Decrease of exosomal miR-21-5p and the increase of CD62p+ exosomes are associated with the development of sepsis in polytraumatized patients.

Sepsis as a severe systemic inflammation leads oftentimes to organ dysfunction and subsequently to death. In polytrauma patients, septic complications represent with 45% the predominant cause of late death and are responsible for extremely high costs in the healthcare system. Therefore, clinicians have to detect as early as possible the begin of sepsis to improve the patient's outcome. One new promising diagnostic tool to diagnose septic complications in polytraumatized patients are exosomes. Plasma samples from polytraumatized patients (Injury Severity Score (ISS) ≥16) which developed sepsis (n = 10) and without sepsis (n = 10), were collected at emergency room (ER), 24h and 5 days after trauma. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with plasma EVs from healthy controls (n = 10). Moreover, exosomal cytokine concentrations were measured via high-sensitive ELISA and were correlated with systemic concentrations. For miRNA cargo analysis, we analysed the miRNAs miR-1298-5p, miR-1262, miR-125b-5p, miR-92a-3p, miR-93-5p, miR-155-5p and miR-21-5p and compared their exosomal concentrations by means of RT-qPCR. CD62p + exosomes were significantly increased in septic polytrauma-patients (p ≤ 0.05), while CD40+exosomes, as well as CD49e + exosomes were diminished (p ≤ 0.05). Furthermore, we observed that the exosomal IL-6 concentration reflects the systemic IL-6 concentration (r2 = 0.63) and did not significantly alter between patients with and without sepsis. The exosomal IL-10 concentration seemed to be constant in all patients and healthy controls. We observed that a decrease of miR-21-5p in exosomes was associated with the development of sepsis (p ≤ 0.05), while exosomal miR-93-5p, miR-155-5p and miR-92a-3p were not specifically altered in septic patients. Taken together, the present study in polytraumatized patients demonstrated that the development of sepsis is associated with an increase of CD62p + exosomes. Furthermore, the exosomal cargo was changed in septic patients: miR-21-5p was diminished.

Development of a Sampling and Storage Protocol of Extracellular Vesicles (EVs)-Establishment of the First EV Biobank for Polytraumatized Patients.

In the last few years, several studies have emphasized the existence of injury-specific EV "barcodes" that could have significant importance for the precise diagnosis of different organ injuries in polytrauma patients. To expand the research potential of the NTF (network trauma research) biobank of polytraumatized patients, the NTF research group decided to further establish a biobank for EVs. However, until now, the protocols for the isolation, characterization, and storage of EVs for biobank purposes have not been conceptualized. Plasma and serum samples from healthy volunteers (n = 10) were used. Three EV isolation methods of high relevance for the work with patients' samples (ultracentrifugation, size exclusion chromatography, and immune magnetic bead-based isolation) were compared. EVs were quantified using nanoparticle tracking analysis, EV proteins, and miRNAs. The effects of different isolation solutions; the long storage of samples (up to 3 years); and the sensibility of EVs to serial freezing-thawing cycles and different storage conditions (RT, 4/-20/-80 °C, dry ice) were evaluated. The SEC isolation method was considered the most suitable for EV biobanking. We did not find any difference in the quantity of EVs between serum and plasma-EVs. The importance of particle-free PBS as an isolation solution was confirmed. Plasma that has been frozen for a long time can also be used as a source of EVs. Serial freezing-thawing cycles were found to affect the mean size of EVs but not their amount. The storage of EV samples for 5 days on dry ice significantly reduced the EV protein concentration.

Diagnostic and Prognostic Potential of Exosomal Cytokines IL-6 and IL-10 in Polytrauma Patients.

Trauma remains a leading cause of morbidity and mortality. Polytraumatized patients need a precise, early diagnosis to avoid complications such as multiorgan failure or sepsis. Inflammatory cytokines, commonly used for diagnosis, have a short half-life, which limits their efficacy as a diagnostic or prognostic marker. In this study, we hypothesized that cytokines in exosomes could have a longer half-life, and therefore could be used as diagnostic and prognostic markers in polytrauma patients. Plasma samples from polytraumatized patients (ISS ≥ 16, n = 18) were collected in the emergency room (ER) 1, 2, 3 and 5 days after trauma. Plasma-exosomes were isolated via size exclusion chromatography from polytraumatized patients and healthy volunteers (n = 10). The systemic and exosomal concentrations of interleukin (IL)-6, IL-10, IL-1ß and TNF were measured using high-sensitive ELISAs. To investigate the diagnostic and prognostic potential of exosomal cytokines, data were correlated with clinical outcome parameters (injury severity, ventilation time, time in ICU and survival) documented in the patients' electronic records. Despite the use of high-sensitive ELISAs, IL-1ß and TNF alpha were not detected in exosomes. IL-6 and IL-10 were detectable in polytraumatized patient exosomes at all time points. A decrease over time of both systemic and exosomal IL-6 concentrations was observed. Furthermore, exosomal and systemic IL-6 concentrations moderately correlated (r = 0.63). Exosomal IL-6 in the ER moderately correlated with the Injury Severity Score (ISS) (mean 35.5 ± 11.5) (r = 0.45) and was associated with non-survival in polytrauma patients (p < 0.05). In contrast to IL-6, no correlation between systemic and exosomal IL-10 concentrations was found. Exosomal IL-10 concentrations remained unchanged throughout the observation time, whereas systemic IL-10 concentrations peaked in the ER and were significantly reduced after 24 h. Data from this study support our hypothesis that some cytokines (IL-10), but not all (IL-6), are detectable in exosomes significantly longer than they are in plasma. This might indicate that they are protected from degradation. Although we did not find a correlation between IL-10 exosomal concentration and patient outcome, our data confirm that exosomal cytokines are of interest as potential diagnostic and prognostic markers in polytrauma patients, and require further detailed research.

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.

A New Perspective for Bone Tissue Engineering: Human Mesenchymal Stromal Cells Well-Survive Cryopreservation on ß-TCP Scaffold and Show Increased Ability for Osteogenic Differentiation.

The clinical breakthrough of bone tissue engineering (BTE) depends on the ability to provide patients routinely with BTE products of consistent pharmacological quality. The bottleneck of this approach is the availability of stem cells. To avoid this, we suggest immobilization of random-donor-derived heterologous osteoinductive MSCs onto osteoconductive matrices. Such BTE products could then be frozen and, after thawing, could be released as ready-to-use products for permanent implantation during surgery. For this purpose, we developed a simple protocol for cryopreservation of BTE constructs and evaluated the effects of this procedure on human MSC (hMSCs) metabolic and osteogenic activity in vitro. Our findings show that hMSCs can be freeze-thawed on a ß-TCP scaffold through a technically simple procedure. Treated cells sustained their metabolic activity and showed favorable osteogenic potential. Mechanistically, HIF1α and YBX1 genes were activated after freeze-thawing, and supposed to be linked to enhanced osteogenesis. However, the detailed mechanisms as to how the cryopreservation procedure beneficially affects the osteogenic potential of hMSCs remains to be evaluated. Additionally, we demonstrated that our BTE products could be stored for 3 days on dry ice; this could facilitate the supply chain management of cryopreserved BTE constructs from the site of manufacture to the operating room.

Epidemiology of complete knee dislocations: an updated classification system.

INTRODUCTION: Current classifications of complete knee dislocations do not capture the extent of the complex concomitant ligamentous and bony injuries, which may have an impact on future outcomes. The purpose of this retrospective study was to evaluate the epidemiology of complete knee dislocations as well as to present an updated classification system based on the author's experience at a Level-I trauma center. MATERIALS AND METHODS: Only patients with complete loss of contact of the articulating bones and ≥ 18 years of age who admitted in our level-I trauma center between 2002 and 2019 were included. Patients were identified using a retrospective systematical query in the Hospital Information System (HIS) using the International Statistical Classification of Diseases and Related Health Problems Version10 (ICD-10) codes of the German Diagnosis Related Groups (G-DRG). RESULTS: Final data included 80 patients, with the majority of patients being male (n = 64; 80.0%). Mean age was 34.9 years (range: 18-70 years). External protective fixation was applied in 32 patients (40.0%). Reconstruction of the posterior cruciate ligament and the anterior cruciate ligament were performed in 56.3% (n = 45) and 55.0% (n = 44) of cases, respectively. The lateral collateral ligament complex was surgically addressed in 47.5% (n = 38), while the medial collateral ligament complex was reconstructed in 40% (n = 32). Surgery of the lateral meniscus and the medial meniscus was needed in 31.1% (n = 25) and 30.0% (n = 24). Neurovascular surgery occurred in 13.8% (n = 11). From the characteristic injury-patterns the authors of this study present a new classification system that ranks the injuries from Grade-A to Grade-D according to their severity. CONCLUSION: This retrospective study demonstrates that the historically used classification systems for dislocations of the knee are insufficient for these severe injuries. Concomitant ligamentous, neurovascular, bony, and meniscal injuries were frequent, and required several staged procedures. Consequently, an updated classification system is proposed.

Seizure related injuries - Frequent injury patterns, hospitalization and therapeutic aspects.

PURPOSE: Epileptic seizures frequently result in distinct physical injuries, fractures, traumatic brain injuries and minor trauma. The aim of this study was to retrospectively determine the frequent injury patterns due to seizure episode and to analyze consecutive acute medical care. METHODS: This retrospective mono-center study was conducted at Frankfurt University Hospital, Frankfurt am Main, Germany between January 2007 and December 2017. Epilepsy patients with seizure-related fractures admitted to the emergency department were identified via a retrospective systematic query in the hospital information system using the ICD-10 German modification codes G40.0-G40.9. Patients with an unclear diagnosis of epilepsy were excluded. Sociodemographic as well as disease specific aspects were analyzed. Descriptive and Kruskal-Wallis one-way analysis of variance were used for statistical analysis. RESULTS: A total number of 62 epilepsy patients were included. The mean age was 58.1 years. Fractures concerned the upper extremity most frequently (43.5%, n = 20), and 70.0% (14/20) were humerus fractures. Admission to intensive care unit for acute trauma care was necessary in 29.0% patients (n = 18), and surgery in 45.2% patients (n = 28). Twenty-five patients (26.6%) showed clinical or radiological signs of traumatic brain injury. Provoking factors were identified in 20 patients (32.3%), i.e., acute withdrawal or excess of alcohol (n = 15), relevant sleep deprivation (n = 2), and intoxication or withdrawal of other illegal drugs or trivial infect (n = 1 for each) and non-compliance with anti-seizure drugs (n = 1). A decreased T-score (-1.04 ± 1.15) and Z-score (-0.84 ± 0.75) compared to healthy subjects were found. CONCLUSION: Fractures in upper extremities, trunk and craniocerebral trauma occur frequently as seizure-induced injuries. Alcohol excess and withdrawal are important provoking factors and should be targeted with preventive measurements to avoid seizure related injuries and accidents.

Patterns of Craniomaxillofacial Trauma After E-Scooter Accidents in Germany.

INTRODUCTION: E-Scooters are trending as an individual transport vehicle with electric drive in Germany. But there is less data about the frequency, demographic details and possible injuries and therapy needs in context with E-scooter accidents. Therefore, the primary aim of this study was to analyze the frequency and the characteristics of facial trauma as well as the consecutive hospitalization and management after injuries with E-scooters in a German clinic specialized in craniomaxillofacial surgery. MATERIALS AND METHODS: Retrospective data analysis of the hospital information system of patients admitted to central emergency unit driving e-scooters and injuries between June and December 2019. RESULTS: A total of 28 consecutive patients were admitted to the emergency care unit of a level one trauma center from June to December 2019. 85% had a minimum of two or more facial injuries. Most common were soft tissue injuries with 64% (n = 18), fractures with 54% (n = 15) and teeth injuries with 39% (n = 11). 82% percent of injuries were related with consumption of alcohol. DISCUSSION: The data show a variety of different injuries from teeth injury, wounds and facial fractures in varying degrees in a predominantly young and male cohort (mean age 33.57, 68% male) often associated with alcohol. As accidents happen especially at nighttime and on weekends personnel capacities should be provided. Still bicycle accidents and following injuries stay a major problem.

11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes.

Epoxyeicosatrienoic acids (EET) facilitate regeneration in different tissues, and their benefit in dermal wound healing has been proven under normal conditions. In this study, we investigated the effect of 11,12 EET on dermal wound healing in diabetes. We induced diabetes by i.p. injection of streptozotocin 2 weeks prior to wound creation on the dorsal side of the mouse ear. 11,12 EET was applied every second day on the wound, whereas the control groups received only solvent. Epithelialization was monitored every second day intravitally up to wound closure. Wounds were stained for VEGF, CD31, TGF-ß, TNF-α, SDF-1α, NF-κB, and Ki-67, and fibroblasts were counted after hematoxylin-eosin stain on days 3, 6, 9, and 16 after wounding. After induction of diabetes, wounds closed on day 13.00 ± 2.20 standard deviation (SD). Local 11,12 ETT application improved wound closure significantly to day 8.40 ± 1.39 SD. EET treatment enhanced VEGF and CD31 expression in wounds on day 3. It also seemed to raise TNF-α level on all days investigated as well as TGF-ß level on days 3 and 6. A decrease in NF-κB could be observed on days 9 and 16 after EET application. The latter findings were not significant. SDF-1α expression was not influenced by EET application, and Ki-67 was significantly less in the EET group on day 9 after EET application. The number of fibroblasts was significantly increased on day 9 after the 11,12 EET application. 11,12 EET improve deteriorated wound healing in diabetes by enhancing neoangiogenesis, especially in the early phase of wound healing. Furthermore, they contribute to the dissolution of the initial inflammatory reaction, allowing the crucial transition from the inflammatory to proliferative phase in wound healing.

[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.

[Interventional control of traumatic injuries of parenchymatous upper abdominal organs and the kidneys]. / Interventionelle Kontrolle traumatischer Verletzungen der parenchymatösen Oberbauchorgane und der Nieren.

Hemorrhage after trauma in the area of the upper abdominal organs and the kidneys can represent a life-threatening situation. The primary treatment options are conservative or surgical treatment. Only in exceptional cases can endovascular treatment with an angiographic depiction of the active bleeding and, if necessary, intervention by means of embolization be used as an alternative.

[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.

Changes in platelet-rich fibrin composition after trauma and surgical intervention.

Reconstruction surgery after trauma has always been a big challenge. The use of platelet-rich fibrin (PRF) as an autologous source could help accelerate the regeneration time of bone and soft tissues. PRF is a blood concentrate system obtained through a one-step centrifugation. The 3D matrix of the PRF clot serves as a reservoir of growth factors. In the present study, PRF from patients after trauma and after surgery was compared to healthy volunteers to evaluate the composition and potential of PRF as a possible autologous tool for growth factor delivering. Two PRF species and blood from healthy volunteers and patients after trauma and after following surgical intervention were compared (n = 10). FACS analysis, ELISA, and histological analysis were performed. The Pro-inflammatory potential after trauma and after the intervention is increased in PRF species whereas cellular and humoral factors with distinct regenerative potential remained on a level comparable to peripheral blood. It was demonstrated that cells in PRF express more pro-inflammatory species when obtained after the surgical intervention compared to PRF from healthy individuals. This pro-inflammatory potential should be considered, when combining PRF with bone substitute materials for reconstruction surgery prone to foreign body giant cell reaction. Accordingly, solid or injectable PRF-based matrices should preferably be prepared prior to a surgical intervention.

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.

[Modified arthroscopic technique to replace the posterior cruciate ligament in multiligament knee injuries : Results compared to open tibial inlay technique]. / Modifizierte arthroskopische Technik zum Ersatz des hinteren Kreuzbands bei multiligamentären Kniegelenkverletzungen : Ergebnisse im Vergleich zur offenen "Tibial-inlay"-Technik.

BACKGROUND: There is no standard procedure regarding surgical treatment of multiligament knee injuries involving rupture of the posterior cruciate ligament. OBJECTIVE: Does the modified and purely arthroscopic operation technique show similarly good results compared to the familiar open tibial inlay technique? METHODS: A total of four patients were surgically treated using the open tibial inlay technique (group A) and seven using the modified arthroscopic approach (group B). The prospectively designed follow-up examination comprised the Lysholm score, the subjective questionnaire of the International Knee Documentation Committee (IKDC) score as well as the specifically extended Orthopedic Working Group Knee (OAK) score for clinical assessment. Tests on translational movability of the knee joint were performed with the Rolimeter®. The level of statistical significance alpha was set at 5%. RESULTS: The follow-up examination took place on average 28.5 ± 19.60 months and 30.6 ± 26.26 months postoperatively in groups A and B, respectively. Groups A and B recorded mean 70.3 ± 5.32 and 69.6 ± 19.82 points in the Lysholm score, respectively. In the subjective IKDC score group A showed 67.3 ± 7.76 points and group B 65.9 ± 12.35 points. The OAK score was 77.5 ± 6.10 points in group A and 75.3 ± 11.31 points in group B. The side difference in the posterior drawer test was 1.75 ± 1.192 mm in group A and 2.50 ± 2.160 mm in group B. In the reverse Lachman test differences of 2.37 ± 2.175 mm and 3.22 ± 2.059 mm were measured in groups A and B, respectively. All values showed no significant differences between the two evaluated groups. CONCLUSION: The results of the two operation techniques were not significantly different. The arthroscopic approach is therefore regarded as the preferred method in this institute.

Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2.

BACKGROUND: Club Cell protein (CC)16 correlates with lung injury and respiratory complications, which are in part triggered by polymorphonuclear leukocytes (PMNL) in severely traumatized patients (TP). CC16 exerts anti-inflammatory and immunosuppressive effects, however, its influence on PMNL functions after trauma is unknown. Here, we evaluated whether CC16 present in sera from TP could modify the biological functions of PMNL. METHODS: Sera from 16 severely injured TP without pneumonia (no P, n = 8) or with pneumonia (P, n = 8) were collected at admission to emergency department (ED) and 1 day prior pneumonia and pre-incubated with or without anti-CC16 antibody for CC16 neutralization. Samples from the equal post-injury days in the corresponding no P group were used. Neutrophils were isolated from healthy volunteers (HV, n = 5) and incubated with 20% of the serum medium from TP, respectively. In PMNL, CD62L, CD11b/CD18 and CD31 expression, migratory capacity, phagocytosis rate, oxidative burst and apoptosis were investigated. In isolated PMNL, CXCR1 and CXCR2 were neutralized before stimulation with CC16, and oxidative burst, phagocytosis and apoptosis were analyzed in neutrophils and their subsets. RESULTS: Serum from the P group enhanced significantly PMNL migration compared to no P group, while CC16-neutralization further increased the migratory rate of PMNL in both groups. CC16-neutralization increased significantly the expression of CD62L in the P group at ED. Oxidative burst was significantly increased in the P group vs. no P during the study period. CC16 seemed to have no influence on oxidative burst and phagocytosis in TP. However, in a more controlled study design, CC16 induced a significant increase of oxidative burst and a decrease of apoptosis of CD16+ granulocytes. These effects were markedly observed in mature CD16brightCD62Lbright and immune suppressive CD16brightCD62Ldim neutrophils. In mature subset, CXCR1 and CXCR2 neutralization diminished CC16-induced effects. CONCLUSIONS: CC16 in sera from multiply traumatized patients, notably of those with pneumonia, has significant effects on PMNL. The results suggest an association of CC16 with CXCR1 and CXCR2. Our data suggest that CC16 reduces the migratory capacity of PMNL and thus modulates their function in patients with respiratory complications after trauma.

Early Chemical Thromboprophylaxis Does not Increase the Risk of Intracranial Hematoma Progression in Patients with Isolated Severe Traumatic Brain Injury.

BACKGROUND: Venous thromboembolism (VTE) is recognized as a factor of morbidity and mortality in trauma patients suffering from severe blunt traumatic brain injury (TBI). The administration of pharmacological prophylaxis is broadly accepted as an effective therapy to prevent VTE events in trauma patients. Regardless of its ascertained efficacy, the risk of hematoma progression complicates the therapy in patients suffering from TBI: therefore, the optimal time to start prophylactic anticoagulation in these patients remains controversial. METHODS: All primary admissions to our level-1-trauma center between January 2012 and December 2016 were screened for severe blunt TBI with a head Abbreviated Injury Scale (AIS) ≥ 3. Patients who died within the first 24 h were excluded. Basic demographic results, thromboembolic events and progression of the intracranial hematoma were extracted from the patient's records. The patients were categorized into 4 groups according to start of VTE chemoprophylaxis: early ( < 24 h after hospitalization), intermediate (24-48 h), late ( > 48 h) and no therapy (no prophylactic anticoagulation within the first five days of hospitalization). A total of 292 patients with severe TBI were analyzed (early: n = 93, intermediate: n = 90, late: n = 74, no therapy: n = 35). The overall rate of intracranial bleeding progression was 13.6% after prophylactic anticoagulation was started. RESULTS: No statistically significant differences were found in the frequency of intracranial bleeding progression comparing the different time groups (early 12.9% vs. intermediate 11.1% vs. late 17.6%; adj. p = 0.13). In patients with VTE chemoprophylaxis, no thromboembolic events were recorded. Male gender, age, head AIS and subarachnoidal hemorrhage were identified as independent risk factors associated with intracranial hematoma progression. CONCLUSION: The early administration of VTE chemoprophylaxis within 24 h after admission in patients with severe TBI did not increase the risk of intracranial bleeding progression.

Influence of concentration and preparation of platelet rich fibrin on human bone marrow mononuclear cells (in vitro).

Large bone defects have always been a big challenge. The use of bone marrow mononuclear cells (BMCs) combined with an osteoconductive scaffold has been proved a good alternative for the treatment of large bone defects. Another autologous source for tissue engineering is platelet rich fibrin (PRF). PRF is a blood concentrate system obtained through a one-step centrifugation. The generated 3D matrix of the PRF clot serves as a reservoir of growth factors. Those growth factors might support the regenerative response of BMC, and therefore the effect of PRF, centrifuged with either high medium (208 g) or low (60 g) relative centrifugation force (RCF) on BMCs was evaluated in vitro in the present study. The two PRF matrices obtained were initially characterized and compared to human serum. Significantly increased concentrations of insulin-like growth factor (IGF), soluble intercellular adhesion molecule-1 (sICAM1) and transforming growth factor (TGF)-ß were found in PRF compared to human serum whereas VEGF concentration was not significantly altered. A dose-response study revealed no further activation of BMC's metabolic activity, if concentration of both PRF matrices exceeded 10% (v/v). Effect of both PRF preparations [10%] on BMC was analyzed after 2, 7, and 14 days in comparison to human serum [10%]. Metabolic activity of BMC increased significantly in all groups on day 14. Furthermore, gene expression of matrix metalloproteinases (MMP)-2, -7, and -9 was significantly stimulated in BMC cultivated with the respective PRF matrices compared to human serum. Apoptotic activity of BMC incubated with PRF was not altered compared to BMC cultivated with serum. In conclusion, PRF could be used as a growth factor delivery system of autologous or allogeneic source with the capability of stimulating cells such as BMC.

Treatment of infection following intramedullary nailing of tibial shaft fractures-results of the ORS/ISFR expert group survey.

OBJECTIVE: The lack of universally accepted treatment principles and protocols to manage infected intramedullary (IM) nails following tibial fractures continues to challenge us, eliciting a demand for clear guidelines. Our response to this problem was to create an ORS/ISFR taskforce to identify potential solutions and trends based on published evidence and practices globally. MATERIALS AND METHODS: A questionnaire of reported treatment methods was created based on a published meta-analysis on the topic. Treatment methods were divided in two groups: A (retained nail) and B (nail removed). Experts scored the questionnaire items on a scale of 1-4 twice, before and after revealing the success rates for each stage of infection. Inter- and intra-observer variability analysis among experts' personal scores and between experts' scores was performed. An agreement mean and correlation degree between experts' scores was calculated. Finally, a success rate report between groups was performed. RESULTS: Experts underestimated success rate of an individual treatment method compared to published data. The mean difference between experts' scores and published results was + 26.3 ± 46 percentage points. Inter-observer agreement mean was poor (< 0.2) for both rounds. Intra-observer agreement mean across different treatment methods showed a wide variability (18.3 to 64.8%). Experts agree more with published results for nail removal on stage 2 and 3 infections. CONCLUSIONS: Experts' and published data strongly agree to retain the implant for stage 1 infections. A more aggressive approach (nail removal) favoured for infection stages 2 and 3. However, literature supports both treatment strategies. EVIDENCE: Clinical Question.

[Costs and proceeds from patients admitted via the emergency room with mild craniocerebral trauma]. / Kosten und Erlöse von über den Schockraum eingelieferten Patienten mit leichtem Schädel-Hirn-Trauma.

The introduction of the diagnosis-related groups (DRG) in 2003 radically changed the billing of the treatment costs. From the very beginning, trauma surgeons questioned whether the introduction of the DRG could have a negative impact on the care of the severely injured. "Trauma centers in need" was the big catchword warning against shortfalls at trauma centers due to the billing via DRG. This situation was confirmed in the first publications after introduction of the DRG, showing a clearly deficient level of care of polytrauma cases. Over the years, adjustments have led to an improvement in the remuneration for polytraumatized patients. In the emergency room, polytrauma is not always the final diagnosis. A considerable proportion of patients are only slightly injured, but must be admitted via the emergency room due to the circumstances of the accident or suspected diagnosis at the scene of the accident to exclude life-threatening injuries. In this study, patients with the billing diagnosis of mild craniocerebral trauma were selected as an example. The proportion of these patients was 22% during the period of observation in 2017. For these patients, the proportional costs during treatment were calculated. It could be shown that 60.36% of the costs during a 2­day treatment of these patients were incurred in the emergency room. Costs for material and personnel could not be considered. Despite not including these expenses, the costs were never covered for any of these patients. For patients with slight injuries after trauma management in the emergency room, the present adjustments to the DRG system by increasing the basic case value seem to be insufficient. Additional remuneration for these patients seems absolutely justified to further ensure adequate quality of care.