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1. Reproducibility of LPS-Induced ex vivo Cytokine Response of Healthy Volunteers Using a Whole Blood Assay

Author

Jorda A, Eberl S, Nussbaumer-Pröll A, Sarhan M, Weber M, Tegrovsky LE, Wahrmann M, al Jalali V, Bergmann F, Pracher L, Leutzendorff A, Farlik M, Jilma B, and Zeitlinger M

Subjects
lps, lipopolysaccharide, inflammation, endotoxin, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Anselm Jorda,1 Sabine Eberl,1 Alina Nussbaumer-Pröll,1 Maysa Sarhan,2 Maria Weber,1 Lara Elisabeth Tegrovsky,1 Markus Wahrmann,2 Valentin al Jalali,1 Felix Bergmann,1,3 Lena Pracher,1 Amelie Leutzendorff,1 Matthias Farlik,4 Bernd Jilma,1 Markus Zeitlinger1 1Medical University of Vienna, Department of Clinical Pharmacology, Vienna, Austria; 2Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis, Vienna, Austria; 3Medical University of Vienna, Department of Plastic, Reconstructive and Aesthetic Surgery, Vienna, Austria; 4Medical University of Vienna, Department of Dermatology, Vienna, AustriaCorrespondence: Markus Zeitlinger, Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria, Tel +43 1 40400 29810, Email markus.zeitlinger@meduniwien.ac.atIntroduction: Lipopolysaccharide (LPS) stimulation of human whole blood ex vivo has been widely used to investigate human innate immune responses. However, there are uncertainties regarding the reproducibility and reliability of this assay.Methods: In this prospective, single-center study, cytokine responses (interleukin 8, interferon-α, interferon-γ, interleukin 10, interleukin 1-β, interleukin 6, and tumor necrosis factor-α) to ex vivo whole blood LPS stimulation were assessed in 12 healthy volunteers. Cytokine levels were measured at 0, 2, and 4 h using a multiplex immunoassay (Luminex ®). Stimulation was repeated after six weeks. We examined reproducibility across technical and biological replicates at baseline and between repeated experiments after 6 weeks based on the area under the curve (AUC) of the individual cytokines using Pearson’s correlation coefficient and the mean coefficient of variation.Results: The lowest mean coefficients of variation were observed for the technical replicates (5.4 to 9.2%), followed by the biological replicates (8.1 to 24.8%), and the repeated experiments after 6 weeks (17 to 31.2%). Between the baseline and 6-week AUCs, the following Pearson correlation coefficients R were observed: interleukin 10, 0.97; interferon-α, 0.84; interleukin 1-β, 0.83; interleukin 8, 0.79; interleukin 6, 0.73; interferon-γ, 0.73; and tumor necrosis factor-α, 0.63.Discussion: The level of agreement between the baseline and week-6 cytokine response to ex vivo LPS stimulation was high across the seven cytokines analyzed. While interleukin 10 exhibited the lowest level of variability over time, tumor necrosis factor-α showed the highest variability in repeated experiments, which should be considered in the design and interpretation of future studies.Keywords: LPS, lipopolysaccharide, inflammation, endotoxin

Published
2024

2. The role and implications of left atrial fibrosis in surgical mitral valve repair as assessed by CMR: the ALIVE study design and rationale

Author

Mathari, S. el, Kluin, J., Hopman, L.H.G.A., Bhagirath, P., Oudeman, M.A.P., Vonk, A.B.A., Nederveen, A.J., Eberl, S., Klautz, R.J.M., Chamuleau, S.A.J., Ooij, P. van, Gotte, M.J.W., Cardiothoracic Surgery, Graduate School, APH - Digital Health, APH - Societal Participation & Health, ACS - Heart failure & arrhythmias, Cardiology, Radiology and Nuclear Medicine, ACS - Diabetes & metabolism, AMS - Ageing & Vitality, AMS - Sports, Anesthesiology, APH - Quality of Care, ACS - Atherosclerosis & ischemic syndromes, and Cardio-thoracic surgery

Subjects
atrial remodeling, ALIVE trial, cardiac magnetic resonance imaging, left atrial fibrosis, mitral regurgitation, Cardiology and Cardiovascular Medicine, mitral valve repair surgery
Abstract

BackgroundPatients with mitral regurgitation (MR) commonly suffer from left atrial (LA) remodeling. LA fibrosis is considered to be a key player in the LA remodeling process, as observed in atrial fibrillation (AF) patients. Literature on the presence and extent of LA fibrosis in MR patients however, is scarce and its clinical implications remain unknown. Therefore, the ALIVE trial was designed to investigate the presence of LA remodeling including LA fibrosis in MR patients prior to and after mitral valve repair (MVR) surgery.MethodsThe ALIVE trial is a single center, prospective pilot study investigating LA fibrosis in patients suffering from MR in the absence of AF (identifier NCT05345730). In total, 20 participants will undergo a CMR scan including 3D late gadolinium enhancement (LGE) imaging 2 week prior to MVR surgery and at 3 months follow-up. The primary objective of the ALIVE trial is to assess the extent and geometric distribution of LA fibrosis in MR patients and to determine effects of MVR surgery on reversed atrial remodelling.ImplicationsThis study will provide novel insights into the pathophysiological mechanism of fibrotic and volumetric atrial (reversed) remodeling in MR patients undergoing MVR surgery. Our results may contribute to improved clinical decision making and patient-specific treatment strategies in patients suffering from MR.

Published
2023
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6. Preoperative anaemia and outcome after elective cardiac surgery: a Dutch national registry analysis

Author

Hazen, Y., Noordzij, P.G., Gerritse, B.M., Scohy, T.V., Houterman, S., Bramer, S., Berendsen, R.R., Bouwman, Ramona W., Eberl, S., Haenen, J.S.E., Hofland, J., Horst, M. van der, Kingma, M.F., Klarenbosch, J. Van, Klok, T. van der, Korte, M.P.J. De, Maaten, J. Van Der, Spanjersberg, A.J., Wietsma, N.E., Li, W.W.L., Meer, N.J. van der, Rettig, T.C., Hazen, Y., Noordzij, P.G., Gerritse, B.M., Scohy, T.V., Houterman, S., Bramer, S., Berendsen, R.R., Bouwman, Ramona W., Eberl, S., Haenen, J.S.E., Hofland, J., Horst, M. van der, Kingma, M.F., Klarenbosch, J. Van, Klok, T. van der, Korte, M.P.J. De, Maaten, J. Van Der, Spanjersberg, A.J., Wietsma, N.E., Li, W.W.L., Meer, N.J. van der, and Rettig, T.C.

Abstract

Item does not contain fulltext, BACKGROUND: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. METHODS: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. RESULTS: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4-1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3-1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4-2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. CONCLUSIONS: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes.

Published
2022

14. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author

Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, Baker, T, Balaji, P, Balan, C, Balandin, A, Balescu-Arion, C, Baliuliene, V, Baltasar Isabel, J, Baluch, S, Bandrabur, D, Bankewitz, C, Barber, K, Barbera, F, Barcraft-Barnes, H, Barletti, V, Barnett, G, Baron, K, Barros, A, Barsan, V, Bartlett, P, Batistaki, C, Baumgarten, G, Baytas, V, Beauchamp, N, Becerra Cayetano, I, Bell, S, Bellandi, M, Belletti, A, Belmonte Cuenca, J, Benitez-Cano, A, Beretta, L, Berger, M, Bergmann, N, Bergmark, K, Bermudez Lopez, M, Bernotaite, M, Beurskens, C, Bidd, H, Bifulco, F, Bignami, E, Bilic, A, Bilskiene, D, Bischoff, P, Bishop, L, Bjonness, T, Blaylock, H, Blethyn, K, Blincoe, T, Blokhin, I, Blunt, N, Boer, C, Bois, G, Bonicolini, E, Booth, J, Borecka-Kedzierska, M, Borstnar, K, Borys, M, Boselli, E, Bouvet, L, Bouwman, A, Bowen, L, Bowrey, S, Boxall, L, Bozic, T, Bradley, T, Branco, T, Brazzi, L, Brazzoni, M, Brear, T, Brogly, N, Brohi, F, Broms, J, Bubliauskas, A, Bucolo, G, Buerkle, H, Buggy, D, Buhre, W, Bukauskas, T, Butturini, F, Byttner, A, Cabrera Diaz, I, Calderon, A, Calhau, R, Callejo, A, Cammu, G, Campesato, M, Can, O, Candeias, M, Cantor, A, Carise, E, Carmona, C, Carreteiro, J, Carrieri, C, Carter, A, Casal, M, Casanova, I, Cascella, M, Casero, L, Casiraghi, G, Castelo-Branco, L, Castro Arranz, C, Cernea, D, Cervantes, J, Chandler, B, Charnock, R, Chatzimicali, A, Chinery, E, Chishti, A, Chondhury, P, Christie, E, Christodoudiles, G, Ciardo, S, Cimpeanu, L, Cindea, I, Cinnella, G, Clark, S, Clayton, M, Cocu, S, Collyer, T, Colvin, C, Cope, S, Copeta, F, Copotoiu, S, Correia de Barros, F, Corso, R, Cortegiani, A, Costa, G, Cowton, A, Cox, N, Craig, J, Cricca, V, Cronin, J, Cunha, M, Cuomo, A, Curley, K, Czuczwar, M, Dabrowska, D, Damster, S, Danguy des Deserts, M, Daniliuc, A, Danninger, T, Darwish, I, Dascalu, C, Davies, K, Davies, S, De Boer, H, De Flaviis, A, De Selincourt, G, Deana, C, Debaene, B, Debreceni, G, Dedhia, J, Delgado Garcia, I, Della Rocca, G, Delroy-Buelles, L, Desai, T, Dhillon, P, Di Giacinto, I, Di Mauro, P, Diaz Gomez, T, Dimitrovski, A, Dinic, V, Dirzu, D, Divander, M, Dolinar, J, Domingues, S, Doolan, J, Downes, C, Dragoescu, N, Droc, G, Dum, E, Dumitrescu, A, Duncan, L, Dzurnakova, P, Eberl, S, Edwards, J, Edwards, M, Ekelund, K, Ekengren, P, Elghouty, E, Ellerkmann, R, Ellis, H, Elme, A, Ernst, T, Errando, C, Estenes, S, Ewaldsson, C, Farid, N, Featherstone, J, Febres, D, Fedorov, S, Feggeler, J, Feijten, P, Fellmann, T, Fernandez Candil, J, Fernandez Castineira, A, Fernandez Castineira, J, Fernando, A, Ferrando, C, Ferreira, L, Ferreira, P, Feyling, A, Filipescu, D, Fleischer, A, Floris, L, Foerster, U, Fox, B, Franke, U, Frasca, D, Frey, C, Frost, V, Fullin, G, Fumagalli, J, Furneval, J, Fusari, M, Gallacher, S, Galushka, S, Gambale, G, Gambino, I, Garcia-Perez, M, Garg, S, Garlak, J, Gavranovic, Z, Gavrilov, R, Gaynor, L, Gecaj Gashi, A, Georghiou, M, Gerjevic, B, Gferer, G, Giarratano, A, Gibson, A, Gievski, V, Giles, J, Gillberg, L, Gilowska, K, Gilsanz Rodriguez, F, Gioia, A, Giovannoni, C, Girotra, V, Gkinas, D, Gkiokas, G, Godoroja, D, Goebel, U, Goel, V, Gonzalez, M, Goranovic, T, Gornik-Wlaszczuk, E, Gosavi, S, Gottfridsson, P, Gottschalk, A, Granell, M, Granstrom, A, Grassetto, A, Greenwood, A, Grigoras, I, Grintescu, I, Gritsan, A, Gritsan, G, Grynyuk, A, Guadagnin, G, Guarnieri, M, Guclu, C, Guerrero Diez, M, Gunenc, F, Gunther, U, Gupta, P, Guttenthaler, V, Hack, Y, Hafisayena, A, Hagau, N, Haldar, J, Hales, D, Hanci, V, Hanna-Jumma, S, Harazim, H, Harlet, P, Harper, D, Harris, B, Harvey, O, Hashimi, M, Hawkins, L, Hayes, C, Heaton, J, Heier, T, Helliwell, L, Hemmes, S, Henderson, K, Hermanides, J, Hermanns, H, Herrera Hueso, B, Hestenes, S, Hettiarachchi, R, Highgate, J, Hodgson, K, Hoelbling, D, Holland, J, Horhota, L, Hormis, A, Hribar, R, Hua, A, Humphreys, S, Humphries, R, Humplikova, S, Hunt, J, Husnain, A, Hussein, A, Hyams, B, Iannuccelli, F, Ilette, K, Ilyas, C, Inan, T, India, I, Ionitav, V, Irwin, F, Jain, V, Janez, B, Jankovic, R, Jenkins, S, Jenko, M, Jimenez, R, Jimenez Gomez, B, Joachim, S, Joelsson-Alm, E, John, J, Jonikaite, L, Jovic, M, Jungwirth, B, Junke, E, Kabakov, B, Kadaoui, S, Kanski, A, Karadag, S, Karbonskiene, A, Karjagin, J, Kasnik, D, Katanolli, F, Katsika, E, Kaufmann, K, Keane, H, Kelly, M, Kent, M, Keraitiene, G, Khudhur, A, Khuenl-Brady, K, Kidd, L, King, S, Kirchgassner, K, Klancir, T, Klucniks, A, Knotzer, J, Knowlden, P, Koers, L, Kompan, J, Koneti, K, Kooij, F, Koolen, E, Koopman - van Gemert, A, Kopp, K, Korfiotis, D, Korolkov, O, Kosinova, M, Kostenberger, M, Kotzinger, O, Kovacevic, M, Kranke, P, Kranke, E, Kraus, C, Kraus, S, Kubitzek, C, Kucharski, R, Kucukguclu, S, Kudrashou, A, Kumar, V, Kummen, L, Kunit, C, Kushakovsky, V, Kuvaki, B, Kuzmanovska, B, Kyttari, A, Landoni, G, Lau, G, Lazarev, K, Legett, S, Legrottaglie, A, Leonardi, S, Leong, M, Lercher, H, Leuvrey, M, Leva, B, Levstek, M, Limb, J, Lindholm, E, Linton, F, Liperi, C, Lipski, F, Lirk, P, Lisi, A, Liskova, K, Lluch Oltra, A, Loganathan, V, Lombardi, S, Lopez, E, Lopez Rodriguez, M, Lorenzini, L, Lowicka, M, Lugovoy, A, Luippold, M, Lumb, A, Macas, A, Macgregor, M, Machado, H, Maciariello, M, Madeira, I, Maitan, S, Majewski, J, Maldini, B, Malewski, G, Manfredini, L, Manner, O, Marchand, B, Marcu, A, Margalef, J, Margarson, M, Marinheiro, L, Markic, A, Markovic Bozic, J, Marrazzo, F, Martin, J, Martin Ayuso, M, Martinez, E, Martino, E, Martinson, V, Marusic-Gaser, K, Mascarenhas, C, Mathis, C, Matsota, P, Mavrommati, E, Mazul Sunko, B, Mccourt, K, Mcgill, N, Mckee, R, Meco, B, Meier, S, Melbourne, S, Melbybrathen, G, Meli, A, Melia, A, Melotti, R, Menga, M, Mercer, P, Merotra, S, Mescolini, S, Metterlein, T, Michalov, M, Michlig, S, Midgley, S, Milic, M, Milojevic, M, Minana, A, Minto, G, Mirabella, L, Mirea, L, Mittelstadt, L, Moeglen, A, Moise, A, Mokini, Z, Molin, A, Molto, L, Monea, M, Montalto, F, Montgomery, J, Montgomery, C, Montillo, G, Moore, S, Moore, F, Moreira, Z, Moreno, T, Moreno, R, Moret, E, Moreton, S, Morgan, M, Moro Velasco, C, Morri, D, Moull, A, Moura, F, Mraz, P, Mrozek, K, Mukhtar, K, Muniyappa, S, Murray, H, Murthy, B, Mushambi, M, Nadolski, M, Nardelli, P, Nardin, G, Navarro Perez, R, Naveiro, A, Negri, M, Nesek Adam, V, Neskovic, V, Neuwersch, S, Neves, M, Nguyen, B, Ni Eochagain, A, Nicholas, C, Nightingale, J, Norrie, K, Novak-Jankovic, V, Novakova, A, Novillo, M, Numan, S, Oduro-Dominah, L, Oldner, A, Oliveira, I, Ologoiu, D, Oloktsidou, I, O'Reilly, R, Orlando, A, Ovezov, A, Ozbilgin, S, Paal, P, Padin Barreiro, L, Palugniok, R, Papaioannou, A, Papapostolou, K, Paranthaman, P, Pardey Bracho, G, Parente, S, Parfeni, A, Pasin, L, Passey, S, Pastor, E, Patch, S, Patil, A, Paunescu, M, Pehboeck, D, Pereira, M, Pereira, C, Perez Caballero, P, Perez Garcia, A, Perez Soto, A, Perez Tejero, G, Perez-Cerda, F, Pesenti, A, Petta, R, Philippe, S, Pickering, D, Pico Veloso, J, Pina, P, Pinho-Oliveira, V, Pinol, S, Pinto, R, Pistidda, L, Pitterle, M, Piwowarczyk, P, Plotnikova, O, Pohl, H, Poldermann, J, Polkovicova, L, Pompei, L, Popescu, M, Popovic, R, Pota, V, Potocnik, M, Potrec, B, Potter, A, Pramod, N, Prchalova, M, Preckel, B, Pugh, R, Pulletz, M, Radoeshki, A, Rafi, A, Ragazzi, R, Raineri Santi, M, Rajamanickam, T, Rajput, Z, Ramachandran, R, Ramasamy, R, Ramessur, S, Rao, R, Rasmussen, A, Rato, A, Razaque, U, Real Navacerrada, M, Reavley, C, Reid, J, Reschreiter, H, Rial, E, Ribas Carrasco, P, Ribeiro, S, Rich, N, Richardson, L, Rimaitis, K, Rimaitis, M, Ringvold, E, Ripke, F, Ristescu, I, Ritchie, K, Rodenas, F, Rodrigues, P, Rogers, E, Rogerson, D, Romagnoli, S, Romero, E, Rondovic, G, Rose, B, Roth, W, Rotter, M, Rousseau, G, Rudjord, A, Rueffert, H, Rundgren, M, Rupprecht, K, Rushton, A, Russotto, V, Rypulak, E, Ryszka, M, Sa, J, Sa Couto, P, Saby, S, Sagic, J, Saleh, O, Sales, G, Sanchez Sanchez, Y, Sanghera, S, Sanli Karip, C, Santiveri Papiol, F, Santos, S, Sarno, S, Saul, D, Saunders, D, Savic, N, Scalco, L, Scanlon, D, Schaller, S, Schax, C, Scheffer, G, Schening, A, Schiavone, V, Schmidt-Ehrenberg, F, Schmidt-Mutter, C, Schonberg, C, Schopflin, C, Schreiber, J, Schultz, M, Schurig, M, Scott, C, Sebestian, S, Sehgal, S, Sem, V, Semenas, E, Serafini, E, Serchan, P, Shields, M, Shobha, R, Shosholcheva, M, Siamansour, T, Siddaiah, N, Siddiqi, K, Sinclair, R, Singh, P, Singh, R, Sinha, A, Skinner, A, Smee, E, Smekalova, O, Smith, N, Smith, T, Smitz, C, Smole, D, Sojcic, N, Soler Pedrola, M, Somanath, S, Sonksen, J, Sorella, M, Sormus, A, Soro, M, Soto, C, Spada, A, Spadaro, S, Spaeth, J, Sparr, H, Spielmann, A, Spindler-Vesel, A, Stamelos, M, Stancombe L, L, Stanculescu, A, Standl, T, Standley, T, Stanek, O, Stanisavljevic, S, Starczewska, M, Stauble, C, Steen, J, Stefan, O, Stell, E, Stera, C, Stevens, M, Stoerckel, M, Stosic, B, Stourac, P, Stroumpoulis, K, Struck, R, Suarez de la Rica, A, Sultanpori, A, Sundara Rajan, R, Suying, O, Svensen, C, Swan, L, Syrogianni, P, Sysiak, J, Szederjesi, J, Taddei, S, Tan Hao, E, Tanou, V, Tarabova, K, Tardaguila Sancho, P, Tarroso, M, Tartaglione, M, Taylor, E, Tbaily, L, Telford, R, Terenzoni, M, Theodoraki, K, Thornley, H, Tiganiuc, L, Toim, H, Tomescu, D, Tommasino, C, Toni, J, Toninelli, A, Toretti, I, Townley, S, Trepenaitis, D, Trethowan, B, Tsaousi, G, Tsiftsi, A, Tudor, A, Turan, G, Turhan, S, Unic-Stojanovic, D, Unterbuchner, C, Unzueta, C, Uranjek, J, Ursic, T, Vaida, S, Valldeperas Ferrer, S, Valldeperas Hernandez, M, Valsamidis, D, Van Beek, R, Van dasselaer, N, Van Der Beek, T, Van Duivenvoorde, Y, van Klei, W, Van Poorter, F, Van Zaane, B, Van Zundert, T, Van Zyl, R, Vargas Munoz, A, Varsani, N, Vasconcelos, P, Vassilakis, G, Vecchiatini, T, Vecera, L, Vercauteren, M, Verdouw, B, Verheyen, V, Verri, M, Vicari Sottosanti, L, Vico, M, Vidal Mitjans, P, Vilardi, A, Vissicchio, D, Vitale, G, Vitkovic, B, Vizcaychipi, M, Voicu, A, Voje, M, Volfova, I, Volta, C, Von Lutterotti, T, von Tiesenhausen, A, Vrecic-Slabe, S, Vukcevic, D, Vukovic, R, Vullo, P, Wade, A, Wallberg, H, Wallden, J, Wallner, J, Walther Sturesson, L, Watson, D, Weber, S, Wegiel Leskiewiq, A, Weller, D, Wensing, C, Werkmann, M, Westberg, H, Wikstrom, E, Williams, B, Wilson, R, Wirth, S, Wittmann, M, Wood, L, Wright, S, Zachoval, C, Zambon, M, Zampieri, S, Zampone, S, Zangrillo, A, Zani, G, Zavackiene, A, Zieglerder, R, Zonneveldt, H, Zsisku, L, Zucker, T, Zukowski, M, Zuleika, M, Zupaneie, D, Kirmeier E., Eriksson L. I., Lewald H., Jonsson Fagerlund M., Hoeft A., Hollmann M., Meistelman C., Hunter J. M., Ulm K., Blobner M., Abad Gurumeta A., Abernethy C., Abigail P., Achaibar K., Adam E., Afshari A., Agudelo Montoya M. E., Akgun F. N., Aletti G., Alkis N., Allan K., Allan A., Allaouchiche B., Allcock C., Almasy E., Amey I., Amigoni M., Andersen E., Andersson P., Anipchenko N., Antunes P., Armstrong E., Aslam T. N., Aslin B., Assuncao J. P., Ausserer J., Avvai M., Awad N., Ayas Montero B., Ayuso M., Azevedo P., Badarau V., Badescu R., Baiardo Redaelli M., Baird C., Baird Y., Baker T., Balaji P., Balan C., Balandin A., Balescu-Arion C., Baliuliene V., Baltasar Isabel J., Baluch S. N., Bandrabur D., Bankewitz C., Barber K., Barbera F., Barcraft-Barnes H., Barletti V., Barnett G., Baron K., Barros A., Barsan V., Bartlett P., Batistaki C., Baumgarten G., Baytas V., Beauchamp N., Becerra Cayetano I. A., Bell S., Bellandi M., Belletti A., Belmonte Cuenca J., Benitez-Cano A., Beretta L., Berger M., Bergmann N., Bergmark K., Bermudez Lopez M., Bernotaite M., Beurskens C., Bidd H., Bifulco F., Bignami E., Bilic A., Bilskiene D., Bischoff P., Bishop L., Bjonness T., Blaylock H., Blethyn K., Blincoe T., Blokhin I., Blunt N., Boer C., Bois G., Bonicolini E., Booth J., Borecka-Kedzierska M., Borstnar K., Borys M., Boselli E., Bouvet L., Bouwman A., Bowen L., Bowrey S., Boxall L., Bozic T., Bradley T., Branco T., Brazzi L., Brazzoni M., Brear T., Brogly N., Brohi F., Broms J., Bubliauskas A., Bucolo G. E., Buerkle H., Buggy D., Buhre W., Bukauskas T., Butturini F., Byttner A., Cabrera Diaz I., Calderon A., Calhau R., Callejo A., Cammu G., Campesato M., Can O. S., Candeias M., Cantor A., Carise E., Carmona C., Carreteiro J., Carrieri C., Carter A., Casal M., Casanova I., Cascella M., Casero L. M., Casiraghi G. M., Castelo-Branco L., Castro Arranz C., Cernea D. D., Cervantes J., Chandler B., Charnock R., Chatzimicali A., Chinery E., Chishti A., Chondhury P., Christie E., Christodoudiles G., Ciardo S., Cimpeanu L., Cindea I., Cinnella G., Clark S., Clayton M., Cocu S., Collyer T., Colvin C., Cope S., Copeta F., Copotoiu S. -M., Correia de Barros F., Corso R. M., Cortegiani A., Costa G., Cowton A., Cox N., Craig J., Cricca V., Cronin J., Cunha M., Cuomo A., Curley K., Czuczwar M., Dabrowska D., Damster S., Danguy des Deserts M., Daniliuc A., Danninger T., Darwish I., Dascalu C., Davies K., Davies S., De Boer H., De Flaviis A., De Selincourt G., Deana C., Debaene B., Debreceni G., Dedhia J., Delgado Garcia I., Della Rocca G., Delroy-Buelles L., Desai T., Dhillon P., Di Giacinto I., Di Mauro P., Diaz Gomez T. V., Dimitrovski A., Dinic V., Dirzu D. -S., Divander M. B., Dolinar J., Domingues S., Doolan J., Downes C., Dragoescu N. A., Droc G., Dum E., Dumitrescu A., Duncan L., Dzurnakova P., Eberl S., Edwards J., Edwards M., Ekelund K., Ekengren P., Elghouty E., Ellerkmann R., Ellis H., Elme A., Ernst T., Errando C. L., Estenes S., Ewaldsson C., Farid N., Featherstone J., Febres D., Fedorov S., Feggeler J., Feijten P., Fellmann T., Fernandez Candil J., Fernandez Castineira A., Fernandez Castineira J., Fernando A., Ferrando C., Ferreira L., Ferreira P., Feyling A., Filipescu D., Fleischer A., Floris L., Foerster U., Fox B., Franke U., Frasca D., Frey C., Frost V., Fullin G., Fumagalli J., Furneval J., Fusari M., Gallacher S., Galushka S., Gambale G., Gambino I., Garcia-Perez M. L., Garg S., Garlak J., Gavranovic Z., Gavrilov R., Gaynor L., Gecaj Gashi A., Georghiou M., Gerjevic B., Gferer G., Giarratano A., Gibson A., Gievski V., Giles J., Gillberg L., Gilowska K., Gilsanz Rodriguez F., Gioia A., Giovannoni C., Girotra V., Gkinas D., Gkiokas G., Godoroja D., Goebel U., Goel V., Gonzalez M., Goranovic T., Gornik-Wlaszczuk E., Gosavi S., Gottfridsson P., Gottschalk A., Granell M., Granstrom A., Grassetto A., Greenwood A., Grigoras I., Grintescu I., Gritsan A., Gritsan G., Grynyuk A., Guadagnin G. M., Guarnieri M., Guclu C., Guerrero Diez M., Gunenc F., Gunther U., Gupta P., Guttenthaler V., Hack Y., Hafisayena A., Hagau N., Haldar J., Hales D., Hanci V., Hanna-Jumma S., Harazim H., Harlet P., Harper D., Harris B., Harvey O., Hashimi M., Hawkins L., Hayes C., Heaton J., Heier T., Helliwell L., Hemmes S., Henderson K., Hermanides J., Hermanns H., Herrera Hueso B., Hestenes S., Hettiarachchi R., Highgate J., Hodgson K., Hoelbling D., Holland J., Horhota L., Hormis A., Hribar R., Hua A., Humphreys S., Humphries R., Humplikova S., Hunt J., Husnain A., Hussein A., Hyams B., Iannuccelli F., Ilette K., Ilyas C., Inan T., India I., Ionitav V., Irwin F., Jain V., Janez B., Jankovic R., Jenkins S., Jenko M., Jimenez R., Jimenez Gomez B., Joachim S., Joelsson-Alm E., John J., Jonikaite L., Jovic M., Jungwirth B., Junke E., Kabakov B., Kadaoui S. -D., Kanski A., Karadag S., Karbonskiene A., Karjagin J., Kasnik D., Katanolli F., Katsika E., Kaufmann K., Keane H., Kelly M., Kent M., Keraitiene G., Khudhur A., Khuenl-Brady K., Kidd L., King S., Kirchgassner K., Klancir T., Klucniks A., Knotzer J., Knowlden P., Koers L., Kompan J., Koneti K. K., Kooij F., Koolen E., Koopman - van Gemert A. W. M. M., Kopp K., Korfiotis D., Korolkov O., Kosinova M., Kostenberger M., Kotzinger O., Kovacevic M., Kranke P., Kranke E., Kraus C., Kraus S., Kubitzek C., Kucharski R., Kucukguclu S., Kudrashou A., Kumar V., Kummen L., Kunit C., Kushakovsky V., Kuvaki B., Kuzmanovska B., Kyttari A., Landoni G., Lau G., Lazarev K., Legett S., Legrottaglie A. M., Leonardi S., Leong M., Lercher H., Leuvrey M., Leva B., Levstek M., Limb J., Lindholm E., Linton F., Liperi C., Lipski F., Lirk P., Lisi A., Liskova K., Lluch Oltra A., Loganathan V., Lombardi S., Lopez E., Lopez Rodriguez M., Lorenzini L., Lowicka M., Lugovoy A., Luippold M., Lumb A., Macas A., Macgregor M., Machado H., Maciariello M., Madeira I., Maitan S., Majewski J., Maldini B., Malewski G., Manfredini L., Manner O., Marchand B., Marcu A., Margalef J., Margarson M., Marinheiro L., Markic A., Markovic Bozic J., Marrazzo F., Martin J., Martin Ayuso M., Martinez E., Martino E. A., Martinson V., Marusic-Gaser K., Mascarenhas C., Mathis C., Matsota P., Mavrommati E., Mazul Sunko B., McCourt K., McGill N., McKee R., Meco B. C., Meier S., Melbourne S., Melbybrathen G., Meli A., Melia A., Melotti R. M., Menga M. R., Mercer P., Merotra S., Mescolini S., Metterlein T., Michalov M., Michlig S., Midgley S., Milic M., Milojevic M., Minana A., Minto G., Mirabella L., Mirea L., Mittelstadt L., Moeglen A., Moise A., Mokini Z., Molin A., Molto L., Monea M. C., Montalto F., Montgomery J., Montgomery C., Montillo G., Moore S., Moore F., Moreira Z., Moreno T., Moreno R., Moret E., Moreton S., Morgan M., Moro Velasco C., Morri D., Moull A., Moura F., Mraz P., Mrozek K., Mukhtar K., Muniyappa S., Murray H., Murthy B. V., Mushambi M., Nadolski M., Nardelli P., Nardin G., Navarro Perez R., Naveiro A., Negri M., Nesek Adam V., Neskovic V., Neuwersch S., Neves M., Nguyen B., Ni Eochagain A., Nicholas C., Nightingale J., Norrie K., Novak-Jankovic V., Novakova A., Novillo M., Numan S., Oduro-Dominah L., Oldner A., Oliveira I., Ologoiu D., Oloktsidou I., O'Reilly R., Orlando A., Ovezov A., Ozbilgin S., Paal P., Padin Barreiro L., Palugniok R., Papaioannou A., Papapostolou K., Paranthaman P., Pardey Bracho G., Parente S., Parfeni A., Pasin L., Passey S., Pastor E., Patch S., Patil A., Paunescu M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero P., Perez Garcia A., Perez Soto A., Perez Tejero G., Perez-Cerda F., Pesenti A., Petta R., Philippe S., Pickering D., Pico Veloso J., Pina P., Pinho-Oliveira V., Pinol S., Pinto R., Pistidda L., Pitterle M., Piwowarczyk P., Plotnikova O., Pohl H., Poldermann J., Polkovicova L., Pompei L., Popescu M., Popovic R., Pota V., Potocnik M., Potrec B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi M., Rajamanickam T., Rajput Z., Ramachandran R., Ramasamy R., Ramessur S., Rao R., Rasmussen A., Rato A., Razaque U., Real Navacerrada M. I., Reavley C., Reid J., Reschreiter H., Rial E., Ribas Carrasco P., Ribeiro S., Rich N., Richardson L., Rimaitis K., Rimaitis M., Ringvold E. -M., Ripke F., Ristescu I., Ritchie K., Rodenas F., Rodrigues P., Rogers E., Rogerson D., Romagnoli S., Romero E., Rondovic G., Rose B. O., Roth W., Rotter M. -T., Rousseau G., Rudjord A., Rueffert H., Rundgren M., Rupprecht K., Rushton A., Russotto V., Rypulak E., Ryszka M., Sa J., Sa Couto P., Saby S., Sagic J., Saleh O., Sales G., Sanchez Sanchez Y., Sanghera S., Sanli Karip C., Santiveri Papiol F. J., Santos S., Sarno S., Saul D., Saunders D., Savic N., Scalco L., Scanlon D., Schaller S., Schax C., Scheffer G. J., Schening A., Schiavone V., Schmidt-Ehrenberg F., Schmidt-Mutter C., Schonberg C., Schopflin C., Schreiber J. -U., Schultz M., Schurig M., Scott C., Sebestian S., Sehgal S., Sem V., Semenas E., Serafini E., Serchan P., Shields M., Shobha R., Shosholcheva M., Siamansour T., Siddaiah N., Siddiqi K., Sinclair R., Singh P., Singh R., Sinha A., Skinner A., Smee E., Smekalova O., Smith N., Smith T., Smitz C., Smole D., Sojcic N., Soler Pedrola M., Somanath S., Sonksen J., Sorella M. C., Sormus A., Soro M., Soto C., Spada A., Spadaro S., Spaeth J., Sparr H., Spielmann A., Spindler-Vesel A., Stamelos M., Stancombe L L., Stanculescu A., Standl T., Standley T., Stanek O., Stanisavljevic S., Starczewska M., Stauble C., Steen J., Stefan O. M., Stell E., Stera C., Stevens M., Stoerckel M., Stosic B., Stourac P., Stroumpoulis K., Struck R., Suarez de la Rica A., Sultanpori A., Sundara Rajan R., Suying O., Svensen C., Swan L., Syrogianni P., Sysiak J., Szederjesi J., Taddei S., Tan Hao E., Tanou V., Tarabova K., Tardaguila Sancho P., Tarroso M., Tartaglione M., Taylor E., Tbaily L., Telford R., Terenzoni M., Theodoraki K., Thornley H., Tiganiuc L., Toim H., Tomescu D., Tommasino C., Toni J., Toninelli A., Toretti I., Townley S., Trepenaitis D., Trethowan B., Tsaousi G., Tsiftsi A., Tudor A., Turan G., Turhan S. C., Unic-Stojanovic D., Unterbuchner C., Unzueta C., Uranjek J., Ursic T., Vaida S., Valldeperas Ferrer S., Valldeperas Hernandez M. I., Valsamidis D., Van Beek R., Van dasselaer N., Van Der Beek T., Van Duivenvoorde Y., van Klei W. A., Van Poorter F., Van Zaane B., Van Zundert T., Van Zyl R., Vargas Munoz A. M., Varsani N., Vasconcelos P., Vassilakis G., Vecchiatini T., Vecera L., Vercauteren M., Verdouw B., Verheyen V., Verri M., Vicari Sottosanti L. G., Vico M., Vidal Mitjans P., Vilardi A., Vissicchio D., Vitale G., Vitkovic B., Vizcaychipi M. P., Voicu A., Voje M., Volfova I., Volta C. A., Von Lutterotti T., von Tiesenhausen A., Vrecic-Slabe S., Vukcevic D., Vukovic R., Vullo P. A., Wade A., Wallberg H., Wallden J., Wallner J., Walther Sturesson L., Watson D., Weber S., Wegiel Leskiewiq A., Weller D., Wensing C., Werkmann M., Westberg H., Wikstrom E., Williams B., Wilson R., Wirth S., Wittmann M., Wood L., Wright S., Zachoval C., Zambon M., Zampieri S., Zampone S., Zangrillo A., Zani G., Zavackiene A., Zieglerder R., Zonneveldt H., Zsisku L., Zucker T. -P., Zukowski M., Zuleika M., Zupaneie D., Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, Baker, T, Balaji, P, Balan, C, Balandin, A, Balescu-Arion, C, Baliuliene, V, Baltasar Isabel, J, Baluch, S, Bandrabur, D, Bankewitz, C, Barber, K, Barbera, F, Barcraft-Barnes, H, Barletti, V, Barnett, G, Baron, K, Barros, A, Barsan, V, Bartlett, P, Batistaki, C, Baumgarten, G, Baytas, V, Beauchamp, N, Becerra Cayetano, I, Bell, S, Bellandi, M, Belletti, A, Belmonte Cuenca, J, Benitez-Cano, A, Beretta, L, Berger, M, Bergmann, N, Bergmark, K, Bermudez Lopez, M, Bernotaite, M, Beurskens, C, Bidd, H, Bifulco, F, Bignami, E, Bilic, A, Bilskiene, D, Bischoff, P, Bishop, L, Bjonness, T, Blaylock, H, Blethyn, K, Blincoe, T, Blokhin, I, Blunt, N, Boer, C, Bois, G, Bonicolini, E, Booth, J, Borecka-Kedzierska, M, Borstnar, K, Borys, M, Boselli, E, Bouvet, L, Bouwman, A, Bowen, L, Bowrey, S, Boxall, L, Bozic, T, Bradley, T, Branco, T, Brazzi, L, Brazzoni, M, Brear, T, Brogly, N, Brohi, F, Broms, J, Bubliauskas, A, Bucolo, G, Buerkle, H, Buggy, D, Buhre, W, Bukauskas, T, Butturini, F, Byttner, A, Cabrera Diaz, I, Calderon, A, Calhau, R, Callejo, A, Cammu, G, Campesato, M, Can, O, Candeias, M, Cantor, A, Carise, E, Carmona, C, Carreteiro, J, Carrieri, C, Carter, A, Casal, M, Casanova, I, Cascella, M, Casero, L, Casiraghi, G, Castelo-Branco, L, Castro Arranz, C, Cernea, D, Cervantes, J, Chandler, B, Charnock, R, Chatzimicali, A, Chinery, E, Chishti, A, Chondhury, P, Christie, E, Christodoudiles, G, Ciardo, S, Cimpeanu, L, Cindea, I, Cinnella, G, Clark, S, Clayton, M, Cocu, S, Collyer, T, Colvin, C, Cope, S, Copeta, F, Copotoiu, S, Correia de Barros, F, Corso, R, Cortegiani, A, Costa, G, Cowton, A, Cox, N, Craig, J, Cricca, V, Cronin, J, Cunha, M, Cuomo, A, Curley, K, Czuczwar, M, Dabrowska, D, Damster, S, Danguy des Deserts, M, Daniliuc, A, Danninger, T, Darwish, I, Dascalu, C, Davies, K, Davies, S, De Boer, H, De Flaviis, A, De Selincourt, G, Deana, C, Debaene, B, Debreceni, G, Dedhia, J, Delgado Garcia, I, Della Rocca, G, Delroy-Buelles, L, Desai, T, Dhillon, P, Di Giacinto, I, Di Mauro, P, Diaz Gomez, T, Dimitrovski, A, Dinic, V, Dirzu, D, Divander, M, Dolinar, J, Domingues, S, Doolan, J, Downes, C, Dragoescu, N, Droc, G, Dum, E, Dumitrescu, A, Duncan, L, Dzurnakova, P, Eberl, S, Edwards, J, Edwards, M, Ekelund, K, Ekengren, P, Elghouty, E, Ellerkmann, R, Ellis, H, Elme, A, Ernst, T, Errando, C, Estenes, S, Ewaldsson, C, Farid, N, Featherstone, J, Febres, D, Fedorov, S, Feggeler, J, Feijten, P, Fellmann, T, Fernandez Candil, J, Fernandez Castineira, A, Fernandez Castineira, J, Fernando, A, Ferrando, C, Ferreira, L, Ferreira, P, Feyling, A, Filipescu, D, Fleischer, A, Floris, L, Foerster, U, Fox, B, Franke, U, Frasca, D, Frey, C, Frost, V, Fullin, G, Fumagalli, J, Furneval, J, Fusari, M, Gallacher, S, Galushka, S, Gambale, G, Gambino, I, Garcia-Perez, M, Garg, S, Garlak, J, Gavranovic, Z, Gavrilov, R, Gaynor, L, Gecaj Gashi, A, Georghiou, M, Gerjevic, B, Gferer, G, Giarratano, A, Gibson, A, Gievski, V, Giles, J, Gillberg, L, Gilowska, K, Gilsanz Rodriguez, F, Gioia, A, Giovannoni, C, Girotra, V, Gkinas, D, Gkiokas, G, Godoroja, D, Goebel, U, Goel, V, Gonzalez, M, Goranovic, T, Gornik-Wlaszczuk, E, Gosavi, S, Gottfridsson, P, Gottschalk, A, Granell, M, Granstrom, A, Grassetto, A, Greenwood, A, Grigoras, I, Grintescu, I, Gritsan, A, Gritsan, G, Grynyuk, A, Guadagnin, G, Guarnieri, M, Guclu, C, Guerrero Diez, M, Gunenc, F, Gunther, U, Gupta, P, Guttenthaler, V, Hack, Y, Hafisayena, A, Hagau, N, Haldar, J, Hales, D, Hanci, V, Hanna-Jumma, S, Harazim, H, Harlet, P, Harper, D, Harris, B, Harvey, O, Hashimi, M, Hawkins, L, Hayes, C, Heaton, J, Heier, T, Helliwell, L, Hemmes, S, Henderson, K, Hermanides, J, Hermanns, H, Herrera Hueso, B, Hestenes, S, Hettiarachchi, R, Highgate, J, Hodgson, K, Hoelbling, D, Holland, J, Horhota, L, Hormis, A, Hribar, R, Hua, A, Humphreys, S, Humphries, R, Humplikova, S, Hunt, J, Husnain, A, Hussein, A, Hyams, B, Iannuccelli, F, Ilette, K, Ilyas, C, Inan, T, India, I, Ionitav, V, Irwin, F, Jain, V, Janez, B, Jankovic, 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Abstract

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary

Published
2019

15. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author

Kirmeier E. a, Eriksson L. I. c, Lewald H. a, Jonsson Fagerlund, M. c Hoeft, A. f Hollmann, M. g Meistelman, C. e Hunter, J. M. d Ulm, K. b Blobner, M. aEmail Author, Abad Gurumeta, A. Abernethy, C. Abigail, P. Achaibar, K. Adam, E. Afshari, Agudelo Montoya, M. E. Akgün, F. N. Aletti, G. Alkış, N. Allan, K. Allan, A. Allaouchiche, B. Allcock, C. Almasy, E. Amey, I. Amigoni, M. Andersen, E. Andersson, P. Anipchenko, N. Antunes, P. Armstrong, E. Aslam, T. N. Aslin, B. Assunção, J. P. Ausserer, J. Avvai, M. Awad, Ayas Montero, B. Ayuso, M. Azevedo, P. Badarau, V. Badescu, Baiardo Redaelli, M. Baird, C. Baird, Y. Baker, T. Balaji, P. Bălan, C. Balandin, A. Balescu-Arion, C. Baliuliene, Baltasar Isabel, J. Baluch, S. N. Bandrabur, D. Bankewitz, C. Barber, K. Barbera, F. Barcraft-Barnes, H. Barletti, V. Barnett, G. Baron, K. Barros, A. Barsan, V. Bartlett, P. Batistaki, C. Baumgarten, G. Baytas, V. Beauchamp, Becerra Cayetano, I. A. Bell, S. Bellandi, M. Belletti, Belmonte Cuenca, J. Benitez-Cano, A. Beretta, L. Berger, M. Bergmann, N. Bergmark, Bermudez Lopez, M. Bernotaite, M. Beurskens, C. Bidd, H. Bifulco, F. Bignami, E. Bilic, A. Bilskiene, D. Bischoff, P. Bishop, L. Bjonness, T. Blaylock, H. Blethyn, K. Blincoe, T. Blokhin, I. Blunt, N. Boer, C. Bois, G. Bonicolini, E. Booth, J. Borecka-Kedzierska, M. Borstnar, K. Borys, M. Boselli, E. Bouvet, L. Bouwman, A. Bowen, L. Bowrey, S. Boxall, L. Božić, T. Bradley, T. Branco, T. Brazzi, L. Brazzoni, M. Brear, T. Brogly, N. Brohi, F. Broms, J. Bubliauskas, A. Bucolo, G. E. Buerkle, H. Buggy, D. Buhre, W. Bukauskas, T. Butturini, F. Byttner, Cabrera Díaz, I. Calderon, A. Calhau, R. Callejo, A. Cammu, G. Campesato, M. Can, Ö. S. Candeias, M. Cantor, A. Carise, E. Carmona, C. Carreteiro, J. Carrieri, C. Carter, A. Casal, M. Casanova, I. Cascella, M. Casero, L. M. Casiraghi, G. M. Castelo-Branco, Castro Arranz, C. Cernea, D. D. Cervantes, J. Chandler, B. Charnock, R. Chatzimicali, A. Chinery, E. Chishti, A. 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Elizabeth, Akgün, Fatma Nur, Aletti, Gabriele, Alkış, Neslihan, Allan, Katie, Allan, Ashley, Allaouchiche, Bernard, Allcock, Clare, Almasy, Emoke, Amey, Isobel, Amigoni, Maria, Andersen, Elin, Andersson, Peder, Anipchenko, Natalya, Antunes, Pedro, Armstrong, Earlene, Aslam, Tayyba Naz, Aslin, Bjorn, Assunção, José Pedro, Ausserer, Julia, Avvai, Mary, Awad, Nahla, Ayas Montero, Begoña, Ayuso, Mercede, Azevedo, Patricia, Badarau, Victoria, Badescu, Roxana, Baiardo Redaelli, Martina, Baird, Colin, Baird, Yolanda, Baker, Tim, Balaji, Packianathaswamy, Bălan, Cristina, Balandin, Alina, Balescu-Arion, Carmen, Baliuliene, Vilda, Baltasar Isabel, Jorge, Baluch, Saif Nasr, Bandrabur, Daniela, Bankewitz, Carla, Barber, Katrina, Barbera, Francesco, Barcraft-Barnes, Helena, Barletti, Valentina, Barnett, Gill, Baron, Kirsty, Barros, Ana, Barsan, Victoria, Bartlett, Pauline, Batistaki, Chrysanthi, Baumgarten, Georg, Baytas, Volkan, Beauchamp, Nigel, Becerra Cayetano, Isabel A., Bell, Stephanie, 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Damster, Sabrine, Danguy des Déserts, Marc, Daniliuc, Aura, Danninger, Thoma, Darwish, Imad, Dascalu, Corina, Davies, Kirsty, Davies, Simon, De Boer, Han, De Flaviis, Adelisa, De Selincourt, Gabrielle, Deana, Cristian, Debaene, Bertrand, Debreceni, Gabor, Dedhia, Jatin, Delgado Garcia, Isabel, Della Rocca, Giorgio, Delroy-Buelles, Llana, Desai, Tejal, Dhillon, Parveen, Di Giacinto, Ida, Di Mauro, Piero, Diaz Gomez, Tamara V., Dimitrovski, Aleksandar, Dinic, Vesna, Dîrzu, Dan-Sebastian, Divander, Mona Britt, Dolinar, Janez, Domingues, Susana, Doolan, Jame, Downes, Charlotte, Dragoescu, Nicoleta Alice, Droc, Gabriela, Dum, Elisabeth, Dumitrescu, Alexandra, Duncan, Louise, Dzurňáková, Paul, Eberl, Susanne, Edwards, Jayne, Edwards, Mark, Ekelund, Kim, Ekengren, Patrik, Elghouty, Eyad, Ellerkmann, Richard, Ellis, Helen, Elme, Andrea, Ernst, Thoma, Errando, Carlos Lui, Estenes, Simao, Ewaldsson, Calli, Farid, Nahla, Featherstone, Jame, Febres, Daniela, Fedorov, Sergey, Feggeler, Johanna, Feijten, Prisca, Fellmann, Tobia, Fernandez Candil, Juan, Fernandez Castineira, Ana, Fernández Castineira, Juan, Fernando, Aruna, Ferrando, Carlo, Ferreira, Leonia, Ferreira, Patrick, Feyling, Ander, Filipescu, Daniela, Fleischer, Andrea, Floris, Leda, Foerster, Ur, Fox, Benjamin, Franke, Uwe, Frasca, Deni, Frey, Christian, Frost, Victoria, Fullin, Giorgio, Fumagalli, Jacopo, Furneval, Julie, Fusari, Maurizio, Gallacher, Stuart, Galushka, Svetlana, Gambale, Giorgio, Gambino, Irene, Garcia-Perez, Maria Luisa, Garg, Sanjeev, Garlak, Justyna, Gavranovic, Zeljka, Gavrilov, Roman, Gaynor, Lame, Gecaj Gashi, Agreta, Georghiou, Maria, Gerjevic, Bozena, Gferer, Gudrun, Giarratano, Antonino, Gibson, Andy, Gievski, Vanja, Giles, Julian, Gillberg, Lar, Gilowska, Katarzyna, Gilsanz Rodriguez, Fernando, Gioia, Antonio, Giovannoni, Cecilia, Girotra, Vandana, Gkinas, Dimitrio, Gkiokas, George, Godoroja, Daniela, Goebel, Ulrich, Goel, Vandana, Gonzalez, Matilde, Goranovic, Tatjana, Gornik-Wlaszczuk, Ewa, Gosavi, Smita, Gottfridsson, peter, Gottschalk, André, Granell, Manuel, Granstrom, Anna, Grassetto, Alberto, Greenwood, Anna, Grigoras, Ioana, Grintescu, Ioana, Gritsan, Alexey, Gritsan, Galina, Grynyuk, Andriy, Guadagnin, Giovanni Maria, Guarnieri, Marcello, Güçlü, Çiğdem, Guerrero Diez, Maria, Gunenc, Ferim, Günther, Ulf, Gupta, Pawan, Guttenthaler, Vera, Hack, Yvonne, Hafisayena, Ade, Hagau, Natalia, Haldar, Jagannath, Hales, Dawn, Hancı, Volkan, Hanna-Jumma, Sameer, Harazim, Hana, Harlet, Pierre, Harper, Daniel, Harris, Benjamin, Harvey, Orla, Hashimi, Medita, Hawkins, Lesley, Hayes, Conrad, Heaton, Jame, Heier, Tom, Helliwell, Laurence, Hemmes, Sabrine, Henderson, Kate, Hermanides, Jeroen, Hermanns, Henning, Herrera Hueso, Berta, Hestenes, Siv, Hettiarachchi, Roshane, Highgate, Judith, Hodgson, Keith, Hoelbling, Daniel, Holland, Jonathan, Horhota, Lucian, Hormis, Anil, Hribar, Renata, Hua, Alina, Humphreys, Sally, Humphries, Ryan, Humpliková, Simona, Hunt, Janez, Husnain, Ali, Hussein, Ahmed, Hyams, Benjamin, Iannuccelli, Fabrizio, Ilette, Katie, Ilyas, Carl, Inan, Turgay, India, Immaculada, Ionițăv, Victor, Irwin, Foo, Jain, Vipul, Janez, Benedikt, Jankovic, Radmilo, Jenkins, Sarah, Jenko, Matej, Jimenez, Raquel, Jiménez Gomez, Bárbara, Joachim, Sugganthi, Joelsson-Alm, Eva, John, John, Jonikaite, Lina, Jovic, Miomir, Jungwirth, Bettina, Junke, Etienne, Kabakov, Bory, Kadaoui, Salah-Din, Kanski, Andrzej, Karadag, Süheyla, Karbonskiene, Aurika, Karjagin, Juri, Kasnik, Darja, Katanolli, Fato, Katsika, Eleni, Kaufmann, Kai, Keane, Helen, Kelly, Martin, Kent, Melanie, Keraitiene, Grazina, Khudhur, Ahmed, Khuenl-Brady, Karin, Kidd, Laurie, King, Siobhan, Kirchgäßner, Katharina, Klancir, Tino, Klucniks, Andri, Knotzer, Johann, Knowlden, Peter, Koers, Lena, Kompan, Janez, Koneti, Kiran K, Kooij, Fabian, Koolen, Eric, Koopman - van Gemert, Anna Wilhelmina Margaretha Maria, Kopp, Kristen, Korfiotis, Dimitrio, Korolkov, Oleg, Kosinová, Martina, Köstenberger, Marku, Kotzinger, Oskar, Kovačević, Marko, Kranke, Peter, Kranke, Eva, Kraus, Christiane, Kraus, Stephanie, Kubitzek, Christiane, Kucharski, Rafal, Kucukguclu, Semih, Kudrashou, Allaksandr, Kumar, Vinayak, Kummen, Live, Kunit, Cornelia, Kushakovsky, Vlad, Kuvaki, Bahar, Kuzmanovska, Biljana, Kyttari, Aikaterina, Landoni, Giovanni, Lau, Gary, Lazarev, Konstantin, Legett, Samantha, Legrottaglie, Anna Maria, Leonardi, Silvia, Leong, Maria, Lercher, Helene, Leuvrey, Matthieu, Leva, Brigitte, Levstek, Meta, Limb, Jame, Lindholm, Espen, Linton, Fiona, Liperi, Corradero, Lipski, Fabian, Lirk, Philipp, Lisi, Alberto, Lišková, Katarina, Lluch Oltra, Aitana, Loganathan, Vinothan, Lombardi, Stefania, Lopez, Eloisa, Lopez Rodríguez, Maria, Lorenzini, Laura, Lowicka, Malgorzata, Lugovoy, Alexander, Luippold, Madeleine, Lumb, Andrew, Macas, Andriu, Macgregor, Mark, Machado, Humberto, Maciariello, Maria, Madeira, Isabel, Maitan, Stefan, Majewski, Jacek, Maldini, Branka, Malewski, Georgia, Manfredini, Livia, Männer, Olja, Marchand, Bahareh, Marcu, Alexandra, Margalef, Jordi, Margarson, Michael, Marinheiro, Lucia, Markic, Ana, Markovic Bozic, Jasmina, Marrazzo, Francesco, Martin, Jane, Martin Ayuso, Maria, Martinez, Esteher, Martino, Enrico Antonio, Martinson, Victoria, Marusic-Gaser, Katarina, Mascarenhas, Catia, Mathis, Cindy, Matsota, Paraskevi, Mavrommati, Eleni, Mazul Sunko, Branka, McCourt, Killian, McGill, Neil, McKee, Raymond, Meço, Başak Ceyda, Meier, Sonja, Melbourne, Susan, Melbybråthen, Grethe, Meli, Andrea, Melia, Aiden, Melotti, Rita Maria, Menga, Maria Rosaria, Mercer, Pauline, Merotra, Susan, Mescolini, Silvia, Metterlein, Thoma, Michalov, Martin, Michlig, Sam, Midgley, Susan, Milić, Morena, Milojevic, Milan, Miñana, Amanda, Minto, Gary, Mirabella, Lucia, Mirea, Liliana, Mittelstädt, Ludger, Moeglen, Aude, Moise, Alida, Mokini, Zhirajr, Molin, Anna, Moltó, Lui, Monea, Maria Concetta, Montalto, Francesca, Montgomery, Jane, Montgomery, Claire, Montillo, Gerardo, Moore, Sally, Moore, Faye, Moreira, Zelia, Moreno, Tania, Moreno, Ricardo, Moret, Enrique, Moreton, Sarah, Morgan, Marianne, Moro Velasco, Concepción, Morri, Davide, Moull, Alice, Moura, Fernando, Mráz, Peter, Mrozek, Katarzyna, Mukhtar, Karim, Muniyappa, Sudeshkumar, Murray, Heather, Murthy, Burra VS, Mushambi, Mary, Nadolski, Maria, Nardelli, Pasquale, Nardin, Giordano, Navarro Pérez, Rosalía, Naveiro, Andrea, Negri, Manuela, Nesek Adam, Visnja, Neskovic, Vojislava, Neuwersch, Stefan, Neves, Miriam, Nguyen, Bavinh, Ní Eochagáin, Aisling, Nicholas, Caroline, Nightingale, Jeremy, Norrie, Kylie, Novak-Jankovic, Vesna, Novakova, Andrea, Novillo, Marta, Numan, Sandra, Oduro-Dominah, Louise, Oldner, Ander, Oliveira, Isabel, Ologoiu, Daniela, Oloktsidou, Irini, O'Reilly, Rosalind, Orlando, Alessandro, Ovezov, Alexey, Ozbilgin, Sule, Paal, Peter, Padin Barreiro, Lidia, Palugniok, Ryszard, Papaioannou, Alexandra, Papapostolou, Konstantino, Paranthaman, Prabhakar, Pardey Bracho, Gilda, Parente, Suzana, Parfeni, Alexandru, Pasin, Laura, Passey, Samuel, Pastor, Ernesto, Patch, Sarah, Patil, Andan, Paunescu, Marilena-Alina, Pehboeck, Daniel, Pereira, Manuela, Pereira, Carla, Perez Caballero, Paula, Pérez García, Aníbal, Pérez Soto, Antonia, Perez Tejero, Gisela, Perez-Cerda, Francisco, Pesenti, Antonio, Petta, Rocco, Philippe, Simon, Pickering, David, Pico Veloso, Jandro, Pina, Pedro, Pinho-Oliveira, Vítor, Pinol, Santiago, Pinto, Rita, Pistidda, Laura, Pitterle, Manuela, Piwowarczyk, Paweł, Plotnikova, Olga, Pohl, Holger, Poldermann, Jorinde, Polkovicová, Lucia, Pompei, Livia, Popescu, Mihai, Popović, Radmila, Pota, Vincenzo, Potocnik, Miriam, Potręć, Beata, Potter, Alison, Pramod, Nalwaya, Prchalova, Martina, Preckel, Benedikt, Pugh, Richard, Pulletz, Mark, Radoeshki, Aleksandar, Rafi, Amir, Ragazzi, Riccardo, Raineri Santi, Maurizio, Rajamanickam, Tamiselvan, Rajput, Zahra, Ramachandran, Rajeskar, Ramasamy, Radhika, Ramessur, Suneil, Rao, Roshan, Rasmussen, Ander, Rato, André, Razaque, Usman, Real Navacerrada, M. Isabel, Reavley, Caroline, Reid, Jame, Reschreiter, Henrik, Rial, Erick, Ribas Carrasco, Patricia, Ribeiro, Sandy, Rich, Nathalie, Richardson, Lydia, Rimaitis, Kestuti, Rimaitis, Mariu, Ringvold, Else-Marie, Ripke, Fabian, Ristescu, Irina, Ritchie, Keith, Ródenas, Frederic, Rodrigues, Patrícia, Rogers, Emma, Rogerson, David, Romagnoli, Stefano, Romero, Esther, Rondovic, Goran, Rose, Bernd Oliver, Roth, Winfried, Rotter, Marie-Therese, Rousseau, Guy, Rudjord, Ander, Rueffert, Henrik, Rundgren, Malin, Rupprecht, Korbinian, Rushton, Andrew, Russotto, Vincenzo, Rypulak, Elżbieta, Ryszka, Maciej, Sà, Jacinta, Sà Couto, Paula, Saby, Sandrine, Sagic, Jelena, Saleh, Omar, Sales, Gabriele, Sánchez Sánchez, Yván, Sanghera, Sumayer, Şanli Karip, Ceren, Santiveri Papiol, Francisco Javier, Santos, Sofia, Sarno, Stephen, Saul, Daniel, Saunders, David, Savic, Nenad, Scalco, Loïc, Scanlon, Deborah, Schaller, Stefan, Schax, Christoph, Scheffer, Gert Jan, Schening, Anna, Schiavone, Vincenzo, Schmidt-Ehrenberg, Florian, Schmidt-Mutter, Catherine, Schönberg, Christina, Schopflin, Christian, Schreiber, Jan-Uwe, Schultz, Marcu, Schurig, Marlen, Scott, Carmen, Sebestian, Siby, Sehgal, Selena, Sem, Victoria, Semenas, Egidiju, Serafini, Elena, Serchan, Pashalitsa, Shields, Martin, Shobha, Ramakrishnan, Shosholcheva, Mirjana, Siamansour, Tanja, Siddaiah, Narendra, Siddiqi, Khalid, Sinclair, Rhona, Singh, Permendra, Singh, Rajendra, Sinha, Aneeta, Sinha, Ashok, Skinner, Amanda, Smee, Elizabeth, Smekalova, Olga, Smith, Neil, Smith, Thoma, Smitz, Carine, Smole, Daniel, Sojčić, Nataša, Soler Pedrola, Maria, Somanath, Sameer, Sonksen, Julian, Sorella, Maria Christina, Sörmus, Alar, Soro, Marina, Soto, Carmen, Spada, Anna, Spadaro, Savino, Spaeth, Johanne, Sparr, Harald, Spielmann, Annika, Spindler-Vesel, Alenka, Stamelos, Matthaio, Stancombe L, Liucia, Stanculescu, Andreea, Standl, Thoma, Standley, Tom, Stanek, Ondrej, Stanisavljević, Snežana, Starczewska, Malgorzata, Stäuble, Christiane, Steen, Julie, Stefan, Oana Maria, Stell, Elizabeth, Stera, Caterina, Stevens, Marku, Stoerckel, Marlène, Stošić, Biljana, Stourac, Petr, Stroumpoulis, Konstantino, Struck, Rafael, Suarez de la Rica, Alejandro, Sultanpori, Altaf, Sundara Rajan, Rajinikanth, Suying, Ong, Svensen, Christer, Swan, Louise, Syrogianni, Paulina, Sysiak, Justyna, Szederjesi, Jano, Taddei, Stefania, Tan Hao, Ern, Tanou, Virginia, Tarabová, Katarina, Tardaguila Sancho, Paula, Tarroso, Maria, Tartaglione, Marco, Taylor, Emma, Tbaily, Lee, Telford, Richard, Terenzoni, Massimo, Theodoraki, Kassiani, Thornley, Helen, Tiganiuc, Liviu, Toim, Hardo, Tomescu, Dana, Tommasino, Concezione, Toni, Jessica, Toninelli, Arturo, Toretti, Ilaria, Townley, Stephen, Trepenaitis, Dariu, Trethowan, Brian, Tsaousi, Georgia, Tsiftsi, Aikaterini, Tudor, Adrada, Turan, Güldem, Turhan, Sanem Çakar, Unic-Stojanovic, Dragana, Unterbuchner, Christoph, Unzueta, Carmen, Uranjek, Jasna, Ursic, Tomaz, Vaida, Simona, Valldeperas Ferrer, Silvia, Valldeperas Hernandez, Maria Inmaculada, Valsamidis, Dimitri, Van Beek, Rienk, Van dasselaer, Nick, Van Der Beek, Tim, Van Duivenvoorde, Yoni, van Klei, Wilton A., Van Poorter, Fran, Van Zaane, Ba, Van Zundert, Tom, Van Zyl, Rebekka, Vargas Munoz, Ana Milena, Varsani, Nimu, Vasconcelos, Pedro, Vassilakis, Georgio, Vecchiatini, Tommaso, Vecera, Lubomir, Vercauteren, Marcel, Verdouw, Ba, Verheyen, Veerle, Verri, Marco, Vicari Sottosanti, Luigi Giancarlo, Vico, Manuel, Vidal Mitjans, Patricia, Vilardi, Anna, Vissicchio, Daniela, Vitale, Giovanni, Vitković, Bibiana, Vizcaychipi, Marcela Paola, Voicu, Alexandra, Voje, Minca, Volfová, Ivana, Volta, Carlo Alberto, Von Lutterotti, Theresa, von Tiesenhausen, Anna, Vrecic-Slabe, Simona, Vukcevic, Dejan, Vukovic, Rade, Vullo, P. Agostina, Wade, Andrew, Wallberg, Hanna, Wallden, Jakob, Wallner, Johann, Walther Sturesson, Louise, Watson, Davina, Weber, Stefan, Wegiel Leskiewiq, Anna, Weller, Debbie, Wensing, Carine, Werkmann, Marku, Westberg, Henrik, Wikström, Erik, Williams, Benedict, Wilson, Robin, Wirth, Steffen, Wittmann, Maria, Wood, Laura, Wright, Stella, Zachoval, Christian, Zambon, Massimo, Zampieri, Silvia, Zampone, Salvatore, Zangrillo, Alberto, Zani, Gianluca, Zavackiene, Asta, Zieglerder, Raphael, Zonneveldt, Harry, Zsisku, Lajo, Zucker, Tom-Philipp, Żukowski, Maciej, Zuleika, Mehrun, and Zupanĕiĕ, Darja

Subjects
Pulmonary and Respiratory Medicine, pulmonary complications, muscle relaxants, Post-anaesthesia complications, Neuromuscular Blockade, pulmonary complication, muscle relaxant, neuromuscular block, postoperative pulmonary complication, business.industry, Retrospective cohort study, post-operative pulmonary complications, Neuromuscular monitoring, Neuromuscular Blocking Agents, Sugammadex, NO, Anaesthesia, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Anesthesia, Medicine, General anaesthesia, Neuromuscular Agents, 030212 general & internal medicine, MED/41 - ANESTESIOLOGIA, Prospective cohort study, business, medicine.drug
Abstract

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj −0·3%, 95% CI −2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; −0·4%, −3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation: We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications. Funding: European Society of Anaesthesiology.

Published
2019
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20. Positive selection of ORF3a and ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic

Author

Eberl S, Douglas P. Gladue, Isabel S. Novella, Selene Zárate, Manuel V. Borca, and Lauro Velazquez-Salinas

Subjects
Genetics, Phylogenetic tree, Positive selection, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pandemic, Epistasis, Biology, Evolutionary dynamics, Genome, Gene
Abstract

In this study, we analyzed full-length SARS-CoV-2 genomes from multiple countries to determine early trends in the evolutionary dynamics of the novel COVID-19 pandemic. Results indicated SARS-CoV-2 evolved early into at least three phylogenetic groups, characterized by positive selection at specific residues of the accessory proteins OFR3a and ORF8a. We also report evidence of epistatic interactions among sites in the genome that may be important in the generation of variants adapted to humans. These observations might impact not only public health, but also suggest more studies are needed to understand the genetic mechanisms that may affect the development of therapeutic and preventive tools, like antivirals and vaccines.

Published
2020
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22. A practical 3D tomographic method for correcting patient head motion in clinical SPECT

Author

Fulton, R.R., Eberl, S., Meikle, S.R., Hutton, B.F., and Braun, M.

Subjects
Tomography -- Usage, SPECT imaging -- Research, Head, Business, Electronics, Electronics and electrical industries
Abstract

Patient motion during brain SPECT studies can degrade resolution and introduce distortion. We have developed a correction method which incorporates a motion tracking system to monitor the position and orientation of the patient's head during acquisition. Correction is achieved by spatially repositioning projections according to measured lead movements and reconstructing these projections with a fully three-dimensional (3D) algorithm. The method has been evaluated in SPECT studies of the Hoffman 3D brain phantom performed on a triple head camera with fan beam collimation. Movements were applied to the phantom and recorded by a head tracker during SPECT acquisition. Fully 3D reconstruction was performed using the motion data provided by the tracker. Correction accuracy was assessed by comparing the corrected and uncorrected studies with a motion free study, visually and by calculating mean squared error (MSE). In all studies, motion correction reduced distortion and improved MSE by a factor of 2 or more. We conclude that this method can compensate for head motion under clinical SPECT imaging conditions.

Published
1999

25. In Reply: Xenon Myocardial Protection in Cardiac Surgery: Effective around the Clock?

Author

Hofland, J., Ouattara, A., Schaller, M., Bein, B., Liefde, I., Fellahi, J.L., Gruenewald, M., Hazebroucq, J., Ecoffey, C., Joseph, P., Heringlake, M., Steib, A., Coburn, M., Amour, J., Rozec, B., Meybohm, P., Preckel, B., Hanouz, J.L., Tritapepe, L., Tonner, P., Benhaoua, H., Roesner, J.P., Tenbrinck, R., Bogers, A.J.J.C., Mik, B.G., Coiffic, A., Renner, J., Steinfath, M., Francksen, H., Broch, O., Haneya, A., Guinet, P., Daviet, L., Brianchon, C., Rosier, S., Lehot, J.J., Paarmann, H., Schon, J., Hanke, T., Ettel, J., Olsson, S., Klotz, S., Samet, A., Laurinenas, G., Thibaud, A., Cristinar, M., Collanges, O., Levy, F., Rossaint, R., Stevanovic, A., Schaelte, G., Stoppe, C., Hamou, N.A., Hariri, S., Quessard, A., Carillion, A., Morin, H., Silleran, J., Robert, D., Crouzet, A.S., Zacharowski, K., Reyher, C., Iken, S., Weber, N.C., Hollmann, M., Eberl, S., Carriero, G., Collacchi, D., Persio, A. Di, Fourcade, O., Bergt, S., and Alms, A.

Subjects
Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Abstract

Item does not contain fulltext

Published
2018

26. TANAMI: Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry

Author

C. Müller, M. Kadler, R. Ojha, R. Schulz, J. Trüstedt, P. G. Edwards, E. Ros, B. Carpenter, R. Angioni, J. Blanchard, M. Böck, P. R. Burd, M. Dörr, M. S. Dutka, T. Eberl, S. Gulyaev, H. Hase, S. Horiuchi, U. Katz, F. Krauß, J. E. J. Lovell, T. Natusch, R. Nesci, C. Phillips, C. Plötz, T. Pursimo, J. F. H. Quick, J. Stevens, D. J. Thompson, S. J. Tingay, A. K. Tzioumis, S. Weston, J. Wilms, J

Published
2018
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30. A topo-graph model for indistinct target boundary definition from anatomical images

Author

Cui, H, Wang, X, Zhou, J, Gong, G, Eberl, S, Yin, Y, Wang, L, Feng, D, Fulham, M, Cui, H, Wang, X, Zhou, J, Gong, G, Eberl, S, Yin, Y, Wang, L, Feng, D, and Fulham, M

Abstract

© 2018 Elsevier B.V. Background and Objective: It can be challenging to delineate the target object in anatomical imaging when the object boundaries are difficult to discern due to the low contrast or overlapping intensity distributions from adjacent tissues. Methods: We propose a topo-graph model to address this issue. The first step is to extract a topographic representation that reflects multiple levels of topographic information in an input image. We then define two types of node connections - nesting branches (NBs) and geodesic edges (GEs). NBs connect nodes corresponding to initial topographic regions and GEs link the nodes at a detailed level. The weights for NBs are defined to measure the similarity of regional appearance, and weights for GEs are defined with geodesic and local constraints. NBs contribute to the separation of topographic regions and the GEs assist the delineation of uncertain boundaries. Final segmentation is achieved by calculating the relevance of the unlabeled nodes to the labels by the optimization of a graph-based energy function. We test our model on 47 low contrast CT studies of patients with non-small cell lung cancer (NSCLC), 10 contrast-enhanced CT liver cases and 50 breast and abdominal ultrasound images. The validation criteria are the Dice's similarity coefficient and the Hausdorff distance. Results: Student's t-test show that our model outperformed the graph models with pixel-only, pixel and regional, neighboring and radial connections (p-values <0.05). Conclusions: Our findings show that the topographic representation and topo-graph model provides improved delineation and separation of objects from adjacent tissues compared to the tested models.

Published
2018

31. Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial

Author

Hofland, J., Ouattara, A., Fellahi, J.L., Gruenewald, M., Hazebroucq, J., Ecoffey, C., Joseph, P., Heringlake, M., Steib, A., Coburn, M., Amour, J., Rozec, B., Liefde, I., Meybohm, P., Preckel, B., Hanouz, J.L., Tritapepe, L., Tonner, P., Benhaoua, H., Roesner, J.P., Bein, B., Hanouz, L., Tenbrinck, R., Bogers, A., Mik, B.G., Coiffic, A., Renner, J., Steinfath, M., Francksen, H., Broch, O., Haneya, A., Schaller, M., Guinet, P., Daviet, L., Brianchon, C., Rosier, S., Lehot, J.J., Paarmann, H., Schon, J., Hanke, T., Ettel, J., Olsson, S., Klotz, S., Samet, A., Laurinenas, G., Thibaud, A., Cristinar, M., Collanges, O., Levy, F., Rossaint, R., Stevanovic, A., Schaelte, G., Stoppe, C., Hamou, N.A., Hariri, S., Quessard, A., Carillion, A., Morin, H., Silleran, J., Robert, D., Crouzet, A.S., Zacharowski, K., Reyher, C., Iken, S., Weber, N.C., Hollmann, M., Eberl, S., Carriero, G., Collacchi, D., Persio, A. Di, Fourcade, O., Bergt, S., Alms, A., APH - Quality of Care, Anesthesiology, ANS - Neuroinfection & -inflammation, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Male, Methyl Ethers, inhalation, Internationality, Xenon, Troponin I, anesthesia, Middle Aged, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Sevoflurane, Postoperative Complications, Treatment Outcome, anesthetics, intravenous, Anesthetics, Inhalation, Anesthesia, Intravenous, Humans, Female, Single-Blind Method, Prospective Studies, aged, anesthetics, inhalation, biomarkers, coronary artery bypass, female, humans, male, methyl ethers, middle aged, postoperative complications, prospective studies, single-blind method, treatment outcome, troponin i, xenon, anesthesia, intravenous, internationality, Coronary Artery Bypass, Biomarkers, Aged
Abstract

Item does not contain fulltext BACKGROUND: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. METHODS: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. RESULTS: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. CONCLUSIONS: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Published
2017

32. Primary lung tumor segmentation from PET-CT volumes with spatial-topological constraint

Author

Cui, H, Wang, X, Lin, W, Zhou, J, Eberl, S, Feng, D, and Fulham, M

Subjects
Nuclear Medicine & Medical Imaging, Lung Neoplasms, Positron-Emission Tomography, Humans, 1103 Clinical Sciences, Cone-Beam Computed Tomography, Lung, Algorithms
Abstract

PURPOSE: Accurate lung tumor segmentation is a prerequisite for effective radiation therapy and surgical planning. However, tumor delineation is challenging when the tumor boundaries are indistinct on PET or CT. To address this problem, we developed a segmentation method to improve the delineation of primary lung tumors from PET-CT images. METHODS: We formulated the segmentation problem as a label information propagation process in an iterative manner. Our model incorporates spatial-topological information from PET and local intensity changes from CT. The topological information of the regions was extracted based on the metabolic activity of different tissues. The spatial-topological information moderates the amount of label information that a pixel receives: The label information attenuates as the spatial distance increases and when crossing different topological regions. Thus, the spatial-topological constraint assists accurate tumor delineation and separation. The label information propagation and transition model are solved under a random walk framework. RESULTS: Our method achieved an average DSC of 0.848 ± 0.036 and HD (mm) of 8.652 ± 4.532 on 40 patients with lung cancer. The t test showed a significant improvement (p value < 0.05) in segmentation accuracy when compared to eight other methods. Our method was better able to delineate tumors that had heterogeneous FDG uptake and which abutted adjacent structures that had similar densities. CONCLUSIONS: Our method, using a spatial-topological constraint, provided better lung tumor delineation, in particular, when the tumor involved or abutted the chest wall and the mediastinum.

Published
2015

33. Routine production of 18F‾ with a beam current of 200 µA on a GE PETtrace cyclotron: Experience over > 18 Months

Author

Eberl, S., Lam, P., Bourdier, T., Henderson, D., Fulham, M., Royal Prince Alfred Hospital, Sydney, NSW, Australia, and University of Sydney, Sydney, NSW Australia

Subjects
ddc:530, 18F, high beam current, 18F, hoher Strahlstrom
Abstract

Introduction The increasing demand for [18F]FDG for clinical PET-CT and the efficiencies associated with large production runs have encouraged endeavors to increase the amount of 18F− produced by cyclotrons in a single run. The amount of 18F− is determined by the saturation yield of the nuclear reaction, the irradiation time and the beam current striking the target. The saturation yield is a function of beam energy (typically fixed for PET cyclotrons), the enrichment of the H218O (typically > 97 %) and the efficiency of the target design. Target design has already been optimized on current systems. Diminishing gains in activity are achieved by extending the irradiation time much beyond 3 hrs, so the main focus has been to increase beam current onto the targets. Increasing the beam current requires: i) a cyclotron capable of producing the increased beam current; ii) targets that tolerate the beam current without appreciable loss in saturation yield; iii) sufficient shielding of the cyclotron and hot cells to accommodate the proportionally larger radiation dose rates during higher current irradiation and from the larger activities delivered to the hot cells. We reported [1] that the self-shielded targets fitted to our cyclotron can accommodate 100 µA currents without appreciable loss in saturation yield. We also identified the potential of routine production at 200 A (100 A per target in dual target irradiation mode), but had not establish its long-term viability in routine use. We present our experience in using 200 µA for routine production of 18F- since September 2012. Material and Methods Our PETtrace cyclotron was installed in 2002 and has been used for routine production of various 18F and 11C tracers since January 2003. It has been upgraded incrementally so that it is now equivalent to a current generation PETtrace 880 cyclotron, which is specified at a total beam current of 130 µA. The only components on our cyclotron currently not part of the standard PETtrace 880 cyclotron configuration are the self-shielded targets and a license which allows total target beam current of 200 µA. The self-shielded targets utilize a W/Cu alloy for the main body of the target surrounding the Havar foil to provide shielding from the Havar foil by a factor of about 10 and shielding of any remnant 18F- activity in the targets by a factor of about 100 [1]. The niobium target chamber is the same size as used in the standard GE Nb25 targets. However, it dispenses with the He cooling and the vacuum foil. Only the water foil is used, which is directly exposed to the vacuum in the chamber. Foil cooling is through the water in the target chamber. One of the issues that we previously identified [1] is beam stripping by gas molecules in the vacuum tank. The amount of beam that is stripped and which impacts on components in the cyclotron is proportional to the beam current. At high currents, this can result in a runaway condition, where the effects of the stripped beam deteriorate vacuum; this then results in more beam stripping and more severe effects. The effect of diffusion pump maintenance on vacuum system performance and on the reduction of beam stripping was investigated as part of this study. We have previously found that running the ion source gas at a low flow rate (2 sccm) when cyclotron is not used greatly reduces deterioration of ion source performance over time and with use [1]. This gas flow also appears to have a beneficial effect on the vacuum. Ion source gas flow when cyclotron is off has been employed throughout the evaluation period. [18F]FDG was produced with TRACERlab MXFDG modules or FASTlab modules using both Phosphate and Citrate cassettes. Stability studies of [18F]FDG were performed to ensure it met specifications over the specified expiry time. Our current stabilization regime did not have to be adjusted for the higher activities produced with the higher beam currents. [18F]FDG yields were calculated using input activity estimates from saturation yield and beam time and current and the non-decay corrected [18F]FDG activity measured at the end of synthesis. Thus yield calculations include target yield variations and losses in the transfer lines and not just synthesis yield. Results and Conclusion The flip-in probe to extraction foil transmissions as a function of ion source gas flow are given in TABLE 1. Transmission decreases with increasing ion source gas flow, as expected for a system with an internal ion source. In addition, diffusion pump maintenance had a positive impact on the transmission and this is of particular benefit at the higher beam currents where minimising beam stripping becomes more critical. The ion source output, however, decreases with decreasing ion source gas flow; hence ion source gas flow is a compromise between ion source output and probe to foil transmission. We currently use a gas flow of 5.5 sccm for our 200 µA runs. Over the period from 1st September 2012 to end of March 2014, a total of 419 [18F]FDG produc-tions were performed at total target beam currents ranging from 160 µA to 200 µA, with 227 production runs being performed at 200 µA. Beam times were typically 90 to 120 min, with some productions up to 180 min. The [18F]FDG yields are summarized in TABLE 2. The yields for the FASTlab phosphate and citrate cassettes have been listed separately in TABLE 2 as they are known to be different [2,3]. The yields obtained with the TRACERlab MXFDG are also shown. The yields at 200 µA total target current are not appreciably different from those at < 200 µA current, irrespective of the synthesis method. Consistency of yield is also not adversely impacted by the higher beam current. For a 180 min, 200 µA test production, the [18F]FDG activity produced using the FASTlab phosphate cassette was 763 GBq (20.6 Ci). Clinical productions with the FASTlab phosphate were limited to 130 min maximum beam time for 200 µA and achieved a maximum [18F]FDG activity of 656 GBq (17.7 Ci). The tolerance to a reduction in performance of the critical components to achieve high current operation (RF, ion source output and vacuum system) is reduced at high beam currents. The requirements for routine maintenance of ion source, targets and extraction system, however, have not increased with the increase in beam current from 160 µA to 200 µA. Extraction foil life and ion source maintenance intervals have remained at about 2000 Ah and >120 µAh, respectively. As more experience has been gained with the self-shielded targets, service interval is actually being extended from about 10,000 µAh to 20,000 µAh, despite the higher beam currents. Diffusion pump maintenance is currently recommended every 5 years, but a 2 year maintenance interval may be advantageous for 200 µA, given the observed deterioration over a 5 year period and the improvement in performance post service (Table 1). The more frequent service is associated with the additional costs of diffusion pump oil and an extra day of scheduled down-time. Typically, vacuum is sufficiently well established 24 h after opening of the vacuum tank to run 200 µA beams with the vacuum and beam conditioning that we employ. The targets generally have coped well with the 100 µA per target current (200 µA total beam current for dual target irradiation) over this 18 month period. However, currents of 80 µA to µ100 A per target in dual target irradiation mode reduce the tolerance to sudden increases in one of the target currents. There were 4 occasions (2 test beams and 2 production beams) when there were sudden increases of target current from 90 µA and 100 µA to about 150 µA. The rapid increase in heat deposited on the foil and target chamber and the resultant rapid pressure rise in the target chamber could not be withstood by the foil and target foil rupture ensued. This compared to 1 target foil issue over a similar period of time (18 months) at lower beam currents on the standard Nb25 target. Three separate causes were identified for these overshoots in target current: 1) behavior of control system when beam is allowed to continue past the set time; 2) large changes of set current of one of the two targets irradiated during a dual irradiation test beam and 3) an issue with DEE voltage regulation caused by the mechanical flap controls. These issues have been addressed by procedural changes (issues 1 and 2) and by fitting an available upgrade of the mechanical flap control mechanism (issue 3). The two target foil ruptures during production did not cause cancellation or delays to patient scanning, as the demand could be met by multi-ple productions and deliveries from the unaf-fected target. No unscheduled down-days occurred during the evaluation period. We have been able to achieve routine operation at 200 µA beam current through careful optimization of the critical components and parameters and a maintenance regime that we have detailed previously [1]. This maintenance scheme has not changed for the routine 200 µA operation. The safety margin, however, is reduced and so careful monitoring of the system is required to ensure that issues in one of the subsystems do not cause major events such as target foil ruptures. Our [18F]FDG yields have been maintained at the higher current and 200 µA allows large quantities of [18F]FDG to be produced routinely in a single run with relatively short beam times.

Published
2015

35. Management of large mediastinal masses: surgical and anesthesiological considerations

Author

Li, W.W.L., Boven, W.J. van, Annema, J.T., Eberl, S., Klomp, H.M., Mol, B.A. de, Li, W.W.L., Boven, W.J. van, Annema, J.T., Eberl, S., Klomp, H.M., and Mol, B.A. de

Abstract

Contains fulltext : 170922.pdf (publisher's version ) (Open Access), Large mediastinal masses are rare, and encompass a wide variety of diseases. Regardless of the diagnosis, all large mediastinal masses may cause compression or invasion of vital structures, resulting in respiratory insufficiency or hemodynamic decompensation. Detailed preoperative preparation is a prerequisite for favorable surgical outcomes and should include preoperative multimodality imaging, with emphasis on vascular anatomy and invasive characteristics of the tumor. A multidisciplinary team should decide whether neoadjuvant therapy can be beneficial. Furthermore, the anesthesiologist has to evaluate the risk of intraoperative mediastinal mass syndrome (MMS). With adequate preoperative team planning, a safe anesthesiological and surgical strategy can be accomplished.

Published
2016

36. Primary lung tumor segmentation from PET-CT volumes with spatial-topological constraint.

Author

Cui, H, Wang, X, Lin, W, Zhou, J, Eberl, S, Feng, D, Fulham, M, Cui, H, Wang, X, Lin, W, Zhou, J, Eberl, S, Feng, D, and Fulham, M

Abstract

PURPOSE: Accurate lung tumor segmentation is a prerequisite for effective radiation therapy and surgical planning. However, tumor delineation is challenging when the tumor boundaries are indistinct on PET or CT. To address this problem, we developed a segmentation method to improve the delineation of primary lung tumors from PET-CT images. METHODS: We formulated the segmentation problem as a label information propagation process in an iterative manner. Our model incorporates spatial-topological information from PET and local intensity changes from CT. The topological information of the regions was extracted based on the metabolic activity of different tissues. The spatial-topological information moderates the amount of label information that a pixel receives: The label information attenuates as the spatial distance increases and when crossing different topological regions. Thus, the spatial-topological constraint assists accurate tumor delineation and separation. The label information propagation and transition model are solved under a random walk framework. RESULTS: Our method achieved an average DSC of 0.848 ± 0.036 and HD (mm) of 8.652 ± 4.532 on 40 patients with lung cancer. The t test showed a significant improvement (p value < 0.05) in segmentation accuracy when compared to eight other methods. Our method was better able to delineate tumors that had heterogeneous FDG uptake and which abutted adjacent structures that had similar densities. CONCLUSIONS: Our method, using a spatial-topological constraint, provided better lung tumor delineation, in particular, when the tumor involved or abutted the chest wall and the mediastinum.

Published
2016

38. Routine production of 18F‾ with a beam current of 200 µA on a GE PETtrace cyclotron: Experience over > 18 Months

Author

Royal Prince Alfred Hospital, Sydney, NSW, Australia, University of Sydney, Sydney, NSW Australia, Eberl, S., Lam, P., Bourdier, T., Henderson, D., Fulham, M., Royal Prince Alfred Hospital, Sydney, NSW, Australia, University of Sydney, Sydney, NSW Australia, Eberl, S., Lam, P., Bourdier, T., Henderson, D., and Fulham, M.

Abstract

Introduction The increasing demand for [18F]FDG for clinical PET-CT and the efficiencies associated with large production runs have encouraged endeavors to increase the amount of 18F− produced by cyclotrons in a single run. The amount of 18F− is determined by the saturation yield of the nuclear reaction, the irradiation time and the beam current striking the target. The saturation yield is a function of beam energy (typically fixed for PET cyclotrons), the enrichment of the H218O (typically > 97 %) and the efficiency of the target design. Target design has already been optimized on current systems. Diminishing gains in activity are achieved by extending the irradiation time much beyond 3 hrs, so the main focus has been to increase beam current onto the targets. Increasing the beam current requires: i) a cyclotron capable of producing the increased beam current; ii) targets that tolerate the beam current without appreciable loss in saturation yield; iii) sufficient shielding of the cyclotron and hot cells to accommodate the proportionally larger radiation dose rates during higher current irradiation and from the larger activities delivered to the hot cells. We reported [1] that the self-shielded targets fitted to our cyclotron can accommodate 100 µA currents without appreciable loss in saturation yield. We also identified the potential of routine production at 200 A (100 A per target in dual target irradiation mode), but had not establish its long-term viability in routine use. We present our experience in using 200 µA for routine production of 18F- since September 2012. Material and Methods Our PETtrace cyclotron was installed in 2002 and has been used for routine production of various 18F and 11C tracers since January 2003. It has been upgraded incrementally so that it is now equivalent to a current generation PETtrace 880 cyclotron, which is specified at a total beam current of 130 µA. The only components on our cyclotron currently not part of the standard PETtrac

Published
2015

39. Katecholamine

Author

Hollmann, M. W., Eberl, S., Zink, Wolfgang, Amsterdam Cardiovascular Sciences, Amsterdam institute for Infection and Immunity, Anesthesiology, and Other Research

Published
2009

40. Preclinical in vivo and in vitro comparison of the translocator protein PET ligands [F]PBR102 and [F]PBR111.

Author

Eberl, S., Katsifis, A., Peyronneau, M., Wen, L., Henderson, D., Loc'h, C., Greguric, I., Verschuer, J., Pham, T., Lam, P., Mattner, F., Mohamed, A., and Fulham, M.

Subjects
LIGANDS (Biochemistry), PROTEIN binding, METABOLITES, BRAIN imaging, MICROSOMES
Abstract

Purpose: To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates ( Papio hamadryas) using PET-CT. Methods: In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography-tandem mass spectrometry. [F]PBR102 and [F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed. Results: Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K was similar for baseline and blocking studies for both radiotracers; V was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain. Conclusions: [F]PBR102 and [F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [F]PBR102 in rodents; the impact in primates was less pronounced. Both [F]PBR102 and [F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands. [ABSTRACT FROM AUTHOR]

Published
2017
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45. A prototype coded aperture detector for small animal SPECT

Author

Meikle, S. R., Kench, P., Weisenberger, A. G., Wojcik, R., Smith, M. F., Majewski, S., Eberl, S., Fulton, R. R., Rosenfeld, Anatoly B., Fullham, M. J., Meikle, S. R., Kench, P., Weisenberger, A. G., Wojcik, R., Smith, M. F., Majewski, S., Eberl, S., Fulton, R. R., Rosenfeld, Anatoly B., and Fullham, M. J.

Abstract

In a previous simulation study, we demonstrated the feasibility of using coded apertures together with pixelated detectors tors for small animal SPECT. In this paper; we further explore the potential of this approach with a prototype detector and simulated multipinhole apertures. We also investigated the effect of multiplexing due to overlapped projections on convergence properties, image signal-to-noise ratio (SNR) and spatial resolution. The detector comprises a 48/spl times/44 array of NaI(Tl) crystals, each 1 mm/spl times/1 mm/spl times/5 mm on a 1.25-mm pitch. The crystal array is directly coupled to a Hamamatsu R3941 8 cm position sensitive photomultiplier tube. Multipinhole apertures were simulated by performing repeated SPECT acquisitions of the same object with a single tungsten pinhole translated to different positions in the aperture plane. Image reconstruction is based on a three-dimensional ray driven projector which is an extension of a method described for single pinhole SPECT with a displaced center of rotation. Image estimates are updated using the maximum likelihood expectation maximization (ML-EM) algorithm. The effect of multiplexing was to slow convergence and reduce the achievable SNR by approximately 15% compared with nonmultiplexed data (but the result may be achieved in a fraction of the time). The reconstructed resolution obtained with a resolution phantom was 1.5-mm full width at half maximum and there was no appreciable difference between the resolution of multiplexed and nonmultiplexed data. These results encourage us to develop a prototype coded aperture system for high sensitivity, high resolution small animal SPECT.

Published
2002

46. CoALA-SPECT: a coded aperture laboratory animal SPECT system for pre clinical imaging

Author

Meikle, S. R., Wojcik, R., Weisenberger, A. G., Smith, M. F., Majewski, S., Kench, P., Eberl, S., Fulton, R. R., Lerch, M. L., Rosenfeld, Anatoly B., Meikle, S. R., Wojcik, R., Weisenberger, A. G., Smith, M. F., Majewski, S., Kench, P., Eberl, S., Fulton, R. R., Lerch, M. L., and Rosenfeld, Anatoly B.

Abstract

We have previously demonstrated the potential of multi-pinhole coded apertures when used in conjunction with compact pixelated detectors for high resolution, high sensitivity small animal SPECT. We are now constructing a prototype SPECT system with three such detectors mounted on a rotating gantry. Each detector comprises a 12 cm diameter circular array of NaI(Tl) crystals, each 1/spl times/1/spl times/5 mm/sup 3/ on a 1.25 mm pitch. Each crystal array is coupled to a Hamamatsu R3292 12.7 cm diameter PS-PMT. Signals from the three detectors are read out by a custom subtractive resistive circuit and multiplexed. Data are acquired by a National Instruments PCI-6110E board running on a Macintosh dual processor G4 computer under Kmax software control. Images are reconstructed using a 3D iterative MAP-EM algorithm based on a multi-pinhole forward and back projector. The trade-off between contrast and variance was studied by simulation for a number of multi-pinhole configurations. We also performed initial planar imaging studies on one of the detectors. Our results indicate that spatial resolution approaching 1 mm full width at half maximum (FWHM) can be achieved with a single pinhole aperture, while improved contrast and variance may result from using optimized multi-pinhole apertures.

Published
2002

49. Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET:I. Theory, error analysis, and stereologic comparison

Author

Iida, H, Law, I, Pakkenberg, B, Krarup-Hansen, A, Eberl, S, Holm, S, Hansen, A K, Gundersen, H J, Thomsen, C, Svarer, C, Ring, P, Friberg, L, Paulson, O B, Iida, H, Law, I, Pakkenberg, B, Krarup-Hansen, A, Eberl, S, Holm, S, Hansen, A K, Gundersen, H J, Thomsen, C, Svarer, C, Ring, P, Friberg, L, and Paulson, O B

Abstract

Limited spatial resolution of positron emission tomography (PET) can cause significant underestimation in the observed regional radioactivity concentration (so-called partial volume effect or PVE) resulting in systematic errors in estimating quantitative physiologic parameters. The authors have formulated four mathematical models that describe the dynamic behavior of a freely diffusible tracer (H215O) in a region of interest (ROI) incorporating estimates of regional tissue flow that are independent of PVE. The current study was intended to evaluate the feasibility of these models and to establish a methodology to accurately quantify regional cerebral blood flow (CBF) corrected for PVE in cortical gray matter regions. Five monkeys were studied with PET after IV H2(15)O two times (n = 3) or three times (n = 2) in a row. Two ROIs were drawn on structural magnetic resonance imaging (MRI) scans and projected onto the PET images in which regional CBF values and the water perfusable tissue fraction for the cortical gray matter tissue (hence the volume of gray matter) were estimated. After the PET study, the animals were killed and stereologic analysis was performed to assess the gray matter mass in the corresponding ROIs. Reproducibility of the estimated parameters and sensitivity to various error sources were also evaluated. All models tested in the current study yielded PVE-corrected regional CBF values (approximately 0.8 mL x min(-1) x g(-1) for models with a term for gray matter tissue and 0.5 mL x min(-1) x g(-1) for models with a term for a mixture of gray matter and white matter tissues). These values were greater than those obtained from ROIs tracing the gray matter cortex using conventional H2(15)O autoradiography (approximately 0.40 mL x min(-1) x g(-1)). Among the four models, configurations that included two parallel tissue compartments demonstrated better results with regards to the agreement of tissue time-activity curve and the Akaike's Information Criter

Published
2000

50. Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET:I. theory, error analysis, and stereologic comparison

Author

IIda, H., Law, I., Pakkenberg, B., Krarup-Hansen, A., Eberl, S., Holm, S., Kornerup Hansen, A., Gundersen, H. J. G., Thomsen, C., Svarer, C., Ring, P., Friberg, L., Paulson, O. B., IIda, H., Law, I., Pakkenberg, B., Krarup-Hansen, A., Eberl, S., Holm, S., Kornerup Hansen, A., Gundersen, H. J. G., Thomsen, C., Svarer, C., Ring, P., Friberg, L., and Paulson, O. B.

Published
2000

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