Ultrafast Optical Control of Exciton Diffusion in WSe2/Graphene Heterostructures Revealed by Heterodyne Transient Grating Spectroscopy.

Using heterodyne transient grating spectroscopy, we observe a significant enhancement of exciton diffusion in a monolayer WSe2 stacked on graphene. The diffusion dynamics can be optically tuned within a few picoseconds by altering the photoexcited carrier density in graphene. The effective diffusion constant in initial picoseconds in the WSe2/graphene heterostructure is (40.3 ± 4.5) cm2 s-1, representing a substantial improvement over (2.1 ± 0.8) cm2 s-1, typical for an isolated WSe2 monolayer. This enhancement can be understood in terms of a transient screening of impurities, charge traps, and defect states in WSe2 by photoexcited charge carriers in graphene. Furthermore, diffusion within WSe2 is affected by interlayer interactions, such as charge transfer, varying with the incident excitation fluence. These findings underscore the dynamical nature of screening and diffusion processes in heterostructures of 2D semiconductors and graphene and provide insights for future applications of these systems in ultrafast optoelectronic devices.

Vascular Ultrasound for In Vivo Assessment of Arterial Pathologies in a Murine Model of Atherosclerosis and Aortic Aneurysm.

Vascular diseases like atherosclerosis and abdominal aortic aneurysm (AAA) are common pathologies in the western world, promoting various potentially fatal conditions. Here, we evaluate high-resolution (HR) ultrasound in mouse models of atherosclerosis and AAA as a useful tool for noninvasive monitoring of early vascular changes in vivo. We used Apolipoprotein E-deficient (ApoE-/-) mice as an atherosclerosis model and induced AAA development by the implementation of Angiotensin II-releasing osmotic minipumps. HR ultrasound of the carotid artery or the abdominal aorta was performed to monitor vascular remodeling in vivo. Images were analyzed by speckle tracking algorithms and correlated to histological analyses and subsequent automated collagen quantification. Consistent changes were observed via ultrasound in both models: Global radial strain (GRS) was notably reduced in the AAA model (23.8 ± 2.8% vs. 12.5 ± 2.5%, p = 0.01) and in the atherosclerotic mice (20.6 ± 1.3% vs. 15.8 ± 0.9%, p = 0.02). In mice with AAA, vessel distensibility was significantly reduced, whereas intima-media thickness was increased in atherosclerotic mice. The area and collagen content of the tunica media were increased in diseased arteries of both models as measured by automated image analysis of Picrosirius Red-stained aortic sections. Correlation analysis revealed a strong correlation of multiple parameters, predicting early vascular damage in HR ultrasound and histological examinations. In conclusion, our findings underscore the potential of HR ultrasound in effectively tracing early alterations in arterial wall properties in murine models of atherosclerosis and AAA.

Retained placenta and postpartum hemorrhage: time is not everything.

PURPOSE: Postpartum hemorrhage is the major cause of maternal mortality worldwide. Retained placenta accounts for nearly 20% of severe cases. We investigated the influence of the time factor and retained placenta etiology on postpartum hemorrhage dynamics. METHODS: Our retrospective study analyzed a single-center cohort of 296 women with retained placenta. Blood loss was measured using a validated and accurate technique based on calibrated blood collection bags, backed by the post- vs pre-partum decrease in hemoglobin. We evaluated the relationship between these two blood loss parameters and the duration of the third stage of labor using Spearman rank correlation, followed by subgroup analysis stratified by third stage duration and retained placenta etiology. RESULTS: Correlation analysis revealed no association between third stage duration and measured blood loss or decrease in hemoglobin. A shorter third stage (< 60 min) was associated with significantly increased uterine atony (p = 0.001) and need for blood transfusion (p = 0.006). Uterine atony was significantly associated with greater decrease in hemoglobin (p < 0.001), higher measured blood loss (p < 0.001), postpartum hemorrhage (p = 0.048), and need for blood transfusion (p < 0.001). CONCLUSION: Postpartum blood loss does not correlate with third stage duration in women with retained placenta. Our results suggest that there is neither a safe time window preceding postpartum hemorrhage, nor justification for an early cut-off for manual removal of the placenta. The prompt detection of uterine atony and immediate prerequisites for manual removal of the placenta are key factors in the management of postpartum hemorrhage.

Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial.

BACKGROUND: Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome. METHODS: In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289. FINDINGS: Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group. INTERPRETATION: An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery. FUNDING: Vifor Pharma and Swiss Foundation for Anaesthesia Research.

Impact of rivaroxaban plasma concentration on perioperative red blood cell loss.

BACKGROUND: This study investigates the impact of preoperative calculated rivaroxaban (RXA) plasma concentration on perioperative red blood cell (RBC) loss. STUDY DESIGN AND METHODS: In this retrospective single-center study, we identified patients with RXA intake according to a preoperative determination of RXA levels within 96 hours before surgery. RXA plasma concentration at the beginning of surgery was then calculated from the last RXA intake using a single-compartment pharmacokinetic model with four categories of RXA concentration (≤20, 21-50, 51-100, and >100 µg/L). Patients were classified into surgery with high (≥500 mL) or low (<500 mL) expected blood loss. Perioperative bleeding was determined by calculating RBC loss. RESULTS: We analyzed 308 surgical interventions in 298 patients during the period from January 2012 to July 2018. Among patients undergoing surgery with low expected blood loss, RBC loss varied from 164 mL (standard deviation [SD], 189) to 302 mL (SD, 397) (p = 0.66), and no association of calculated RXA concentration with RBC loss was observed. In patients undergoing surgery with high expected blood loss, we found a significant correlation of calculated RXA concentration with RBC loss (Pearson's correlation coefficient, 0.29; p = 0.002). RBC loss increased with rising RXA concentration from 575 mL (SD, 365) at RXA concentration of 20 µg/L or less up to 1400 mL (SD, 1300) at RXA concentration greater than 100 µg/L. RXA concentration greater than 100 µg/L was associated with a significant increase of in RBC loss of 840 mL (95% confidence interval, 360-1300; p < 0.001). Transfusion of RBC and fresh frozen plasma units tended to increase in patients with RXA concentrations greater than 100 µg/L. The proportion of patients treated with prothrombin complex concentrate and coagulation factor XIII concentrate increased significantly with higher RXA concentrations. CONCLUSION: Only in surgery with high expected blood loss, a calculated RXA concentration of greater than 100 µg/L was associated with a significant increase of perioperative RBC loss.

Screening for iron deficiency in surgical patients based on noninvasive zinc protoporphyrin measurements.

BACKGROUND: Approximately every third surgical patient is anemic. The most common form, iron deficiency anemia, results from persisting iron-deficient erythropoiesis (IDE). Zinc protoporphyrin (ZnPP) is a promising parameter for diagnosing IDE, hitherto requiring blood drawing and laboratory workup. STUDY DESIGN AND METHODS: Noninvasive ZnPP (ZnPP-NI) measurements are compared to ZnPP reference determination of the ZnPP/heme ratio by high-performance liquid chromatography (ZnPP-HPLC) and the analytical performance in detecting IDE is evaluated against traditional iron status parameters (ferritin, transferrin saturation [TSAT], soluble transferrin receptor-ferritin index [sTfR-F], soluble transferrin receptor [sTfR]), likewise measured in blood. The study was conducted at the University Hospitals of Frankfurt and Zurich. RESULTS: Limits of agreement between ZnPP-NI and ZnPP-HPLC measurements for 584 cardiac and noncardiac surgical patients equaled 19.7 µmol/mol heme (95% confidence interval, 18.0-21.3; acceptance criteria, 23.2 µmol/mol heme; absolute bias, 0 µmol/mol heme). Analytical performance for detecting IDE (inferred from area under the curve receiver operating characteristics) of parameters measured in blood was: ZnPP-HPLC (0.95), sTfR (0.92), sTfR-F (0.89), TSAT (0.87), and ferritin (0.67). Noninvasively measured ZnPP-NI yielded results of 0.90. CONCLUSION: ZnPP-NI appears well suited for an initial IDE screening, informing on the state of erythropoiesis at the point of care without blood drawing and laboratory analysis. Comparison with a multiparameter IDE test revealed that ZnPP-NI values of 40 µmol/mol heme or less allows exclusion of IDE, whereas for 65 µmol/mol heme or greater, IDE is very likely if other causes of increased values are excluded. In these cases (77% of our patients) ZnPP-NI may suffice for a diagnosis, while values in between require analyses of additional iron status parameters.

Clinical practice of pre-hospital analgesia: An observational study of 20,978 missions in Switzerland.

BACKGROUND: Pain is a frequent problem faced by emergency medical services (EMS) in pre-hospital settings. This large observational study aims to assess the prevalence of sufficiently provided analgesia and to analyze the efficacy of different analgesics. Moreover, we evaluated if quality of analgesia changed with an emergency physician on scene or depended on paramedics' gender. METHODS: This is a retrospective analysis of all pre-hospital medical charts from adults and adolescents treated by the municipal EMS Schutz & Rettung Zürich over a period of 4 years from 2013 to 2016. Inclusion criteria were age ≥16 years, initial GCS > 13, NACA score ≥I and ≤V, an initial numeric rating scale (NRS) ≥ I and a documented NRS at hospital admission. 20,978 out of 142,484 missions fulfilled the inclusion criteria and therefore underwent further investigation. Descriptive, univariate and multivariate analyses were applied. RESULTS: Initial NRS on scene was on average 5.2 ± 3.0. Mean NRS reduction after treatment was 2.2 ± 2.5 leading to a NRS at hospital admission of 3.0 ± 1.9. This resulted in sufficient analgesia for 77% of included patients. Among analgesics, the highest odds ratio for sufficient analgesia was observed for ketamine (OR 4.7, 95%CI 2.2-10.4, p < 0.001) followed by fentanyl (OR 1.4, 95%CI 1.1-1.7, p = 0.004). Female paramedics provided better analgesia (OR 1.2, 95%CI 1.1-1.2; p < 0.001). Patient's sex had no influence on analgesia. In patients with a NACA score > 2, the presence of an emergency physician on scene improved the quality of analgesia significantly. CONCLUSIONS: Pre-hospital analgesia is mostly adequate, especially when done with ketamine or fentanyl. Female paramedics provided better analgesia and in selected patients, an emergency physician on scene improved quality of analgesia in critical patients.

Long-term results after open repair of inflammatory infrarenal aortic aneurysms.

OBJECTIVE: The objective of this study was to investigate the long-term outcome after open repair of inflammatory infrarenal aortic aneurysms. METHODS: A total of 62 patients (mean age, 68.9 ± 8.8 years; 91.9% male) undergoing open surgery for inflammatory aortic aneurysm from 1995 until 2014 in a high-volume vascular center were retrospectively evaluated. The patients' demographics, preoperative and postoperative clinical characteristics, imaging measurements, and procedural data were collected. Study end points were preoperative and postoperative sac diameter, evolution of periaortic fibrosis and development of hydroureteronephrosis detected by computed tomography (CT) scan, and mortality and morbidity after 30 days and at the time of maximum follow-up. RESULTS: The mean abdominal aortic aneurysm diameter was 67.3 ± 16.7 mm. A total of 30 patients (48.4%) were asymptomatic, 27 patients (43.5%) were symptomatic, and 5 patients (8.1%) were treated for ruptured aneurysm. In 25 patients (40.3%), an aorta-aortic tube graft was implanted; in 37 patients (59.7%), an aortic bifurcation graft was used. Median operating time was 208 minutes (range, 83-519 minutes). Median aortic clamping time was 31 minutes (range, 14-90 minutes); in 25 patients (40.3%), suprarenal aortic cross-clamping was necessary. Hydroureteronephrosis was preoperatively diagnosed by CT scan in 16 patients (25.8%), with the need for a ureteral stent in 11 patients (17.7%). Aneurysm- and procedure-associated 30-day mortality was 11.3% (n = 7), with septic multiple organ failure in four patients and cardiac arrest in three patients. The overall perioperative complication rate was 33.9% (n = 21 patients). Median follow-up was 71.0 months (range, 0.2-231.6 months). At 1 year, 2 years, 4 years, and 6 years, overall survival was 83.4%, 79.6%, 79.6%, and 72.6%, respectively. Six patients (9.7%) required a reintervention during follow-up, predominantly aneurysm related and caused by aortoenteric fistula and graft infection (three of five patients). Median maximum thickness of preoperative perianeurysmal inflammation on CT was 10 mm (range, 2-22 mm), which decreased in 15 of 16 (94%) patients with available postoperative CT scans. Postoperative median thickness of perianeurysmal inflammation on CT was 6 mm (range, 0-13 mm). Hydroureteronephrosis persisted in two of nine (22.2%) patients at the end of follow-up. CONCLUSIONS: Surgery in patients with inflammatory abdominal aortic aneurysms is associated with a substantial amount of perioperative complications. After surgery, the perianeurysmal inflammation decreases in most patients on follow-up CT. However, because the inflammatory process does not totally resolve, patients require lifelong surveillance for hydroureteronephrosis and development of aortoenteric fistulas.

Woad extract containing cream improves significantly dry, irritated, and pruritic skin.

Objective of this open, noninterventional, noncontrolled study was to investigate the tolerability and performance of a woad extract containing cream in subjects with dry, pruritic skin after twice daily application over 2 weeks. Assessments included sensorial characteristics, skin condition, pruritus (numeric rating scale [NRS], dynamic pruritus score [DPS]), skin dryness (itch-controlled days [ItchCD], overall dry skin [ODS]), transepidermal water loss (TEWL), skin hydration and quality of life (5PLQ, DLQI). All sensorial characteristics were well perceived (>4), with tolerability (4.77 ± 0.47) and no negative skin feelings (4.73 ± 0.74) achieving the highest scores (0-5 scale). Dry skin and symptoms improved significantly (p < .001) for all variables: NRS (from 4.8 ± 1.74 to 1.83 ± 2.18), ItchCD (from 8.23 ± 4.40 to 4.81 ± 4.07), ODS (from 1.80 ± 0.85 to 0.65 ± 0.65), hydration (23.33 ± 1.33 to 40.70 ± 1.86), and quality of life (5PLQ: from 7.12 ± 4.25 to 4.24 ± 3.67; DLQI: from 5.29 ± 4.79 to 3.00 ± 3.98). The DPS revealed a moderate antipruritic effect. The TEWL decreased slightly (p = .511). No side effects were reported. The study suggests that, the cream is effective, and well tolerated in treating dry, irritated, and pruritic skin.

The Impact of Prehospital Tranexamic Acid on Blood Coagulation in Trauma Patients.

BACKGROUND: There is limited data on prehospital administration of tranexamic acid (TXA) in civilian trauma. The aim of this study was to evaluate changes in coagulation after severe trauma from on-scene to the hospital after TXA application in comparison to a previous study without TXA. METHODS: The study protocol was registered at ClinicalTrials.gov (NCT02354885). A prospective, multicenter, observational study investigating coagulation status in 70 trauma patients receiving TXA (1 g intravenously) on-scene versus a control group of 38 patients previously published without TXA. To account for potential differences in patient and trauma epidemiology, crystalloid and colloidal resuscitation fluid, 2 propensity score matched groups (n = 24 per group) were created. Measurements included ROTEM, standard coagulation tests and blood gas analyses on-scene and emergency department admission. Presented values are mean and [standard deviation], and difference in means and 95% confidence intervals. RESULTS: Patient epidemiology was not different between groups. Coagulation assays on-scene were comparable between the TXA and C. Prehospital hyperfibrinolysis was blunted in all 4 patients in the TXA group. Viscoelastic FIBTEM maximum clot firmness (MCF), representing functional fibrinogen levels, did not change from on-scene to the emergency department in the TXA group, whereas MCF decreased -3.7 [1.8] mm in the control group. Decrease of MCF was significantly reduced in the TXA group in EXTEM by 9.2 (7.2-11.2) mm (P < .001) and INTEM by 6.8 (4.7-9.0) mm (P < .001) in favor of the TXA group. Production of fibrinogen fragments (represented by D-dimers) was significantly lower in the TXA group compared to group C. CONCLUSIONS: Early prehospital administration of TXA leads to clot stabilization and a reduction of fibrinolytic activity, causing a decrease in fibrin degradation products buildup (D-dimer).

A smartphone application to determine body length for body weight estimation in children: a prospective clinical trial.

The aim of this study was to test the feasibility and accuracy of a smartphone application to measure the body length of children using the integrated camera and to evaluate the subsequent weight estimates. A prospective clinical trial of children aged 0-<13 years admitted to the emergency department of the University Children's Hospital Zurich. The primary outcome was to validate the length measurement by the smartphone application «Optisizer¼. The secondary outcome was to correlate the virtually calculated ordinal categories based on the length measured by the app to the categories based on the real length. The third and independent outcome was the comparison of the different weight estimations by physicians, nurses, parents and the app. For all 627 children, the Bland Altman analysis showed a bias of -0.1% (95% CI -0.3-0.2%) comparing real length and length measured by the app. Ordinal categories of real length were in excellent agreement with categories virtually calculated based upon app length (kappa = 0.83, 95% CI 0.79-0.86). Children's real weight was underestimated by physicians (-3.3, 95% CI -4.4 to -2.2%, p < 0.001), nurses (-2.6, 95% CI -3.8 to -1.5%, p < 0.001) and parents (-1.3, 95% CI -1.9 to -0.6%, p < 0.001) but overestimated by categories based upon app length (1.6, 95% CI 0.3-2.8%, p = 0.02) and categories based upon real length (2.3, 95% CI 1.1-3.5%, p < 0.001). Absolute weight differences were lowest, if estimated by the parents (5.4, 95% CI 4.9-5.9%, p < 0.001). This study showed the accuracy of length measurement of children by a smartphone application: body length determined by the smartphone application is in good agreement with the real patient length. Ordinal length categories derived from app-measured length are in excellent agreement with the ordinal length categories based upon the real patient length. The body weight estimations based upon length corresponded to known data and limitations. Precision of body weight estimations by paediatric physicians and nurses were comparable and not different to length based estimations. In this non-emergency setting, parental weight estimation was significantly better than all other means of estimation (paediatric physicians and nurses, length based estimations) in terms of precision and absolute difference.

Point-of-Care Coagulation Monitoring in Trauma Patients.

Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-directed way based on point-of-care (POC) and routine laboratory measurements. Viscoelastic POC measurement of the developing clot in whole blood and POC platelet function testing allow rapid and tailored coagulation and transfusion treatment based on goal-directed, factor concentrate-based algorithms. The first studies have been published showing that this concept reduces the need for allogeneic blood transfusion and improves outcome. This review highlights the concept of goal-directed POC coagulation management in trauma patients, introduces a selection of POC devices, and presents algorithms which allow a reduction in allogeneic blood product transfusion and an improvement of trauma patient outcome.

Factors Influencing Quality of Pain Management in a Physician Staffed Helicopter Emergency Medical Service.

BACKGROUND: Pain is frequently encountered in the prehospital setting and needs to be treated quickly and sufficiently. However, incidences of insufficient analgesia after prehospital treatment by emergency medical services are reported to be as high as 43%. The purpose of this analysis was to identify modifiable factors in a specific emergency patient cohort that influence the pain suffered by patients when admitted to the hospital. METHODS: For that purpose, this retrospective observational study included all patients with significant pain treated by a Swiss physician-staffed helicopter emergency service between April and October 2011 with the following characteristics to limit selection bias: Age > 15 years, numerical rating scale (NRS) for pain documented at the scene and at hospital admission, NRS > 3 at the scene, initial Glasgow coma scale > 12, and National Advisory Committee for Aeronautics score < VI. Univariate and multivariable logistic regression analyses were performed to evaluate patient and mission characteristics of helicopter emergency service associated with insufficient pain management. RESULTS: A total of 778 patients were included in the analysis. Insufficient pain management (NRS > 3 at hospital admission) was identified in 298 patients (38%). Factors associated with insufficient pain management were higher National Advisory Committee for Aeronautics scores, high NRS at the scene, nontrauma patients, no analgesic administration, and treatment by a female physician. In 16% (128 patients), despite ongoing pain, no analgesics were administered. Factors associated with this untreated persisting pain were short time at the scene (below 10 minutes), secondary missions of helicopter emergency service, moderate pain at the scene, and nontrauma patients. Sufficient management of severe pain is significantly better if ketamine is combined with an opioid (65%), compared to a ketamine or opioid monotherapy (46%, P = .007). CONCLUSIONS: In the studied specific Swiss cohort, nontrauma patients, patients on secondary missions, patients treated only for a short time at the scene before transport, patients who receive no analgesic, and treatment by a female physician may be risk factors for insufficient pain management. Patients suffering pain at the scene (NRS > 3) should receive an analgesic whenever possible. Patients with severe pain at the scene (NRS ≥ 8) may benefit from the combination of ketamine with an opioid. The finding about sex differences concerning analgesic administration is intriguing and possibly worthy of further study.

Failure rate of prehospital chest decompression after severe thoracic trauma.

INTRODUCTION: Chest decompression can be performed by different techniques, like needle thoracocentesis (NT), lateral thoracostomy (LT), or tube thoracostomy (TT). The aim of this study was to report the incidence of prehospital chest decompression and to analyse the effectiveness of these techniques. MATERIAL AND METHODS: In this retrospective case series study, all medical records of adult trauma patients undergoing prehospital chest decompression and admitted to the resuscitation area of a level-1 trauma center between 2009 and 2015 were reviewed and analysed. Only descriptive statistics were applied. RESULTS: In a 6-year period 24 of 2261 (1.1%) trauma patients had prehospital chest decompression. Seventeen patients had NT, six patients TT, one patient NT as well as TT, and no patients had LT. Prehospital successful release of a tension pneumothorax was reported by the paramedics in 83% (5/6) with TT, whereas NT was effective in 18% only (3/17). In five CT scans all thoracocentesis needles were either removed or extrapleural, one patient had a tension pneumothorax, and two patients had no pneumothorax. No NT or TT related complications were reported during hospitalization. CONCLUSION: Prehospital NT or TT is infrequently attempted in trauma patients. Especially NT is associated with a high failure rate of more than 80%, potentially due to an inadequate ratio between chest wall thickness and catheter length as previously published as well as a possible different pathophysiological cause of respiratory distress. Therefore, TT may be considered already in the prehospital setting to retain sufficient pleural decompression upon admission.

Indications and Risks of Fibrinogen in Surgery and Trauma.

Fibrinogen has a central role in coagulation. Following trauma and perioperatively, low fibrinogen levels have been found to be risk factors for exaggerated bleeding, transfusion needs, and adverse outcome. Conversely, treatment with exogenous fibrinogen in critically bleeding patients with low fibrinogen levels has been shown to decrease transfusion needs. Because following trauma and in many perioperative situations fibrinogen is the first coagulation "element" to become critically low, it appears reasonable to target fibrinogen in clinical coagulation algorithms aiming at early specific and goal-directed treatment. A low fibrinogen can be a low plasma concentration or a low functional fibrinogen as assessed by point-of-care techniques such as thromboelastography (TEG) or thromboelastometry (ROTEM). This review summarizes the evidence base for perioperative algorithm-based fibrinogen administration, including the exact thresholds for fibrinogen administration used in the different algorithms. Algorithm-based individualized goal-directed use of fibrinogen resulted in highly significant reduction in transfusion needs, adverse outcomes, in certain studies even mortality, and where investigated reduced costs, with high safety levels at the same time. Best evidence exists in cardiac surgery, followed by trauma, postpartum hemorrhage, and liver transplantation. The introduction of these concepts is highly demanding and requires a tremendous educational effort to familiarize all health care workers with the necessary knowledge and the skills of how to run TEG/ROTEM tests. Future research is needed to compare the efficacy, safety, and costs of different algorithms. This, however, should not prevent us from introducing these expedient point-of-care-based algorithms clinically today.

Evidence base for restrictive transfusion triggers in high-risk patients.

UNLABELLED: Liberal versus restrictive red blood cell (RBC) transfusion triggers have been debated for years. This review illustrates the human body's physiologic response to acute anemia and summarizes the evidence from prospective randomized trials (RCTs) for restrictive use of RBC transfusions in high-risk patients. During progressive anemia, the human body maintains the oxygen delivery to the tissues by an increase in cardiac output and peripheral oxygen extraction. Seven RCTs with a total of 5,566 high-risk patients compared a restrictive hemoglobin (Hb) transfusion trigger (Hb < 70 or < 80 g/l) with a liberal Hb transfusion trigger (Hb < 90 or < 100 g/l). Unanimously these studies show non-inferiority, safety, and a significant reduction in RBC transfusions in the restrictive groups. In one RCT mortality was higher in the liberal Hb transfusion group, and in two additional RCTs mortality of subgroups or after risk adjustment was significantly higher in the liberal Hb transfusion trigger groups. CONCLUSION: Strong RCT evidence suggests the safety of restrictive transfusion triggers. As a consequence, an Hb transfusion trigger of <70 g/l is recommended for high risk patients.

Point of care and factor concentrate-based coagulation algorithms.

In the last years it has become evident that the use of blood products should be reduced whenever possible. There is increasing evidence regarding serious adverse events, including higher mortality and morbidity, related to transfusions. The use of point of care (POC) devices integrated in algorithms is one of the important mechanisms to limit blood product exposure. Any type of algorithm, especially the POC-based ones, allows goal-directed transfusions of blood products and even better targeted factor concentrate substitutions. Different types of algorithms in different surgical settings (cardiac surgery, trauma, liver surgery etc.) have been established with growing interest in their use as they offer objective therapy for management and reduction of blood product use. The use of POC devices with evidence-based algorithms is important in the bleeding patient independent of its origin (traumatic vs. surgical). The use of factor concentrates compared to the classical blood products can be cost-saving, beneficial for the patient, and in agreement with the WHO-requested standard of care. The empiric and uncontrolled use of blood products such as fresh frozen plasma, red blood cells, and platelets without POC monitoring should no longer be followed with regard to actual evidence in literature. Furthermore, the use of factor concentrates may provide better outcomes and potential for cost saving.

Transfusion strategy in multiple trauma patients.

PURPOSE OF REVIEW: To point out the tolerance of anemia, the possible use of alternatives to allogeneic blood products as well as the pathophysiological effects of transfusions in the context of multiple trauma patients. RECENT FINDINGS: Restrictive transfusion triggers are beneficial for patient outcome in trauma.The actual European Trauma Treatment Guidelines suggest the use of point-of-care devices, the use of transfusion algorithms and factor concentrates to control coagulopathy. The use of high ratios of plasma to red blood cells to improve survival has been shown to suffer from a time-dependent survival bias. In massive bleeding, factor-based treatment of coagulopathy is feasible and preferable to plasma transfusion, if available. In nonmassive bleeding, allogeneic transfusion of blood products increases the appearance of serious adverse events and mortality and should be avoided unless clearly indicated. SUMMARY: Transfusion in trauma has to be an individual decision for a specific patient, not for a specific laboratory value. Transfusion management must aim at reducing or even avoiding the use of allogeneic blood products. This may lead to a new gold standard with cost reduction and amelioration of outcome of major trauma patients.

Applying 'Patient Blood Management' in the trauma center.

PURPOSE OF REVIEW: The purpose of this review is to highlight the use of tranexamic acid, point-of-care testing, algorithm-based treatment of trauma-associated coagulopathy with factor concentrates to reduce blood loss and transfusion requirements in order to improve outcome. In addition, the management of patients on new oral anticoagulants, drugs with renewed interest and the tolerance of relatively low hemoglobin levels in the context of trauma will be discussed. RECENT FINDINGS: Early administration of tranexamic acid reduces mortality without increasing the risk of thromboembolic events. Point-of-care testing is increasingly recommended. Goal-directed individualized coagulation algorithms with the use of factor concentrates allow reducing the amount of allogeneic blood products to be administered. Treatment of trauma patients with one of the new oral anticoagulants is challenging. Furthermore, new mechanisms have been discovered such as deep neuromuscular blockade to better tolerate acute anemia. SUMMARY: Applying Patient Blood Management concept to the trauma patient is possible and efficacious. Antihyperfibrinolytics such as tranexamic acid, point-of-care testing and coagulation algorithms with the use of factor concentrates allow a reduction of the number of transfusions, the costs and will likely ameliorate outcome of major trauma patients.