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To determine whether open reduction and internal fixation (ORIF) of periprosthetic Vancouver B2 fractures can lead to successful fracture healing in selected patients, when attention is given to the surgical exposure and the creation of a balanced extramedullary construct.Retrospective.Two Level-1 trauma centers in Germany and United Kingdom.Patients with a B2 fracture receiving solely ORIF using a polyaxial locking plate were included for analysis. Patients with other fracture types, or treated with other methods, or with follow-up less than 12 months were excluded. Clinical characteristics, including the Charlson index, the American Society for Anesthesiologists score, and their preinjury functional levels, were recorded. Main outcome measures were 1-year mortality, revision rate, and radiological healing according to the Beals-Tower criteria.A total of 32 patients (mean age ,79 ± 12 years) were enrolled. Six patients died within the first year (1-year mortality: 19%), and 5 were unavailable for follow-up studies. The remaining 21 patients had a mean follow-up of 30 months. Of 21, 20 had an excellent/good result using the criteria of Beals-Tower. One patient required revision surgery due to loosening and secondary subsidence of the stem.ORIF can be offered to selected patients suffering from B2 fractures, especially if their functional demand is limited, and perioperative risk high for revision arthroplasty. In this challenging cohort of patients, ORIF was a safe and effective therapeutic option.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

ZusammenfassungAtraumatische Nackenschmerzen sind ein häufiger Vorstellungsgrund für Patienten in der Notaufnahme. Für die behandelnden Ärzte ist dabei der Ausschluss möglicherweise lebensbedrohlicher Erkrankungen, wie Spondylodiszitis, retropharyngealer Abszess oder Meningitis, oft eine große Herausforderung. In dieser Kasuistik wird der seltene Fall der retropharyngealen Tendinitis vorgestellt, einer wenig bekannten und dadurch sicherlich unterdiagnostizierten Entität. Sie ist charakterisiert durch einen stark reduzierten Bewegungsumfang der HWS, erhöhte Infektparameter und einen pathognomonischen MRT-Befund.Zusätzlich zur Fallpräsentation soll im Rahmen eines kurzen Reviews die Charakteristik der retropharyngealen Tendinitis noch genauer dargestellt werden. So ist es das Ziel dieser Arbeit, die behandelnden Ärzte für dieses Krankheitsbild zu sensibilisieren, um in Zukunft falsche bzw. unnötige Therapien zu vermeiden.

(1) Background: Current findings emphasize the potential contribution of platelets to the immunological response after severe trauma. As clinical relevance remains unclear, this study aims to analyze the correlation between platelets and lung dysfunction in severely injured patients. (2) Methods: We retrospectively enrolled all multiple trauma patients presenting to our level 1 trauma center from 2015 to 2016 with an Injury-Severity Score (ISS) ≥ 16. Apart from demographic data, platelet counts and PaO2/FiO2 as an approximate indicator for lung physiology were analyzed and correlated on subsequent days after admission. (3) Results: 83 patients with a median ISS of 22 (IQR 18–36) were included. Compared to day 1, platelet counts were decreased on day 3 (p ≤ 0.001). Platelet counts were significantly lower on day 3 in patients with an ISS ≥ 35 (p = 0.011). There were no differences regarding PaO2/FiO2 index. Correlation analysis revealed a positive link between increased platelet counts and PaO2/FiO2 index on day 1 only in severely injured patients (p = 0.007). (4) Conclusions: This work supports the concept of platelets modulating the posttraumatic immune response by affecting lung dysfunction in the early phase after multiple trauma in dependence of injury severity. Our findings contribute to the understanding of the impact of platelets on systemic processes in multiple trauma patients.

With a prevalence of approximately 0.4%, distal femoral fractures are a rare entity. Nevertheless, due to the high mortality rates, which are comparable to proximal femoral fractures, these fractures are highly important. The clinical symptoms are often quite striking. In combination with preoperative computed tomography (CT) and if necessary, supplemented by CT angiography, the morphological situation can be assessed and the decision making facilitated. There are several different treatment options and the appropriate one should be selected for each individual case. The use of external fixation of the complete knee joint in the sense of damage control surgery, is useful. For definitive treatment retrograde intramedullary nailing and locking plates with angle stable screws are the main options. Modern angle stable and anatomically preformed implants enable surgical treatment using minimally invasive approaches to protect the soft tissues, with a better overall outcome.

Atraumatic neck pain is a frequent reason for patients to attend the emergency department (ED). It remains a challenge for the treating physician to rule out possible life-threatening causes, such as a retropharyngeal abscess, meningitis or septic spondylodiscitis. Herein, we report the rare case of a patient suffering from retropharyngeal tendinitis. This rare cause of atraumatic neck pain is characterized by a significant decrease in the range of motion of the cervical spine, elevated infection parameters and pathognomonic MRI findings. In addition to presenting the rare case of retropharyngeal tendinitis, we also review selected previous case reports and thereby not only raise awareness for this rare disease but also suggest the best practice for treatment.Atraumatische Nackenschmerzen sind ein häufiger Vorstellungsgrund für Patienten in der Notaufnahme. Für die behandelnden Ärzte ist dabei der Ausschluss möglicherweise lebensbedrohlicher Erkrankungen, wie Spondylodiszitis, retropharyngealer Abszess oder Meningitis, oft eine große Herausforderung. In dieser Kasuistik wird der seltene Fall der retropharyngealen Tendinitis vorgestellt, einer wenig bekannten und dadurch sicherlich unterdiagnostizierten Entität. Sie ist charakterisiert durch einen stark reduzierten Bewegungsumfang der HWS, erhöhte Infektparameter und einen pathognomonischen MRT-Befund.Zusätzlich zur Fallpräsentation soll im Rahmen eines kurzen Reviews die Charakteristik der retropharyngealen Tendinitis noch genauer dargestellt werden. So ist es das Ziel dieser Arbeit, die behandelnden Ärzte für dieses Krankheitsbild zu sensibilisieren, um in Zukunft falsche bzw. unnötige Therapien zu vermeiden.

Background and objective: Platelets contribute to the immunological response after multiple trauma. To determine the clinical impact, this study analyzes the association between platelets and creatinine concentration as an indicator of kidney function in polytraumatized patients. Methods: We investigated all patients presenting an Injury Severity Score (ISS) ≥16 for a 2-year period at our trauma center. Platelet counts and creatinine concentrations were analyzed, and correlation analysis was performed within 10 days after multiple trauma. Results: 83 patients with a median ISS of 22 were included. Platelet count was decreased on day 3 (p ≤ 0.001) and increased on day 10 (p ≤ 0.001). Platelet count was elevated on day 10 in younger patients and diminished in severely injured patients (ISS ≥35) on day 1 (p = 0.012) and day 3 (p = 0.011). Creatinine concentration was decreased on day 1 (p = 0.003) and day 10 (p ≤ 0.001) in female patients. Age (p = 0.01), male sex (p = 0.004), and injury severity (p = 0.014) were identified as factors for increased creatinine concentration on day 1, whereas platelets (p = 0.046) were associated with decreased creatinine concentrations on day 5 after multiple trauma. Conclusions: Kinetics of platelet count and creatinine concentration are influenced by age, gender, and trauma severity. There was no clear correlation between platelet counts and creatinine concentration. However, platelets seem to have a modulating effect on creatinine concentrations in the vulnerable phase after trauma.

Background: Accidents and injuries are the leading causes of mortality in young people. CD4+ regulatory T cells (CD4+ Tregs), Th17 cells and platelets could be identified as key players in post-traumatic immunological dysfunction, which is a common cause of late mortality in trauma patients. The mechanisms of activation of these cell types and their interaction remain mostly unclear. Since CD69 is not only a leukocyte marker but has also immunoregulatory functions, we postulate a role for CD69 after trauma. The present study investigates the expression of CD69 on CD4+ Tregs and Th17 cells, as well as the posttraumatic expansion of platelets and hemostatic function. Subgroup analysis was performed to assess the differences between polytrauma patients with and without severe traumatic brain injury (TBI). Methods: In this non-interventional prospective clinical trial, we analyzed sequential blood samples over a period of 10 days from 30 patients after multiple traumas with an ISS ≥ 16. Platelet function was assessed by rotational thromboelastometry (ROTEM analysis). CD4+ Tregs and Th17 cells were stained with surface markers and analyzed by flow cytometry. Results: We were able to demonstrate a significantly increased expression of CD69 on CD4+ Tregs after trauma. Subgroup analysis revealed that the absence of severe TBI is associated with a significantly higher expression of CD69 on CD4+ Tregs and on Th17 cells. Platelets expanded and showed signs of dysfunction, while an overall tendency of posttraumatic hypercoagulation was detected. Conclusions: Our results support the concept of injury-specific immune responses and add to a further understanding of the complex pathophysiology of post-traumatic immune dysfunction.

CD4

Background The aim of this study was to evaluate the clinical and/or radiologic outcome using different polyaxial locking plates for the treatment of proximal tibia fractures, the Non-Contact-Briding plate (NCB-PT®) by Zimmer or the Variable Angle Locking Compression Plate (VA-LCP®) by Synthes. Methods This study enrolled 28 patients with proximal tibia fractures (AO/ OTA 41 B-C) and indication for locking plate osteosynthesis. All patients were treated with a polyaxial locking plate system. Depending on the fracture morphology, patients were either treated with a NCB-PT® or VA-LCP®. The implant was chosen according to the surgeon’s experience and preference, in case of a higher degree of comminution the tendency was observed to use the NCB-PT® plate. After a time interval of 12 months postoperative we conducted clinical (e.g.e.g. exempli gratia range of motion, the Rasmussen score) and radiological (e.g. primary/secondary loss of reduction) follow-ups. Results Patients provided with the NCB-PT® (9 patients) showed longer operation time, use of longer implants, longer interval from injury to surgery and lower clinical scores after the 12 months follow-up compared with the VA-LCP® group (19 patients). Interestingly, the results showed no significant differences regarding the clinical and radiologic outcome. Conclusions The small number of patients as well as the heterogeneity of fractures constitute a limitation of this study. Nevertheless, the differentiated use of implants is associated with comparable clinical and radiological outcomes. This trial emphasizes the need for further prospective randomised trials with higher patient numbers. Trial registration Retrospectively registered 21.12.2020. Registration number NCT04680247 .

CD4+FoxP3+ regulatory T cells (CD4+ Tregs) are known to dampen inflammation following severe trauma. Platelets were shown to augment their posttraumatic activation in burn injury, but the exact mechanisms remain unclear. We hypothesized that platelet activation mechanisms via GPIIb/IIIa, fibrinogen, and PAR4 have an immunological effect and modulate CD4+ Treg activation early after trauma. Therefore, C57Bl/6 N mice were injected with tirofiban (GPIIb/IIIa inhibition), ancrod (fibrinogen splitting enzyme), or tcY-NH2 (selective PAR4 antagonist peptide) before inducing a third-degree burn injury of 25% of the total body surface area. Changes in coagulation, and local and systemic CD4+ Treg activity were assessed via rotational thromboelastometry (ROTEM®) and phospho-flow cytometry 1 h post intervention. The inhibition of GPIIb/IIIa and fibrinogen locally led to a higher basic activity of CD4+ Tregs compared to non-inhibited animals. In contrast, PAR4 disruption on platelets locally led to an increased posttraumatic activation of CD4+ Tregs. Fibrinogen led to complete elimination of coagulation, whereas GPIIb/IIIa or PAR4 inhibition did not. GPIIb/IIIa receptor and fibrinogen inhibition increase CD4+ Tregs activity independently of trauma. Both are crucial for thrombus formation. We suggest platelets trapped in thrombi are unable to interact with CD4+ Tregs but augment their activity when circulating freely. In contrast, PAR4 seems to reduce CD4+ Treg activation following trauma. In summary, GPIIb/IIIa-, PAR4-, and fibrinogen-dependent pathways in platelets modulate CD4+ Treg baseline activity, independently from their hemostatic functionality. PAR4-dependent pathways modulate the posttraumatic interplay of platelets and CD4+ Tregs.

CD4+ FoxP3+ regulatory T cells (CD4+ Tregs) are important for the posttraumatic anti-inflammatory host response. As described previously, platelets are able to modulate CD4+ Treg activity in a reciprocally activating interaction following injury. The underlying mechanisms of the posttraumatic interaction between platelets and CD4+ Tregs remain unclear. We investigated the potential influence of CD40L and P-selectin, molecules known to be involved in direct cell contact of these cell types. In a murine burn injury model, the potential interaction pathways were addressed using CD40L- and P-selectin-deficient mice. Draining lymph nodes were harvested following trauma (1 h) and following a sham procedure. Early rapid activation of CD4+ Tregs was assessed by phospho-flow cytometry (signaling molecules (p)PKC-δ and (p)ZAP-70). Platelet function was analyzed performing rotational thromboelastometry (ROTEM). We hypothesized that disruption of the direct cell-cell contact via CD40L and P-selectin would affect posttraumatic activation of CD4+ Tregs and influence the hemostatic function of platelets. Indeed, while injury induced early activation of CD4+ Tregs in wild-type mice (ZAP-70: p = 0.13, pZAP-70: p < 0.05, PKC-δ: p < 0.05, pPKC-δ: p < 0.05), disruption of CD40L-dependent interaction (ZAP-70: p = 0.57, pZAP-70: p = 0.68, PKC-δ: p = 0.68, pPKC-δ: p = 0.9) or P-selectin-dependent interaction (ZAP-70: p = 0.78, pZAP-70: p = 0.58, PKC-δ: p = 0.81, pPKC-δ: p = 0.73) resulted in reduced posttraumatic activation. Furthermore, hemostatic function was impaired towards hypocoagulability in either deficiency. Our results suggest that the posttraumatic activation of CD4+ Tregs and hemostatic function of platelets are affected by direct cell-cell-signaling via CD40L and P-selectin.

With a prevalence of approximately 0.4%, distal femoral fractures are a rare entity. Nevertheless, due to the high mortality rates, which are comparable to proximal femoral fractures, these fractures are highly important. The clinical symptoms are often quite striking. In combination with preoperative computed tomography (CT) and if necessary, supplemented by CT angiography, the morphological situation can be assessed and the decision making facilitated. There are several different treatment options and the appropriate one should be selected for each individual case. The use of external fixation of the complete knee joint in the sense of damage control surgery, is useful. For definitive treatment retrograde intramedullary nailing and locking plates with angle stable screws are the main options. Modern angle stable and anatomically preformed implants enable surgical treatment using minimally invasive approaches to protect the soft tissues, with a better overall outcome.

Infection is a common and severe complication of burn injury: Sepsis accounts for 47% of postburn mortality. Burn-induced T cell suppression likely contributes to the increased infection susceptibility in burn patients. However, little is known about the kinetics of T cell dysfunction after burn and its underlying mechanisms. In this study, we show in a murine scald injury model that T cell activation of both CD4+ and CD8+ T cells as well as T cell cytokine production is suppressed acutely and persistently for at least 11 days after burn injury. Purified T cells from scald-injured mice exhibit normal T cell functions, indicating an extrinsically mediated defect. We further show that T cell dysfunction after burn appears to be cell-to-cell contact dependent and can be ameliorated by depletion of myeloid-derived suppressor cells. These cells expand after burn injury, particularly a subset expressing the checkpoint inhibitor CD172a, and infiltrate germinal centers. Expression of CD172a appears to be driven by ingestion of immature reticulocytes. Immature reticulocytes are drastically increased in the spleen of scald mice and may contribute to immunosuppression through more direct mechanisms as well. Overall, our study newly identifies two cell populations, myeloid-derived suppressor cells and immature reticulocytes, as well as the CD47/CD172a-signaling pathways as mediators of T cell suppressors after burn and thus opens up new research opportunities in the search for new therapies to combat increased infection susceptibility and the associated morbidity and mortality in burn victims.

Introduction The current treatment concepts of fracture-related infection (FRI) [Consensus Conference (Anti-Infection Task Force (AITF)) on the definition of acute or chronic osteomyelitis (cOM)] are associated with unsolved challenges and problems, underlining the need for ongoing medical research. Method Literature review of treatments for FRI and description of own cases. Results We could include eight papers with 394 patients reporting treatments and outcome in FRI. The infection was resolved in 92.9% (mean) of all treatments. The mean follow-up was 25 months with a persistent non-union in 7% of the patients. We diagnosed 35 (19f/16m; 56.4 ± 18.6 years) patients with bone infections anatomically allocated to the proximal and distal femur (12×), the pelvis (2×), distal tibia (3×), tibial diaphysis (11×), the ankle joint (4×) and calcaneus (3×). These 35 patients were treated (1) with surgical debridement; (2) with antibiotic-eluting ceramic bone substitutes; (3) bone stabilization (including nail fixation, arthrodesis nails, plates, or external ring fixation), (4) optionally negative pressure wound therapy (NPWT) and (5) optionally soft tissue closure with local or free flaps. The mean follow-up time was 14.9 ± 10.6 months (min/max: 2/40 month). The overall recurrence rate is low (8.5%, 3/35). Prolonged wound secretion was observed in six cases (17.1%, 6/35). The overall number of surgeries was a median of 2.5. Conclusion The results in the literature and in our case series are explicitly promising regarding the treatment of posttraumatic fracture-related infection.

Platelets modulate the immune system following injury by interacting with CD4+ T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFα)-, Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10). In the murine burn injury model, CD4+ Treg activation pathways were selectively addressed using TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC-θ was analyzed using phospho-flow cytometry to detect rapid cell activation. Thromboelastometry (ROTEM®) was used to assess platelet activation. Injury induced significant early activation of CD4+ Tregs, disruption of TNFR2 and TLR4 activation pathways resulted in lower activity. The disruption of IL-10 crosstalk had no significant impact. Selective disruption of paracrine interactions is associated with changes in posttraumatic hemostasis parameters. TNFR2- and TLR4-dependent pathways modulate the activation of CD4+ Tregs following trauma. In contrast, we did not observe a role of IL-10 in the posttraumatic activation of CD4+ Tregs. One sentence summary TLR4- and TNFR2-dependent mechanisms, but not IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs following trauma.

Micro-RNAs (miRNAs) have been getting more and more attention over the last few years due to their great potential as biomarkers for diagnostic approaches. miRNAs in bone are still not well explored and their influence on the gene expression is not completely understood by now. Some studies show that miRNAs have an impact on bone formation. Thus, the following work was looking at the expression level of miR-100-5p in osteoblasts as potential influencer of bone formation.

Wound management is one of the major tasks in emergency departments. The surrounding intact skin but not the wound itself should be disinfected before starting definitive wound treatment. Hair should first be removed by clipping to 1-2 mm above the skin with scissors or clippers as shaving the area with a razor damages the hair follicles and increases the risk of wound infections. Administration of local anesthetics should be performed directly through the exposed edges of the wound. After wound examination, irrigation is performed with Ringer's solution, normal saline or distilled water. The next step is debridement of contaminated and devitalized tissue. There are several wound closure techniques available, including adhesive tapes, staples, tissue adhesives and numerous forms of sutures. Management of specific wounds requires particular strategies. A bleeding control problem frequently occurs with scalp lacerations. Superficial scalp lacerations can be closed by alternative wound closure methods, for example by twisting and fixing hair and the use of tissue adhesives, i.e. hair apposition technique (HAT). For strongly bleeding lacerations of the scalp, the epicranial aponeurosis should be incorporated into the hemostasis. Aftercare varies depending on both the characteristics of the wound and those of the patient and includes adequate analgesia as well as minimizing the risk of infection. Sufficient wound aftercare starts with the treating physician informing the patient about the course of events, potential complications and providing relevant instructions.

A paradigm shift in the treatment of elderly patients has recently taken place leading to an increase in joint replacement surgery. The aim of this article is to highlight new developments and to present a treatment algorithm for femoral neck fractures. The age limit must be individually determined considering the comorbidities and perioperative risk profile. Pertrochanteric femoral fractures are nearly exclusively treated by osteosynthesis regardless of age. The situation for femoral neck fractures is more complex. Patients younger than 65 years should generally be treated by osteosynthesis but patients older than 65 years benefit from hemiarthroplasty or total hip arthroplasty. In patients aged between 65 and 75 years with high functional demands and a justifiable perioperative risk, total joint replacement is the treatment of choice. In physically less active patients older than 75 years and poor general condition, preference should be given to hemiarthroplasty.

Periprosthetic fractures around the knee joint are of increasing relevance due to increasing numbers of total knee replacements and increasing life expectations. These fractures can be a real challenge due to an often limited patient compliance, reduced bone quality and impaired bone perfusion of potential intramedullary shafts resulting in poor healing and lack of fixation options for screws. These fractures necessitate special knowledge and approaches, which are systematically dealt with in this article, beginning with the correct diagnostics through to the most recent developments in the field of osteosynthetic techniques. The trends of minimally invasive techniques are presented and the options and limitations are described.

Beckenfrakturen sind seltene, jedoch potenziell lebensbedrohliche Verletzungen. Der Blutverlust bei instabilen Beckenverletzungen ist die fuhrende Todesursache. Das initiale Erkennen der pelvinen Blutung ist ausschlaggebend fur das Uberleben des Patienten und erfordert eine sofortige Notfallbehandlung mit dem Ziel der Blutungskontrolle. Dabei kommt der detaillierten Kenntnis der anatomischen und pathophysiologischen Grundlagen grose Bedeutung zu; der Grosteil der verletzungsbedingten pelvinen Blutungen ist venosen Ursprungs. Deren Kontrolle gelingt am besten uber Tamponade, die jedoch bei frakturbedingter Instabilitat zunachst nicht gelingen kann. Daher kommt dem Konzept der Stabilisierung gefolgt von Tamponade immer grosere Bedeutung zu, was sich auch in den neuesten Empfehlungen der Literatur widerspiegelt. Diese werden im folgenden Beitrag dargestellt, aktuelle Entwicklungen in der Therapie ausgedehnter Beckenverletzungen werden besprochen, und es wird versucht, einen klar strukturierten Handlungsablauf zu skizzieren.

Aims and Objectives: The use of polyaxial locking plates is an established technique for the treatment of proximal tibia fractures. At the moment different polyaxial locking implants from numerous manufactures are available, though at the moment there are no clinical trials regarding their differences. In this prospective clinical trail we compared the NCB-PT® (Zimmer) and the VA-LCP® (Synthes) by analysing primary and secondary quality criteria of the osteosynthesis (clinical and radiological). Materials and Methods: This study enrolled 28 patients suffering from a proximal tibia fracture (AO/ASIF 41 B-C). The follow-up examinations were conducted over 12 months after the surgery. Clinical (e.g. range of motion, Rasmussen score, Tegner score) as well as radiological parameters (e.g. primary and secondary loss of reduction, fracture healing) were collected. For the analysis of continuous parametric variables the Student’s t-test was used and for non-parametric variables the Mann-Whitney U test. For binominal variables the Fisher’s exact test was preformed. In all analysis the significance level was set at a p-value Results: Comparing the epidemiologic data of both groups only very small or no differences with no statistical significance could be found. The intraoperative data showed a significant longer surgery duration for the NCB-group (NCB-PT® 196,3 min vs. VA-LCP® 121,7 min, p-value 0,0335). Furthermore the median length of implants used in each group proved to be significant longer in the NCB-group (NCB-PT® 8,1 holes vs. VA-LCP® 5,1 holes, p-value 0,0007), most likely because of the imbalance of severe fractures in between the groups (type C fractures: NCB-PT® 78% vs. VA-LCP® 26%). The analysis of the clinical data as well as the clinical scores showed reduced scoring values of the NCB-group. Only the results of the Lysholm score (p-value: 0,03) and MKQ (Munich Knee Questionnaire) (p-value: < 0,0001) proved to be statistically significant. Regarding the radiological data only the radiologic Rasmussen score had a significant difference in favour of the VA-LCP®-group (p-value 0,0153). Conclusion: This study constitutes the first prospective clinical trial to compare the outcome of the VALCP® an NCB-PT® for the treatment of proximal tibia fractures. Despite the limitation of this study, low case numbers and heterogeneity of fracture types, differences regarding the clinical and radiological outcome could be found. The treatment with the VA-LCP® had a significantsuperior outcome in separate clinical scores (Lyshom score/ Munich Knee Questionnaire) as well as in a single radiologic score (radiologic Rasmussen score) in comparison to the treatment with the NCB-PT®. Our data underlines the necessity for an extended study with a higher case number.

Background The issue of patient volume related to trauma outcomes is still under debate. This study aimed to investigate the relationship between number of severely injured patients treated and mortality in German trauma hospitals. Methods This was a retrospective analysis of the TraumaRegister DGU® (2009–2013). The inclusion criteria were patients in Germany with a severe trauma injury (defined as Injury Severity Score (ISS) of at least 16), and with data available for calculation of Revised Injury Severity Classification (RISC) II score. Patients transferred early were excluded. Outcome analysis (observed versus expected mortality obtained by RISC‐II score) was performed by logistic regression. Results A total of 39 289 patients were included. Mean(s.d.) age was 49·9(21·8) years, 27 824 (71·3 per cent) were male, mean(s.d.) ISS was 27·2(11·6) and 10 826 (29·2 per cent) had a Glasgow Coma Scale score below 8. Of 587 hospitals, 98 were level I, 235 level II and 254 level III trauma centres. There was no significant difference between observed and expected mortality in volume subgroups with 40–59, 60–79 or 80–99 patients treated per year. In the subgroups with 1–19 and 20–39 patients per year, the observed mortality was significantly greater than the predicted mortality (P < 0·050). High‐volume hospitals had an absolute difference between observed and predicted mortality, suggesting a survival benefit of about 1 per cent compared with low‐volume hospitals. Adjusted logistic regression analysis (including hospital level) identified patient volume as an independent positive predictor of survival (odds ratio 1·001 per patient per year; P = 0·038). Conclusion The hospital volume of severely injured patients was identified as an independent predictor of survival. A clear cut‐off value for volume could not be established, but at least 40 patients per year per hospital appeared beneficial for survival., No clear volume cut‐off

Purpose of review To provide an update on the relevant and recent studies on whole-body computed tomography (WBCT) imaging of severely injured patients. Recent findings The advantages of WBCT in time saving, diagnostic accuracy and even in survival have been proven in numerous studies. WBCT can also be beneficial in haemodynamically unstable major trauma patients. The CT scanner should be located close to the emergency department or even in the trauma room. The issue of radiation is still quite important, however, iterative as well as split-bolus protocols can nowadays reduce radiation significantly. The question: which trauma patient should receive WBCT and which not is not yet solved sufficiently. Postmortem WBCT has a promising potential to promptly define the definitive cause of death of trauma victims comparably to traditional autopsy. Summary On account of the recent advances, whole-body CT has become a crucial part of the initial in-hospital assessment of severely injured patients. It is recommended as the standard radiological tool for the emergency diagnostic work-up in major trauma patients.

Osteosarcoma is the leading primary bone cancer in young adults and exhibits high chemoresistance rates. Therefore, characterization of both alternative treatment options and the underlying mechanisms is essential. Simvastatin, a cholesterol-lowering drug, has among its pleiotropic effects anticancer potential. Characterizing this potential and the underlying mechanisms in osteosarcoma is the subject of the present study. Human osteosarcoma cells (SaOS-2 and U2OS) were treated with simvastatin (4-66 µM) for 48 or 72 h. The effects of downstream substrate mevalonate (MA) or substrates for isoprenylation farnesyl pyrophosphate (FPP) and geranylgeranyl-pyrophosphate (GGPP) were evaluated using add-back experiments. Tumour growth using MTT assay, apoptosis, cell cycle and signalling cascades involved in simvastatin-induced manipulation were analysed. The results revealed that simvastatin dose-dependently inhibited cell growth. Simvastatin significantly induced apoptosis, increased the Bax/Bcl-2 ratio, and cleavage of caspase-3 and PARP protein. Simvastatin impaired cell cycle progression as shown by significantly increased percentages of cells in the G0/G1 phase and lower percentages of cells in the S phase. Gene expression levels of cell cycle-regulating genes (TP53, CDKN1A and CDK1) were markedly altered. These effects were not completely abolished by FPP, but were reversed by MA and GGPP. JNK and c-Jun phosphorylation was enhanced after simvastatin treatment, while those were abolished when either MA or GGPP were added. In conclusion, simvastatin acts primarily by reducing prenylation to induce apoptosis and reduce osteosarcoma cell growth. Particularly enhanced activation of c-Jun seems to play a pivotal role in osteosarcoma cell death.

Die operative Korrektur von Restfehlstellungen verlangt eine grundliche praoperative Untersuchung, klinisch und radiologisch. Mittels standardisierter Verfahren (z. B. Malalignment-Test oder CORA-Methode) wird eine praoperative Planung der Korrektur der Restfehlstellung durchgefuhrt. Die Umsetzung der Korrektur der Fehlstellung ist abhangig von der Compliance des Patienten, der lokalen Infektsituation sowie der lokalen Gefas und Weichteilsituation. Gegebenenfalls ist vor Korrektur einer Fehlstellung eine Infektsanierung notwendig. Als Techniken zur operativen Korrektur von Fehlstellungen kommen der intramedullare Krafttrager, Platten und Schrauben sowie Fixateure in Betracht. Die Vor- und Nachteile dieser Verfahren und der differenzierte Einsatz werden hier diskutiert.

Die konventionelle Plattenosteosynthese befindet sich im Wandel. Hierbei hat das Konzept der Winkelstabilitat einen besonderen Stellenwert. Die monoaxiale winkelstabile Plattenosteosynthese uberzeugte durch rasche Knochenheilung via Kallus, minimale Weichteilirritation und Uberlegenheit im osteoporotischen Knochen. Einige Implantate erlauben die polyaxiale Kopfverriegelung. Die ersten Ergebnisse von biomechanischen und klinischen Vergleichsuntersuchungen der mono- und polyaxialen winkelstabilen Plattensysteme werden prasentiert.

CD4+ T regulatory cells (Tregs) are activated during auto-immune, injury, and inflammatory responses, however, the molecular events that trigger Treg activation are poorly understood. The purpose of this study was to investigate whether Tregs (FoxP3+ CD4+ T cells) and non-Treg CD4+ T cells might display differences in T cell receptor (TCR) dependent signaling responses following in vitro or in vivo stimulation. This study used phospho-flow cytometry as a tool to profile the kinetics and extent of TCR signaling (ZAP-70 and PKC-θ phosphorylation and expression) in Tregs and non-Tregs. We found that in vitro stimulation with anti-CD3ε induces early and transient activation of ZAP-70 and PKC-θ in both Tregs and non-Tregs. However, the response in Tregs was more rapid and higher in magnitude than responses seen in non-Tregs. In contrast, bacterial superantigen or antigen-specific TCR stimulation did not significantly activate these signaling pathways in Tregs or non-Tregs. Additional experiments tested the kinetics of in vivo TCR signaling in Tregs and non-Tregs in mice challenged with bacterial superantigen. The results of these experiments showed that superantigen rapidly activated ZAP-70 and PKC-θ in lymph node Tregs, but not in non-Tregs. In summary, we demonstrate the versatility of using phospho-flow cytometry to measure cell signaling in CD4+ T cells. The results of these in vitro and in vivo studies demonstrate that Tregs and non-Treg CD4+ T cells show marked differences in their reactivity to TCR-dependent stimulation and contribute new insights into basic mechanisms that lead to Treg activation.

The inflammasome is activated in response to pathogen or endogenous danger signals and acts as an initiator and mediator of inflammatory reactions. In this study, we wished to identify whether the inflammasome is activated in vivo by injury. And if so, we wanted to characterize the kinetics, the immune cell distribution, and the functional impact of inflammasome activation on the injury response. Because caspase-1 activation is the final product of the inflammasome pathway, we used cleaved caspase-1 p10 and p20 as a measure for inflammasome activation in cells. We first developed a procedure to stain for caspase-1 p10 and p20 by flow cytometry (FACS) in lipopolysaccharide + adenosine triphosphate-stimulated spleen cells. This method for measuring caspase-1 activation was validated using FLICA (fluorochrome inhibitor of caspase), a fluorescently tagged specific binding reagent for activated caspase-1. Once validated by in vitro studies, we measured caspase-1 activation by FACS in immune cell subsets prepared from the lymph nodes and spleens of sham- or burn-injured mice at different time points. Lastly, the functional significance of inflammasome activation following burn injury was tested in mice treated with the specific caspase-1 inhibitor, AC-YVAD-CMK. The results of in vitro studies indicated that adenosine triphosphate and lipopolysaccharide stimulation induced significant caspase-1 activation in dendritic cells, macrophages, and natural killer (NK) cells. This approach also revealed caspase-1 activation in CD4 and CD8 T cells as well as B cells. We then measured caspase-1 activation in cells prepared from the lymph nodes and spleens of sham- or burn-injured mice. Significant caspase-1 activation was detected in macrophages and dendritic cells by 4 h after injury and peaked by day 1 after injury. FLICA staining confirmed that caspase-1 activation occurred in these cells at 1 day after injury. We also found significant injury-induced caspase-1 activation in NK cells, CD4 T cells, and B cells, but CD8 T cells did not demonstrate caspase-1 activation. Surprisingly, we found that blocking caspase-1 activation with AC-YVAD-CMK in vivo caused significantly higher mortality in burn-injured mice (P < 0.01). Taken together, these findings document that injury induces inflammasome activation in many immune cell subsets, but primarily in macrophages, and that inflammasome activation plays a protective role in the host response to severe injury.

Background. Mechanisms mediating CD4 + T-cell recruitment during alloantigen-independent hepatic ischemia-reperfusion (I/R) remain not fully understood. We hypothesized that Kupffer cells activate CD4 + T-cells in the postischemic liver, by the release of free oxygen radicals and cytokines. Methods. Recruitment of freshly isolated and fluorescence-labeled CD4 + T-cell was analyzed after hepatic I/R (90/30-120 min) using intravital microscopy in sham-operated mice, in mice after hepatic I/R and in postischemic groups after Kupffer cell depletion, after treatment with antioxidant glutathione, in interleukin (IL)-6-/- mice; and in wild-type mice after infusion of tumor necrosis factor (TNF) receptor-1-/-CD4+ T-cells. Using flow cytometry and immunohistochemistry, we assessed whether Kupffer cell-derived mediators activate CD4 + T-cells and sinusoidal endothelial cells. The clearance kinetics of fluorescence-labeled latex beads was determined as a marker of Kupffer cell activity in vivo. Results. I/R-induced accumulation of CD4 + T-cells in hepatic sinusoids was significantly attenuated on Kupffer cell depletion, after scavenging of free radicals and after interruption of the IL-6- and TNF-alpha-dependent pathways. These mediators directly activate CD4 + T-cells and up-regulated the expression of T cell-relevant adhesion molecules on sinusoidal endothelial cells. Postischemic activity of Kupffer cells was significantly impaired in wild-type mice, and was even more depressed in CD4-/- animals. Conclusion. Kupffer cells trigger recruitment of CD4 + T-cells in the postischemic liver by the release of reactive oxygen species, IL-6, and TNF-a. These mediators are capable of activating CD4 + T-cells and sinusoidal endothelial cells. CD4 + T-cells, in turn, influence the activation of Kupffer cells.

Background The effects of private transportation (PT) to definitive trauma care in comparison to transportation using Emergency Medical Services (EMS) have so far been addressed by a few studies, with some of them finding a beneficial effect on survival. The aim of the current study was to investigate epidemiology, pre- and in-hospital times as well as outcomes in patients after PT as compared to EMS recorded in the TraumaRegister DGU®. Methods All patients in the database of the TraumaRegister DGU® (TR-DGU) from participating European trauma centers treated in 2009 to 2013 with available data on the mode of transportation, ISS ≥ 4 and ICU treatment were included in the study. Epidemiological data, pre- and in-hospital times were analysed. Outcomes were analysed after adjustment for RISC-II scores. Results 76,512 patients were included in the study, of which 1,085 (1.4 %) were private transports. Distribution of ages and trauma mechanisms showed a markedly different pattern following PT, with more children

CD4+ T regulatory cells (Tregs) play a pivotal role in the anti-inflammatory immune response following trauma. The mechanisms of CD4+ Treg activation are mostly unknown. Here, we hypothesize that platelets regulate CD4+ Treg activation following trauma. In a murine burn injury model (male C57Bl/6N mice), depletion of platelets or CD4+ Tregs was conducted. Draining lymph nodes, blood and spleen were harvested 2 h and 7 days after trauma. CD4+ Treg activation was measured using phospho- and conventional flow cytometry. Platelet activation was analyzed using thromboelastometry and flow cytometry. Trauma differentially activates CD4+ T cells, early after trauma only CD4+ Tregs are activated. Following burn injury, platelets augment the activation of CD4+ Tregs. This effect could only be seen early after trauma. While CD4+ Tregs influence hemostasis early following trauma, platelet activation markers were unchanged. Beyond their role in hemostasis, platelets are able to modulate the immunologic host response to trauma-induced injury by augmenting the activation of CD4+ Tregs. CD4+ Treg activation following trauma is considered protective. In addition, CD4+ Tregs are capable of modulating the hemostatic function of platelets. For the first time, we could show reciprocal activation of platelets and CD4+ Tregs as part of the protective immune response following trauma.

The mechanisms by which T cells contribute to the hepatic inflammation during antigen-independent ischemia/reperfusion (I/R) are not fully understood. We analyzed the recruitment of T cells in the postischemic hepatic microcirculation in vivo and tested the hypothesis that T cells interact with platelets and activate sinusoidal endothelial cells, resulting in microvascular dysfunction followed by tissue injury. Using intravital videofluorescence microscopy, we show in mice that warm hepatic I/R (90/30-140 min) induces accumulation and transendothelial migration of CD4+, but not CD8+ T cells in sinusoids during early reperfusion. Simultaneous visualization of fluorescence-labeled CD4+ T cells and platelets showed that approximately 30% of all accumulated CD4+ T cells were colocalized with platelets, suggesting an interaction between both cell types. Although interactions of CD4+/CD40L-/- T cells with CD40L-/- platelets in wild-type mice were slightly reduced, they were almost absent if CD4+ T cells and platelets were from CD62P-/- mice. CD4 deficiency as well as CD40-CD40L and CD28-B7 disruption attenuated postischemic platelet adherence in the same manner as platelet inactivation with a glycoprotein IIb/IIIa antagonist and reduced neutrophil transmigration, sinusoidal perfusion failure, and transaminase activities. Treatment with an MHC class II antibody, however, did not affect I/R injury. In conclusion, we describe the type, kinetic, and microvascular localization of T cell recruitment in the postischemic liver. CD4+ T cells interact with platelets in postischemic sinusoids, and this interaction is mediated by platelet CD62P. CD4+ T cells activate endothelium, increase I/R-induced platelet adherence and neutrophil migration via CD40-CD40L and CD28-B7-dependent pathways, and aggravate microvascular/hepatocellular injury.

Treatment of patients with traumatic macroamputations is challenging. The aim of this study is to analyze the significance of this type of injury in TraumaRegister DGU® (TR-DGU) and to depict the rate of formal surgical ablation of the traumatically induced amputation, epidemiologic data, as well as outcome in severely injured patients with amputations. We acquired data from the TR-DGU of the German Trauma Society (DGU). The inclusion criteria for our study were Injury Severity Score (ISS) greater than 9, macroamputation, and available data about the Abbreviated Injury Scale (AIS) code. A total of 48,908 of 67,425 patients had an ISS greater than 9 and available data about the AIS code. In total, 926 (1.9%) of 48,908 patients had an immediate traumatic macroamputation on-scene. Thereof, 298 patients (32.2%) had a macroamputation of the arms, 605 patients (65.3%) had an amputation of the legs, and 23 patients (2.5%) had both. Among them, 457 patients (49.4%) with a macroamputation had monotrauma. In total, 126 patients (13.6%) underwent replantation and 800 patients (86.4%) underwent formal surgical ablation of the traumatically induced amputation. Seventy-six (23.7%) of 321 patients with upper-extremity amputations and 53 (8.4%) of 628 patients with lower-extremity amputations underwent replantation. Mortality in patients with replantation was lower (5.6% vs. 19.6%, P < 0.001). Standardized mortality rate was lower for patients with replantation (0.71, 95% confidence interval, 0.20-1.21 vs. 0.94, 95% confidence interval, 0.80-1.10; P = 0.26). Glasgow Outcome Scale (GOS) was significantly better for patients with replantation (34.0%; GOS score 5) as compared with patients without replantation (20.7%; GOS score 5; P < 0.001). In borderline patients (defined according to the orthopedic damage control principles), 91.5% received formal surgical ablation of the traumatically induced amputation and 8.5% underwent replantation. The rate of formal surgical ablation of the traumatically induced amputation is higher when principles of damage control surgery are applied. The replantation rate in the upper extremity is higher than in the lower extremity. The less ISS and base excess and the higher blood pressure, hemoglobin value, and thromboplastin time are, the safer the decision for replantation seems to be.