points were biomechanically tested by defining a virtual rotation axis through the center of the talus to allow early active motion in the ankle joint. Long-term follow-up was performed after an average of 7.3 years. Results were graded with the American Orthopaedic Foot and Ankle Society (AOFAS) score. Radiographs were reviewed according to Sanders classification. Four open fractures and 33 cases with extremely swollen soft tissue, blisters, or compartment syndromes were treated. In 24 cases (64.9%), the hinged fixator was the final method of treatment (group I). A change to open reduction with internal fixation was performed in 13 fractures (35.1%) when soft tissue problems were minimal (group II). There were no late amputations, osteomyelitis, or malunions. According to Sanders classification, group I consisted of 14 type II, 8 type III, and 2 type IV fractures. Pin loosening or pin infection was seen in 4 cases, but there was no redislocation. The Böhler's angle improved in 43%, gaps in the posterior facet were closed in 41%, and any shortening or deviation of the axis was corrected in 82% of the cases. The AOFAS score for the group averaged 66.5. According to Sanders classification, group II consisted of 8 type II and 5 type III fractures. The Böhler's angle improved in 88%, and gaps in the posterior facet were closed in 87%. Any shortening or deviation of the axis was corrected in 95%, and the AOFAS score averaged 61.3. Significant differences in patient outcome scores between open reduction with internal fixation and hinged fixator were not found. P value was > .05. The hinged external fixator frame can be used in all calcaneus fracture types without soft tissue limitation. The hinged fixator allows early movement in the ankle joint, the risk of infection is minimized, and secondary plate fixation remains possible.