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.

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.

[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.

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.