Author: "Melanie, Meersch" / Publication Year Range: Last 50 years - Searchworks@Jio Institute Digital Library Search Results

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103 results on '"Melanie, Meersch"'

1. Biomarkers in acute kidney injury

Author: Marlies Ostermann, Matthieu Legrand, Melanie Meersch, Nattachai Srisawat, Alexander Zarbock, and John A. Kellum
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Acute kidney injury (AKI) is a multifactorial syndrome with a high risk of short- and long-term complications as well as increased health care costs. The traditional biomarkers of AKI, serum creatinine and urine output, have important limitations. The discovery of new functional and damage/stress biomarkers has enabled a more precise delineation of the aetiology, pathophysiology, site, mechanisms, and severity of injury. This has allowed earlier diagnosis, better prognostication, and the identification of AKI sub-phenotypes. In this review, we summarize the roles and challenges of these new biomarkers in clinical practice and research.
Published: 2024
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2. Perioperative point-of-care-testing of plasmacholinesterases identifies older patients at risk for postoperative delirium: an observational prospective cohort study

Author: Matthias S. Gruendel, Wibke Brenneisen, Jakob Wollborn, Gerrit Haaker, Melanie Meersch, Simone Gurlit, and Ulrich Goebel
Subjects: Cholinesterases, Orthopaedics, Traumatology, Delirium, Geriatrics, RC952-954.6
Abstract: Abstract Background Postoperative delirium (POD) is a severe perioperative complication that may increase mortality and length-of-stay in older patients. Moreover, POD is a major economic burden to any healthcare system. An altered expression of Acetylcholine- and Butyrylcholinesterases (AChE, BuChE) due to an unbalanced neuroinflammatory response to trauma or an operative stimulus has been reported to play an essential role in the development of POD. We investigated if perioperative measurement of cholinesterases (ChEs) can help identifying patients at risk for the occurrence of POD in both, scheduled and emergency surgery patients. Methods This monocentric prospective observational cohort study was performed in a tertiary hospital (departments of orthopaedic surgery and traumatology). One hundred and fifty-one patients aged above 75 years were enrolled for scheduled (n = 76) or trauma-related surgery (n = 75). Exclusion criteria were diagnosed dementia and anticholinergic medication. Plasma samples taken pre- and postoperatively were analysed regarding AChE and BuChE activity. Furthermore, perioperative assessment using different cognitive tests was performed. The type of anaesthesia (general vs. spinal anaesthesia) was analysed. Primary outcome was the incidence of POD assessed by the approved Confusion Assessment Method (CAM) in combination with the expression of AChE and BuChE. Results Of 151 patients included, 38 (25.2%) suffered from POD; 11 (14%) in scheduled and 27 (36%) in emergency patients. AChE levels showed no difference throughout groups or time course. Trauma patients had lower BuChE levels prior to surgery than scheduled patients (p
Published: 2024
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3. Evaluation of Proenkephalin A 119–159 for liberation from renal replacement therapy: an external, multicenter pilot study in critically ill patients with acute kidney injury

Author: Thilo von Groote, Felix Albert, Melanie Meersch, Raphael Koch, Joachim Gerss, Birte Arlt, Mahan Sadjadi, Christian Porschen, Peter Pickkers, Alexander Zarbock, and the RICH investigators
Subjects: Acute kidney injury, Biomarker, Critical illness, Proenkephalin, Renal replacement therapy, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Introduction Recent evidence suggests an association of plasma Proenkephalin A 119–159 (penKid) with early and successful liberation from continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury. However, these exploratory results are derived from a monocentric trial and therefore require external validation in a multicenter cohort. Methods Data and plasma samples from the “Effect of Regional Citrate Anticoagulation versus Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury—A Randomized Clinical Trial” (RICH Trial) were used for this validation study. PenKid was measured in all plasma samples available at CRRT initiation and at day 3 of CRRT. Patients were categorized into low and high penKid groups with a cutoff at 100 pmol/l. Competing-risk time-to-event analyses were performed. Competing risk endpoints were successful and unsuccessful liberation from CRRT, the latter meaning death or initiation of a new RRT within one week of discontinuation of primary CRRT. Then penKid was compared to urinary output. Results Low pre-CRRT penKid levels at CRRT initiation were not associated with early and successful liberation from CRRT compared to patients with high pre-CRRT penKid levels [subdistribution hazard ratio (sHR) 1.01, 95% CI 0.73–1.40, p = 0.945]. However, the landmark analysis on day 3 of ongoing CRRT demonstrated an association between low penKid levels and successful liberation from CRRT (sHR 2.35, 95% CI 1.45–3.81, p 436 ml/d) was even stronger associated with successful liberation (sHR 2.91, 95% CI 1.80–4.73, p
Published: 2023
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4. Recombinant Alpha-1-Microglobulin (RMC-035) to Prevent Acute Kidney Injury in Cardiac Surgery Patients: Phase 1b Evaluation of Safety and Pharmacokinetics

Author: Raphael Weiss, Melanie Meersch, Carola Wempe, Thilo von Groote, Tobias Agervald, and Alexander Zarbock
Subjects: acute kidney injury, alpha-1-microglobulin, cardiac surgery, inflammation, perioperative medicine, prevention, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Introduction: Acute kidney injury (AKI) is a common complication in cardiac surgery patients and prevention is needed to improve clinical outcomes. Alpha-1-microglobulin (A1M) is a physiological antioxidant with strong tissue-protective and cell-protective properties that has demonstrated renoprotective effects. RMC-035, a recombinant variant of endogenous human A1M, is being developed for the prevention of AKI in cardiac surgery patients. Methods: In this phase 1b, randomized, double-blind, and parallel group clinical study, 12 cardiac surgery patients undergoing elective, open-chest, on-pump coronary artery bypass graft and/or valve surgery with additional predisposing AKI risk factors were enrolled to receive in total 5 intravenous doses of either RMC-035 or placebo. The primary objective was to evaluate the safety and tolerability of RMC-035. The secondary objective was to evaluate its pharmacokinetic properties. Results: RMC-035 was well tolerated. The nature and frequency of adverse events (AEs) were consistent with the expected background rates in the underlying patient population with no AEs reported as related to study drug. No clinically relevant changes were observed for vital signs or laboratory parameters except for renal biomarkers. Several established AKI urine biomarkers were reduced at 4 hours after first dose administration in the treatment group, indicating a reduced perioperative tubular cell injury following RMC-035 treatment. Conclusion: Multiple intravenous doses of RMC-035 were well tolerated in patients undergoing cardiac surgery. Observed RMC-035 plasma exposures were safe and in the range of expected pharmacological activity. Furthermore, urine biomarkers suggest reduced perioperative kidney cell injury, warranting further investigation of RMC-035 as a potential renoprotective treatment.
Published: 2023
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5. Inhaled prostacyclin therapy in the acute respiratory distress syndrome: a randomized controlled multicenter trial

Author: Helene A. Haeberle, Stefanie Calov, Peter Martus, Lina Maria Serna-Higuita, Michael Koeppen, Almuth Goll, Alice Bernard, Alexander Zarbock, Melanie Meersch, Raphael Weiss, Martin Mehrländer, Gernot Marx, Christian Putensen, Tamam Bakchoul, Harry Magunia, Bernhard Nieswandt, Valbona Mirakaj, and Peter Rosenberger
Subjects: ARDS, Prostacyclin, COVID-19, Inflammation, Therapy, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Acute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS. Methods We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events. Results Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO2/FiO2 ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups. Conclusions The primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS. Trial registration: The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.
Published: 2023
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6. Proenkephalin A 119–159 predicts early and successful liberation from renal replacement therapy in critically ill patients with acute kidney injury: a post hoc analysis of the ELAIN trial

Author: Thilo von Groote, Felix Albert, Melanie Meersch, Raphael Koch, Christian Porschen, Oliver Hartmann, Deborah Bergmann, Peter Pickkers, and Alexander Zarbock
Subjects: Acute kidney injury, AKI, Biomarker, ELAIN, Renal replacement therapy, Proenkephalin A, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Renal replacement therapy (RRT) remains the key rescue therapy for critically ill patients with severe acute kidney injury (AKI). However, there are currently no tools available to predict successful liberation from RRT. Biomarkers may allow for risk stratification and individualization of treatment strategies. Proenkephalin A 119–159 (penKid) has been suggested as a promising marker of kidney function in the context of AKI, but has not yet been evaluated for RRT liberation in critically ill patients with AKI. Methods This post hoc analysis included 210 patients from the randomized clinical ELAIN trial and penKid levels were measured in the blood of these patients. Competing risk time-to-event analyses were performed for pre-RRT penKid at initiation of RRT and in a landmark analysis at day 3 after initiation of RRT. Competing risk endpoints were successful liberation from RRT or death without prior liberation from RRT. Results Low pre-RRT penKid levels (penKid ≤ 89 pmol/l) at RRT initiation were associated with early and successful liberation from RRT compared to patients with high pre-RRT penKid levels (subdistribution hazard ratio (sHR) 1.83, 95%CI 1.26–2.67, p = 0.002, estimated 28d-cumulative incidence function (28d-CIF) of successful liberation from RRT 61% vs. 45%, p = 0.022). This association persisted in the landmark analysis on day 3 of RRT (sHR 1.78, 95%CI 1.17–2.71, p = 0.007, 28d-CIF of successful liberation from RRT 67% vs. 47%, p = 0.018). For both time points, no difference in the competing event of death was detected. Conclusions In critically ill patients with RRT-dependent AKI, plasma penKid appears to be a useful biomarker for the prediction of shorter duration and successful liberation from RRT and may allow an individualized approach to guide strategies of RRT liberation in critically ill patients with RRT-dependent AKI. Trial registration: The ELAIN trial was prospectively registered at the German Clinical Trial Registry (Identifier: DRKS00004367) on 28th of May 2013. Graphical Abstract
Published: 2022
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7. 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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8. Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells

Author: Katharina Thomas, Lisa Zondler, Nadine Ludwig, Marina Kardell, Corinna Lüneburg, Katharina Henke, Sina Mersmann, Andreas Margraf, Tilmann Spieker, Tobias Tekath, Ana Velic, Richard Holtmeier, Juliane Hermann, Vera Jankowski, Melanie Meersch, Dietmar Vestweber, Martin Westphal, Johannes Roth, Michael A. Schäfers, John A. Kellum, Clifford A. Lowell, Jan Rossaint, and Alexander Zarbock
Subjects: Immunology, Nephrology, Medicine
Abstract: Acute kidney injury (AKI) represents a common complication in critically ill patients that is associated with increased morbidity and mortality. In a murine AKI model induced by ischemia/reperfusion injury (IRI), we show that glutamine significantly decreases kidney damage and improves kidney function. We demonstrate that glutamine causes transcriptomic and proteomic reprogramming in murine renal tubular epithelial cells (TECs), resulting in decreased epithelial apoptosis, decreased neutrophil recruitment, and improved mitochondrial functionality and respiration provoked by an ameliorated oxidative phosphorylation. We identify the proteins glutamine gamma glutamyltransferase 2 (Tgm2) and apoptosis signal-regulating kinase (Ask1) as the major targets of glutamine in apoptotic signaling. Furthermore, the direct modulation of the Tgm2-HSP70 signalosome and reduced Ask1 activation resulted in decreased JNK activation, leading to diminished mitochondrial intrinsic apoptosis in TECs. Glutamine administration attenuated kidney damage in vivo during AKI and TEC viability in vitro under inflammatory or hypoxic conditions.
Published: 2022
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9. Remote ischemic preconditioning causes transient cell cycle arrest and renal protection by a NF-κB–dependent Sema5B pathway

Author: Jan Rossaint, Melanie Meersch, Katharina Thomas, Sina Mersmann, Martin Lehmann, Jennifer Skupski, Tobias Tekath, Peter Rosenberger, John A. Kellum, Hermann Pavenstädt, and Alexander Zarbock
Subjects: Immunology, Nephrology, Medicine
Abstract: Acute kidney injury increases morbidity and mortality, and previous studies have shown that remote ischemic preconditioning (RIPC) reduces the risk of acute kidney injury after cardiac surgery. RIPC increases urinary high mobility group box protein-1 (HMGB1) levels in patients, and this correlates with kidney protection. Here, we show that RIPC reduces renal ischemia-reperfusion injury and improves kidney function in mice. Mechanistically, RIPC increases HMGB1 levels in the plasma and urine, and HMGB1 binds to TLR4 on renal tubular epithelial cells, inducing transcriptomic modulation of renal tubular epithelial cells and providing renal protection, whereas TLR4 activation on nonrenal cells was shown to contribute to renal injury. This protection is mediated by activation of induction of AMPKα and NF-κB; this induction contributes to the upregulation of Sema5b, which triggers a transient, protective G1 cell cycle arrest. In cardiac surgery patients at high risk for postoperative acute kidney injury, increased HMGB1 and Sema5b levels after RIPC were associated with renal protection after surgery. The results may help to develop future clinical treatment options for acute kidney injury.
Published: 2022
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10. Prediction of Acute Kidney Injury in the Intensive Care Unit: Preliminary Findings in a European Open Access Database.

Author: Michael Fujarski, Christian Porschen, Lucas Plagwitz, Alexander Brenner, Narges Ghoreishi, Patrick Thoral, Harm-Jan de Grooth, Paul W. G. Elbers, Raphael Weiss, Melanie Meersch, Alexander Zarbock, Thilo Caspar von Groote, and Julian Varghese
Published: 2022
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11. EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): study protocol for a multicentre, observational trial

Author: Melanie Meersch, Mira Küllmar, Carola Wempe, Alexander Zarbock, Ke Peng, Sigismond Lasocki, Thomas Rimmele, Maria Martin, Olivier Desebbe, Michele Rossi, Matthias Heringlake, Christina Massoth, Raphael Weiss, Andreas Höhn, Gael Pradel, Ana Kowark, Ahmed mohamed Ibrahim, Orestis Ioannidis, Andrea Cortegiani, Maxime Leger, Emmanuel Rineau, Pierre-Yves Egreteau, Andrea Russo, Laura Kerschke, Savino Spadaro, Carole Ichai, Vincent Cottenceau, Sebastian Ziemann, Maria Gomez, Julien Nadaud, Olivier Pérus, Philippe Magazzeni, Philippe Montravers, Deniz Karakaya, Christophe Aveline, Alexander Bentley, Tulay Ozkan Seyhan, Jean-François Pittet, Sébastien Ponsonnard, Pierre Garcon, Ana Serrano, Gulay Ok, Pierre Vautier, Jean François Gautier, Sergi Sabaté, Yusuf Tunali, Valérie Cerro, Stephanie Suria, Khaschayar Saadat-Gilani, Hichem Makhloufi, Anis Cherak, Lamine Lakhel Ghanem, Zohier Gouaglia, Dina Nasrine Guadouri, Fayrouz Naouel Hama, Mustafa Kara, Omayma Saadi, Rachida Sakhraoui, Fadila Bourou, Abdelhadi Cherifi, Rahmoune Ghania Sadaoui, Amel Ouyahia, Ilhem Ouahab, Souad Bouaoud, Meriem Abdoun, Anisse Tidjane, Benali Tabeti, Nabil Boudjenan-Serradj, Carlos Jose Pérez Rivera, Paulo Cabrer, Julián Corso, Juan Pablo García, Sharon Idarraga, Christopher Montoya, Rafael Figueroa, Eduar Aldana, María Alejandra Torrado, Zheng-min Ma, Yu-fan Yang, Ya-juan Zhu, Peter Sklienka, Michal Frelich, Vojtech Jarkulis, Pavel Sevcik, Vojtech Vodicka, Mohamed Gamal Elbahnasawy, Shady Elsalhawy, Sara Motawea, Zeinab Othman, Mohamed Sahma, Ahmed Mahmoud Nafea, Nermin Ahmed, Doaa Ali Attia, Moataz Maher Emara, Mohamed Mamdouh Bonna, Mohamed Ahmed Gabr, Amany Ismail Tarbay, Ibrahim Abdelmonaem Abdehaleem, Esraa Elsayed Mohamed, Amr Mahmoud Eldeeb, Ahmed Mohamed Abbas, John Ashraf Magdy, Zyad Hassan Hamed, Hany Mostafa Esmaeil Osman, Mostafa Samy Abbas, Oliver Joannes-Boyau, Nicolas Barraud, Corentin Berthelot, Thibault Camus, Anissa Dahmi, Mylène Defaye, Sébastien Derville, Younes El-Boustani, Elsa Deloge, Hélène Jacob, Simon Monziols, Fred Priem, Jean-Jacques Robin, Vincent Legros, Therry Floch, Salvatore Muccio, Claire Geneve, Marie Lim Legouge, Stéphanie Tao Mauny, Willy Mfam, Léa Pascot, Mireille Chartier, Benjamin Duteurtre, Aidren Le Cousin, Nathalie Begel, Claire-Annissa Chekirine, Vincent Derlon, Elodie Grein, Marie-Annick Lehair, Laurent Magazzeni, Carsten Potter, Catherine Roth, Florence Voivret, Jamil Elmawieh, Annabelle Stoclin, Cédric Cirenei, Gregoire Andrieu, Sven Couloumy, Jeremy Falcone, Marion Fajardy, Arsène Gagneuil, Emeline Girardet, Agnès Mazereeuw, Mélanie Bertel, Simon Bocher, Vanessa Carn, Lenaïg Le Guen, Guillaume Le Loup, Montaine Lefevre, Amanita Diop, Vanessa Jean-Michel, Sylvie Devlieger, Juliette Duthoit, Mohamed El Kadiri, Viviane Cassisa, Charline Masson, Pierre Verrier, Axel Coquerel, Enora Atchade, Charles-Edouard Rochon, Céline Delerue, Vidal Quentin, Vanessa Latry, Nina Queixalos, Thierry Braun, Saad Bouzoubaa, Basile Christ, Audrey Geiger, Joachim Gomille, Vianney Kieffer, Simone Mangeant, Christelle Prochilo, Christian Schmitt, Stefan Skwirba, Hubert Grand, Frédérique Boury, Nicolas Mayeur, Marie Pasquie, Vincent Bruckert, Vincent Arnould, Mona Bonciu, Thibault Chapelle, Luc Facchino, Florence Fagot-Gandet, Andrea Iachim, Elena Mannu, Rémi Plattier, Romain Rozier, Michel Boudinaud, Marie-Hélène Hausermann, My Hue Nguyen, Andersen Ramorasata, Amélie Barreau, Anne-Hélène Boivin, Céline Ravry, Nicolas Mottard, Johanne Beuvelot, Florence Prunier Bossion, Christian Dörr, Thilo Caspar von Groote, Linda Grüßer, Pia Wittig, Timo Brandenburger, Thomas Dimski, Niklas Döhmen, Laura Huthmann, Daniela Kaierle, Claude Pelletier, Manon Schleß, Sebastian Cleophas, Stephanie Haunhorst, Marina Jansen, Alexandra Schmitt, Julia Soisch, Kilian Sturm, Peter Rosenberger, Alexander Bendig, Lena Flohr, Helene Häberle, Pascal Hofmann, Jonathan Kuhle, Nora Michaela Leser, Kathrin Pfister, Stefanie Prohaska, Franziska Sennholz, Lena Stetz, Kathrin Weber, Sebastian Stehr, Stephan Klaus, Marco Sadlo, Matthias Boschin, Christian Sengelhoff, Ulrich Michael Göbel, Jan Gerrit Haaker, Carina-Kristin Göttker, Matthias Gründel, Romina Baumgärtel, Astrid Berggren, Madeleine Gülzow, Lennart Muras, Hauke Paarmann, Serge Thal, Dschamil El-Masri, Eleni Arnaoutoglou, Maria Ntalouka, Paula Stratigopoulou, Anastasia Analytis, Efthymios Mavrommatis, Petros Tzimas, Agathi Karakosta, Danai Pantazi, Antonia Dimakopoulou, Katerina Dimitropoulou, Humam Jalaawiy, Aeshah Anwar, Hashim Talib Hashim, Hogir Imad Rasheed Aldawoody, Giulia Catalisano, Gilia Ingoglia, Mariachiara Ippolito, Silvia De Rosa, Lucia Cattin, Andrea Bianchin, Marisa Barone, Gianluca Paternoster, Salvatore Lucio Cutuli, Liliana Sollazzi, Laura Cascarano, Massimo Antonelli, Paola Aceto, Bruno Romanò, Vincenzo Francesco Tripodi, Rosamaria Scappatura, Maria Cristina Vadalà, Diego Fiume, Maria Teresa Strano, Giulia Oddo, Clemente Santorsola, Bilal Abu Hussain, Adnan Raed Alnaser, Anas Hassouneh Ghassan, Khaled Hasanein, Mohammed Theab, Seokyung Shin, Seungho Jung, Kyuho Lee, Sung Mee Jung, Jongyoon Baek, Muhammed K. Elhadi, Issa Abuzeid, Mohammed Albaraesi, Sarah Aldressi, Wegdan Khalel, Eman Abdulwahed, Akram Abdulhamid Ashur Abujrad, Amer Almaghrabi, Muhand Mohammed Alteleeb, Entisar Ahmed Ali Alshareea, Marwa Isa Biala, Abdulqudus Deeknah, Dooua Ali Gheddim, Reem Ghmagh, Nawras Salih Ali AbuIkhrays, Marwa Sinan, Enas Soula, Sumayyah Ghayth Bahroun, Khawla Derwish, Aya Munir Mohamed, Eman Sayed Younes, Rayet Al Islam Benjouira, Mohamed Aliwa, Najwa Abdullah Altashani, Mohammed Omar Alteb, Ahmed Msherghi, Fatima Alagelli, Sufyan Albarouni, Ahmed Albishti, Sarah Aljamal, Mohamed Alsori, Taha Ekhuja, Suha Elzwai, Mohammed Ghula, Tahani Mustafa, Ahmed Tuwaib, Haifa Zriba, Hamza Mahmoud Agilla, Toky Andriamahefa Rafanomezantsoa, Anne Marie Camilleri Podesta, Denise Mifsud Bonnici, Tiziana Pirotta, Gilberto Adrián Gasca López, Maja Mojsova Mijovska, Tatjana Davitkovska, Aleksandra Gavrilovska, Sanja Lukikj, Marija Vesova, Dina Zafirova, Sarah Amro, Baraa N. F. Hajjaj, Muawia Alkhazendar, Yousuf Barakat, Sewar Abdulaziz Elejla, Ahmed Elhissi, Ahmed Khader, Ali Salem, Rita de Freitas Regufe, André Filipe de Oliveira Eloy, Lisbete Marisa Neto Cordeiro Perdigão, Evgeny Grigoriev, Artem Ivkin, Roman Kornelyuk, Michael Yaroustovsky, Marina Abramyan, Ekaterina Komardina, Nataliya Lesteva, Medina Aybazova, Elmira Kumykova, Svetlana Lesina, Gennady Rybakov, Alexey Shestov, Abdulnaser Ahmad Ahmad Barmou, Bushra Lotfi Altayeb Ahmed, Aisha Mohammad Eliyas, Yousra Emadeldin, Alexander Kaserer, Clara Castellucci, Julian Rössler, Samira Akbas, Andreja Möller Petrun, Irena Gregorcic, Vesna Sok, Roman Čičak, Elizabeth Bárcena, Antonio Guisado, Ismail Wi, Javier Ripollés Melchor, Ángel Becerra-Bolaños, Sergio Cabrera-Doreste, Ancor Domínguez-Arbelo, María Candelaria Delgado-Alonso, Virginia Muiño-Palomar, Aurelio Rodríguez-Pérez, Javier Mata Estévez, Maria Begona Covas Munoz, Juan Mulet Matas, Sara Perez Palao, Maria Dolores Mira Quirós, Alisia Cezara Teslev, Mercedes Garcia Alvarez, Marga Argilaga, María Campos, Albert Bainac, Astrid Batalla, Marta Giné, Gracia Herránz, Ignacio Hinojal, Margarita Logroño Ejea, Noelia de la Rosa Ruiz, María Gastaca Abasolo, Carla Rosario Houhton Acuna, Ibai Iriarte Zaranton, Ana Mendigurenmurua, María José Munoz Sanz, Erika Olea de la Fuente, María Pilar Pérez Vaquero, Ana Soto Iglesias, Ana Ugarte Mieres, Alaitz Urtiaga Urrestizala, Lourdes Ferreira, Félix Lobato, Marta Aguado Sevilla, Andres Erazo, Pere Miró, Diana Vernetta, Berta Castellano Paulis, Anabel Adell Perez, Marta Aseguinolaza Pagola, Elena delVal Peciña, Ainhoa Garmendia Odriozola, Amaia Lopetegi Aizpurua, Olatz Pavón Piquer, Pilar Plou Garcia, Paula Ortega Rezola, Antia Osorio Lopez, Isabel de la Calle Gil, Rosalía Navarro Casado, Peter Adamove, Roser Bayona Domenge, Francho Miguel Blasco Blasco, Adriana Alexandra Rueda Villamizar, Maria Antonia Perelló Llaneras, Jose Ignacio García-Sánchez, Laura Fernandez Téllez, Sara García Zamorano, Natalia Gijón Herreros, Andrea Rodriguez Esteve, Pablo Monedero Rodríguez, Isabel García Trigo, Agustín Alcaraz, Andrea Lara Jiménez, Iñigo Rubio, Nuria García, Raquel Callejas, Angel Manuel Candela Toha, Eli Claros, Pilar Cobeta, Pascual Crespo, Trini Dorado, Elena Elías, Javier Felices, Diego Gil, Nuria Mané, Adolfo Martínez, Lucía Pereira, Alberto Balvis Noemí Samaranch, Carlos Tiscar, Judith VillaHoz, Patricia Galán Menéndez, Elena Cardona, Anna Conesa, Veronica Estepa, Laura Llinares Espí, Yuri Loaiza Aldeán, Susana Manrique, Víctor Morales Ariza, Laura Villarino Villa, Elfayadh Saidahmed Mohamed Amed Suliman, Hytham Hamid, Modather Mohamed Saeed, Orhan Sungur Mukadder, Demet Altun, Nur Canbolat, Müşerref Beril Dinçer, Serap Aktaş Yıldırım, Müzeyyen İyigün, Davut Yapıcı, Levent Özdemir, Aslinur Sagun, Neval Boztug, Yesim Cetintas, Bora Dinc, Emel Gündüz, Hakkı Ünlügenç, Demet Lafli Tunay, Ozgur Komurcu, Özlem Korkmaz Dilmen, Eren Fatma Akcil, Eda Tok Alsina, Özge Hakli, Cengiz Polat, Namigar Turgut, Nurcan Kızılcık, Özge Köner, Öznur Şen, Nurdan Aydin, Burcu Basaran, Emre Sertac Bingul, Kamil Darcin, Semra Ugur, Kemal Tolga Saracoglu, Asli Demir, Özgök Aysegül, Eda Balci, Behic Girgin, Aygun Guler, Ümit Karadeniz, Nihal Özaslan, Yigit Özay Hülya, Namik Ozcan, Aysun Postaci, Mehmet Sahap, Nevriye Salman, Özlem Sağır, Bulent Atik, Murat Bicakcioglu, Hafize Fisun Demir, Ugün Fatih, Nazan Kocaoglu, Hüseyin ilksen Toprak, Duygu Demiröz Aslan, Yusuf Ziya Colak, Mustafa Soner Ozcan, Mehmet Yilmaz, Umran Karaca, Sevtap Hekimoglu Sahin, Özlem Ersoy Karka, Gizem Demir Şenoğlu, Süheyla Erkoç Karadağ, Neslihan Alkis, Volkan Baytaş, Engin Erturk, Ali Akdogan, Ahmet Besir, Dilek Kutanis, Sedat Saylan, Ersagun Tugcugil, Pinar Ayvat, Berrin Günaydın, Beyza Mehri Büyükgebiz, Omer Faruk Boran, Feyza Calisir, Yavuz Orak, Bahar Kuvaki Balkan, Sibel Büyükcoban, Erol Gökel, Sakize Ferim Günenc, Sule Özbilgin, Suna Göre, Selcan Akesen, Seda Cansabuncu, Natalia Momot, Anna Panchenko, and Kristen Rutledge
Subjects: Medicine
Abstract: Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI.Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI.Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials.Trial registration number NCT04165369.
Published: 2021
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12. Liberal transfusion strategy to prevent mortality and anaemia-associated, ischaemic events in elderly non-cardiac surgical patients – the study design of the LIBERAL-Trial

Author: Patrick Meybohm, Simone Lindau, Sascha Treskatsch, Roland Francis, Claudia Spies, Markus Velten, Maria Wittmann, Erdem Gueresir, Christian Stoppe, Ana Kowark, Mark Coburn, Sixten Selleng, Marcel Baschin, Gregor Jenichen, Melanie Meersch, Thomas Ermert, Alexander Zarbock, Peter Kranke, Markus Kredel, Antonia Helf, Rita Laufenberg-Feldmann, Marion Ferner, Eva Wittenmeier, Karl-Heinz Gürtler, Peter Kienbaum, Marcel Gama de Abreu, Michael Sander, Michael Bauer, Timo Seyfried, Matthias Gruenewald, Suma Choorapoikayil, Markus M. Mueller, Erhard Seifried, Oana Brosteanu, Holger Bogatsch, Dirk Hasenclever, Kai Zacharowski, and LIBERAL Collaboration Group
Subjects: Red blood cell transfusion, anaemia, surgery, elderly patients, Medicine (General), R5-920
Abstract: Abstract Background Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. Methods The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9–10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5–9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. Discussion The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. Trial registration ClinicalTrials.gov (identifier: NCT03369210).
Published: 2019
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13. Analysis of Leukocyte Recruitment in Continuous Veno-Venous Hemofiltration with Regional Citrate vs. Systemic Heparin Anticoagulation

Author: Andreas Margraf, Chang Liu, Mira Küllmar, Melanie Meersch, Jan Rossaint, and Alexander Zarbock
Subjects: acute kidney injury, CVVH, anticoagulation, citrate, heparin, leukocytes, Cytology, QH573-671
Abstract: Acute kidney injury (AKI) is a frequent complication in critically ill patients. Supportive treatment of AKI patients is based on renal-replacement therapy, including continuous veno-venous hemofiltration (CVVH). To limit clotting events on extracorporeal surfaces, anticoagulants are administered, including systemic heparin and local citrate. The differential and comparative effects of these anticoagulants on leukocyte function in acute kidney injury patients are, so far, insufficiently understood. In this bio-add-on-study, AKI patients were randomized as part of a parallel-group trial to either systemic heparin or regional citrate anticoagulation. Patient samples were collected upon inclusion, prior to CVVH initiation at day 0, day 1, day 3 and day 5, following CVVH initiation, and one day after cessation of CVVH, then immediately analyzed. Flow cytometric assessment of surface-receptor molecules was conducted. Whole-blood-perfused human microfluidic chambers were used for the analysis of neutrophil rolling and adhesion. Acute kidney injury was associated with significant changes in the surface expression of CD182 and CD16 throughout CVVH treatment, independent of the anticoagulation regime. AKI furthermore abrogated selectin-induced slow leukocyte rolling and diminished chemokine-induced leukocyte arrest. Subgroup analyses of citrate vs. heparin treatment showed no significant differences between groups, independent of the duration of CVVH treatment. CD182 and CD16 expression remained low in both groups throughout CVVH therapy. These data confirm that AKI impairs selectin-mediated leukocyte slow rolling and chemokine-induced leukocyte arrest in vitro. Systemic heparin or local citrate anticoagulation have no differential effect on the leukocyte recruitment steps examined in this study.
Published: 2022
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14. Implementation of the Kidney Disease Improving Global Outcomes guidelines for the prevention of acute kidney injury after cardiac surgery

Author: Christina Massoth, Mira Küllmar, Azucena Pajares Moncho, González-Suárez Susana, Evgeny Grigoryev, Artem Ivkin, Vera von Dossow, Sascha Ott, Nadine Rau, Melanie Meersch, and Alexander Zarbock
Subjects: Anesthesiology and Pain Medicine
Published: 2023
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15. Individualized treatment in anesthesiology and intensive care medicine

Author: Mahan Sadjadi and Melanie Meersch-Dini
Published: 2023
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16. Biomarker-guided implementation of the KDIGO guidelines to reduce the occurrence of acute kidney injury in patients after cardiac surgery (PrevAKI-multicentre): protocol for a multicentre, observational study followed by randomised controlled feasibility trial

Author: Joachim Gerss, Melanie Meersch, Carola Wempe, Alexander Zarbock, Gudrun Kunst, Marlies Ostermann, Sara Campos, Neus Grau Novellas, Gary Thomson, Michael Haffner, Christian Arndt, Hinnerk Wulf, Marc Irqsusi, Fabrizio Monaco, Ambra Di Prima, Mercedes Garcia Alvarez, Stefano Italiano, Virginia Cegarra SanMartin, Shrijit Nair, Camilla L'Acqua, Eric A J Hoste, Wim Vandenberghe, John Kellum, Lui Forni, Philippe Grieshaber, Raphael Weiss, and Patrick M Honore
Subjects: Medicine
Abstract: Introduction Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.Methods and analysis We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes.Ethics and dissemination The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial.Trial registration number NCT03244514.
Published: 2020
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17. 6% Hydroxyethyl starch (HES 130/0.4) diminishes glycocalyx degradation and decreases vascular permeability during systemic and pulmonary inflammation in mice

Author: Andreas Margraf, Jan M. Herter, Katharina Kühne, Anika Stadtmann, Thomas Ermert, Manuel Wenk, Melanie Meersch, Hugo Van Aken, Alexander Zarbock, and Jan Rossaint
Subjects: Hydroxyethyl starch 130/0.4, Inflammation, Vascular permeability, Glycocalyx, Sepsis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Increased vascular permeability is a pathophysiological hallmark of sepsis and results in increased transcapillary leakage of plasma fluid, hypovolemia, and interstitial edema formation. 6% hydroxyethyl starch (HES 130/0.4) is commonly used to treat hypovolemia to maintain adequate organ perfusion and oxygen delivery. The present study was designed to investigate the effects of 6% HES 130/0.4 on glycocalyx integrity and vascular permeability in lipopolysaccharide (LPS)-induced pulmonary inflammation and systemic inflammation in mice. Methods 6% HES 130/0.4 or a balanced electrolyte solution (20 ml/kg) was administered intravenously 1 h after cecal ligation and puncture (CLP) or LPS inhalation. Sham-treated animals receiving 6% HES 130/0.4 or the electrolyte solution served as controls. The thickness of the endovascular glycocalyx was visualized by intravital microscopy in lung (LPS inhalation model) or cremaster muscle (CLP model). Syndecan-1, hyaluronic acid, and heparanase levels were measured in blood samples. Vascular permeability in the lungs, liver, kidney, and brain was measured by Evans blue extravasation. Results Both CLP induction and LPS inhalation resulted in increased vascular permeability in the lung, liver, kidney, and brain. 6% HES 130/0.4 infusion led to significantly reduced plasma levels of syndecan-1, heparanase, and hyaluronic acid, which was accompanied by a preservation of the glycocalyx thickness in postcapillary venules of the cremaster (0.78 ± 0.09 μm vs. 1.39 ± 0.10 μm) and lung capillaries (0.81 ± 0.09 μm vs. 1.49 ± 0.12 μm). Conclusions These data suggest that 6% HES 130/0.4 exerts protective effects on glycocalyx integrity and attenuates the increase of vascular permeability during systemic inflammation.
Published: 2018
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18. Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup

Author: Alexander Zarbock, Mitra K. Nadim, Peter Pickkers, Hernando Gomez, Samira Bell, Michael Joannidis, Kianoush Kashani, Jay L. Koyner, Neesh Pannu, Melanie Meersch, Thiago Reis, Thomas Rimmelé, Sean M. Bagshaw, Rinaldo Bellomo, Vicenzo Cantaluppi, Akash Deep, Silvia De Rosa, Xose Perez-Fernandez, Faeq Husain-Syed, Sandra L. Kane-Gill, Yvelynne Kelly, Ravindra L. Mehta, Patrick T. Murray, Marlies Ostermann, John Prowle, Zaccaria Ricci, Emily J. See, Antoine Schneider, Danielle E. Soranno, Ashita Tolwani, Gianluca Villa, Claudio Ronco, and Lui G. Forni
Subjects: All institutes and research themes of the Radboud University Medical Center, Nephrology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Abstract: Item does not contain fulltext Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research. 01 juni 2023
Published: 2023

19. Interleukin 24 promotes cell death in renal epithelial cells and is associated with acute renal injury

Author: Katharina Schütte-Nütgen, Maria Edeling, Dominik Kentrup, Barbara Heitplatz, Veerle Van Marck, Alexander Zarbock, Melanie Meersch-Dini, Hermann Pavenstädt, and Stefan Reuter
Subjects: Mice, Inbred C57BL, Mice, Transplantation, Reperfusion Injury, Interleukins, Animals, Immunology and Allergy, Apoptosis, Epithelial Cells, Pharmacology (medical), Acute Kidney Injury, Kidney
Abstract: Ischemia-reperfusion injury is a major cause of acute kidney injury. Many cytokines are involved in the pathogenesis of renal ischemia-reperfusion injury. IL24 is a member of the IL10 family and has gained importance because of its apoptosis-inducing effects in tumor disease besides its immunoregulative function. Littles is known about the role of IL24 in kidney disease. Using a mouse model, we found that IL24 is upregulated in the kidney after renal ischemia-reperfusion injury and that tubular epithelial cells and infiltrating inflammatory cells are the source of IL24. Mice lacking IL24 are protected from renal injury and inflammation. Cell culture studies showed that IL24 induces apoptosis in renal tubular epithelial cells, which is accompanied by an increased endoplasmatic reticulum stress response. Moreover, IL24 induces robust expression of endogenous IL24 in tubular cells, fostering ER-stress and apoptosis. In kidney transplant recipients with delayed graft function and patients at high risk to develop acute kidney injury after cardiac surgery IL24 is upregulated in the kidney and serum. Taken together, IL24 can serve as a biomarker, plays an important mechanistic role involving both extracellular and intracellular targets, and is a promising therapeutic target in patients at risk of or with ischemia-induced acute kidney injury.
Published: 2022
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20. Implementation of Nephroprotective Measures to Prevent Acute Kidney Injury in Septic Patients: A Retrospective Cohort Study

Author: Mahan Sadjadi, Christian Porschen, Thilo von Groote, Felix Albert, John A. Kellum, Hernando Gomez, Melanie Meersch, and Alexander Zarbock
Subjects: Anesthesiology and Pain Medicine
Published: 2023
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21. Acute kidney injury

Author: Michael Joannidis, Melanie Meersch-Dini, and Lui G. Forni
Subjects: Critical Care and Intensive Care Medicine
Published: 2023
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22. The Role of Cell Cycle Arrest Biomarkers for Predicting Acute Kidney Injury in Critically Ill COVID-19 Patients: A Multicenter, Observational Study

Author: Raphael Weiss, Thilo von Groote, Marlies Ostermann, Nuttha Lumlertgul, Kittisak Weerapolchai, Manuel Ignacio Monge Garcia, Jose Maria Martin Cano, Beatriz Diez del Corral, María Jesús Broch-Porcar, Marcos Perez Carrasco, Arsenio De la Vega Sanchez, Eduardo Sousa, Ana Catarino, Antonio Jorge Betbesé Roig, Jaume Baldira Martinez de Irujo, Silvia de Rosa, Manuel Garcia-Montesinos de la Peña, Teresa Tomasa, Matteo Brivio, Francisco Javier Gonzalez De Molina, Joachim Gerss, John A. Kellum, Carola Wempe, Anna Leidereiter, Melanie Meersch, and Alexander Zarbock
Subjects: Critical Care and Intensive Care Medicine
Published: 2023
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23. 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: Thilo von Groote, Melanie Meersch, Stefano Romagnoli, Marlies Ostermann, Javier Ripollés-Melchor, Antoine Guillaume Schneider, Wim Vandenberghe, Céline Monard, Silvia De Rosa, Lucia Cattin, Tim Rahmel, Michael Adamzik, Diego Parise, Angel Candela-Toha, Jan Gerrit Haaker, Ulrich Göbel, Alice Bernard, Nuttha Lumlertgul, Paula Fernández-Valdes-Bango, Irene Romero Bhathal, A Suarez-de-la-Rica, Jan Larmann, Gianluca Villa, Savino Spadaro, Hinnerk Wulf, Christian Arndt, Christian Putensen, Raquel García-Álvarez, Timo Brandenburger, Antonio Siniscalchi, Richard Ellerkmann, Florian Espeter, Christian Porschen, Mahan Sadjadi, Khaschayar Saadat-Gilani, Raphael Weiss, Joachim Gerss, John Kellum, and Alexander Zarbock
Subjects: Medizin, General Medicine, ddc:610
Abstract: IntroductionPrevious 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 analysisThe 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 disseminationThe 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 numberNCT04647396.
Published: 2023

24. Effect of Glutamine Administration After Cardiac Surgery on Kidney Damage in Patients at High Risk for Acute Kidney Injury: A Randomized Controlled Trial

Author: Raphael Weiss, Melanie Meersch, Mena Gerke, Carola Wempe, Michael Schäfers, John A. Kellum, and Alexander Zarbock
Subjects: Anesthesiology and Pain Medicine
Published: 2022
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25. Biomarkers for the Prediction and Judgement of Sepsis and Sepsis Complications: A Step towards

Author: Thilo, von Groote and Melanie, Meersch-Dini
Abstract: Sepsis and septic shock are a major public health concern and are still associated with high rates of morbidity and mortality. Whilst there is growing understanding of different phenotypes and endotypes of sepsis, all too often treatment strategies still only employ a "one-size-fits-all" approach. Biomarkers offer a unique opportunity to close this gap to more precise treatment approaches by providing insight into clinically hidden, yet complex, pathophysiology, or by individualizing treatment pathways. Predicting and evaluating systemic inflammation, sepsis or septic shock are essential to improve outcomes for these patients. Besides opportunities to improve patient care, employing biomarkers offers a unique opportunity to improve clinical research in patients with sepsis. The high rate of negative clinical trials in this field may partly be explained by a high degree of heterogeneity in patient cohorts and a lack of understanding of specific endotypes or phenotypes. Moving forward, biomarkers can support the selection of more homogeneous cohorts, thereby potentially improving study conditions of clinical trials. This may finally pave the way to a
Published: 2022

26. When the kidneys hurt, the other organs suffer

Author: Celine Monard, Melanie Meersch-Dini, and Michael Joannidis
Subjects: Critical Care and Intensive Care Medicine
Published: 2022

27. Prevention of Cardiac Surgery–Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial

Author: Wim Vandenberghe, Fabrizio Monaco, Alexander Zarbock, Shrijit Nair, Carola Wempe, Gianluca Lucchese, Joachim Gerss, Jordi Miralles Bagan, Ronak Rajani, Gudrun Kunst, Lui G. Forni, Armando Cennamo, Hinnerk Wulf, Marlies Ostermann, Christina Massoth, Melanie Meersch, Camilla L'Acqua, John A. Kellum, Patrick M. Honore, Christian Arndt, Marc Irqsusi, Philippe Grieshaber, Stefano Italiano, Stuart McCorkell, Ambra Licia Di Prima, Mira Küllmar, Mercedes Garcia Alvarez, Kamran Baig, Raphael Weiss, and Eric Hoste
Subjects: Male, medicine.medical_specialty, Time Factors, Risk Assessment, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Predictive Value of Tests, Risk Factors, 030202 anesthesiology, law, Internal medicine, Clinical endpoint, Humans, Medicine, Cardiac Surgical Procedures, Aged, Tissue Inhibitor of Metalloproteinase-2, business.industry, Acute kidney injury, Absolute risk reduction, Guideline, Acute Kidney Injury, Middle Aged, medicine.disease, Confidence interval, Cardiac surgery, Europe, Insulin-Like Growth Factor Binding Proteins, Treatment Outcome, Anesthesiology and Pain Medicine, Practice Guidelines as Topic, Feasibility Studies, Female, Guideline Adherence, business, Biomarkers, Patient Care Bundles, 030217 neurology & neurosurgery, Kidney disease
Abstract: BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.
Published: 2021
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28. Kinetic Changes of Plasma Renin Concentrations Predict Acute Kidney Injury in Cardiac Surgery Patients

Author: Manuel Núñez Cortés, Joachim Gerss, Danilo Fliser, Raphael Weiss, Anas Lagan, Mira Küllmar, Alexander Zarbock, Lakhmir S. Chawla, Khaschayar Saadat-Gilani, Christina Massoth, and Melanie Meersch
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Fluid homeostasis, Acute kidney injury, Renal function, Critical Care and Intensive Care Medicine, medicine.disease, Plasma renin activity, Cardiac surgery, 03 medical and health sciences, 0302 clinical medicine, Blood pressure, 030228 respiratory system, Internal medicine, Renin–angiotensin system, medicine, Cardiology, 030212 general & internal medicine, business
Abstract: Rationale: The renin–angiotensin–aldosterone system is a major pathway in regulating blood pressure, glomerular filtration, and fluid homeostasis. During inflammatory diseases, generation of angiot...
Published: 2021
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29. Sichere Anästhesie und Arbeitszeitgesetz: Wechsel von Personal erlaubt?

Author: Melanie Meersch and Christina Massoth
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, business.industry, medicine, Postoperative outcome, 030208 emergency & critical care medicine, General Medicine, business
Abstract: Arbeitszeitbeschrankungen in der Medizin nehmen im Hinblick auf die Patientensicherheit eine ambivalente Stellung ein. Sie erfordern eine Abwagung von Behandlungskontinuitat mit nachlassender Leistungsfahigkeit auf der einen Seite, mit Personalwechseln und damit einhergehenden Informationsverlusten auf der anderen Seite. Intraoperative Anasthesistenwechsel werden im klinischen Alltag haufig durchgefuhrt, besitzen aber moglicherweise das Potenzial, die postoperative Morbiditat und Mortalitat negativ zu beeinflussen. Die Relevanz der anasthesiologischen Betreuung fur das postoperative Outcome scheint auserdem in Abhangigkeit vom jeweiligen Fachgebiet zu variieren. Standardisierte Ubergabeprotokolle erreichen nur eine begrenzte Effektivitat bei der Verbesserung des Informationstransfers, stellen aber dennoch einen sinnvollen Ansatz zur Optimierung der interprofessionellen Kommunikation und der Reduktion von Behandlungsfehlern dar.
Published: 2021
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30. Der Einfluss intraoperativer Anästhesistenwechsel auf das postoperative Patientenoutcome – die randomisiert-kontrollierte HandiCAP-Studie

Author: HandiCAP Investigators, Christina Massoth, Melanie Meersch, and Khaschayar Saadat-Gilani
Subjects: medicine.medical_specialty, Anesthesiology and Pain Medicine, Handover, business.industry, Pain medicine, Anesthesiology, MEDLINE, Medicine, General Medicine, Medical emergency, business, medicine.disease
Published: 2021
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31. Inhaled Prostacyclin Improves Oxygenation in Patients with COVID-19-induced Acute Respiratory Distress Syndrome – a randomized controlled multicenter trial

Author: Helene A. Haeberle, Stefanie Calov, Peter Martus, Lina Maria Serna Higuita, Michael Koeppen, Almuth Goll, Alexander Zarbock, Melanie Meersch, Raphael Weiss, Martin Mehrländer, Gernot Marx, Christian Putensen, Tamam Bakchoul, Harry Magunia, Bernhard Nieswandt, Valbona Mirakaj, and Peter Rosenberger
Abstract: Background. Acute Respiratory Distress Syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS. Methods. We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride. The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events. Results. Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline oxygenation index did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than NaCl (p = 0·17). Oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0·04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups. Conclusions. Although the primary result of our study was negative, our data suggest that inhaled prostacyclin might be a more beneficial treatment than standard care for patients with ARDS. Trial registration: The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016-003168-37) and registered at clinicaltrials.gov (NCT03111212).
Published: 2022
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32. Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials

Author: Niklas S. Campos, Thomas Bluth, Sabrine N.T. Hemmes, Julian Librero, Natividad Pozo, Carlos Ferrando, Lorenzo Ball, Guido Mazzinari, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J. Schultz, A. Serpa Neto, Sabrine NT. Hemmes, Paolo Severgnini, Markus W. Hollmann, Jan M. Binnekade, Hermann Wrigge, Jaume Canet, Michael Hiesmayr, Werner Schmid, Edda Tschernko, Samir Jaber, Göran Hedenstierna, Christian Putensen, Agnes Marti, Alessandro Bacuzzi, Alexander Brodhun, Alexandre Molin, Alfred Merten, Ana Parera, Andrea Brunelli, Andrea Cortegiani, Andreas Güldner, Andreas W. Reske, Angelo Gratarola, Antonino Giarratano, Bea Bastin, Bjorn Heyse, Branka Mazul-Sunko, Bruno Amantea, Bruno Barberis, Christopher Uhlig, Conrado Minguez Marín, Cristian Celentano, Daniela La Bella, David D’Antini, David Velghe, Demet Sulemanji, Edoardo De Robertis, Eric Hartmann, Francesca Montalto, Francesco Tropea, Gary H. Mills, Gilda Cinnella, Giorgio Della Rocca, Girolamo Caggianelli, Giulia Pellerano, Giuseppina Mollica, Guillermo Bugedo, Jan-Paul Mulier, Jeroen Vandenbrande, Johann Geib, Jonathan Yaqub, Jorge Florez, Juan F. Mayoral, Juraj Sprung, Jurgen Van Limmen, Lieuwe DJ. Bos, Luc de Baerdemaeker, Luc Jamaer, Luigi Spagnolo, Lydia Strys, Manuel Granell Gil, Marcos F. Vidal Melo, Maria Carmen Unzueta, Maria Victoria Moral, Marion Ferner, Martin Weiss, Massimo Vanoni, Maximilian S. Schaefer, Mercè Prieto, Michele Grio, Peter Markus Spieth, Philipp Simon, Phoebe Bodger, Pilar Sierra, Rita Laufenberg-Feldmann, Roberta Rusca, Rodolfo Proietti, Santi Maurizio Raineri, Santo Caroleo, Sergi Sabaté, Stefan De Hert, Stefano Pezzato, Tanja A. Treschan, Tatjana Goranovic, Thea Koch, Thomas Kiss, Valter Perilli, Virginia Cegarra, Javier Belda, Marina Soro, Carmen Unzueta, Fernando Suarez-Sipmann, Julián Librero, Alicia Llombart, Lucas Rovira, Manuel Granell, César Aldecoa, Oscar Diaz-Cambronero, Jaume Balust, Ignacio Garutti, Rafael Gonzalez, Lucia Gallego, Santiago Garcia del Valle, Javier Redondo, David Pestaña, Aurelio Rodríguez, Javier García, Manuel de la Matta, Maite Ibáñez, Francisco Barrios, Samuel Hernández, Vicente Torres, Salvador Peiró, Abigail Villena, Albert Carramiñana, Alberto Gallego-Casilda, Alejandro Duca, Amalia Alcón, Amanda Miñana, Ana Asensio, Ana Colás, Ana Isabel Galve, Ana Izquierdo, Ana Jurado, Ana María Pérez, Ana Mugarra, Andrea Gutierrez, Ángeles De Miguel, Angels Lozano, Antonio Katime, Antonio Romero, Beatriz Garrigues, Begoña Ayas, Blanca Arocas, Carlos Delgado, Carmen Fernández, Carolina Romero, Clara Gallego, Cristina Garcés, Cristina Lisbona, Cristina Parrilla, Daniel López-Herrera, Domingo González, Eduardo Llamazares, Elena Del Rio, Elena Lozano, Ernesto Pastor, Estefanía Chamorro, Estefanía Gracia, Ester Sánchez, Esther Romero, Fernando Díez, Ferran Serralta, Francisco Daviu, Francisco Sandín, Gerardo Aguilar, Gerardo Tusman, Gonzalo Azparren, Graciela Martínez-Pallí, Inmaculada Benítez, Inmaculada Hernandéz, Inmaculada India, Irene León, Isabel Fuentes, Isabel Ruiz, Jaume Puig, Javie Ignacio Román, Jesús Acosta, Jesús Rico-Feijoo, Jonathan Olmedo, Jose A. Carbonell, Jose M. Alonso, Jose María Pérez, Jose Miguel Marcos, Jose Navarro, Jose Valdivia, Juan Carrizo, Laura Piqueras, Laura Soriano, Laura Vaquero, Lisset Miguel, Lorena Muñoz, Lucia Valencia, Luis Olmedilla, Mᵃ Justina Etulain, Manuel Tisner, María Barrio, María Dolores Alonso, María García, María J. Hernández, María José Alberola, María Parra, María Pilar Argente, María Vila, Mario De Fez, Marta Agilaga, Marta Gine, Mercedes Ayuso, Mercedes García, Natalia Bejarano, Natalia Peña, Nazario Ojeda, Nilda Martínez, Nuria García, Oto Padrón, Pablo García, Paola Valls, Patricia Cruz, Patricia Piñeiro, Pedro Charco, Rafael Anaya, Ramiro López, Rayco Rodríguez, Rocío Martínez, Roger Pujol, Rosa Dosdá, Rosa Lardies, Ruben Díaz, Rubén Villazala, Sara Zapatero, Sergio Cabrera, Sergio Sánchez, Silvia Martin, Suzana Diaz, Tania Franco, Tania Moreno, Tania Socorro, Vicente Gilabert, Victor Balandrón, Victoria Moral, Virgina Cegarra, Viviana Varón, Fernando Abelha, Sühayla Abitağaoğlu, Marc Achilles, Afeez Adebesin, Ine Adriaensens, Charles Ahene, Fatima Akbar, Mohammed Al Harbi, Rita Al Khoury al Kallab, Xavier Albanel, Florence Aldenkortt, Rawan Abdullah Saleh Alfouzan, Reef Alruqaie, Fernando Altermatt, Bruno Luís de Castro Araujo, Genaro Arbesú, Hanna Artsi, Caterina Aurilio, Omer Hilmi Ayanoglu, Harris Baig, Yolanda Baird, Konstantin Balonov, Samantha Banks, Xiaodong Bao, Mélanie Baumgartner, Isabel Belda Tortosa, Alice Bergamaschi, Lars Bergmann, Luca Bigatello, Elena Biosca Pérez, Katja Birr, Elird Bojaxhi, Chiara Bonenti, Iwona Bonney, Elke M.E. Bos, Sara Bowman, Leandro Gobbo Braz, Elisa Brugnoni, Sorin J. Brull, Iole Brunetti, Andrea Bruni, Shonie L. Buenvenida, Cornelius Johannes Busch, Giovanni Camerini, Beatrice Capatti, Javiera Carmona, Jaime Carungcong, Marta Carvalho, Anat Cattan, Carla Cavaleiro, Davide Chiumello, Stefano Ciardo, Mark Coburn, Umberto Colella, Victor Contreras, Pelin Corman Dincer, Elizabeth Cotter, Marcia Crovetto, William Darrah, Simon Davies, Enrique Del Cojo Peces, Ellise Delphin, John Diaper, Paulo do Nascimento Junior, Valerio Donatiello, Jing Dong, Maria do Socorro Dourado, Alexander Dullenkopf, Felix Ebner, Hamed Elgendy, Christoph Ellenberger, Dilek Erdoğan Arı, Thomas Ermert, Fadi Farah, Ana Fernandez-Bustamante, Cristina Ferreira, Marco Fiore, Ana Fonte, Christina Fortià Palahí, Andrea Galimberti, Najia Garofano, Luca Gregorio Giaccari, Fernando Gilsanz, Felix Girrbach, Luca Gobbi, Marc Bernard Godfried, Nicolai Goettel, Peter A. Goldstein, Or Goren, Andrew Gorlin, Juan Graterol, Pierre Guyon, Kevin Haire, Philippe Harou, Antonia Helf, Gunther Hempel, María José Hernández Cádiz, Björn Heyse, Ivan Huercio, Jasmina Ilievska, Lien Jakus, Vijay Jeganath, Yvonne Jelting, Minoa Jung, Barbara Kabon, Aalok Kacha, Maja Karaman Ilić, Arunthevaraja Karuppiah, Ayse Duygu Kavas, Gleicy Keli Barcelos, Todd A. Kellogg, Johann Kemper, Romain Kerbrat, Suraya Khodr, Peter Kienbaum, Bunyamin Kir, Selin Kivrak, Vlasta Klarić, Ceren Köksal, Ana Kowark, Peter Kranke, Bahar Kuvaki, Biljana Kuzmanovska, John Laffey, Mirko Lange, Marília Freitas de Lemos, Marc-Joseph Licker, Manuel López-Baamonde, Antonio López-Hernández, Mercedes Lopez-Martinez, Stéphane Luise, Mark MacGregor, Danielle Magalhães, Julien Maillard, Patrizia Malerbi, Natesan Manimekalai, Michael Margarson, Klaus Markstaller, Archer K. Martin, David P. Martin, Yvette N. Martin, Julia Martínez-Ocon, Ignacio Martin-Loeches, Emilio Maseda, Idit Matot, Niamh McAuliffe, Travis J. McKenzie, Paulina Medina, Melanie Meersch, Angelika Menzen, Els Mertens, Bernd Meurer, Tanja Meyer-Treschan, Changhong Miao, Camilla Micalizzi, Morena Milić, Norma Sueli Pinheiro Módolo, Pierre Moine, Patrick Mölders, Ana Montero-Feijoo, Enrique Moret, Markus K. Muller, Zoe Murphy, Pramod Nalwaya, Filip Naumovski, Paolo Navalesi, Lais Helena Navarro e Lima, Višnja Nesek Adam, Claudia Neumann, Christopher Newell, Zoulfira Nisnevitch, Junaid Nizamuddin, Cecilia Novazzi, Michael O'Connor, Günther Oprea, Mukadder Orhan Sungur, Şule Özbilgin, Maria Caterina Pace, Marcos Pacheco, Balaji Packianathaswamy, Estefania Palma Gonzalez, Fotios Papaspyros, Sebastián Paredes, Maria Beatrice Passavanti, Juan Cristobal Pedemonte, Sanja Peremin, Christoph Philipsenburg, Daniela Pinho, Silvia Pinho, Linda M. Posthuma, Vincenzo Pota, Benedikt Preckel, Paolo Priani, Mohamed Aymen Rached, Aleksandar Radoeshki, Riccardo Ragazzi, Tamilselvan Rajamanickam, Arthi Rajamohan, Harish Ramakrishna, Desikan Rangarajan, Christian Reiterer, J. Ross Renew, Thomas Reynaud, Rhidian Rhys, Eva Rivas, Luisa Robitzky, Rolf Rossaint, Francesca Rubulotta, Humberto S. Machado, Catarina S. Nunes, Giovanni Sabbatini, Jon D. Samuels, Josep Martí Sanahuja, Pasquale Sansone, Alice Santos, Mohamed Sayedalahl, Martin Scharffenberg, Eduardo Schiffer, Nadja Schliewe, Raoul Schorer, Roman Schumann, Gabriele Selmo, Mar Sendra, Mert Senturk, Kate Shaw, Mirjana Shosholcheva, Abdulrazak Sibai, Francesca Simonassi, Claudia Sinno, Nukhet Sivrikoz, Vasiliki Skandalou, Neil Smith, Maria Soares, Tania Socorro Artiles, Diogo Sousa Castro, Miguel Sousa, Savino Spadaro, Emmanouil Stamatakis, Luzius A. Steiner, Andrea Stevenazzi, Alejandro Suarez-de-la-Rica, Mélanie Suppan, Robert Teichmann, José Maria Tena Guerrero, Bram Thiel, Raquel Tolós, Gulbin Tore Altun, Michelle Tucci, Zachary A. Turnbull, Žana Turudić, Matthias Unterberg, Yves Van Nieuwenhove, Julia Van Waesberghe, Marcos Francisco Vidal Melo, Bibiana Vitković, Luigi Vivona, Marcela Vizcaychipi, Carlo Alberto Volta, Anne Weber, Toby N. Weingarten, Jakob Wittenstein, Piet Wyffels, Julio Yagüe, David Yates, Ayşen Yavru, Lilach Zac, Jing Zhong, Anesthesiology, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, ACS - Microcirculation, Campos, Niklas S, Bluth, Thoma, Hemmes, Sabrine N T, Librero, Julian, Pozo, Natividad, Ferrando, Carlo, Ball, Lorenzo, Mazzinari, Guido, Pelosi, Paolo, Gama de Abreu, Marcelo, Schultz, Marcus J, Serpa Neto, A, investigators for the PROVHILO study including, Cortegiani, Andrea, Raineri, Santi Maurizio, and Giarratano, Antonino
Subjects: Adult, Lung Diseases, PEEP, postoperative pulmonary complications, mechanical ventilation, Positive-Pressure Respiration, surgery, Anesthesiology and Pain Medicine, Postoperative Complications, Tidal Volume, Humans, Postoperative Period, Lung, Randomized Controlled Trials as Topic
Abstract: BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).
Published: 2022

33. Prediction of Acute Kidney Injury in the Intensive Care Unit: Preliminary Findings in a European Open Access Database

Author: Michael, Fujarski, Christian, Porschen, Lucas, Plagwitz, Alexander, Brenner, Narges, Ghoreishi, Patrick, Thoral, Harm-Jan, de Grooth, Paul, Elbers, Raphael, Weiss, Melanie, Meersch, Alexander, Zarbock, Thilo Caspar, von Groote, and Julian, Varghese
Subjects: Access to Information, Intensive Care Units, Databases, Factual, Critical Illness, Humans, Acute Kidney Injury
Abstract: Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with long-term complications and an increased mortality. This work presents preliminary findings from the first freely available European intensive care database released by Amsterdam UMC. A machine learning (ML) model was developed to predict AKI in the intensive care unit 12 hours before the actual event. Main features of the model included medications and hemodynamic parameters. Our models perform with an accuracy of 81.8% on moderate to severe AKI and 79.8% on all AKI patients. Those results can compete with models reported in the literature and introduce an ML model for AKI based on European patient data.
Published: 2022

34. The Effect of Filter Lifespan during Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury on the Rate of New-Onset Infection: Analysis from the RICH Randomized Controlled Trial

Author: Joachim Gerss, Melanie Meersch, Detlef Kindgen-Milles, Timo Brandenburger, Carsten Willam, John A. Kellum, and Alexander Zarbock
Subjects: Pulmonary and Respiratory Medicine, Renal Replacement Therapy, Continuous Renal Replacement Therapy, Critical Illness, Longevity, Medizin, Humans, Acute Kidney Injury, Critical Care and Intensive Care Medicine
Published: 2022

35. Qualitätsverbessernde Maßnahmen in der Versorgung von kritisch kranken Intensivpatienten mit Nierenersatztherapie bei akuter Nierenschädigung

Author: Peter Heering, Michael Schmitz, S. John, Alexander Zarbock, Michael Oppert, Achim Jörres, Detlef Kindgen-Milles, Melanie Meersch-Dini, and Carsten Willam
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, Emergency Medicine, Internal Medicine, Medicine, 030212 general & internal medicine, Emergency Nursing, Critical Care and Intensive Care Medicine, business
Abstract: ZusammenfassungDie Nierenersatztherapie ist neben der Beatmung eines der wichtigsten und am häufigsten angewendeten Organersatzverfahren in der täglichen Praxis in der Intensivmedizin. Im Gegensatz zur Beatmungstherapie sind Qualitätsstandards für die Nierenersatztherapie weniger gut definiert und bekannt. In diesem Positionspapier der Deutschen Interdisziplinären Vereinigung für Intensivmedizin (DIVI) beschreiben wir Qualitätsstandards zur Nierenersatztherapie mit dem Ziel die Behandlungsqualität der Patienten mit einem schweren akuten Nierenversagen zu verbessern.
Published: 2020
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36. Effects of Different Doses of Remote Ischemic Preconditioning on Kidney Damage Among Patients Undergoing Cardiac Surgery: A Single-Center Mechanistic Randomized Controlled Trial

Author: Melanie Meersch, John A. Kellum, Laura Kerschke, Sven Martens, Pia Klausmeyer, Mira Küllmar, Jan Rossaint, Hermann Pavenstädt, Elisa A Schmidt, and Alexander Zarbock
Subjects: Male, medicine.medical_specialty, Urinary system, Critical Care and Intensive Care Medicine, Single Center, law.invention, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Clinical endpoint, medicine, Cardiopulmonary bypass, Humans, Cardiac Surgical Procedures, Ischemic Preconditioning, Aged, Tissue Inhibitor of Metalloproteinase-2, Cardiopulmonary Bypass, business.industry, Acute kidney injury, Acute Kidney Injury, medicine.disease, Cardiac surgery, Insulin-Like Growth Factor Binding Proteins, Cardiology, Ischemic preconditioning, Female, business
Abstract: We have previously shown that remote ischemic preconditioning reduces acute kidney injury (acute kidney injury) in high-risk patients undergoing cardiopulmonary bypass and that the protective effect is confined to patients who exhibit an increased urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 in response to remote ischemic preconditioning. The purpose of this study was to determine the optimal intensity of remote ischemic preconditioning to induce required [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] changes and further explore mechanisms of remote ischemic preconditioning.Observational and randomized controlled, double-blind clinical trial.University Hospital of Muenster, Germany.High-risk patients undergoing cardiac surgery as defined by the Cleveland Clinic Foundation Score.In the interventional part, patients were randomized to receive either one of four different remote ischemic preconditioning doses (3 × 5 min, 3 × 7 min, 3 × 10 min remote ischemic preconditioning, or 3 × 5 min remote ischemic preconditioning + 2 × 10 min remote ischemic preconditioning in nonresponders) or sham-remote ischemic preconditioning (control).The primary endpoint of the interventional part was change in urinary [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] between pre- and postintervention. To examine secondary objectives including acute kidney injury incidence, we included an observational cohort. A total of 180 patients were included in the trial (n = 80 observational and n = 100 randomized controlled part [20 patients/group]). The mean age was 69.3 years (10.5 yr), 119 were men (66.1%). Absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] were significantly higher in all remote ischemic preconditioning groups when compared with controls (p0.01). Although we did not observe a dose-response relationship on absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] across the four different remote ischemic preconditioning groups, in the 15 patients failing to respond to the lowest dose, nine (60%) responded to a subsequent treatment at a higher intensity. Compared with controls, fewer patients receiving remote ischemic preconditioning developed acute kidney injury within 72 hours after surgery as defined by both Kidney Disease: Improving Global Outcomes criteria (30/80 [37.5%] vs 61/100 [61.0%]; p = 0.003).All doses of remote ischemic preconditioning significantly increased [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] and significantly decreased acute kidney injury compared with controls. High-dose remote ischemic preconditioning could stimulate [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] increases in patients refractory to low-dose remote ischemic preconditioning.
Published: 2020
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37. A Multinational Observational Study Exploring Adherence With the Kidney Disease

Author: Mercedes García-Alvarez, Patrick M. Honore, Mar Felipe Correoso, Marc Irqsusi, Gary Thomson, Neus Grau Novellas, Mira Küllmar, Marlies Ostermann, Eric Hoste, Carola Wempe, Melanie Meersch, John A. Kellum, Shrijit Nair, Christian Arndt, Ambra Licia Di Prima, Gudrun Kunst, Philippe Grieshaber, Sara Campos, Lui G. Forni, Camilla L'Acqua, Wim Vandenberghe, Hinnerk Wulf, Stefano Italiano, Michael Haffner, Alexander Zarbock, Fabrizio Monaco, and Raphael Weiß
Subjects: Adult, Male, medicine.medical_specialty, Acute Lung Injury, Renal function, Kidney Function Tests, law.invention, Cohort Studies, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Prevalence, Humans, Medicine, Prospective Studies, Cardiac Surgical Procedures, Prospective cohort study, Aged, Monitoring, Physiologic, business.industry, Incidence, Acute kidney injury, Postoperative complication, Length of Stay, Middle Aged, medicine.disease, Clinical trial, Anesthesiology and Pain Medicine, Creatinine, Emergency medicine, Female, Kidney Diseases, Guideline Adherence, business, 030217 neurology & neurosurgery, Cohort study, Kidney disease
Abstract: BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] +/- 1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD +/- 1.1] vs 3.5 [SD +/- 1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.
Published: 2020
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38. The Association Between Angiotensin II and Renin Kinetics in Patients After Cardiac Surgery

Author: Melanie Meersch, Raphael Weiss, Christina Massoth, Mira Küllmar, Khaschayar Saadat-Gilani, Manuel Busen, Lakhmir Chawla, Giovanni Landoni, Rinaldo Bellomo, Joachim Gerss, Alexander Zarbock, Meersch, Melanie, Weiss, Raphael, Massoth, Christina, Küllmar, Mira, Saadat-Gilani, Khaschayar, Busen, Manuel, Chawla, Lakhmir, Landoni, Giovanni, Bellomo, Rinaldo, Gerss, Joachim, and Zarbock, Alexander
Subjects: Kinetics, Norepinephrine, Anesthesiology and Pain Medicine, Angiotensin II, Renin, Humans, Cardiac Surgical Procedures, Retrospective Studies
Abstract: Background: Hyperreninemia after cardiac surgery is associated with cardiovascular instability. Angiotensin II (AT-II) could potentially attenuate hyperreninemia while maintaining target blood pressure. This study assesses the association between AT-II usage and renin levels in cardiac surgery patients with postoperative hyperreninemia and vasoplegia. Methods: Between September 2020 and March 2021, we retrospectively identified 40 cardiac surgery patients with high Δ-renin levels (4 hours after cardiopulmonary bypass [CPB] minus preoperative levels) (defined as higher than 3.7 µU/mL) and vasopressor use who received a vasopressor therapy with either AT-II or continued norepinephrine alone. The primary outcome was the renin plasma level at 12 hours after surgery, adjusted by the renin plasma level at 4 hours after surgery. Results: Overall, the median renin plasma concentration increased from a baseline with median of 44.3 µU/mL (Q1-Q3, 14.6-155.5) to 188.6 µU/mL (Q1-Q3, 29.8-379.0) 4 hours after CPB. High Δ-renin (difference between postoperation and preoperation) patients (higher than 3.7 µU/mL) were then treated with norepinephrine alone (median dose of 3.25 mg [Q1-Q3, 1.00-4.75]) or with additional AT-II (norepinephrine dose: 1.33 mg [Q1-Q3, 0.78-2.04]; AT-II dose: 0.34 mg [Q1-Q3, 0.29-0.78]). At 12 hours after surgery, AT-II patients had lower renin levels than standard of care patients (71.7 µU/mL [Q1-Q3, 21.9-211.4] vs 130.6 µU/mL [Q1-Q3, 62.9-317.0]; P = .034 adjusting for the renin plasma level at 4 hours after surgery). Conclusions: In cardiac surgery patients with hypotonia and postoperative high Δ-renin levels, AT-II was associated with reduced renin plasma levels for at 12 hours and significantly decreased norepinephrine use, while norepinephrine alone was associated with increased renin levels. Further studies of AT-II in cardiac surgery appear justified.
Published: 2022

39. Comparison of C-C motif chemokine ligand 14 with other biomarkers for adverse kidney events after cardiac surgery

Author: Christina Massoth, Mira Küllmar, Dominic Enders, John A. Kellum, Lui G. Forni, Melanie Meersch, Alexander Zarbock, Raphael Weiss, Khaschayar Saadat-Gilani, Tamara Roy-Ali, and Jan Rossaint
Subjects: Pulmonary and Respiratory Medicine, Chemokine, medicine.medical_specialty, medicine.medical_treatment, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Renal replacement therapy, Kidney, biology, business.industry, Acute kidney injury, Area under the curve, medicine.disease, medicine.anatomical_structure, 030228 respiratory system, biology.protein, Biomarker (medicine), Surgery, Cardiology and Cardiovascular Medicine, business, Kidney disease
Abstract: Objective Outcomes after acute kidney injury are affected by both the severity and the duration of the insult. Patients with persistent acute kidney injury have higher major adverse kidney events, including 90-day mortality, renal replacement therapy, and persistent kidney dysfunction. Methods to identify these patients are urgently needed to improve outcomes. The purpose of this study was to evaluate whether biomarkers, including C-C motif chemokine ligand 14, were able to predict persistent acute kidney injury and major adverse kidney events after cardiac surgery. Methods This study was a single-center, prospective, observational study. Patients who developed moderate or severe acute kidney injury (Kidney Disease Improving Global Outcomes 2 or 3) within 72 hours after cardiac surgery were enrolled with a primary end point of persistent severe acute kidney injury (Kidney Disease Improving Global Outcomes 3) lasting 72 hours or more. Results A total of 100 patients were available for the primary analysis, and 37 met the primary end point. C-C motif chemokine ligand 14 was the most predictive biomarker for the primary end point with an area under the curve of 0.930 (95% confidence interval, 0.881-0.979). The area under the curve of C-C motif chemokine ligand 14 was significantly higher than the area under the curve for the other biomarkers analyzed. C-C motif chemokine ligand 14 was significantly higher in end point positive patients at enrollment (4.47 ng/mL [2.35-11.5] vs 0.67 ng/mL [0.38-1.07]; P = .001). Sensitivity and specificity were 78% and 95% at a cutoff value of 2.21 ng/mL, respectively. C-C motif chemokine ligand 14 was also highly accurate for predicting renal replacement therapy within 7 days (area under the curve, 0.915; 95% confidence interval, 0.858-0.972; P Conclusions Elevated C-C motif chemokine ligand 14 levels predict persistent acute kidney injury in cardiac surgery patients with moderate or severe acute kidney injury. This new biomarker may help stratify patients destined to receive renal replacement therapy and identify patients who may benefit from novel therapeutic approaches to acute kidney injury.
Published: 2023
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40. Outcomes From Intraoperative Handovers of Anesthesia Care—Reply

Author: Melanie, Meersch, Daniel I, Sessler, and Alexander, Zarbock
Subjects: Treatment Outcome, Intraoperative Care, Anesthesiology, Patient Handoff, Humans, Anesthesia, General Medicine
Published: 2022
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41. Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries

Author: Russotto V., Myatra S. N., Laffey J. G., Tassistro E., Antolini L., Bauer P., Lascarrou J. B., Szuldrzynski K., Camporota L., Pelosi P., Sorbello M., Higgs A., Greif R., Putensen C., Agvald-Ohman C., Chalkias A., Bokums K., Brewster D., Rossi E., Fumagalli R., Pesenti A., Foti G., Bellani G., Hazem Abdelkarem Ahmed, Neill K J Adhikari, Kehari Agrawal, Nipun Agrawal, Hernan Aguirre-Bermeo, Christina Agvald-Öhman, Meraj Ahmad, Samareh Ajami, Shazia N Akhtar, Adnan Alghamdi, Abdulmueti Alhadi, Syed M Ali, Mohd N Ali, Anita Alias, Ghaleb Almekhlafi, Julio Alonso, Diana Alvarez Montenegro, Rubina Aman, Matthew Anstey, Irene Aragão, Eleni Arnaoutoglou, Elie Azoulay, Laura Baccari, Nishanth Baliga, Ramya Ballekatte Manjunath, Shrirang Bamane, Anna Bandert, Roland Bartholdy, Marta Basto, Vera Baturova, Philippe R Bauer, Agrippino Bellissima, Vladislav Belsky, Prashant Bendre, Annalisa Benini, Sebastien Besset, Mahuya Bhattacharyya, Piotr Bielanski, Luca Bigatello, Florence Boissier, Kristaps Bokums, Elisa Boni, Iwona Bonney, David Bowen, Alexandre Boyer, Luca Brazzi, David Brewster, Lina Broman, Alexander Browne, Cedric Bruel, Yannick Brunin, Guillermo Bugedo, Italo Calamai, Patricia Campos, Federico G Canavosio, Iacopo Cappellini, Marco Cascella, Nuno Catorze, Athanasios Chalkias, Benoit Champigneulle, Juhi Chandwani, Anne Chao, Satish Chaurasia, Rajesh Chawla, Aakanksha Chawla, Olivia Cheetham, Frank Chemouni, Lee Chew Kiok, Jung-Yien Chien, Timothy Chimunda, Ching-Tang Chiu, Fernando Chiumiento, Nai-Kuan Chou, Nicolas Chudeau, Sandra Colica, Gwenhael Colin, Jean-Michel Constantin, Damien Contou, Andrea Cortegiani, Paulo F Costa, Vasco Costa, Andrea Costamagna, Antonella Cotoia, Andrea N Cracchiolo, Petra Crone, Rui P Cunha, Renata Curić Radivojević, Amit Das, Sampat Dash, Gennaro De Pascale, Silvia De Rosa, Lorenzo Del Sorbo, Valentina Della Torre, Barbara Di Caprio, Raffaele Di Fenza, Ida Di Giacinto, Aikaterini Dimitropoulou, Marcel Dudda, Christopher Edmunds, Stefan F Ehrentraut, Nadia El-Fellah, Muhammed Elhadi, Ahmed Elhadi, Patricia Escudero-Acha, Missael Espinoza, Clelia Esposito, Fabrizio Fabretti, Daniel G Fein, Massimo Ferluga, Marco Fernandes, Alexis Ferre, Janet Ferrier, Marek Flaksa, Fernando Flores, Jesus Flores Gonzalez, Xavier E Fonseca Fuentes, Roland Francis, Daniela G Franco, Pawel Franczyk, Jean-Pierre Frat, Mikhail Furman, Maurizio Fusari, Piotr Galkin, Alice Gallo de Moraes, Renato Gammaldi, Maria F García Aguilera, Eugenio Garofalo, Tomasz Gaszynski, Jonathan Gatward, Mohamed Ghula, Angelo Giacomucci, Ilaria Giovannini, Kingsly Gnanadurai, Thomas Godet, Alberto Goffi, Gemma Goma Fernandez, Maria Gonzalez, Daira González, Alejandro González-Castro, Kadarapura N Gopalakrishna, Eric Gottesman, Alexandre Gros, Christophe Guervilly, Christophe Guitton, Manish Gupta, Kulbhusahn Gupta, Tarikul Hamid, Olfa Hamzaoui, Katrin Hannesdottir, Shahnaz Hasan, Mozaffer Hossain, Sazzad Hossein, Sami Hraiech, Chun-Kai Huang, Cameron Hypes, Soad Imhmed Alkhumsi, Motiul Islam, Muhamad A Ismail, Višnja Ivančan, Sophie Jacquier, Bharat Jagiasi, Nikhilesh Jain, Muhamad Fadhil Hadi Jamaluddin, Milosz Jankowski, Deepak Jeswani, Deepti Jeswani, Simant Jha, Laura Jones, Benjamin Jones, Mathieu Jozwiak, Aleksandra Jumić, Oliver Kamp, Ilias Karametos, Alexey Karelov, Panagiotis Katsoulis, David A Kaufman, Shuchi Kaushik, Callum T Kaye, Subba R Kesavarapu, Ala Khaled, Hapiz Khalidah, Akram Khan, Sudhir Khunteta, Detlef Kindgen-Milles, Sara V Korula, Amol Kothekar, Salman S Koul, Ditte Krog, Shih-Chi Ku, Mira Kuellmar, Lu-Cheng Kuo, Swarna D Kuragayala, Aikaterini Kyparissi, Gonzalo Labarca, John G Laffey, Jaya Lalwani, Antonio Landaverde, Jean-Baptiste Lascarrou, Andres Laserna, Chien-Chang Lee, Stephane Legriel, Andrew Lehr, Tiago Leonor, Yongxing Li, Anna Lisa Licciardi, Edward Litton, Vladimir Lomivorotov, Federico Longhini, Claudia L Lopez Nava, Luis R Loza Gallardo, Ramona Lungu, Annalisa Luzi, Wuhua Ma, Marat Magomedov, Alexandros Makris, Harish Mallapura Maheshwarappa, Tommaso Maraffi, Maria E Marcelli, Karim Mariano, Nathalie Marin, Nadezhda Marova, Maelle Martin, Mayra Martinez Gonzalez, Emilio Maseda, Fiore Mastroianni, Marijana Matas, Dubier Matos, Jessica G Maugeri, Mohd Z Mazlan, Melanie Meersch, Ranjan Meher, Tasneem H Mehesry, Maria Meirik, Armand Mekontso Dessap, Kwabena Mensah, Emmanuelle Mercier, Pavel Michalek, Abhirup Midya, Slobodan Mihaljević, Adrien Mirouse, Prasanna Mishra, Ravi Mistry, Mate Moguš, Norbaniza Mohd Nordin, Noryani Mohd Samat, Luca Montini, Giorgia Montrucchio, Valeria Moro, Diego Morocho Tutillo, Jarrod Mosier, Sircar Mrinal, Wojciech Mudyna, Grégoire Muller, Kartik Munta, Satheesh Munusamy, Stefania Musso, Stefano Muttini, Ismail Nahla Irtiza, Evi Nakou, Amit Narkhede, Joseph Nates, Moana R Nespoli, Francesca Nespoli, Artem Nikitenko, Carla Nogueira, Ross O'Grady, Yewande E Odeyemi, Annika Ohlsson, Alberto Orsello, Vijayanand Palaniswamy, Daniela M Palma, Salvatore Palmese, Jesus N Pantoja Leal, Eleni Papandreou, Metaxia Papanikolaou, Matteo Parotto, Mayur Patel, Mario Pavlek, Niccolò Pedrotti, Ngu Pei Hwa, Lorella Pelagalli, Miryam Pérez Ruiz, Elin Persson, Athanasia Petsiou, Angelo Pezzi, Sam Philip, Francois Philippard, Mariusz Piegat, Sébastien Pili-Floury, Riccardo Pinciroli, Marcia Pinto, Gael Piton, Gaetan Plantefeve, Caroline Pouplet, Sofia Pouriki, Andrea Pradella, Kumar Prashant, Christian Putensen, Alice Quayle, Lua Rahmani, Ian Randall, Banambar Ray, Adrian Regli, Syed T Reza, Jean Damien Ricard, Ivano Riva, Oriol Roca, Roberto Rona, Jon Rosell, Rebecca Rowley, Sheng-Yuan Ruan, Kay Rumschuessel, Annalisa Rundo, Pierpaolo Russo, Vincenzo Russotto, Samir Sahu, Gabriele Sales, Charlotte Salmon-Gandonnière, Nandyelly San Juan Roman, Luis Sánchez-Hurtado, Benjamin J Sandefur, Manel Santafe, Lida Santoro, Rhik Sanyal, Lakshmikanthcharan Saravanabavan, Bhagyesh Shah, Mehul Shah, Ming-Hann Shin, Monica Silva, Shannon Simpson, Ayush Sinah, Atul K Singh, Dinesh K Singh, Nitesh Singh, Lalit Singh, Lukasz Skowronski, Miguel A Sosa, Savino Spadaro, Martin Spangfors, Jesper Sperber, Rosario Spina, Anand Srivastava, Andrew Steel, Alejandro Suarez de la Rica, Singh Sujeet Kumar, Omprakash Sundrani, Nilu Sunil, Bharadwaj Suparna, Manimala R Surath, Yadullah Syed, Tamas Szakmany, Benjamin Sztrymf, Alexis Tabah, Stefano Tarantino, Maria Tileli, Hugo Tirape-Castro, Otoniel Toledo-Salinas, Jacopo Tramarin, Dimitrios Tsiftsis, Iva Tucić, Jose A Tutillo León, Lorenzo Tutino, Vijay N Tyagi, Kyriaki Vagdatli, Sneha Varkey, Maria M Vera, Magnus Von Seth, Carl Wahlstrom, Wan Mohd N Wan Hassan, Wan N Wan Ismail, Kuo-Chuan Wang, Hadrien Winiszewski, Jiayan Wu, Lun Wu, Yu-Chang Yeh, Paul Young, Gianluca Zani, Jonathan Zarka, Dawn Zhao, Diane Zlotnik, Russotto, V, Myatra, S, Laffey, J, Tassistro, E, Antolini, L, Bauer, P, Lascarrou, J, Szuldrzynski, K, Camporota, L, Pelosi, P, Sorbello, M, Higgs, A, Greif, R, Putensen, C, Agvald-Öhman, C, Chalkias, A, Bokums, K, Brewster, D, Rossi, E, Fumagalli, R, Pesenti, A, Foti, G, Bellani, G, Russotto V., Myatra S.N., Laffey J.G., Tassistro E., Antolini L., Bauer P., Lascarrou J.B., Szuldrzynski K., Camporota L., Pelosi P., Sorbello M., Higgs A., Greif R., Putensen C., Agvald-Ohman C., Chalkias A., Bokums K., Brewster D., Rossi E., Fumagalli R., Pesenti A., Foti G., Bellani G., and Hazem Abdelkarem Ahmed, Neill K J Adhikari, Kehari Agrawal, Nipun Agrawal, Hernan Aguirre-Bermeo, Christina Agvald-Öhman, Meraj Ahmad, Samareh Ajami, Shazia N Akhtar, Adnan Alghamdi, Abdulmueti Alhadi, Syed M Ali, Mohd N Ali, Anita Alias, Ghaleb Almekhlafi, Julio Alonso, Diana Alvarez Montenegro, Rubina Aman, Matthew Anstey, Irene Aragão, Eleni Arnaoutoglou, Elie Azoulay, Laura Baccari, Nishanth Baliga, Ramya Ballekatte Manjunath, Shrirang Bamane, Anna Bandert, Roland Bartholdy, Marta Basto, Vera Baturova, Philippe R Bauer, Agrippino Bellissima, Vladislav Belsky, Prashant Bendre, Annalisa Benini, Sebastien Besset, Mahuya Bhattacharyya, Piotr Bielanski, Luca Bigatello, Florence Boissier, Kristaps Bokums, Elisa Boni, Iwona Bonney, David Bowen, Alexandre Boyer, Luca Brazzi, David Brewster, Lina Broman, Alexander Browne, Cedric Bruel, Yannick Brunin, Guillermo Bugedo, Italo Calamai, Patricia Campos, Federico G Canavosio, Iacopo Cappellini, Marco Cascella, Nuno Catorze, Athanasios Chalkias, Benoit Champigneulle, Juhi Chandwani, Anne Chao, Satish Chaurasia, Rajesh Chawla, Aakanksha Chawla, Olivia Cheetham, Frank Chemouni, Lee Chew Kiok, Jung-Yien Chien, Timothy Chimunda, Ching-Tang Chiu, Fernando Chiumiento, Nai-Kuan Chou, Nicolas Chudeau, Sandra Colica, Gwenhael Colin, Jean-Michel Constantin, Damien Contou, Andrea Cortegiani, Paulo F Costa, Vasco Costa, Andrea Costamagna, Antonella Cotoia, Andrea N Cracchiolo, Petra Crone, Rui P Cunha, Renata Curić Radivojević, Amit Das, Sampat Dash, Gennaro De Pascale, Silvia De Rosa, Lorenzo Del Sorbo, Valentina Della Torre, Barbara Di Caprio, Raffaele Di Fenza, Ida Di Giacinto, Aikaterini Dimitropoulou, Marcel Dudda, Christopher Edmunds, Stefan F Ehrentraut, Nadia El-Fellah, Muhammed Elhadi, Ahmed Elhadi, Patricia Escudero-Acha, Missael Espinoza, Clelia Esposito, Fabrizio Fabretti, Daniel G Fein, Massimo Ferluga, Marco Fernandes, Alexis Ferre, Janet Ferrier, Marek Flaksa, Fernando Flores, Jesus Flores Gonzalez, Xavier E Fonseca Fuentes, Roland Francis, Daniela G Franco, Pawel Franczyk, Jean-Pierre Frat, Mikhail Furman, Maurizio Fusari, Piotr Galkin, Alice Gallo de Moraes, Renato Gammaldi, Maria F García Aguilera, Eugenio Garofalo, Tomasz Gaszynski, Jonathan Gatward, Mohamed Ghula, Angelo Giacomucci, Ilaria Giovannini, Kingsly Gnanadurai, Thomas Godet, Alberto Goffi, Gemma Goma Fernandez, Maria Gonzalez, Daira González, Alejandro González-Castro, Kadarapura N Gopalakrishna, Eric Gottesman, Alexandre Gros, Christophe Guervilly, Christophe Guitton, Manish Gupta, Kulbhusahn Gupta, Tarikul Hamid, Olfa Hamzaoui, Katrin Hannesdottir, Shahnaz Hasan, Mozaffer Hossain, Sazzad Hossein, Sami Hraiech, Chun-Kai Huang, Cameron Hypes, Soad Imhmed Alkhumsi, Motiul Islam, Muhamad A Ismail, Višnja Ivančan, Sophie Jacquier, Bharat Jagiasi, Nikhilesh Jain, Muhamad Fadhil Hadi Jamaluddin, Milosz Jankowski, Deepak Jeswani, Deepti Jeswani, Simant Jha, Laura Jones, Benjamin Jones, Mathieu Jozwiak, Aleksandra Jumić, Oliver Kamp, Ilias Karametos, Alexey Karelov, Panagiotis Katsoulis, David A Kaufman, Shuchi Kaushik, Callum T Kaye, Subba R Kesavarapu, Ala Khaled, Hapiz Khalidah, Akram Khan, Sudhir Khunteta, Detlef Kindgen-Milles, Sara V Korula, Amol Kothekar, Salman S Koul, Ditte Krog, Shih-Chi Ku, Mira Kuellmar, Lu-Cheng Kuo, Swarna D Kuragayala, Aikaterini Kyparissi, Gonzalo Labarca, John G Laffey, Jaya Lalwani, Antonio Landaverde, Jean-Baptiste Lascarrou, Andres Laserna, Chien-Chang Lee, Stephane Legriel, Andrew Lehr, Tiago Leonor, Yongxing Li, Anna Lisa Licciardi, Edward Litton, Vladimir Lomivorotov, Federico Longhini, Claudia L Lopez Nava, Luis R Loza Gallardo, Ramona Lungu, Annalisa Luzi, Wuhua Ma, Marat Magomedov, Alexandros Makris, Harish Mallapura Maheshwarappa, Tommaso Maraffi, Maria E Marcelli, Karim Mariano, Nathalie Marin, Nadezhda Marova, Maelle Martin, Mayra Martinez Gonzalez, Emilio Maseda, Fiore Mastroianni, Marijana Matas, Dubier Matos, Jessica G Maugeri, Mohd Z Mazlan, Melanie Meersch, Ranjan Meher, Tasneem H Mehesry, Maria Meirik, Armand Mekontso Dessap, Kwabena Mensah, Emmanuelle Mercier, Pavel Michalek, Abhirup Midya, Slobodan Mihaljević, Adrien Mirouse, Prasanna Mishra, Ravi Mistry, Mate Moguš, Norbaniza Mohd Nordin, Noryani Mohd Samat, Luca Montini, Giorgia Montrucchio, Valeria Moro, Diego Morocho Tutillo, Jarrod Mosier, Sircar Mrinal, Wojciech Mudyna, Grégoire Muller, Kartik Munta, Satheesh Munusamy, Stefania Musso, Stefano Muttini, Ismail Nahla Irtiza, Evi Nakou, Amit Narkhede, Joseph Nates, Moana R Nespoli, Francesca Nespoli, Artem Nikitenko, Carla Nogueira, Ross O'Grady, Yewande E Odeyemi, Annika Ohlsson, Alberto Orsello, Vijayanand Palaniswamy, Daniela M Palma, Salvatore Palmese, Jesus N Pantoja Leal, Eleni Papandreou, Metaxia Papanikolaou, Matteo Parotto, Mayur Patel, Mario Pavlek, Niccolò Pedrotti, Ngu Pei Hwa, Lorella Pelagalli, Miryam Pérez Ruiz, Elin Persson, Athanasia Petsiou, Angelo Pezzi, Sam Philip, Francois Philippard, Mariusz Piegat, Sébastien Pili-Floury, Riccardo Pinciroli, Marcia Pinto, Gael Piton, Gaetan Plantefeve, Caroline Pouplet, Sofia Pouriki, Andrea Pradella, Kumar Prashant, Christian Putensen, Alice Quayle, Lua Rahmani, Ian Randall, Banambar Ray, Adrian Regli, Syed T Reza, Jean Damien Ricard, Ivano Riva, Oriol Roca, Roberto Rona, Jon Rosell, Rebecca Rowley, Sheng-Yuan Ruan, Kay Rumschuessel, Annalisa Rundo, Pierpaolo Russo, Vincenzo Russotto, Samir Sahu, Gabriele Sales, Charlotte Salmon-Gandonnière, Nandyelly San Juan Roman, Luis Sánchez-Hurtado, Benjamin J Sandefur, Manel Santafe, Lida Santoro, Rhik Sanyal, Lakshmikanthcharan Saravanabavan, Bhagyesh Shah, Mehul Shah, Ming-Hann Shin, Monica Silva, Shannon Simpson, Ayush Sinah, Atul K Singh, Dinesh K Singh, Nitesh Singh, Lalit Singh, Lukasz Skowronski, Miguel A Sosa, Savino Spadaro, Martin Spangfors, Jesper Sperber, Rosario Spina, Anand Srivastava, Andrew Steel, Alejandro Suarez de la Rica, Singh Sujeet Kumar, Omprakash Sundrani, Nilu Sunil, Bharadwaj Suparna, Manimala R Surath, Yadullah Syed, Tamas Szakmany, Benjamin Sztrymf, Alexis Tabah, Stefano Tarantino, Maria Tileli, Hugo Tirape-Castro, Otoniel Toledo-Salinas, Jacopo Tramarin, Dimitrios Tsiftsis, Iva Tucić, Jose A Tutillo León, Lorenzo Tutino, Vijay N Tyagi, Kyriaki Vagdatli, Sneha Varkey, Maria M Vera, Magnus Von Seth, Carl Wahlstrom, Wan Mohd N Wan Hassan, Wan N Wan Ismail, Kuo-Chuan Wang, Hadrien Winiszewski, Jiayan Wu, Lun Wu, Yu-Chang Yeh, Paul Young, Gianluca Zani, Jonathan Zarka, Dawn Zhao, Diane Zlotnik
Subjects: Male, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, Aged, Female, Heart Arrest, Humans, Hypotension, Hypoxia, Intensive Care Units, Intubation, Intratracheal, Logistic Models, Medical Errors, Middle Aged, Prospective Studies, Respiration, Artificial, Respiratory Insufficiency, Vasoconstrictor Agents, 01 natural sciences, NO, tracheal intubation, adverse peri-intubation events, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Medicine, Intubation, Intubation, Critical Care, 030212 general & internal medicine, 0101 mathematics, 610 Medicine & health, Prospective cohort study, business.industry, Respiration, 010102 general mathematics, Tracheal intubation, General Medicine, Intratracheal, Intubation procedure, Respiratory failure, Artificial, Emergency medicine, Airway management, business
Abstract: Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation
Published: 2021

42. Vascular Adhesion Protein-1 Is Associated With Acute Kidney Injury in High-Risk Patients After Cardiac Surgery

Author: Eike Bormann, Ronny W. Renfurm, Melanie Meersch, Andreas Margraf, Mira Küllmar, and Alexander Zarbock
Subjects: Male, medicine.medical_specialty, Time Factors, Urology, Vascular Cell Adhesion Molecule-1, Adhesion (medicine), Risk Assessment, law.invention, chemistry.chemical_compound, Risk Factors, law, Cardiopulmonary bypass, Humans, Medicine, Prospective Studies, Cardiac Surgical Procedures, Aged, Randomized Controlled Trials as Topic, Creatinine, Cardiopulmonary Bypass, business.industry, Acute kidney injury, Acute Kidney Injury, Middle Aged, medicine.disease, Up-Regulation, Cardiac surgery, Treatment Outcome, Anesthesiology and Pain Medicine, chemistry, Ischemic preconditioning, Female, business, Complication, Biomarkers, Kidney disease
Abstract: Acute kidney injury is a common complication after cardiac surgery, with a high impact on morbidity and mortality. Vascular adhesion protein-1 is involved in inflammation, which, in turn, is part of the development of acute kidney injury after cardiac surgery.In this ancillary study to the RENal effects of Remote Ischemic Preconditioning in cardiac surgery trial, we investigated whether vascular adhesion protein-1 might be associated with the development of acute kidney injury in high-risk patients after cardiac surgery. In total, 114 patients were included in this data set. Acute kidney injury was defined by the Kidney Disease: Improving Global Outcomes criteria serum creatinine and/or urine output. Vascular adhesion protein-1 concentrations were measured at baseline (before surgery), 4 hours, and 12 hours after cardiopulmonary bypass.Vascular adhesion protein-1 levels at 12 hours were significantly higher in patients with acute kidney injury (no acute kidney injury, 271 ng/mL [Q1, Q3, 179, 364 ng/mL] versus acute kidney injury, 384 ng/mL [Q1, Q3, 311, 478 ng/mL]; P.001). Moreover, patients developing acute kidney injury had higher differences in vascular adhesion protein-1 levels between 12 hours and baseline (P.001) and between 12 and 4 hours (P.001) after cardiopulmonary bypass. At a cut point difference value of 99 ng/mL (95% CI, 63-133) between 12 hours and baseline, patients with differences99 ng/mL showed a higher occurrence rate of acute kidney injury (acute kidney injury, 78.6% versus no acute kidney injury, 31.5%; P.001). Receiver-operating characteristic curve analyses demonstrated best performance for vascular adhesion protein-1 levels at 12 hours for acute kidney injury within 72 hours after surgery, especially in the subgroup of patients with chronic kidney disease (area under the receiver-operating characteristic curve, 0.78; P.001).Vascular adhesion protein-1 is elevated in patients developing acute kidney injury assuming that vascular adhesion protein-1 plays a crucial role in the development of acute kidney injury in high-risk patients after cardiac surgery.
Published: 2019
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43. In Response

Author: Alexander Zarbock, Khaschayar Saadat-Gilani, and Melanie Meersch
Subjects: Anesthesiology and Pain Medicine
Published: 2021

44. Acute Kidney Injury in Cardiac Surgery

Author: Melanie Meersch, Alexander Zarbock, and Christina Massoth
Subjects: medicine.medical_specialty, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, law, Risk Factors, medicine, Global health, Cardiopulmonary bypass, Humans, Dexmedetomidine, Cardiac Surgical Procedures, Intensive care medicine, business.industry, Incidence (epidemiology), Incidence, Acute kidney injury, 030208 emergency & critical care medicine, General Medicine, Perioperative, Acute Kidney Injury, medicine.disease, 3. Good health, Cardiac surgery, 030228 respiratory system, business, Kidney disease, medicine.drug
Abstract: Acute kidney injury (AKI) occurs frequently after cardiac surgery and is associated with high morbidity and mortality. Although the number of cardiac surgical procedures is constantly growing worldwide, incidence of cardiac surgery-associated AKI is still around 40% and has a significant impact on global health care costs. Numerous trials attempted to identify strategies to prevent AKI and attenuate its detrimental consequences. Effective options remained elusive. Current evidence supports a multimodal risk-stratification approach with biomarker-guided management of high-risk patients, perioperative administration of dexmedetomidine, and implementation of a care bundle as recommended by the Kidney Disease: Improving Global Outcomes group.
Published: 2021

45. [Impact of handover of anesthesia care on adverse postoperative outcomes-The HandiCAP trial]

Author: Christina, Massoth, Khaschayar, Saadat-Gilani, and Melanie, Meersch
Subjects: Anesthesiology, Patient Handoff, Humans, Anesthesia, Postoperative Period
Published: 2021

46. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery.

Author: Melanie Meersch, Christoph Schmidt, Hugo Van Aken, Sven Martens, Jan Rossaint, Kai Singbartl, Dennis Görlich, John A Kellum, and Alexander Zarbock
Subjects: Medicine, Science
Abstract: BACKGROUND: Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients. METHODS: We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge. RESULTS: 26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1-3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery. CONCLUSIONS: Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery. CLINICAL TRIAL REGISTRATION INFORMATION: www.germanctr.de/, DRKS-ID: DRKS00005062.
Published: 2014
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47. Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery.

Author: Melanie Meersch, Christoph Schmidt, Hugo Van Aken, Jan Rossaint, Dennis Görlich, Dirk Stege, Edward Malec, Katarzyna Januszewska, and Alexander Zarbock
Subjects: Medicine, Science
Abstract: The lack of early biomarkers for acute kidney injury (AKI) seriously inhibits the initiation of preventive and therapeutic measures for this syndrome in a timely manner. We tested the hypothesis that insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, function as early biomarkers for AKI after congenital heart surgery with cardiopulmonary bypass (CPB).We prospectively studied 51 children undergoing cardiac surgery with CPB. Serial urine samples were analyzed for [TIMP-2]•[IGFBP7]. The primary outcome measure was AKI defined by the pRIFLE criteria within 72 hours after surgery.12 children (24%) developed AKI within 1.67 (SE 0.3) days after surgery. Children who developed AKI after cardiac surgery had a significant higher urinary [TIMP-2]•[IGFBP7] as early as 4 h after the procedure, compared to children who did not develop AKI (mean of 1.93 ((ng/ml)²/1000) (SE 0.4) vs 0.47 ((ng/ml)²/1000) (SE 0.1), respectively; p
Published: 2014
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48. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Author: François-Xavier Lescure, Hitoshi Honda, Robert A Fowler, Jennifer Sloane Lazar, Genming Shi, Peter Wung, Naimish Patel, Owen Hagino, Ignacio J. Bazzalo, Marcelo M. Casas, Sebastián A. Nuñez, Yael Pere, Carlos M. Ibarrola, Marco A. Solis Aramayo, Maria C. Cuesta, Andrea E. Duarte, Pablo M. Gutierrez Fernandez, Maria A. Iannantuono, Erica A. Miyazaki, Javier P. Silvio, Dario G. Scublinsky, Alessandra Bales, Daniela Catarino, Elie Fiss, Sara Mohrbacher, Victor Sato, Antonio Baylao, Adilson Cavalcante, Francini Correa, Celso A. de Andrade, Juvencio Furtado, Nelson Ribeiro Filho, Valéria Telles, Leopoldo T. Trevelin, Ricardo Vipich, Rodrigo Boldo, Paula Borges, Suzana Lobo, Graziela Luckemeyer, Luana Machado, Maysa B. Alves, Ana C. Iglessias, Marianna M. Lago, Daniel W. Santos, Hugo Chapdelaine, Emilia L. Falcone, Rahima Jamal, Me-Linh Luong, Madeleine Durand, Stephane Doucet, François-Martin Carrier, Bryan A. Coburn, Lorenzo Del Sorbo, Sharon L. Walmsley, Sara Belga, Luke Y. Chen, Allison D. Mah, Theodore Steiner, Alissa J. Wright, J. Hajek, Neill Adhikari, Robert A. Fowler, Nick Daneman, Kosar A. Khwaja, Jason Shahin, Carolina Gonzalez, Rafael Silva, Marcelo Lindh, Gabriel Maluenda, Patricia Fernandez, Maite Oyonarte, Martin Lasso, Alexandre Boyer, Didier Bronnimann, Hoang-Nam Bui, Charles Cazanave, Helene Chaussade, Arnaud Desclaux, Mailys Ducours, Alexandre Duvignaud, Denis Malvy, Lisa Martin, Didier Neau, Duc Nguyen, Thierry Pistone, Gaetane Soubrane-Wirth, Julie Leitao, Clotilde Allavena, Charlotte Biron, Sabelline Bouchez, Benjamin Gaborit, Antoine Gregoire, Paul Le Turnier, Anne-Sophie Lecompte, Raphael Lecomte, Maeva Lefebvre, Francois Raffi, David Boutoille, Pascale H. Morineau, Romain Guéry, Emmanuel Chatelus, Nathalie Dumoussaud, Renaud Felten, Florina Luca, Bernard Goichot, Francis Schneider, Marie-Caroline Taquet, Matthieu Groh, Mathilde Roumier, Mathilde Neuville, Antoine Bachelard, Valentina Isernia, F-Xavier Lescure, Bao-Chau Phung, Anne Rachline, Aurelie Sautereau, Dorothee Vallois, Yves Bleher, Delphine Boucher, Clémentine Coudon, Jean Esnault, Thomas Guimard, Sophie Leautez-Nainville, Dominique Merrien, Marine Morrier, Pauline Motte-Vincent, Romain Gabeff, Hélène Leclerc, Céline Cozic, Romain Decours, Ronan Février, Gwenhael Colin, Sophie Abgrall, Dorothee Vignes, Raluca Sterpu, Mira Kuellmar, Melanie Meersch-Dini, Raphael Weiss, Alexander Zarbock, Christiane Antony, Marc Berger, Thorsten Brenner, Christian Taube, Frank Herbstreit, Sebastian Dolff, Margarethe Konik, Karsten Schmidt, Markus Zettler, Oliver Witzke, Boris Boell, Jorge Garcia Borrega, Philipp Koehler, Thomas Zander, Fabian Dusse, Othman Al-Sawaf, Philipp Köhler, Dennis Eichenauer, Matthias Kochanek, Alexander Shimabukuro-Vornhagen, Sibylle Mellinghoff, Annika Claßen, Jan-Michel Heger, Charlotte Meyer-Schwickerath, Paul Liedgens, Katrin Heindel, Ana Belkin, Asaf Biber, Mayan Gilboa, Itzchak Levy, Vladislav Litachevsky, Galia Rahav, Anat Finesod Wiedner, Tal Zilberman-Daniels, Yonatan Oster, Jacob Strahilevitz, Sigal Sviri, Elena M. Baldissera, Corrado Campochiaro, Giulio Cavalli, Lorenzo Dagna, Giacomo De Luca, Emanuel Della Torre, Alessandro Tomelleri, Davide Bernasconi De Luca, Amedeo F. Capetti, Massimo Coen, Maria V. Cossu, Massimo Galli, Andrea Giacomelli, Guido A. Gubertini, Stefano Rusconi, Giulia J. Burastero, Margherita Digaetano, Giovanni Guaraldi, Marianna Meschiari, Cristina Mussini, Cinzia Puzzolante, Sara Volpi, Marina Aiello, Alarico Ariani, Alfredo A. Chetta, Annalisa Frizzelli, Andrea Ticinesi, Domenico Tuttolomondo, Stefano Aliberti, Francesco B. Blasi, Marta F. Di Pasquale, Sofia Misuraca, Tommaso Pilocane, Edoardo Simonetta, Alessio M. Aghelmo, Claudio Angelini, Enrico Brunetta, Giorgio W. Canonica, Michele Ciccarelli, Sara Dal Farra, Maria De Santis, Sebastian Ferri, Marco Folci, Giacomo M. Guidelli, Enrico M. Heffler, Ferdinando Loiacono, Giacomo Malipiero, Giovanni Paoletti, Rosa Pedale, Francesca A. Puggioni, Francesca Racca, Aurora Zumbo, Morihiko Satou, Tatyana Lisun, Denis Protsenko, Nikolay Rubtsov, Irina Beloglazova, Daria Fomina, Mariana Lysenko, Sofia Serdotetskova, Vitali Firstov, Ivan Gordeev, Ilia Kokorin, Ksenia Komissarova, Nina Lapochkina, Elena Luchinkina, Valentin Malimon, Sevinch Mamedguseyinova, Ksenia Polubatonova, Natalia Suvorova, Jose Arribas, Alberto M. Borobia Perez, Fernando de la Calle Prieto, Juan Carlos Figueira, Rocio Motejano Sanchez, Marta Mora-Rillo, Concepcion Prados Sanchez, Javier Queiruga Parada, Francisco Fernandez Arnalich, Maria Guerro Barrientos, Alejandro Bendala Estrada, Aranzazu Caballero Marcos, Maria E. Garcia Leoni, Rita García-Martínez, Ana María Collado, Patricia Munoz Garcia, Ana Torres do Rego, María V. Villalba García, Almudena Burrillo, Maricela Valerio Minero, Paloma Gijon Vidaurreta, Sonsoles Infante Herrero, Elena Velilla, Marina Machado, Maria Olmedo, Blanca Pinilla, Benito Almirante Gragera, Maria de la Esperanza Cañas Ruano, Sofia Contreras Medina, Alejandro Cortés Herrera, Vicenç Falcó Ferrer, Ricard Ferrer Roca, Xavier Nuvials Casals, Esteve Ribera Pascuet, Paula Suanzes Diez, Pedro Rebollo Castro, Felipe Garcia Alcaide, Alejandro Soriano, Aina Oliver Caldes, Ana González Cordón, Celia Cardozo, Lorena De la Mora Cañizo, Romina Pena López, Sandra Chamorro, Clara Crespillo-Andujar, Rosa Escudero Sanchez, Jesús Fortún-Abete, Begoña Monge-Maillo, Ana Moreno Zamora, Francesca Norman, Matilde Sanchez Conde, Sergio Serrano Villar, Pilar Vizcarra, Lescure, F. -X., Honda, H., Fowler, R. A., Lazar, J. S., Shi, G., Wung, P., Patel, N., Hagino, O., Bazzalo, I. J., Casas, M. M., Nunez, S. A., Pere, Y., Ibarrola, C. M., Solis Aramayo, M. A., Cuesta, M. C., Duarte, A. E., Gutierrez Fernandez, P. M., Iannantuono, M. A., Miyazaki, E. A., Silvio, J. P., Scublinsky, D. G., Bales, A., Catarino, D., Fiss, E., Mohrbacher, S., Sato, V., Baylao, A., Cavalcante, A., Correa, F., de Andrade, C. A., Furtado, J., Ribeiro Filho, N., Telles, V., Trevelin, L. T., Vipich, R., Boldo, R., Borges, P., Lobo, S., Luckemeyer, G., Machado, L., Alves, M. B., Iglessias, A. C., Lago, M. M., Santos, D. W., Chapdelaine, H., Falcone, E. L., Jamal, R., Luong, M. -L., Durand, M., Doucet, S., Carrier, F. -M., Coburn, B. A., Del Sorbo, L., Walmsley, S. L., Belga, S., Chen, L. Y., Mah, A. D., Steiner, T., Wright, A. J., Hajek, J., Adhikari, N., Daneman, N., Khwaja, K. A., Shahin, J., Gonzalez, C., Silva, R., Lindh, M., Maluenda, G., Fernandez, P., Oyonarte, M., Lasso, M., Boyer, A., Bronnimann, D., Bui, H. -N., Cazanave, C., Chaussade, H., Desclaux, A., Ducours, M., Duvignaud, A., Malvy, D., Martin, L., Neau, D., Nguyen, D., Pistone, T., Soubrane-Wirth, G., Leitao, J., Allavena, C., Biron, C., Bouchez, S., Gaborit, B., Gregoire, A., Le Turnier, P., Lecompte, A. -S., Lecomte, R., Lefebvre, M., Raffi, F., Boutoille, D., Morineau, P. H., Guery, R., Chatelus, E., Dumoussaud, N., Felten, R., Luca, F., Goichot, B., Schneider, F., Taquet, M. -C., Groh, M., Roumier, M., Neuville, M., Bachelard, A., Isernia, V., Phung, B. -C., Rachline, A., Sautereau, A., Vallois, D., Bleher, Y., Boucher, D., Coudon, C., Esnault, J., Guimard, T., Leautez-Nainville, S., Merrien, D., Morrier, M., Motte-Vincent, P., Gabeff, R., Leclerc, H., Cozic, C., Decours, R., Fevrier, R., Colin, G., Abgrall, S., Vignes, D., Sterpu, R., Kuellmar, M., Meersch-Dini, M., Weiss, R., Zarbock, A., Antony, C., Berger, M., Brenner, T., Taube, C., Herbstreit, F., Dolff, S., Konik, M., Schmidt, K., Zettler, M., Witzke, O., Boell, B., Garcia Borrega, J., Koehler, P., Zander, T., Dusse, F., Al-Sawaf, O., Kohler, P., Eichenauer, D., Kochanek, M., Shimabukuro-Vornhagen, A., Mellinghoff, S., Classen, A., Heger, J. -M., Meyer-Schwickerath, C., Liedgens, P., Heindel, K., Belkin, A., Biber, A., Gilboa, M., Levy, I., Litachevsky, V., Rahav, G., Finesod Wiedner, A., Zilberman-Daniels, T., Oster, Y., Strahilevitz, J., Sviri, S., Baldissera, E. M., Campochiaro, C., Cavalli, G., Dagna, L., De Luca, Giacomo., Della Torre, E., Tomelleri, A., Bernasconi De Luca, D., Capetti, A. F., Coen, M., Cossu, M. V., Galli, M., Giacomelli, A., Gubertini, G. A., Rusconi, S., Burastero, G. J., Digaetano, M., Guaraldi, G., Meschiari, M., Mussini, C., Puzzolante, C., Volpi, S., Aiello, M., Ariani, A., Chetta, A. A., Frizzelli, A., Ticinesi, A., Tuttolomondo, D., Aliberti, S., Blasi, F. B., Di Pasquale, M. F., Misuraca, S., Pilocane, T., Simonetta, E., Aghelmo, A. M., Angelini, C., Brunetta, E., Canonica, G. W., Ciccarelli, M., Dal Farra, S., De Santis, M., Ferri, S., Folci, M., Guidelli, G. M., Heffler, E. M., Loiacono, F., Malipiero, G., Paoletti, G., Pedale, R., Puggioni, F. A., Racca, F., Zumbo, A., Satou, M., Lisun, T., Protsenko, D., Rubtsov, N., Beloglazova, I., Fomina, D., Lysenko, M., Serdotetskova, S., Firstov, V., Gordeev, I., Kokorin, I., Komissarova, K., Lapochkina, N., Luchinkina, E., Malimon, V., Mamedguseyinova, S., Polubatonova, K., Suvorova, N., Arribas, J., Borobia Perez, A. M., de la Calle Prieto, F., Figueira, J. C., Motejano Sanchez, R., Mora-Rillo, M., Prados Sanchez, C., Queiruga Parada, J., Fernandez Arnalich, F., Guerro Barrientos, M., Bendala Estrada, A., Caballero Marcos, A., Garcia Leoni, M. E., Garcia-Martinez, R., Collado, A. M., Munoz Garcia, P., Torres do Rego, A., Villalba Garcia, M. V., Burrillo, A., Valerio Minero, M., Gijon Vidaurreta, P., Infante Herrero, S., Velilla, E., Machado, M., Olmedo, M., Pinilla, B., Almirante Gragera, B., Canas Ruano, M. D. L. E., Contreras Medina, S., Cortes Herrera, A., Falco Ferrer, V., Ferrer Roca, R., Nuvials Casals, X., Ribera Pascuet, E., Suanzes Diez, P., Rebollo Castro, P., Garcia Alcaide, F., Soriano, A., Oliver Caldes, A., Gonzalez Cordon, A., Cardozo, C., De la Mora Canizo, L., Pena Lopez, R., Chamorro, S., Crespillo-Andujar, C., Escudero Sanchez, R., Fortun-Abete, J., Monge-Maillo, B., Moreno Zamora, A., Norman, F., Sanchez Conde, M., Serrano Villar, S., and Vizcarra, P.
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, International Cooperation, Population, Antibodies, Monoclonal, Humanized, Placebo, Severity of Illness Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Intensive care, Severity of illness, medicine, Clinical endpoint, Humans, Immunologic Factors, 030212 general & internal medicine, Mortality, education, Respiratory Distress Syndrome, education.field_of_study, Dose-Response Relationship, Drug, SARS-CoV-2, business.industry, Hazard ratio, COVID-19, Articles, Middle Aged, Receptors, Interleukin-6, Sarilumab, Treatment Outcome, 030228 respiratory system, Female, Drug Monitoring, Cytokine Release Syndrome, business
Abstract: Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.
Published: 2021

49. EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): study protocol for a multicentre, observational trial

Author: Weiss, Raphael, Saadat-Gilani, Khaschayar, Kerschke, Laura, Wempe, Carola, Meersch, Melanie, Zarbock, Alexander Hichem Makhloufi, Anis, Cherak, Lamine Lakhel Ghanem, Zohier, Gouaglia, Dina Nasrine Guadouri, Fayrouz Naouel Hama, Mustafa, Kara, Omayma, Saadi, Rachida, Sakhraoui, Fadila, Bourou, Abdelhadi, Cherifi, Rahmoune Ghania Sadaoui, Amel, Ouyahia, Ilhem, Ouahab, Souad, Bouaoud, Meriem, Abdoun, Anisse, Tidjane, Benali, Tabeti, Nabil, Boudjenan-Serradj, Carlos Jose Pérez Rivera, Paulo, Cabrer, Julián, Corso, Juan Pablo García, Sharon, Idarraga, Christopher, Montoya, Rafael, Figueroa, Eduar, Aldana, María Alejandra Torrado, Peng, Ke, Zheng-Min, Ma, Yu-Fan, Yang, Ya-Juan, Zhu, Peter, Sklienka, Michal, Frelich, Vojtech, Jarkulis, Pavel, Sevcik, Vojtech, Vodicka, Mohamed Gamal Elbahnasawy, Shady, Elsalhawy, Sara, Motawea, Zeinab, Othman, Mohamed, Sahma, Ahmed Mahmoud Nafea, Nermin, Ahmed, Doaa Ali Attia, Moataz Maher Emara, Mohamed Mamdouh Bonna, Mohamed Ahmed Gabr, Amany Ismail Tarbay, Ibrahim Abdelmonaem Abdehaleem, Esraa Elsayed Mohamed, Amr Mahmoud Eldeeb, Ahmed Mohamed Abbas, John Ashraf Magdy, Zyad Hassan Hamed, Hany Mostafa Esmaeil Osman, Mostafa Samy Abbas, Oliver, Joannes-Boyau, Nicolas, Barraud, Corentin, Berthelot, Thibault, Camus, Anissa, Dahmi, Mylène, Defaye, Sébastien, Derville, Younes, El-Boustani, Elsa, Deloge, Hélène, Jacob, Simon, Monziols, Fred, Priem, Jean-Jacques, Robin, Vincent, Legros, Therry, Floch, Salvatore, Muccio, Claire, Geneve, Marie Lim Legouge, Stéphanie Tao Mauny, Willy, Mfam, Léa, Pascot, Christophe, Aveline, Mireille, Chartier, Benjamin, Duteurtre, Jean Francois Gautier, Aidren Le Cousin, Pierre, Vautier, Julien, Nadaud, Nathalie, Begel, Claire-Annissa, Chekirine, Vincent, Derlon, Elodie, Grein, Marie-Annick, Lehair, Laurent, Magazzeni, Philippe, Magazzeni, Carsten, Potter, Catherine, Roth, Florence, Voivret, Thomas, Rimmelé, Valérie, Cerro, Stéphanie, Suria, Jamil, Elmawieh, Annabelle, Stoclin, Cédric, Cirenei, Gregoire, Andrieu, Sven, Couloumy, Jeremy, Falcone, Marion, Fajardy, Arsène, Gagneuil, Emeline, Girardet, Agnès, Mazereeuw, Sébastien, Ponsonnard, Pierre-Yves, Egreteau, Mélanie, Bertel, Simon, Bocher, Vanessa, Carn, Lenaïg Le Guen, Guillaume Le Loup, Montaine, Lefevre, Carole, Ichai, Amanita, Diop, Vanessa, Jean-Michel, Sylvie, Devlieger, Juliette, Duthoit, Mohamed El Kadiri, Maxime, Léger, Viviane, Cassisa, Sigismond, Lasocki, Charline, Masson, Emmanuel, Rineau, Pierre, Verrier, Axel, Coquerel, Philippe, Montravers, Enora, Atchade, Charles-Edouard, Rochon, Céline, Delerue, Vidal, Quentin, Vanessa, Latry, Nina, Queixalos, Vincent, Cottenceau, Thierry, Braun, Saad, Bouzoubaa, Basile, Christ, Audrey, Geiger, Joachim, Gomille, Vianney, Kieffer, Simone, Mangeant, Christelle, Prochilo, Christian, Schmitt, Stefan, Skwirba, Hubert, Grand, Frédérique, Boury, Nicolas, Mayeur, Marie, Pasquie, Pierre, Garçon, Vincent, Bruckert, Vincent, Arnould, Mona, Bonciu, Thibault, Chapelle, Luc, Facchino, Florence, Fagot-Gandet, Andrea, Iachim, Elena, Mannu, Olivier, Perus, Rémi, Plattier, Romain, Rozier, Gaël, Pradel, Michel, Boudinaud, Marie-Hélène, Hausermann, My Hue Nguyen, Andersen, Ramorasata, Amélie, Barreau, Anne-Hélène, Boivin, Céline, Ravry, Nicolas, Mottard, Johanne, Beuvelot, Florence Prunier Bossion, Olivier, Desebbe, Alexander, Zarbock, Christian, Dörr, Thilo Caspar von Groote, Mira, Küllmar, Christina, Massoth, Melanie, Meersch, Khaschayar, Saadat-Gilani, Raphael, Weiss, Carola, Wempe, Sebastian, Ziemann, Linda, Grüßer, Ana, Kowark, Pia, Wittig, Timo, Brandenburger, Thomas, Dimski, Niklas, Döhmen, Laura, Huthmann, Daniela, Kaierle, Claude, Pelletier, Manon, Schleß, Andreas, Hohn, Sebastian, Cleophas, Stephanie, Haunhorst, Marina, Jansen, Alexandra, Schmitt, Julia, Soisch, Kilian, Sturm, Peter, Rosenberger, Alexander, Bendig, Lena, Flohr, Helene, Häberle, Pascal, Hofmann, Jonathan, Kuhle, Nora Michaela Leser, Kathrin, Pfister, Stefanie, Prohaska, Franziska, Sennholz, Lena, Stetz, Kathrin, Weber, Sebastian, Stehr, Stephan, Klaus, Marco, Sadlo, Matthias, Boschin, Christian, Sengelhoff, Ulrich Michael Göbel, Jan Gerrit Haaker, Carina-Kristin, Göttker, Matthias, Gründel, Matthias, Heringlake, Romina, Baumgärtel, Astrid, Berggren, Madeleine, Gülzow, Lennart, Muras, Hauke, Paarmann, Serge, Thal, Alexander, Bentley, Dschamil, El-Masri, Anne, Sebastiani, Eleni, Arnaoutoglou, Maria, Ntalouka, Paula, Stratigopoulou, Anastasia, Analytis, Efthymios, Mavrommatis, Petros, Tzimas, Agathi, Karakosta, Danai, Pantazi, Antonia, Dimakopoulou, Katerina, Dimitropoulou, Orestis, Ioannidis, Humam, Jalaawiy, Aeshah, Anwar, Hashim Talib Hashim, Hogir Imad Rasheed Aldawoody, Andrea, Cortegiani, Giulia, Catalisano, Gilia, Ingoglia, Mariachiara, Ippolito, De Rosa, Silvia, Lucia, Cattin, Andrea, Bianchin, Marisa, Barone, Gianluca, Paternoster, Salvatore Lucio Cutuli, Andrea, Russo, Liliana, Sollazzi, Laura, Cascarano, Massimo, Antonelli, Paola, Aceto, Bruno, Romanò, Savino, Spadaro, Vincenzo Francesco Tripodi, Michele, Rossi, Rosamaria, Scappatura, Maria Cristina Vadalà, Diego, Fiume, Maria Teresa Strano, Giulia, Oddo, Clemente, Santorsola, Bilal Abu Hussain, Adnan Raed Alnaser, Anas Hassouneh Ghassan, Khaled, Hasanein, Mohammed, Theab, Seokyung, Shin, Seungho, Jung, Kyuho, Lee, Sung Mee Jung, Jongyoon, Baek, Muhammed, K Elhadi, Issa, Abuzeid, Mohammed, Albaraesi, Sarah, Aldressi, Wegdan, Khalel, Eman, Abdulwahed, Akram Abdulhamid Ashur Abujrad, Amer, Almaghrabi, Muhand Mohammed Alteleeb, Entisar Ahmed Ali Alshareea, Marwa Isa Biala, Abdulqudus, Deeknah, Dooua Ali Gheddim, Reem, Ghmagh, Nawras Salih Ali AbuIkhrays, Marwa, Sinan, Enas, Soula, Sumayyah Ghayth Bahroun, Khawla, Derwish, Aya Munir Mohamed, Eman Sayed Younes, Rayet Al Islam Benjouira, Mohamed, Aliwa, Najwa Abdullah Altashani, Mohammed Omar Alteb, Ahmed, Msherghi, Fatima, Alagelli, Sufyan, Albarouni, Ahmed, Albishti, Sarah, Aljamal, Mohamed, Alsori, Taha, Ekhuja, Suha, Elzwai, Mohammed, Ghula, Tahani, Mustafa, Ahmed, Tuwaib, Haifa, Zriba, Hamza Mahmoud Agilla, Toky Andriamahefa Rafanomezantsoa, Anne Marie Camilleri Podesta, Denise Mifsud Bonnici, Tiziana, Pirotta, Gilberto Adrián Gasca López, Maja Mojsova Mijovska, Tatjana, Davitkovska, Aleksandra, Gavrilovska, Sanja, Lukikj, Marija, Vesova, Dina, Zafirova, Sarah, Amro, Baraa N, F Hajjaj, Muawia, Alkhazendar, Yousuf, Barakat, Sewar Abdulaziz Elejla, Ahmed, Elhissi, Ahmed, Khader, Ali, Salem, Rita de Freitas Regufe, André Filipe de Oliveira Eloy, Lisbete Marisa Neto Cordeiro Perdigão, Evgeny, Grigoriev, Artem, Ivkin, Roman, Kornelyuk, Michael, Yaroustovsky, Marina, Abramyan, Ekaterina, Komardina, Nataliya, Lesteva, Medina, Aybazova, Elmira, Kumykova, Svetlana, Lesina, Gennady, Rybakov, Alexey, Shestov, Abdulnaser Ahmad Ahmad Barmou, Bushra Lotfi Altayeb Ahmed, Aisha Mohammad Eliyas, Yousra, Emadeldin, Alexander, Kaserer, Clara, Castellucci, Julian, Rössler, Samira, Akbas, Andreja Möller Petrun, Irena, Gregorcic, Vesna, Sok, Roman, Čičak, Elizabeth, Bárcena, Antonio, Guisado, Ismail, Wi, Javier Ripollés Melchor, Ángel, Becerra-Bolaños, Sergio, Cabrera-Doreste, Ancor, Domínguez-Arbelo, María Candelaria Delgado-Alonso, Virginia, Muiño-Palomar, Aurelio, Rodríguez-Pérez, Javier Mata Estévez, Maria Begona Covas Munoz, Juan Mulet Matas, Sara Perez Palao, Maria Dolores Mira Quirós, Alisia Cezara Teslev, Mercedes Garcia Alvarez, Marga, Argilaga, María, Campos, Albert, Bainac, Astrid, Batalla, Marta, Giné, Gracia, Herránz, Ignacio, Hinojal, Margarita Logroño Ejea, Noelia de la Rosa Ruiz, María Gastaca Abasolo, Carla Rosario Houhton Acuna, Ibai Iriarte Zaranton, Ana, Mendigurenmurua, María José Munoz Sanz, Erika Olea de la Fuente, María Pilar Pérez Vaquero, Ana Soto Iglesias, Ana Ugarte Mieres, Alaitz Urtiaga Urrestizala, Lourdes, Ferreira, Félix, Lobato, Marta Aguado Sevilla, Andres, Erazo, Pere, Miró, Sergi, Sabaté, Diana, Vernetta, Berta Castellano Paulis, Anabel Adell Perez, Marta Aseguinolaza Pagola, Elena delVal Peciña, Ainhoa Garmendia Odriozola, Amaia Lopetegi Aizpurua, Olatz Pavón Piquer, Pilar Plou Garcia, Paula Ortega Rezola, Antia Osorio Lopez, Isabel de la Calle Gil, Rosalía Navarro Casado, Peter, Adamove, Roser Bayona Domenge, Francho Miguel Blasco Blasco, Adriana Alexandra Rueda Villamizar, Maria Antonia Perelló Llaneras, Jose Ignacio García-Sánchez, Laura Fernandez Téllez, Sara García Zamorano, Natalia Gijón Herreros, Andrea Rodriguez Esteve, Pablo Monedero Rodríguez, Isabel García Trigo, Agustín, Alcaraz, Andrea Lara Jiménez, Iñigo, Rubio, Nuria, García, Raquel, Callejas, Angel Manuel Candela Toha, Eli, Claros, Pilar, Cobeta, Pascual, Crespo, Trini, Dorado, Elena, Elías, Javier, Felices, Diego, Gil, María, Gómez, Nuria, Mané, María, Martín, Adolfo, Martínez, Lucía, Pereira, Alberto Balvis Noemí Samaranch, Ana, Serrano, Carlos, Tiscar, Judith, Villahoz, Patricia Galán Menéndez, Elena, Cardona, Anna, Conesa, Veronica, Estepa, Patricia, Galán, Laura Llinares Espí, Yuri Loaiza Aldeán, Susana, Manrique, Víctor Morales Ariza, Laura Villarino Villa, Elfayadh Saidahmed Mohamed Amed Suliman, Hytham, Hamid, Ahmed Mohamed Ibrahim, Modather Mohamed Saeed, Orhan Sungur Mukadder, Demet, Altun, Nur, Canbolat, Müşerref Beril Dinçer, Tulay Özkan Seyhan, Serap Aktaş Yıldırım, Müzeyyen, İyigün, Davut, Yapıcı, Levent, Özdemir, Aslinur, Sagun, Neval, Boztug, Yesim, Cetintas, Bora, Dinc, Emel, Gündüz, Hakkı, Ünlügenç, Demet Lafli Tunay, Deniz, Karakaya, Burhan, Dost, Ozgur, Komurcu, Özlem Korkmaz Dilmen, Eren Fatma Akcil, Yusuf, Tunali, Gülay, Ok, Eda Tok Alsina, Özge, Hakli, Cengiz, Polat, Namigar, Turgut, Nurcan, Kızılcık, Özge, Köner, Öznur, Şen, Nurdan, Aydin, Burcu, Basaran, Emre Sertac Bingul, Yavuz, Gürkan, Kamil, Darcin, Semra, Ugur, Kemal Tolga Saracoglu, Asli, Demir, Özgök, Aysegül, Eda, Balci, Behic, Girgin, Aygun, Guler, Ümit, Karadeniz, Nihal, Özaslan, Yigit Özay Hülya, Namik, Ozcan, Aysun, Postaci, Mehmet, Sahap, Nevriye, Salman, Özlem, Sağır, Bulent, Atik, Murat, Bicakcioglu, Hafize Fisun Demir, Ugün, Fatih, Nazan, Kocaoglu, Hüseyin Ilksen Toprak, Duygu Demiröz Aslan, Yusuf Ziya Colak, Mustafa Soner Ozcan, Mehmet, Yilmaz, Umran, Karaca, Sevtap Hekimoglu Sahin, Özlem Ersoy Karka, Gizem Demir Şenoğlu, Süheyla Erkoç Karadağ, Neslihan, Alkis, Volkan, Baytaş, Engin, Erturk, Ali, Akdogan, Ahmet, Besir, Dilek, Kutanis, Sedat, Saylan, Ersagun, Tugcugil, Pinar, Ayvat, Berrin, Günaydın, Beyza Mehri Büyükgebiz, Omer Faruk Boran, Feyza, Calisir, Yavuz, Orak, Bahar Kuvaki Balkan, Sibel, Büyükcoban, Erol, Gökel, Sakize Ferim Günenc, Sule, Özbilgin, Suna, Göre, Selcan, Akesen, Seda, Cansabuncu, Natalia, Momot, Anna, Panchenko, Jean-Francois, Pittet, Kristen, Rutledge, Tıp Fakültesi, Weiss, R, Saadat-Gilani, K, Kerschke,L, Wempe,C, Meersch, M, Zarbock, A, Cortegiani, A, and Ippolito, M
Subjects: Epidemiology, urologic and male genital diseases, acute renal failure, Adult Intensive & Critical Care, Anaesthesia, Cohort Studies, surgery, chronic renal failure, Humans, Multicenter Studies as Topic, Prospective Studies, adult intensive & critical care, urogenital system, Incidence, General Medicine, Acute Kidney Injury, female genital diseases and pregnancy complications, critical care, Renal Replacement Therapy, Observational Studies as Topic, epidemiology, Acute Renal Failure, Surgery, adult intensive &amp, Chronic Renal Failure
Abstract: Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©
Published: 2021

50. Perioperative Renoprotection: Clinical Implications

Author: Melanie Meersch, Khaschayar Saadat-Gilani, and Alexander Zarbock
Subjects: medicine.medical_specialty, medicine.medical_treatment, Renal function, urologic and male genital diseases, Kidney, Perioperative Care, Nephrotoxicity, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Lipocalin-2, 030202 anesthesiology, medicine, Humans, Renal replacement therapy, Cardiac Surgical Procedures, Intensive care medicine, Tissue Inhibitor of Metalloproteinase-2, business.industry, Acute kidney injury, Kidney metabolism, Perioperative, Acute Kidney Injury, medicine.disease, Anesthesiology and Pain Medicine, medicine.anatomical_structure, business, 030217 neurology & neurosurgery, Biomarkers, Kidney disease
Abstract: Acute kidney injury (AKI) remains a common complication in the perioperative setting affecting patients' short- and long-term outcome. Because therapeutic options are restricted to the use of renal replacement therapy, preventive strategies have become increasingly important. Several substances have been investigated for preventing AKI with limited to no effects. The lacking effectiveness of all these therapies might be caused by the fact that the therapy was started too late. In all the studies, therapy was initiated once a reduced kidney function occurred. In contrast to the classical functional biomarkers, new renal biomarkers allow to identify kidney damage without a loss of function thus enabling the implementation of preventive measures at the stage of renal stress. The most promising preventive strategy to date seems to implement a bundle of supportive measures in patients at high risk for AKI as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) group. This strategy includes the avoidance of nephrotoxic drugs and contrast agents, avoidance of hyperglycemia, optimization of perfusion pressure and hemodynamics with consideration of a functional hemodynamic monitoring, and close monitoring of renal function in patients at high risk for AKI. This review discusses new renal biomarkers for identifying kidney damage, the background of why the different measures of the KDIGO bundle might positively affect renal function and prevent the development of AKI, and presents the current literature of biomarker-based approaches in AKI.
Published: 2020

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