[Current diagnostics and treatment of ankle sprains in German]. / Aktuelle Diagnostik und Behandlung der Sprunggelenks-Distorsion in Deutschland.

BACKGROUND: Ankle sprains are one of the most frequent injuries of the musculoskeletal system. The injury pattern determines the treatment and are crucial for the outcome. Nonoperative treatment is commonly recommended for isolated injuries of the lateral ligaments but no standard strategy exists in combined ankle ligament injuries. The goal of this national survey was to achieve an overview about the current diagnostic strategies and common treatment concepts in Germany. MATERIAL AND METHODS: All members of the German Society for Orthopaedics and Trauma Surgery (DGOU) were invited to participate in an anonymous survey about the diagnostic and therapeutic approach in cases of ankle sprains. The online survey consisted of 20 questions. Besides questions about the speciality and scope of activities the participants were ask to depict their diagnostic and therapeutic strategy. RESULTS: A total of 806 participants completed the survey. Most of them were orthopedic trauma surgeons and worked in a hospital. During the first presentation the anterior drawer test (89.5%) and the inversion/eversion test (81.6%) were most commonly used, 88.1% always make an X­ray examination and 26.5% an ultrasonography examination. Isolated injuries of the anterior fibulotalar ligament (LFTA) were treated nonoperatively by 99.7% of the participants, 78.8% recommend full weight bearing in an orthesis, 78.8% treat the complete rupture of the lateral ligaments without operation whereas 30.1% stated that they would treat a combined lateral ligaments rupture with an injury of the syndesmosis nonoperatively. DISCUSSION: Due to the heterogeneity of injury patterns after ankle sprain no consistent recommendations for diagnostics and treatment exist. The Ottawa ankle rules and ultrasonography were not often utilized despite of the good evidence. The isolated rupture of the LFTA is diagnosed and treated according to the national guidelines by most of the participants. In cases of combined injuries of the lateral and medial ankle ligaments the majority choose a nonoperative treatment strategy which is justified by the guidelines with a low level of evidence. Combined injuries of the syndesmosis and the lateral ankle ligaments were treated operatively, which also correlates with the recommendations in the literature. The standard care of ankle sprain in Germany is in accordance with the recommendations from the current literature.

Evaluation of in vitro biocompatibility of human pulp stem cells with allogeneic, alloplastic, and xenogeneic grafts under the influence of extracellular vesicles.

Therapies using dental pulp stem cells (DPSCs) or stem cell-derived extracellular vesicles (EVs) have shown promising applications for bone tissue engineering. This in vitro experiment evaluated the joint osteogenic capability of DPSCs and EVs on alloplastic (maxresorp), allogeneic (maxgraft), and xenogeneic (cerabone) bone grafts. We hypothesize that osteogenic differentiation and the proliferation of human DPSCs vary between bone grafts and are favorable under the influence of EVs. DPSCs were obtained from human wisdom teeth, and EVs derived from DPSCs were isolated from cell culture medium. DPSCs were seeded on alloplastic, allogeneic, and xenogeneic bone graft substitutes for control, and the same scaffolds were administered with EVs in further groups. The cellular uptake of EVs into DPSC cells was assessed by confocal laser scanning microscopy. Cell vitality staining and calcein acetoxymethyl ester staining were used to evaluate cell attachment and proliferation. Cell morphology was determined using scanning electron microscopy, and osteogenic differentiation was explored by alkaline phosphatase and Alizarin red staining. Within the limitations of an in vitro study without pathologies, the results suggest that especially the use of xenogeneic bone graft substitutes with DPSCS and EVs may represent a promising treatment approach for alveolar bone defects.

Effect of Injury Patterns on the Development of Complications and Trauma-Induced Mortality in Patients Suffering Multiple Trauma.

Patients that suffer from severe multiple trauma are highly vulnerable to the development of complications that influence their outcomes. Therefore, this study aimed to evaluate the risk factors that can facilitate an early recognition of adult patients at risk. The inclusion criteria were as follows: admission to a level 1 trauma center, injury severity score (ISS) ≥ 16 (severe injury was defined by an abbreviated injury score (AIS) ≥ 3) and ≥18 years of age. Injury- and patient-associated factors were correlated with the development of four complication clusters (surgery-related, infection, thromboembolic events and organ failure) and three mortality time points (immediate (6 h after admission), early (>6 h-72 h) and late (>72 h) mortality). Statistical analysis was performed using a Chi-square, Mann-Whitney U test, Cox hazard regression analysis and binominal logistic regression analysis. In total, 383 patients with a median ISS of 24 (interquartile range (IQR) 17-27) were included. The overall mortality rate (27.4%) peaked in the early mortality group. Lactate on admission significantly correlated with immediate and early mortality. Late mortality was significantly influenced by severe head injuries in patients with a moderate ISS (ISS 16-24). In patients with a high ISS (≥25), late mortality was influenced by a higher ISS, older age and higher rates of organ failure. Complications were observed in 47.5% of all patients, with infections being seen most often. The development of complications was significantly influenced by severe extremity injuries, the duration of mechanical ventilation and length of ICU stay. Infection remains the predominant posttraumatic complication. While immediate and early mortality is mainly influenced by the severity of the initial trauma, the rates of severe head injuries influence late mortality in moderate trauma severity, while organ failure remains a relevant factor in patients with a high injury severity.

Adherence to the transfer recommendations of the German Trauma Society in severely injured children: a retrospective study from the TraumaRegister DGU.

Particularly for pediatric trauma patients, it is of utmost importance that the right patient be treated in the right place at the right time. While unnecessary interhospital transfers must be avoided, the decision against transfer should not lead to higher complication rates in trauma centers without added pediatric qualifications. We therefore identified independent predictive factors for an early transfer of severely injured patients and compared these factors with the current transfer recommendations of the German Trauma Society. Additionally, the quality of the self-assessment based on the mortality of children who were not transferred was evaluated. A national dataset from the TraumaRegister DGU® was used to retrospectively identify factors for an early interhospital transfer (< 48 h) to a superordinate trauma center. Severely injured pediatric patients (age < 16 years) admitted between 2010 and 2019 were included in this analysis. Adjusted odds ratios (OR) with 95% confidence intervals (CI) for early transfer were calculated from a multivariable model. Prognostic factors for hospital mortality in non-transferred patients were also analyzed. In total, 6069 severely injured children were included. Of these, 65.2% were admitted to a Level I trauma center, whereas 27.7% and 7.1% were admitted to Level II and III centers, respectively. After the initial evaluation in the emergency department, 25.5% and 50.1% of children primarily admitted to a Level II or III trauma center, respectively, were transferred early. Statistically significant predictors of an early transfer were: Serious traumatic brain injury (OR 1.76, 95% CI 1.28-2.43), Injury severity score (ISS) ≥ 16 points (ISS 16-24: OR 2.06, 95% CI 1.59-2.66; ISS 25-33: OR 3.0, 95% CI 2.08-4.31; ISS 34-75: OR 5.42, 95% CI 3.0-9.81, reference category: ISS 9-15), age < 10 years (age 0-1: OR 1.91, 95% CI 1.34-2.71; age 2-5: 2.04, 95% CI 1.50-2.78; age 6-9: 1.62, 95% CI 1.23-2.14; reference category: age 10-15). The most important independent factor for mortality in non-transferred patients was age < 10 years (age 0-1: 5.35, 95% CI 3.25-8.81; age 2-5: 2.46, 95% CI 1.50-4.04; age 6-9: OR 1.7, 95% CI 1.05-2.75; reference category: age 10-15). Knowing the independent predictors for an early transfer, such as a young patient's age, a high injury severity, serious traumatic brain injury (TBI), may improve the choice of the appropriate trauma center. This may guide the rapid decision for an early interhospital transfer. There is still a lack of outcome data on children with early interhospital transfers in Germany, who are the most vulnerable group.

Predicting tracheostomy in multiple injured patients with severe thoracic injury (AIS ≥ 3) with the new T3P-Score: a multivariable regression prediction analysis.

Multiple trauma patients with severe chest trauma are at increased risk for tracheostomy. While the risk factors associated with the need for tracheostomy are well established in the general critical care population, they have not yet been validated in a cohort of patients suffering severe thoracic trauma. This retrospective cohort study analysed data on patients aged 18 years or older who were admitted to one of the six participating academic level I trauma centres with multiple injuries, including severe thoracic trauma (AISThorax ≥ 3) between 2010 and 2014. A multivariable binary regression was used to identify predictor variables for tracheostomy and to develop the Tracheostomy in Thoracic Trauma Prediction Score (T3P-Score). The study included 1019 adult thoracic trauma patients, of whom 165 underwent tracheostomy during their intensive care unit (ICU) stay. Prehospital endotracheal intubation (adjusted OR [AOR]: 2.494, 95% CI [1.412; 4.405]), diagnosis of pneumonia during the ICU stay (AOR: 4.374, 95% CI [2.503; 7.642]), duration of mechanical ventilation (AOR: 1.008/hours of intubation, 95% CI [1.006; 1.009]), and an AISHead ≥ 3 (AOR 1.840, 95% CI [1.039; 3.261]) were independent risk factors for tracheostomy. Patients with sepsis had a lower risk of tracheostomy than patients without sepsis (AOR 0.486, 95% CI [0.253; 0.935]). The T3P-Score had high predictive validity for tracheostomy (ROCAUC = 0.938, 95% CI [0.920, 0.956]; Nagelkerke's R2 was 0.601). The T3P-Score's specificity was 0.68, and the sensitivity was 0.96. The severity of thoracic trauma did not predict the need for tracheostomy. Follow-up studies should validate the T3P-Score in external data sets and study the reasons for the reluctant use of tracheostomy in patients with severe thoracic trauma and subsequent sepsis.Trial registration: The study was applied for and registered a priori with the respective ethics committees.

In vitro comparison of the osteogenic capability of human pulp stem cells on alloplastic, allogeneic, and xenogeneic bone scaffolds.

BACKGROUND: A rigorous search for alternatives to autogenous bone grafts to avoid invasiveness at the donor site in the treatment of maxillomandibular bone defects. Researchers have used alloplastic, allogeneic, and xenogeneic bone graft substitutes in clinical studies with varying degrees of success, although their in vitro effects on stem cells remain unclear. Dental pulp stem cells (DPSCs) can potentially enhance the bone regeneration of bone graft substitutes. The present in vitro study investigates the osteogenic capability of DPSCs on alloplastic (biphasic calcium phosphate [BCP]), allogeneic (freeze-dried bone allografts [FDBAs]), and xenogeneic (deproteinized bovine bone mineral [DBBM]) bone grafts. METHODS: Human DPSCs were seeded on 0.5 mg/ml, 1 mg/ml, and 2 mg/ml of BCP, FDBA, and DBBM to evaluate the optimal cell growth and cytotoxicity. Scaffolds and cell morphologies were analyzed by scanning electron microscopy (SEM). Calcein AM and cytoskeleton staining were performed to determine cell attachment and proliferation. Alkaline phosphatase (ALP) and osteogenesis-related genes expressions was used to investigate initial osteogenic differentiation. RESULTS: Cytotoxicity assays showed that most viable DPSCs were present at a scaffold concentration of 0.5 mg/ml. The DPSCs on the DBBM scaffold demonstrated a significantly higher proliferation rate of 214.25 ± 16.17 (p < 0.001) cells, enhancing ALP activity level and upregulating of osteogenesis-related genes compared with other two scaffolds. CONCLUSION: DBBP scaffold led to extremely high cell viability, but also promoted proliferation, attachment, and enhanced the osteogenic differentiation capacity of DPSCs, which hold great potential for bone regeneration treatment; however, further studies are necessary.

Local YB-1, Epo, and EpoR concentrations in fractured bones: results from a porcine model of multiple trauma.

Little is known about the impact of multiple trauma (MT)-related systemic hypoxia on osseous protein concentration of the hypoxia transcriptome. To shed light on this issue, we investigated erythropoietin (Epo), erythropoietin receptor (EpoR), and Y-box binding protein 1 (YB-1) concentrations in the fracture zone in a porcine MT + traumatic hemorrhage (TH) model. Sixteen male domestic pigs were randomized into two groups: an MT + TH group and a sham group. A tibia fracture, lung contusion, and TH were induced in the MT + TH group. The total observation period was 72 h. YB-1 concentrations in bone marrow (BM) were significantly lower in the fracture zone of the MT + TH animals than in the sham animals. Significant downregulation of BM-localized EpoR concentration in both unfractured and fractured bones was observed in the MT + TH animals relative to the sham animals. In BM, Epo concentrations were higher in the fracture zone of the MT + TH animals compared with that in the sham animals. Significantly higher Epo concentrations were detected in the BM of fractured bone compared to that in cortical bone. Our results provide the first evidence that MT + TH alters hypoxia-related protein concentrations. The impacts of both the fracture and concomitant injuries on protein concentrations need to be studied in more detail to shed light on the hypoxia transcriptome in fractured and healthy bones after MT + TH.

Complications associated using the reamer-irrigator -aspirator (RIA) system: a systematic review and meta-analysis.

INTRODUCTION: Complications associated with the application of the Reamer-irrigator-Aspirator (RIA) system are described in the literature. However, to date a systematic review and meta-analysis to assess prevalence of complications associated with the use of the RIA system have not been conducted. MATERIALS AND METHODS: The review is registered with PROSPERO (CRD42021269982). MEDLINE, the Web of Science Core Collection, and Embase were searched from the inception to 10 August 2021. The primary objective was to assess complications and blood loss associated with the use of the RIA system. RESULTS: Forty-seven studies involving 1834 procedures performed with the RIA system were finally included. A total of 105 complications were reported, with a pooled estimated overall prevalence of 1.7% with a 95% confidence interval (CI) of 0.40 to 3.60, with cortex perforation being the largest reported complication with a total of 34 incidences. A significant subgroup difference was observed (p = 0.02). In subgroup 1 (bone graft harvesting), complication prevalence was 1.4% (95% CI 0.2-3.4); in subgroup 2 (clearance intramedullary canal) it was 0.7% (95% CI 0.00-6.30) and in subgroup 3 (reaming with RIA system prior to nail fixation) 11.9% (95% CI 1.80-26.40). No statistically significant difference for tibia and femur as RIA system application site was observed (CI 0.69-4.19). In studies reporting blood loss, a mean volume of 803.29 ml, a mean drop of hemoglobin of 3.74 g/dl and a necessity of blood transfusion in 9.72% of the patients were observed. CONCLUSIONS: The systematic review and meta-analysis demonstrate a low overall prevalence rate of complications associated with the RIA system. However, especially the risk of cortical perforation and the frequently reported relevant intraoperative blood loss are complications that should be anticipated in perioperative management and ultimately considered when using the RIA system.

I-FABP as a Potential Marker for Intestinal Barrier Loss in Porcine Polytrauma.

Polytrauma and concomitant hemorrhagic shock can lead to intestinal damage and subsequent multiple organ dysfunction syndrome. The intestinal fatty acid-binding protein (I-FABP) is expressed in the intestine and appears quickly in the circulation after intestinal epithelial cell damage. This porcine animal study investigates the I-FABP dynamics in plasma and urine after polytrauma. Furthermore, it evaluates to what extent I-FABP can also act as a marker of intestinal damage in a porcine polytrauma model. Eight pigs (Sus scrofa) were subjected to polytrauma which consisted of lung contusion, tibial fracture, liver laceration, and hemorrhagic shock followed by blood and fluid resuscitation and fracture fixation with an external fixator. Eight sham animals were identically instrumented but not injured. Afterwards, intensive care treatment including mechanical ventilation for 72 h followed. I-FABP levels in blood and urine were determined by ELISA. In addition, immunohistological staining for I-FABP, active caspase-3 and myeloperoxidase were performed after 72 h. Plasma and urine I-FABP levels were significantly increased shortly after trauma. I-FABP expression in intestinal tissue showed significantly lower expression in polytraumatized animals vs. sham. Caspase-3 and myeloperoxidase expression in the immunohistological examination were significantly higher in the jejunum and ileum of polytraumatized animals compared to sham animals. This study confirms a loss of intestinal barrier after polytrauma which is indicated by increased I-FABP levels in plasma and urine as well as decreased I-FABP levels in immunohistological staining of the intestine.

Polytrauma scoring revisited: prognostic validity and usability in daily clinical practice.

PURPOSE: Scores are widely used for the assessment of injury severity and therapy guidance in severely injured patients. They differ vastly regarding complexity, applicability, and prognostic accuracy. The objective of this study was to compare well-established with more recently developed trauma scores as well as intensive care unit (ICU) scores. METHODS: Retrospective analysis of severely injured patients treated at a level I trauma centre from 2010 to 2015. INCLUSION CRITERIA: Age ≥ 18 years, Injury Severity Score ≥ 16 and ICU treatment. Primary endpoint was in-hospital mortality. Several scores (ISS, APACHE II, RTS, Marshall Score, SOFA, NISS, RISC II, EAC and PTGS) were assessed to determine their predictive quality for mortality. Statistical analysis included correlation analysis and receiver operating characteristic (ROC). RESULTS: 444 patients were included. 71.8% were males, mean age was 51 ± 20.26 years. 97.4% sustained a blunt trauma. The area under the ROC curve (AUROC) revealed RISC II (0.92) as strongest predictor regarding mortality, followed by APACHE II (0.81), Marshall score (0.69), SOFA (0.70), RTS (0.66), NISS (0.62), PTGS (0.61) and EAC (0.60). ISS did not reach statistical significance. CONCLUSIONS: RISC II provided the strongest predictive capability for mortality. In comparison, more simple scores focusing on injury pattern (ISS, NISS), physiological abnormalities (RTS, EAC), or a combination of both (PTGS) only provided inferior mortality prediction. Established ICU scores like APACHE II, SOFA and Marshall score were proven to be helpful tools in severely injured trauma patients.

Surgical Treatment of Bone Sarcoma.

Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic approach. While radiotherapy plays a role especially in Ewing sarcoma and chemotherapy in Ewing sarcoma and osteosarcoma, surgery remains the main pillar of treatment in all three entities. After complete tumor resection, the created bone defects need to be reconstructed. Possible strategies are implantation of allografts or autografts including vascularized bone grafts (e.g., of the fibula). Around the knee joint, rotationplasty can be performed or, as an alternative, the implantation of (expandable) megaprostheses can be performed. Challenges still associated with the implantation of foreign materials are aseptic loosening and infection. Future improvements may come with advances in 3D printing of individualized resection blades/implants, thus also securing safe tumor resection margins while at the same time shortening the required surgical time. Faster osseointegration and lower infection rates may possibly be achieved through more elaborate implant surface structures.

Club cell protein (CC)16 as potential lung injury marker in a porcine 72 h polytrauma model.

BACKGROUND: Polytrauma and respiratory tract damage after thoracic trauma cause about 25% of mortality among severely injured patients. Thoracic trauma can lead to the development of severe lung complications such as acute respiratory distress syndrome, and is, therefore, of great interest for monitoring in intensive care units (ICU). In recent years, club cell protein (CC)16 with its antioxidant properties has proven to be a potential outcome-related marker. In this study, we evaluated whether CC16 constitutes as a marker of lung damage in a porcine polytrauma model. METHODS: In a 72 h ICU polytrauma pig model (thoracic trauma, tibial fracture, hemorrhagic shock, liver laceration), blood plasma samples (0, 3, 9, 24, 48, 72 h), BAL samples (72 h) and lung tissue (72 h) were collected. The trauma group (PT) was compared to a sham group. CC16 as a possible biomarker for lung injury in this model, and IL-8 concentrations as known indicator for ongoing inflammation during trauma were determined by ELISA. Histological analysis of ZO-1 and determination of total protein content were used to show barrier disruption and edema formation in lung tissue from the trauma group. RESULTS: Systemic CC16 levels were significantly increased early after polytrauma compared vs. sham. After 72 h, CC16 concentration was significantly increased in lung tissue as well as in BAL in PT vs. sham. Similarly, IL-8 and total protein content in BAL were significantly increased in PT vs. sham. Evaluation of ZO-1 staining showed significantly lower signal intensity for polytrauma. CONCLUSION: The data confirm for the first time in a larger animal polytrauma model that lung damage was indicated by systemic and/or local CC16 response. Thus, early plasma and late BAL CC16 levels might be suitable to be used as markers of lung injury in this polytrauma model.

Sulforaphane Exerts Beneficial Immunomodulatory Effects on Liver Tissue via a Nrf2 Pathway-Related Mechanism in a Murine Model of Hemorrhagic Shock and Resuscitation.

Our research explores the immunomodulatory effects of sulforaphane (SFN), a well-known nuclear factor erythroid 2-related factor 2 (Nrf2) pathway agonist, on the sterile inflammation of and ischemia-reperfusion injuries to the liver after hemorrhagic shock (HS) followed by resuscitation (R). Male C57/BL6 wild-type and transgenic ARE-luc mice were exposed to mean arterial pressure-controlled HS. Fluid resuscitation was performed after 90 min of HS, and SFN was administrated intraperitoneally after that. The animals were sacrificed at 6 h, 24 h, and 72 h after resuscitation, and their livers were extracted to perform H&E staining and myeloperoxidase (MPO) activity analysis. The Kupffer cells were isolated for cytokines profile measurements and Nrf2 immunofluorescence staining. Further, the ARE-luc mice were used to assess hepatic Nrf2 activity in vivo. We identified that SFN-activated Kupffer cells' Nrf2 pathway and modulated its cytokines expression, including TNF-α, MCP-1, KC/CXCL1, IL-6, and IL-10. Furthermore, SFN mitigated liver ischemia-reperfusion injury, as evidenced by the downregulation of the Suzuki score and the enhanced hepatic Nrf2 activity. The in vivo SFN treatment decreased neutrophils infiltration, as shown by the decreased MPO levels. Our study shows that SFN can decrease HS/R-induced hepatic ischemia-reperfusion injury and modulate the activity of Kupffer cells via an Nrf2-dependent pathway.

Predictors for wound healing complications and prolonged hospital stay in patients with isolated calcaneal fractures.

PURPOSE: Surgically treated calcaneal fractures have a high risk of postoperative wound healing complications and a prolonged length of hospital stay (LOS). The aim of this study was to identify predictor variables of impaired wound healing (IWH) and LOS in surgically treated patients with isolated calcaneal fractures. METHODS: This retrospective cohort study analyzed data on patients aged 18 years or older who were admitted to a level I trauma center with isolated calcaneal fractures between 2008 and 2018. Multivariable regression models were used to identify predictor variables. RESULTS: In total, 89 patients (age: 45.4 years; SD: 15.1) were included. In 68 of these patients, low-profile locking plate osteosynthesis was performed, and a minimally invasive approach (MIA) (percutaneous single screws/K-wire or low-profile locking plating via a sinus tarsi approach) was applied in 21 patients. Multivariable regression analysis revealed that a higher preoperative Böhler's angle (ß = - 0.16 days/degree, 95% CI [- 0.25, - 0.08], p = 0.004) and MIA (ß = - 5.04 days, 95% CI [- 8.52, - 1.56], p = 0.002) reduced the LOS. A longer time-to-surgery (ß = 1.04 days/days, 95% CI [0.66, 1.42] p = 0.001) and IWH increased the LOS (ß = 7.80 days, 95% CI [4.48, 11.12], p = 0.008). In a subsequent multivariable regression analysis, two variables, open fractures (OR: 14.6, 95% CI [1.19, 180.2], p = 0.030) and overweight (BMI > 24) (OR: 3.65, 95% CI [1.11, 12.00], p = 0.019), increased the risk of IWH. CONCLUSION: Advanced treatment algorithms for open fractures are needed to reduce the risk of IWH.

Sulforaphane-Dependent Up-Regulation of NRF2 Activity Alleviates Both Systemic Inflammatory Response and Lung Injury After Hemorrhagic Shock/Resuscitation in Mice.

ABSTRACT: Hemorrhagic shock/resuscitation (HS/R) is closely associated with overwhelming oxidative stress and systemic inflammation. As an effective activator of the nuclear factor-erythroid factor 2 related factor 2 (Nrf2) pathway, sulforaphane (SFN) exerts antioxidant and anti-inflammatory effects. We explored SFN's effects on alveolar macrophages (AMs), systemic inflammation, and pulmonary damage in an isolated murine HS/R model. Male C57/BL6 wild type and transgenic antioxidant response element (ARE)-luciferase (luc) mice (both n = 6 per group) were exposed to either pressure-controlled HS/R (mean arterial pressure 35-45 mm Hg for 90 min) or sham procedure (surgery without HS/R) or were sacrificed without intervention (control group). Fluid resuscitation was performed via the reinfusion of withdrawn blood and 0.9% saline. Sulforaphane or 0.9% saline (vehicle) was administrated intraperitoneally. Mice were sacrificed 6, 24, or 72 h after resuscitation. Bioluminescence imaging of ARE-luc mice was conducted to measure pulmonary Nrf2 activity. Plasma was collected to determine systemic cytokine levels. Alveolar macrophages were isolated before measuring cytokines in the supernatant and performing immunofluorescence staining, as well as Western blot for intracellular Nrf2. Histological damage was assessed via the acute lung injury score and wet/dry ratio.Hemorrhagic shock/resuscitation was associated with pulmonary Nrf2 activation. Sulforaphane enhanced pulmonary Nrf2 activity and the Nrf2 activation of AM, while it decreased lung damage. Sulforaphane exerted down-regulatory effects on AM-generated and systemic pro-inflammatory mediators, while it did not have such effects on IL-10.In conclusion, SFN beneficially enhances pulmonary Nrf2 activity and promotes Nrf2 accumulation in AMs' nuclei. This may exert not only local protective effects but also systemic effects via the down-regulation of pro-inflammatory cytokines. The administration of Nrf2 activator post-HS/R may represent an innovative treatment strategy.

mTICCS and its inter-rater reliability to predict the need for massive transfusion in severely injured patients.

PURPOSE: The modified Trauma-Induced Coagulopathy Clinical Score (mTICCS) presents a new scoring system for the early detection of the need for a massive transfusion (MT). This easily applicable score was validated in a large trauma cohort and proven comparable to more established complex scoring systems. However, the inter-rater reliability of the mTICCS has not yet been investigated. METHODS: Therefore, a dataset of 15 randomly selected and severely injured patients (ISS ≥ 16) derived from the database of a level I trauma centre (2010-2015) was used. Moreover, 15 severely injured subjects that received MT were chosen from the same databank. A web-based survey was sent to medical professionals working in the field of trauma care asking them to evaluate each patient using the mTICCS. RESULTS: In total, 16 raters (9 residents and 7 specialists) completed the survey. Ratings from 15 medical professionals could be evaluated and led to an ICC of 0.7587 (95% Bootstrap confidence interval (BCI) 0.7149-0.8283). A comparison of working experience specific ICC (n = 7 specialists, ICC: 0.7558, BCI: 0.7076-0.8270; n = 8 residents, ICC: 0.7634, BCI: 0.7183-0.8335) showed no significant difference between the two groups (p = 0.67). CONCLUSION: In summary, reliability values need to be considered when making clinical decisions based on scoring systems. Due to its easy applicability and its almost perfect inter-rater reliability, even with non-specialists, the mTICCS might therefore be a useful tool to predict the early need for MT in multiple trauma.

Strategies for the treatment of femoral fractures in severely injured patients: trends in over two decades from the TraumaRegister DGU®.

PURPOSE: Treatment strategies for femoral fracture stabilisation are well known to have a significant impact on the patient's outcome. Therefore, the optimal choices for both the type of initial fracture stabilisation (external fixation/EF, early total care/ETC, conservative treatment/TC) and the best time point for conversion from temporary to definitive fixation are challenging factors. PATIENTS: Patients aged ≥ 16 years with moderate and severe trauma documented in the TraumaRegister DGU® between 2002 and 2018 were retrospectively analysed. Demographics, ISS, surgical treatment strategy (ETC vs. EF vs. TC), time for conversion to definitive care, complication (MOF, sepsis) and survival rates were analysed. RESULTS: In total, 13,091 trauma patients were included. EF patients more often sustained high-energy trauma (car: 43.1 vs. 29.5%, p < 0.001), were younger (40.6 vs. 48.1 years, p < 0.001), were more severely injured (ISS 25.4 vs. 19.1 pts., p < 0.001), and had higher sepsis (11.8 vs. 5.4%, p < 0.001) and MOF rates (33.1 vs. 16.0%, p < 0.001) compared to ETC patients. A shift from ETC to EF was observed. The time until conversion decreased for femoral fractures from 9 to 8 days within the observation period. Sepsis incidences decreased in EF (20.3 to 12.3%, p < 0.001) and ETC (9.1-4.8%, p < 0.001) patients. CONCLUSIONS: Our results show the changes in the surgical treatment of severely injured patients with femur fractures over a period of almost two decades caused by the introduction of modern surgical strategies (e.g., Safe Definitive Surgery). It remains unclear which subgroups of trauma patients benefit most from these strategies.

Internal fixation versus hip arthroplasty in patients with nondisplaced femoral neck fractures: short-term results from a geriatric trauma registry.

PURPOSE: To determine whether internal fixation (IF) or hip arthroplasty (HA) is associated with superior outcomes in geriatric nondisplaced femoral neck fracture (FNF) patients. METHODS: Data from the Registry for Geriatric Trauma of the German Trauma Society (ATR-DGU) were analyzed (IF Group 449 and HA Group 1278 patients). In-hospital care and a 120-day postoperative follow-up were conducted. Primary outcomes, including mobility, residential status, reoperation rate, and a generic health status measure (EQ-5D score), and the secondary outcome of mortality were compared between groups. Multivariable analyses were performed to assess independent treatment group associations (odds ratios, ORs) with the primary and secondary end points. RESULTS: Patients in the HA group were older (83 vs. 81 years, p < 0.001) and scored higher on the Identification of Seniors at Risk screening (3 vs. 2, p < 0.001). We observed no differences in residential status, reoperation rate, EQ-5D score, or mortality between groups. After adjusting for key covariates, including prefracture ambulatory capacity, the mobility of patients in the HA group was more frequently impaired at the 120-day follow-up (OR 2.28, 95% confidence interval = 1.11-4.74). CONCLUSION: Treatment with HA compared to treatment with IF led to a more than twofold increase in the adjusted odds of impaired ambulation at the short-term follow-up, while no significant associations with residential status, reoperation rate, EQ-5D index score, or mortality were observed. Thus, IF for geriatric nondisplaced FNFs was associated with superior mobility 120 days after surgery. However, before definitive treatment recommendations can be made, prospective, randomized, long-term studies must be performed to confirm our findings.

Impact of anticoagulation and antiplatelet drugs on surgery rates and mortality in trauma patients.

Preinjury anticoagulation therapy (AT) is associated with a higher risk for major bleeding. We aimed to evaluated the influence of preinjury anticoagulant medication on the clinical course after moderate and severe trauma. Patients in the TraumaRegister DGU ≥ 55 years who received AT were matched with patients not receiving AT. Pairs were grouped according to the drug used: Antiplatelet drugs (APD), vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC). The primary end points were early (< 24 h) and total in-hospital mortality. Secondary endpoints included emergency surgical procedure rates and surgery rates. The APD group matched 1759 pairs, the VKA group 677 pairs, and the DOAC group 437 pairs. Surgery rates were statistically significant higher in the AT groups compared to controls (APD group: 51.8% vs. 47.8%, p = 0.015; VKA group: 52.4% vs. 44.8%, p = 0.005; DOAC group: 52.6% vs. 41.0%, p = 0.001). Patients on VKA had higher total in-hospital mortality (23.9% vs. 19.5%, p = 0.026), whereas APD patients showed a significantly higher early mortality compared to controls (5.3% vs. 3.5%, p = 0.011). Standard operating procedures should be developed to avoid lethal under-triage. Further studies should focus on detailed information about complications, secondary surgical procedures and preventable risk factors in relation to mortality.