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FIBTEM provides early prediction of massive transfusion in trauma
Herbert Sch?chl, Bryan Cotton, Kenji Inaba, Ulrike Nienaber, Henrik Fischer, Wolfgang Voelckel, Cristina Solomon
Critical Care , 2011, DOI: 10.1186/cc10539
Abstract: This retrospective study included patients admitted to the AUVA Trauma Centre, Salzburg, Austria, with an injury severity score ≥16, from whom blood samples were taken immediately upon admission to the emergency room (ER). ROTEM? analyses (extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor and the platelet inhibitor cytochalasin D (FIBTEM) tests) were performed. We divided patients into two groups: massive transfusion (MT, those who received ≥10 units red blood cell concentrate within 24 hours of admission) and non-MT (those who received 0 to 9 units).Of 323 patients included in this study (78.9% male; median age 44 years), 78 were included in the MT group and 245 in the non-MT group. The median injury severity score upon admission to the ER was significantly higher in the MT group than in the non-MT group (42 vs 27, P < 0.0001). EXTEM and INTEM clotting time and clot formation time were significantly prolonged and maximum clot firmness (MCF) was significantly lower in the MT group versus the non-MT group (P < 0.0001 for all comparisons). Of patients admitted with FIBTEM MCF 0 to 3 mm, 85% received MT. The best predictive values for MT were provided by hemoglobin and Quick value (area under receiver operating curve: 0.87 for both parameters). Similarly high predictive values were observed for FIBTEM MCF (0.84) and FIBTEM A10 (clot amplitude at 10 minutes; 0.83).FIBTEM A10 and FIBTEM MCF provided similar predictive values for massive transfusion in trauma patients to the most predictive laboratory parameters. Prospective studies are needed to confirm these findings.Trauma-induced coagulopathy (TIC) affects 25 to 34% of all trauma patients upon emergency room (ER) admission and can be observed even before fluid resuscitation [1-3]. TIC increases the risk of massive transfusion (MT) which is associated with mortality rates up to 54% [1,4-6].MT
Early and individualized goal-directed therapy for trauma-induced coagulopathy
Herbert Sch?chl, Marc Maegele, Cristina Solomon, Klaus G?rlinger, Wolfgang Voelckel
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2012, DOI: 10.1186/1757-7241-20-15
Abstract: Major brain injury and uncontrolled blood loss remain the primary causes of early trauma-related mortality [1-3]. One-quarter to one-third of trauma patients exhibit trauma-induced coagulopathy (TIC) [4,5], which is associated with increased rates of massive transfusion (MT) and multiple organ failure (MOF), prolonged intensive care unit and hospital stays, and a four-fold increase in mortality [4]. Most patients with coagulopathy also have uncontrolled bleeding, and early diagnosis of the underlying coagulation disorder is paramount for effective treatment.One major challenge in treating severely bleeding trauma patients is to determine whether the blood loss is attributable to surgical causes or coagulopathy. If the patient is coagulopathic, it is paramount to characterize the cause of the coagulopathy and whether thrombin generation is impaired or clot quality or stability is diminished. Recent data suggest that whole-blood viscoelastic tests, such as thromboelastometry (ROTEM?, Tem International GmbH, Munich, Germany) or thrombelastography (TEG?, Haemonetics Corp., Braintree, MA, USA) portray trauma induced coagulopathy (TIC) more accurately and substantially faster than standard coagulation tests [6-8]. There is increasing evidence that these coagulation monitoring devices are helpful in guiding coagulation therapy for heavily bleeding trauma patients according to their actual needs [9].The intention of this review is to examine the concept of individualized, early, goal-directed therapy for TIC, using viscoelastic tests and targeted coagulation therapy. In addition, the AUVA Trauma Hospital algorithm for managing TIC is presented.Fast, reliable diagnosis and characterization of TIC is important. Standard coagulation tests (e.g. prothrombin time [PT], international normalized ratio [INR], prothrombin time index [PTI] and activated partial thromboplastin time [aPTT]) fail to accurately describe the complex nature of TIC for several reasons [4,5]. In vivo coagula
Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM?)-guided administration of fibrinogen concentrate and prothrombin complex concentrate
Herbert Sch?chl, Ulrike Nienaber, Georg Hofer, Wolfgang Voelckel, Csilla Jambor, Gisela Scharbert, Sibylle Kozek-Langenecker, Cristina Solomon
Critical Care , 2010, DOI: 10.1186/cc8948
Abstract: This retrospective analysis included trauma patients who received ≥ 5 units of red blood cell concentrate within 24 hours. Coagulation management was guided by thromboelastometry (ROTEM?). Fibrinogen concentrate was given as first-line haemostatic therapy when maximum clot firmness (MCF) measured by FibTEM (fibrin-based test) was <10 mm. Prothrombin complex concentrate (PCC) was given in case of recent coumarin intake or clotting time measured by extrinsic activation test (EXTEM) >1.5 times normal. Lack of improvement in EXTEM MCF after fibrinogen concentrate administration was an indication for platelet concentrate. The observed mortality was compared with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score.Of 131 patients included, 128 received fibrinogen concentrate as first-line therapy, 98 additionally received PCC, while 3 patients with recent coumarin intake received only PCC. Twelve patients received FFP and 29 received platelet concentrate. The observed mortality was 24.4%, lower than the TRISS mortality of 33.7% (P = 0.032) and the RISC mortality of 28.7% (P > 0.05). After excluding 17 patients with traumatic brain injury, the difference in mortality was 14% observed versus 27.8% predicted by TRISS (P = 0.0018) and 24.3% predicted by RISC (P = 0.014).ROTEM?-guided haemostatic therapy, with fibrinogen concentrate as first-line haemostatic therapy and additional PCC, was goal-directed and fast. A favourable survival rate was observed. Prospective, randomized trials to investigate this therapeutic alternative further appear warranted.Coagulopathy has been shown to be present in approximately 25 to 35% of all trauma patients on admission to the emergency room (ER) [1,2]. This represents a serious problem for major trauma patients and accounts for 40% of all trauma-related deaths [3]. Coagulopathy forces a strategy of early and rapid haemostatic treatment to prevent exsanguination. F
Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy
Herbert Sch?chl, Ulrike Nienaber, Marc Maegele, Gerald Hochleitner, Florian Primavesi, Beatrice Steitz, Christian Arndt, Alexander Hanke, Wolfgang Voelckel, Cristina Solomon
Critical Care , 2011, DOI: 10.1186/cc10078
Abstract: This retrospective analysis compared patients from the Salzburg Trauma Centre (Salzburg, Austria) treated with fibrinogen concentrate and/or PCC, but no FFP (fibrinogen-PCC group, n = 80), and patients from the TraumaRegister DGU receiving ≥ 2 units of FFP, but no fibrinogen concentrate/PCC (FFP group, n = 601). Inclusion criteria were: age 18-70 years, base deficit at admission ≥2 mmol/L, injury severity score (ISS) ≥16, abbreviated injury scale for thorax and/or abdomen and/or extremity ≥3, and for head/neck < 5.For haemostatic therapy in the emergency room and during surgery, the FFP group (ISS 35.5 ± 10.5) received a median of 6 units of FFP (range: 2, 51), while the fibrinogen-PCC group (ISS 35.2 ± 12.5) received medians of 6 g of fibrinogen concentrate (range: 0, 15) and 1200 U of PCC (range: 0, 6600). RBC transfusion was avoided in 29% of patients in the fibrinogen-PCC group compared with only 3% in the FFP group (P< 0.001). Transfusion of platelet concentrate was avoided in 91% of patients in the fibrinogen-PCC group, compared with 56% in the FFP group (P< 0.001). Mortality was comparable between groups: 7.5% in the fibrinogen-PCC group and 10.0% in the FFP group (P = 0.69).TEM-guided haemostatic therapy with fibrinogen concentrate and PCC reduced the exposure of trauma patients to allogeneic blood products.In patients with severe trauma, coagulopathy represents a frequent cause of death [1,2]. Prompt haemostatic intervention is necessary to prevent and correct life-threatening bleeding. Standard coagulation therapy consists of fresh frozen plasma (FFP), platelet concentrate and, in some countries, cryoprecipitate [3,4]. One approach proposed for preventing exsanguination has been to treat patients with a fixed ratio of FFP to red blood cells (RBC), but the optimal value of this ratio is still under debate [5-8]. It has been recently suggested that the time to intervention may also be an important determinant of patient outcomes [9,10].Our group has been exp
Vasopressin improves survival in a porcine model of abdominal vascular injury
Karl H Stadlbauer, Horst G Wagner-Berger, Anette C Krismer, Wolfgang G Voelckel, Alfred Konigsrainer, Karl H Lindner, Volker Wenzel
Critical Care , 2007, DOI: 10.1186/cc5977
Abstract: During general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rate had declined progressively, experimental therapy was initiated. At that point, animals were randomly assigned to receive vasopressin (0.4 U/kg; n = 7), fluid resuscitation (25 ml/kg lactated Ringer's and 25 ml/kg 3% gelatine solution; n = 7), or a single injection of saline placebo (n = 5). Vasopressin-treated animals were then given a continuous infusion of 0.08 U/kg per min vasopressin, whereas the remaining two groups received saline placebo at an equal rate of infusion. After 30 min of experimental therapy bleeding was controlled by surgical intervention, and further fluid resuscitation was performed. Thereafter, the animals were observed for an additional hour.After 68 ± 19 min (mean ± standard deviation) of uncontrolled bleeding, experimental therapy was initiated; at that time total blood loss and mean arterial blood pressure were similar between groups (not significant). Mean arterial blood pressure increased in both vasopressin-treated and fluid-resuscitated animals from about 15 mmHg to about 55 mmHg within 5 min, but afterward it decreased more rapidly in the fluid resuscitation group; mean arterial blood pressure in the placebo group never increased. Seven out of seven vasopressin-treated animals survived, whereas six out of seven fluid-resuscitated and five out of five placebo pigs died before surgical intervention was initiated (P < 0.0001).Vasopressin, but not fluid resuscitation or saline placebo, ensured short-term survival in this vascular injury model with uncontrolled haemorrhagic shock in sedated pigs.For haemodynamic stabilization of critically injured patients with uncontrolled haemorrhagic shock, current advanced trauma life support guidelines recommend infusion of crystalloid or colloid solutions. Intere
On the Modal and Non-Modal Model Reduction of Metallic Structures with Variable Boundary Conditions  [PDF]
Wolfgang Witteveen
World Journal of Mechanics (WJM) , 2012, DOI: 10.4236/wjm.2012.26037
Abstract: Vibration mode based model reduction methods like Component Mode Synthesis (CMS) will be compared to methods coming from control engineering, namely moment matching (MM) and balanced truncation (BT). Conclusions based on the theory together with a numerical demonstration will be presented. The key issues on which the paper is focused are the reduction of metallic structures, the sensitivity of the reduced model to varying boundary conditions, full system response, accurate statics and the possibility to determine “a priori” the number of needed modes (trial vectors). These are important topics for the use of reduction methods in general and in particular for the implementation of FE models in multi body system dynamics where model reduction is widely used. The intention of this paper is to give insight into the methods nature and to clarify the strengths and limitations of the three methods. It turns out, that in the considered framework CMS delivers the best results together with a clear strategy for an “a priori” selection of the modes (trial vectors).
Sequences and Limits  [PDF]
Wolfgang Mueckenheim
Advances in Pure Mathematics (APM) , 2015, DOI: 10.4236/apm.2015.52007
Abstract: It is widely held that irrational numbers can be represented by infinite digit-sequences. We will show that this is not possible. A digit sequence is only an abbreviated notation for an infinite sequence of rational partial sums. As limits of sequences, irrational numbers are incommensurable with any grid of decimal fractions.
Human Dimensions Approach towards Integrating Sustainable Transportation and Urban Planning Policies: A Decision Support System (DSS) Based on Stated Preferences Data  [PDF]
Wolfgang Rid
Theoretical Economics Letters (TEL) , 2017, DOI: 10.4236/tel.2017.74059
Abstract: While a lot of progress has been made in Germany to reduce CO2 emissions in the past years in almost all sectors of economy, however, the sector of transportation shows increasing CO2 emissions in the same period of time. Likewise, sustainability objectives of German land use policies have not been met so far, especially with regard of the continuously high rate of greenfield land used up for new housing development. In this paper, it is argued that environmental issues of both sectors have to be addressed by integrating urban housing development and transportation infrastructure planning policies. The paper reports on a stated preferences survey among house buyers in Germany, using a discrete choice approach, where parameters of sustainable urban design and sustainable transport are both integrated into one model. Building on concepts of behavioral economics, preferences are elicited for sub-samples of different “environmental awareness”. Results show differences in tastes for higher building densities to reduce land consumption as well as differences in tastes for transport infrastructure development and frequency of public transport parameters. In addition, a decision support system is developed to analyze the impact of individual parameters on choosing one alternative over the other. Form this, conclusions on potential market shares for sustainable housing and transport development are drawn and recommendations are given to implement integrated urban design and transportation infrastructure policies.
Within and between Whorls: Comparative Transcriptional Profiling of Aquilegia and Arabidopsis
Claudia Voelckel,Justin O. Borevitz,Elena M. Kramer,Scott A. Hodges
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009735
Abstract: The genus Aquilegia is an emerging model system in plant evolutionary biology predominantly because of its wide variation in floral traits and associated floral ecology. The anatomy of the Aquilegia flower is also very distinct. There are two whorls of petaloid organs, the outer whorl of sepals and the second whorl of petals that form nectar spurs, as well as a recently evolved fifth whorl of staminodia inserted between stamens and carpels.
Cutoffs and k-mers: implications from a transcriptome study in allopolyploid plants
Nicole Gruenheit, Oliver Deusch, Christian Esser, Matthias Becker, Claudia Voelckel, Peter Lockhart
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-92
Abstract: Here we report a successful strategy for the assembly of two transcriptomes made using 75 bp Illumina reads from Pachycladon fastigiatum and Pachycladon cheesemanii. Both are allopolyploid plant species (2n = 20) that originated in the New Zealand Alps about 0.8 million years ago. In a systematic analysis of 19 different coverage cutoffs and 20 different k-mer sizes we showed that i) none of the genes could be assembled across all of the parameter space ii) assembly of each gene required an optimal set of parameter values and iii) these parameter values could be explained in part by different gene expression levels and different degrees of similarity between genes.To obtain optimal transcriptome assemblies for allopolyploid plants, k-mer size and k-mer coverage need to be considered simultaneously across a broad parameter space. This is important for assembling a maximum number of full length ESTs and for avoiding chimeric assemblies of homeologous and paralogous gene copies.Whole genome duplication (WGD) associated with autopolyploidy and allopolyploidy has been a recurrent and prevalent phenomenon in plant evolution, linked to species diversification and species radiation [1-3]. Difficulty in studying the genomic complexity that WGD entails has slowed progress in understanding the genetic basis of adaptation and speciation in non-model systems [4]. Recently, with the advent of high throughput sequencing, many researchers have turned to analyses of transcriptomes to advance knowledge of evolutionary relationships, and to identify traits and candidate genes potentially important in adaptive diversification. One current international initiative seeks to assemble the transcriptomes of 1000 plant species (http://www.onekp.com/ webcite).Transcriptome assembly has "many informatics challenges" [5] including markedly different expression levels of genes and homeologues, as well as potentially high levels of sequence similarity between duplicated gene copies (for homeologu
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