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1. Critical care hepatology: definitions, incidence, prognosis and role of liver failure in critically ill patients

Author: Aritz Perez Ruiz de Garibay, Andreas Kortgen, Julia Leonhardt, Alexander Zipprich, and Michael Bauer
Subjects: Acute liver failure, Acute-on-chronic liver failure, Secondary liver failure, Intensive care unit, Multiple organ failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Organ dysfunction or overt failure is a commonplace event in the critically ill affecting up to 70% of patients during their stay in the ICU. The outcome depends on the resolution of impaired organ function, while a domino-like deterioration of organs other than the primarily affected ones paves the way for increased mortality. “Acute Liver Failure” was defined in the 1970s as a rare and potentially reversible severe liver injury in the absence of prior liver disease with hepatic encephalopathy occurring within 8 weeks. Dysfunction of the liver in general reflects a critical event in “Multiple Organ Dysfunction Syndrome” due to immunologic, regulatory and metabolic functions of liver parenchymal and non-parenchymal cells. Dysregulation of the inflammatory response, persistent microcirculatory (hypoxic) impairment or drug-induced liver injury are leading problems that result in “secondary liver failure,” i.e., acquired liver injury without underlying liver disease or deterioration of preexisting (chronic) liver disease (“Acute-on-Chronic Liver Failure”). Conventional laboratory markers, such as transaminases or bilirubin, are limited to provide insight into the complex facets of metabolic and immunologic liver dysfunction. Furthermore, inhomogeneous definitions of these entities lead to widely ranging estimates of incidence. In the present work, we review the different definitions to improve the understanding of liver dysfunction as a perpetrator (and therapeutic target) of multiple organ dysfunction syndrome in critical care. Graphic Abstract
Published: 2022
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2. Circulating Bile Acids in Liver Failure Activate TGR5 and Induce Monocyte DysfunctionSummary

Author: Julia Leonhardt, Raphael S. Haider, Christoph Sponholz, Silke Leonhardt, Julia Drube, Katrin Spengler, Diana Mihaylov, Sophie Neugebauer, Michael Kiehntopf, Nevin A. Lambert, Andreas Kortgen, Tony Bruns, Frank Tacke, Carsten Hoffmann, Michael Bauer, and Regine Heller
Subjects: Liver Failure, Bile Acids, TGR5, GPBAR1, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Retention of bile acids in the blood is a hallmark of liver failure. Recent studies have shown that increased serum bile acid levels correlate with bacterial infection and increased mortality. However, the mechanisms by which circulating bile acids influence patient outcomes still are elusive. Methods: Serum bile acid profiles in 33 critically ill patients with liver failure and their effects on Takeda G-protein–coupled receptor 5 (TGR5), an immunomodulatory receptor that is highly expressed in monocytes, were analyzed using tandem mass spectrometry, novel highly sensitive TGR5 bioluminescence resonance energy transfer using nanoluciferase (NanoBRET, Promega Corp, Madison, WI) technology, and in vitro assays with human monocytes. Results: Twenty-two patients (67%) had serum bile acids that led to distinct TGR5 activation. These TGR5-activating serum bile acids severely compromised monocyte function. The release of proinflammatory cytokines (eg, tumor necrosis factor α or interleukin 6) in response to bacterial challenge was reduced significantly if monocytes were incubated with TGR5-activating serum bile acids from patients with liver failure. By contrast, serum bile acids from healthy volunteers did not influence cytokine release. Monocytes that did not express TGR5 were protected from the bile acid effects. TGR5-activating serum bile acids were a risk factor for a fatal outcome in patients with liver failure, independent of disease severity. Conclusions: Depending on their composition and quantity, serum bile acids in liver failure activate TGR5. TGR5 activation leads to monocyte dysfunction and correlates with mortality, independent of disease activity. This indicates an active role of TGR5 in liver failure. Therefore, TGR5 and bile acid metabolism might be promising targets for the treatment of immune dysfunction in liver failure.
Published: 2021
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3. Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: a narrative review

Author: Yasser Sakr, Manuela Giovini, Marc Leone, Giacinto Pizzilli, Andreas Kortgen, Michael Bauer, Tommaso Tonetti, Gary Duclos, Laurent Zieleskiewicz, Samuel Buschbeck, V. Marco Ranieri, and Elio Antonucci
Subjects: SARS-CoV-2, COVID-19, Pulmonary embolism, Thromboprophylaxis, Venous thromboembolism, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Preliminary reports have described significant procoagulant events in patients with coronavirus disease-2019 (COVID-19), including life-threatening pulmonary embolism (PE). Main text We review the current data on the epidemiology, the possible underlying pathophysiologic mechanisms, and the therapeutic implications of PE in relation to COVID-19. The incidence of PE is reported to be around 2.6–8.9% of COVID-19 in hospitalized patients and up to one-third of those requiring intensive care unit (ICU) admission, despite standard prophylactic anticoagulation. This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells. Conclusion Thromboprophylaxis should be started in all patients with suspected or confirmed COVID-19 admitted to the hospital. The use of an intermediate therapeutic dose of low molecular weight (LMWH) or unfractionated heparin can be considered on an individual basis in patients with multiple risk factors for venous thromboembolism, including critically ill patients admitted to the ICU. Decisions about extending prophylaxis with LMWH after hospital discharge should be made after balancing the reduced risk of venous thromboembolism (VTE) with the risk of increased bleeding events and should be continued for 7–14 days after hospital discharge or in the pre-hospital phase in case of pre-existing or persisting VTE risk factors. Therapeutic anticoagulation is the cornerstone in the management of patients with PE. Selection of an appropriate agent and correct dosing requires consideration of underlying comorbidities.
Published: 2020
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4. Identification of cardiovascular and molecular prognostic factors for the morbidity and mortality in COVID-19-sepsis (ICROVID): Protocol for a prospective multi-centre cohort study

Author: Charles Neu, Philipp Baumbach, André Scherag, Andreas Kortgen, Juliane Götze, and Sina M. Coldewey
Subjects: Medicine, Science
Abstract: Introduction Severe COVID-19 constitutes a form of viral sepsis. Part of the specific pathophysiological pattern of this condition is the occurrence of cardiovascular events. These include pulmonary embolism, arrhythmias and cardiomyopathy as manifestations of extra-pulmonary organ dysfunction. Hitherto, the prognostic impact of these cardiovascular events and their predisposing risk factors remains unclear. This study aims to explore this question in two cohorts of viral sepsis–COVID-19 and influenza–in order to identify new theragnostic strategies to improve the short- and long-term outcome of these two diseases. Methods and analysis In this prospective multi-centre cohort study, clinical assessment will take place during the acute and post-acute phase of sepsis and be complemented by molecular laboratory analyses. Specifically, echocardiography and cardiovascular risk factor documentation will be performed during the first two weeks after sepsis onset. Aside from routine haematological and biochemical laboratory tests, molecular phenotyping will comprise analyses of the metabolome, lipidome and immune status. The primary endpoint of this study is the difference in 3-month mortality of patients with and without septic cardiomyopathy in COVID-19 sepsis. Patients will be followed up until 6 months after onset of sepsis via telephone interviews and questionnaires. The results will be compared with a cohort of patients with influenza sepsis as well as previous cohorts of patients with bacterial sepsis and healthy controls. Ethics and dissemination Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (2020-2052-BO). The results will be published in peer-reviewed journals and presented at appropriate conferences. Trial registration DRKS00024162.
Published: 2022

5. Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry.

Author: Fatime Hawchar, Dana Tomescu, Karl Träger, Dominik Joskowiak, Klaus Kogelmann, Jens Soukup, Singrun Friesecke, David Jacob, Jan Gummert, Andreas Faltlhauser, Filippo Aucella, Martijn van Tellingen, Manu L N G Malbrain, Ralph Bogdanski, Günter Weiss, Andreas Herbrich, Stefan Utzolino, Axel Nierhaus, Andreas Baumann, Andreas Hartjes, Dietrich Henzler, Evgeny Grigoryev, Harald Fritz, Friedhelm Bach, Stefan Schröder, Andreas Weyland, Udo Gottschaldt, Matthias Menzel, Olivier Zachariae, Radovan Novak, Jernej Berden, Hendrik Haake, Michael Quintel, Stephan Kloesel, Andreas Kortgen, Stephanie Stecher, Patricia Torti, Frieder Nestler, Markus Nitsch, Detlef Olboeter, Philip Muck, Michael Findeisen, Diane Bitzinger, Jens Kraßler, Martin Benad, Martin Schott, Ulrike Schumacher, Zsolt Molnar, and Frank Martin Brunkhorst
Subjects: Medicine, Science
Abstract: The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).
Published: 2022
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6. Infliximab against severe COVID-19-induced cytokine storm syndrome with organ failure—a cautionary case series

Author: Andreas Stallmach, Andreas Kortgen, Falk Gonnert, Sina M. Coldewey, Philipp Reuken, and Michael Bauer
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2020
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7. Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery – a sub-analysis of the RIPHeart-Study

Author: Sabine Westphal, Christian Stoppe, Matthias Gruenewald, Berthold Bein, Jochen Renner, Jochen Cremer, Mark Coburn, Gereon Schaelte, Andreas Boening, Bernd Niemann, Frank Kletzin, Jan Roesner, Ulrich Strouhal, Christian Reyher, Rita Laufenberg-Feldmann, Marion Ferner, Ivo F. Brandes, Martin Bauer, Andreas Kortgen, Sebastian N. Stehr, Maria Wittmann, Georg Baumgarten, Rafael Struck, Tanja Meyer-Treschan, Peter Kienbaum, Matthias Heringlake, Julika Schoen, Michael Sander, Sascha Treskatsch, Thorsten Smul, Ewa Wolwender, Thomas Schilling, Frauke Degenhardt, Andre Franke, Soeren Mucha, Lukas Tittmann, Madeline Kohlhaas, Georg Fuernau, Oana Brosteanu, Dirk Hasenclever, Kai Zacharowski, Patrick Meybohm, and RIPHeart-Study Collaborators
Subjects: Genome-wide association study, Cardiac surgery, Atrial fibrillation, Delirium, Myocardial infarction, Acute kidney injury, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract 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
Published: 2019
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8. Short-term treatment with taurolidine is associated with liver injury

Author: René Fahrner, Anika Möller, Adrian T. Press, Andreas Kortgen, Michael Kiehntopf, Falk Rauchfuss, Utz Settmacher, and Alexander S. Mosig
Subjects: Cytokines, Liver injury, Liver biochip, Taurolidine, Liver enzymes, Therapeutics. Pharmacology, RM1-950, Toxicology. Poisons, RA1190-1270
Abstract: Abstract Background Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver. Methods In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology. Results In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment. Conclusions Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation.
Published: 2017
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9. RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow‐Up

Author: Patrick Meybohm, Madeline Kohlhaas, Christian Stoppe, Matthias Gruenewald, Jochen Renner, Berthold Bein, Martin Albrecht, Jochen Cremer, Mark Coburn, Gereon Schaelte, Andreas Boening, Bernd Niemann, Michael Sander, Jan Roesner, Frank Kletzin, Haitham Mutlak, Sabine Westphal, Rita Laufenberg‐Feldmann, Marion Ferner, Ivo F. Brandes, Martin Bauer, Sebastian N. Stehr, Andreas Kortgen, Maria Wittmann, Georg Baumgarten, Tanja Meyer‐Treschan, Peter Kienbaum, Matthias Heringlake, Julika Schoen, Sascha Treskatsch, Thorsten Smul, Ewa Wolwender, Thomas Schilling, Georg Fuernau, Holger Bogatsch, Oana Brosteanu, Dirk Hasenclever, and Kai Zacharowski
Subjects: cardio‐vascular surgery, ischemia/reperfusion injury, remote ischemic preconditioning, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundRemote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham‐RIPC. Methods and ResultsIn this follow‐up paper, we present 1‐year follow‐up of the composite primary end point and its individual components (all‐cause mortality, myocardial infarction, stroke and acute renal failure), in a sub‐group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1‐year composite primary end point (RIPC versus sham‐RIPC 16.4% versus 16.9%) and its individual components (all‐cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. ConclusionsSimilar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long‐term outcome in cardiac surgery patients undergoing propofol anesthesia. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.
Published: 2018
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10. Anticoagulation Strategies in Venovenous Hemodialysis in Critically Ill Patients: A Five-Year Evaluation in a Surgical Intensive Care Unit

Author: Christoph Sponholz, Ole Bayer, Björn Kabisch, Karin Wurm, Katharina Ebert, Michael Bauer, and Andreas Kortgen
Subjects: Technology, Medicine, Science
Abstract: Renal failure is a common complication among critically ill patients. Timing, dosage, and mode of renal replacement (RRT) are under debate, but also anticoagulation strategies and vascular access interfere with dialysis success. We present a retrospective, five-year evaluation of patients requiring RRT on a multidisciplinary 50-bed surgical intensive care unit of a university hospital with special regard to anticoagulation strategies and vascular access. Anticoagulation was preferably performed with unfractionated heparin or regional citrate application (RAC). Bleeding and suspected HIT-II were most common causes for RAC. In CVVHD mode filter life span was significantly longer under RAC compared to heparin or other anticoagulation strategies (P=0.001). Femoral vascular access was associated with reduced filter life span (P=0.012), especially under heparin anticoagulation (P=0.015). Patients on RAC had higher rates of metabolic alkalosis (P=0.001), required more transfusions (P=0.045), and showed higher illness severity measured by SOFA scores (P=0.001). RRT with unfractionated heparin represented the most common anticoagulation strategy in this study population. However, patients with bleeding risk and severe organ dysfunction were more likely placed on RAC. Citrate provided longer filter life spans regardless of vascular access site. Attention has to be paid to metabolic disturbances.
Published: 2014
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11. Liver dysfunction and phosphatidylinositol-3-kinase signalling in early sepsis: experimental studies in rodent models of peritonitis.

Author: Peter Recknagel, Falk A Gonnert, Martin Westermann, Sandro Lambeck, Amelie Lupp, Alain Rudiger, Alex Dyson, Jane E Carré, Andreas Kortgen, Christoph Krafft, Jürgen Popp, Christoph Sponholz, Valentin Fuhrmann, Ingrid Hilger, Ralf A Claus, Niels C Riedemann, Reinhard Wetzker, Mervyn Singer, Michael Trauner, and Michael Bauer
Subjects: Medicine
Abstract: BackgroundHepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests.Methods and findingsIn a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87).ConclusionsLiver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is necessary to extend these concepts into clinical practice. Please see later in the article for the Editors' Summary.
Published: 2012
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12. Evaluation of a polymerase chain reaction assay for pathogen detection in septic patients under routine condition: an observational study.

Author: Frank Bloos, Svea Sachse, Andreas Kortgen, Mathias W Pletz, Marc Lehmann, Eberhard Straube, Niels C Riedemann, Konrad Reinhart, and Michael Bauer
Subjects: Medicine, Science
Abstract: BACKGROUND: Treatment of septic shock relies on appropriate antimicrobial therapy. Current culture based methods deliver final results after days, which may delay potentially lifesaving adjustments in antimicrobial therapy. This study was undertaken to compare PCR with blood culture results under routine conditions regarding 1. impact on antimicrobial therapy, and 2. time to result, in patients with presumed sepsis. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational study in a 50 beds ICU of a university hospital. In 245 patients with suspected sepsis, 311 concomitant blood cultures and blood for multiplex PCR (VYOO(®)) were obtained. 45 of 311 blood cultures (14.5%) and 94 of 311 PCRs (30.1%) were positive. However, blood culture or microbiological sampling from the presumed site of infection rarely confirmed PCR results and vice versa. Median time to positivity and interquartile range were 24.2 (18.0, 27.5) hours for the PCR and 68 (52.2, 88.5) hours for BC (p
Published: 2012
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13. Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients

Author: Martin Dres, Marcelo Gama de Abreu, Hamid Merdji, Holger Müller-Redetzky, Dominic Dellweg, Winfried J. Randerath, Satar Mortaza, Boris Jung, Christian Bruells, Onnen Moerer, Martin Scharffenberg, Samir Jaber, Sébastien Besset, Thomas Bitter, Arnim Geise, Alexander Heine, Maximilian V. Malfertheiner, Andreas Kortgen, Jonathan Benzaquen, Teresa Nelson, Alexander Uhrig, Olaf Moenig, Ferhat Meziani, Alexandre Demoule, Thomas Similowski, François Beloncle, Pierre-Yves Olivier, Marie Lemerle, Pierre Asfar, Alain Mercat, Katharina Böllinger, Marc Giesa, Carmen Garcia, Till Jacobi, Nikolas Lambiris, Felix Machleid, Panagiotis Pergantis, Bastian Grube, Damien Roux, Santiago Freita Ramos, Noemie Zucman, Louis Marie Dumont, Laura Federici, Marc Amouretti, Jean-Damien Ricard, Didier Dreyfuss, Jakob Wittenstein, Andreas Güldner, Max Ragaller, Peter Spieth, Christopher Uhlig, Lars-Olav Harnisch, Frank Bloos, Daniel O. Thomas-Rüddel, Gérald Chanques, Mathieu Capdevila, Yassir Aarab, Fanny Garnier, Vincent Brunot, Kada Klouche, Valérie Moulaire, Philippe Corne, Fernand Macone, François Durand, Charles Hugo Marquette, Julie Delemazure, Julien Mayaux, Elise Morawiec, Alexandra Monnier, Hassene Rahmani, Louise-Marie Jandeaux, Antoine Studer, Julie Helms, and Raphaël Clere-Jehl
Subjects: Pulmonary and Respiratory Medicine, Critical Care and Intensive Care Medicine
Published: 2022

14. Which Patient Should Be Chosen? The National Transferal System for the Management of COVID-19 Intensive Care Patients. A Retrospective Multicentre Cohort Study in Germany, 2020 – 2022

Author: Sebastian Lang, Jonas Brock, Pia Lautenbach, Paul Korbmacher, Katja Bär, Daniel Thomas-Rüddel, Andreas Kortgen, Stefan Russwurm, Heinrich V. Groesdonk, Raimondo Laubinger, Michael Bauer, and Petra Dickmann
Published: 2023

15. The clinical spectrum of pulmonary thromboembolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: A European case series

Author: Andreas Kortgen, Samuel Buschbeck, Marc Leone, V. Marco Ranieri, Yasser Sakr, Giacinto Pizzilli, Tommaso Tonetti, Laurent Zieleskiewicz, Manuela Giovini, Gary Duclos, Elio Antonucci, Michael Bauer, Sakr Y., Giovini M., Leone M., Pizzilli G., Kortgen A., Bauer M., Tonetti T., Duclos G., Zieleskiewicz L., Buschbeck S., Ranieri V.M., Antonucci E., Jena University Hospital [Jena], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Bologna/Università di Bologna, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Care and Intensive Care Medicine, medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, In patient, Thromboprophylaxis, ComputingMilieux_MISCELLANEOUS, Coronavirus, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, business.industry, Pulmonary embolism, COVID-19, 030208 emergency & critical care medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Pneumonia, 030228 respiratory system, Concomitant, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Thromboprophylaxi, Complication, business, Venous thromboembolism
Abstract: Purpose To describe the clinical characteristics and outcomes of coronavirus disease-2019 (COVID-19)-associated pulmonary thromboembolism (PTE). Materials and methods A case series of five patients, representing the clinical spectrum of COVID-19 associated PTE. Patients were admitted to four hospitals in Germany, Italy, and France. Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was confirmed using a real-time reverse transcription polymerase chain reaction test. Results The onset of PTE varied from 2 to 4 weeks after the occurrence of the initial symptoms of SARS-CoV-2 infection and led to deterioration of the clinical picture in all cases. PTE was the primary reason for hospital admission after a 2-week period of self-isolation at home (1 patient) and hospital readmission after initial uncomplicated hospital discharge (2 patients). Three of the patients had no past history of clinically relevant risk factors for venous thromboembolism (VTE). Severe disease progression was associated with concomitant increases in IL-6, ferritin, and D-Dimer levels. The outcome from PTE was related to the extent of vascular involvement, and associated complications. Conclusion PTE is a potential life-threatening complication, which occurs frequently in patients with COVID-19. Intermediate therapeutic dose of anticoagulants and extend thromboprophylaxis are necessary after meticulous risk-benefit assessment., Highlights • Pulnonary thromboembolism (PTE) is a frequent life-threatening complication in patients with coronavirsus disease-2019 (COVID-19). • The onset of PTE varies from 2 to 4 weeks after the occurrence of the initial symptoms and may occur during home self-isolation or after hospital discharge of primarily uncomplicated hospital admission. • PTE may occur in patients without clinically relevant past history of risk factors for venous thromboembolism and in those receiving standard prophylactic anticoagulation. • Intermediate therapeutic dose of anticoagulants and extend thromboprophylaxis are necessary in these patients after meticulous risk-benefit assessment.
Published: 2021

16. 'Coronavirus disease 2019' (COVID-19): update für Anästhesisten und Intensivmediziner März 2020

Author: Johannes Winning, Michael Bauer, Uwe Janssens, Dominique Ouart, Andreas Kortgen, Daniel Thomas-Rüddel, and Petra Dickmann
Subjects: Cross infection, Gynecology, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030208 emergency & critical care medicine, General Medicine, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, Medicine, business, Coronavirus Infections
Abstract: Die neu aufgetretene Atemwegserkrankung „coronavirus disease 2019“ (COVID-19) hat Deutschland erreicht. Die Erkrankung verlauft in den meisten Fallen leicht, aber der kleinere Anteil an schwer Erkrankten wird stationar und auch intensivmedizinisch behandelt werden. Im Gegensatz zu anderen akuten Infektionskrankheiten zeigen die schweren Verlaufe eine langsame Progredienz von den ersten Symptomen bis zur lebensbedrohlichen Verschlechterung. Die Diagnosestellung erfolgt mithilfe der Polymerase-Kettenreaktion (PCR) aus Proben des Respirationstrakts. Ein schweres „acute respiratory distress syndrome“ (ARDS) ist charakteristisch fur die kritischen Verlaufe. Der Vermeidung nosokomialer Infektionen, insbesondere durch korrekte Anwendung der Schutzausrustung, und der Aufrechterhaltung des Krankenhausbetriebs kommen zentrale Bedeutung zu. Auch in der Anasthesie und Notfallmedizin ist mit erheblichen Herausforderungen zu rechnen.
Published: 2020

17. Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry

Author: Fatime Hawchar, Dana Tomescu, Karl Träger, Dominik Joskowiak, Klaus Kogelmann, Jens Soukup, Singrun Friesecke, David Jacob, Jan Gummert, Andreas Faltlhauser, Filippo Aucella, Martijn van Tellingen, Manu L. N. G. Malbrain, Ralph Bogdanski, Günter Weiss, Andreas Herbrich, Stefan Utzolino, Axel Nierhaus, Andreas Baumann, Andreas Hartjes, Dietrich Henzler, Evgeny Grigoryev, Harald Fritz, Friedhelm Bach, Stefan Schröder, Andreas Weyland, Udo Gottschaldt, Matthias Menzel, Olivier Zachariae, Radovan Novak, Jernej Berden, Hendrik Haake, Michael Quintel, Stephan Kloesel, Andreas Kortgen, Stephanie Stecher, Patricia Torti, Frieder Nestler, Markus Nitsch, Detlef Olboeter, Philip Muck, Michael Findeisen, Diane Bitzinger, Jens Kraßler, Martin Benad, Martin Schott, Ulrike Schumacher, Zsolt Molnar, and Frank Martin Brunkhorst
Subjects: Multidisciplinary, C-Reactive Protein, ROC Curve, Interleukin-6, Critical Illness, Sepsis, Humans, Registries, Prognosis, Procalcitonin, Shock, Septic, Biomarkers
Abstract: The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and “other” reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).
Published: 2021

18. Intraoperative reduction of vasopressors using processed electroencephalographic monitoring in patients undergoing elective cardiac surgery: a randomized clinical trial

Author: C. Schelenz, Torsten Doenst, Michael Bauer, Andreas Kortgen, L Koenig, Christoph Sponholz, H Hoyer, C Schuwirth, and Sina M. Coldewey
Subjects: Male, medicine.medical_specialty, Population, Coronary Artery Bypass, Off-Pump, Blood Pressure, Health Informatics, Intraoperative Awareness, Critical Care and Intensive Care Medicine, law.invention, Norepinephrine, 03 medical and health sciences, Catecholamines, 0302 clinical medicine, Randomized controlled trial, Anesthesiology, Risk Factors, 030202 anesthesiology, law, Clinical endpoint, medicine, Cardiopulmonary bypass, Humans, Vasoconstrictor Agents, Anesthesia, Cardiac Surgical Procedures, education, Adverse effect, Aged, Inflammation, education.field_of_study, Cardiopulmonary Bypass, business.industry, Hemodynamics, Electroencephalography, 030208 emergency & critical care medicine, Middle Aged, Cardiac surgery, Anesthesiology and Pain Medicine, Female, business
Abstract: Intraoperative vasopressor and fluid application are common strategies against hypotension. Use of processed electroencephalographic monitoring (pEEG) may reduce vasopressor application, a known risk factor for organ dysfunction, in elective cardiac surgery patients. Randomized single-centre clinical trial at Jena University Hospital. Adult patients operated on cardiopulmonary bypass or off-pump coronary artery bypass grafting were randomised to receive anesthesia with visible or blinded pEEG using Narcotrend™. In blinded-Narcotrend (NT) depth of anesthesia was extrapolated from clinical signs, hemodynamic response and anesthetic concentration, supplemented by target indices between 37 and 64 in the visible-NT group. Intraoperative norepinephrine requirement (primary endpoint), fluid balance, extubation time, delirium occurrence and adverse events were evaluated. Patients of the intent-to-treat population (visible-NT: n = 123, blinded-NT: n = 122) had similar patient and procedural characteristics. Adjusted for type of surgery intraoperative Norepinephrine application was significantly reduced in visible-NT (n = 120, robust mean of cumulative dose 4.71 µg/kg bodyweight) compared to blinded-NT patients (n = 119, 6.14 µg/kg bodyweight) (adjusted robust mean difference 1.71 (95% CI 0.33-3.10) µg/kg bodyweight). Although reduction in patients operated on cardiopulmonary bypass was higher the interaction was not significant in post-hoc subgroup analysis. Intraoperative fluid balance was similar among both groups and strata. Extubation time was non-significantly lower in visible than in blinded-NT group. Overall postoperative delirium risk was 16.4% without differences among the groups. Adverse events-sudden movement/coughing, perspiration or hypertension-occurred more often with visible-NT, while one blinded-NT patient experienced intraoperative awareness. Titration of depth of anesthesia in elective cardiac surgery patients using pEEG allows to reduce application of norepinephrine.
Published: 2019

19. The Effect of Extracorporeal Albumin Dialysis (ECAD) on Pruritus Using MARS Versus New Adsorbent Recirculation (OPAL)

Author: Alexandra Rivera Luna, Hartmut Schmidt, Hans Ulrich Gerth, Claudia Pfensig, Jan Stange, Christoph Sponholz, Sebastian Klammt, Christian Wilms, Kristin Bruederlein, Andreas Kortgen, Michael Hinz, Steffen Mitzner, Matthias M. Dollinger, Raoul Benedikt Sauer, Victoria Rivera Luna, Adrian Dominik, and Sebastian Koball
Subjects: Liver disease, medicine.medical_specialty, Refractory, business.industry, Albumin, Urology, Medicine, Mars Exploration Program, business, medicine.disease, Dialysis (biochemistry), Extracorporeal
Published: 2020

20. Coronavirus disease 2019 (COVID-19): update for anesthesiologists and intensivists March 2020

Author: Michael Bauer, Daniel Thomas-Rüddel, Petra Dickmann, Andreas Kortgen, Johannes Winning, Dominique Ouart, and Uwe Janssens
Subjects: medicine.medical_specialty, ARDS, Disease, medicine.disease_cause, Sepsis, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Germany, Anesthesiology, Intensive care, medicine, Humans, Infection control, Intensive care medicine, Coronavirus, SARS-CoV-2, business.industry, COVID-19, Outbreak, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Anesthesiologists, Anesthesiology and Pain Medicine, business
Abstract: The current outbreak of coronavirus disease (COVID-19) has reached Germany. The majority of people infected present with mild disease, but there are severe cases that need intensive care. Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function. Diagnosis relies on PCR using specimens from the respiratory tract. Severe ARDS reflects the hallmark of a critical course of the disease. Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals' operational capability are of utmost importance. Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges.Die neu aufgetretene Atemwegserkrankung „coronavirus disease 2019“ (COVID-19) hat Deutschland erreicht. Die Erkrankung verläuft in den meisten Fällen leicht, aber der kleinere Anteil an schwer Erkrankten wird stationär und auch intensivmedizinisch behandelt werden. Im Gegensatz zu anderen akuten Infektionskrankheiten zeigen die schweren Verläufe eine langsame Progredienz von den ersten Symptomen bis zur lebensbedrohlichen Verschlechterung. Die Diagnosestellung erfolgt mithilfe der Polymerase-Kettenreaktion (PCR) aus Proben des Respirationstrakts. Ein schweres „acute respiratory distress syndrome“ (ARDS) ist charakteristisch für die kritischen Verläufe. Der Vermeidung nosokomialer Infektionen, insbesondere durch korrekte Anwendung der Schutzausrüstung, und der Aufrechterhaltung des Krankenhausbetriebs kommen zentrale Bedeutung zu. Auch in der Anästhesie und Notfallmedizin ist mit erheblichen Herausforderungen zu rechnen.
Published: 2020
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21. Comparison of albumin dialysis devices molecular adsorbent recirculating system and ADVanced Organ Support system in critically ill patients with liver failure-A retrospective analysis

Author: Christoph Falkensteiner, Andreas Kortgen, Michael Bauer, Julia Leonhardt, and Christoph Sponholz
Subjects: Adult, Male, medicine.medical_specialty, Bilirubin, medicine.drug_class, medicine.medical_treatment, Critical Illness, 030232 urology & nephrology, Urology, 030204 cardiovascular system & hematology, Extracorporeal, Hospitals, University, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Renal Dialysis, Detoxification, Albumins, medicine, Humans, Platelet, Citrates, Adverse effect, Dialysis, Aged, Retrospective Studies, business.industry, Anticoagulant, Albumin, Anticoagulants, Hematology, Equipment Design, Middle Aged, chemistry, Nephrology, Female, business, Liver Failure
Abstract: Extracorporeal albumin dialysis (ECAD) represents a supplemental therapy for patients with liver failure. Most experience was gained with the molecular adsorbent recirculating system (MARS). However, the ADVanced Organ Support (ADVOS) system was recently introduced. This study aims to compare effects of MARS and ADVOS on biochemical and clinical parameters in critically ill patients with liver failure using a retrospective analysis of ECAD at Jena University Hospital. Laboratory parameters, health scoring values, and need for transfusion were recorded before and after treatment. Generalized estimating equations were used to account for repeated measurements of multiple ECAD cycles per patient. Between 2012 and 2017, n = 75 MARS and n = 58 ADVOS cycles were evaluated. Although ADVOS runs significantly longer, both devices provided comparable reduction rates of bilirubin (MARS: -48 [-80.5 to -18.5] μmol/L vs ADVOS: -35 [-87.8 to -2.0] μmol/L, P = .194), a surrogate for detoxification capacity, while urea and lactate levels were more significantly lowered by the ADVOS system. In cycles with similar treatment times, both systems provided comparable reduction rates for bilirubin, renal replacement, coagulation, and metabolic parameters. Citrate was the preferred anticoagulant in case of bleeding. Neither bleeding tendency nor fibrinogen levels or platelets were altered by the type of anticoagulation. No adverse events were reported, but two sessions (one MARS and one ADVOS) were terminated early due to filter clotting. Experience is needed in the application of ADVOS and more prospective trials comparing the detoxification capacity of ECAD devices are needed to support and enlarge the findings of the current evaluation.
Published: 2020

22. Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial

Author: Melanie Meersch, Carola Wempe, John A. Kellum, Christian Putensen, Bartosz Tyczynski, Joachim Gerss, Andreas Kortgen, Stefan Kluge, Peter Rosenberger, Michael Jahn, Patrick Meybohm, Ulrich Jaschinski, Onnen Moerer, Philipp Deetjen, Nils Mülling, Sean M. Bagshaw, Mira Küllmar, Thomas Dimski, Torsten Slowinski, Stefan Wirtz, Detlef Kindgen-Milles, Rich Investigators, Philipp Simon, Gernot Marx, Alexander Zarbock, Jens-Christian Schewe, Timo Brandenburger, Martin Mehrländer, Tim Philipp Simon, Dominik Jarczak, and Marc Bodenstein
Subjects: Male, Time Factors, Continuous Renal Replacement Therapy, Critical Illness, medicine.medical_treatment, Medizin, Hemorrhage, Kaplan-Meier Estimate, Infections, 01 natural sciences, Citric Acid, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Germany, medicine, Humans, 030212 general & internal medicine, Renal replacement therapy, 0101 mathematics, Dialysis, Original Investigation, Aged, Proportional Hazards Models, medicine.diagnostic_test, Heparin, business.industry, 010102 general mathematics, Acute kidney injury, Anticoagulants, General Medicine, Acute Kidney Injury, medicine.disease, 3. Good health, Clinical trial, Anesthesia, Early Termination of Clinical Trials, Calcium, Female, Partial Thromboplastin Time, Hemodialysis, business, Filtration, Partial thromboplastin time
Abstract: IMPORTANCE: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. OBJECTIVE: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTS: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONS: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P
Published: 2020

23. What does critical illness do to the liver?

Author: Michael Bauer and Andreas Kortgen
Subjects: medicine.diagnostic_test, Bilirubin, business.industry, Acute-phase protein, Inflammation, Systemic inflammation, Bioinformatics, chemistry.chemical_compound, chemistry, Pharmacokinetics, Shock (circulatory), medicine, Liver function, medicine.symptom, Liver function tests, business
Abstract: Common pathophysiologic states in critically ill patients, such as systemic inflammation or shock, lead to profound alterations in liver function with a reprogramming of protein synthesis referred to as ‘acute phase response’. In parallel, a disruption of phase I and II biotransformation and bile transport is frequently observed. Complex mechanisms to regulate liver blood flow might be impaired, leading to hypoperfusion, shunting and ultimately to cell death primarily in the pericentral region. The incidence and severity of liver impairment is underestimated when exclusively traditional “static” biomarkers, such as bilirubin and serum transaminases, are used while “dynamic” tests evaluating excretory or metabolic functions, such as plasma disappearance rate of indocyanine green or methacetin breath test, are more sensitive. Nevertheless, even slight elevations of bilirubin are associated with worse outcome in critical care patients. Changes in liver function lead to unpredictable changes in pharmacokinetics and pharmacodynamics, particularly in multidrug therapy frequently initiated in the critically ill. For some drugs, such as sedatives or analgesics, careful clinical assessment might be sufficient. Whenever possible, therapeutic monitoring should be performed. Sometimes, liver function tests and scoring systems can be helpful to adapt dosage. In principal, drugs solely metabolized via phase II metabolism should be preferred as this pathway is often less impaired. In contrast, the hepatobiliary excretory machinery appears exceptionally sensitive to inflammation. Hepatotoxic drugs should be avoided whenever possible to prevent additional liver damage.
Published: 2020

24. Contributors

Author: Gareth L. Ackland, Adeel Rafi Ahmed, Djillali Annane, Eman Ansari, Hubertus Axer, Jan Bakker, Ian J. Barbash, John James Bates, Michael Bauer, Amy L. Bellinghausen, William S. Bender, Matthew R. Biery, Alexandra Binnie, Thomas P. Bleck, Christina Boncyk, Jason C. Brainard, Scott C. Brakenridge, Frank Martin Brunkhorst, Tara Cahill, BSc(Physio), Christina Campbell, Jonathan Dale Casey, Jean-Marc Cavaillon, Maurizio Cereda, David J. Cooper, Craig M. Coopersmith, Jennifer Cruz, Cheston B. Cunha, Gerard F. Curley, Allison Dalton, Daniel De Backer, Clifford S. Deutschman, David Devlin, Claudia C. Dos, Tomas Drabek, Laura Dragoi, Martin Dres, Anne M. Drewry, Stephen Duff, Philip A. Efron, Sinéad Egan, MB, Ali A. El, E. Wesley Ely, Laura Evans, Jessica Falco-Walter, Jonathan K. Frogel, Niall D. Ferguson, Joseph S. Fernandez-Moure, Jakub Furmaga, David Foster Gaieski, Ognjen Gajic, Alice Gallo De, Kelly R. Genga, Pierce Geoghegan, Evangelos J. Giamarellos-Bourboulis, Rick Gill, Ewan C. Goligher, Emily K. Gordon, W. Robert Grabenkort, Garima Gupta, Jacob T. Gutsche, Goksel Guven, Paige Guyatt, Nicholas Heming, Cheralyn J. Hendrix, McKenzie K. Hollen, Steven M. Hollenberg, Vivien Hong Tuan Ha, Shahd Horie, Catherine L. Hough, Can Ince, Theodore J. Iwashyna, Judith Jacobi, Marc Jeschke, Nicholas J. Johnson, Jeremy M. Kahn, Lewis J. Kaplan, Mark T. Keegan, Jordan Anthony Kempker, Leo G. Kevin, Yasin A. Khan, Ruth Kleinpell, Kurt Kleinschmidt, Michael Klompas, Patrick M. Kochanek, W. Andrew Kofke, Benjamin Kohl, Andreas Kortgen, David Kung, John G. Laffey, Joel Lage, David William Lappin, Francois Lamontagne, Daniel E. Leisman, Ron Leong, Joshua M. Levine, Andrew T. Levinson, Mitchell M. Levy, Ariane Lewis, Ariel Tamara Slavin, Olivier Lheureux, Vincent X. Liu, Craig Lyons, Jason H. Maley, Atul Malhotra, Joshua A. Marks, Greg S. Martin, Niels D. Martin, Claire Masterson, Yunis Mayasi, Virginie Maxime, Bairbre Aine McNicholas, Jakob McSparron, Maureen O. Meade, Mark E. Mikkelsen, Alicia M. Mohr, Peter Moran, Stephanie Royer Moss, Patrick T. Murray, Patrick J. Neligan, Larry X. Nguyen, Alistair D. Nichol, Katherine Lyn Nugent, Mark E. Nunnally, Michael F. O’Connor, Yewande Odeyemi, Steven M. Opal, Anthony O’Regan, John O’Regan, Michelle O’Shaughnessy, Robert L. Owens, Pratik Pandharipande, Ithan D. Peltan, Anders Perner, Michael R. Pinsky, Greta Piper, Lauren A. Plante, Ariella Pratzer, Jean-Charles Preiser, Hallie C. Prescott, Megan T. Quintana, Lindsay Raab, Jason S. Radowsky, Jesse M. Raiten, Bryan T. G. Reidy, Patrick M. Reilly, Kenneth E. Remy, Emanuele Rezoagli, Zaccaria Ricci, Lisbi Rivas, Bram Rochwerg, Kristen Carey Rock, Claudio Ronco, James A. Russell, Danielle K. Sandsmark, Joshua Iokepa Santos, Babak Sarani, Damon C. Scales, Michael Scully, Jon Sevransky, Sam D. Shemie, Carrie A. Sims, Brian P. Smith, Audrey E. Spelde, Robert David Stevens, B. Taylor Thompson, Samuel A. Tisherman, Mark Trinder, Isaiah R. Turnbull, Ida-Fong Ukor, MBBS, Tom van der Poll, Tjitske S.R. van Engelen, Charles R. Vasquez, Michael A. Vella, William J. Vernick, Gianluca Villa, Jean-Louis Vincent, Amy C. Walker, Keith R. Walley, Lorraine B. Ware, Stuart J. Weiss, Anna E. Garcia, and Pauline Whyte
Published: 2020

25. Quality improvement of end‑of‑life decision-making and communication in the ICU : Effect on clinicians' burnout and relatives' distress

Author: Albrecht Guenther, Christine Pausch, Daniel Schwarzkopf, Christiane S. Hartog, Andreas Kortgen, and Konrad Reinhart
Subjects: medicine.medical_specialty, Quality management, Psychological intervention, Emergency Nursing, Burnout, Burnout, Psychological, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Intensive care, Intervention (counseling), Internal Medicine, Medicine, Humans, 030212 general & internal medicine, Depression (differential diagnoses), Terminal Care, business.industry, Communication, Quality Improvement, Distress, Intensive Care Units, Family medicine, Emergency Medicine, Anxiety, medicine.symptom, business
Abstract: End-of-life (EOL) decision-making is stressful. We conducted a quality improvement initiative to EOL decision-making and reduce stress for clinicians and patients’ relatives. A before–after study running from 2010–2014 at four interdisciplinary intensive care units (ICU) in a German university hospital was performed. Between periods, a multifaceted intervention was implemented to improve timeliness, clinician involvement, and organisational support. Consecutive patients with severe sepsis and therapy limitations were included. Relatives were interviewed by telephone after 90 days to assess their psychological symptoms. Clinician burnout was assessed by staff surveys in each period. Participation in the pre- and postintervention period was 84/145 and 90/159 among relatives, and 174/284 and 122/297 among ICU clinicians. Staff judged intervention elements as mostly helpful, but implementation of intervention elements was heterogeneous. From pre- to postintervention, relatives’ risk of posttraumatic stress, depression and anxiety did not change (all p ≥ 0.464). Clinicians’ risk of burnout increased (29% vs. 41%, p = 0.05). Relatives were highly satisfied in both periods (median of 9 vs. 9.2 on a 1–10 scale each). Attendings involved residents and nurses more often (both p ≤ 0.018). Nurses more often had sufficient information to talk with relatives (41% vs. 62%, p = 0.002). Time to first EOL decision as well as barriers and facilitators of EOL decision-making did not change. The intervention may have increased involvement in EOL decision-making, but was accompanied by an increased risk of clinician burnout maybe due to lack of improving communication skills and organisational support. More research is needed to understand which interventions can decrease clinician burnout.
Published: 2019

26. Hepatic cirrhosis and recovery as reflected by Raman spectroscopy: information revealed by statistical analysis might lead to a prognostic biomarker

Author: Ute Neugebauer, Andreas Kortgen, Kerstin Galler, Esther Fröhlich, Jürgen Popp, and Michael Bauer
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Cirrhosis, H&E stain, Analytical chemistry, Liver Cirrhosis, Experimental, Spectrum Analysis, Raman, Immunofluorescence, 01 natural sciences, Biochemistry, Analytical Chemistry, 010309 optics, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0103 physical sciences, medicine, Animals, Statistical analysis, Prognostic biomarker, Rats, Wistar, Carbon Tetrachloride, Staining and Labeling, medicine.diagnostic_test, Catabolism, Chemistry, Prognosis, medicine.disease, 030104 developmental biology, Liver, Data Interpretation, Statistical, Carbon tetrachloride, symbols, Raman spectroscopy, Biomarkers
Abstract: Hepatic cirrhosis is a severe chronic disease of the liver accompanied by massive changes in the physiology of the cells constituting the hepatic tissue. Success or failing of a therapeutic effort is difficult to recognize because of its late manifestation in the tissue morphology. In this study, the complex course of hepatic cirrhosis and its regression is followed in a rodent carbon tetrachloride model. Raman spectroscopy, which senses molecular vibrations and reflects the molecular composition of a sample, was applied to gain label- and destruction-free insights into the process of cirrhosis and to conclude on the hepatic disease state on the cellular level. Hematoxylin and eosin staining and immunofluorescence labeling were used to obtain complementary information. False color images derived from maps of Raman spectra by spectral unmixing revealed individual nucleus positions giving structural information. Spectral data unraveled chemical changes associated with liver damage on the cellular level. Upon carbon tetrachloride treatment, a higher lipid content and the presence of catabolic products indicated cirrhosis in tissue samples. Furthermore, 77 % of the Raman spectra recorded from treated rats were classified as diseased, whereas 96 % of the Raman spectra recorded from untreated rats were classified as healthy. Importantly, samples from rats that experienced a recovery period revealed a chemical composition highly similar to the ones from healthy rats while morphologically clear signs of tissue damage were still obvious. Eighty-three percent of their Raman spectra were classified as healthy. The vibrational fingerprint of tissue provides characteristic information that might serve as prognostic biomarker. Graphical Abstract Images of hematoxylin and eosin stained tissue slices together with an average Raman spectrum belonging to healthy and cirrhotic rat liver, respectively, visualize morphological and spectral differences between the two states of the liver.
Published: 2016

27. Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study

Author: Sabine, Westphal, Christian, Stoppe, Matthias, Gruenewald, Berthold, Bein, Jochen, Renner, Jochen, Cremer, Mark, Coburn, Gereon, Schaelte, Andreas, Boening, Bernd, Niemann, Frank, Kletzin, Jan, Roesner, Ulrich, Strouhal, Christian, Reyher, Rita, Laufenberg-Feldmann, Marion, Ferner, Ivo F, Brandes, Martin, Bauer, Andreas, Kortgen, Sebastian N, Stehr, Maria, Wittmann, Georg, Baumgarten, Rafael, Struck, Tanja, Meyer-Treschan, Peter, Kienbaum, Matthias, Heringlake, Julika, Schoen, Michael, Sander, Sascha, Treskatsch, Thorsten, Smul, Ewa, Wolwender, Thomas, Schilling, Frauke, Degenhardt, Andre, Franke, Soeren, Mucha, Lukas, Tittmann, Madeline, Kohlhaas, Georg, Fuernau, Oana, Brosteanu, Dirk, Hasenclever, Kai, Zacharowski, Patrick, Meybohm, and Norbert, Roewer
Subjects: Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Myocardial Infarction, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Atrial Fibrillation, Clinical endpoint, Phosphoprotein Phosphatases, Multicenter Studies as Topic, 030212 general & internal medicine, Myocardial infarction, Stroke, Randomized Controlled Trials as Topic, Acute kidney injury, Atrial fibrillation, Acute Kidney Injury, Middle Aged, Cardiac surgery, 3. Good health, Treatment Outcome, Cohort, Cardiology, Dual-Specificity Phosphatases, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Research Article, medicine.medical_specialty, Genome-wide association study, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Cardiac Surgical Procedures, Aged, business.industry, HSC70 Heat-Shock Proteins, Delirium, Ryanodine Receptor Calcium Release Channel, medicine.disease, Cytoskeletal Proteins, lcsh:RC666-701, Mitogen-Activated Protein Kinase Phosphatases, business
Abstract: 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
Published: 2018

28. What matters most to sepsis survivors: a qualitative analysis to identify specific health-related quality of life domains

Author: Bastian Matt, Andreas Kortgen, Christian König, Christiane S. Hartog, and Alison E. Turnbull
Subjects: Gerontology, Adult, Male, Coping (psychology), Family support, Health Status, Population, Article, 03 medical and health sciences, 0302 clinical medicine, Survivorship curve, Sepsis, Surveys and Questionnaires, Health care, Activities of Daily Living, Medicine, Humans, Survivors, education, Fatigue, Aged, Aged, 80 and over, education.field_of_study, Interpretative phenomenological analysis, business.industry, 030503 health policy & services, Public Health, Environmental and Occupational Health, Middle Aged, humanities, Self Concept, 030220 oncology & carcinogenesis, Quality of Life, Patient-reported outcome, Female, 0305 other medical science, business, human activities, Qualitative research
Abstract: PURPOSE: It is unknown how sepsis survivors conceptualize health-related quality of life (HRQL). We aimed to identify important HRQL domains for this population. METHODS: A literature search was performed to inform an interview guide. Open-ended interviews were held with 15 purposefully sampled sepsis survivors. Interview transcripts were analyzed by interpretative phenomenological analysis to allow themes to develop organically. Resulting codes were reviewed by an independent expert. The preliminary list of domains was rated in a two-round Delphi consensus procedure with therapists and survivors. RESULTS: Eleven domains emerged as critically important: Psychological impairment, Fatigue, Physical impairment, Coping with daily life, Return to normal living, Ability to walk, Cognitive impairment, Self-perception, Control over one’s life, Family support and Delivery of health care. Sepsis survivors want a “normal life”, to walk again, to regain control without cognitive impairment. Family support is essential to overcome sepsis aftermaths. CONCLUSIONS: Survivors described many HRQL domains which are not captured by the QoL instruments that have traditionally been used to study ICU survivorship (i.e. SF-36 and EQ-5D). Future studies of QoL in ICU survivors should consider using both a traditional instrument so that results are comparable to previous research, as well as a more holistic QoL measurement instrument like the WHOQOL-BREF.
Published: 2018

29. Organersatz auf der Intensivstation – Extrakorporaler Leberersatz

Author: Andreas Kortgen, Christoph Sponholz, Falk A. Gonnert, and Michael Bauer
Published: 2015

30. Fast simultaneous assessment of renal and liver function using polymethine dyes in animal models of chronic and acute organ injury

Author: Andreas Kortgen, T. P. Haider, Mark G. Clemens, Sophie Neugebauer, Christine Weber, Michael Bauer, Ulrich S. Schubert, Michael Kiehntopf, M. J. Butans, and Adrian T. Press
Subjects: Pathology, medicine.medical_specialty, Indoles, 030232 urology & nephrology, lcsh:Medicine, Renal function, Kidney, Kidney Function Tests, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Medicine, Animals, Renal Insufficiency, Chronic, lcsh:Science, Fluorescent Dyes, Multidisciplinary, business.industry, Liver Diseases, lcsh:R, Organ dysfunction, Kidney metabolism, 030208 emergency & critical care medicine, Acute Kidney Injury, Renal Elimination, Liver, Renal physiology, Acute Disease, Chronic Disease, lcsh:Q, Liver function, medicine.symptom, business, Intravital microscopy
Abstract: Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.
Published: 2017

31. Biomarkers in Inflammation

Author: Michael Bauer and Andreas Kortgen
Subjects: Pentraxins, biology, Lipopolysaccharide, business.industry, C-reactive protein, Inflammation, Adrenomedullin, chemistry.chemical_compound, chemistry, Calcitonin, Immunology, biology.protein, medicine, medicine.symptom, business
Published: 2017

32. Short-term treatment with taurolidine is associated with liver injury

Author: Andreas Kortgen, Alexander S. Mosig, Utz Settmacher, Adrian T. Press, Falk Rauchfuss, Anika Möller, Michael Kiehntopf, and René Fahrner
Subjects: Male, Pathology, medicine.medical_specialty, Cell Survival, Taurine, Peritonitis, Pharmacology, Liver injury, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Blood serum, Glutamate Dehydrogenase, In vivo, lcsh:RA1190-1270, medicine, Cell Adhesion, Animals, Humans, Pharmacology (medical), Viability assay, Aspartate Aminotransferases, lcsh:Toxicology. Poisons, Taurolidine, Thiadiazines, business.industry, Caspase 3, lcsh:RM1-950, Interleukin, medicine.disease, Liver enzymes, Liver biochip, medicine.anatomical_structure, lcsh:Therapeutics. Pharmacology, chemistry, Liver, Rats, Inbred Lew, 030220 oncology & carcinogenesis, Hepatocyte, Chemical and Drug Induced Liver Injury, Chronic, Cytokines, 030211 gastroenterology & hepatology, business, Research Article
Abstract: Background Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver. Methods In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology. Results In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment. Conclusions Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation. Electronic supplementary material The online version of this article (doi:10.1186/s40360-017-0168-z) contains supplementary material, which is available to authorized users.
Published: 2017

33. Impact of perioperative liver dysfunction on in-hospital mortality and long-term survival in infective endocarditis patients

Author: C von Loeffelholz, Michael Bauer, Mahmoud Diab, P. Scheffel, Christoph Sponholz, G. Färber, Andreas Kortgen, Torsten Doenst, Thomas Lehmann, and Mathias W. Pletz
Subjects: Microbiology (medical), Male, medicine.medical_specialty, Staphylococcus aureus, 030204 cardiovascular system & hematology, Chronic liver disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Risk Factors, Internal medicine, Germany, medicine, Cardiopulmonary bypass, Endocarditis, Humans, 030212 general & internal medicine, Hospital Mortality, Perioperative Period, Aged, Retrospective Studies, Proportional hazards model, business.industry, Incidence, Liver Diseases, Organ dysfunction, General Medicine, Perioperative, Length of Stay, Middle Aged, Staphylococcal Infections, medicine.disease, Prognosis, Surgery, Cardiac surgery, Infectious Diseases, Infective endocarditis, Female, medicine.symptom, business
Abstract: Infective endocarditis (IE) is often associated with multiorgan dysfunction and mortality. The impact of perioperative liver dysfunction (LD) on outcome remains unclear and little is known about factors leading to postoperative LD. We performed a retrospective, single-center analysis on 285 patients with left-sided IE without pre-existing chronic liver disease referred to our center between 2007 and 2013 for valve surgery. Sequential organ failure assessment (SOFA) score was used to evaluate organ dysfunction. Chi-square, Cox regression, and multivariate analyses were used for evaluation. Preoperative LD (Bilirubin >20 μmol/L) was present in 68 of 285 patients. New, postoperative LD occurred in 54 patients. Hypoxic hepatitis presented the most common origin of LD, accompanied with high short-term mortality. In-hospital mortality was higher in patients with preoperative and postoperative LD compared to patients without LD (51.5, 24.1, and 10.4%, respectively, p
Published: 2017

34. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Author: Walid Habre, Nicola Disma, Katalin Virag, Karin Becke, Tom G Hansen, Martin Jöhr, Brigitte Leva, Neil S Morton, Petronella M Vermeulen, Marzena Zielinska, Krisztina Boda, Francis Veyckemans, Walter Klimscha, Regina Konecny, Robert Luntzer, Ulrike Morawk-Wintersperger, Franz Neiger, Lydia Rustemeyer, Christian Breschan, Denise Frey, Manuela Platzer, Reinhard Germann, Joachim Oeding, Birgit Stoegermüller, Bernhard Ziegler, Philipp Brotatsch, Anton Gutmann, Gerlinde Mausser, Brigitte Messerer, Wolfgang Toller, Maria Vittinghoff, Gregor Zangl, Natascha Seidel-Ahyai, Christoph Hochhold, Ruth Kroess, Peter Paal, Steven Cnudde, Patricia Coucke, Birgit Loveniers, John Mitchell, David Kahn, Thierry Pirotte, Caroline Pregardien, Marc Coppens, Stefan De Hert, Björn Heyse, Martine Neckebroek, Aliaksandra Parashchanka, Jurgen Van Limmen, Nancy Van Den Eynde, Caroline Vanpeteghem, Piet Wyffels, Michaël Lalot, Jean-Paul Lechat, France Stevens, Sari Casaer, Françoise De Groote, Françoise De Pooter, Andrée De Villé, Marc Gerin, Natalia Magasich, Cristel Sanchez Torres, Denise Van Deenen, Johan Berghmans, Dirk Himpe, Eva Roofthooft, Ellen Joukes, Carine Smitz, Veronique Van Reeth, Christel Huygens, Julie Lauweryns, Karen De Smet, Nadia Najafi, Jan Poelaert, Anne Van de Velde, Veerle Van Mossevelde, Ivan Bekavac, Diana Butkovic, Dubravka Heli Litvic, Ivana Kerovec Soric, Hrvoje Maretic, Djurdjica Moscatello, Ljiljana Popovic, Slobodan Micici, Ivana Stuck Tus, Lada Kalagac Fabris, Tatjana Simurina, Nina Sulen, Gordana Kesic-Valpotic, Dajana Djapic, Jirí Žurek, Lucie Jureckova, Iveta Mackova, Monika Skacel, Stanislava Weinlichova, Jan Divák, Michal Frelich, René Urbanec, Vera Biskupova, Vladimir Mixa, Jana Pavlickova, Arash Afshari, Morten Bøttger, Marguerite B. Ellekvist, Mathias Johansen, Birgitte Ingeborg Madsen, Jens Christian Nilsson, Birgitte MB Schousboe, Nicola G. Clausen, Tom G. Hansen, Nick Phaff Steen, Mari-Liis Ilmoja, Virge Tonise, Juri Karjagin, Reet Kikas, Mika Isohanni, Anniina Lyly, Annika Takala, Johanna Happo, Kai Kiviluoma, Kati Martikainen, Riku Aantaa, Tuula Manner, Sanna Vilo, Catherine Amory, Hugues Ludot, Patricia Lambotte, René Busche, Olivier Jacqmarcq, Corinne Lejus, Julien Corouge, Christian Erb, Delphine Garrigue, Patricia Gillet, Anne Laffargue, Veronique Lambelin, Hélène Le Freche, Daliana Peresbota, Pierre Richart, Jerome Berton, Catherine Chapotte, Laurent Colbus, Thierry Lehousse, Jean Monrigal, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Hélène Batoz, Maryline Bordes, Anne Didier, Yann Hamonic, Sylvaine Lagarde, Karine Nouette-Gaulain, François Semjen, Brigitte Zaghet, Jacky Dekens, Axelle Delcuze, Hervé Dupont, Aurélien Legrand, Celine Raffoflandreur, Noémie Audren, Blandine Camus, Marielle Cartal, Chantal Chazelet, Isabelle Davin, Marion Guillier, Luc Desjeux, Claire Larcher, Elodie Grein, Mickeal Leclercq, Roxana Levitchi, Lilica Rosu, Dominique Simon, Aurélien Zang, Anne Migeon, Anne-Charlotte Gagey, Nathalie Bourdaud, Anne-Charlotte Carre, Frédéric Duflo, Jean-Claude Riche, Philippe Robert, Emilie Druot, Olivier Maupain, Gilles Orliaguet, Lucie Sabau, Hanna Taright, Lynn Uhrig, Juliette Verchere-Montmayeur, Lise Debrabant, Clotaire Pilla, Alexandre Podvin, Benjamin Roth, Souhayl Dahmani, Florence Julien-Marsollier, Nada Sabourdin, Bogdan Alexandri, Gilles Brezac, Francois de la Brière, Catherine Hayem, Elizabeth Lhubat, Jean Paul Mission, Charlotte Rémond, Christophe Dadure, Maud Maniora, Anais Marie, Philippe Pirat, Anne-Charlotte Saour, Chrystelle Sola, Claude Ecoffey, Eric Wodey, Christian Adam, Thomas Standl, Ehrenfried Schindler, Tomohiro Yamamoto, Michael Brackhahn, Christoph Bernhard Eich, Holger Guericke, Petra Kindermann, Michael Laschat, Cornel Schink, Frank Wappler, Claudia Hoehne, Natalia Skordou, Johanna Ulrici, Martin Jetzek-Zader, Peter Kienbaum, Tanja Meyer-Treschan, Olaf Picker, Maximilian S. Schaefer, Golo Mielke, Sabine Baethge, Axel Ramminger, Martin Bauer, Matthias Bollinger, José Hinz, Michael Quintel, Sebastian G. Russo, Michael Bauer, Dfominik Geil, Andreas Kortgen, Niels-Peter Preussler, Ulrich Hofmann, Manfred Raber, Doris Reindl, Karin Oppenrieder, Bettina Schierlinger, Jens Roth, Wolfgang Funk, Thomas Fischer, Christian Gernoth, Christina Wiefelspütz, Hauke Volger, Nicole Zederer, Anja Diers, Matthias Huber, Clemens Schorer, Andreas Weyland, Konrad Schwarzkopf, Catharina Grau, Winfried Roth, Rolf Holy, Thomas Mader, Laura Peter, Hauke Supthut, Thomas Kuehhirt, Alexander Milde, Fritz Fiedler, Carsten Isselhorst, Ulrich Grundmann, Alexander Pattar, Jennifer Reinert, Birgit Ehm, Katrin Fritzsche, Ralf Gaebler, Patrick Meybohm, Maximilian Hein, Ines Guzman, Johanna Jokinen, Peter Kranke, Ulrich Goebel, Sarah Harris, Christoph Eisner, Miriam Ochsenreiter, Michael Schoeler, Elke Thil, Richard Ellerkmann, Andreas Hoeft, Claudia Neumann, Stefan Weber, Julia Keilhauer, Jan Kloessing, Michael Schramm, Uwe Trieschmann, Kristina Knauss, Barbara Sinner, Johannes Steinmann, Herbert Koessler, Evagelia Kalliardou, Anna Malisiova, Adelais Tsiotou, Pelagia Chloropoulou, Mpratzou Chrysi, Despoina Iordanidou, Merkourios Ntavlis, Krisztina B Boda, Christilynn Guerin, Janice Irwin, Claire Magner, Solmaz Nakhjavani, Brendan O'Hare, Deborah Galvin, Yosry Jamil, Carlos Lesmes, Yuri Barak, Haran Fisher, Ludmyla Kachko, Jacob Katz, Dmitry Kirilov, Michael Levinzon, Yair Manevich, Konstantin Nekrasov, Elia Peled, Elena Sanko, Dmitri Schmain, Olga Sheinkin, Eliahu Simhi, Alex Tarabikin, Evelina Trabkin, Irena Yagudaev, Yelena Zeitlin, Igor Zunser, Elisabetta Cerutti, Maria Maddalena Schellino, Silvia Valzan, Rosa Lucia Pinciroli, Luciano Bortone, Giorgia Cerati, Fabiana Salici, Leonardo Bussolin, Giuliana Rizzo, Francesca Rossetti, Laura Marchesini, Simonetta Tesoro, Brita De Lorenzo, Fabio Guarracino, Beate Kuppers, Marinella Astuto, Sofia Pitino, Rita Scalisi, Lucia Scordo, Sandra D'Alessandro, Luigi Dei Giudici, Ivano Farinelli, Giuseppe Lofino, Giuliano Marchetti, Sergio Giuseppe Picardo, Simone Reali, Alessandro Vittori, Francesco Antonio Idone, Maria Sammartino, Fabio Sbaraglia, Cinzia Barbera, Michela Bevilacqua, Valeria Cento, Svetlana Kotzeva, Leila Mameli, Giovanni Montobbio, Leandro Passariello, Cinzia Punzo, Rosanna Sileo, Rosanna Viacava, Claudia Volpe, Clelia Zanaboni, Edoardo Calderini, Daniele Genco, Simona Neri, Davide Ottolina, Anna Camporesi, Francesca Izzo, Ida Salvo, Andrea Wolfler, Andrea Sanna, Angela Sciascia, Paolo Stoia, Annamaria Guddo, Maria Lapi, Giorgio Ivani, Annalisa Longobardo, Valeria Mossetti, Dino Pedrotti, Maurizia Grazzini, Luisa Meneghini, Salvatore Metrangolo, Stefania Michelon, Carmelo Minardi, Costanza Tognon, Nicola Zadra, Ilaria Busi, Magda Khotcholava, Bruno Guido Locatelli, Valter Sonzogni, Giusi Starita, Nicole Almenrader, Caterina Aurilio, Pasquale Sansone, Raffaella Albarello, Paolo Bracci, Mariateresa Cecini, Maria Cristina Mondardini, Lorena Pasini, Milo Vason, Gianluca Zani, Roberto Zoppellari, Laura Pistidda, Andrea Cortegiani, Santi Maurizio Raineri, Antigona Hasani, Medita Hashimi, Agris Ancupans, Arta Barzdina, Zane Straume, Anda Zundane, Mikhail Chlopin, Dalia Gestautaite, Laura Lukosiene, Evelina Paliokaite, Ilona Razlevice, Inesa Armoniene, Aurelija Bernotiene, Vidunas Daugelavicius, Ilona Dockiene, Lina Gaidelyte, Nijole Saviciene, Jolita Krikstaponiene, Dominika Sidlovskaite-Baltake, Vladyslav Stasevski, Agne Vaitoskaite, David Gatt, Stephanie Mifsud, Simone Zammit, Celia Allison, Hamid Aslami, Susanne Eberl, Mireille F M van Stijn, Markus F Stevens, Kees Punt, Rob van Osch, Arthur Bauwman, Harm Scholten, Vesna Svircevic, Veronique Adriaens, Maaike Dirckx, Jaap Dogger, Ilse Dons-Sinke, Andreas Machotta, Xavier Moors, Mandana Rad, Lonneke Staals, Anouk van der Knijff - van Dortmont, Caroline van der Marel, Anne Sieben, Tim van der Zwan, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Nicole Engel, Carine Vossen, Ravin Mahadewsing, Patrick Meijer, Volker Gerling, Roelof van der Schatte Olivier, Thea van Doorn, Kristy Vons Mark Hendriks, Sandra Lako, Gert jan Scheffer, Luc Tielens, Marieke Voet, Anthony Absalom, Margot Bergsma, Vera Spanjer, Rob Spanjersberg, Yvette van de Riet, Martin Volkers, Jurgen C. de Graaff, Geranne A.J. Hopman, Teus H. Kappen, J. Hannie, A.M. Megens, Sandra C. Numan, Anton N.J. Schouten, Nigel M. Turner, Désirée B.M. Van Der Werff, Renee T.M. Wensing, Erik Ephraim, Claire Nolte, Tore Reikvam, Ole Fredrik Lund, Lene Skaaden, Kari Marthe Ballovarre, Wenche Bakken Boerke, Guro Grindheim, Pal H H Lindenskov, Anne Beate Solas, Sjur Sponheim, Kyrre Ullensvang, Oddbjorn Viken, Inger Marie Drage, Kasper Gymoese Berthelsen, Bjørn Anders Kroken, Unni Bergland, Miroslaw Pryzmont, Mariola Talalaj, Malgorzata Wasiluk, Dorota Zalewska, Maria Damps, Jadzia Siemek-Mitela, Pawel Wieczorek, Magdalena Juzwa, Jowita Rosada-Kurasinska, Alicja Bartkowska-Sniatkowska, Maciej Cettler, Renata Kopycinska, Iwona Rudewicz, Jaek Sobczyk, Dariusz Wojciechowski, Artur Baranowski, Ewa Basiewicz, Magdalena Mierzewska-Schmidt, Wlodzimierz Retka, Piotr Sawicki, Magdalena Checinska, Magdalena Zurawska, Teresa Leal, Catia Mascarenhas, António Pedro Pina, Maria Joao Susano, Antonio Moniz, Maria Teresa Rocha, Carolina Calvao Santos, M Domingas Patuleia, Ricardo Pereira, Helena Roxo, Rosa Amaral, Isabel Guedes, Cristina Gomes, Marta Gonçalves, Helena Salgado, Maria Santos, Sara Rodrigues, Angela Sa, Elvira Machado, Sandra Pé d'Arca, Manuel Seabra, Ligia Mihaela Gheorghe, Constantin Ivascu, Lucia Moraru-Draghici, Mirela Suvejan, Remus Babici, Kovacs Eniko, Cristiana Hogea, Dubau Mihaela, Daraban Nicoleta, Danut Barbunc, Alina Maria Nistor, Violeta Stefan, Gabriela Catalina Ionescu, Irina Davidescu, Alina Teodora Nastase, Florin Dumitru Rusu, Victoria Badarau, Iulia Cindea, Melania Moscaliuc, Dana Olteanu, Luxita Petrescu, Daniela Ceuca, Irena Galinescu, Rodica Badeti, Alin Capusan, Cosmina Cucui-Cozma, Barbura Popescu, Luminita Cimpeanu, Mihaela-Petronela Birliba, Magdalena Miulescu, Stefania Balamat, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Darina Pick, Rodica Sirghie, Radu Tabacaru, Irinel Trante, Lucian Horhota, Daniela Bandrabur, Tudor Ciobanu, Veaceslav Cuciuc, Valentin Munteanu, Valentin Olaru, Corneliu Paiu, Anca Savu, Oana Trifan, Anca Elena Malos, Anton Glazunov, Alexander Ivanov, Evgeny Poduskov, Alexander Popov, Igor Guskov, Alexander Lugovoy, Vladislav Nechaev, Alexey Ovezov, Mikhail Basov, Vladimir Kochkin, Vladimir Lazarev, Dmitri Chizhov, Ivan Ostreikov, Konstantin Tolasov, Ivana Budic, Vesna Marjanovic, Biljana Draskovic, Marina Pandurov, Jovana Simin, Vladimir Dolinaj, Dusanka Janjevic, Ana Mandras, Maja Mircetic, Sladjana Petrovic, Vlatka Rebac, Bojana Slavkovic, Vesna Stevanovic, Ana Velcev, Mirjana Knezevic, Irina Milojevic, Selena Puric, Irena Simic, Marija Stevic, Vladimir Stranjanac, Dusica Simic, Barbora Cabanova, Miloslav Hanula, Andry Grynyuk, Jelena Berger, Uros Cerne, Andraz Nastran, Dejan Pirc, Rok Popic, Spela Stupnik, Paloma Rubio, Cristina del Río, Pilar Benito, Gema Pino, Ignacio Gutierrez, Andrea Gutierrez Valcarcel, Irene León Carsi, Anibal Perez Garcia, Sílvia López Galera, Joan Marco Valls, Laura Ricol Lainez, Andrea Vallejo Tarrat, David Artes, Ester Banus, Luca Chirichiello, Leidy De Abreu, Belen De Josemaria, M Helena Gaitan, Antonio Garces, Juan J Lazaro, Ferran Manen Berga, Dolors Molies, Enric Monclus, Montserrat Navaro, Carmen Pamies, Marina Perelló, Mar Prat, Laura Ribo, M Angeles Sanz, Silvia Serrano, Eva Sola Ruiz, Blanca Anuncia Escontrela Rodríguez, Andrea Maria Gago Martinez, Alberto Martínez Ruiz, Fausto De La Cruz Benito, Gustavo Gabilondo Garcia, Ever Martinez Maldonado, Bryant Noriega, Lara Oller Duque, Alberto Olmos Mendez, Antonio Perez- Ferrer, Francisco Reinoso Barbero, Ismael Acevedo Bambaren, Fernando Domínguez, Teresa Franco, Anabel Jiménez, Alicia Melero, Montserrat Feliu, Irene García, Núria Montferrer, Francisca Munar, Cristina Muro, Rosario Nuño, Remel Perera, Erika Schmucker, Glenda Börjesson, Lars Gillberg, Albert Castellheim, Kerstin Sandström, Annette Bauer, Torbjörn Roos, Lars Hedlund, Yann Boegli, Mirko Dolci, Carine Marcucci, Isabelle Spahr-Schopfer, Michel Pellegrini, Malte Book, Loreen Errass, Christine Riggenbach, Mattias Casutt, Martin Hölzle, Thomas Hurni, Jacqueline Mauch, Luciano Anselmi, Irene Anselmi, Alfred Jacomet, Markus Oberhauser, Stephanie Wossner, Angelika Zettl, Thomas Erb, Tomasz Mackiewicz, Helena Simitzes, Yetkin Ozer, Arzu Takil, Zekeriyya Alanoglu, Onat Bermede, K.Sanem Cakar Turhan, Neslihan Alkis, Cigdem Yildirim Guclu, Basak Ceyda Meco, Zehra Hatipoglu, Dilek Ozcengiz, Zekine Begec, Huseyin Ilksen Toprak, Pinar Kendigelen, Ayse Cigdem Tütüncü, Meltem Savran Karadeniz, Tulay Seyhan Ozkan, Nuket Sivrikoz, Mustafa Kemal Arslantas, Ayse Hizal, Gülbin Tore Altun, Tumay Umuroglu, Sibel Baris, Zuleyha Kazak Bengisun, Galyna Goncharenko, Maksym Khrapak, Tetyana Klymenko, Vitaliy Pavlenko, Dmytro Prysiazhniuk, Olga Rudio, Mykhailo Varyvoda, Sergii Vodianytskyi, Ivanna Boryshkevych, Iryna Kyselova, Nikolay Trikash, Andrew Albokrinov, Valentina Perova-Sharonova, Vitaliy Sklyar, Denis Surkov, Amr Abdelaal, Nicola Barber, Sarah Checuti, Leisha Godsiff, Lynch Johanne, Joanna Simpson, Helen Underhill, Rishi Diwan, Nivedita Kelgeri, Nuria Masip, Radha Ravi, Steve Roberts, Annagrazia Cillis, Ritchie Marcus, Federica Merella, David Love, Paolo Baraggia, Victoria Bird, Joseph Hussey, Peter Alderson, Karen Bartholomew, Michael Moncreiff, Sarah Davidson, Alison Hare, Ami Kotecha, Corina Lee, Ganga Liyanage, Shivali Patel, Amee Samani, Mark Abou-Samra, Matthew Boyd, Laurence Hullatt, David Levy, Mark Pauling, Sarah-Jane Sharman, Natalie Smith, John Rutherford, Alison Cavalier, Christie Locke, Frederic Sage, Smita Bapat, Jacinda Hammerschlag, Ioannis Ioannou, Stephanie King, Rachel Pegg, Vishal Salota, Jonathan Sketcher, Muthu Thadsad, Deborah Zeitlin, Ewan Jack, Colin Lang, Samira Ahmed, Reema Ayyash, Francoise Bari, Sarah J Bell, Claire Elizabeth Biercamp, Sandra Briggs, Maria Gabriella Elena Clement, Mark Dalton, Mohamed Ali Eissa Eid, Monica Gandhi, Idse Harmen Herrema, Ranj Khaffaf, Savio Jeng Min Law, Joanna McClintock, Nicholas Ireland, Mohammed Majid Saleem, Fiona Smith, Marc Cohen, Clover-Ann Lee, Lizanne O'Donahue, Alex Powell, Ellen Rawlinson, Aarjan Snoek, Katja Weiss, Hugo Wellesley, Michael Crawford, Mostafa Abdel-Hafiz, Alexandra Day, Balaji Rajamani, Rita Saha, Dave Wright, Lew-Chin Chee, Stephanie Bew, Rachel Homer, Nalini Malarkkan, Juliet Wolfe Barry, Pradeep Angadi, Brid Cagney, Eric De Melo, Elsa Dekker, Emma Helm, Gareth Jones, Kawshala Peiris, William Russell, Patricia Slater, Puja Sodhi, Mike Browning, Trudie Phillips, Rachel Van Hecke, Vimty Muir, Piyush Singh, Tereza Soskova, Craig Cumming, Pamela Farquharson, Karen Pearson, Neil Shaw, Jonathan Whiteside, Emma Whyte, Gordon Byers, Kay Davies, Thomas Engelhardt, Isabella Faliszewski, Graham Johnston, Nils Kaufmann, Zuzana Kusnirikova, Graham Wilson, Peter Carachi, Andrew Makin, Brian Foster, Dariusz Lipczynski, Rebecca Mawer, William Rutherford, David Rogerson, Sarah Rushman, Christopher Taylor, William Tomlinson, Philippa Dix, Tom Woodward, Graham Bell, David Boyle, Marianne Cloherty, Julia Cullen, Pauline Cullen, Ross Fairgrieve, Robert Ghent, Russell Glasgow, Elena Gordeeva, Alison Harden, Sarah Hivey, Kevin Jerome, Lesley McKee, Neil Morton, Vicky Pribul, John Sinclair, Maria Steiner, Heather Steward, Lorraine Sweeney, Wendy Thomson, Jeanette Whiteside, Andrew Dalton, Mark Ross, Carolyn Smith, Claire Allen, Nicola Anders, Victoria Barlow, Mike Bassett, Leanne Darwin, Rachel Davison, Jacques Diacono, Amy Hobbs, Adel Hutchinson, Bernadette Lomas, Hannah Lonsdale, Leila Nasser, Vimmi Oshan, Pradip Patel, Christopher Raistrick, Victoria Scott-Warren, Laura Talbot, Carolynn Wai, Sophie Childs, Matthew Dickinson, Tom Bloomfield, Sweyn Garrioch, Karen Watson, James Gaynor, Richard Harrison, Juliette Lee, Elizabeth Blythe, Teresa Dorman, Ayman Eissa, James Ellwood, Ingrid Gooch, Robert Hearn, Vanessa Hodgetts, Robert John, Christine Kirton, Nadia Ladak, Judith Morgan, Nina Plant, Elizabeth Shepherd, Judith Short, Charles Stack, Simon Steel, Matthew Taylor, Deborah Thomas, Catharine Wilson, Elaine Wilson-Smith, Carol L. Bradbury, Nageena Hussain, Antonia Mayell, Ahmed Mesbah, Arif Qureshi, Chandra Vaidyanath, Tim Geary, Chris Hawksworth, Tamaraichelvi Parasuraman, Nicole Perry, Indrani Banerjee, Katharine Barr, Patrick Butler, Jack Davies, Lisa Flewin, Richard Gande, James Montague, James Plumb, Thomas Pratt, Paul Sutherland, Hannah Vail, Andrew Wilkins, Catherine Hunter, Susan Russell, Alun Thomas, Mark Mifsud, Dominic Strachan, Benoit Plichon, Pierre Harlet, Anesthesiology, APH - Quality of Care, Graduate School, Other Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Neuroinfection & -inflammation, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), APRICOT Grp European Soc Anaesthes, Habre, Walid, Disma, Nicola, Virag, Katalin, Becke, Karin, Hansen, Tom G, Jöhr, Martin, Leva, Brigitte, Morton, Neil S, Vermeulen, Petronella M, Zielinska, Marzena, Boda, Krisztina, Veyckemans, Franci, Klimscha, Walter, Konecny, Regina, Luntzer, Robert, Morawk Wintersperger, Ulrike, Neiger, Franz, Rustemeyer, Lydia, Breschan, Christian, Frey, Denise, Platzer, Manuela, Germann, Reinhard, Oeding, Joachim, Stoegermüller, Birgit, Ziegler, Bernhard, Brotatsch, Philipp, Gutmann, Anton, Mausser, Gerlinde, Messerer, Brigitte, Toller, Wolfgang, Vittinghoff, Maria, Zangl, Gregor, Seidel Ahyai, Natascha, Hochhold, Christoph, Kroess, Ruth, Paal, Peter, Cnudde, Steven, Coucke, Patricia, Loveniers, Birgit, Mitchell, John, Kahn, David, Pirotte, Thierry, Pregardien, Caroline, Coppens, Marc, De Hert, Stefan, Heyse, Björn, Neckebroek, Martine, Parashchanka, Aliaksandra, Van Limmen, Jurgen, Van Den Eynde, Nancy, Vanpeteghem, Caroline, Wyffels, Piet, Lalot, Michaël, Lechat, Jean Paul, Stevens, France, Casaer, Sari, De Groote, Françoise, De Pooter, Françoise, De Villé, Andrée, Gerin, Marc, Magasich, Natalia, Sanchez Torres, Cristel, Van Deenen, Denise, Berghmans, Johan, Himpe, Dirk, Roofthooft, Eva, 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Aantaa, Riku, Manner, Tuula, Vilo, Sanna, Amory, Catherine, Ludot, Hugue, Lambotte, Patricia, Busche, René, Jacqmarcq, Olivier, Lejus, Corinne, Corouge, Julien, Erb, Christian, Garrigue, Delphine, Gillet, Patricia, Laffargue, Anne, Lambelin, Veronique, Le Freche, Hélène, Peresbota, Daliana, Richart, Pierre, Berton, Jerome, Chapotte, Catherine, Colbus, Laurent, Lehousse, Thierry, Monrigal, Jean, Baujard, Catherine, Roulleau, Philippe, Staiti, Giuseppe, Batoz, Hélène, Bordes, Maryline, Didier, Anne, Hamonic, Yann, Lagarde, Sylvaine, Nouette Gaulain, Karine, Semjen, Françoi, Zaghet, Brigitte, Dekens, Jacky, Delcuze, Axelle, Dupont, Hervé, Legrand, Aurélien, Raffoflandreur, Celine, Audren, Noémie, Camus, Blandine, Cartal, Marielle, Chazelet, Chantal, Davin, Isabelle, Guillier, Marion, Desjeux, Luc, Larcher, Claire, Grein, Elodie, Leclercq, Mickeal, Levitchi, Roxana, Rosu, Lilica, Simon, Dominique, Zang, Aurélien, Migeon, Anne, Gagey, Anne Charlotte, Bourdaud, Nathalie, Carre, Anne Charlotte, Duflo, Frédéric, Riche, Jean Claude, Robert, Philippe, Druot, Emilie, Maupain, Olivier, Orliaguet, Gille, Sabau, Lucie, Taright, Hanna, Uhrig, Lynn, Verchere Montmayeur, Juliette, Debrabant, Lise, Pilla, Clotaire, Podvin, Alexandre, Roth, Benjamin, Dahmani, Souhayl, Julien Marsollier, Florence, Sabourdin, Nada, Alexandri, Bogdan, Brezac, Gille, de la Brière, Francoi, Hayem, Catherine, Lhubat, Elizabeth, Paul Mission, Jean, Rémond, Charlotte, Dadure, Christophe, Maniora, Maud, Marie, Anai, Pirat, Philippe, Saour, Anne Charlotte, Sola, Chrystelle, Ecoffey, Claude, Wodey, Eric, Adam, Christian, Standl, Thoma, Schindler, Ehrenfried, Yamamoto, Tomohiro, Brackhahn, Michael, Bernhard Eich, Christoph, Guericke, Holger, Kindermann, Petra, Laschat, Michael, Schink, Cornel, Wappler, Frank, Hoehne, Claudia, Skordou, Natalia, Ulrici, Johanna, Jetzek Zader, Martin, Kienbaum, Peter, Meyer Treschan, Tanja, Picker, Olaf, Schaefer, Maximilian S., Mielke, Golo, Baethge, Sabine, Ramminger, 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M., Ephraim, Erik, Nolte, Claire, Reikvam, Tore, Fredrik Lund, Ole, Skaaden, Lene, Marthe Ballovarre, Kari, Bakken Boerke, Wenche, Grindheim, Guro, Lindenskov, Pal H. H, Beate Solas, Anne, Sponheim, Sjur, Ullensvang, Kyrre, Viken, Oddbjorn, Marie Drage, Inger, Gymoese Berthelsen, Kasper, Anders Kroken, Bjørn, Bergland, Unni, Pryzmont, Miroslaw, Talalaj, Mariola, Wasiluk, Malgorzata, Zalewska, Dorota, Damps, Maria, Siemek Mitela, Jadzia, Wieczorek, Pawel, Juzwa, Magdalena, Rosada Kurasinska, Jowita, Bartkowska Sniatkowska, Alicja, Cettler, Maciej, Kopycinska, Renata, Rudewicz, Iwona, Sobczyk, Jaek, Wojciechowski, Dariusz, Baranowski, Artur, Basiewicz, Ewa, Mierzewska Schmidt, Magdalena, Retka, Wlodzimierz, Sawicki, Piotr, Checinska, Magdalena, Zurawska, Magdalena, Leal, Teresa, Mascarenhas, Catia, Pedro Pina, António, Joao Susano, Maria, Moniz, Antonio, Teresa Rocha, Maria, Calvao Santos, Carolina, Domingas Patuleia, M., Pereira, Ricardo, Roxo, Helena, Amaral, Rosa, Guedes, Isabel, Gomes, Cristina, Gonçalves, Marta, Salgado, Helena, Santos, Maria, Rodrigues, Sara, Sa, Angela, Machado, Elvira, Pé d'Arca, Sandra, Seabra, Manuel, Mihaela Gheorghe, Ligia, Ivascu, Constantin, Moraru Draghici, Lucia, Suvejan, Mirela, Babici, Remu, Eniko, Kovac, Hogea, Cristiana, Mihaela, Dubau, Nicoleta, Daraban, Barbunc, Danut, Maria Nistor, Alina, Stefan, Violeta, Catalina Ionescu, Gabriela, Davidescu, Irina, Teodora Nastase, Alina, Dumitru Rusu, Florin, Badarau, Victoria, Cindea, Iulia, Moscaliuc, Melania, Olteanu, Dana, Petrescu, Luxita, Ceuca, Daniela, Galinescu, Irena, Badeti, Rodica, Capusan, Alin, Cucui Cozma, Cosmina, Popescu, Barbura, Cimpeanu, Luminita, Birliba, Mihaela Petronela, Miulescu, Magdalena, Balamat, Stefania, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Pick, Darina, Sirghie, Rodica, Tabacaru, Radu, Trante, Irinel, Horhota, Lucian, Bandrabur, Daniela, Ciobanu, Tudor, Cuciuc, Veaceslav, Munteanu, Valentin, Olaru, Valentin, Paiu, Corneliu, Savu, Anca, Trifan, Oana, Elena Malos, Anca, Glazunov, Anton, Ivanov, Alexander, Poduskov, Evgeny, Popov, Alexander, Guskov, Igor, Lugovoy, Alexander, Nechaev, Vladislav, Ovezov, Alexey, Basov, Mikhail, Kochkin, Vladimir, Lazarev, Vladimir, Chizhov, Dmitri, Ostreikov, Ivan, Tolasov, Konstantin, Budic, Ivana, Marjanovic, Vesna, Draskovic, Biljana, Pandurov, Marina, Simin, Jovana, Dolinaj, Vladimir, Janjevic, Dusanka, Mandras, Ana, Mircetic, Maja, Petrovic, Sladjana, Rebac, Vlatka, Slavkovic, Bojana, Stevanovic, Vesna, Velcev, Ana, Knezevic, Mirjana, Milojevic, Irina, Puric, Selena, Simic, Irena, Stevic, Marija, Stranjanac, Vladimir, Simic, Dusica, Cabanova, Barbora, Hanula, Miloslav, Grynyuk, Andry, Berger, Jelena, Cerne, Uro, Nastran, Andraz, Pirc, Dejan, Popic, Rok, Stupnik, Spela, Rubio, Paloma, del Río, Cristina, Benito, Pilar, Pino, Gema, Gutierrez, Ignacio, Gutierrez Valcarcel, Andrea, León Carsi, Irene, Perez Garcia, Anibal, López Galera, Sílvia, Marco Valls, Joan, Ricol Lainez, Laura, Vallejo Tarrat, Andrea, Artes, David, Banus, Ester, Chirichiello, Luca, De Abreu, Leidy, De Josemaria, Belen, Helena Gaitan, M., Garces, Antonio, Lazaro, Juan J, Manen Berga, Ferran, Molies, Dolor, Monclus, Enric, Navaro, Montserrat, Pamies, Carmen, Perelló, Marina, Prat, Mar, Ribo, Laura, Angeles Sanz, M., Serrano, Silvia, Sola Ruiz, Eva, Anuncia Escontrela Rodríguez, Blanca, Maria Gago Martinez, Andrea, Martínez Ruiz, Alberto, De La Cruz Benito, Fausto, Gabilondo Garcia, Gustavo, Martinez Maldonado, Ever, Noriega, Bryant, Oller Duque, Lara, Olmos Mendez, Alberto, Perez Ferrer, Antonio, Reinoso Barbero, Francisco, Acevedo Bambaren, Ismael, Domínguez, Fernando, Franco, Teresa, Jiménez, Anabel, Melero, Alicia, Feliu, Montserrat, García, Irene, Montferrer, Núria, Munar, Francisca, Muro, Cristina, Nuño, Rosario, Perera, Remel, Schmucker, Erika, Börjesson, Glenda, Gillberg, Lar, Castellheim, Albert, Sandström, Kerstin, Bauer, Annette, Roos, Torbjörn, Hedlund, Lar, Boegli, Yann, Dolci, Mirko, Marcucci, Carine, Spahr Schopfer, Isabelle, Pellegrini, Michel, Book, Malte, Errass, Loreen, Riggenbach, Christine, Casutt, Mattia, Hölzle, Martin, Hurni, Thoma, Mauch, Jacqueline, Anselmi, Luciano, Anselmi, Irene, Jacomet, Alfred, Oberhauser, Marku, Wossner, Stephanie, Zettl, Angelika, Erb, Thoma, Mackiewicz, Tomasz, Simitzes, Helena, Ozer, Yetkin, Takil, Arzu, Alanoglu, Zekeriyya, Bermede, Onat, Cakar Turhan, K. Sanem, Alkis, Neslihan, Yildirim Guclu, Cigdem, Ceyda Meco, Basak, Hatipoglu, Zehra, Ozcengiz, Dilek, Begec, Zekine, Ilksen Toprak, Huseyin, Kendigelen, Pinar, Cigdem Tütüncü, Ayse, Karadeniz, Meltem Savran, Seyhan Ozkan, Tulay, Sivrikoz, Nuket, Kemal Arslantas, Mustafa, Hizal, Ayse, Tore Altun, Gülbin, Umuroglu, Tumay, Baris, Sibel, Kazak Bengisun, Zuleyha, Goncharenko, Galyna, Khrapak, Maksym, Klymenko, Tetyana, Pavlenko, Vitaliy, Prysiazhniuk, Dmytro, Rudio, Olga, Varyvoda, Mykhailo, Vodianytskyi, Sergii, Boryshkevych, Ivanna, Kyselova, Iryna, Trikash, Nikolay, Albokrinov, Andrew, Perova Sharonova, Valentina, Sklyar, Vitaliy, Surkov, Deni, Abdelaal, Amr, Barber, Nicola, Checuti, Sarah, Godsiff, Leisha, Johanne, Lynch, Simpson, Joanna, Underhill, Helen, Diwan, Rishi, Kelgeri, Nivedita, Masip, Nuria, Ravi, Radha, Roberts, Steve, Cillis, Annagrazia, Marcus, Ritchie, Merella, Federica, Love, David, Baraggia, Paolo, Bird, Victoria, Hussey, Joseph, Alderson, Peter, Bartholomew, Karen, Moncreiff, Michael, Davidson, Sarah, Hare, Alison, Kotecha, Ami, Lee, Corina, Liyanage, Ganga, Patel, Shivali, Samani, Amee, Abou Samra, Mark, Boyd, Matthew, Hullatt, Laurence, Levy, David, Pauling, Mark, Sharman, Sarah Jane, Smith, Natalie, Rutherford, John, Cavalier, Alison, Locke, Christie, Sage, Frederic, Bapat, Smita, Hammerschlag, Jacinda, Ioannou, Ioanni, King, Stephanie, Pegg, Rachel, Salota, Vishal, Sketcher, Jonathan, Thadsad, Muthu, Zeitlin, Deborah, Jack, Ewan, Lang, Colin, Ahmed, Samira, Ayyash, Reema, Bari, Francoise, Bell, Sarah J, Elizabeth Biercamp, Claire, Briggs, Sandra, Gabriella Elena Clement, Maria, Dalton, Mark, Ali Eissa Eid, Mohamed, Gandhi, Monica, Harmen Herrema, Idse, Khaffaf, Ranj, Jeng Min Law, Savio, Mcclintock, Joanna, Ireland, Nichola, Majid Saleem, Mohammed, Smith, Fiona, Cohen, Marc, Lee, Clover Ann, O'Donahue, Lizanne, Powell, Alex, Rawlinson, Ellen, Snoek, Aarjan, Weiss, Katja, Wellesley, Hugo, Crawford, Michael, Abdel Hafiz, Mostafa, Day, Alexandra, Rajamani, Balaji, Saha, Rita, Wright, Dave, Chee, Lew Chin, Bew, Stephanie, Homer, Rachel, Malarkkan, Nalini, Wolfe Barry, Juliet, Angadi, Pradeep, Cagney, Brid, De Melo, Eric, Dekker, Elsa, Helm, Emma, Jones, Gareth, Peiris, Kawshala, Russell, William, Slater, Patricia, Sodhi, Puja, Browning, Mike, Phillips, Trudie, Van Hecke, Rachel, Muir, Vimty, Singh, Piyush, Soskova, Tereza, Cumming, Craig, Farquharson, Pamela, Pearson, Karen, Shaw, Neil, Whiteside, Jonathan, Whyte, Emma, Byers, Gordon, Davies, Kay, Engelhardt, Thoma, Faliszewski, Isabella, Johnston, Graham, Kaufmann, Nil, Kusnirikova, Zuzana, Wilson, Graham, Carachi, Peter, Makin, Andrew, Foster, Brian, Lipczynski, Dariusz, Mawer, Rebecca, Rutherford, William, Rogerson, David, Rushman, Sarah, Taylor, Christopher, Tomlinson, William, Dix, Philippa, Woodward, Tom, Bell, Graham, Boyle, David, Cloherty, Marianne, Cullen, Julia, Cullen, Pauline, Fairgrieve, Ro, Ghent, Robert, Glasgow, Russell, Gordeeva, Elena, Harden, Alison, Hivey, Sarah, Jerome, Kevin, Mckee, Lesley, Morton, Neil, Pribul, Vicky, Sinclair, John, Steiner, Maria, Steward, Heather, Sweeney, Lorraine, Thomson, Wendy, Whiteside, Jeanette, Dalton, Andrew, Ross, Mark, Smith, Carolyn, Allen, Claire, Anders, Nicola, Barlow, Victoria, Bassett, Mike, Darwin, Leanne, Davison, Rachel, Diacono, Jacque, Hobbs, Amy, Hutchinson, Adel, Lomas, Bernadette, Lonsdale, Hannah, Nasser, Leila, Oshan, Vimmi, Patel, Pradip, Raistrick, Christopher, Scott Warren, Victoria, Talbot, Laura, Wai, Carolynn, Childs, Sophie, Dickinson, Matthew, Bloomfield, Tom, Garrioch, Sweyn, Watson, Karen, Gaynor, Jame, Harrison, Richard, Lee, Juliette, Blythe, Elizabeth, Dorman, Teresa, Eissa, Ayman, Ellwood, Jame, Gooch, Ingrid, Hearn, Robert, Hodgetts, Vanessa, John, Robert, Kirton, Christine, Ladak, Nadia, Morgan, Judith, Plant, Nina, Shepherd, Elizabeth, Short, Judith, Stack, Charle, Steel, Simon, Taylor, Matthew, Thomas, Deborah, Wilson, Catharine, Wilson Smith, Elaine, Bradbury, Carol L., Hussain, Nageena, Mayell, Antonia, Mesbah, Ahmed, Qureshi, Arif, Vaidyanath, Chandra, Geary, Tim, Hawksworth, Chri, Parasuraman, Tamaraichelvi, Perry, Nicole, Banerjee, Indrani, Barr, Katharine, Butler, Patrick, Davies, Jack, Flewin, Lisa, Gande, Richard, Montague, Jame, Plumb, Jame, Pratt, Thoma, Sutherland, Paul, Vail, Hannah, Wilkins, Andrew, Hunter, Catherine, Russell, Susan, Thomas, Alun, Mifsud, Mark, Strachan, Dominic, Plichon, Benoit, Harlet, Pierre, Child and Adolescent Psychiatry / Psychology, Morawk-Wintersperger, Ulrike, Seidel-Ahyai, Natascha, Lechat, Jean-Paul, Kesic-Valpotic, Gordana, Ilmoja, Mari-Lii, Nouette-Gaulain, Karine, Gagey, Anne-Charlotte, Carre, Anne-Charlotte, Riche, Jean-Claude, Verchere-Montmayeur, Juliette, Julien-Marsollier, Florence, Saour, Anne-Charlotte, Jetzek-Zader, Martin, Meyer-Treschan, Tanja, Preussler, Niels-Peter, Sidlovskaite-Baltake, Dominika, van Stijn, Mireille F M, Dons-Sinke, Ilse, van der Knijff - van Dortmont, Anouk, Hopman, Geranne A.J., Megens, A.M., Schouten, Anton N.J., Van Der Werff, Désirée B.M., Wensing, Renee T.M., Lindenskov, Pal H H, Siemek-Mitela, Jadzia, Rosada-Kurasinska, Jowita, Bartkowska-Sniatkowska, Alicja, Mierzewska-Schmidt, Magdalena, Moraru-Draghici, Lucia, Cucui-Cozma, Cosmina, Birliba, Mihaela-Petronela, Perez- Ferrer, Antonio, Spahr-Schopfer, Isabelle, Cakar Turhan, K.Sanem, Perova-Sharonova, Valentina, Abou-Samra, Mark, Sharman, Sarah-Jane, McClintock, Joanna, Lee, Clover-Ann, Abdel-Hafiz, Mostafa, Chee, Lew-Chin, McKee, Lesley, Scott-Warren, Victoria, and Wilson-Smith, Elaine
Subjects: Male, Pediatrics, Health Status, OPERATING-ROOM, Respiratory Tract Diseases, CHILDREN, 0302 clinical medicine, REGIONAL ANESTHESIA, Postoperative Complications, 030202 anesthesiology, CARDIAC-ARREST, Medicine, General anaesthesia, Prospective Studies, Prospective cohort study, Child, Intraoperative Complications, COMPLICATIONS, ddc:617, Incidence (epidemiology), Mortality rate, musculoskeletal, neural, and ocular physiology, Incidence, Age Factors, Hospitals, Europe, Cardiovascular Diseases, Child, Preschool, RESPIRATORY ADVERSE EVENTS, Female, Clinical Competence, Cohort study, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, macromolecular substances, Anesthesia, General, Drug Hypersensitivity, 03 medical and health sciences, MORBIDITY, Journal Article, Humans, business.industry, Infant, Newborn, Infant, 030208 emergency & critical care medicine, Perioperative, nervous system, PROSPECTIVE COHORT, Relative risk, RISK-FACTORS, Observational study, Human medicine, Nervous System Diseases, business, SYSTEM
Abstract: Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6Â·35 years (SD 4Â·50) were included. The incidence of perioperative severe critical events was 5Â·2% (95% CI 5Â·0â5Â·5) with an incidence of respiratory critical events of 3Â·1% (2Â·9â3Â·3). Cardiovascular instability occurred in 1Â·9% (1Â·7â2Â·1), with an immediate poor outcome in 5Â·4% (3Â·7â7Â·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0Â·88, 95% CI 0Â·86â0Â·90; p
Published: 2017

35. Anästhesie in der Allgemein- und Viszeralchirurgie

Author: Andreas Kortgen
Abstract: In der Allgemein- und Viszeralchirurgie reicht die Bandbreite der Operationen von kleineren Eingriffen mit geringem perioperativen Risiko, wie bei Leistenhernien-Operationen, bis hin zu sehr grosen Operationen mit hohem perioperativen Risiko wie bei der thorakoabdominellen Osophagusresektion. Der zunehmende Anteil alterer Patienten mit erheblicher Komorbiditat und groser Operation stellt eine besondere perioperative Herausforderung dar. Eingriffe mit dringlicher oder Notfallindikation konnen das perioperative Risiko zusatzlich erhohen. Diese Aspekte werden in diesem Kapitel erortert.
Published: 2017

36. Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy in the Perioperative Care of Liver Transplant Recipients: A Single Center Experience

Author: Christoph Sponholz, Andreas Kortgen, Michael Bauer, and Utz Settmacher
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Hematology, Liver transplantation, Single Center, medicine.disease, Surgery, Nephrology, Intensive care, medicine, Base excess, Renal replacement therapy, Hemodialysis, Hypernatremia, business, Dialysis
Abstract: Kidney injury with concomitant hemodialysis is a common finding in perioperative care of liver transplant patients. The aim of this study was to evaluate disturbances in acid-base status, electrolyte balance and citrate accumulation during hemodialysis with regional citrate anticoagulation in perioperative care of liver transplant recipients. A retrospective, single center evaluation was conducted of patients with severe liver dysfunction receiving renal replacement therapy in the perioperative care of liver transplantation in a multidisciplinary ICU of a university hospital. Within 5 days of ICU stay, 89 patients undergoing liver transplantation received regional citrate anticoagulation for hemodialysis. During the study period pH (7.39 [7.33/7.43] vs. 7.44 [7.39/7.47], P-value = 0.014), base excess values (−0.9 [−5.08/2.35] vs. 4.3 [1.93/8.21], P-value = 0.001) and standard bicarbonate (23.6 [20/26.9] vs. 28.2 [26.2/32.2], P-value = 0.001) significantly increased, whereas lactate levels (2.6 [1.60/4.45] vs. 1.25 [0.98/1.9], P-value = 0.071) and Catot/Caion-ratio decreased or remained below the upper reference. Hypocalcemia appeared mostly within 48 h after dialysis initiation. Although sodium levels increased during the observation, rates of hypernatremia were comparable between hemodialysis days 1 and 5. Hemodialysis using regional citrate anticoagulation remains a challenge in the perioperative care of liver transplant recipients. Major attention must be paid to acid-base disturbances and citrate accumulation within 48 h after dialysis initiation. Nevertheless, regional citrate anticoagulation in liver dysfunction is a feasible and valuable tool, when limitations and pitfalls are adequately considered.
Published: 2014

37. Monitoring der Leberfunktion bei Intensivpatienten

Author: Andreas Kortgen, Michael Bauer, Falk A. Gonnert, and Christoph Sponholz
Subjects: Gynecology, medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, medicine, General Medicine, business
Abstract: Eine hepatische Dysfunktion stellt den Intensivmediziner vor diagnostische und therapeutische Herausforderungen. Neben einem Leberversagen sui generis kommen u. a. die hypoxische Hepatitis, eine Sepsis oder die (sekundar-)sklerosierende Cholangitis als auslosendes Agens einer Leberdysfunktion bei chirurgischen Patienten in Betracht. Nicht selten munden diese Krankheitsentitaten in ein Multiorganversagen und sind somit fur den Patienten pro-gnoselimitierend. Als diagnostische Hilfsmittel stehen dem Intensivmediziner neben den „statischen“ auch „dynamische“ Leberfunktionsparameter zur Verfugung, um eine hepatische Dysfunktion erkennen und rechtzeitig behandeln zu konnen. Ziel des vorliegenden Beitrags ist es, Aspekte des Leberfunktionsmonitorings darzustellen und einen klinischen Leitfaden zur Diagnostik haufiger Leberfunktionsstorungen auf der Intensivstation zu vermitteln.
Published: 2014

38. Attributable costs of patients with candidemia and potential implications of polymerase chain reaction–based pathogen detection on antifungal therapy in patients with sepsis

Author: Eberhard Straube, Konrad Reinhart, Svea Sachse, Ole Bayer, Andreas Kortgen, and Frank Bloos
Subjects: medicine.medical_specialty, medicine.diagnostic_test, Septic shock, business.industry, Case-control study, Retrospective cohort study, Critical Care and Intensive Care Medicine, medicine.disease, Intensive care unit, law.invention, Sepsis, law, Internal medicine, Multiplex polymerase chain reaction, medicine, Blood culture, Intensive care medicine, business, Polymerase chain reaction
Abstract: Purpose The purposes of this study were to calculate attributable costs of candidemia in patients with severe sepsis and to obtain preliminary data regarding the potential effects of polymerase chain reaction–based pathogen detection on antifungal therapy for these patients. Methods Patients treated between 2004 and 2010 because of severe sepsis were included into this retrospective analysis. The hospital management provided annual fixed costs per patient-day; data for variable intensive care unit costs were taken from the literature. Multiplex polymerase chain reaction (PCR) was used (VYOO®, SIRS-Lab, Jena, Germany) for pathogen detection in the blood. Results Thirty-two patients with candidemia were identified. Of 874 patients with sepsis, propensity score matching found 32 corresponding patients with sepsis but without candida infection but similar risk factors for developing candidemia. Attributable costs of candidemia were 7713.79 Euro (cost increase, 19.4%). Initiation of antifungal therapy was reduced from 67.5 (52.4, 90) hours in the group, where candida infection was determined by blood culture, to 31.0 (28.0, 37.5; P Conclusions Candidemia increases costs of care in patients with septic shock. Polymerase chain reaction–based pathogen detection significantly reduces the time to initiation of antifungal therapy. This might impact on the clinical course of the disease but need to be confirmed in further trials.
Published: 2013

39. Immunoproteomic Analysis of Antibody Responses to Extracellular Proteins of Candida albicans Revealing the Importance of Glycosylation for Antigen Recognition

Author: Evangelos J. Giamarellos-Bourboulis, Axel A. Brakhage, Uwe Knüpfer, Andreas Kortgen, Olaf Kniemeyer, Lydia Kasper, Ting Luo, Michael Bauer, Natalie Wielsch, Thomas Krüger, George Dimopoulos, and Bernhard Hube
Subjects: 0301 basic medicine, Proteomics, Glycosylation, Hyphae, Biochemistry, Immunoproteomics, Antibodies, Microbiology, Antigen-Antibody Reactions, Fungal Proteins, 03 medical and health sciences, chemistry.chemical_compound, Antigen, Polysaccharides, Tandem Mass Spectrometry, Candida albicans, Aspartic Acid Endopeptidases, Humans, Fungal protein, biology, General Chemistry, biology.organism_classification, Acquired immune system, Corpus albicans, 030104 developmental biology, chemistry, Host-Pathogen Interactions, biology.protein, Antibody, Chromatography, Liquid
Abstract: During infection, the human pathogenic fungus Candida albicans undergoes a yeast-to-hypha transition, secretes numerous proteins for invasion of host tissues, and modulates the host's immune response. Little is known about the interplay of C. albicans secreted proteins and the host adaptive immune system. Here, we applied a combined 2D gel- and LC-MS/MS-based approach for the characterization of C. albicans extracellular proteins during the yeast-to-hypha transition, which led to a comprehensive C. albicans secretome map. The serological responses to C. albicans extracellular proteins were investigated by a 2D-immunoblotting approach combined with MS for protein identification. On the basis of the screening of sera from candidemia and three groups of noncandidemia patients, a core set of 19 immunodominant antibodies against secreted proteins of C. albicans was identified, seven of which represent potential diagnostic markers for candidemia (Xog1, Lip4, Asc1, Met6, Tsa1, Tpi1, and Prx1). Intriguingly, some secreted, strongly glycosylated protein antigens showed high cross-reactivity with sera from noncandidemia control groups. Enzymatic deglycosylation of proteins secreted from hyphae significantly impaired sera antibody recognition. Furthermore, deglycosylation of the recombinantly produced, secreted aspartyl protease Sap6 confirmed a significant contribution of glycan epitopes to the recognition of Sap6 by antibodies in patient's sera.
Published: 2016

40. A Transcriptomic Biomarker to Quantify Systemic Inflammation in Sepsis - A Prospective Multicenter Phase II Diagnostic Study

Author: Michael Bauer, Andriy Ruryk, Olivier Thierry Rutschmann, Britta Wlotzka, John C. Marshall, Jean-Marc Cavaillon, Evangelos J. Giamarellos-Bourboulis, Matthias Kohl, Andreas Kortgen, Karen Felsmann, Orlando Guntinas-Lichius, Eva Möller, Konrad Reinhart, Stefan Dr. Rußwurm, Center for Sepsis Control & Care, Jena University Hospital, University of Athens Medical School [Athens], Analytik-Jena AG, Cytokines et Inflammation, Institut Pasteur [Paris], Department of Otolaryngology and the Institut of Phoniatry and Pedaudiology, Jena University Hospital [Jena], Department of Community, Geneva University Hospital, Geneva, Geneva University Hospital, Geneva-Geneva University Hospital, Geneva, Faculty of Medical and Life Sciences, Hochschule Furtwangen University [Furtwangen] (HFU), State Development Corporation of Thuringia, St Michael's Hospital, University of Toronto, Department of Anesthesiology and Intensive Care, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], The works were supported by the BMBF within the framework of the 'MetaZIK'/ZIK Septomics Jena (03Z2J521), the Thuringian Ministry of Education, Science and Art (projects B-309-00014 and A 309-04002), and by Thüringer Aufbaubank ('RNA Score 2007 FE 014'). Part of the study was funded by the Hellenic Institute for the Study of Sepsis., and Institut Pasteur [Paris] (IP)
Subjects: Genetic Markers, 0301 basic medicine, Microarray, Point-of-Care Systems, Adaptive immunity, Biology, Bioinformatics, Systemic inflammation, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Host response, Humans, Prospective Studies, 030212 general & internal medicine, Oligonucleotide Array Sequence Analysis, Transcriptomic profiling, Clusterin, Gene Expression Profiling, RT-qPCR, General Medicine, Prognosis, Acquired immune system, medicine.disease, Clinical utility, Immunity, Innate, 3. Good health, Gene expression profiling, 030104 developmental biology, Gene Expression Regulation, Point-of-care, Immunology, biology.protein, Biomarker (medicine), [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Research Paper
Abstract: Development of a dysregulated immune response discriminates sepsis from uncomplicated infection. Currently used biomarkers fail to describe simultaneously occurring pro- and anti-inflammatory responses potentially amenable to therapy. Marker candidates were screened by microarray and, after transfer to a platform allowing point-of-care testing, validated in a confirmation set of 246 medical and surgical patients. We identified up-regulated pathways reflecting innate effector mechanisms, while down-regulated pathways related to adaptive lymphocyte functions. A panel of markers composed of three up- (Toll-like receptor 5; Protectin; Clusterin) and 4 down-regulated transcripts (Fibrinogen-like 2; Interleukin-7 receptor; Major histocompatibility complex class II, DP alpha1; Carboxypeptidase, vitellogenic-like) described the magnitude of immune alterations. The created gene expression score was significantly greater in patients with definite as well as with possible/probable infection than with no infection (median (Q25/Q75): 80 (60/101)) and 81 (58/97 vs. 49 (27/66), AUC-ROC = 0.812 (95%-CI 0.755–0.869), p, Highlights • Pro- and anti-inflammatory signaling occurs simultaneously in the host response to infection. • This response is currently monitored using biomarkers restricted to the pro-inflammatory component of innate immunity. • We developed a biomarker panel consisting of 7 transcripts that can assess both facets at the point of care. The concept that a selective, overwhelming systemic inflammation, the “Systemic Inflammatory Response Syndrome (SIRS)”, triggers organ failure subsequent to infection has lately been abandoned as it neglects parallel occurring anti-inflammatory responses or defects in the adaptive immune system. The present findings suggest that a compound panel of nucleic acid biomarkers that was developed in independent training and verification cohorts and transferred to a point-of-care platform can more comprehensively describe the host response. Quantification of an enhanced innate immunity might inform studies of anti-inflammatory therapies, while measurement of derangements in specific immunity might guide strategies to restore immune effector functions.
Published: 2016

41. Hepatic function in the critically ill

Author: Andreas Kortgen and Michael Bauer
Abstract: The liver with its parenchymal and non-parenchymal cells plays a key role in the organism with manifold functions of metabolism, synthesis, detoxification, excretion, and host response. This requires a portfolio of different tests to obtain an overview of hepatic function. In the critically ill hepatic dysfunction is common and potentially leading to extrahepatic organ dysfunctions culminating in multi-organ failure. Conventional laboratory measures are used to evaluate hepatocellular damage, cholestasis, or synthesis. They provide valuable (differential) diagnostic data and can yield prognostic information in chronic liver diseases, especially when used in scoring systems such as the ‘model for end-stage liver disease’. However, they have short-comings in the critically ill in assessing rapid changes in hepatic function and liver blood flow. In contrast, dynamic quantitative liver function tests measure current liver function with respect to the ability to eliminate and/or metabolize a specific substance. In addition, they are dependent on sinusoidal blood flow. Liver function tests have prognostic significance in the critically ill and may be used to guide therapy.
Published: 2016

42. The effect of acute hepatic failure on drug handling in the critically ill

Author: Andreas Kortgen and Michael Bauer
Abstract: Impaired hepatic function is a common event in intensive care unit patients and as the liver plays a central role in drug metabolism and excretion this may lead to profound changes in pharmacokinetics. Underlying mechanisms are altered enzyme function of phase I and phase II metabolism, altered transporter protein function together with cholestasis and hepatic perfusion disorders. Moreover, multidrug therapy may lead to induction and inhibition of these enzymes and transporter proteins. In addition, changes in plasma protein binding and volumes of distribution of drugs are common. Altogether, these changes may not only lead to sometimes unpredictable plasma levels of xenobiotics, but also to drug-induced liver injury when hepatocellular accumulation of noxious substances occurs. Concomitant renal dysfunction may further complicate this situation. Pharmacodynamic alterations might also occur. In conclusion, the clinician must carefully evaluate medication given to patients with hepatic failure. Therapeutic drug monitoring should be performed wherever available to guide therapy.
Published: 2016

43. Mechanisms and functional consequences of liver failure substantially differ between endotoxaemia and faecal peritonitis in rats

Author: Peter Recknagel, Falk A. Gonnert, Andreas Kortgen, Michael Trauner, Mervyn Singer, Amelie Lupp, Mieczyslaw Gajda, Nayla Jbeily, Ralf A. Claus, Ignacio Rubio, Emina Halilbasic, and Michael Bauer
Subjects: Lipopolysaccharides, medicine.medical_specialty, Lipopolysaccharide, Bilirubin, medicine.medical_treatment, Intraperitoneal injection, Peritonitis, medicine.disease_cause, Statistics, Nonparametric, Sepsis, chemistry.chemical_compound, Cholestasis, Internal medicine, Leukocytes, medicine, Animals, Hepatology, business.industry, Histological Techniques, Organ dysfunction, medicine.disease, Endotoxemia, Rats, Oxidative Stress, Endocrinology, Liver, chemistry, Immunology, Cytokines, Tumor necrosis factor alpha, medicine.symptom, business, Biomarkers, Injections, Intraperitoneal, Liver Failure, Oxidative stress
Abstract: Background Many of the concepts describing molecular mechanisms of sepsis-induced liver failure are derived from endotoxin models. However, the biological significance of such models is questionable as the complexity of clinical sepsis and associated organ failure is only partially replicated. Aims Comparison of cytokine response, leucocyte recruitment, oxidative stress and markers of hepatic organ dysfunction in rat models of endotoxaemia or peritoneal contamination and infection (PCI). Methods Endotoxemia and polymicrobial sepsis were induced in rats by intraperitoneal injection of lipopolysaccharide (LPS) or stool suspension, respectively. Results Both insults produced clinical and laboratory signs of multiple organ dysfunction, including hepatic excretory dysfunction. However, TNF alpha, oxidative stress responses and the degree of cell death were significantly higher in endotoxaemia compared to PCI (e.g. serum TNF levels (pg/ml) at 1.5 h post-insult: sham 5 ± 1.4, LPS 1 mg/kg bw 2176.92 ± 373.78, sepsis below detection limit; P P
Published: 2012

44. Does the time of onset of severe sepsis in a surgical intensive care unit influence mortality rates: a single-center retrospective analysis

Author: Konrad Reinhart, Andreas Kortgen, Martin Brauer, Utz Settmacher, Yasser Sakr, Suzana Margareth Lobo, and E Rezende
Subjects: Male, medicine.medical_specialty, Time Factors, Critical Care, Late onset, Surgical intensive care unit, Critical Care and Intensive Care Medicine, Single Center, Sepsis, Risk Factors, Internal medicine, medicine, Humans, Hospital Mortality, Aged, Retrospective Studies, business.industry, Abdominal Infection, Mortality rate, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Surgery, Intensive Care Units, Treatment Outcome, Female, business
Abstract: Purpose The purpose of this study was to investigate possible differences in characteristics and mortality rates between early- and late-onset severe sepsis in surgical intensive care unit (ICU) patients. Materials and Methods Prospectively collected data from all adult patients (>18 years) admitted to our 50-bed surgical ICU between 1st March 2004 and 30th July 2006 were analyzed retrospectively. Results Of 5925 patients admitted during the study period, 234 patients (3.9%) had severe sepsis: 74 (31.6%) early onset and 160 (68.4%) late onset. Respiratory infections (48.1 versus 27.0%, P = .002) and infections of unknown origin (21.9 versus 12.2%, P = .005) were recorded more frequently in patients with late-onset than in those with early-onset severe sepsis; abdominal infections were more frequent in early-onset than in late-onset severe sepsis (20.3% versus 7.5%, P = .005). Gram-positive infections were more frequent in late-onset than in early-onset severe sepsis (63.1 versus 51.4%, P = .036). The time of onset of severe sepsis was not independently associated with an increased risk of ICU (early versus late: odds ratio, 1.1; confidence interval, 0.78-0.59; P = .786) or in-hospital (early versus late: odds ratio, 0.68; 95% confidence interval, 0.36-1.29; P = .689) death. Conclusions Patterns of infection are different in patients with early-onset and those with late-onset severe sepsis. The time of onset of severe sepsis in surgical ICU patients has no impact on mortality. These data may be important in risk stratification and may be useful in resource allocation in the ICU.
Published: 2010

45. Low and 'supranormal' central venous oxygen saturation and markers of tissue hypoxia in cardiac surgery patients: a prospective observational study

Author: Andreas Kortgen, Konrad Reinhart, Thomas Uhlig, Matthias Kohl, Donald L. Bredle, Suzanne Perz, and Michael Bauer
Subjects: Male, medicine.medical_specialty, Hyperoxia, Critical Care and Intensive Care Medicine, law.invention, Postoperative Complications, Reference Values, law, Anesthesiology, medicine, Humans, Prospective Studies, Cardiac Surgical Procedures, Hypoxia, Prospective cohort study, Gastric tonometry, Aged, business.industry, Mortality rate, Perioperative, Middle Aged, Hypoxia (medical), Intensive care unit, Cell Hypoxia, Cardiac surgery, Oxygen, Anesthesia, Female, medicine.symptom, business, Biomarkers
Abstract: To characterize incidence of low, normal and “supranormal” central venous oxygen saturation (ScvO2) and the relation to markers of tissue hypoxia, course and outcome in cardiac surgery patients. Prospective, observational study in a university multidisciplinary 50-bed intensive care unit including 205 consecutive patients undergoing elective cardiac surgery. Data were split into training and test data sets and subjected to 50 replications of fivefold cross-validation to estimate lower and upper bounds of ScvO2 indicative of impaired tissue oxygenation. Both low (≤60.8%) and supranormal (≥77.4%) ScvO2 were associated with an unfavorable course, while the logistic EuroSCORE for risk adjustment was comparable between groups. Incidences of abnormal ScvO2 were 13.2% low and 30.7% supranormal. Patients with low ScvO2 and an uneventful course initially presented with normal lactate levels, whereas patients with supranormal ScvO2 displayed consistently higher serum lactate levels. High ScvO2 values were associated with the use of β-mimetics and signs of systemic inflammation. Mortality rates were comparable for patient populations presenting either low (14.8%) or supranormal ScvO2 (7.9%) and higher than normals (0%, p
Published: 2010

46. Opal, but not MARS improves patients albumin binding function measured by Electron Spin Resonance (ESR) in a prospective multicenter trial

Author: Andreas Kortgen, Hans U. Gerth, Tarek Hassanein, Christoph Sponholz, Steffen Mitzner, Jan Stange, Christian Wilms, Matthias M. Dollinger, and Hartmut Schmidt
Subjects: 0301 basic medicine, Binding function, Materials science, Hepatology, Albumin, Mars Exploration Program, law.invention, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Nuclear magnetic resonance, law, Multicenter trial, 030211 gastroenterology & hepatology, Electron paramagnetic resonance
Published: 2018

47. Abstract 19408: Impact of Perioperative Liver Dysfunction on In-hospital Mortality and Long-term Survival in Infective Endocarditis Patients

Author: Mahmoud Diab, Christoph Sponholz, Michael Bauer, Andreas Kortgen, Philipp Scheffel, Thomas Lehmann, Gloria Faerber, Matthias W Pletz, and Torsten Doenst
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Background: Infective endocarditis (IE) is a dangerous disease with high mortality (20-40%). A leading cause of death is multi-organ failure (MODS) with liver dysfunction (LD) as major contributor. Data on LD in IE patients are scarce. We assessed the impact of preoperative - and newly occurring LD on in-hospital mortality and long-term survival in IE patients. Methods: We retrospectively reviewed our database for surgery of left-sided endocarditis between 1/07 and 4/13. We used the hepatic Sepsis-related Organ Failure Assessment (hSOFA) score to assess the degree of LD. We performed Chi-Square, Cox regression and multivariate analyses. Results: The 308 patients had a mean age of 62 ±13.9. Preoperative LD (hSOFA > 0, Bilirubin > 32 μmol/L) was present in 1/4 (n=81) of patients and was associated with severely elevated in-hospital mortality (51.9% vs.14.6% without preoperative LD, p
Published: 2015

48. A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery

Author: Matthias Gruenewald, Mark Coburn, Jochen Cremer, Christian Reyher, Julika Schön, Bernd Niemann, Peter Kienbaum, Rita Laufenberg-Feldmann, Andreas Böning, Matthias Heringlake, Marion Ferner, Michael Sander, Martin Bauer, U. Strouhal, Andreas Kortgen, Oana Brosteanu, Thorsten Smul, Sascha Treskatsch, Tanja Meyer-Treschan, Christian Stoppe, Thomas F. Schilling, Sebastian Stehr, I. F. Brandes, Georg Fuernau, Maria Wittmann, Kai Zacharowski, Berthold Bein, Jan P. Roesner, G. Schaelte, Ewa Wolwender, Patrick Meybohm, Georg Baumgarten, Dirk Hasenclever, and Frank Kletzin
Subjects: Male, medicine.medical_specialty, Kaplan-Meier Estimate, law.invention, Upper Extremity, Postoperative Complications, Randomized controlled trial, Double-Blind Method, law, Ischemia, Multicenter trial, medicine, Cardiopulmonary bypass, Clinical endpoint, Humans, Myocardial infarction, Prospective Studies, Treatment Failure, Cardiac Surgical Procedures, Ischemic Preconditioning, Stroke, Propofol, Aged, Cardiopulmonary Bypass, business.industry, Sham Intervention, General Medicine, Length of Stay, Middle Aged, medicine.disease, Heart Surgery, Troponin, 3. Good health, Surgery, Cardiac surgery, Elective Surgical Procedures, Anesthesia, Anesthesia, Intravenous, Female, business
Abstract: BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.). peerReviewed
Published: 2015

49. Unmet Medical Needs in Life-Threatening Infections - Caring for the Critically Ill

Author: Andreas Kortgen, Mervyn Singer, and Michael Bauer
Subjects: Healthcare associated infections, Sepsis, medicine.medical_specialty, Critically ill, business.industry, medicine, medicine.disease, Intensive care medicine, business, Life-threatening infections
Published: 2015

50. Sepsis—Current Aspects of Pathophysiology and Implications for Diagnosis and Management

Author: Andreas Kortgen, Michael Bauer, and Gunther Olaf Hofmann
Subjects: medicine.medical_specialty, Surviving Sepsis Campaign, business.industry, Septic shock, Mortality rate, Psychological intervention, Dysfunctional family, Disease, medicine.disease, Sepsis, medicine, Surgery, business, Intensive care medicine, Protein C, medicine.drug
Abstract: Sepsis is characterized by disrupted inflammatory homeostasis due to infection. While a localized and controlled inflammatory reaction helps to eliminate and control infection, a dysregulated host response triggers multiple organ failure determining course and prognosis. Consequent surgical source control paralleled by adequate and early antibiotic therapy remains the cornerstone of care. Nevertheless, mortality remains as high as 50–60% for severe sepsis and septic shock. As the molecular mechanisms are becoming increasingly better defined, interventions aiming to interfere with the host response to infection have been undertaken, largely with disappointing results. Thus, many evidence-based recommendations suggest waiving of resource-consuming interventions, such as supplementation of antithrombin or immunoglobulins. Nevertheless, several seminal studies have indicated that meticulous supportive care according to pathophysiological principles, most notably early goal-directed therapy, low-dose hydrocortisone and activated protein C, can disrupt dysfunctional cascades favorably influencing the course of the disease. In parallel, there is increasing evidence from national and international surveys that therapy of severe sepsis on ICUs worldwide is generally in poor compliance with current guidelines, while personal perception of the physicians in charge would suggest high rates of adherence to evidence-based recommendations. Thus, strategies of change management, such as implementation of ‘sepsis bundles’, are warranted to achieve better standards of care toward the aim of the “surviving sepsis campaign”, i.e. a reduction of mortality rates by 25% within the next years.
Published: 2006

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