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Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: Hemostasis of patients suffering from liver cirrhosis is challenging due to both, pro- and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation. Pathological changes in conventional coagulation analysis and platelet count are common manifestations of decreased liver synthesis of coagulation factors and reduced platelet count in these patients. However, conventional coagulation analysis and platelet count do not reflect in-vivo coagulation status or platelet function. The purpose of this present observational study was therefore to assess the haemostatic profile including plasmatic coagulation using thrombelastometry and impedance aggregometry for platelet function in patients suffering from liver cirrhosis., Aim: To assess the hemostatic profile of cirrhotic patients according to model for end-stage liver disease (MELD) score., Methods: Our study included both in- and outpatients suffering from liver cirrhosis attending the out- and inpatient care of the department of hepatology. Demographic and biochemical data as well as medical history including cause of liver cirrhosis, end stage kidney failure and medication with anticoagulants were recorded. To assess the hemostatic profile, platelet function was analyzed by multiple electrode aggregometry (MEA) using Multiplate ® (ADP-, ASPI- and TRAP-test) and thrombelastometry using ROTEM ® (EXTEM, INTEM, FIBTEM). Data were compared using Mann-Whitney U - or χ 2 -test. Spearman correlation was performed to analyze the association between MELD Score and results of thrombelastometry and MEA., Results: A total of 68 patients attending the out- and inpatient care suffering from liver cirrhosis were screened. Of these, 50 patients were included and assigned to groups according to MELD score 6 to 11 ( n = 25) or ≥ 17 ( n = 25). Baseline patient characteristics revealed significant differences for MELD score (8 vs 22, P < 0.0001) and underlying laboratory parameters (international normalized ratio, bilirubine, creatinine) as well as fibrinogen level (275 mg/dL vs 209 mg/dL, P = 0.006) and aPTT (30 s vs 35 s, P = 0.047). MEA showed a moderately impaired platelet function (medians: AUC ADP = 43U, AUC ASPI = 71U, AUC TRAP = 92U) but no significant differences between both groups. Thrombelastometry using ROTEM ® (EXTEM, INTEM, FIBTEM) revealed values within normal range in both groups. No significant correlation was observed between MELD score and results of MEA/thrombelastometry., Conclusion: Our data demonstrate a partially impaired hemostatic profile in liver cirrhosis patients unrelated to MELD score. An individual assessment of a potential coagulopathy should therefore be considered., Competing Interests: Conflict-of-interest statement: EHA received honoraria for scientific lectures from CSL Behring and Fresenius Kabi GmbH. KZ department is receiving unrestricted educational grants from B. Braun Melsungen AG, Fresenius Kabi GmbH, CSL Behring GmbH and Vifor Pharma GmbH. In the past 3 years, KZ has received honoraria or travel support for consulting or lecturing from the following companies: Abbott GmbH &Co KG, Aesculap Akademie GmbH, AQAI GmbH, Astellas Pharma GmbH, Astra Zeneca GmbH, Aventis Pharma GmbH, B. Braun Melsungen AG, Baxter Deutschland GmbH, Biosyn GmbH, Biotest AG, Bristol-Myers Squibb GmbH, CSL Behring GmbH, Dr. F. Köhler Chemie GmbH, Dräger Medical GmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, Fresenius Medical Care, Gambro Hospal GmbH, Gilead, GlaxoSmithKline GmbH, Grünenthal GmbH, Hamilton Medical AG, HCCM Consulting GmbH, Heinen + Löwenstein GmbH, Janssen-Cilag GmbH, med Update GmbH, Medivance EU B.V., MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH, P. J. Dahlhausen & Co. GmbH, Pfizer Pharma GmbH, Pulsion Medical Systems S.E., Siemens Healthcare, Teflex Medical GmbH, Teva GmbH, TopMedMedizintechnik GmbH, Verathon Medical, ViforPharma GmbH. SZ received honoraria for consultancy and/or scientific lectures from Abbvie, Gilead, Intercept, Janssen, Merck/MSD. CW received honoraria for scientific lectures from CSL Behring, Haemonetics, Biotest, Verum Diagnostica and Roche. NW received speaker’s fees from Astellas and Novartis as well as travel support from Abbvie, Astellas and Novartis., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: The aim of the RUBY study was to evaluate novel candidate biomarkers to enable prediction of persistence of renal dysfunction as well as further understand potential mechanisms of kidney tissue damage and repair in acute kidney injury (AKI)., Methods: The RUBY study was a multi-center international prospective observational study to identify biomarkers of the persistence of stage 3 AKI as defined by the KDIGO criteria. Patients in the intensive care unit (ICU) with moderate or severe AKI (KDIGO stage 2 or 3) were enrolled. Patients were to be enrolled within 36 h of meeting KDIGO stage 2 criteria. The primary study endpoint was the development of persistent severe AKI (KDIGO stage 3) lasting for 72 h or more (NCT01868724)., Results: 364 patients were enrolled of whom 331 (91%) were available for the primary analysis. One hundred ten (33%) of the analysis cohort met the primary endpoint of persistent stage 3 AKI. Of the biomarkers tested in this study, urinary C-C motif chemokine ligand 14 (CCL14) was the most predictive of persistent stage 3 AKI with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.83 (0.78-0.87). This AUC was significantly greater than values for other biomarkers associated with AKI including urinary KIM-1, plasma cystatin C, and urinary NGAL, none of which achieved an AUC > 0.75., Conclusion: Elevated urinary CCL14 predicts persistent AKI in a large heterogeneous cohort of critically ill patients with severe AKI. The discovery of CCL14 as a predictor of persistent AKI and thus, renal non-recovery, is novel and could help identify new therapeutic approaches to AKI.

Competing Interests: There are no conflicts of interest.

Background: Cardiothoracic surgery is associated with major blood loss and allogeneic transfusion of red blood cell concentrates. To minimize allogeneic red blood cell (RBC) transfusion, intraoperative cell salvage has been effectively used for years. The objective of this study was to evaluate the impact of cell salvage on blood coagulation factors., Methods: We enrolled 30 patients scheduled for cardiac surgery in a prospective single-center observational cohort study at an academic hospital. Blood samples from the cell salvage system were obtained from both the reservoir and the processed red blood cell concentrate. Coagulation factors, fibrinogen, antithrombin and von Willebrand activity, and antigen were assessed before and after cell salvage. Statistical analysis was performed using Wilcoxon matched-pairs signed rank test., Results: Our results revealed a significant decrease of fibrinogen (P < .001), coagulation factors II (P = .004), factors VII, X, and XIII (P < .001), and all other measured coagulation factor concentrations/activities in the processed red blood cell concentrate, when compared to the concentrations/activities of the reservoir., Conclusions: The results of the present study revealed a significant reduction of coagulation factor concentrations/activities by the washing process. Therefore, physicians need to consider adequate management of coagulation in patients with major blood loss and the need of large volumes of RBC transfusion.

Background: Point of care devices for performing targeted coagulation substitution in patients who are bleeding have become increasingly important in recent years. New on the market is the Quantra. It is a device that uses sonorheometry, a sonic estimation of elasticity via resonance, which is a novel ultrasound-based technology that measures viscoelastic properties of whole blood. Several studies have already shown the comparability of the Quantra with devices already established on the market, such as the rotational thromboelastometry (ROTEM) device., Objective: In contrast to existing studies, this study is the first prospective interventional study using this new system in a cardiac surgical patient cohort. We will investigate the noninferiority between an already existing coagulation algorithm based on the ROTEM/Multiplate system and a new algorithm based on the Quantra system for the treatment of coagulopathic cardiac surgical patients., Methods: The study is divided into two phases. In an initial observation phase, whole blood samples of 20 patients obtained at three defined time points (prior to surgery, after completion of cardiopulmonary bypass, and on arrival in the intensive care unit) will be analyzed using both the ROTEM/Multiplate and Quantra systems. The obtained threshold values will be used to develop a novel algorithm for hemotherapy. In a second intervention phase, the new algorithm will be tested for noninferiority against an algorithm used routinely for years in our department., Results: The main objective of the examination is the cumulative loss of blood within 24 hours after surgery. Statistical calculations based on the literature and in-house data suggest that the new algorithm is not inferior if the difference in cumulative blood loss is <150 mL/24 hours., Conclusions: Because of the comparability of the Quantra sonorheometry system with the ROTEM measurement methods, the existing hemotherapy treatment algorithm can be adapted to the Quantra device with proof of noninferiority., Trial Registration: ClinicalTrials.gov NCT03902275; https://clinicaltrials.gov/ct2/show/NCT03902275., International Registered Report Identifier (irrid): DERR1-10.2196/17206., (©Sophie Michel, Florian Piekarski, Jan-Hendrik Fischer, Vanessa Hettler, Elisabeth Hannah Adam, Lars Holzer, Gösta Lotz, Thomas Walther, Kai Zacharowski, Florian Jürgen Raimann. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.04.2020.)

Anemia is common in patients with cardiac disease. Iron deficiency is the cause of anemia in about 80% of all cases. Preoperative anemia is associated with an increased morbidity and mortality in patients undergoing cardiac surgery. The risk of receiving red blood cell transfusions, which are potentially associated with severe side effects, is very high in these patients. Patient Blood Management (PBM) is a multidisciplinary approach to manage anemia, minimize unnecessary blood loss, and optimize transfusion therapy. PBM comprises 3 pillars: (1) detection and treatment of preoperative anemia, (2) reduction of perioperative blood loss, and (3) optimization of allogeneic blood therapy. The World Health Organization has urged all Member States to implement PBM. This narrative review focuses on pre-, intra-, and postoperative strategies to detect, prevent, and treat anemia as part of PBM in cardiac surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose of Review: Red cell transfusions are commonly used in management of hemorrhage in trauma patients. The appropriate indications and criteria for transfusion are still debated. Here, we summarize the recent findings on the use of red cell transfusion in trauma setting., Recent Findings: Recent evidence continues to support the long-established link between allogeneic transfusion and worse clinical outcomes, reinstating the importance of more judicious use of allogeneic blood and careful consideration of benefits versus risks when making transfusion decisions. Studies support restrictive transfusion strategies (often based on hemoglobin thresholds of 7-8 g/dl) in most patient populations, although some argue more caution in specific populations (e.g. patients with traumatic brain injury) and more studies are needed to determine if these patients benefit from less restrictive transfusion strategies. It should be remembered that anemia remains an independent risk factor for worse outcomes and red cell transfusion does not constitute a lasting treatment. Anemia should be properly assessed and managed based on the cause and using hematinic medications as indicated., Summary: Although the debate on hemoglobin thresholds for transfusion continues, clinicians should not overlook proper management of the underlying issue (anemia).

Background and Objectives: Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce., Materials and Methods: To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016., Results: Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron., Conclusion: Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia., (© 2019 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Purpose: Surgical re-exploration due to postoperative bleeding is associated with increased morbidity and mortality. The aim of our study was to assess a potential association between the level of postoperative FXIII activity and need for re-exploration due to bleeding in patients undergoing cardiothoracic surgery., Materials and Methods: In our prospective single center observational cohort study, we enrolled patients who underwent elective cardiothoracic surgery. Patients who required re-exploration (RE group) were matched to patients from the study population (non-RE group)., Results: The study included 64 patients, out of a cohort of 678 patients, of whom 32 required surgical re-exploration due to bleeding within the first 24 h. Between patients of the RE and non-RE group, a significantly reduced FXIII activity was observed postoperatively (59.0 vs 71.1; p = .014). Multivariable analysis revealed reduced FXIII activity (p = .048) as a parameter independently associated with surgical re-exploration. Further, reduced FXIII activity (p = .037) and surgical re-exploration (p = .01) were significantly associated with increased 30 day mortality. In multivariable analysis re-exploration was independently associated with increased risk of 30 day mortality (p = .004, HR 9.68)., Conclusions: Reduced postoperative FXIII activity may be associated with the need for surgical re-exploration. Postoperative assessment of FXIII activity should therefore be considered in patients undergoing elective cardiothoracic surgery., Competing Interests: Declaration of Competing Interest EHA received honoraria for scientific lectures from CSL Behring and Fresenius Kabi GmbH. PM received research grants from the German Research Foundation (ME 3559/1-1, ME 3559/3-1), International Anesthesia Research Society, German Society of Anaesthesiology and Intensive Care Medicine, European Society of Anaesthesiology, grants by B. Braun Mel- sungen, CSL Behring, Fresenius Kabi and Vifor Pharma for the implementation of Frankfurt‘s Patient Blood Management Program; by Pfizer for investigator-initiated trial; honoraria for scientific lectures from B. Braun Melsungen, Vifor Pharma, Ferring, CSL Behring, Heinen & Löwenstein, and Aesculap Academy. CW received honoraria for scientific lectures from CSL Behring, Haemonetics, Biotest, Verum Diagnostica and Roche. KZ's department is receiving unrestricted educational grants from B. Braun Melsungen AG, Fresenius Kabi GmbH, CSL Behring GmbH and Vifor Pharma GmbH. In the past 3 years, KZ has received honoraria or travel support for consulting or lecturing from the following companies: Abbott GmbH &Co KG, Aesculap Akademie GmbH, AQAI GmbH, Astellas Pharma GmbH, Astra Zeneca GmbH, Aventis Pharma GmbH, B. Braun Melsungen AG, Baxter Deutschland GmbH, Biosyn GmbH, Biotest AG, Bristol-Myers Squibb GmbH, CSL Behring GmbH, Dr. F. Köhler Chemie GmbH, Dräger Medical GmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, Fresenius Medical Care, Gambro Hospal GmbH, Gilead, GlaxoSmithKline GmbH, Grünenthal GmbH, Hamilton Medical AG, HCCM Consulting GmbH, Heinen + Löwenstein GmbH, Janssen-Cilag GmbH, med Update GmbH, Medivance EU B.V., MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH, P. J. Dahlhausen & Co. GmbH, Pfizer Pharma GmbH, Pulsion Medical Systems S.E., Siemens Healthcare, Teflex Medical GmbH, Teva GmbH, TopMedMedizintechnik GmbH, Verathon Medical, ViforPharma GmbH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Approximately one in three patients has untreated preoperative anaemia, which in turn is associated with an increased need for transfusion of allogenic red blood cell concentrates (RBC) and complications in the context of a surgical intervention. Here, the prevalence of preoperative and postoperative anaemia as well as their effects on transfusion rate, hospital length of stay and hospital mortality in primary hip and knee arthroplasty has been analysed., Methods: From January 2012 to September 2018, 378,069 adult inpatients from 13 German hospitals were analysed on the basis of an anonymized registry. Of these, n = 10,017 patients had a hip and knee joint primary arthroplasty. The primary endpoint was the incidence of preoperative anaemia, which was analysed by the first available preoperative haemoglobin value according to the WHO definition. Secondary endpoints included in-hospital length of stay, number of patients with red blood cell concentrate transfusion, incidence of hospital-acquired anaemia, number of deceased patients, and postoperative complications., Results: The preoperative anaemia rate was 14.8% for elective knee joint arthroplasty, 22.9% for elective hip joint arthroplasty and 45.0% for duo-prosthesis implantation. Preoperative anaemia led to a significantly higher transfusion rate (knee: 8.3 vs. 1.8%; hip: 34.5 vs. 8.1%; duo-prosthesis: 42.3 vs. 17.4%), an increased red blood cell concentrate consumption (knee: 256 ± 107 vs. 29 ± 5 RBC/1000 patients; hip: 929 ± 60 vs. 190 ± 16 RBC/1000 patients; duo-prosthesis: 1411 ± 98 vs. 453 ± 42 RBC/1000 patients). Pre-operative anaemia was associated with prolonged hospital stay (12.0 [10.0; 17.0] d vs. 11.0 [9.0; 13.0] d; p < 0.001) and increased mortality (5.5% [4.6 - 6.5%] vs. 0.9% [0.7 - 1.2%]; Fisher p < 0.001) compared to non-anaemic patients. In patients aged 80 years and older, the incidence of preoperative anaemia and thus the transfusion rate was almost twice as high as in patients under 80 years of age., Summary: Preoperative anaemia is common in knee and hip primary arthroplasty and was associated with a relevant increase in red blood cell concentrate consumption. In the context of patient blood management, a relevant potential arises, especially in elective orthopaedic surgery, to better prepare elective patients, to avoid unnecessary transfusions and thus to conserve the valuable resource blood., Competing Interests: P. M. and K. Z. received funding from B. Braun Melsungen, CSL Behring, Fresenius Kabi and Vifor Pharma for an examiner-initiated study to implement the Patient Blood Management Program at four university hospitals. P. M. and/or K. Z. received grants or travel expense funding for consultations and lectures from the following companies: Abbott GmbH &Co KG, Aesculap Akademie GmbH, AQAI GmbH, Astellas Pharma GmbH, AstraZeneca GmbH, Aventis Pharma GmbH, B, Braun Melsungen AG, Baxter Deutschland GmbH, Biosyn Arzneimittel GmbH, Biotest AG, Bristol-Myers Squibb GmbH, CSL Behring GmbH, Dr, F, Köhler Chemie GmbH, Dräger Medical GmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, Fresenius Medical Care, Gambro Hospal GmbH, Gilead Sciences GmbH, GlaxoSmithKline GmbH, Grünenthal GmbH, Hamilton Medical AG, HCCM Consulting GmbH, Heinen + Löwenstein GmbH, Janssen-Cilag GmbH, med Update GmbH, Medivance EU B. V., MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH, P. J. Dahlhausen & Co. GmbH, Pfizer Pharma GmbH, Pulsion Medical Systems S. E., Siemens Healthcare, Teflex Medical GmbH, Teva GmbH, TopMedMedizintechnik GmbH, Verathon Medical, Vifor Pharma GmbH. K. S. received grants or travel expense funding for lectures from the companies HAEMA AG and Vifor Pharma GmbH./P. M. und K. Z. erhielten finanzielle Förderungen von B. Braun Melsungen, CSL Behring, Fresenius Kabi und Vifor Pharma für eine prüferinitiierte Studie zur Implementierung des Patient Blood Management Programms an 4 Universitätskliniken. P. M. und/oder K. Z. erhielten Förderungen oder Reisekostenunterstützung für Beratungen und Vorträge der folgenden Firmen: Abbott GmbH &Co KG, Aesculap Akademie GmbH, AQAI GmbH, Astellas Pharma GmbH, AstraZeneca GmbH, Aventis Pharma GmbH, B, Braun Melsungen AG, Baxter Deutschland GmbH, Biosyn Arzneimittel GmbH, Biotest AG, Bristol-Myers Squibb GmbH, CSL Behring GmbH, Dr, F, Köhler Chemie GmbH, Dräger Medical GmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, Fresenius Medical Care, Gambro Hospal GmbH, Gilead Sciences GmbH, GlaxoSmithKline GmbH, Grünenthal GmbH, Hamilton Medical AG, HCCM Consulting GmbH, Heinen + Löwenstein GmbH, Janssen-Cilag GmbH, med Update GmbH, Medivance EU B. V., MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH, P. J. Dahlhausen & Co. GmbH, Pfizer Pharma GmbH, Pulsion Medical Systems S. E., Siemens Healthcare, Teflex Medical GmbH, Teva GmbH, TopMed Medizintechnik GmbH, Verathon Medical, Vifor Pharma GmbH. K. S. erhielt Förderungen oder Reisekostenunterstützung für Vorträge von den Firmen HAEMA AG und Vifor Pharma GmbH., (Georg Thieme Verlag KG Stuttgart · New York.)

Regulatory T cells (T regs ) are important mediators of immunological self-tolerance and homeostasis. Being cluster of differentiation 4 + Forkhead box protein3 + (CD4 + FOXP3 + ), these cells are a subset of CD4 + T lymphocytes and can originate from the thymus (tT regs ) or from the periphery (pT regs ). The malfunction of CD4 + T regs is associated with autoimmune responses such as rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D), inflammatory bowel diseases (IBD), psoriasis, systemic lupus erythematosus (SLE), and transplant rejection. Recent evidence supports an opposed role in sepsis. Therefore, maintaining functional T regs is considered as a therapy regimen to prevent autoimmunity and allograft rejection, whereas blocking T reg differentiation might be favorable in sepsis patients. It has been shown that T regs can be generated from conventional naïve T cells, called iT regs , due to their induced differentiation. Moreover, T regs can be effectively expanded in vitro based on blood-derived tT regs . Taking into consideration that the suppressive role of T regs has been mainly attributed to the expression and function of the transcription factor Foxp3, modulating its expression and binding to the promoter regions of target genes by altering the chromatin histone acetylation state may turn out beneficial. Hence, we discuss the role of histone deacetylation inhibitors as epigenetic modulators of T regs in this review in detail.

Objective: This study aimed to investigate the association of anesthetists' academic and educational status with self-confidence, self-rated knowledge and objective knowledge about rational antibiotic application. Therefore, anesthetists in Germany were asked about their self-confidence, self-rated knowledge and objective knowledge on antibiotic therapy via the Multiinstitutional Reconnaissance of practice with Multiresistant bacteria (MR2) survey. Other analysis from the survey have been published elsewhere, before., Results: 361 (52.8%) questionnaires were completed by specialists and built the study group. In overall analysis the Certification in Intensive Care (CIC) was significantly associated with self-confidence (p < 0.001), self-rated knowledge (p < 0.001) and objective knowledge (p = 0.029) about antibiotic prescription. Senior consultant status was linked to self-confidence (p < 0.001) and self-rated knowledge (p = 0.005) but not objective knowledge. Likewise, working on Intensive Care Unit (ICU) during the last 12 months was significantly associated with self-rated knowledge and self-confidence (all p < 0.001). In a logistic regression model, senior consultant status was not associated with any tested influence factor. This analysis unveiled that CIC and working on ICU were more associated with anesthesiologists' self-confidence and self-rated knowledge than senior consultant status. However, neither of the characteristics was thoroughly associated with objective knowledge.

Competing Interests: Aesculap Akademie GmbH, Affinites Sante, Ashai Kasai Pharma, B. Braun AG, B. Braun Avitum AG, Bayer AG, Biotest AG, Christian Doppler Stiftung, CSL Behring GmbH, Cyto Sorbents GmbH, Edward Lifescience Corporation, Executive Insight AG, Fresenius Kabi GmbH, Fresenius Medical Care, Haemonetics Corporation, Hartmannbund Landesverband, Health Advances GmbH, Heinen+Löwenstein GmbH, Hexal AG, INC Research, Johnson & Johnson, Josef Gassner, Maquet GmbH, Markus Lücke Kongress Organisation, Masimo International, med Update GmbH, Medizin & Markt Gesundheitsnetzwerk, MSD Sharp&Dohme GmbH, Nordic Group, Nordic Pharma, Novo Nordisk Pharma GmbH, Pfizer Pharma GmbH, Pharmacosmos, Ratiopharm GmbH, Salvia Medical GmbH, Schering Stiftung, Schöchl Medical Österreich, Serumwerke, Verlag für Printmedien und PR, Forum Sanitas, Vifor Pharma GmbH, Wellington, Werfen

Background: Every third surgical patient already suffers from anemia before surgery. The main cause is iron deficiency., Objective: This article describes the perioperative risk of iron deficiency with/without anemia and summarizes potential preventive measures., Material and Methods: Presentation of various current original papers, guidelines and own experiences from the German patient blood management network., Results and Conclusion: Preoperative iron deficiency with/without anemia is an underestimated risk factor for perioperative complications. The implementation of preoperative diagnostics and treatment as part of a comprehensive patient blood management reduces complications and increases patient safety.

Background and Objectives: Patient Blood Management (PBM) is the timely application of evidence-based medical and surgical concepts designed to improve haemoglobin concentration, optimize haemostasis and minimize blood loss in an effort to improve patient outcomes. The focus of this cost-benefit analysis is to analyse the economic benefit of widespread implementation of a multimodal PBM programme., Materials and Methods: Based on a recent meta-analysis including 17 studies (>235 000 patients) comparing PBM with control care and data from the University Hospital Frankfurt, a cost-benefit analysis was performed. Outcome data were red blood cell (RBC) transfusion rate, number of transfused RBC units, and length of hospital stay (LOS). Costs were considered for the following three PBM interventions as examples: anaemia management including therapy of iron deficiency, use of cell salvage and tranexamic acid. For sensitivity analysis, a Monte Carlo simulation was performed., Results: Iron supplementation was applied in 3·1%, cell salvage in 65% and tranexamic acid in 89% of the PBM patients. In total, applying these three PBM interventions costs €129·04 per patient. However, PBM was associated with a reduction in transfusion rate, transfused RBC units per patient, and LOS which yielded to mean savings of €150·64 per patient. Thus, the overall benefit of PBM implementation was €21·60 per patient. In the Monte Carlo simulation, the cost savings on the outcome side exceeded the PBM costs in approximately 2/3 of all repetitions and the total benefit was €1 878 000 in 100·000 simulated patients., Conclusion: Resources to implement a multimodal PBM concept optimizing patient care and safety can be cost-effectively., (© 2019 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Objectives: Postoperative delirium (POD) is a common complication after elective cardiac surgery. Recent evidence indicates that a disruption in the normal activity of the cholinergic system may be associated with delirium., Design: Prospective observational study., Setting: Single-centre at a European academic hospital., Primary and Secondary Outcome Measures: In our study the enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined preoperatively as well as on the first and second postoperative day. The confusion assessment method for the intensive care unit was used to screen patients for the presence of POD., Results: A total of 114 patients were included in the study. POD was associated with a decrease in BChE activity on postoperative day 1 (p=0.03). In addition, patients who developed POD, had significantly lower preoperative AChE activity than patients without POD (p<0.01). Multivariate analysis identified a preoperatively decreased AChE activity (OR 3.1; 95% CI 1.14 to 8.46), anticholinergic treatment (OR 5.09; 95% CI 1.51 to 17.23), elevated European System for Cardiac Operative Risk Evaluation (OR 3.68; 95% CI 1.04 to 12.99) and age (OR 3.02; 95% CI 1.06 to 8.62) to be independently associated with the development of POD., Conclusions: We conclude that a reduction in the acetylcholine hydrolysing enzyme activity in patients undergoing cardiac surgery may correlate with the development of POD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The i-gel mask is a second-generation, single-use supraglottic airway device which does not have an inflatable cuff. The cuff consists of a thermoplastic elastomer and its mechanism of sealing still remains unclear. Various theories such as temperature-dependent changes in hardness and volume expansion as well as fluid absorption have been discussed. The aim of the present study is to investigate changes in volume, weight and density caused by temperature changes., Material and Methods: Three i-gel masks (sizes 3, 4 and 5) were heated in a water bath from 10°C to 50°C in 5°C steps. The changes in weight, volume, and density were measured at each temperature step. In a second study, the identical parameters of masks (n = 5 of sizes 3, 4 and 5) used in patients were investigated. Results of volume and density between benchtop and patient measurements were examined for correlation., Results: All masks investigated, regardless of the size, showed a significant linear temperature-dependent volume expansion (sizes 3, 4 and 5: P < 0.001), a weight increase (sizes 3: P = 0.018; 4: P = 0.027; and 5: P = 0.006) and a linear decrease in density (sizes 3, 4 and 5: P < 0.001). There was a very strong correlation between the results of benchtop and patient measurements (volume: P < 0.001; density: P < 0.001)., Conclusions: We observed significant changes in all three properties investigated. Thus, a temperature-dependent volume expansion and weight increasement was observed, which can be considered as a further explanation for improved sealing after insertion.

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., (© 2019 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Background: Over the last decade, awake craniotomy for tumor resection has become a standard to maximize tumor resection and minimize the risk of permanent neurological deficits. Different techniques and medication regimes have been tested for this procedure. Until today there is no consensus on the optimal approach. Therefore, we investigated the effect of dexmedetomidine as an adjunct in awake cerebral tumor surgery and evaluated our improved technique., Methods: Data of patients who underwent awake craniotomy for tumor resection at our institution between 09/2006 and 05/2018 were retrospectively analyzed. All patients were kept awake after cortical mapping. After changing our standard anesthetic procedure from propofol/remifentanil alone to propofol/remifentanil and dexmedetomidine, we performed an evaluation of time to arousal, drug dosages, patients' cooperation and the occurrence of periprocedural adverse events., Results: Eighty-four patients received propofol/remifentanil alone (SG). A further 17 patients additionally received dexmedetomidine following craniotomy in order to induce rapid arousal (DG). In the dexmedetomidine group a significantly reduced infusion time for propofol (169.2 ± 47.4 vs. 212.9 ± 63.3 minutes; P = 0.008) and non-significantly shorter time to arousal (12.0 [10.0/16.5] vs. 15.0 [10.0/20.0] minutes; P = 0.271) could be identified. In general, the overall procedure was very well tolerated by all patients., Conclusions: The asleep-awake technique is a well-accepted and safe procedure. It allows continuous surveillance of the patient's neurological function during tumor resection and the postoperative phase, minimizing complications. In addition, our data show that the use of dexmedetomidine results in a shorter time to arousal.

Background: As a part of the German academic system the scientific habilitation is a significant individual qualification in research and teaching. In a pilot project, we recently reported the number of habilitations in anesthesiology, visceral surgery, gynecology and internal medicine. Here, we analyze habilitations from 13 additional clinical specialties., Methods: Habilitations in clinical specialties published in the German Medical Journal (Dtsch Arztebl) between 2010 and 2017 were quantitatively analyzed. For data validation, the dean offices of all German medical schools were requested to forward all accomplished habilitations. The percentage of women and the numbers with respect to the specialty were analyzed for each university hospital. Data are presented as medians (interquartile ranges)., Results: In this study, 2,264 accomplished habilitations were analyzed. Annually, 45 (36-56) habilitations were reported in orthopedic/trauma surgery, 40 (36-48) in radiology and 37 (29-46) in neurology, while the medians in the other analyzed specialties were lower. The highest percentage of women earning a habilitation degree was reported for pediatrics (37 %), dermatology (33 %), and ophthalmology (32 %)., Conclusions: Here, the output of completed habilitations from 13 medical specialties was analyzed for each German medical school. As a habilitation stands for a sustainable scientific contribution, this study may help to identify further career development needs for junior and for female scientists., (Copyright © 2019. Published by Elsevier GmbH.)

Background: The potential harmful effects of particle-contaminated infusions for critically ill adult patients are yet unclear. So far, only significant improved outcome in critically ill children and new-borns was demonstrated when using in-line filters, but for adult patients, evidence is still missing., Methods: This single-centre, retrospective controlled cohort study assessed the effect of in-line filtration of intravenous fluids with finer 0.2 or 1.2 μm vs 5.0 μm filters in critically ill adult patients. From a total of n = 3215 adult patients, n = 3012 patients were selected by propensity score matching (adjusting for sex, age, and surgery group) and assigned to either a fine filter cohort (with 0.2/1.2 μm filters, n = 1506, time period from February 2013 to January 2014) or a control filter cohort (with 5.0 μm filters, n = 1506, time period from April 2014 to March 2015). The cohorts were compared regarding the occurrence of severe vasoplegia, organ dysfunctions (lung, kidney, and brain), inflammation, in-hospital complications (myocardial infarction, ischemic stroke, pneumonia, and sepsis), in-hospital mortality, and length of ICU and hospital stay., Results: Comparing fine filter vs control filter cohort, respiratory dysfunction (Horowitz index 206 (119-290) vs 191 (104.75-280); P = 0.04), pneumonia (11.4% vs 14.4%; P = 0.02), sepsis (9.6% vs 12.2%; P = 0.03), interleukin-6 (471.5 (258.8-1062.8) ng/l vs 540.5 (284.5-1147.5) ng/l; P = 0.01), and length of ICU (1.2 (0.6-4.9) vs 1.7 (0.8-6.9) days; P <  0.01) and hospital stay (14.0 (9.2-22.2) vs 14.8 (10.0-26.8) days; P = 0.01) were reduced. Rate of severe vasoplegia (21.0% vs 19.6%; P > 0.20) and acute kidney injury (11.8% vs 13.7%; P = 0.11) was not significantly different between the cohorts., Conclusions: In-line filtration with finer 0.2 and 1.2 μm filters may be associated with less organ dysfunction and less inflammation in critically ill adult patients., Trial Registration: The study was registered at ClinicalTrials.gov (number: NCT02281604).

Background: Tracheal intubation still represents the "gold standard" in securing the airway of unconscious patients in the prehospital setting. Especially in cases of restricted access to the patient, video laryngoscopy became more and more relevant., Objectives: The aim of the study was to evaluate the performance and intubation success of four different video laryngoscopes, one optical laryngoscope, and a Macintosh blade while intubating from two different positions in a mannequin trial with difficult access to the patient., Methods: A mannequin with a cervical collar was placed on the driver's seat. Intubation was performed with six different laryngoscopes either through the driver's window or from the backseat. Success, C/L score, time to best view (TTBV), time to intubation (TTI), and number of attempts were measured. All participants were asked to rate their favored device., Results: Forty-two physicians participated. 100% of all intubations performed from the backseat were successful. Intubation success through the driver's window was less successful. Only with the Airtraq® optical laryngoscope, 100% success was achieved. Best visualization (window C/L 2a; backseat C/L 2a) and shortest TTBV (window 4.7 s; backseat 4.1 s) were obtained when using the D-Blade video laryngoscope, but this was not associated with a higher success through the driver's window. Fastest TTI was achieved through the window (14.2 s) when using the C-MAC video laryngoscope and from the backseat (7.3 s) when using a Macintosh blade., Conclusions: Video laryngoscopy revealed better results in visualization but was not associated with a higher success. Success depended on the approach and familiarity with the device. We believe that video laryngoscopy is suitable for securing airways in trapped accident victims. The decision for an optimal device is complicated and should be based upon experience and regular training with the device., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Florian J. Raimann et al.)

We have shown previously that during myocardial ischemia/reperfusion (MI/R), toll-like receptor 2 (TLR2) signaling regulates connexin 43 (Cx43) subcellular localization and function and dampens arrhythmia formation. We aimed to identify sites capable of TLR2-dependent redox modification within Cx43. Post-ischemic TLR2 -/- or wild-type (WT) mouse hearts were analyzed by OxICAT. Cx43 was mutated to exclude redox modification and transfected into HL-1 cardiomyocytes (CM) that were challenged with a TLR2 agonist. We identified Cys260 of Cx43 to be susceptible to reversible oxidation MI/R; TLR2 -/- leads to reduced H 2 O 2 production in post-ischemic isolated mitochondria and subsequently reduced oxidation of Cx43 at Cys260. Cx43 was dephosphorylated in WT, while phosphorylation was preserved in TLR2 -/- . Mutation of Cx43 (C260A) and lentiviral transfection in HL-1 CM accelerated pacemaker activity and reduced activity after TLR2 ligand stimulation. We here provide evidence for TLR2-dependent reversible oxidation of Cx43 at Cys260, which led to decreased Cx43 phosphorylation and affected CM pacemaker frequency and intercellular communication.

Background: Collective specific variegated alterations in the hemostatic system cast doubt on the uncritical usage of standard hemotherapy algorithms in patients with chronic liver disease. The aims of the present study were to examine the applicability of commonly used early viscoelastic parameters in this particular collective and to develop first-time thresholds for the early detection of clinically relevant platelet dysfunction., Methods: Patients suffering from advanced chronic liver disease were enrolled in this prospective single-centre study and consecutively allocated to Group 1 (MELD (Model for End-Stage Liver Disease) score 6 - 11) or Group 2 (MELD score > 16). We performed conventional laboratory coagulation analyses, as well as viscoelastometry (ROTEM®, EXTEM test, and FIBTEM test) and aggregometry (Multiplate®, ASPItest, and ADPtest), in each patient to analyze their hemostatic capacity. We analyzed the association between the A10 values (clot firmness 10 minutes after the initiation of clot building) in the EXTEM and FIBTEM tests and the corresponding Maximum Clot Firmness (MCF) values and performed receiver operating characteristic (ROC) curve analyses to investigate the ability of early parameters from the ASPItest and ADPtest (Aggregation Units (AU) 1 minute (T1), 2 minutes (T2) and 3 minutes (T3) after induction of platelet aggregation) of the Multiplate® system to predict clinically relevant platelet dysfunction., Results: In the complete study collective (n = 50) and in Group 1 and Group 2 (each n = 25), A10 values correlated highly significantly with corresponding MCF values. The bias between the A10 and the MCF values was 5.1 ± 2.4 mm and 1.2 ± 1.1 mm for the EXTEM test and FIBTEM test, respectively. The highest sensitivity and specificity values for the prediction of clinically relevant platelet dysfunction at measuring point T3 were analyzed to be the values 54.9 AU/min in the ASPItest and 50.1 AU/min in the ADPtest., Conclusions: The results of the study indicate that the basic principle of using the A10 values as so-called early vis-coelastic parameters for the estimation of MCF values is legitimate. The presumably divergent bias between the A10 and MCF values necessitates the development of collective specific thresholds in hemotherapy algorithms for coagulopathic patients suffering from advanced chronic liver disease.

More than 30% of all patients undergoing surgery suffer from preoperative anemia. Iron deficiency anemia is the most common type of anemia. The diagnostics and treatment of iron deficiency anemia can be carried out before patients undergo surgery as an alternative to blood transfusion and is an interdisciplinary task. This article gives an overview of various billing modalities and payment arrangements for management of preoperative anemia in the German healthcare system.

Background: Refugees have a significant risk of carrying multidrug-resistant organisms (MDRO), including multidrug-resistant gram-negative organisms (MDRGN) and methicillin-resistant Staphylococcus aureus (MRSA). Since the duration of MDRGN colonization has been shown to last for several months, we hypothesize that the prevalence of MDRO in refugees gradually declines during their stay in Germany to the level of MDRO prevalence in non-refugee patients. Knowledge about the dynamics of refugees' MDRO prevalence might provide the basis for appropriate infection control measures for refugees in hospitals as well as refugees' MDRO epidemiology in general. Material and methods: MDRO prevalence in 109 refugees admitted to the University Hospital Frankfurt, Germany, were compared to 819 adult controls and 224 pediatric patients admitted to the intensive care unit between June 2016 and May 2017. Results: 41.3% (95% confidence interval=31.9-51.1) of the refugees, 5.7% (4.2-7.6) of the adult controls and 8.9% (5.5-13.5) of the pediatric controls were positive for at least one MDRGN. The highest MDRGN prevalence was found in refugees who recently arrived (≤3 months) in Germany (72.4%; 52.8-87.3). Refugees' MDRGN prevalence declined continuously over time, reaching the adult and pediatric controls' MDRGN prevalence 18 months at the earliest after their arrival in Germany, i.e., 14.9% (1.8-42.8). Conclusion: This study demonstrates that refugees' MDRGN prevalence is declining over time since their arrival in Germany. 18 months after their arrival, refugees' and locals' MDRGN prevalence no longer differs significantly, although the refugees' MDRGN prevalence is still higher. A decline of MRSA prevalence was found 18 months after refugees' arrival. However, MRSA prevalence was still 14%, and thus 8 times higher than that of controls, indicating that precautionary measures continue to be necessary to prevent MRSA transmission., Competing Interests: The authors declare that they have no competing interests.

Objective: To assess the effect of a 5-hydroxytryptamine-3 receptor antagonist (granisetron) on the use of sympathomimetic (cafedrine/theodrenaline) and uterotonic (oxytocin) agents after spinal anesthesia during cesarean delivery., Methods: A retrospective observational analysis was conducted using intraoperative records (n=240) created at a single hospital in Germany between November 1, 2016, and July 31, 2017. The granisetron group (n=120) had received 3 mg of granisetron immediately before induction of spinal anesthesia. The control group (n=120) had not received granisetron. The primary endpoints were the intraoperative requirements for sympathomimetic and uterotonic agents. The secondary endpoints were parameters of intraprocedural maternal hemodynamic and clinical states., Results: More patients in the granisetron group than in the control group received intraoperative cafedrine/theodrenaline (P=0.045), with the cumulative intraoperative dosage also increased in the granisetron group (P=0.016). By contrast, the cumulative intraoperative dose of oxytocin was lower in the granisetron group than in the control group (P<0.001). Decreases in heart rate and mean arterial blood pressure were lower in the granisetron group versus the control group (P=0.015 and P=0.002, respectively)., Conclusion: Treatment with granisetron immediately before cesarean delivery did not reduce the perioperative requirement for sympathomimetics but did reduce the need for uterotonics. REGISTERED AT CLINICALTRIALS.GOV (NCT03318536)., (© 2019 International Federation of Gynecology and Obstetrics.)

BACKGROUND GLUT1-deficiency-syndrome (G1DS) is an autosomal dominant genetic disorder based on a mutation of the SLC2A1 gene. This mutation can lead to an encephalopathy due to abnormal glucose transport in the brain. G1DS is a rare disease, with an estimated incidence of 1: 90 000. CASE REPORT We report a case of a 10-year-old female who presented with recurrent fever, headaches, and vertigo for more than 3 days within 2 weeks following pneumonia. A bilateral mastoiditis was proven by a cerebral magnetic resonance imaging and a cranial computed tomography scan. The patient had to undergo mastoidectomy and thus, her first general anesthesia. Half a year previously she was diagnosed with G1DS. According to the standard of care, a ketogenic diet had been administered since the patient's diagnosis 6 months earlier. Our patient received a total intravenous anesthesia (TIVA) using propofol, fentanyl, and rocuronium administered without any incidents. CONCLUSIONS We recommend normoglycemia during the perioperative phase and avoidance of glucose-based medication to keep a patient's ketotic state. Our case highlights that TIVA, with the outlined medication used in this case, was safe when the patient's ketotic state and periprocedural blood glucose was monitored continuously. Nevertheless, we would suggest using remifentanil instead of fentanyl for future TIVAs due to a reduced increase in blood glucose level in our patient.

Objectives: To determine whether a multidisciplinary, multimodal Patient Blood Management (PBM) program for patients undergoing surgery is effective in reducing perioperative complication rate, and thereby is effective in improving clinical outcome., Background: PBM is a medical concept with the focus on a comprehensive anemia management, to minimize iatrogenic (unnecessary) blood loss, and to harness and optimize patient-specific physiological tolerance of anemia., Methods: A systematic review and meta-analysis was performed. Eligible studies had to address each of the 3 PBM pillars with at least 1 measure per pillar, for example, preoperative anemia management plus cell salvage plus rational transfusion strategy. The study protocol has been registered with PROSPERO (CRD42017079217)., Results: Seventeen studies comprising 235,779 surgical patients were included in this meta-analysis (100,886 pre-PBM group and 134,893 PBM group). Implementation of PBM significantly reduced transfusion rates by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55-0.68, P < 0.00001], 0.43 red blood cell units per patient (mean difference -0.43, 95% CI -0.54 to -0.31, P < 0.00001), hospital length of stay (mean difference -0.45, 95% CI -0.65 to -0.25, P < 0,00001), total number of complications (RR 0.80, 95% CI 0.74-0.88, P <0.00001), and mortality rate (RR 0.89, 95% CI 0.80-0.98, P = 0.02)., Conclusions: Overall, a comprehensive PBM program addressing all 3 PBM pillars is associated with reduced transfusion need of red blood cell units, lower complication and mortality rate, and thereby improving clinical outcome. Thus, this first meta-analysis investigating a multimodal approach should motivate all executives and health care providers to support further PBM activities.

Introduction: Balanced fluid replacement solutions can possibly reduce the risks for electrolyte imbalances, for acid-base imbalances, and thus for renal failure. To assess the intraoperative change of base excess (BE) and chloride in serum after treatment with either a balanced gelatine/electrolyte solution or a non-balanced gelatine/electrolyte solution, a prospective, controlled, randomized, double-blind, dual centre phase III study was conducted in two tertiary care university hospitals in Germany., Material and Methods: 40 patients of both sexes, aged 18 to 90 years, who were scheduled to undergo elective abdominal surgery with assumed intraoperative volume requirement of at least 15 mL/kg body weight gelatine solution were included. Administration of study drug was performed intravenously according to patients need. The trigger for volume replacement was a central venous pressure (CVP) minus positive end-expiratory pressure (PEEP) <10 mmHg (CVP <10 mmHg). The crystalloid:colloid ratio was 1:1 intra- and postoperatively. The targets for volume replacement were a CVP between 10 and 14 mmHg minus PEEP after treatment with vasoactive agent and mean arterial pressure (MAP) > 65 mmHg., Results: The primary endpoints, intraoperative changes of base excess -2.59 ± 2.25 (median: -2.65) mmol/L (balanced group) and -4.79 ± 2.38 (median: -4.70) mmol/L (non-balanced group)) or serum chloride 2.4 ± 1.9 (median: 3.0) mmol/L and 5.2 ± 3.1 (median: 5.0) mmol/L were significantly different (p = 0.0117 and p = 0.0045, respectively). In both groups (each n = 20) the investigational product administration in terms of volume and infusion rate was comparable throughout the course of the study, i.e. before, during and after surgery., Discussion: Balanced gelatine solution 4% combined with a balanced electrolyte solution demonstrated significant smaller impact on blood gas analytic parameters in the primary endpoints BE and serum chloride when compared to a non-balanced gelatine solution 4% combined with NaCl 0.9%. No marked treatment differences were observed with respect to haemodynamics, coagulation and renal function., Trial Registration: ClinicalTrials.gov (NCT01515397) and clinicaltrialsregister.eu, EudraCT number 2010-018524-58., Competing Interests: This study was supported by a restricted grant of B. Braun Meldungen AG, Germany. GM received honoria for consulting and research grants by B. Braun Melsungen AG and Adrenomed, lecture fees by B. Braun Melsungen AG. KZ has received payments for lectures and consulting from B. Braun Melsungen AG and Fresenius Kabi as well as funding for a clinical trial. PM has received payments for lectures and consulting from B. Braun Melsungen AG and Fresenius Kabi as well as funding for a clinical trial. RR received honoria for consulting from Fresenius; he received lecture fees from Fresenius and B. Braun Melsungen AG and is Editor-in-Chief of Der Anaesthesist and editor of the European Journal of Anaesthesiology. TS received honoria for board membership by Astellas Pharma GmbH, lecture fees by Astellas Pharma, Bayer Health Care, B. Braun Melsungen AG and Astra Zeneca and research grants by Bayer Health Care and Astellas Pharma GmbH. All the other authors declare that they have no competing interests. This does not alter our adherence to PLOS One policies on sharing data and materials.

Background: Postpartum hemorrhage is the leading cause of maternal death. Recently, the WOMAN trial showed that early administration of tranexamic acid leads to a reduced mortality due to bleeding. The aim was to study whether the results of the WOMAN trial have influenced the institutional standard operating procedures in treating postpartum hemorrhage., Methods: We performed a paper-based survey during the German Perinatal Congress in 2017 located in Berlin. A total of thirteen questions covered the fields of incidence, training, and treatment of postpartum hemorrhage., Results: 250 questionnaires were handed out to all participants of three different sessions during the congress. 72 questionnaires were returned, resulting in a return rate of 29%. 94% (n = 65) of all participants stated that they had implemented a standard operating procedure to treat postpartum hemorrhage prior to the WOMAN trial. 18 of these standard operating procedures were revised after the publication of the WOMAN trial, resulting in an early inclusion of tranexamic acid in 100% of all standard operating procedures., Conclusion: We recognized a correlation between the publication of the WOMAN trial and the administration of tranexamic acid at an early time-point in all standard operating procedures of the participating institutions to treat postpartum hemorrhage. In all those clinics whose algorithms initially did not contain any tranexamic acid, it was supplemented. This resulted in a 100% implementation of tranexamic acid., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Objective . Evaluation of C-MAC PM® in combination with a standard Macintosh blade size 3 in direct and indirect laryngoscopy and D-Blade® in indirect laryngoscopy in a simulated difficult airway. Primary outcome was defined as the best view of the glottic structures. Secondary endpoints were subjective evaluation and assessment of the intubation process. Methods . Prospective monocentric, observational study on 48 adult patients without predictors for difficult laryngoscopy/tracheal intubation undergoing orthopedic surgery. Every participant preoperatively received a cervical collar to simulate a difficult airway. Direct and indirect laryngoscopy w/o the BURP maneuver with a standard Macintosh blade and indirect laryngoscopy w/o the BURP maneuver using D-Blade® were performed to evaluate if blade geometry and the BURP maneuver improve the glottic view as measured by the Cormack-Lehane score. Results . Using a C-MAC PM® laryngoscope, D-Blade® yielded improved glottic views compared with the Macintosh blade used with either the direct or indirect technique. Changing from direct laryngoscopy using a Macintosh blade to indirect videolaryngoscopy using C-MAC PM® with D-Blade® improved the Cormack-Lehane score from IIb, III, or IV to I or II in 31 cases. Conclusion . The combination of C-MAC PM® and D-Blade® significantly enhances the view of the glottis compared to direct laryngoscopy with a Macintosh blade in patients with a simulated difficult airway. Trial Registration Number . This trial is registered under number NCT03403946.

Background: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum)., Methods/design: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival., Discussion: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine., Trial Registration: EudraCT, 2016-001788-34; ClinicalTrials.gov, NCT03334006 . Registered on 17 Nov 2017. Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort).

Re-infusion of washed autologous blood cell salvage from the operative field and wound drainages is used as part of blood conservation strategy within Patient Blood Management (PBM). Cell salvage is an effective method to reduce allogeneic blood transfusion. A main advantage of cell salvage is the prevention of storage-related damage to the erythrocytes.Cell salvage has wide applications in surgeries with expected blood loss higher than 500 ml like cardiac, vascular, orthopedic surgery, and by the use of blood irradiation also in cancer surgery., Competing Interests: P. M. und K. Z. erhielten finanzielle Förderungen von B. Braun Melsungen, CSL Behring, Fresenius Kabi und Vifor Pharma für eine Investigator-initiierte Studie zur Implementierung des Patient Blood Management Programms in vier Universitätsklinika. P. M. und/oder K. Z. erhielten Förderungen oder Reisekostenunterstützung für Beratungen und Vorträge der folgenden Firmen: Abbott GmbH & Co KG, AesculapAkademie GmbH, AQAI GmbH, AstellasPharma GmbH, AstraZeneca GmbH, Aventis Pharma GmbH, B. Braun Melsungen AG, Baxter Deutschland GmbH, Biosyn GmbH, Biotest AG, Bristol-Myers Squibb GmbH, CSL Behring GmbH, Dr. F. KöhlerChemie GmbH, Dräger Medical GmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, Fresenius Medical Care, Gambro Hospal GmbH, Gilead, GlaxoSmithKline GmbH, Grünenthal GmbH, Hamilton Medical AG, HCCM Consulting GmbH, Heinen + Löwenstein GmbH, Janssen-Cilag GmbH, med Update GmbH, Medivance EU B. V., MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH, P. J. Dahlhausen & Co. GmbH, Pfizer Pharma GmbH, Pulsion Medical Systems S.E., Siemens Healthcare, Teflex Medical GmbH, Teva GmbH, TopMedMedizintechnik GmbH, Verathon Medical, ViforPharma GmbH., (Georg Thieme Verlag KG Stuttgart · New York.)

Preoperative anemia is independently associated with increased morbidity and mortality and represents the strongest predictor for transfusion of red blood cells. Iron deficiency anemia is the most frequent form of anemia and could easily be treated by supplementation with iron. Patient Blood Management (PBM) focusses on prevention and management of anemia to optimize the patient and reduce unnecessary allogeneic blood products., Competing Interests: P. M. und K. Z. erhielten finanzielle Förderungen von B. Braun Melsungen, CSL Behring, Fresenius Kabi und Vifor Pharma für eine Investigator-initiierte Studie zur Implementierung des Patient Blood Management Programms in vier Universitäts klinika. P. M. und/oder K. Z. erhielten Förderungen oder Reisekostenunterstützung für Beratungen und Vorträge der folgenden Firmen: Abbott GmbH & Co KG, AesculapAkademie GmbH, AQAI GmbH, AstellasPharma GmbH, AstraZeneca GmbH, Aventis Pharma GmbH, B. Braun Melsungen AG, Baxter Deutschland GmbH, Biosyn GmbH, Biotest AG, Bristol-Myers Squibb GmbH, CSL Behring GmbH, Dr. F. KöhlerChemie GmbH, Dräger Medical GmbH, Essex Pharma GmbH, Fresenius Kabi GmbH, Fresenius Medical Care, Gambro Hospal GmbH, Gilead, GlaxoSmithKline GmbH, Grünenthal GmbH, Hamilton Medical AG, HCCM Consulting GmbH, Heinen + Löwenstein GmbH, Janssen-Cilag GmbH, med Update GmbH, Medivance EU B. V., MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Novo Nordisk Pharma GmbH, P. J. Dahlhausen & Co. GmbH, Pfizer Pharma GmbH, Pulsion Medical Systems S. E., Siemens Healthcare, Teflex Medical GmbH, Teva GmbH, TopMedMedizintechnik GmbH, Verathon Medical, ViforPharma GmbH., (Georg Thieme Verlag KG Stuttgart · New York.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy., Methods: The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9-10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5-9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect., Discussion: The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery., Trial Registration: ClinicalTrials.gov (identifier: NCT03369210 ).

Although blood transfusions have been used for more than 100 years and their potential to save lives is indisputable, there is still limited data on medium- and long-term outcomes after hemotherapy. Until recently, red blood cell transfusions represented the most commonly employed treatment for cancer anemia. As transfusions have been related to worse patient outcome in oncologic surgery, preventive strategies and alternative treatment approaches in the perioperative setting are warranted. This review aims to evaluate the evidence concerning the impact of transfusion on the course of malignant diseases with a focus on oncologic surgery and to provide a bundle of measures to improve patient care. The perioperative period is pivotal in determining long-term cancer outcome. An increasingly recognized area for improvement during this highly sensitive period is the treatment of anemia for three main reasons: Firstly, anemia has been recognized as an independent predictor of poor prognosis in cancer patients. Secondly, anemia is largely undertreated. Thirdly and probably most importantly, anemia therapy relied and often still relies heavily on red blood cell (RBC) transfusions, which may be an often suboptimal stopgap treatment. Perioperative RBC transfusions should be kept to a minimum due to growing concerns regarding the associated risks, which this review tries to clarify by providing an update of recent literature. This review furthermore discusses treatments for anemia and provides best-practice approaches to improve perioperative management of oncology patients undergoing surgery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sphingosine-1-phosphate (S1P) is involved in the regulation of important cellular processes, including immune-cell trafficking and proliferation. Altered S1P signaling is strongly associated with inflammation, cancer progression, and atherosclerosis; however, the mechanisms underlying its pathophysiologic effects are only partially understood. This study evaluated the effects of S1P in vitro and in vivo on the biosynthesis of leukotrienes (LTs), which form a class of lipid mediators involved in the pathogenesis of inflammatory diseases. Here, we report for the first time that S1P potently suppresses LT biosynthesis in Ca 2+ -ionophore-stimulated intact human neutrophils. S1P treatment resulted in intracellular Ca 2+ mobilization, perinuclear translocation, and finally irreversible suicide inactivation of the LT biosynthesis key enzyme 5-lipoxygenase (5-LO). Agonist studies and S1P receptor mRNA expression analysis provided evidence for a S1P receptor 4-mediated effect, which was confirmed by a functional knockout of S1P4 in HL60 cells. Systemic administration of S1P in wild-type mice decreased both macrophage and neutrophil migration in the lungs in response to LPS and significantly attenuated 5-LO product formation, whereas these effects were abrogated in 5-LO or S1P4 knockout mice. In summary, targeting the 5-LO pathway is an important mechanism to explain S1P-mediated pathophysiologic effects. Furthermore, agonism at S1P4 represents a novel effective strategy in pharmacotherapy of inflammation.-Fettel, J., Kühn, B., Guillen, N. A., Sürün, D., Peters, M., Bauer, R., Angioni, C., Geisslinger, G., Schnütgen, F., Meyer zu Heringdorf, D., Werz, O., Meybohm, P., Zacharowski, K., Steinhilber, D., Roos, J., Maier, T. J. Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity.

Background: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery., Methods: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery., Results: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10 - 8 ) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10 - 5 from the GWAS., Conclusions: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery., Trial Registration: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Patient blood management (PBM) is a multidisciplinary concept focused on the management of anaemia, minimisation of iatrogenic blood loss and rational use of allogeneic blood products. The aims of this study were: (i) to analyse post-operative outcome in patients with liberal vs restrictive exposure to allogeneic blood products and (ii) to evaluate the cost-effectiveness of PBM in patients undergoing surgery., Materials and Methods: A systematic literature review and meta-analysis were performed to compare post-operative complications in predominantly non-transfused patients (restrictive transfusion group) and patients who received one to three units of red blood cells (liberal transfusion group). Outcome measures included sepsis with/without pneumonia, acute renal failure, acute myocardial infarction and acute stroke. In a second step, a health economic model was developed to calculate cost-effectiveness of PBM (PBM-arm vs control-arm) for simulated cohorts of 10,000 cardiac and non-cardiac surgical patients based on the results of the meta-analysis and costs., Results: Out of 478 search results, 22 studies were analysed in the meta-analysis. The pooled relative risk of any complication in the restrictive transfusion group was 0.43 for non-cardiac and 0.34 for cardiac surgical patients. In the simulation model, PBM was related to reduced complications (1,768 vs 1,245) and complication-related deaths (411 vs 304) compared to standard care. PBM-related costs of therapy exceeded costs of the control arm by € 150 per patient. However, total costs, including hospitalisation, were higher in the control-arm for both non-cardiac (€ 2,885.11) and cardiac surgery patients (€ 1,760.69). The incremental cost-effectiveness ratio including hospitalisation showed savings of € 30,458 (non-cardiac and cardiac surgery patients) for preventing one complication and € 128,023 (non-cardiac and cardiac surgery patients) for prevention of one complication-related death in the PBM-arm., Discussion: Our results indicate that PBM may be associated with fewer adverse clinical outcomes compared to control management and may, thereby, be cost-effective.

Background: The use of cell salvage and autologous blood transfusion has become an important method of blood conservation. So far, there are no clinical data about the performance of the continuous autotransfusion device CATSmart., Methods: In total, 74 patients undergoing either cardiac or orthopedic surgery were included in this prospective, bicenter and observational technical evaluation to validate red cell separation process and washout quality of CATSmart. The target of red cell separation process was defined as a hematocrit value in the packed red cell unit of 55-75% and of washout quality of 80-100% removal ratio., Results: Hematocrit values measured by CATSmart and laboratory analysis were 78.5% [71.3%; 84.0%] and 73.7% [67.5%; 75.5%], respectively. Removal ratios for platelets 94.7% [88.2%; 96.7%], free hemoglobin 89.3% [85.2%; 94.9%], albumin 97.9% [96.6%; 98.5%], heparin 99.9% [99.9%; 100.0%], and potassium 92.5% [90.8%; 95.0%] were within the target range while removal of white blood cells was slightly worse 72.4% [57.9%; 87.3%]., Conclusion: The new autotransfusion device enables sufficient red cell separation and washout quality.

Introduction: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse., Methods and Analysis: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60. ETHICS AND DISSEMINATION: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals., Trial Registration Number: DRKS00013644; Pre-results., Competing Interests: Competing interests: MC received a grant for this trial from the Federal Ministry for Education and Research (BMBF), Bonn, Germany. MDN is currently funded by the US Patient-Centered Outcomes Research Institute for related work (grant PCS 1406-18876), and he is the principal investigator of the REGAIN Trial (Clinicaltrials.gov number NCT02507505)., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)