Settlement Is at the End-Common Trauma Scores Require a Critical Reassessment Due to the Possible Dynamics of Traumatic Brain Injuries in Patients' Clinical Course.

Background: Scientific studies on severely injured patients commonly utilize the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS) for injury assessment and to characterize trauma cohorts. However, due to potential deterioration (e.g., in the case of an increasing hemorrhage) during the clinical course, the assessment of injury severity in traumatic brain injury (TBI) can be challenging. Therefore, the aim of this study was to investigate whether and to what extent the worsening of TBI affects the AIS and ISS. Methods: We retrospectively evaluated 80 polytrauma patients admitted to the trauma room of our level I trauma center with computed-tomography-confirmed TBI. The initial AIS, ISS, and Trauma and Injury Severity Score (TRISS) values were reevaluated after follow-up imaging. Results: A total of 37.5% of the patients showed a significant increase in AIShead (3.7 vs. 4.1; p = 0.002) and the ISS (22.9 vs. 26.7, p = 0.0497). These changes resulted in an eight percent reduction in their TRISS-predicted survival probability (74.82% vs. 66.25%, p = 0.1835). Conclusions: The dynamic nature of intracranial hemorrhage complicates accurate injury severity assessment using the AIS and ISS, necessitating consideration in clinical studies and registries to prevent systematic bias in patient selection and subsequent data analysis.

Identification of novel blood-based extracellular vesicles biomarker candidates with potential specificity for traumatic brain injury in polytrauma patients.

Objective: The goal of this study was to identify changes in extracellular vesicles (EV) surface proteins specific to traumatic brain injury (TBI), which could be used as a diagnostic and prognostic tool in polytrauma patients. Summary Background Data: Known serum TBI-specific biomarkers (S100B, NSE, and GFAP), which can predict the severity and outcome of isolated TBI, lose their predictive value in the presence of additional extracranial injuries. Extracellular vesicles (EVs) are released from cells in response to various stimuli and carry specific cargo/surface molecules that could be used for tracking injury-responding cells. Methods: EVs were isolated using size exclusion chromatography (SEC) from the plasma of two groups of patients (with isolated TBI, ISS≥16, AIShead≥4, n=10; and polytraumatized patients without TBI ISS≥16, AIShead=0, n=10) collected in the emergency room and 48 h after trauma. EVs' surface epitope expression was investigated using a neurospecific multiplex flow cytometry assay and compared with healthy controls (n=10). Three enrichments of EV epitopes found to be specific to TBI were validated by western blot. Results: The expression of 10 EV epitopes differed significantly among the patient and control groups, and five of these epitopes (CD13, CD196, MOG, CD133, and MBP) were TBI-specific. The increased expression of CD196, CD13, and MOG-positive EVs was validated by western blot. Conclusion: Our data showed that TBI is characterized by a significant increase of CD13, CD196, MOG, CD133, and MBP-positive EVs in patients' plasma. A high level of MOG-positive EVs negatively correlated with the Glasgow Coma Scale score at admission and could be an indicator of poor neurological status.

Who, When, Why?-Traumatological Patients in the Emergency Department of a Maximum Care Provider.

Nationwide, there is an annual increase in the number of patients in German emergency departments resulting in a growing workload for the entire emergency department staff. Several studies have investigated the situation in emergency departments, most of which were interdisciplinary, but there are no data on a solely traumatological patient population. The present study therefore aims to investigate the situation in a university-based trauma surgery emergency department. A total of 8582 traumatological patients attending a university hospital from 1 January 2019 to 31 December 2019 were studied. Various variables, such as reason for presentation, time of accident, diagnosis, and diagnostic as well as therapeutic measures performed were analyzed from the admission records created. The mean age was 36.2 years, 60.1% were male, 63.3% presented on their own to the emergency department, and 41.2% presented during regular working hours between 8:00 a.m. and 6:00 p.m., Monday through Friday. The most common reason for presentation was outdoor falls at 17.4%, and 63.3% presented to the emergency department within the first 12 h after the sustained trauma. The most common diagnosis was bruise (27.6%), and 14.2% of patients were admitted as inpatients. Many of the emergency room patients suffered no relevant trauma sequelae. In order to reduce the number of patients in emergency rooms in the future, existing institutions in the outpatient emergency sector must be further expanded and effectively advertised to the public. In this way, the emergency medical resources of clinics, including staff, can be relieved to provide the best possible care for actual emergency patients.

EVALUATION OF CYFRA 21-1, ANGIOPOETIN-2, PENTRAXIN-3, SRAGE, IL-6, AND IL-10 IN POLYTRAUMATIZED PATIENTS WITH CONCOMITANT THORACIC TRAUMA-HELPFUL MARKERS TO PREDICT PNEUMONIA?

ABSTRACT: Background: Pneumonia is a frequent complication after polytrauma. This study aims to evaluate the ability of different serum markers to identify patients at risk of developing pneumonia after polytrauma. Methods: A retrospective analysis of prospectively collected data in polytraumatized patients with concomitant thoracic trauma (Injury Severity Score ≥16, Abbreviated Injury Scale Thorax ≥ 3) was performed. The study cohort was divided into patients with and without pneumonia during the clinical course. Serum levels of lung epithelial (CYFRA 21-1), endothelial (Ang-2), and inflammatory (PTX-3, sRAGE, IL-6, IL-10) markers were measured upon arrival in the trauma room and on days 2 and 5. Results: A total of 73 patients and 16 healthy controls were included in this study. Of these, 20 patients (27.4%) developed pneumonia. Polytraumatized patients showed significantly increased CYFRA 21-1 levels with a distinct peak after admission compared with healthy controls. Serum PTX-3 significantly increased on day 2 in polytraumatized patients compared with healthy controls. Injury Severity Score and demographic parameters were comparable between both groups (pneumonia vs. no pneumonia). No statistically significant difference could be observed for serum levels of CYFRA 21-1, Ang-2, PTX-3, sRAGE, IL-6, and IL-10 between the groups (pneumonia vs. no pneumonia) on all days. Logistic regression revealed a combination of IL-6, IL-10, sRAGE, and PTX-3 to be eventually helpful to identify patients at risk of developing pneumonia and our newly developed score was significantly higher on day 0 in patients developing pneumonia ( P < 0.05). Conclusion: The investigated serum markers alone are not helpful to identify polytraumatized patients at risk of developing pneumonia, while a combination of IL-6, IL-10, PTX-3, and sRAGE might be.

The sequence of the treatment of combined fractures of the pelvis, spine, and extremities in polytraumatized patients.

'Damage control' is the therapeutic strategy in the treatment of polytraumatized patients and aims at securing vital functions and controlling bleeding with a favorable effect on the post-traumatic immune response. The post-traumatic immune dysfunction is based on a disturbed balance between immunostimulatory and anti-inflammatory mechanisms. The extent of the immunological 'second hit' can be limited by delaying deferable surgical therapies until organ stabilization has been achieved by the treating surgeon. Pelvic sling is easy to apply and noninvasive with effective pelvic reduction. Pelvic angiography vs pelvic packing are not antagonistic, but rather should be considered as complementary methods. Operating as early as possible on unstable spinal injuries with confirmed or suspected neurological deficits by decompression and stabilization with a dorsal internal fixator. Dislocations, unstable or open fracture, vascular involvement, and compartment syndrome are considered emergency indications. In extremity fracture treatment, primary definitive osteosynthesis is often dispensed with and instead, temporary stabilization with an external fixator is performed.

Release of exosomes in polytraumatized patients: The injury pattern is reflected by the surface epitopes.

Background: Trauma is still a leading cause of morbidity and mortality, especially in the younger population. Trauma patients need a precise, early diagnostic to avoid complications like multiorgan failure and sepsis. Exosomes were described as markers and mediators in trauma. The aim of the present study was to analyze, whether the surface epitopes of plasma-exosomes can reflect the injury pattern in polytrauma. Material and Methods: Polytraumatized patients (Injury Severity Score = ISS ≥16, n = 38) were subdivided according to the predominant injury in either abdominal trauma, chest trauma or traumatic brain injury (TBI). Plasma exosomes were isolated via size exclusion chromatography. The concentration and size distribution of the plasma exosomes from emergency room samples were measured by nanoparticle tracking analysis. The exosomal surface antigens were investigated by bead-based multiplex flow cytometry and compared with healthy controls (n=10). Results: In contrast to other studies, we did not observe an increase in the total amount of plasma exosomes in polytrauma patients (1,15x109 vs. 1,13x109 particles/ml), but found changes in the exosomal surface epitopes. We found a significant reduction of CD42a+ (platelet-derived) exosomes in polytrauma patients, CD209+ (dendritic cell-derived) exosomes in the patients with predominant abdominal trauma, and CD11+ (monocyte-derived) exosomes in the patients with chest trauma. The group of patients with TBI was characterized in contrast by an increase of CD62p+ (endothelial/platelet-derived) exosomes (*p<0.05). Conclusion: Our data showed that the polytrauma injury pattern might be reflected by the cellular origin/surface epitopes of plasma-released exosomes immediately after trauma. The observed reduction of CD42+ exosomes in polytrauma patients was not associated with a reduction of total platelets in polytrauma patients.

Cranial CT is a mandatory tool to exclude asymptomatic cerebral hemorrhage in elderly patients on anticoagulation.

Background: Traumatic brain injury (TBI) after falls causes death and disability with immense socioeconomic impact through medical and rehabilitation costs in geriatric patients. Diagnosing TBI can be challenging due to the absence of initial clinical symptoms. Misdiagnosis is particularly dangerous in patients on permanent anticoagulation because minimal trauma might result in severe intracranial hemorrhage. The aim of this study is to evaluate the diagnostic necessity of cranial computed tomography (cCT) to rule out intracranial hemorrhage, particularly in the absence of neurologic symptoms in elderly patients on permanent anticoagulation in their premedication. Patients and methods: Retrospective cohort analysis of elderly trauma patients (≥ 65 years) admitted to the emergency department (ED) of the level-1-trauma center of the University Hospital Frankfurt from 01/2017 to 12/2019. The study included patients who suffered a ground-level fall with suspected TBI and subsequently underwent CT because of preexisting anticoagulation. Results: A total of 227 patients met the inclusion criteria. In 17 of these patients, cCT showed intracranial hemorrhage, of which 14 were subdural hematomas (SDH). In 8 of the patients with bleeding showed no clinical symptoms, representing 5% (n = 160) of all symptom-free patients. Men and women were equally to suffer a post-traumatic hemorrhage. Patients with intracranial bleeding were hospitalized for 14.5 (±10.4) days. Acetylsalicylic acid (ASA) was the most prescribed anticoagulant in both patient cohorts-with or without intracerebral bleeding (70.6 vs. 77.1%, p = 0.539). Similarly, patients taking new oral anticoagulant (NOAC) (p = 0.748), coumarins, or other platelet inhibitors (p > 0.1) did not show an increased bleeding incidence. Conclusion: Acetylsalicylic acid and NOAC use are not associated with increased bleeding risk in geriatric trauma patients (≥ 65 years) after fall-related TBI. Even in asymptomatic elderly patients on anticoagulation, intracranial hemorrhage occurs in a relevant proportion after minor trauma to the head. Therefore, cCT is an obligatory tool to rule out cerebral hemorrhage in elderly patients under anticoagulation.

Early start of thromboprophylaxis does not increase risk of intracranial hematoma progression in multiply injured patients with traumatic brain injury.

BACKGROUND: Venous thromboembolism (VTE) in severely injured patients with severe traumatic brain injury (TBI) is a risk during the clinical course. Data on the safety of an early initiation of pharmacological VTE prophylaxis in severely injured patients with concomitant severe TBI is sparse. METHODS: Admissions to our level-1-trauma center between January 2015 and December 2018 were screened. Patients suffering from severe TBI (Abbreviated Injury Scale (AIS) of the head ≥3) and at least one further AIS ≥ 3 in any other body region were included. Demographic data, thromboembolic events, and progression of the intracranial hemorrhage were extracted from the patient's charts. According to the first application of pharmacological thromboprophylaxis (VTEp), patients were categorized either to the early, the late (later than 24 h) or the no therapy group. RESULTS: In 79 patients (early: n = 35, late: n = 29, no therapy: n = 15) the Injury Severity Score (ISS) was 36.7 ± 12.7 points (AIShead 4.1 ± 0.8). No differences were found regarding the progression of the intracranial hemorrhage after initiation of the VTE prophylaxis (adj. p = 0.8). The VTE rate was low (n = 1, 1.6%). CONCLUSION: In severely injured patients with severe TBI, the early administration of pharmacological thromboprophylaxis did not result in a higher rate of intracranial hematoma progression.

Health Economic Challenge: Geriatric Trauma-An Age-Based Observational Analysis of Treatment Costs and Reimbursement Issues.

Demographic change is having a major impact on the economic and structural development of the healthcare system. People stay active longer and the number of mild traumatic brain injury [mTBI] in patients ≥ 65 years of age consequently increases. The aim of this comparative analysis is to illustrate the impact of demographic change and the increasing treatment of geriatric trauma patients on the cost structure of the health care system using mTBI as an example diagnosis. Patients and Methods: The 12-month retrospective analysis included 220 in-patients treated with mTBI and remunerated under the German Diagnosis Related Group [G-DRG] B80Z. For comparative analysis, the patient population was divided into two study groups according to age [U65 18−64 years, G65 ≥ 65 years]. For the cost and proceeds calculation, itemized cost reports (personnel, supply, material, and equipment costs, etc.) were created. Results: 163 patients U65 and 57 patients G65 were included. In the G65 group, the most frequent accident mechanism was a fall from a short distance (84.1 vs. U65 36.7%; p = 0.007). For the inpatient admission of G65, the use of anticoagulants (p < 0.001) and comorbidity (p = 0.002) played a primary role, while for younger patients it was more neurological symptoms (p < 0.001) and alcohol (p < 0.001) that led to inpatient monitoring. The mean length of hospitalization of G65 patients was significantly longer than that of younger patients (G65 2.4 ± 1.9 days > U65 1.7 ± 0.8 days; p = 0.007) and radiological examinations (G65 94.7% > U65 23.3%; p = 0.013) were performed more frequently. Comparing analysis of the cost and proceeds of U65 vs. G65 results in a proceeds difference of €51,753.91 per year for the G-DRG B80Z compared to U65. Conclusions: It has been shown that there is a difference in costs and proceeds when comparing younger and older patients, resulting in a reimbursement deficit. In view of the demographic development in Europe, flat-rate remuneration will lead to a considerable discrepancy between DRG reimbursement and the coverage of hospitals' running costs. Providing health care to an increasingly aging society represents one of the major personnel and financial challenges for the public health system in the coming decades. Further adaptation of the DRG system to the growing costs caused by older patients is imperative.

Lung failure after polytrauma with concomitant thoracic trauma in the elderly: an analysis from the TraumaRegister DGU®.

BACKGROUND: In developed countries worldwide, the number of older patients is increasing. Pulmonary complications are common in multiple injured patients with chest injuries. We assessed whether geriatric patients develop lung failure following multiple trauma with concomitant thoracic trauma more often than younger patients. METHODS: A retrospective analysis of severely injured patients with concomitant blunt thoracic trauma registered in the TraumaRegister DGU® (TR-DGU) between 2009 and 2018 was performed. Patients were categorized into four age groups: 55-64 y, 65-74 y, 75-84 y, and ≥ 85 y. Adult patients aged 18-54 years served as a reference group. Lung failure was defined as PaO2/FIO2 ≤ 200 mm Hg, if mechanical ventilation was performed. RESULTS: A total of 43,289 patients were included, of whom 9238 (21.3%) developed lung failure during their clinical stay. The rate of posttraumatic lung failure was seen to increase with age. While lung failure markedly increased the length of hospital stay, duration of mechanical ventilation, and length of ICU stay independent of the patient's age, differences between younger and older patients with lung failure in regard to these parameters were clinically comparable. In addition, the development of respiratory failure showed a distinct increase in mortality with higher age, from 16.9% (18-54 y) to 67.2% (≥ 85 y). CONCLUSION: Development of lung failure in severely injured patients with thoracic trauma markedly increases hospital length of stay, length of ICU stay, and duration of mechanical ventilation in patients, regardless of age. The development of respiratory failure appears to be related to the severity of the chest trauma rather than to increasing patient age. However, the greatest effects of lung failure, particularly in terms of mortality, were observed in the oldest patients.

The effect of age and sex on outcomes following isolated moderate to severe traumatic brain injury.

PURPOSE: The impact of female sex on traumatic brain injury (TBI) outcomes remains controversial. The combined impact of age and sex on TBI outcomes must be clarified. We hypothesized that females have better outcomes than males in the premenopausal age group. METHODS: Data from the 2007-2016 National Trauma Data Bank of the Committee on Trauma-American College of Surgeons were used. Of a total of 686,549 patients with moderate to severe TBI (AIS ≥ 3), 251,491 were female. Comparison analyses of clinical characteristics and outcomes between females and males were conducted at different age groups: < 45 years, 45-55, and > 55 years. Logistic regressions were performed to assess the impact of age and female sex on mortality and complications. RESULTS: Mortality rate between females and males aged < 45 and 45-55 years was similar, but significantly reduced in the > 55 years group. After multivariate logistic regression analysis controlling for multiple confounding factors, we found that females aged > 55 years had markedly decreased risk of mortality (AOR: 0.857, 95% CI 0.835-0.879, p < 0.001) and complications. CONCLUSION: Female patients in the postmenopausal stage have better outcomes following TBI than males, but pre- and perimenopausal females do not, suggesting that female sexual hormones may not provide a significant protective effect on clinical outcomes following isolated moderate to severe TBI.

Influence of Antibiotic Management on Microbial Selection and Infectious Complications After Trauma.

Background: The inflammatory response and post-traumatic complications like infections play an important role in the pathophysiology of severe injuries. This study examines the microbiological aspects in anti-infective treatment of trauma patients and their inflammatory response in post-traumatic infections complications. Patients and Methods: A retrospective analysis of prospectively collected data in trauma patients (ISS ≥ 16) over a 1-year period (01/2018 to 12/2018) is provided. Patient population was stratified into severely injured patients without post-traumatic infection (inf-PT), and severely injured patients who developed an infection (inf+PT). Results: Of 114 trauma patients, 45 suffered from post-traumatic infection during the first 10 days of hospitalization. Severely injured patients with concomitant traumatic brain injury (PT+TBI) showed the highest rate of post-traumatic infection. Pro-inflammatory reaction was tracked by levels of Interleukin (IL-)6 (day 3: inf+T 190.8 ± 359.4 pg/dL > inf-PT 56.2 ± 57.7 pg/mL (mean ± SD); p = 0.008) and C-Reactive-Protein (CRP, day 3: inf+PT 15.3 mg/dL > inf-PT 6.7 mg/dL, p = 0.001) which were significantly higher in trauma patients who develop an infectious complication and showed a significant positive correlation with the occurrence of infection. The leading entity of infection was pneumonia followed by infections of the urinary tract mainly caused by gram-negative Enterobacteriaceae. 67.5% of all trauma patients received single-shot antibiosis during initial care in trauma bay. The development of secondary colonization was not relevant positively correlated with single-shot antibiosis (r = 0.013, p = 0.895) and prophylactically calculated antibiotic administration (r = 0.066, p = 0.500). Conclusion: Severely injured trauma patients have an increased risk for development of infectious complications, which mainly is pneumonia followed by infection of the urinary tract mainly caused by gram-negative Enterobacteriaceae. Based on the data in this study, the one-time antibiotic and prophylactic calculated use of antibiotics, like Cephalosporins must be critically discussed in terms of their role in the development of post-traumatic infections and microbial selection.

[Admission diagnosis contusion: etiology, epidemiology and cost-causing factors]. / Aufnahmediagnose Prellung: Ätiologie, Epidemiologie und Kostenfaktoren.

BACKGROUND: The admission of patients with minor injuries, such as contusions is a regular practice in acute care hospitals. The pathophysiological changes resulting from the accident are seldom the primary reason for hospitalization. The aim of this retrospective monocentric study was therefore to examine the etiology as well as the cost-causing factors and refinancing on admission. METHODS: Patients were identified due to a retrospective query in the hospital information system (HIS) according to the ICD-10 German modification codes at discharge. A total of 117 patients were enrolled over a period of 2 years. The classification was carried out according to the accident mechanism and the division into age groups. In addition, the cost calculation was based on department and clinic-specific daily rates. RESULTS: In terms of etiology low impact falls in the domestic environment were the most common cause (48.7%), followed by high-energy trauma (22.8%). Within the group with domestic falls, the mean age was 77.8 years. This group also showed the longest length of stay (LOS) with 5.2 days. As part of the calculated costs, the group of domestic falls showed the highest costs of 2596.24 € with an average DRG cost revenue of 1464.51 €. DISCUSSION: The evaluation of the clinic internal data confirmed the subjective perception that the majority of patients admitted with the diagnosis of contusions came from the age group >65 years. Admission is primarily based on the increasing comorbidities and to avert secondary diseases and the consequences of immobilization. It could also be shown that the resulting costs are relevant to health economics and that the treatment does not appear to cover the costs.

[Cost factor "outpatient wound care" in the emergency department : Cost-revenue deficit of outpatient wound treatment in a German university hospital]. / Kostenfaktor "ambulante Wundversorgung" in der Notaufnahme : Kosten-Erlös-Defizit der ambulanten Wundversorgung in einer deutschen Universitätsklinik.

BACKGROUND: In addition to highly specialized medicine, the initial treatment of wounds and minor surgical interventions are generally necessary basic services of emergency care in hospitals. The reimbursement of outpatient emergency services for persons with statutory insurance is currently based on the uniform assessment standard (EBM), where the recording of business expenses in the private practice sector serves as the basis for the calculation. Hospitals have considerably higher maintenance costs than medical practices. OBJECTIVE: In this article the resulting cost-revenue ratio of outpatient wound care in an emergency department is analyzed through the reimbursement according to EBM. MATERIAL AND METHODS: The data were collected in the emergency surgical department of the University Hospital Frankfurt am Main over 12 months. Included were all patients who received sutured wound care during this period. The costs incurred were compared to the remuneration according to EBM 01210 (or 01212) with the additional flat rate for small surgical procedures EBM 02301. RESULTS: During the observation period 1548 patients were treated, i.e. 19.52% of all trauma surgery cases. The resulting costs of a standard wound care of 45.40 € are offset by a remuneration of 31.83 €. The calculation of the total revenue shows a deficit amount of 13.57 € per outpatient case, this corresponds to an annual deficit of 21,006.36 €. CONCLUSION: It could be shown that even without consideration of the relevant holding costs, cost coverage cannot be achieved in any case. The previous reimbursement of outpatient wound care on the basis of the EBM appears to be inadequate. In the future, an adjustment or supplementary remuneration seems to be necessary in order to ensure sufficient quality of care.

Registry-Based Mortality Analysis Reveals a High Proportion of Patient Decrees and Presumed Limitation of Therapy in Severe Geriatric Trauma.

BACKGROUND: The treatment of severely injured patients, especially in older age, is complex, and based on strict guidelines. METHODS: We conducted a retrospective study by analyzing our internal registry for mortality risk factors in deceased trauma patients. All patients that were admitted to the trauma bay of our level-1-trauma center from 2014 to 2018, and that died during the in-hospital treatment, were included. The aim of this study was to carry out a quality assurance concerning the initial care of severely injured patients. RESULTS: In the 5-year period, 135 trauma patients died. The median (IQR) age was 69 (38-83) years, 71% were male, and the median (IQR) Injury Severity Score (ISS) was 25 (17-34) points. Overall, 41% of the patients suffered from severe traumatic brain injuries (TBI) (AIShead ≥ 4 points). For 12.7%, therapy was finally limited owing to an existing patient's decree; in 64.9% with an uncertain prognosis, a 'therapia minima' was established in consensus with the relatives. CONCLUSION: Although the mortality rate was primarily related to the severity of the injury, a significant number of deaths were not exclusively due to medical reasons, but also to a self-determined limitation of therapy for severely injured geriatric patients. The conscientious documentation concerning the will of the patient is increasingly important in supporting medical decisions.

miR-142-3p Expression Is Predictive for Severe Traumatic Brain Injury (TBI) in Trauma Patients.

BACKGROUND: Predictive biomarkers in biofluids are the most commonly used diagnostic method, but established markers in trauma diagnostics lack accuracy. This study investigates promising microRNAs (miRNA) released from affected tissue after severe trauma that have predictive values for the effects of the injury. METHODS: A retrospective analysis of prospectively collected data and blood samples of n = 33 trauma patients (ISS ≥ 16) is provided. Levels of miR-9-5p, -124-3p, -142-3p, -219a-5p, -338-3p and -423-3p in severely injured patients (PT) without traumatic brain injury (TBI) or with severe TBI (PT + TBI) and patients with isolated TBI (isTBI) were measured within 6 h after trauma. RESULTS: The highest miR-423-3p expression was detected in patients with severe isTBI, followed by patients with PT + TBI, and lowest levels were found in PT patients without TBI (2-∆∆Ct, p = 0.009). A positive correlation between miR-423-3p level and increasing AIShead (p = 0.001) and risk of mortality (RISC II, p = 0.062) in trauma patients (n = 33) was found. ROC analysis of miR-423-3p levels revealed them as statistically significant to predict the severity of brain injury in trauma patients (p = 0.006). miR-124-3p was only found in patients with severe TBI, miR-338-3p was shown in all trauma groups. miR-9-5p, miR-142-3p and miR-219a-5p could not be detected in any of the four groups. CONCLUSION: miR-423-3p expression is significantly elevated after isolated traumatic brain injury and predictable for severe TBI in the first hours after trauma. miR-423-3p could represent a promising new biomarker to identify severe isolated TBI.

Severe Traumatic Brain Injury (TBI) Modulates the Kinetic Profile of the Inflammatory Response of Markers for Neuronal Damage.

The inflammatory response plays an important role in the pathophysiology of multiple injuries. This study examines the effects of severe trauma and inflammatory response on markers of neuronal damage. A retrospective analysis of prospectively collected data in 445 trauma patients (Injury Severity Score (ISS) ≥ 16) is provided. Levels of neuronal biomarkers (calcium-binding Protein B (S100b), Enolase2 (NSE), glial fibrillary acidic protein (GFAP)) and Interleukins (IL-6, IL-10) in severely injured patients (with polytrauma (PT)) without traumatic brain injury (TBI) or with severe TBI (PT+TBI) and patients with isolated TBI (isTBI) were measured upon arrival until day 5. S100b, NSE, GFAP levels showed a time-dependent decrease in all cohorts. Their expression was higher after multiple injuries (p = 0.038) comparing isTBI. Positive correlation of marker level after concomitant TBI and isTBI (p = 0.001) was noted, while marker expression after PT appears to be independent. Highest levels of IL-6 and -10 were associated to PT und lowest to isTBI (p < 0.001). In all groups pro-inflammatory response (IL-6/-10 ratio) peaked on day 2 and at a lower level on day 4. Severe TBI modulates kinetic profile of inflammatory response by reducing interleukin expression following trauma. Potential markers for neuronal damage have a limited diagnostic value after severe trauma because undifferentiated increase.

ATF3 reduces migration capacity by regulation of matrix metalloproteinases via NFκB and STAT3 inhibition in glioblastoma.

Glioblastoma is associated with poor survival and a high recurrence rate in patients due to inevitable uncontrolled infiltrative tumor growth. The elucidation of the molecular mechanisms may offer opportunities to prevent relapses. In this study we investigated the role of the activating transcription factor 3 (ATF3) in migration of GBM cells in vitro. RNA microarray revealed that gene expression of ATF3 is induced by a variety of chemotherapeutics and experimental agents such as the nitric oxide donor JS-K (O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate). We found NFκB and STAT3 to be downstream targets inhibited by overexpression of ATF3. We demonstrate that ATF3 is directly involved in the regulation of matrix metalloproteinase expression and activation. Overexpression of ATF3 therefore leads to a significantly reduced migration capacity and induction of tissue inhibitors of matrix metalloproteinases. Our study for the first time identifies ATF3 as a potential novel therapeutic target in glioblastoma.