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1. Effects of salinity stress on the seed germination and seedling characters of carrots (Daucus carota L.)

Author: Md. Harun Ar Rashid, Mst. Fatema Tuz- Zahura, Kaniz Fatema Suchi, Nafisa Anjum, Mst. Tamanna Tasmim, and Philipp Simon
Subjects: carrot, salinity stress, seed germination, seedling characters, varieties, Agriculture
Abstract: Carrot is an important root vegetable and salinity has strong effect on its seed germination and seedling characters. An experiment was conducted at the Postgraduate Laboratory of the Department of Horticulture, Bangladesh Agricultural University, Mymensingh during the period from July to August, 2023 to study the effect of salinity stress on the seed germination and seedling characters of four carrot varieties. The two-factor experiment consisted of four carrot varieties viz. Orange king, Orange star, Sangal and Red lady, and five salinity levels viz. control (tap water), 25 mM, 50 mM, 75 mM and 100 mM NaCl. The experiment was laid out in completely randomized design with three replications. Results revealed that salinity and carrot varieties significantly influenced all the parameters studied. The highest seed germination (44.44%) was obtained from Orange king while the lowest (32.89%) was obtained from Red lady. The highest seed germination (41.11%) was obtained from 100 mM NaCl solution and the lowest (34.44%) was found from 75 mM NaCl. Among the treatment combinations, the highest seed germination (60.00%) was obtained from Orange king along with 50 mM NaCl. The maximum radicle (15.46 mm) and plumule length (12.36 mm), leaf size (5.50 mm), number of leaves (2.73) and seedling height (27.82 mm) was obtained from Orange king. Maximum plumule length (13.27 mm), leaf size (5.98 mm) and seedling height (23.27mm) was obtained from control treatment and maximum number of leaves (2.08) from 25 mM NaCl solution. Among the treatment combinations, highest radicle length (18.27 mm), plumule length (17.40 mm), leaf size (7.60 mm), seedling height (35.67 mm) was obtained from Orange king along with 25 mM NaCl solution. Therefore, Orange king along with 50 mM NaCl solution and 25 mM NaCl solution was found to be better in respect of seed germination and seedling characters of carrots compared to other treatments respectively. [Fundam Appl Agric 2024; 9(2.000): 113-121]
Published: 2024
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2. Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release

Author: Sarah Rösing, Fabian Ullrich, Susann Meisterfeld, Franziska Schmidt, Laura Mlitzko, Marijana Croon, Ryan G Nattrass, Nadia Eberl, Julia Mahlberg, Martin Schlee, Anja Wieland, Philipp Simon, Daniel Hilbig, Ulrike Reuner, Alexander Rapp, Julia Bremser, Peter Mirtschink, Stephan Drukewitz, Thomas Zillinger, Stefan Beissert, Katrin Paeschke, Gunther Hartmann, Aleksandra Trifunovic, Eva Bartok, and Claudia Günther
Subjects: Science
Abstract: Abstract Myotonic dystrophy type 2 (DM2) is a tetranucleotide CCTG repeat expansion disease associated with an increased prevalence of autoimmunity. Here, we identified an elevated type I interferon (IFN) signature in peripheral blood mononuclear cells and primary fibroblasts of DM2 patients as a trigger of chronic immune stimulation. Although RNA-repeat accumulation was prevalent in the cytosol of DM2-patient fibroblasts, type-I IFN release did not depend on innate RNA immune sensors but rather the DNA sensor cGAS and the prevalence of mitochondrial DNA (mtDNA) in the cytoplasm. Sublethal mtDNA release was promoted by a chronic activation of the ATF6 branch of the unfolded protein response (UPR) in reaction to RNA-repeat accumulation and non-AUG translated tetrapeptide expansion proteins. ATF6-dependent mtDNA release and resulting cGAS/STING activation could also be recapitulated in human THP-1 monocytes exposed to chronic endoplasmic reticulum (ER) stress. Altogether, our study demonstrates a novel mechanism by which large repeat expansions cause chronic endoplasmic reticulum stress and associated mtDNA leakage. This mtDNA is, in turn, sensed by the cGAS/STING pathway and induces a type-I IFN response predisposing to autoimmunity. Elucidating this pathway reveals new potential therapeutic targets for autoimmune disorders associated with repeat expansion diseases.
Published: 2024
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3. Predicting Successful Weaning from Mechanical Ventilation by Reduction in Positive End-expiratory Pressure Level Using Machine Learning.

Author: Seyedmostafa Sheikhalishahi, Mathias Kaspar, Sarra Zaghdoudi, Julia Sander, Philipp Simon, Benjamin P Geisler, Dorothea Lange, and Ludwig Christian Hinske
Subjects: Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Weaning patients from mechanical ventilation (MV) is a critical and resource intensive process in the Intensive Care Unit (ICU) that impacts patient outcomes and healthcare expenses. Weaning methods vary widely among providers. Prolonged MV is associated with adverse events and higher healthcare expenses. Predicting weaning readiness is a non-trivial process in which the positive end-expiratory pressure (PEEP), a crucial component of MV, has potential to be indicative but has not yet been used as the target. We aimed to predict successful weaning from mechanical ventilation by targeting changes in the PEEP-level using a supervised machine learning model. This retrospective study included 12,153 mechanically ventilated patients from Medical Information Mart for Intensive Care (MIMIC-IV) and eICU collaborative research database (eICU-CRD). Two machine learning models (Extreme Gradient Boosting and Logistic Regression) were developed using a continuous PEEP reduction as target. The data is splitted into 80% as training set and 20% as test set. The model's predictive performance was reported using 95% confidence interval (CI), based on evaluation metrics such as area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), F1-Score, Recall, positive predictive value (PPV), and negative predictive value (NPV). The model's descriptive performance was reported as the variable ranking using SHAP (SHapley Additive exPlanations) algorithm. The best model achieved an AUROC of 0.84 (95% CI 0.83-0.85) and an AUPRC of 0.69 (95% CI 0.67-0.70) in predicting successful weaning based on the PEEP reduction. The model demonstrated a Recall of 0.85 (95% CI 0.84-0.86), F1-score of 0.86 (95% CI 0.85-0.87), PPV of 0.87 (95% CI 0.86-0.88), and NPV of 0.64 (95% CI 0.63-0.66). Most of the variables that SHAP algorithm ranked to be important correspond with clinical intuition, such as duration of MV, oxygen saturation (SaO2), PEEP, and Glasgow Coma Score (GCS) components. This study demonstrates the potential application of machine learning in predicting successful weaning from MV based on continuous PEEP reduction. The model's high PPV and moderate NPV suggest that it could be a useful tool to assist clinicians in making decisions regarding ventilator management.
Published: 2024
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4. When too much closeness harms: circumflex artery injury during mitral valve surgery

Author: Christian Dumps, Philipp Simon, Evaldas Girdauskas, and Felix Girrbach
Subjects: mitral valve, cardiac surgery, minimally invasive surgery, valvular annuloplasty, heart valve prosthesis implantation, mitral valve insufficiency, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Occlusion of the left coronary circumflex artery (LCX) during surgical procedures of the mitral valve is an infrequent but potentially life-threatening complication (1–3). Due to its close anatomical relationship to the posterior mitral valve annulus, there is a relevant risk of causing a stenosis or an occlusion of the left circumflex artery, especially by surgical annular sutures. The perioperative clinical course is heterogeneous, ranging from—initially—asymptomatic or solely electrocardiographic abnormalities to cardiogenic shock. Both severely impaired ventricular contractility or malignant arrhythmia may potentially lead to a weaning failure from cardiopulmonary bypass (CPB) and eventually result in chronic heart failure with persistently reduced ejection fraction. Possible therapeutic strategies include the immediate reopening of causal sutures, aortocoronary bypass grafting or percutaneous coronary intervention (PCI), yet PCI seems to be the preferred method at present.
Published: 2023
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5. Variation in Seed Germination and Amylase Activity of Diverse Carrot [Daucus carota (L.)] Germplasm under Simulated Drought Stress

Author: Aneela Nijabat, Saba Manzoor, Samia Faiz, Naima Huma Naveed, Adam Bolton, Bilal Ahmad Khan, Aamir Ali, and Philipp Simon
Subjects: abiotic stress, amylase activity, carrot breeding, daucus carota, diverse germplasm, drought tolerance, osmotic pressure, polyethylene glycol, Plant culture, SB1-1110
Abstract: Drought is one of the major environmental challenges constraining the production of agricultural crops, including carrot. Seed germination is the initial and most critical stage of crop establishment, and it is very sensitive to drought stress because water scarcity affects the enzymatic solubilization of stored metabolites in seeds that provide energy for the growth of germinating embryo. Few studies evaluating the effect of drought stress on carrot seed germination of more than a few cultivars grown under stress have been published. Therefore, the present study was designed to define the appropriate osmotic potential for evaluating drought tolerance of carrot, evaluate the response of diverse carrot germplasm to drought stress during seed germination to identify drought-tolerant accessions that may be used by plant breeders, and evaluate the relation between amylase activity and germination rate of drought-tolerant and drought-sensitive accessions. To identify an appropriate screening osmotic potential, two commercial cultivars and two United States Department of Agriculture inbreeds were evaluated at six osmotic potentials (00, −0.30, −0.51, −0.58, −0.80, and −1.05 MPa); −0.58 MPa was identified as the optimal osmotic potential for screening the drought tolerance of carrot seed. Cultivated and wild carrot plant introductions (PIs) (n = 200 and n = 50, respectively) from the National Plant Germplasm System were evaluated for drought tolerance under nonstress and simulated drought stress conditions (00 MPa and −0.58 MPa, respectively) by calculating the absolute decrease (AD) in percent germination, inhibition index (II), relative drought tolerance (RDT), and drought tolerance index (DTI). All measurements of drought tolerance identified significant differences among accessions; the AD in seed germination ranged from 0.0% to 69.3%, II ranged from 0.0% to 80.2%, RDT ranged from 0.2 to 1.0, and DTI ranged from 0.13 to 1.47. All wild carrot accessions displayed low levels of drought tolerance, but PI 652387 and PI 177381 (both from Turkey) and PI 274297 (Pakistan) were most drought-sensitive, whereas cultivated accessions PI 643114 (United States), PI 652208 (China), and PI 502347 (Uzbekistan) were most drought-tolerant. Tolerant accessions displayed much higher α-amylase activity under nonstress conditions than sensitive accessions, and α-amylase activity of tolerant accessions was also reduced less with seed germination under increasing osmotic potential (range, 0.0 to −1.05 MPa) than sensitive accessions over 24, 48, and 72 hours of seed germination. This is the first evaluation of drought stress tolerance during seed germination and the enzymatic response of diverse carrot germplasms under simulated drought stress.
Published: 2023

6. A multifaceted educational intervention improved anti-infectious measures but had no effect on mortality in patients with severe sepsis

Author: Daniel Schwarzkopf, Claudia Tanja Matthaeus-Kraemer, Daniel O. Thomas-Rüddel, Hendrik Rüddel, Bernhard Poidinger, Friedhelm Bach, Herwig Gerlach, Matthias Gründling, Matthias Lindner, Christian Scheer, Philipp Simon, Manfred Weiss, Konrad Reinhart, Frank Bloos, and MEDUSA study group
Subjects: Medicine, Science
Abstract: Abstract Sepsis is a major reason for preventable hospital deaths. A cluster-randomized controlled trial on an educational intervention did not show improvements of sepsis management or outcome. We now aimed to test an improved implementation strategy in a second intervention phase in which new intervention hospitals (former controls) received a multifaceted educational intervention, while controls (former intervention hospitals) only received feedback of quality indicators. Changes in outcomes from the first to the second intervention phase were compared between groups using hierarchical generalized linear models controlling for possible confounders. During the two phases, 19 control hospitals included 4050 patients with sepsis and 21 intervention hospitals included 2526 patients. 28-day mortality did not show significant changes between study phases in both groups. The proportion of patients receiving antimicrobial therapy within one hour increased in intervention hospitals, but not in control hospitals. Taking at least two sets of blood cultures increased significantly in both groups. During phase 2, intervention hospitals showed higher proportion of adequate initial antimicrobial therapy and de-escalation within 5 days. A survey among involved clinicians indicated lacking resources for quality improvement. Therefore, quality improvement programs should include all elements of sepsis guidelines and provide hospitals with sufficient resources for quality improvement. Trial registration: ClinicalTrials.gov, NCT01187134. Registered 23 August 2010, https://www.clinicaltrials.gov/ct2/show/study/NCT01187134 .
Published: 2022
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7. Adverse effects of delayed antimicrobial treatment and surgical source control in adults with sepsis: results of a planned secondary analysis of a cluster-randomized controlled trial

Author: Hendrik Rüddel, Daniel O. Thomas-Rüddel, Konrad Reinhart, Friedhelm Bach, Herwig Gerlach, Matthias Lindner, John C. Marshall, Philipp Simon, Manfred Weiss, Frank Bloos, Daniel Schwarzkopf, and the MEDUSA study group
Subjects: Sepsis, Infection control, Anti-biotic agents, Time-to-treatment, Patient care bundles, Surgical source control, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Timely antimicrobial treatment and source control are strongly recommended by sepsis guidelines, however, their impact on clinical outcomes is uncertain. Methods We performed a planned secondary analysis of a cluster-randomized trial conducted from July 2011 to May 2015 including forty German hospitals. All adult patients with sepsis treated in the participating ICUs were included. Primary exposures were timing of antimicrobial therapy and delay of surgical source control during the first 48 h after sepsis onset. Primary endpoint was 28-day mortality. Mixed models were used to investigate the effects of timing while adjusting for confounders. The linearity of the effect was investigated by fractional polynomials and by categorizing of timing. Results Analyses were based on 4792 patients receiving antimicrobial treatment and 1595 patients undergoing surgical source control. Fractional polynomial analysis identified a linear effect of timing of antimicrobials on 28-day mortality, which increased by 0.42% per hour delay (OR with 95% CI 1.019 [1.01, 1.028], p ≤ 0.001). This effect was significant in patients with and without shock (OR = 1.018 [1.008, 1.029] and 1.026 [1.01, 1.043], respectively). Using a categorized timing variable, there were no significant differences comparing treatment within 1 h versus 1–3 h, or 1 h versus 3–6 h. Delays of more than 6 h significantly increased mortality (OR = 1.41 [1.17, 1.69]). Delay in antimicrobials also increased risk of progression from severe sepsis to septic shock (OR per hour: 1.051 [1.022, 1.081], p ≤ 0.001). Time to surgical source control was significantly associated with decreased odds of successful source control (OR = 0.982 [0.971, 0.994], p = 0.003) and increased odds of death (OR = 1.011 [1.001, 1.021]; p = 0.03) in unadjusted analysis, but not when adjusted for confounders (OR = 0.991 [0.978, 1.005] and OR = 1.008 [0.997, 1.02], respectively). Only, among patients with septic shock delay of source control was significantly related to risk-of death (adjusted OR = 1.013 [1.001, 1.026], p = 0.04). Conclusions Our findings suggest that management of sepsis is time critical both for antimicrobial therapy and source control. Also patients, who are not yet in septic shock, profit from early anti-infective treatment since it can prevent further deterioration. Trial registration ClinicalTrials.gov ( NCT01187134 ). Registered 23 August 2010, NCT01187134
Published: 2022
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8. Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial

Author: Joachim Gerss, Javier Ripollés-Melchor, Emmanuel Futier, Melanie Meersch, Carola Wempe, Detlef Kindgen-Milles, Alexander Zarbock, Markus W Hollmann, Sigismond Lasocki, Thomas Rimmele, Tim Rahmel, Michael Adamzik, Hartmuth Nowak, Ingeborg Welters, Brian Johnston, Ane Abad-motos, Alfredo Abad-gurumeta, Marc Moritz Berger, Davide Ricci, Maurizio Cecconi, Gudrun Kunst, Christian Stoppe, Christian Putensen, Marlies Ostermann, Sascha Ott, Brijesh Patel, Gabriele Baldini, Antoine Lamblin, Karen Williams, Elena Mancini, Christian Arndt, Hinnerk Wulf, Marc Irqsusi, Wim Vandenberghe, John Kellum, Raphael Weiss, Jackie Donovan, Lui G Forni, Giacomo Monti, Céline Monard, Markus A Weigand, Thorsten Brenner, Ulrich Jaschinski, Carlos Lopez, Maxime Leger, Emmanuel Rineau, Philipp Simon, María Gómez-Rojo, Lars Bergmann, Alicia Waite, Savino Spadaro, Alexander Wolf, Andrew Spence, Simon Dubler, Alexander PJ Vlaar, Patrick Schober, Ben C Creagh-Brown, Nandor Marczin, Emilio Maseda, Christian Strauss, Stefano Romagnoli, Christian Nusshag, Ulrich Gobel, Ángel Candela-Toha, Jon Silversides, Nuttha Lumlertgul, Khaschayar Saadat-Gilani, Vincent Legros, Timo Brandenburger, Thomas Dimski, Laura Huthmann, Claude Pelletier, Manon Schleß, Peter Rosenberger, Helene Häberle, Jan Gerrit Haaker, Matthias Gründel, Lucia Cattin, Laura Villarino Villa, Juan Victor Lorente, Christine Martin, Jan Larmann, Wolfgang Bauer, Giovanni Borghi, Benjamin O’Brien, Thilo von Groote, Antoine Guillaume Schneider, Silvia De Rosa, Diego Parise, Alice Bernard, Paula Fernández-Valdes-Bango, Irene Romero Bhathal, A Suarez-de-la-Rica, Gianluca Villa, Raquel García-Álvarez, Antonio Siniscalchi, Richard Ellerkmann, Florian Espeter, Christian Porschen, Mahan Sadjadi, Michael Storck, Tobias Brix, Dana Meschede, Wida Amini, Carina Stenger, Julius Freytag, Jens Brands, Matthias Unterberg, Britta Marko, Fabian Dusse, Wolfgang A Wetsch, Sandra E Stoll, Hendrik Drinhaus, Bernd W Böttiger, Onnen Mörer, Lars-Olav Harnisch, Roswitha Lubjuhn, Daniel Heise, Christian Bode, Andrea Sauer, Konrad Peukert, Lennart Wild, Philippe Kruse, Jan Menzenbach, Valbona Mirakaj, Sabine Hermann, Stefanie Decker, Mona Jung-König, Tobias Hölle, Sarah Dehne, Jörg Reutershan, Thomas Prüfer, Stefan Pielmeier, Indra Wimmelmeier, Michaela Scholz, Andrea Paris, Isabel Christina Gallego Zapata, Holger Pohl, Nirmeen Fayed, Kai Dielmann, Evelyn Martin, Tilo Koch, Alexander Mück, Philipp Deetjen, Ngoc Bich Mehlmann, Peter M Spieth, Andreas Güldner, Axel Rand, Maximillian Ragaller, Martin Mirus, Rebecca Bockholt, Marc Herzog, Maren Kleine-Brüggeney, Ant Isabelle Cristiani, Marion Ohl, Monica Vieira Da Silva, Gilda Filipe de Castro Reblo, Matthias Hilty, Katharina Spanaus, Benedetta Mura, Eleonora Terreni, Francesco Magiotti, Lorenzo Turi, Cristiana Laici, Chiara Capozzi, Andrea Castelli, Massimiliano Greco, Antonio Messina, Gianluca Castellani, Romina Aceto, Vinicio Danzi, Alessandro Rigobello, Massimo De Cal, Monica Zanella, Gaetano Scaramuzzo, Riccardo La Rosa, Paolo Priani, Alberto Volta Carlo, Stefano Turi, Martina Baiardo Redaelli, Marilena Marmiere, Kittisak Weerapolchai, Shelley Lorah, Fabiola D’Amato, Aneta Bociek, Rosario Lim, Benjie Cendreda, Reynaldo Dela Cuesta, Eirini Kosifidou, Zoka Milan, Juliana Fernanda, Emma Clarey, Daveena Meeks, Nicholas J Lees, Marco Scaramuzzi, Orinta Kviatkovske, Adam Glass, Christine Turley, Charlotte Quinn, Syeda Haider, Adam Rossiter, Syed Nasser, Ned Gilbert-Kawai, Tatjana Besse-Hammer, Eric Hoste, Hannah Schaubroeck, Jan De Waele, Jenni Breel, Eline de Klerk, Harm-Jan de Grooth, Lothar Schwarte, Alexander Loer, Alicia Ruiz-Escobar, Diana Fernández-García, Nerea Gómez-Pérez, Pascual Crespo-Aliseda, Cristina Cerro-Zaballos, Cristina Fernández-Martín, Eduardo Martín-Montero, Alejandro Suarez de la Rica, Héctor Berges Gutiérrez, Maria del Pino Heredia Pérez, Maria de los Reyes Bellido Fernández, Liena Izquierdo López, Javier Valiente Lourtau, Ma Angeles Ferre Colomer, Ma Azucena Pajares Moncho, Maria Jesús Montero Hernández, Esther Pérez Sancho, Silvia Polo Matínez, Pedro Rivera Soria, Maider Puyada Jáuregui, Hugo Rivera Ramos, Marta Antelo Adrán, Ramón Adalia Bartolomé, Patricia Galán Menéndez, Laura Llinares Espin, Yuri Santiago Loaiza Aldean, Víctor MoralesAriza, Rosalía Navarro-Perez, Luis Santé-Serna, Pedro de la Calle-Elguezabal, Rubén Sánchez-Martín, Inés De Soto, Pau Vallhonrat Alcántara, Laura Perelló Cerdà, Gal·la Rouras Hurtado, Paula Rodriguez Nieto, John Narros Sicluna, Angel Molero Molinero, Juan Pablo Nocete, Elena Murcia Sánchez, Stanislas Abrard, Marie-Luce Parrouffe, Frank Bidar, Lucie Aupetitgendre, Ugo Schiff, Bertille Paquette, Gaëlle Sellier, Nathalie Borgnetta, Benjamin Brochet, Thierry Floch, Julien Coffinet, and Marion Leclercq-Rouget
Subjects: Medicine
Abstract: Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysis The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and dissemination The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration number NCT04647396.
Published: 2023
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9. Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

Author: Daniel O. Thomas-Rüddel, Peter Hoffmann, Daniel Schwarzkopf, Christian Scheer, Friedhelm Bach, Marcus Komann, Herwig Gerlach, Manfred Weiss, Matthias Lindner, Hendrik Rüddel, Philipp Simon, Sven-Olaf Kuhn, Reinhard Wetzker, Michael Bauer, Konrad Reinhart, Frank Bloos, and the MEDUSA study group
Subjects: Fever, Sepsis, Outcome, Mortality, Body temperature, PCT, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates. Methods We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia. Results With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever. Conclusions Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question. Trial registration The original trial whose dataset was analyzed was registered at ClinicalTrials.gov (NCT01187134) on August 23, 2010, the first patient was included on July 1, 2011.
Published: 2021
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10. Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)

Author: Michael Bauer, MD, Andreas Weyland, MD, Gernot Marx, MD, Frank Bloos, MD, PhD, Stephan Weber, Dipl. Stat., Norbert Weiler, MD, Stefan Kluge, MD, Anja Diers, MD, Tim Philipp Simon, MD, Ingmar Lautenschläger, MD, Matthias Gründling, MD, Ulrich Jaschinski, MD, Philipp Simon, MD, Axel Nierhaus, MD, Onnen Moerer, MD, Lorenz Reill, MD, Achim Jörres, MD, Renfeng Guo, MD, Markus Loeffler, MD, Konrad Reinhart, MD, Niels Riedemann, MD, and for the SepNet-Study Group
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: IMPORTANCE:. Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction. OBJECTIVES:. This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock. DESIGN:. Multicenter, randomized, and placebo-controlled study. SETTING AND PARTICIPANTS:. Eleven multidisciplinary ICUs across Germany. Adult patients with severe sepsis or septic shock and with early onset of infection-associated organ dysfunction. MAIN OUTCOMES AND MEASURES:. Patients were randomly assigned in a ratio of 2:1 to three subsequent dosing cohorts for IV vilobelimab or placebo receiving either 2 × 2 mg/kg (0 and 12 hr), 2 × 4 mg/kg (0 and 24 hr), and 3 × 4 mg/kg (0, 24, and 72 hr). Co-primary endpoints were pharmacodynamics (assessed by C5a concentrations), pharmacokinetics (assessed by vilobelimab concentrations), and safety of vilobelimab. Preliminary efficacy was evaluated by secondary objectives. RESULTS:. Seventy-two patients were randomized (16 patients for each vilobelimab dosing cohort and eight patients for each placebo dosing cohort). Vilobelimab application was associated with dosing dependent decrease in C5a compared with baseline (p < 0.001). Duration of C5a decrease increased with more frequent dosing. Membrane attack complex lysis capacity measured by 50% hemolytic complement was not affected. Vilobelimab was well tolerated with similar safety findings in all dose cohorts. No vilobelimab-specific adverse events emerged. For vilobelimab-treated patients, investigators attributed less treatment-emergent adverse events as related compared with placebo. Dosing cohorts 2 and 3 had the highest ICU-free and ventilator-free days. There was no difference in mortality, vasopressor-free days, or renal replacement therapy-free days between the groups. CONCLUSIONS AND RELEVANCE:. Administration of vilobelimab in patients with severe sepsis and septic shock selectively neutralizes C5a in a dose-dependent manner without blocking formation of the membrane attack complex and without resulting in detected safety issues. The data warrant further investigation of C5a inhibition in sepsis.
Published: 2021
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11. Cell Membrane Stability and Relative Cell Injury in Response to Heat Stress during Early and Late Seedling Stages of Diverse Carrot (Daucus carota L.) Germplasm

Author: Aneela Nijabat, Adam Bolton, Muhammad Mahmood-ur-Rehman, Adeel Ijaz Shah, Rameez Hussain, Naima Huma Naveed, Aamir Ali, and Philipp Simon
Subjects: abiotic stress, carrot breeding, developmental variation, genetic diversity, heat tolerance, high temperature, Plant culture, SB1-1110
Abstract: Heat waves occur with more regularity and they adversely affect the yield of cool season crops including carrot (Daucus carota L.). Heat stress influences various biochemical and physiological processes including cell membrane permeability. Ion leakage and increase in cell permeability are indicators of cell membrane stability and have been used to evaluate the stress tolerance response in numerous crops and inform plant breeders for improving heat tolerance. No study has been published about the effects of heat stress on cell membrane stability and relative cell injury of carrot. Therefore, the present study was designed to estimate these stress indicators in response to heat stress at the early and late seedling developmental stages of 215 diverse accessions of wild and cultivated carrot germplasm. The article identifies the relationship between early and late stages of seedling tolerance across carrot genotypes and identifies heat-tolerant genotypes for further genetic analysis. Significant genetic variation among these stress indicators was identified with cell membrane stability and relative cell injury ranging from 6.3% to 97.3% and 2.8% to 76.6% at the early seedling stage, respectively; whereas cell membrane stability and relative cell injury ranged from 2.0% to 94.0% and 2.5% to 78.5%, respectively, at the late seedling stage under heat stress. Broad-sense heritability ranged from 0.64 to 0.91 for traits of interest under study, which indicates a relatively strong contribution of genetic factors in phenotypic variation among accessions. Heat tolerance varied widely among both wild and cultivated accessions, but the incidence of tolerance was higher in cultivated carrots than in wild carrots. The cultivated carrot accessions PI 326009 (Uzbekistan), PI 451754 (Netherlands), L2450 (USA), and PI 502654 (Pakistan) were identified as the most heat-tolerant accessions with highest cell membrane stability. This is the first evaluation of cell membrane stability and relative cell injury in response to heat stress during carrot development.
Published: 2020
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12. Changes in the core endophytic mycobiome of carrot taproots in response to crop management and genotype

Author: Sahar Abdelrazek, Sulbha Choudhari, Jyothi Thimmapuram, Philipp Simon, Micaela Colley, Tesfaye Mengiste, and Lori Hoagland
Subjects: Medicine, Science
Abstract: Abstract Fungal endophytes can influence production and post-harvest challenges in carrot, though the identity of these microbes as well as factors affecting their composition have not yet been determined, which prevents growers from managing these organisms to improve crop performance. Consequently, we characterized the endophytic mycobiome in the taproots of three carrot genotypes that vary in resistance to two pathogens grown in a trial comparing organic and conventional crop management using Illumina sequencing of the internal transcribed spacer (ITS) gene. A total of 1,480 individual operational taxonomic units (OTUs) were identified. Most were consistent across samples, indicating that they are part of a core mycobiome, though crop management influenced richness and diversity, likely in response to differences in soil properties. There were also differences in individual OTUs among genotypes and the nematode resistant genotype was most responsive to management system indicating that it has greater control over its endophytic mycobiome, which could potentially play a role in resistance. Members of the Ascomycota were most dominant, though the exact function of most taxa remains unclear. Future studies aimed at overcoming difficulties associated with isolating fungal endophytes are needed to identify these microbes at the species level and elucidate their specific functional roles.
Published: 2020
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13. The role of generalized trust in COVID-19 vaccine acceptance.

Author: Philipp Simon Eisnecker, Martin Kroh, and Simon Kühne
Subjects: Medicine, Science
Abstract: Immunization by vaccination is one of the most important tools for fighting the COVID-19 pandemic. Yet in many countries, immunization campaigns have been hampered by vaccine hesitancy within the population. Building on the idea that vaccination decisions are embedded in the broader societal context, we study the role of generalized trust-the belief that most people can generally be trusted-in vaccine acceptance. Immunization campaigns face an inherent collective action problem: As all individuals benefit collectively from high immunization rates regardless of individual contribution, especially those with a low risk of severe COVID infection have an incentive to decide against the (perceived) costs and risks of vaccination. We argue that generalized trust may help to overcome this problem by encouraging the belief that cooperation for the common good is achievable and that those who cooperate are unlikely to be exploited by others. We further argue that the positive effect of generalized trust on vaccination decisions is weaker among individuals who are at higher risk of severe outcomes from the disease, as the collective action problem is less pronounced in this group. To test our predictions, we used data from the SOEP-CoV survey, which queried a representative probability sample of Germany's population between January and February 2021 on topics connected to the pandemic. Using multiple logistic regression models, and in line with expectations, we found a positive and robust link between generalized trust and the willingness to accept vaccination as soon as offered. However, overall, our examination of heterogeneous effects does not unequivocally support the idea that the role of generalized trust varies according to individual COVID risk.
Published: 2022
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14. Algorithmic surveillance of ICU patients with acute respiratory distress syndrome (ASIC): protocol for a multicentre stepped-wedge cluster randomised quality improvement strategy

Author: Stefan Kluge, Gernot Marx, Christian Putensen, Danny Ammon, Silke Haferkamp, Saskia Deffge, Thomas Wendt, Daniel Tiller, André Scherag, Philipp Simon, Johannes Bickenbach, Sebastian Johannes Fritsch, Julian Benedict Kunze, Oliver Maassen, Jennifer Kistermann, Irina Lutz, Nora Kristiana Voellm, Volker Lowitsch, Richard Polzin, Konstantin Sharafutdinov, Hannah Mayer, Lars Kuepfer, Rolf Burghaus, Walter Schmitt, Joerg Lippert, Morris Riedel, Chadi Barakat, André Stollenwerk, Simon Fonck, Sven Zenker, Felix Erdfelder, Daniel Grigutsch, Rainer Kram, Susanne Beyer, Knut Kampe, Jan Erik Gewehr, Friederike Salman, Patrick Juers, Emilia Wisotzki, Sebastian Gross, Lorenz Homeister, Frank Bloos, Susanne Mueller, Julia Palm, Nora Jahn, Markus Loeffler, Tobias Schuerholz, Petra Groeber, and Andreas Schuppert
Subjects: Medicine
Abstract: Introduction The acute respiratory distress syndrome (ARDS) is a highly relevant entity in critical care with mortality rates of 40%. Despite extensive scientific efforts, outcome-relevant therapeutic measures are still insufficiently practised at the bedside. Thus, there is a clear need to adhere to early diagnosis and sufficient therapy in ARDS, assuring lower mortality and multiple organ failure.Methods and analysis In this quality improvement strategy (QIS), a decision support system as a mobile application (ASIC app), which uses available clinical real-time data, is implemented to support physicians in timely diagnosis and improvement of adherence to established guidelines in the treatment of ARDS. ASIC is conducted on 31 intensive care units (ICUs) at 8 German university hospitals. It is designed as a multicentre stepped-wedge cluster randomised QIS. ICUs are combined into 12 clusters which are randomised in 12 steps. After preparation (18 months) and a control phase of 8 months for all clusters, the first cluster enters a roll-in phase (3 months) that is followed by the actual QIS phase. The remaining clusters follow in month wise steps. The coprimary key performance indicators (KPIs) consist of the ARDS diagnostic rate and guideline adherence regarding lung-protective ventilation. Secondary KPIs include the prevalence of organ dysfunction within 28 days after diagnosis or ICU discharge, the treatment duration on ICU and the hospital mortality. Furthermore, the user acceptance and usability of new technologies in medicine are examined. To show improvements in healthcare of patients with ARDS, differences in primary and secondary KPIs between control phase and QIS will be tested.Ethics and dissemination Ethical approval was obtained from the independent Ethics Committee (EC) at the RWTH Aachen Faculty of Medicine (local EC reference number: EK 102/19) and the respective data protection officer in March 2019. The results of the ASIC QIS will be presented at conferences and published in peer-reviewed journals.Trial registration number DRKS00014330.
Published: 2021
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15. Mid-German Sepsis Cohort (MSC): a prospective observational study of sepsis survivorship

Author: André Scherag, Stephanie Platzer, Michael Bauer, Carolin Fleischmann-Struzek, Dominique Ouart, Konrad Reinhart, Miriam Kesselmeier, Christiane S. Hartog, Sven Bercker, Michael Bucher, Andreas Meier-Hellmann, Sirak Petros, Torsten Schreiber, Philipp Simon, Lorenz Weidhase, Sebastian Born, Anke Braune, Hicham Chkirni, Cornelia Eichhorn, Sandra Fiedler, Christin Gampe, Christian König, Heike Romeike, and Kristin Töpfer
Subjects: Medicine
Abstract: Purpose The Mid-German Sepsis Cohort (MSC) aims to investigate mid-term and long-term functional disabilities in sepsis survivors from intensive care unit (ICU) discharge until 1 year after. Secondary, post-acute mortality and morbidity, health-related quality of life and healthcare utilisation will be investigated.Participants The MSC comprises adult (aged ≥18 years) patients who were treated for (severe) sepsis or septic shock on ICU. The participants were recruited between 15 April 2016 and 30 November 2018 from five German centres. Three thousand two hundred and ten patients with sepsis were identified, of which 1968 survived their ICU stay and were eligible for enrolment in the follow-up cohort. Informed consent for follow-up assessment was provided by 907 patients (46.1% of eligible patients).Findings to date The recruitment of the participants for follow-up assessments and the baseline data collection is completed. Incidence of sepsis was 116.7 patients per 1000 ICU patients. In this cohort profile, we provide an overview of the demographics and the clinical characteristics of both the overall sepsis cohort and the ICU survivors who provided informed consent for follow-up assessment (907 out of 1968 ICU survivors (46.1%)).Future plans The follow-ups are conducted 3, 6 and 12 months after ICU discharge. Another yearly follow-up up to 5 years after ICU discharge is pursued. Several cooperation and satellite projects were initiated. This prospective cohort offers a unique resource for research on long-term sequelae of sepsis survivors.Trial registration number German Clinical Trials Registry (DRKS00010050).
Published: 2021
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16. Crop management system and carrot genotype affect endophyte composition and Alternaria dauci suppression.

Author: Sahar Abdelrazek, Philipp Simon, Micaela Colley, Tesfaye Mengiste, and Lori Hoagland
Subjects: Medicine, Science
Abstract: Managing pests in carrot production is challenging. Endophytic microbes have been demonstrated to improve the health and productivity of many crops, but factors affecting endophyte dynamics in carrot is still not well understood. The goal of this study was to determine how crop management system and carrot genotype interact to affect the composition and potential of endophytes to mitigate disease caused by Alternaria dauci, an important carrot pathogen. Twenty-eight unique isolates were collected from the taproots of nine diverse genotypes of carrot grown in a long-term trial comparing organic and conventional management. Antagonistic activity was quantified using an in vitro assay, and potential for individual isolates to mitigate disease was evaluated in greenhouse trials using two carrot cultivars. Results confirm that carrot taproots are colonized by an abundant and diverse assortment of bacteria and fungi representing at least distinct 13 genera. Soils in the organic system had greater total organic matter, microbial biomass and activity than the conventional system and endophyte composition in taproots grown in this system were more abundant and diverse, and had greater antagonistic activity. Carrot genotype also affected endophyte abundance as well as potential for individual isolates to affect seed germination, seedling growth and tolerance to A. dauci. The benefits of endophytes on carrot growth were greatest when plants were subject to A. dauci stress, highlighting the importance of environmental conditions in the functional role of endophytes. Results of this study provide evidence that endophytes can play an important role in improving carrot performance and mediating resistance to A. dauci, and it may someday be possible to select for these beneficial plant-microbial relationships in carrot breeding programs. Implementing soil-building practices commonly used in organic farming systems has potential to promote these beneficial relationships and improve the health and productivity of carrot crops.
Published: 2020
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17. Clinical Frailty Scale (CFS) reliably stratifies octogenarians in German ICUs: a multicentre prospective cohort study

Author: Johanna M. Muessig, Amir M. Nia, Maryna Masyuk, Alexander Lauten, Anne Lena Sacher, Thorsten Brenner, Marcus Franz, Frank Bloos, Henning Ebelt, Stefan J. Schaller, Kristina Fuest, Christian Rabe, Thorben Dieck, Stephan Steiner, Tobias Graf, Rolf A. Jánosi, Patrick Meybohm, Philipp Simon, Stefan Utzolino, Tim Rahmel, Eberhard Barth, Michael Schuster, Malte Kelm, and Christian Jung
Subjects: Frailty, Clinical frailty scale, VIP1, Intensive care outcome, Geriatrics, RC952-954.6
Abstract: Abstract Background In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs. Methods This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality. Results Patients had a median age of 84 [IQR 82–87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival. Conclusions The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany. Trial registration The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807) on May 1, 2017.
Published: 2018
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18. Similar Piperacillin/Tazobactam Target Attainment in Obese versus Nonobese Patients despite Differences in Interstitial Tissue Fluid Pharmacokinetics

Author: David Busse, Philipp Simon, David Petroff, Christoph Dorn, Lisa Schmitt, Davide Bindellini, Alexander Kratzer, Arne Dietrich, Markus Zeitlinger, Wilhelm Huisinga, Robin Michelet, Hermann Wrigge, and Charlotte Kloft
Subjects: piperacillin/tazobactam, target-site, obesity, Pharmacy and materia medica, RS1-441
Abstract: Precision dosing of piperacillin/tazobactam in obese patients is compromised by sparse information on target-site exposure. We aimed to evaluate the appropriateness of current and alternative piperacillin/tazobactam dosages in obese and nonobese patients. Based on a prospective, controlled clinical trial in 30 surgery patients (15 obese/15 nonobese; 0.5-h infusion of 4 g/0.5 g piperacillin/tazobactam), piperacillin pharmacokinetics were characterized in plasma and at target-site (interstitial fluid of subcutaneous adipose tissue) via population analysis. Thereafter, multiple 3–4-times daily piperacillin/tazobactam short-term/prolonged (recommended by EUCAST) and continuous infusions were evaluated by simulation. Adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target-attainment (PTA ≥ 90%) based on time unbound piperacillin concentrations exceed the minimum inhibitory concentration (MIC) during 24 h (%fT>MIC). Lower piperacillin target-site maximum concentrations in obese versus nonobese patients were explained by the impact of lean (approximately two thirds) and fat body mass (approximately one third) on volume of distribution. Simulated steady-state concentrations were 1.43-times, 95%CI = (1.27; 1.61), higher in plasma versus target-site, supporting targets of %fT>2×MIC instead of %fT>4×MIC during continuous infusion to avoid target-site concentrations constantly below MIC. In all obesity and renally impairment/hyperfiltration stages, at MIC = 16 mg/L, adequate PTA required prolonged (thrice-daily 4 g/0.5 g over 3.0 h at %fT>MIC = 50) or continuous infusions (24 g/3 g over 24 h following loading dose at %fT>MIC = 98) of piperacillin/tazobactam.
Published: 2021
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19. Fine Mapping, Transcriptome Analysis, and Marker Development for Y2, the Gene That Conditions β-Carotene Accumulation in Carrot (Daucus carota L.)

Author: Shelby Ellison, Douglas Senalik, Hamed Bostan, Massimo Iorizzo, and Philipp Simon
Subjects: carotenoids, Daucus carota L., genotyping-by-sequencing, RNA-sequencing, QTL, Genetics, QH426-470
Abstract: Domesticated carrots, Daucus carota subsp. sativus, are the richest source of β-carotene in the US diet, which, when consumed, is converted into vitamin A, an essential component of eye health and immunity. The Y2 locus plays a significant role in beta-carotene accumulation in carrot roots, but a candidate gene has not been identified. To advance our understanding of this locus, the genetic basis of β-carotene accumulation was explored by utilizing an advanced mapping population, transcriptome analysis, and nucleotide diversity in diverse carrot accessions with varying levels of β-carotene. A single large effect Quantitative Trait Locus (QTL) on the distal arm of chromosome 7 overlapped with the previously identified β-carotene accumulation QTL, Y2. Fine mapping efforts reduced the genomic region of interest to 650 kb including 72 genes. Transcriptome analysis within this fine mapped region identified four genes differentially expressed at two developmental time points, and 13 genes differentially expressed at one time point. These differentially expressed genes included transcription factors and genes involved in light signaling and carotenoid flux, including a member of the Di19 gene family involved in Arabidopsis photomorphogenesis, and a homolog of the bHLH36 transcription factor involved in maize carotenoid metabolism. Analysis of nucleotide diversity in 25 resequenced carrot accessions revealed a drastic decrease in diversity of this fine-mapped region in orange cultivated accessions as compared to white and yellow cultivated and to white wild samples. The results presented in this study provide a foundation to identify and characterize the gene underlying β-carotene accumulation in carrot.
Published: 2017
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20. Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial

Author: Philipp Simon, David Petroff, David Busse, Jana Heyne, Felix Girrbach, Arne Dietrich, Alexander Kratzer, Markus Zeitlinger, Charlotte Kloft, Frieder Kees, Hermann Wrigge, and Christoph Dorn
Subjects: antibiotic dosing, concentrations, meropenem, microdialysis, obesity, pharmacokinetics, Therapeutics. Pharmacology, RM1-950
Abstract: Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) ≥ 35 kg/m2) and age-/sex-matched nonobese (18.5 kg/m2 ≥ BMI ≤ 30 kg/m2) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid chromatography-ultraviolet (HPLC-UV) in the plasma and microdialysate from the interstitial fluid (ISF) of subcutaneous tissue up to eight h after dosing. An analysis was performed in the plasma and ISF by noncompartmental methods. Results: The maximum plasma concentrations in 15 obese (BMI 49 ± 11 kg/m2) and 15 nonobese (BMI 24 ± 2 kg/m2) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: −18.3 to −3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6–9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, −1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05–0.37) and fairly similar area under the curve (AUC)8h (78.7 vs. 89.2 mg*h/L, −21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, −16.8 to −0.8) but not the AUC8h (28.5 vs. 42.0 mg*h/L, −33.9 to 5.4). Time above the MIC (T > MIC) in the plasma and ISF did not differ significantly for MICs of 0.25–8 mg/L. Conclusions: In morbidly obese patients, meropenem has lower maximum concentrations and higher volumes of distribution. However, due to the slightly longer half-life, obesity has no influence on the T > MIC, so dose adjustments for obesity seem unnecessary.
Published: 2020
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21. Feasibility and Safety of Bariatric Surgery in High-Risk Patients: A Single-Center Experience

Author: Yusef Moulla, Orestis Lyros, Matthias Blüher, Philipp Simon, and Arne Dietrich
Subjects: Internal medicine, RC31-1245
Abstract: Introduction. Despite the feasibility and safety of bariatric procedures nowadays, high-risk patients with vast obesity and severe comorbidities demonstrate relatively high perioperative morbidity and mortality rates and, therefore, form a distinguished challenge for the bariatric surgeons. Methods. We retrospectively analyzed high-risk patients, who underwent bariatric surgery in University Hospital Leipzig between May 2012 and December 2016. High-risk patients were defined when (Bergeat et al., 2016) at least one of the following risk factors was met: age ≥ 70 years, body mass index (BMI) > 70 kg/m2, liver cirrhosis, end-organ failure, or immunosuppression by status after organ transplantation along with (Birkmeyer et al., 2010) at least two comorbidities associated with obesity. Our analysis included early postoperative complications. Results. A total of 25 high-risk obese patients were identified. All patients had a standardized postoperative management with a mean length of hospital stay of 4 ± 1.4 days. One patient required an operative revision due to a stapler line leak after sleeve gastrectomy. No other major postoperative complications occurred. Conclusion. Bariatric surgery for severe high-risk patients can be performed safely in high-volume centers following standardized procedures.
Published: 2018
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22. Characterising the mechanisms of uromodulin secretion and trafficking with salt loading from the thick ascending limb in hypertension

Author: Boder, Philipp Simon and Boder, Philipp Simon
Published: 2024

23. DYRK1B regulates Hedgehog-induced microtubule acetylation

Author: Singh, Rajeev, Holz, Philipp Simon, Roth, Katrin, Hupfer, Anna, Meissner, Wolfgang, Müller, Rolf, Buchholz, Malte, Gress, Thomas M., Elsässer, Hans-Peter, Jacob, Ralf, and Lauth, Matthias
Published: 2019
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24. THE INFORMED CONSENT TO RECORD LINKAGE IN PANEL STUDIES: OPTIMAL STARTING WAVE, CONSENT REFUSALS, AND SUBSEQUENT PANEL ATTRITION

Author: EISNECKER, PHILIPP SIMON and KROH, MARTIN
Published: 2017

25. Macroscopic manifestation of domain-wall magnetism and magnetoelectric effect in a Néel-type skyrmion host

Author: Geirhos, Korbinian, Gross, Boris, Szigeti, Bertalan G., Mehlin, Andrea, Philipp, Simon, White, Jonathan S., Cubitt, Robert, Widmann, Sebastian, Ghara, Somnath, Lunkenheimer, Peter, Tsurkan, Vladimir, Neuber, Erik, Ivaneyko, Dmytro, Milde, Peter, Eng, Lukas M., Leonov, Andrey O., Bordács, Sándor, Poggio, Martino, and Kézsmárki, István
Published: 2020
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26. How do my earnings compare? Pay referents and just earnings.

Author: Eisnecker, Philipp Simon and Adriaans, Jule
Subjects: WAGES, EMPLOYMENT references, OCCUPATIONAL sociology, EARNED income, EMPLOYEE value proposition
Abstract: Comparisons are crucial in shaping evaluations of one's own position. Following this notion, we investigated the role of historical, financial, partner, occupational, and regional pay referents in predicting the just gross hourly earnings in a representative sample of German workers. Looking at this broad range of pay referents, we find that higher reference earnings were generally associated with higher just earnings. In particular, controlling for actual gross hourly earnings, higher occupational, regional, and partners' hourly earnings were associated with higher just gross hourly earnings. One's own pay history, in form of average hourly earnings over the past 10 years, did not shape just earnings. Financial needs on the household level, however, mapped on to higher just earnings and this association was particularly pronounced among men. Overall, occupational and financial referents showed the strongest association with just earnings followed by partner earnings. These findings underscore that, while referents closely related to one's job (e.g. occupational referents) are important, referents that extend beyond the sphere of work (e.g. regional, financial, and partner referents) are also relevant in shaping ideas of the just reward. [ABSTRACT FROM AUTHOR]
Published: 2024
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27. Figure S3 from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway

Author: Dhanyamraju, Pavan Kumar, primary, Holz, Philipp Simon, primary, Finkernagel, Florian, primary, Fendrich, Volker, primary, and Lauth, Matthias, primary
Published: 2023
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28. Data from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway

Author: Dhanyamraju, Pavan Kumar, primary, Holz, Philipp Simon, primary, Finkernagel, Florian, primary, Fendrich, Volker, primary, and Lauth, Matthias, primary
Published: 2023
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29. Supplemental Material from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway

Author: Dhanyamraju, Pavan Kumar, primary, Holz, Philipp Simon, primary, Finkernagel, Florian, primary, Fendrich, Volker, primary, and Lauth, Matthias, primary
Published: 2023
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30. Supplemental figure legends from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway

Author: Dhanyamraju, Pavan Kumar, primary, Holz, Philipp Simon, primary, Finkernagel, Florian, primary, Fendrich, Volker, primary, and Lauth, Matthias, primary
Published: 2023
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31. Supplemental Material from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway

Author: Matthias Lauth, Volker Fendrich, Florian Finkernagel, Philipp Simon Holz, and Pavan Kumar Dhanyamraju
Abstract: Material lists
Published: 2023
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32. Supplemental figure legends from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway

Author: Matthias Lauth, Volker Fendrich, Florian Finkernagel, Philipp Simon Holz, and Pavan Kumar Dhanyamraju
Abstract: Legends to figures S1-S6
Published: 2023
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33. Figure S2 from Histone Deacetylase 6 Represents a Novel Drug Target in the Oncogenic Hedgehog Signaling Pathway

Author: Matthias Lauth, Volker Fendrich, Florian Finkernagel, Philipp Simon Holz, and Pavan Kumar Dhanyamraju
Abstract: This file contains various control experiments such as siRNA validation, impact on cell toxicity or the effects of HDAC6 knock-down on the expression of other HDAC family members.
Published: 2023
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34. How do my earnings compare? Pay referents and just earnings

Author: Eisnecker, Philipp Simon, primary and Adriaans, Jule, additional
Published: 2023
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35. Quantum magnetometry with OPM: Novel applications in non-destructive testing?

Author: Blug, Andreas, primary, Thiemann, Kerstin, additional, Philipp, Simon, additional, Straub, Thomas, additional, and Bertz, Alexander, additional
Published: 2023
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36. Proenkephalin A and bioactive adrenomedullin are useful for risk prognostication in cardiac surgery

Author: Aileen Hill, Deborah Bergmann, Janin Schulte, Rashad Zayat, Gernot Marx, Tim-Philipp Simon, Jana Mossanen, Anne Brücken, and Christian Stoppe
Subjects: Cardiology and Cardiovascular Medicine
Abstract: IntroductionVarious clinical scores have been developed to predict organ dysfunction and mortality in patients undergoing cardiac surgery, but outcome prediction may be inaccurate for some patient groups. Proenkephalin A (penKid) and bioactive adrenomedullin (bio-ADM) have emerged as promising biomarkers correlating with shock and organ dysfunction. This imposes the question of whether they can be used as prognostic biomarkers for risk stratification in the perioperative setting of cardiac surgery.MethodsPatients undergoing cardiac surgery were prospectively enrolled in this observational study. PenKid and bio-ADM plasma levels, as well as markers evaluating inflammation and organ dysfunction, were measured at five perioperative time points from before the induction of anesthesia to up to 48 h postoperatively. Clinical data regarding organ dysfunction and patient outcomes were recorded during the intensive care unit (ICU)-stay with a special focus on acute kidney injury (AKI).ResultsIn 136 patients undergoing cardiac surgery, the bio-ADM levels increased and the penKid levels decreased significantly over time. PenKid was associated with chronic kidney disease (CKD), the incidence of AKI, and renal replacement therapy (RRT). Bio-ADM was associated with lactate and the need for vasopressors. PenKid was useful to predict an ICU-length of stay (LOS)>1 day and added prognostic value to the European System for Cardiac Operative Risk Evaluation Score (EuroSCORE) II when measured after the end of cardiopulmonary bypass and 24 h after cardiac surgery. For bio-ADM, the same was true when measured 24 h after surgery. PenKid also added prognostic value to the EuroSCORE II for the combined outcome “ICU length of stay >1 day and in-hospital mortality.”ConclusionThe combination of preoperative EuroSCORE II and intraoperative measurement of penKid may be more useful to predict a prolonged ICU LOS and increased mortality than EuroSCORE II alone. Bio-ADM correlates with markers of shock. More research is encouraged for early risk stratification and validation of penKid and bio-ADM as a tool involved in clinical decisions, which may enable the early initiation of organ protective strategies.
Published: 2023
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37. Kein idealer Endzustand : Eine holistische Betrachtung der architektonischen Handlungsmöglichkeiten für ökosozial nachhaltigen Mehr-Als-Wohnbau

Author: Stützner, Philipp Simon
Subjects: Nachhaltigkeit, Wohnbau, sustainability, housing
Abstract: Betrachtet man die Gegenwart der Architektur im Bezug auf ihren Umgang mit der Klimakrise, so scheint auch die Architektur in einer Krise zu stecken: Gebäude, die zur Lösung der Klimakrise beitragen sollen, verstecken sich hinter gut gemeinten Vorsätzen, wohlwollenden Versprechungen und oberflächlichen Lösungsansätzen. Während sie damit die Situation weiter verschlechtern, werden sie dennoch zu immer höheren Preisen verkauft und täuschen Veränderung und Fortschritt vor, ohne tatsächlich dazu beizutragen.Um die schlimmsten Auswirkungen der Klimakrise zu verhindern, müssen sich die Art und Weise auf die wir Architektur schaffen dringend verändern. Angesichts dieses Umstandes und der ihm inhärenten Fragestellungen, werden in dieser Arbeit die Gegenwart der Architektur, sowie die ihr zugrundeliegenden historischen, gesellschaftlichen und ökonomischen Hintergründe analysiert, um anhand der Erkenntnisse potenzielle Lösungen für die Zukunft zu finden. Die enge Beziehung zwischen sozialen Themen und Problemen, zu Fragen des Klimas in der Architektur und folglich die Komplexität gesellschaftlicher, politischer und ökonomischer Systeme und ihrer Interdependenzen stehen dabei besonders im Fokus. Auf Basis einer Literaturanalyse werden drei Handlungsfelder – Boden, Raum und Ressourcen – erarbeitet und Zusammenhänge, Missstände und Potentiale identifiziert, um so relevante Handlungsmöglichkeiten hervorzubringen. Diese Analyse stellt die Basis eines Manifests dar, welches die gewonnenen Erkenntnisse mit Forderungen vereint um im zweiten Teil der Arbeit als Grundlage eines Entwurfskonzepts experimentell prototypisch auf seine Anwendbarkeit geprüft zu werden., Considering present architecture in terms of how it is dealing with the climate crisis, architecture too seems to be stuck in a crisis: buildings that are supposed to contribute to solving the climate crisis, are hiding behind well-intentioned resolutions, benevolent promises and superficial solutions. While making things worse, they are sold at ever rising prices, simulating change and progress without actually contributing to it.To prevent the worst effects of the climate crisis, the way we create architecture urgently needs to change. In view of this very circumstance and the questions inherent in it, this thesis analyzes the present of architecture and its underlying historical, social and economic background in order to find potential solutions for the future based on the findings. The close relationship between social questions, questions of climate in architecture and consequently the complexity of social, political and economic systems and their interdependencies are of particular interest to this thesis.On the basis of a literature analysis, three fields of action – ground, space and resources – as well as their connections, deficits and potentials are being identified in order to produce relevant options for action. This analysis lays the groundwork of a manifesto that combines the knowledge gained. In the second part of the work the manifesto is applied to an experimental, prototypical design.
Published: 2023
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38. How do my earnings compare? Pay referents and just earnings

Author: Philipp Simon Eisnecker and Jule Adriaans
Subjects: Sociology and Political Science
Abstract: Comparisons are crucial in shaping evaluations of one’s own position. Following this notion, we investigated the role of historical, financial, partner, occupational, and regional pay referents in predicting the just gross hourly earnings in a representative sample of German workers. Looking at this broad range of pay referents, we find that higher reference earnings were generally associated with higher just earnings. In particular, controlling for actual gross hourly earnings, higher occupational, regional, and partners’ hourly earnings were associated with higher just gross hourly earnings. One’s own pay history, in form of average hourly earnings over the past 10 years, did not shape just earnings. Financial needs on the household level, however, mapped on to higher just earnings and this association was particularly pronounced among men. Overall, occupational and financial referents showed the strongest association with just earnings followed by partner earnings. These findings underscore that, while referents closely related to one’s job (e.g., occupational referents) are important, referents that extend beyond the sphere of work (e.g., regional, financial, and partner referents) are also relevant in shaping ideas of the just reward.
Published: 2023
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39. G-Quadruplex Resolving by Specific Helicases

Author: Philipp Schult, Philipp Simon, and Katrin Paeschke
Published: 2023
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40. Location and pressure dependent transmission of human and porcine sclera: an anterior to posterior examination

Author: Koelbl, Philipp Simon, Klante, Pia, Koch, Frank, Lingenfelder, Christian, Werner, Jens Ulrich, Enders, Christian, and Hessling, Martin
Published: 2017
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41. Comparative Plasma and Interstitial Tissue Fluid Pharmacokinetics of Meropenem Demonstrate the Need for Increasing Dose and Infusion Duration in Obese and Non-obese Patients

Author: David Busse, Philipp Simon, Lisa Schmitt, David Petroff, Christoph Dorn, Arne Dietrich, Markus Zeitlinger, Wilhelm Huisinga, Robin Michelet, Hermann Wrigge, and Charlotte Kloft
Subjects: characterisation, Pharmacology, meropenem population pharmacokinetics, Meropenem, Microbial Sensitivity Tests, ddc:615, Anti-Bacterial Agents, 615 Pharmazie, Humans, adequate dosing regimens, Pharmacology (medical), ddc:610, Obesity, Prospective Studies, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik, Monte Carlo Method
Abstract: Background and objectives: A quantitative evaluation of the PK of meropenem, a broad-spectrum ��-lactam antibiotic, in plasma and interstitial space fluid (ISF) of subcutaneous adipose tissue of obese patients is lacking as of date. The objective of this study was the characterisation of meropenem population pharmacokinetics in plasma and ISF in obese and non-obese patients for identification of adequate dosing regimens via Monte-Carlo simulations. Methods: We obtained plasma and microdialysate concentrations after administration of meropenem 1000 mg to 15 obese and 15 non-obese surgery patients from a prospective clinical trial. After characterizing plasma- and microdialysis-derived ISF pharmacokinetics via population pharmacokinetic analysis, we simulated thrice-daily (TID) meropenem short-term (0.5 h), prolonged (3.0 h), and continuous infusions. Adequacy of therapy was assessed by the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) analysis based on time unbound concentrations exceeded minimum inhibitory concentrations (MIC) on treatment day 1 (%fT > MIC) and the sum of PTA weighted by relative frequency of MIC values for infections by pathogens commonly treated with meropenem. To avoid interstitial tissue fluid concentrations below MIC for the entire dosing interval during continuous infusions, a more conservative PK/PD index was selected (%fT > 4 �� MIC). Results: Adjusted body weight (ABW) and calculated creatinine clearance (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.5-81.5 kg/m2) explained a considerable proportion of the between-patient pharmacokinetic variability (15.1-31.0% relative reduction). The ISF:plasma ratio of %fT > MIC was relatively similar for MIC �� 2 mg/L but decreased for MIC = 8 mg/L over ABW = 60-120 kg (0.50-0.20). Steady-state concentrations were 2.68 times (95% confidence interval [CI] = 2.11-3.37) higher in plasma than in ISF, supporting PK/PD targets related to four times the MIC during continuous infusions to avoid suspected ISF concentrations constantly below the MIC. A 3000 mg/24 h continuous infusion was sufficient at MIC = 2 mg/L for patients with CLCRCG_ABW �� 100 mL/min and ABW < 90 kg, whereas 2000 mg TID prolonged infusions were adequate for those with CLCRCG_ABW �� 100 mL/min and ABW > 90 kg. For MIC = 2 mg/L and %fT> MIC = 95, PTA was adequate in patients over the entire investigated range of body mass and renal function using a 6000 mg continuous infusion. A prolonged infusion of meropenem 2000 mg TID was sufficient for MIC �� 8 mg/L and all investigated ABW and CLCRCG_ABW when employing the PK/PD target %fT > MIC = 40. Short-term infusions of 1000 mg TID were sufficient for CLCRCG_ABW �� 130 mL/min and distributions of MIC values for Escherichia coli, Citrobacter freundii, and Klebsiella pneumoniae but not for Pseudomonas aeruginosa. Conclusions: This analysis indicated a need for higher doses (�� 2000 mg) and prolonged infusions (�� 3 h) for obese and non-obese patients at MIC �� 2 mg/L. Higher PTA was achieved with prolonged infusions in obese patients and with continuous infusions in non-obese patients.
Published: 2021
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42. Binding and Modulation of G-quadruplex DNA and RNA Structures by Proteins

Author: Philipp Simon, Philipp Schult, and Katrin Paeschke
Published: 2022
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43. The role of generalized trust in COVID-19 vaccine acceptance

Author: Eisnecker, Philipp Simon, primary, Kroh, Martin, additional, and Kühne, Simon, additional
Published: 2022
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44. Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study

Author: Amado-Rodríguez, Laura, Rodríguez-Garcia, Raquel, Bellani, Giacomo, Pham, Tài, Fan, Eddy, Madotto, Fabiana, Laffey, John G, Albaiceta, Guillermo M, Antonio Pesenti, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, DanielF McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, Frank Van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Sanatorio Las Lomas, San Isidro, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, JonasI Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, MarlusM Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid BinHJAbul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, ShouH Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, ChristianM Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, BorisG Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, FrancescoL Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, DanieleM Combaux, Fabien Grelon, Charlene Le Moal, EliseP Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, RachanaV Rhayakar, Nagarajan Ramakrishnan, VallishK Bhardwaj, HeeraL Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, EimhinS Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, ColinS Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, RobertoR Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, EttoreR Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, YvesD Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, AsiscloJ Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M Van Wezel, SergeJ Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, DanielleJ Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, BritÅ Sjøbø, AnneB Guttormsen, Hector H LeonYoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, AnaM Araujo, NunoT Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, IsabelM Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, AhmedS AlJabbary, Edgardo Tabhan, YaseenM Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, JuanC Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, GuillermoM Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, AntonioL RuizAguilar, LuisM Claraco-Vega, Juan Alfonso Soler, Maria Del CarmenLorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, JuanB López-Messa, ManuelP Perez, CesarP Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, M Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, AntonioG Jimenez, FranciscoP Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, CorcolesG Virgilio, NoeliaN Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, KarinE Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, SilviaL Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, HervéO Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, OnatO Akyol, SuleymanS Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, ChristopherJ Scott, HelenE Ellis, Stuart Mckechnie, PaulaJ Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, MichaelN Dean, JuliusH Cranshaw, EmmaL Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, PieterD Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, SimonK Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, KatieH McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, DonaldA Irvine, Charing Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, SamanthaJ Hagan, JadeM Cole, Caroline C MacFie, AnnaT Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M BannerGoodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz Mesar, DaleJ Yeatts, Jessica Warren, MichaelJ Lanspa, Russel R Miller, ColinK Grissom, SamuelM Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, RobertL Owens, Ashley Schomer, Amado-Rodríguez, Laura, Rodríguez-Garcia, Raquel, Bellani, Giacomo, Pham, Tài, Fan, Eddy, Madotto, Fabiana, Laffey, John G, Albaiceta, Guillermo M, Antonio Pesenti, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, DanielF McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, Frank Van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, DanielF McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Sanatorio Las Lomas, San Isidro, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, JonasI Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, MarlusM Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid BinHJAbul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, 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Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Oleg, Oss, Peteri, Haddad, Youssef, Liew, Kong Y., Ñamendys-Silva, Silvio A., Jarquin-Badiola, Yvesd, Sanchez-Hurtado, Luis A., Gomez-Flores, Saira S., Marin, Maria C., Lemus, Jordana S., Fierro, Jonathan M., Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flore, Dector, Dulce, Rojas, Alejandro, Gonzalez, Daniel R., Estrella, Claudia R., Sanchez-Medina, Jorge R., Ramirez-Gutierrez, Alvaro, George, Fernando G., Aguirre, Janet S., Buensuseso, Juan A., Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M., Schouten, Jeroen A., Rinia, Myra, Raaijmakers, Monique, Van Wezel, Hellen M., Heines, Sergej, Strauch, Ulrich, Buise, Marc P., Simonis, Fabienne D., Schultz, Marcus J., Goodson, Jennifer C., Browne, Troy S., Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A., Bailey, Mathew B., Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Daniellej, Andersen, Finn H., Dolva, Merete S., Laake, Jon H., Barratt-Due, Andrea, Noremark, Kim Andre L., Søreide, Eldar, Sjøbø, Britå, Guttormsen, Anneb, Leonyoshido, Hector H., Aguilar, Ronald Zumaran, Oscanoa, Fredy A. Monte, Alisasis, Alain U., Robles, Joanne B., Pasanting-Lim, Rossini Abbie B., Tan, Beatriz C., Andruszkiewicz, Pawel, Jakubowska, Karina, Coxo, Cristina M., Alvarez, António M., Oliveira, Bruno S., Montanha, Gustavo M., Barros, Nelson C., Pereira, Carlos S., Messias, António M., Monteiro, Jorge M., Araujo, Anam, Catorze, Nunot, Marum, Susan M., Bouw, Maria J., Gomes, Rui M., Brito, Vania A., Castro, Silvia, Estilita, Joana M., Barros, Filipa M., Serra, Isabelm, Martinho, Aurelia M., Tomescu, Dana R., Marcu, Alexandra, Bedreag, Ovidiu H., Papurica, Mariu, Corneci, Dan E., Negoita, Silvius Ioan, Grigoriev, Evgeny, Gritsan, Alexey I., Gazenkampf, Andrey A., Almekhlafi, Ghaleb, Albarrak, Mohamad M., Mustafa, Ghanem M., Maghrabi, Khalid A., Salahuddin, Nawal, Aisa, Tharwat M., Aljabbary, Ahmed, Tabhan, Edgardo, Arabi, Yaseenm, Arabi, Yaseen M., Trinidad, Olivia A., Al Dorzi, Hasan M., Bumbasirevic, Vesna, Jovanovic, Bojan, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juanc, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermom, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruizaguilar, Antoniol, Claraco-Vega, Luism, Soler, Juan Alfonso, del CarmenLorente, Maria, Hermosa, Cecilia, Gordo, Federico, Prietogonzález, Miryam, López-Messa, Juanb, Perez, Manuelp, Perez, Cesarp, Allue, Raquel Montoiro, Rochecampo, Ferran, Ibañez-Santacruz, Marco, Temprano, Susana, Pintado, Maria C., De Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesia, Jurado, M. Teresa, Arizmendi, Alfon, Piacentini, Enrique A., Franco, Nieve, Honrubia, Teresa, Cheng, Meisy Perez, Losada, Elena Perez, Blanco, Javier, Yuste, Luis J., Carbayo-Gorriz, Cecilia, Cazorla-Barranquero, Francisca G., Alonso, Javier G., Alda, Rosa S., Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Marcos, Diego Pastor, Montero, Laura Alvarez, Para, Luis Herrera, Sanchez, Roberto Jimenez, Navalpotro, Miguel Angel Blasco, Abad, Ricardo Diaz, González, Raquel Montiel, Toribio, Dácil Parrilla, Castro, Alejandro G., Artiga, Maria Jose D., Penuelas, Oscar, Roser, Tomas P., Olga, Moreno F., Curto, Elena Gallego, Sánchez, Rocío Manzano, Imma, Vallverdu P., Elisabet, Garcia M., Claverias, Laura, Magret, Monica, Pellicer, Ana M., Rodriguez, Lucia L., Sánchez-Ballesteros, Jesú, González-Salamanca, Ángela, Jimenez, Antoniog, Huerta, Franciscop, Diaz, Juan Carlos J. Sotillo, Lopez, Esther Bermejo, Moya, David D. Llinare, Alfonso, Alec A. Tallet, Luis, Palazon Sanchez Eugenio, Cesar, Palazon Sanchez, Rafael, Sánchez I., Virgilio, Corcolesg, Recio, Noelian, Adamsson, Richard O., Rylander, Christian C., Holzgraefe, Bernhard, Broman, Lars M, Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Han, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lar, Helleberg, Johan, Eriksson, Karine, Glietsch, Rita, Larsson, Nikla, Nygren, Ingela, Nunes, Silvial, Morin, Anna-Karin, Kander, Thoma, Adolfsson, Anne, Zender, Hervéo, Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Souissi, Asma Ben, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onato, Derman, Suleyman, Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, Mcauley, Danny, Hopkins, Phil, Mellis, Clare, Kakar, Vivek, Hadfield, Dan, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K., Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S., Fawkes, Danielle A., Watt, Philip, Twohey, Linda, Jha, Rajeev R., Thomas, Matthew, Morton, Alex, Kadaba, Varsha, Smith, Mark J., Hormis, Anil P., Kannan, Santhana G., Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolc, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopherj, Ellis, Helene, Mckechnie, Stuart, Hutton, Paulaj, Di Tomasso, Nora N., Vitale, Michela N., Griffin, Ruth O., Dean, Michaeln, Cranshaw, Juliush, Willett, Emmal, Ioannou, Nichola, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieterd, Williams, Alexandra J, Boyd, Owen, de Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simonk, Wenham, Tim, Szakmany, Tama, Toth-Tarsoly, Piroska, Mccalman, Katieh, Alexander, Peter, Stephenson, Lorraine, Collyer, Thoma, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M, Sim, Malcolm, Wrathall, David W, Irvine, Donalda, Zantua, Charing Kim S., Adams, John C., Burtenshaw, Andrew J., Sellors, Gareth P., Welters, Ingeborg D., Williams, Karen E., Hessell, Robert J., Oldroyd, Matthew G., Battle, Ceri E., Pillai, Suresh, Kajtor, Istvan, Sivashanmugavel, Mageswaran, Okane, Sinead C., Donnelly, Adrian, Frigyik, Aniko D., Careless, Jon P., May, Martin M, Stewart, Richard, Trinder, T. John, Hagan, Samanthaj, Cole, Jadem, Macfie, Caroline C., Dowling, Annat, Nin, Nicolá, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C., Santos, Cristina, França, Ana G, Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Bannergoodspeed, Valerie M., Beitler, Jeremy R., Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Shinn III, John O., Gomaa, Dina, Tainter, Christopher, Lee, Jarone, Mesar, Tomaz, Yeatts, Dalej, Warren, Jessica, Lanspa, Michaelj, Miller, Russel R., Grissom, Colink, Brown, Samuelm, Bauer, Philippe R., Gosselin, Ryan J., Kitch, Barrett T., Cohen, Jason E., Beegle, Scott H., Choudry, Shazia, Gueret, Renaud M., Tulaimat, Aiman, Stigler, William, Batra, Hitesh, Huff, Nidhi G., Lamb, Keith D., Oetting, Trevor W., Mohr, Nicholas M., Judy, Claine, Saito, Shigeki, Kheir, Fayez M., Kheir, Fayez, Schlichting, Adam B., Delsing, Angela, Crouch, Daniel R., Elmasri, Mary, Ismail, Dina, Dreyer, Kyle R., Blakeman, Thomas C., Baro, Rebecca M., Hou, Peter C., Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robertl, Schomer, Ashley, Amado-Rodríguez, L, Rodríguez-Garcia, R, Bellani, G, Pham, T, Fan, E, Madotto, F, Laffey, J, and Albaiceta, G
Subjects: Ventilator-induced lung injury, Cardiogenic pulmonary edema, Driving pressure, Mechanical ventilation, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Settore MED/41 - ANESTESIOLOGIA, Critical Care and Intensive Care Medicine
Abstract: Supported by Centro de Investigación Biomédica en Red (CIBER)‑Enfermedades respiratorias, Madrid, Spain (CB17/06/00021) and Fundación para el Fomento en Asturias de la Investigación Científica aplicada y la tecnología (FICYT, AYUD2021/52014). RRG is the recipient of a grant from Instituto de Salud Carlos III, Madrid, Spain (CM20/00083)., Amado-Rodríguez L., Rodríguez-Garcia R., Bellani G., Pham T., Fan E., Madotto F., Laffey J.G., Albaiceta G.M., Pesenti A., Brochard L., Esteban A., Gattinoni L., van Haren F., Larsson A., McAuley D.F., Ranieri M., Rubenfeld G., Taylor Thompson B., Wrigge H., Slutsky A.S., Rios F., Van Haren F., Sottiaux T., Depuydt P., Lora F.S., Azevedo L.C., Bugedo G., Qiu H., Gonzalez M., Silesky J., Cerny V., Nielsen J., Jibaja M., Wrigge H., Matamis D., Ranero J.L., Amin P., Hashemian S.M., Clarkson K., Kurahashi K., Villagomez A., Zeggwagh A.A., Heunks L.M., Laake J.H., Palo J.E., do Vale Fernandes A., Sandesc D., Arabi Y.M., Bumbasierevic V., Nin N., Lorente J.A., Larsson A., Piquilloud L., Abroug F., McAuley D.F., McNamee L., Hurtado J., Bajwa E., Démpaire G., Sula H., Nunci L., Cani A., Zazu A., Dellera C., Insaurralde C.S., Las Lomas S., Isidro S., Alejandro R.V., Daldin J., Vinzio M., Fernandez R.O., Cardonnet L.P., Bettini L.R., Bisso M.C., Osman E.M., Setten M.G., Lovazzano P., Alvarez J., Villar V., Pozo N.C., Grubissich N., Plotnikow G.A., Vasquez D.N., Ilutovich S., Tiribelli N., Chena A., Pellegrini C.A., Saenz M.G., Estenssoro E., Brizuela M., Gianinetto H., Gomez P.E., Cerrato V.I., Bezzi M.G., Borello S.A., Loiacono F.A., Fernandez A.M., Knowles S., Reynolds C., Inskip D.M., Miller J.J., Kong J., Whitehead C., Bihari S., Seven A., Krstevski A., Rodgers H.J., Millar R.T., McKenna T.E., Bailey I.M., Hanlon G.C., Aneman A., Lynch J.M., Azad R., Neal J., Woods P.W., Roberts B.L., Kol M.R., Wong H.S., Riss K.C., Staudinger T., Wittebole X., Berghe C., Bulpa P.A., Dive A.M., Verstraete R., Lebbinck H., Depuydt P., Vermassen J., Meersseman P., Ceunen H., Rosa J.I., Beraldo D.O., Piras C., Rampinelli A.M., Nassar Jr A.P., Mataloun S., Moock M., Thompson M.M., Gonçalves C.H., Antônio A.C.P., Ascoli A., Biondi R.S., Fontenele D.C., Nobrega D., Sales V.M., BinHJAbul Wahab A.Y., Ismail M., Shindhe S., Laffey J., Beloncle F., Davies K.G., Cirone R., Manoharan V., Ismail M., Goligher E.C., Jassal M., Nishikawa E., Javeed A., Curley G., Rittayamai N., Parotto M., Ferguson N.D., Mehta S., Knoll J., Pronovost A., Canestrini S., Bruhn A.R., Garcia P.H., Aliaga F.A., Farías P.A., Yumha J.S., Ortiz C.A., Salas J.E., Saez A.A., Vega L.D., Labarca E.F., Martinez F.T., Carreño N.G., Lora P., Liu H., Qiu H., Liu L., Tang R., Luo X., An Y., Zhao H., Gao Y., Zhai Z., Ye Z.L., Wang W., Li W., Li Q., Zheng R., Yu W., Shen J., Li X., Yu T., Lu W., Wu Y.Q., Huang X.B., He Z., Lu Y., Han H., Zhang F., Sun R., Wang H.X., Qin S.H., Zhu B.H., Zhao J., Liu J., Li B., Liu J.L., Zhou F.C., Li Q.J., Zhang X.Y., Li-Xin Z., Xin-Hua Q., Jiang L., Gao Y.N., Zhao X.Y., Li Y.Y., Li X.L., Wang C., Yao Q., Yu R., Chen K., Shao H., Qin B., Huang Q.Q., Zhu W.H., Hang A.Y., Hua M.X., Li Y., Xu Y., Di Y.D., Ling L.L., Qin T.H., Wang S.H., Qin J., Han Y., Zhou S., Vargas M.P., Jimenez J.I.S., Rojas 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Mochizuki K., Hashida T., Tanaka H., Nakamura T., Niimi D., Ueda T., Kashiwa Y., Uchiyama A., Sabelnikovs O., Oss P., Haddad Y., Liew K.Y., Ñamendys-Silva S.A., Jarquin-Badiola Y.D., Sanchez-Hurtado L.A., Gomez-Flores S.S., Marin M.C., Lemus J.S., Fierro J.M., Cervantes M.R., Mejia F.J.F., Dector D., Rojas A., Gonzalez D.R., Estrella C.R., Sanchez-Medina J.R., Ramirez-Gutierrez A., George F.G., Aguirre J.S., Buensuseso J.A., Poblano M., Dendane T., Zeggwagh A.A., Balkhi H., Elkhayari M., Samkaoui N., Ezzouine H., Benslama A., Amor M., Maazouzi W., Cimic N., Beck O., Bruns M.M., Schouten J.A., Rinia M., Raaijmakers M., Heunks L.M., Van Wezel H.M., Heines S.J., Strauch U., Buise M.P., Simonis F.D., Schultz M.J., Goodson J.C., Browne T.S., Navarra L., Hunt A., Hutchison R.A., Bailey M.B., Newby L., McArthur C., Kalkoff M., Mcleod A., Casement J., Hacking D.J., Andersen F.H., Dolva M.S., Laake J.H., Barratt-Due A., Noremark K.A.L., Søreide E., Sjøbø B.Å., Guttormsen A.B., LeonYoshido H.H., Aguilar R.Z., Oscanoa F.A.M., Alisasis A.U., Robles J.B., Pasanting-Lim R.A.B., Tan B.C., Andruszkiewicz P., Jakubowska K., Coxo C.M., Alvarez A.M., Oliveira B.S., Montanha G.M., Barros N.C., Pereira C.S., Messias A.M., Monteiro J.M., Araujo A.M., Catorze N.T., Marum S.M., Bouw M.J., Gomes R.M., Brito V.A., Castro S., Estilita J.M., Barros F.M., Serra I.M., Martinho A.M., Tomescu D.R., Marcu A., Bedreag O.H., Papurica M., Corneci D.E., Negoita S.I., Grigoriev E., Gritsan A.I., Gazenkampf A.A., Almekhlafi G., Albarrak M.M., Mustafa G.M., Maghrabi K.A., Salahuddin N., Aisa T.M., AlJabbary A.S., Tabhan E., Trinidad O.A., Al Dorzi H.M., Bumbasirevic V., Jovanovic B., Bolon S., Smith O., Mancebo J., Aguirre-Bermeo H., Lopez-Delgado J.C., Esteve F., Rialp G., Forteza C., De Haro C., Artigas A., Albaiceta G.M., De Cima-Iglesias S., Seoane-Quiroga L., Ceniceros-Barros A., RuizAguilar A.L., Claraco-Vega L.M., Soler J.A., del CarmenLorente M., Hermosa C., Gordo F., PrietoGonzález M., López-Messa J.B., Perez M.P., Perez C.P., Allue R.M., RocheCampo F., Ibañez-Santacruz M., Temprano S., Pintado M.C., De Pablo R., Gómez P.R.A., Ruiz S.R., Moles S.I., Jurado M.T., Arizmendi A., Piacentini E.A., Franco N., Honrubia T., Cheng M.P., Losada E.P., Blanco J., Yuste L.J., Carbayo-Gorriz C., Cazorla-Barranquero F.G., Alonso J.G., Alda R.S., Algaba Á., Navarro G., Cereijo E., Diaz-Rodriguez E., Marcos D.P., Montero L.A., Para L.H., Sanchez R.J., Navalpotro M.A.B., Abad R.D., González R.M., Toribio D.P., Castro A.G., Artiga M.J.D., Penuelas O., Roser T.P., Olga M.F., Curto E.G., Sánchez R.M., Imma V.P., Elisabet G.M., Claverias L., Magret M., Pellicer A.M., Rodriguez L.L., Sánchez-Ballesteros J., González-Salamanca Á., Jimenez A.G., Huerta F.P., Diaz J.C.J.S., Lopez E.B., Moya D.D.L., Alfonso A.A.T., Luis P.S.E., Cesar P.S., Rafael S.I., Virgilio C.G., Recio N.N., Adamsson R.O., Rylander C.C., Holzgraefe B., Broman L.M., Wessbergh J., Persson L., Schiöler F., Kedelv H., Tibblin A.O., Appelberg H., Hedlund L., Helleberg J., Eriksson K.E., Glietsch R., Larsson N., Nygren I., Nunes S.L., Morin A.-K., Kander T., Adolfsson A., Zender H.O., Leemann-Refondini C., Elatrous S., Bouchoucha S., Chouchene I., Ouanes I., Souissi A.B., Kamoun S., Demirkiran O., Aker M., Erbabacan E., Ceylan I., Girgin N.K., Ozcelik M., Ünal N., Meco B.C., Akyol O.O., Derman S.S., Kennedy B., Parhar K., Srinivasa L., McNamee L., McAuley D., Hopkins P., Mellis C., Kakar V., Hadfield D., Vercueil A., Bhowmick K., Humphreys S.K., Ferguson A., Mckee R., Raj A.S., Fawkes D.A., Watt P., Twohey L., Jha R.R., Thomas M., Morton A., Kadaba V., Smith M.J., Hormis A.P., Kannan S.G., Namih M., Reschreiter H., Camsooksai J., Kumar A., Rugonfalvi S., Nutt C., Oneill O., Seasman C., Dempsey G., Scott C.J., Ellis H.E., Mckechnie S., Hutton P.J., Di Tomasso N.N., Vitale M.N., Griffin R.O., Dean M.N., Cranshaw J.H., Willett E.L., Ioannou N., Gillis S., Csabi P., Macfadyen R., Dawson H., Preez P.D., Williams A.J., Boyd O., de Gordoa L.O.-R., Bramall J., Symmonds S., Chau S.K., Wenham T., Szakmany T., Toth-Tarsoly P., McCalman K.H., Alexander P., Stephenson L., Collyer T., Chapman R., Cooper R., Allan R.M., Sim M., Wrathall D.W., Irvine D.A., Zantua C.K.S., Adams J.C., Burtenshaw A.J., Sellors G.P., Welters I.D., Williams K.E., Hessell R.J., Oldroyd M.G., Battle C.E., Pillai S., Kajtor I., Sivashanmugavel M., Okane S.C., Donnelly A., Frigyik A.D., Careless J.P., May M.M., Stewart R., Trinder T.J., Hagan S.J., Cole J.M., MacFie C.C., Dowling A.T., Hurtado J., Nin N., Hurtado J., Nuñez E., Pittini G., Rodriguez R., Imperio M.C., Santos C., França A.G., Ebeid A., Deicas A., Serra C., Uppalapati A., Kamel G., BannerGoodspeed V.M., Beitler J.R., Mukkera S.R., Kulkarni S., Shinn III J.O., Gomaa D., Tainter C., Lee J., Mesar T., Yeatts D.J., Warren J., Lanspa M.J., Miller R.R., Grissom C.K., Brown S.M., Bauer P.R., Gosselin R.J., Kitch B.T., Cohen J.E., Beegle S.H., Choudry S., Gueret R.M., Tulaimat A., Stigler W., Batra H., Huff N.G., Lamb K.D., Oetting T.W., Mohr N.M., Judy C., Saito S., Kheir F.M., Kheir F., Schlichting A.B., Delsing A., Crouch D.R., Elmasri M., Crouch D.R., Ismail D., Dreyer K.R., Blakeman T.C., Baro R.M., Hou P.C., Seethala R., Aisiku I., Henderson G., Frendl G., Hou S.-K., Owens R.L., Schomer A.
Published: 2022

45. [Safe position check of gastric tubes: an often underestimated topic to prevent possible severe complications]

Author: Fridolin, Streibert, Claudia, Bernhardt, Philipp, Simon, Peter, Hilbert-Carius, and Hermann, Wrigge
Abstract: The insertion of a gastric tube in the operating room (OR) or in an intensive care unit (ICU) is a routine procedure. Although the tube is often inserted by nursing staff, the indications and selection of the procedure for position control remain the physician's responsibility. For immediate position control, the injection of air through the inserted tube with simultaneous auscultation of the epigastrium is probably the most simple and common clinical method. A typical "bubbling" is often regarded as a sufficiently reliable sign of correct gastric tube position. This procedure can be described as a routine standard both in the OR and the ICU; however, numerous examples from clinical practice and quality reviews show gastric tube mispositioning in esophageal, bronchial, pulmonary or even pleural positions in individual cases. Since auscultation findings are misinterpreted as tracheal, bronchial, or pleural secretions, mispositioning may remain undetected. In addition, adequate documentation of the procedure is lacking. In the worst case, hyperosmolar tube feeding occurs via the malpositioned tube into the lungs or pleural space causing subsequent severe pneumonia or pleuritis, which is often fatal for the patient outcome. In contrast to many other similar procedures in intensive care medicine, such as the installation of central venous catheters or endotracheal intubation, to our knowledge there is no uniform standard for forensic verification of the correct position after gastric tube positioning. The present work provides an overview of existing practices and the scientific background for confirmation of gastric tube positioning without ionizing radiation.Die Anlage einer Magensonde im OP oder auf einer Intensivstation (ITS) stellt eine alltäglich durchgeführte Prozedur dar. Obwohl die Sonde häufig durch Pflegekräfte eingebracht wird, verbleiben die Indikationsstellung und Auswahl des Verfahrens zur Lagekontrolle im ärztlichen Verantwortungsbereich. Zur unmittelbaren Lagekontrolle wird klinisch wohl am gebräuchlichsten die Injektion von Luft durch die gelegte Sonde bei gleichzeitiger Auskultation des Epigastriums durchgeführt. Ein typisches „Blubbern“ wird oft als hinreichend sicheres Zeichen für eine korrekte Lage der Sonde im Magen angesehen. Dieses Verfahren darf sowohl im OP als auch auf der ITS als praktizierter Standard bezeichnet werden. Zahlreiche Beispiele aus der klinischen und gutachterlichen Praxis zeigen allerdings immer wieder, dass es in Einzelfällen ösophageale, bronchiale, pulmonale oder sogar pleurale Fehllagen geben kann, bei denen der Auskultationsbefund durch tracheales, bronchiales oder pleurales Sekret irreführend fehlgedeutet wird. Gleichzeitig wird regelhaft nicht dokumentiert, wie und durch wen die Sondenlage kontrolliert wurde. Kommt es im schlimmsten Falle zu einer Applikation von hyperosmolarer Sondenkost über die fehlliegende Sonde, wird die nachfolgende schwere Pneumonie oder Pleuritis, abhängig von den Begleiterkrankungen des Patienten, oft nicht überlebt. Im Gegensatz zu vielen anderen vergleichbaren Verfahren der Intensivmedizin, wie beispielsweise der Anlage zentraler Venenkatheter oder der endotrachealen Intubation, besteht unseres Wissens kein einheitlicher Standard für die forensische Sicherung eines Nachweises der korrekten Lage nach Anlage von Magensonden. Die vorliegende Arbeit gibt eine Übersicht über bestehende Praktiken und den wissenschaftlichen Hintergrund zur nichtinvasiven Lagekontrolle von Magensonden ohne ionisierende Strahlung.
Published: 2022

46. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author: Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, 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Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A 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C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs
Subjects: Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract: BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Published: 2021
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47. Body mass index and leptin levels in serum and cerebrospinal fluid in relation to delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage

Author: Anke Hoellig, Walid Albanna, Michael Veldeman, Tim Philipp Simon, Hans Clusmann, and Miriam Weiss
Subjects: Leptin, medicine.medical_specialty, Subarachnoid hemorrhage, Perfusion scanning, 030204 cardiovascular system & hematology, Overweight, Gastroenterology, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, medicine, Humans, Delayed cerebral ischemia, Body mass index, business.industry, Cerebral infarction, Glasgow Outcome Scale, Cerebral Infarction, General Medicine, medicine.disease, Original Article, Surgery, Neurology (clinical), medicine.symptom, Fat metabolism, business, 030217 neurology & neurosurgery
Abstract: Neurosurgical review 44(6), 3547-3556 (2021). doi:10.1007/s10143-021-01541-1, Published by Springer, Berlin ; Heidelberg ; New York
Published: 2021
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48. Obesity and Positive End-expiratory Pressure: Reply

Author: Philipp Simon, Felix Girrbach, David Petroff, and Hermann Wrigge
Subjects: Positive-Pressure Respiration, medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, Internal medicine, medicine, Cardiology, Humans, Obesity, medicine.disease, business, Positive end-expiratory pressure
Published: 2021
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49. Development and first assessment of a RGBW-LED diaphanoscope

Author: Johannes Busshardt, Philipp Simon Koelbl, Christian Lingenfelder, Martin Hessling, and Nicole Sieber
Subjects: Diaphanoscopy, Optics, genetic structures, business.industry, Medicine, Transillumination, business
Abstract: Background: Diaphanoscopy is an old but still useful technique in ophthalmic diagnostics. Its application suffers somewhat from the fact that the light is strongly attenuated and red-shifted in color when the eye wall is transilluminated. Material and methods: A color adjustable diaphanoscope prototype is developed based on a powerful red-green-blue-white light-emitting diode (RGBW-LED). Its optical and thermal properties are measured and tested on the porcine eyes of a local butcher. In addition, based on the technical data, the assumed retinal hazard to human eyes is assessed according to the standard DIN EN ISO 15004-2: 2007-6. Results: The investigated porcine eyes were brightly illuminated with all LED colors. The calculated values for judging the thermal and photochemical hazard were below the limits given in DIN EN ISO 15004-2: 2007-6. Conclusion: Based on the standard mentioned above, there is no recognizable danger to the human retina when applied for a limited time, and at least in the porcine model, the presented RGBW-LED diaphanoscope allows an adjustable ophthalmological transillumination without the requirement of the more elaborated devices that are usually employed in operating rooms.
Published: 2021
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50. [41/f-ARDS and long-term dependence on a ventilator after ECMO treatment : Preparation course anesthesiological intensive care medicine: case 28]

Author: Philipp, Simon and Hermann, Wrigge
Subjects: Respiratory Distress Syndrome, Extracorporeal Membrane Oxygenation, Ventilators, Mechanical, Critical Care, Humans
Published: 2022

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