Attitude toward second opinions in Germany - a survey of the general population.

BACKGROUND: Second medical opinions (SOs) can assist patients in making informed treatment decisions and improve the understanding of their diagnosis. In Germany, there are different approaches to obtain a structured SO procedure: SO programs by health insurers and SOs according to the SO Directive. Through a direct survey of the population, we aimed to assess how structured SOs should be provided to fulfil patients' needs. METHODS: A stratified sample of 9990 adults (≥18 years) living in the federal states of Berlin and Brandenburg (Germany) were initially contacted by post in April and sent a reminder in May 2020. The survey results were analyzed descriptively. RESULTS: Among 1349 participants (response rate 14%), 56% were female and the median age was 58 years (interquartile range (IQR) 44-69). Participants wanted to be informed directly and personally about the possibility of obtaining an SO (89%; 1201/1349). They preferred to be informed by their physician (93%; 1249/1349). A majority of participants would consider it important to obtain an SO for oncological indications (78%; 1049/1349). Only a subset of the participants would seek an SO via their health insurer or via an online portal (43%; 577/1349 and 16%; 221/1349). A personally delivered SO was the preferred route of SO delivery, as 97% (1305/1349) would (tend to) consider this way of obtaining an SO. Participants were asked to imagine having moderate knee pain for years, resulting in a treatment recommendation for knee joint replacement. They were requested to rate potential qualification criteria for a physician providing the SO. The criteria rated to be most important were experience with the recommended diagnosis/treatment (criterion (very) important for 93%; 1257/1349) and knowledge of the current state of research (criterion (very) important for 86%; 1158/1349). Participants were willing to travel 60 min (median; IQR 60-120) and wait 4 weeks (median; IQR 2-4) for their SO in the hypothetical case of knee pain. CONCLUSION: In general, SOs were viewed positively. We found that participants have clear preferences regarding SOs. We propose that these preferences should be taken into account in the future design and development of SO programs.

Variants in FIX propeptide associated with vitamin K antagonist hypersensitivity: functional analysis and additional data confirming the common founder mutations.

One of the most common and unwanted side effects during oral anticoagulant therapy (OAT) is bleeding complications. In rare cases, vitamin K antagonist (VKA)-related bleeding events are associated with mutations affecting the F9 propeptide at amino acid position 37 due to a substitution of alanine to either valine or threonine. Based on our actual cohort of 18 patients, we update the knowledge on this rare phenotype and its origin. A founder mutation for both variants was reconfirmed by haplotype analysis of intronic and extragenic short tandem repeat (STR) polymorphisms with a higher prevalence in Switzerland than in other regions of Europe. Screening of healthy individuals for the presence of these F9 gene mutations did not identify any of these variants, thus proving the rare occurrence of this genotype. Furthermore, both variants were expressed in vitro and warfarin dose responses were studied. Our warfarin dose response analysis confirmed higher sensitivity of both variants to warfarin with the effect being more apparent for Ala37Thr. Thus, although F9 propeptide mutation-associated hypersensitivity to VKA is a rare phenomenon, awareness towards this bleeding phenotype is important to identify patients at risk.

[Viscoelasticity-based treatment of bleeding injuries]. / Viskoelastizitätsbasierte Therapie beim blutenden Schwerverletzten.

Uncontrolled bleeding is the leading preventable cause of death in patients with multiple injuries. Currently, trauma-induced coagulopathy is seen as an independent disease entity influencing survival. Severely bleeding trauma patients are often treated with classical blood products in predefined ratios (damage control resuscitation). Viscoelasticity-based and target-oriented approaches could possibly be given priority. Viscoelasticity-based diagnostics and therapy enable the qualitative investigation of whole blood and provide therapeutically usable information on initiation, dynamics and sustainability of thrombus formation. Due to the ease of handling and timely results this lends itself as a point-of-care procedure. This article presents the clinical issues with using viscoelastic procedures and current expert recommendations taking the literature into consideration.

Discovery, Structure Elucidation, and Biological Characterization of Nannocystin†A, a Macrocyclic Myxobacterial Metabolite with Potent Antiproliferative Properties.

Microbial natural products are a rich source of bioactive molecules to serve as drug leads and/or biological tools. We investigated a little-explored myxobacterial genus, Nannocystis sp., and discovered a novel 21-membered macrocyclic scaffold that is composed of a tripeptide and a polyketide part with an epoxyamide moiety. The relative and absolute configurations of the nine stereocenters was determined by NMR spectroscopy, molecular dynamics calculations, chemical degradation, and X-ray crystallography. The compound, named nannocystin A (1), was found to inhibit cell proliferation at low nanomolar concentrations through the early induction of apoptosis. The mode of action of 1 could not be matched to that of standard drugs by transcriptional profiling and biochemical experiments. An initial investigation of the structure-activity relationship based on seven analogues demonstrated the importance of the epoxide moiety for high activity.

[Overdosing of direct oral anticoagulants]. / Überdosierung von direkten oralen Antikoagulanzien.

BACKGROUND: Direct oral anticoagulants (DOAC) are increasingly used for prophylaxis and treatment of thromboembolic events. Incorrectly dosed DOAC treatment is associated with excess mortality. PURPOSE: This article aims at raising awareness of DOAC overdosing and its causes as well as presenting a diagnostic and therapeutic work-up. MATERIAL AND METHODS: Based on a case presentation, a structured review of the current literature on DOAC overdosing was performed and treatment recommendations were extracted. RESULTS: In addition to wittingly or unwittingly increased DOAC intake, common causes of overdose are inadequate dose adjustment for concomitant medication or comorbidities. Global coagulation testing should be supplemented with DOAC-specific testing. Severe bleeding and the need for invasive diagnostics or urgent surgery represent indications for treating DOAC overdoses. Based on the cause of an DOAC overdose, active charcoal, endoscopic pill rescue, antagonization with idarucizumab or andexanet alfa and the targeted substitution of coagulation factors represent treatment options. CONCLUSION: The sensitization of clinicians is important to ensure a timely diagnosis and adequate treatment of DOAC overdosing. This report provides an overview of current knowledge on diagnostics and treatment; however, further studies are necessary to improve the existing algorithms.

Evaluation of Prehospital Undertriage in Relation to Trauma Team Activation-Results from a Prospective Study in 12 Level one German Trauma Centers.

Background/Objective: This prospective, multicenter observational cohort study was carried out in 12 trauma centers in Germany and Switzerland. Its purpose was to evaluate the rate of undertriage, as well as potential consequences, and relate these with different Trauma Team Activation Protocols (TTA-Protocols), as this has not been done before in Germany. Methods: Each trauma center collected the data during a three-month period between December 2019 and February 2021. All 12 participating hospitals are certified as supra-regional trauma centers. Here, we report a subgroup analysis of undertriaged patients. Those included in the study were all consecutive adult patients (age ≥ 18 years) with acute trauma admitted to the emergency department of one of the participating hospitals by the prehospital emergency medical service (EMS) within 6 h after trauma. The data contained information on age, sex, trauma mechanism, pre- and in-hospital physiology, emergency interventions, emergency surgical interventions, intensive care unit (ICU) stay, and death within 48 h. Trauma team activation (TTA) was initiated by the emergency medical services. This should follow the national guidelines for severe trauma using established field triage criteria. We used various denominators, such as ISS, and criteria for the appropriateness of TTA to evaluate the undertriage in four groups. Results: This study included a total of 3754 patients. The average injury severity score was 5.1 points, and 7.0% of cases (n = 261) presented with an injury severity score (ISS) of 16+. TTA was initiated for a total of 974 (26%) patients. In group 1, we evaluated how successful the actual practice in the EMS was in identifying patients with ISS 16+. The undertriage rate was 15.3%, but mortality was lower in the undertriage cohort compared to those with a TTA (5% vs. 10%). In group 2, we evaluated the actual practice of EMS in terms of identifying patients meeting the appropriateness of TTA criteria; this showed a higher undertriage rate of 35.9%, but as seen in group 1, the mortality was lower (5.9% vs. 3.3%). In group 3, we showed that, if the EMS were to strictly follow guideline criteria, the rate of undertriage would be even higher (26.2%) regarding ISS 16+. Using the appropriateness of TTA criteria to define the gold standard for TTA (group 4), 764 cases (20.4%) fulfilled at least one condition for retrospective definition of TTA requirement. Conclusions: Regarding ISS 16+, the rate of undertriage in actual practice was 15.3%, but those patients did not have a higher mortality.

Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening.

Kappa-opioid (KOP) receptor agonists exhibit analgesic effects without activating reward pathways. In the search for nonaddictive opioid therapeutics and novel chemical tools to study physiological functions regulated by the KOP receptor, we screened in silico its recently released inactive crystal structure. A selective novel KOP receptor agonist emerged as a notable result and is proposed as a new chemotype for the study of the KOP receptor in the etiology of drug addiction, depression, and/or pain.

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.

Behavioral effects and central nervous system levels of the broadly available κ-agonist hallucinogen salvinorin A are affected by P-glycoprotein modulation in vivo.

Active blood-brain barrier mechanisms, such as the major efflux transporter P-glycoprotein (mdr1), modulate the in vivo/central nervous system (CNS) effects of many pharmacological agents, whether they are used for nonmedical reasons or in pharmacotherapy. The powerful, widely available hallucinogen salvinorin A (from the plant Salvia divinorum) is a high-efficacy, selective κ-opioid agonist and displays fast-onset behavioral effects (e.g., within 1 min of administration) and relatively short duration of action. In vitro studies suggest that salvinorin A may be a P-glycoprotein substrate; thus, the functional status of P-glycoprotein may influence the behavioral effects of salvinorin A or its residence in CNS after parenteral administration. We therefore studied whether a competing P-glycoprotein substrate (the clinically available agent loperamide; 0.032-0.32 mg/kg) or a selective P-glycoprotein blocker, tariquidar (0.32-3.2 mg/kg) could enhance unconditioned behavioral effects (ptosis and facial relaxation, known to be caused by κ-agonists in nonhuman primates) of salvinorin A, as well as its entry and residence in the CNS, as measured by cerebrospinal fluid sampling. Pretreatment with either loperamide or tariquidar dose-dependently enhanced salvinorin A-induced ptosis, but not facial relaxation. In a control study, loperamide and tariquidar were inactive when given as a pretreatment to ((+)-(5α,7α,8ß)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U69,593), a κ-agonist known to be a very poor P-glycoprotein substrate. Furthermore, pretreatment with tariquidar (3.2 mg/kg) also enhanced peak levels of salvinorin A in cerebrospinal fluid after intravenous administration. These are the first studies in vivo showing the sensitivity of salvinorin A effects to modulation by the P-glycoprotein transporter, a major functional component of the blood-brain barrier.

Global Coagulation Testing in Acute Care Medicine: Back to Bedside?

OBJECTIVES: Detailed and decisive information about the patients' coagulation status is important in various emergency situations. Conventional global coagulation testing strategies are often used to provide a quick overview, but several limitations particularly in the trauma setting are well described. With the introduction of direct oral anticoagulations (DOACs), a milestone for several disease entities resulting in overall improved outcomes could be reached, but at the same time providing new diagnostic challenges for the emergency situation. DESIGN: As an alternative to conventional coagulation tests, there is increasing clinical and scientific interest in the use of early whole blood strategies to provide goal-directed coagulation therapies (GDCT) and hemostatic control in critically ill patients. Viscoelastic hemostatic assays (VHAs) were therefore introduced to several clinical applications and may provide as a bedside point-of-care method for faster information on the underlying hemostatic deficiency. CONCLUSION: The use of VHA-based algorithms to guide hemostatic control in emergency situations now found its way to several international guidelines for patients at risk of bleeding. With this qualitative review, we would like to focus on VHA-based GDCT and review the current evidence for its use, advantages, and challenges in the two different clinical scenarios of trauma and intracerebral bleeding/stroke management.

[Future implications of navigation in total knee arthroplasty]. / Gibt es noch Gründe für die Navigation in der Knieendoprothetik?

BACKGROUND: After more than two decades of experience with computer-assisted knee arthroplasty, extensive experience and study data are available, allowing a profound evaluation. Undoubtedly, computer-assisted knee arthroplasty has been proven to achieve excellent results for implant positioning and long-leg axis reconstruction. Thus, computer-assisted knee arthroplasty represents the current gold standard to avoid unintended malpositioning of total knee components for neutrally aligned implants and individualized implant alignment (kinematic alignment, adjusted mechanical alignment, and others). Previous studies could not show significant differences in functional outcomes and patient satisfaction. However, recent meta-analyses showed relevant advantages of computer-assisted knee arthroplasty. These results could be based on further developments in software-assisted soft tissue balancing and more sensitive evaluation methods of follow-up examinations. LONG-TERM OUTCOME: Further, international registries show advantages of computer-assisted knee arthroplasty regarding long-term outcomes. In particular, the Australian arthroplasty registry describes a significantly lower revision rate due to aseptic loosening/osteolysis in the computer-assisted knee arthroplasty group, analyzing a period of up to 17 years. These positive effects can already be proven six months following surgery. FUTURE PROSPECTS: However, despite demonstrated benefits, computer-assisted knee arthroplasty has not yet become established in daily routine, and wide regional variations in its use are observed. Newer developments such as robotic-assisted knee arthroplasty, primarily based on navigation techniques, are currently being heavily promoted. However, this new technology must justify its enormous additional costs and prove its advantages compared to computer-assisted knee arthroplasty. In the backdrop of the development of computer-assisted knee arthroplasty, this might be a difficult task.

Plasmatic coagulation profile after major traumatic injury: a prospective observational study.

PURPOSE: Uncontrolled hemorrhage is still the major cause of preventable death after trauma and is aggravated by trauma-induced coagulopathy (TIC). The underlying pathophysiology of TIC is still elusive, but several key effectors such as the thrombin-generation capacity, the protein C (PC) pathway, and the fibrinolytic activity could be identified. The aim of this prospective observational study was to investigate plasma coagulation markers attributed to reflect the course of TIC and to identify the mechanisms being responsible for the coagulopathy after major trauma. METHODS: Seventy-three consecutive patients after major trauma and admission to a level-1-trauma unit were included to the study. During early trauma management, extended coagulation testing including the measurement of circulating thrombin markers and activated PC (APC) was performed and correlated with standard shock parameters and the patients' clinical course and outcome. RESULTS: In contrast to standard coagulation parameters, thrombin markers and APC were found to be increased in correlation with injury severity. Even in patients with lower impact mechanisms, early endogenous accumulation of thrombin markers and APC (ISS < 16: 0.5 ng/ml; ISS ≥ 16-26: 1.5 ng/ml; ISS > 26: 4.1 ng/ml) were observed. Furthermore, APC showed ISS- and injury-dependent patterns while ROC curve analysis revealed that especially APC plasma levels were predictive for coagulopathy and general patient outcome. CONCLUSION: Increased levels of APC and thrombin markers in patients after major trauma were positively correlated with injury severity. APC showed an ISS- and injury-dependent kinetic and might serve as candidate biomarker to identify patients at risk for developing TIC.

Is ROTEM Diagnostic in Trauma Care Associated with Lower Mortality Rates in Bleeding Patients?-A Retrospective Analysis of 7461 Patients Derived from the TraumaRegister DGU®.

INTRODUCTION: Death from uncontrolled trauma haemorrhage and subsequent trauma-induced coagulopathy (TIC) is potentially preventable. Point-of-care devices such as rotational thromboelastometry (ROTEM®) are advocated to detect haemostatic derangements more rapidly than conventional laboratory diagnostics. Regarding reductions in RBC transfusion, the use of ROTEM has been described as being efficient and associated with positive outcomes in several studies. OBJECTIVE: The effect of ROTEM use was assessed on three different outcome variables: (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality in severely injured patients. METHODS AND MATERIAL: A retrospective analysis of a large data set of severely injured patients collected into the TraumaRegister DGU® between 2009 and 2016 was conducted. The data of 7461 patients corresponded to the inclusion criteria and were subdivided into ROTEM-using and ROTEM-non-using groups. Both groups were analysed regarding (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality. RESULTS: A lower mortality rate in ROTEM-using groups was observed (p = 0.043). Furthermore, more patients received haemostatic medication when ROTEM was used. In ROTEM-using groups, there was a statistically relevant higher application of massive transfusion. CONCLUSIONS: In this retrospective study, the use of ROTEM was associated with reduced mortality and an increased application of haemostatics and RBC transfusions. Prospective evidence is needed for further evidence-based recommendations.

Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A.

As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan-containing natural products.

Plasmatic and cell-based enhancement by microparticles originated from platelets and endothelial cells under simulated in vitro conditions of a dilutional coagulopathy.

BACKGROUND: Aggressive fluid management and other external factors may lead to hypothermia, acidosis and hemodilution (defined as Lethal Triad, LT) contributing to a trauma-induced coagulopathy (TIC) that worsens patients' outcomes. Procoagulant microparticles (MP) are crucial players at the interface of cellular and plasmatic coagulation. However, their functions remain largely unexplored. This study aimed to characterize effects of MP subtypes and concentrations on functional coagulation under in vitro simulated conditions. METHODS: Blood from eleven volunteers were collected to simulate in vitro conditions of hemodilution (HD) and LT, respectively. HD was induced by replacing a blood volume of 33% by crystalloids and for LT, samples were further processed by reducing the temperature to 32 °C and lowering the pH to 6.8. MP were obtained either from platelet concentrates (platelet-derived MP, PDMP) or from cell culture (ECV304 cells for endothelial-derived MP, EDMP) by targeted stimulation. After introducing MP to in vitro conditions, we measured their concentration-dependent effects (1.000, 10.000 and 15.000 MP/µl blood) on coagulation compared to whole blood (WB). For each condition, coagulation was characterized by flow cytometric platelet activation and by quantification of fibrin clot propagation using Thrombodynamics® technology. RESULTS: MP originated from platelets and endothelial cells affected blood coagulation in a concentration-dependent manner. Particularly, high PDMP quantities (10.000 and 15.000 PDMP/µl blood) significantly induced platelet activation and fibrin clot growth and size in HD conditions. In LT conditions as well, only high PDMP concentration induced platelet activation, clot growth and size. In contrast, EDMP did not induce platelet activation, but resulted in enhanced formation of spontaneous clots, irrespective of simulated condition. With increasing EDMP concentration, the time until the onset of spontaneous clotting decreased in both HD and LT conditions. DISCUSSION: The study demonstrates an essential role of MP within the coagulation process under simulated coagulopathic conditions. PDMP affected platelets promoting clot formation likely by providing a surface enlargement. EDMP presumably affected clotting factors of the plasmatic coagulation resulting in an increased formation of spontaneous clots. CONCLUSION: Under simulated conditions of a dilutional coagulopathy, MP from different cellular origin indicate a divergent but both procoagulant mechanism within the coagulation process.

Improvement of Sec-dependent secretion of a heterologous model protein in Bacillus subtilis by saturation mutagenesis of the N-domain of the AmyE signal peptide.

Due to the lack of an outer membrane, Gram-positive bacteria (e.g., Bacillus species) are considered as promising host organisms for the secretory production of biotechnologically relevant heterologous proteins. However, the yields of the desired target proteins were often reported to be disappointingly low. Here, we used saturation mutagenesis of the positively charged N-domain (positions 2-7) of the signal peptide of the Bacillus subtilis alpha-amylase (AmyE) as a novel approach for the improvement of the secretion of a heterologous model protein, cutinase from Fusarium solani pisi, by the general secretory pathway of B. subtilis. Automated high-throughput screening of the resulting signal peptide libraries allowed for the identification of four single point mutations that resulted in significantly increased cutinase amounts, three of which surprisingly reduced the net charge of the N-domain from +3 to +2. Characterization of the effects of the identified mutations on protein synthesis and export kinetics by pulse-chase analyses indicates that an optimal balance between biosynthesis and the flow of the target protein through all stages of the B. subtilis secretion pathway is of crucial importance with respect to yield and quality of secreted heterologous proteins.

Do elderly trauma patients receive the required treatment? Epidemiology and outcome of geriatric trauma patients treated at different levels of trauma care.

PURPOSE: In an ageing society, geriatric trauma displays an increasing challenge in trauma care. Due to comorbidities and reduced physiologic reserves, these patients might benefit from an immediate specialised care. The current study aims to clarify the prevalence and outcome of geriatric trauma depending on the level of the primary trauma centre. METHODS: Data sets of 124,641 patients entered in the TR-DGU between 2009 and 2016 were included. Geriatric trauma was defined above 65 years and ISS ≥ 9. Analysing the prevalence, the age structure of all trauma cases registered in 2014 was compared to demographic data of the German Federal Statistical Office. Differences in injury pattern, in-hospital care and outcome between the primary levels of care were analysed. RESULTS: In comparison to their share of population, geriatric patients are highly overrepresented in the TR-DGU. Despite minor injury mechanisms, severe head injuries are common. A tendency to under-triage can be observed, as level II and III trauma centres receive a higher percentage of older patients. Nevertheless, there is no effect on the mortality. 10% of these patients require an early transfer to a higher levelled trauma centres mainly due to severe head and spine injuries. Surprisingly, pre-clinical available signs such as GCS or blood pressure were not altered in these patients. CONCLUSION: Patients above the age of 65 years represent a second group with high risk for traumatic injuries besides younger adults. Despite low-energy trauma mechanisms, these patients are prone to suffer from severe injuries, which require specialised care. Current admission practice appears adequate, as pre-clinical available symptoms did not correlate with injuries that demanded an early inter-hospital transfer. Specialised geriatric triage scores might further improve admission practice.

Microparticles profiling in trauma patients: high level of microparticles induce activation of platelets in vitro.

PURPOSE: Trauma-induced coagulopathy (TIC) is recognised as an own clinical entity which includes all components of haemostasis following rapidly tissue injury, hypoperfusion and shock. Microparticles (MP) are known to be released in large quantities from different cell types after trauma. The present study aimed to perform a phenotypic MP profiling after major trauma and to elucidate potential procoagulative function of MP under simulated conditions of lethal triad. METHODS: For MP isolation, 20 trauma patients (median ISS 24) were included. To produce a Standard MP Phenotype Profile after trauma, samples were pooled, extracted and concentrated by using an ultracentrifuge protocol. Specific cell surface markers were measured by flow cytometry. Our Standard MP Phenotype Profile was subsequently added in high and low concentration to an in vitro lethal triad assay, simulating coagulopathy via induced hypothermia, dilution and acidosis. A comprehensive analysis of coagulation function was performed. RESULTS: Within our Standard MP Phenotype Profile, PDMP (56%) were found as predominant phenotype followed by EDMP (33%) and MDMP (11%). EDMP characterized by CD144, CD62E and Annexin were determined most frequently but also EDMP expressing CD62P. In addition, tissue factor (TF) was expressed on all MP entities (EDMP 63%, PDMP 30%, MDMP 7%). Within our lethal triad simulation assay, the addition of low and high concentrated MP did not cause any significant alteration in standard coagulation assays, coagulation initiation, clot kinetics or stability. Addition of high concentrated MP increased platelet function and P-selectin expression significantly. CONCLUSION: Our data confirm the assumption that there is a characteristic MP phenotype pattern in trauma, which may alter haemostatic capacity at least in part mediated via augmenting in primary haemostasis resulting in an improved contribution of platelets to clot formation. There are indications that expression of selectins on MP surface is involved in this activation process, but this pathway needs to be investigated in more detail.

The influence of an injury prevention program on young road users: a German experience.

PURPOSE: Trauma remains a leading cause of mortality and morbidity in youth. The Prevent Alcohol and Risk Related Trauma in Youth (P.A.R.T.Y.) program is an injury prevention program. The aim of the study was to analyze the influence on risk-taking behaviors and risk awareness on young road users by a pre-post-questionnaire. METHODS: A pre-post intervention study was performed using a standardized questionnaire. The questionnaire contained three sections with different items (in total 22) to identify differences regarding students' risk behavior and risk awareness. Data were analyzed using the Wilcoxon signed-rank test with significance defined as p < 0.05. RESULTS: The study sample contains 193 students (age 14-17, 44% male). We found significant differences for asking if a student "fastens his/her helmet's chinstrap when driving a motorbike" (p = 0.001) and for the question "Do you wear a helmet when you go rollerblading" (p = 0.008). After attending the program, participants would decrease the use of a mobile phone while driving (p = 0.038) and the understanding of the risk "speeding" and "cycling without a helmet" significantly increased. CONCLUSIONS: The P.A.R.T.Y. program focuses on items like "use of helmet and mobile phones" and "alcohol/drug abuse". Evaluating the program helps to uncover vulnerabilities and to enhance important effects. Some of these items are addressed by the program, whereas some are not. It will be important to improve the program according to address topics that have not shown significant improvements, so that students learn more about the dangers and the right behavior in road traffic.

Changes in anaesthetic use for trauma patients in German HEMS - a retrospective study over a ten-year period.

BACKGROUND: Airway management and use of intravenous anaesthetics to facilitate tracheal intubation after major trauma remains controversial. Numerous agents are available and used for pre-hospital rapid-sequence induction (RSI). The aim was to investigate usage and potential changes in administration of intravenous anaesthetics for pre-hospital RSI in trauma patients over a ten-year period. METHODS: Based on a large helicopter emergency medical service (HEMS) database in Germany between 2006 and 2015, a total of 9720 HEMS missions after major trauma leading to RSI on scene were analysed. Administration practice of sedatives and opioids were investigated, while neuromuscular blocking agents were not documented in the database. RESULTS: With respect to administration of sedatives, independent from trauma mechanism and specific injury patterns the use of Etomidate decreased dramatically (52 to 6%) in favour of a more frequent use of Propofol (3 to 32%) and Ketamine (9 to 24%; all p < 0.001) from 2006 to 2015. The use of Benzodiazepines increased slightly, while the utilization rate of Barbiturates remained constant. In patients with Shock Index > 1 at initial contact, the administration rate of Etomidate dropped significantly as well. This decline was mainly substituted by Ketamine and particularly Propofol. In patients with GCS ≤ 8 upon initial contact, a similar distribution compared to the general trauma population could be observed. With respect to opioids, mainly Fentanyl has been administered for RSI in trauma patients (2006: 69,6% to 2015: 60.2%; p < 0.001), while the use of sufentanyl showed a significant increase (0.2 to 8.8%; p < 0.001). CONCLUSIONS: This large study analysed prehospital administration of anaesthetics in trauma patients, showing a substantial change from 2006 to 2015 despite the lack of any high-level evidence. Etomidate has shifted from the main sedative substance to virtual absence, indicating that the recommendation of an established national guideline was transferred into clinical practice, although based on weak evidence as well. The pre-hospital use of Propofol showed a particular increase. Fentanyl has been the main opioid drug for RSI in trauma, however Sufentanyl has become increasingly popular. The mechanisms and advantages of the different substances still have to be elucidated, especially in head injury and bleeding trauma.