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10. Peri-interventional outcome study in the elderly in Europe : A 30-day prospective cohort study

Author

Kowark, Ana, Rossaint, Rolf, Rückbeil, Marcia V., Hilgers, Ralf-Dieter, Bilotta, Federico, Bollheimer, Leo C., Buhre, Wolfgang, Guenther, Ulf, Hoeft, Andreas, Lee, Peter, Matot, Idit, Rex, Steffen, Steinmetz, Jacob, Tournoy, Jos, Alanoglu, Zekeriyya, Berger, Marc M., Falières, Xavier, Goettel, Nicolai, Kartalov, Andrijan, Katsanoulas, Konstantinos, Kenig, Jakub, Khoronenko, Victoria, Lundstrøm, Lars H., Macharadze, Tamar, Milenovic, Miodrag, Molliex, Serge, Órfão, Rosário, Soro, Marina, Stefan, Mihai, Sungur, Zerrin, Szakmany, Tamas, Baños, Victoria, Rodriguez, Mireia, Martinez, Selene, Saller, Thomas, Schäfer, Simon T., Clermond, Edouard, Martin, Charlotte, Le Moal, Charlene, Staikowsky, Frederik, Delannoy, Bertand, Desebbe, Olivier, Missant, Carlo, Desmet, Matthias, Gillmann, Hans-Joerg, Stueber, Thomas, Dalsø, Sille M., Vester-Andersen, Morten, Ranft, Andreas, Schneider, Gerhard, Huygens, Christel, Meeusen, Roselien, Cruz, Patricia, Fernández, Carmen, Otto, Mareike, Giltaire, Agathe, Hofmann, Pascal, Gurlit, Simone, Fernández, Alejandro Romero, Castelli, Federica, Ntouba, Alexandre, Lanoiselée, Julien, Schulz, Regina, Opperer, Mathias, Van Waesberghe, Julia, Ziemann, Sebastian, Refaeli-Awin, Einat, Bengisun, Zuleyha Kazak, Buchman, Immanuel, Yahav-Shafir, Dana, Dimakopoulou, Antonia, Le Guen, Morgan, Rodríguez-Pérez, Aurelio, Beran, Maud, Bonnal, Aurelien, Garot, Matthias, Maupain, Olivier, Michel, Denis, Fernandes, Sofia, Sanabra, Maria, Mangoubi, Eitan, Boselli, Emmanuel, Switzer, Timothy, García-Sánchez, Jose I., Boisson, Matthieu, Stamoulis, Konstantinos, García, María Merino, Wulf, Hinnerk, Gouraud, David, Lebrun, Christophe, Lasocki, Sigismond, Steiner, Luzius A., Bergmann, Lars, Baenziger, Bertram, Karpetas, Georgios, Meco, Basak C., Hızal, Ayşe, Hernández, Rosa Méndez, Smit-Fun, Valerie, Charco, Pedro, Nickel, Frank, Grau Torradeflot, Laura, Coburn, Mark, Berger, Marc, Farcher, Helmut, Adriaensens, Ine, Saldien, Vera, Berghmans, Johan, Van Hove, Sofie, Eerdekens, Gert-Jan, Mesotten, Dieter, Timmers, Maxim, Vandermeulen, Elly, De Bruyne, Ann, De Hert, Stefan, De Ruyter, Hendrik, Van Belleghem, Vincent, Boscart, Isabelle, De Corte, Wouter, Carlier, Stefaan, Castelain, Charlotte, Demeyer, Caroline, Vandenbossche, Carl, Detienne, Hans, Devroe, Sarah, Dewinter, Geertrui, Hoogma, Danny, Van de Velde, Marc, Poels, Stéphanie, Soetens, Filiep, Fenger-Eriksen, Christian, Draegert, Christina, Santos, Sofia Gaspar, Soelling, Christine, Andersen, Gertrud, Haderslev, Pernille, Rasmussen, Vibe M., Sommer, Tine G., Kirkegaard, Johan, Olesen, Christian M., Paramanathan, Sansu, Jensen, Lisbet Tokkesdal, Knudsen, Halfdan H., Schmidt, Jens C., Stehen, Nick P., Dupont, Hervé, Herbinet, Clément, Lorne, Emmanuel, Mahjoub, Yazine, Fritsch, Marine, Garcia, Manuela, Petit Phan, Jonathan, Lieutaud, Thomas, Bonneric, Laura, Gaillet, Maxime, des Déserts, Marc Danguy, Montelescaut, Etienne, Lamblin, Antoine, Muller, Violaine, Lagrange, Celine, Robert, Alain, Lebas, Benoit, Lebuffe, Gilles, Beuvelot, Johanne, Dejour, David, Deligne, Emmanuel, Gignoux, Benoit, Guillaud, Olivier, Nloga, Joseph, Prunier-Bossion, Florence, Sibellas, Franck, Abraham, Paul, Bidon, Cyril, Rimmele, Thomas, Bruge-Ansel, Marie-Hélène, Friggeri, Arnaud, Lukaszewicz, Anne-Claire, Dziadzko, Mikhail, Leone, Marc, Meresse, Zoe, Pastene, Bruno, Odin, Isabelle, Bouic, Nicolas, Trinh Duc, Pierre, Pillant, Thomas, Riboulet, Fabien, Degoul, Samuel, Saumier, Nicolas, Wasilewski, Marion, Asehnoune, Karim, Roquilly, Antoine, Glasman, Pauline, Puybasset, Louis, Garnier, Fanny, Verdonk, Franck, Samama, Charles M., Towa, Line, Blet, Alice, Barrau, Stéphanie, Debaene, Bertrand, Frasca, Denis, Imzi, Nadia, Delvaux, Bernard, Huynh, Davy, Mercadal, Luc, Zanoun, Nabil, de Baene, Armelle, Boulay-Maninovsky, Catherine, Fernandes, Olivier, Gomis, Philippe, Malinovsky, Jean-Marc, Romain, François-Xavier, Calmelet, Astrid, Dupont, Ségolène, Millet, Sophie, Simonneau, Frédéric, Charret, Francoise, Couturier, Charlène, Lornage, Estelle, Mallard, Jeremy, Milati, Ryan, Passot, Sylvie, Vallier, Sylvain, Agavriloaia, Mihaela L., Badoux, Quentin, Lewandowski, Mehdi, Mermet, Yanis, Kiskira, Olga, Adjavon, Sherifa, Dumans, Virginie, Josserand, Julien, Ma, Sabrina, Castanera, Jeremy, Massiera, Benjamin, Petua, Philippe, Bounes-Vardon, Fanny, Bosc, Gaëlle, Bosch, Laëtitia, Ferre, Fabrice, Labaste, François, Menut, Rémi, Minville, Vincent, Srairi, Mohamed, Tarasi, Maria, Varin, Florent, Grüßer, Linda, Nowak, Hartmuth, Oprea, Günther, Rump, Katharina, Unterberg, Matthias, Vogelsang, Heike, Klutzny, Mitja, Neumann, Claudia, Soehle, Martin, Wittmann, Maria, Scharffenberg, Martin, Wittenstein, Jakob, Hinterberg, Jonas, Kienbaum, Peter, Lurati-Buse, Giovanna, Schäfer, Maximilian, Lindau, Simone, Meybohm, Patrick, Piekarski, Florian, Kaufhold, Theresa A., Koppert, Wolfgang, Leffler, Andreas, Reiffen, Hans-Peter, Rudolph, Diana, Starke, Henning, Bischoff, Petra, Haberecht, Heinz, Plehn, Heiko, Bauer, Michael, Kortgen, Andreas, Sponholz, Christoph, Krüger, Uwe, Müller-Esch, Sabine, Rempf, Christian, Schmidt, Christian, Schumacher, Dunja, Blazek, Juliane, Büttner, Christin, Leibeling, Andrea, Rüsch, Dirk, Burow, Karsten, El-Hilali, Eugen A., Greke, Christian, Großmann, Paul, Kluth, Mario, Dridi, Sofiane, Popovska, Ivana, Brenes, Andrés, Feddersen, Pia, Gerstmeyer, Dominik, Fthenakis, Philippe, Miketta, Dirk, von Dossow, Vera, Groene, Philipp, Höchter, Dominik, Hofmann-Kiefer, Klaus, Kammerer, Tobias, Kamrath, Malte, Schaefer, Simon T., Tomasi, Roland, Wiedemann, Tobias, Zeuzem-Lampert, Catharina, Zwissler, Bernhard, Braune, Stephan, Brune, Mona, Hemping-Bovenkerk, André, Möllmann, Michael, Santamaria, Mario, Schirwitz, Leonie M., Meersch, Melanie, Zarbock, Alexander, Decker, Stefanie, Drexler, Berthold, Hipp, Silvia, Müller, Markus, Roth, Judith, Seiß, Miriam, Adam, Christian, Schwartges, Ingo, Kranke, Peter, Chloropoulou, Pelagia, Andreeva, Antonia, Douma, Amalia, Gregoriadou, Iphigeneia, Koutsouli, Evelina, Mendrinou, Konstantina, Mavrommati, Eirini, Stathopoulos, Anastasios, Batistaki, Chrysanthi, Matsota, Paraskevi, Kalopita, Konstantina, Skandalou, Vasiliki, Balanika, Marina, Papathanakos, Georgios, Tzimas, Petros, Ketikidou, Evgenia, Vachlioti, Anastasia, Kiamiloglou, Bioulent, Nikouli, Evangelia, Arnaoutoglou, Eleni, Kolonia, Konstantina, Laou, Eleni, Vlachakis, Epaminondas, Lianou, Ioanna, Spyraki, Maria, Tatani, Irini, Panagiotou, Eleni, Samara, Evangelia, Kolesnikova, Anna, Sifaki, Freideriki, Zarzava, Eirini, Bampzelis, Athanasios, Georgopoulou, Eleni, Christidou, Eleni, Tsaousi, Georgia, Nastou, Maria, Ioannidis, Orestis, Dolzenko, Eugene, Geleve, Georgia, Logotheti, Eleni, Yfantidis, Fotios, Rajamanickam, Senbagam, Ramaswamy, Shanmuga, Das Punshi, Gurmukh, Srinivasan, Karthikeyan, Gilmartin, Michael, Morris, Osmond, Gozal, Yaacov, Merissat, Amar, Peled, Reut, Willner, Dafna, Chariski, Hila A., Eidelman, Leonid A., Livne, Michal Y., Berkenstadt, Haim, Orlcin, Dina, Aharonov, Rita, Cattan, Anat, Felman, Lior, Steinberg, Yohai, Zabeeda, Wisam, Kuzmanovska, Biljana, Naumovski, Filip, Toleska, Marija, Sivevski, Atanas, Andriessen, Anouk, Kortekaas, Minke, Van Gorp, Roos, de Korte-de Boer, Dianne, Theunissen, Maurice, Droger, Mirjam, van den Enden, Toine, Koopman, Seppe, Marsman, Marije, van Schaik, Eva, Azenha, Marta, Lanzaro, Camile, Borrego, Andreia, Branquinho, Pedro, Laires, Miguel, de Noronha, Denise, Ferraz, Inês, Pires, Ana, Silva, Joana, Corneci, Dan, Oprea, Oana, Zahiu, Stefan-Vladimir, Tomescu, Dana R., Grintescu, Ioana M., Filipescu, Daniela, Stefanescu, Elena, Vazenin, Andrey, Baskakov, Danil, Tipisev, Dmitry, Kozlova, Ksenia, Marinkovic, Olivera, Sekulic, Ana, Rajkovic, Marija, Djukanovic, Marija, Nikolic, Jovanka, Sreckovic, Svetlana, Stojanovic, Marina, Ladjevic, Nebojsa, Jovicic, Jelena, Unic-Stojanovic, Dragana, Stosic, Biljana, Bulasevic, Aleksandra, Espinosa-Moreno, Alma M., Martín-Vaquerizo, Beatriz, Morandeira-Rivas, Clara, Zamudio, Diana, Guadalupe, Nerea, Herranz, Gracia, Baute, Javier, Madrona, Vanesa, de Jose, Roser, Miralles, Jordi, Merten, Alfred, Muñoz, Rolando, Delgado, Anabel, Moral, Victoria, Blesa, Aleix Carmona, Espejo, Sara, Grau Torredeflot, Laura, Pujol, Pere Serra, Alvira Uribe, Maria J., Perez, Astrid Alvarez, Brunetto, Espedito, Aguirre, Jorge Gonzalez, Villar, Adriana Herivas, Rojas, Guido Munoz, Montero, Natalia, González, Víctor Baladrón, Becerra-Bolaños, Ángel, Santana-Ortega, Luis, Suárez-Romero, Vanessa, Torres-Machí, María L., Ferrero de Paz, Javier, Marcos-Vidal, Jose M., Garcia, Ana Martín, Diaz, Consuelo Rego, Santiago, Ana Crespo, Laso, Lourdes Ferreira, Solores, Felix Lobato, Burgos, Alba, Calvo, Alberto, Fernández, Ignacio, Garutti, Ignacio, Higuero, Fernando, Martinez, David, Piñeiro, Patricia, Carazo, Sonia Expósito, Rodríguez, Mar Orts, Rueda, Fernando Ramasco, Abad-Motos, Ane, Ripollés-Melchor, Javier, López, Carmen Pastor, Perez-Palao, Sara, Sancho-Iñigo, Laura, Segura, Nasara, Utrera, Esther, Albinarrate, Ania, Fondarella, Ana M., Gallego-Ligorit, Lucia, Torrijos, Luisa Lacosta, Bandschapp, Oliver, Blum, Andrea A., Seeberger, Esther, Thomann, Alessandra E., Frei, Seraina, Hoehn, Susan, Capaldo, Giuliana, Christ, Daniel, Doerig, Ramon, Hodel, Daniel, Weiss, Andreas, Witt, Lukas, Schumacher, Philippe, Siebing, Dirk A., Akbuz, Seyma Orcan, Kazbek, Baturay K., Koksoy, Ulku C., Terzi, Engin Z., Yilmaz, Hakan, Alkis, Neslihan, Turhan, Sanem Cakar, Hajiyeva, Konul, Guclu, Cigdem Yildirim, Ergil, Jülide, Ceran, Emine Unal, Ozcelik, Menekse, Bülent, Atik, Gökhan, Kilinc, Saracoglu, Kemal T., Kir, Bunyamin, Koltka, Kemalettin, Sivrikoz, Nükhet, Dincer, Pelin Corman, Canbolat, Nur, Kudsioglu, Turkan, Aydin, Gaye, Mucuoglu, Ceren Aygün, Inal, Duriye G., Kucukguclu, Semih, Egilmez, Ayse I., Kozanhan, Betul, Yildiz, Munise, Pinar, Hüseyin U., Erdivanlı, Başar, Karagöz, Emre, Kazdal, Hızır, Özdemir, Abdullah, Tas Tuna, Ayca, Gulgun, Gamze, and Oleg, Dolya

Abstract

European journal of anaesthesiology : EJA 39(3), 198-209 (2022). doi:10.1097/EJA.0000000000001639, Published by Lippincott Williams & Wilkins, Philadelphia, Pa.

Published
2022
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12. Acute Exercise in Hypobaric Hypoxia Attenuates Endothelial Shedding in Subjects Unacclimatized to High Altitudes

Author

Kröpfl, Julia M., Kammerer, Tobias, Faihs, Valentina, Gruber, Hans-Jürgen, Stutz, Jan, Rehm, Markus, Stelzer, Ingeborg, Schäfer, Simon T., and Spengler, Christina M.

Subjects
Unacclimatized, Matrix remodeling, High altitude, Hematopoietic progenitor cell, Endothelial shedding
Abstract

Travel of unacclimatized subjects to a high altitude has been growing in popularity. Changes in endothelial shedding [circulating endothelial cells (ECs)] and hematopoietic stem and progenitor cells (CPCs) during physical exercise in hypobaric hypoxia, however, are not well understood. We investigated the change in ECs and CPCs when exposed to high altitude, after acute exercise therein, and after an overnight stay in hypobaric hypoxia in 11 healthy unacclimatized subjects. Blood withdrawal was done at baseline (520 m a.s.l.; baseline), after passive ascent to 3,883 m a.s.l. (arrival), after acute physical exercise (±400 m, postexercise) and after an overnight stay at 3,883 m a.s.l. (24 h). Mature blood cells, ECs, and CPCs were assessed by a hematology analyzer and flow cytometry, respectively. The presence of matrix metalloproteinases (MMPs), their activity, and hematopoietic cytokines were assessed in serum and plasma. EC and CPC concentrations significantly decreased after exercise (p = 0.019, p = 0.007, respectively). CPCs remained low until the next morning (24 h, p = 0.002), while EC concentrations returned back to baseline. MMP-9 decreased at arrival (p = 0.021), stayed low postexercise (p = 0.033), and returned to baseline at 24 h (p = 0.035 to postexercise). MMP-activity did not change throughout the study. Circulating MMP-9 concentrations, but not MMP-activity, were associated with EC concentrations (rrm = 0.48, p = 0.010). CPC concentrations were not linked to hematopoietic cytokines. Acute exercise at high altitude attenuated endothelial shedding, but did not enhance regenerative CPCs. Results were not linked to endothelial matrix remodeling or CPC mobilization. These results provide information to better understand the endothelium and immature immune system during an active, short-term sojourn at high altitude., Frontiers in Physiology, 10, ISSN:1664-042X

Published
2020

19. Comparison of Two Different Fibrinogen Concentrates in an in vitro Model of Dilutional Coagulopathy.

Author

Groene, Philipp, Wiederkehr, Tobias, Kammerer, Tobias, Möhnle, Patrick, Maerte, Melanie, Bayer, Andreas, Görlinger, Klaus, Rehm, Markus, and Schäfer, Simon T.

Abstract

Introduction: Fibrinogen concentrates are widely used to restore clot stability in situations of bleeding. Fibrinogen preparations are produced using different production methods, resulting in different compounds. Thus, different preparations might have a distinct impact on blood coagulation. We tested the effect of fibrinogen concentrates Haemocomplettan® (CSL Behring, Marburg, Germany) and fibryga® (Octapharma GmbH, Langenfeld, Germany) on the impairments induced by 60% dilutional coagulopathy in vitro. Materials and Methods: The influence of the fibrinogen concentrates fibryga® and Haemocomplettan® on colloid (gelatine, hydroxyethyl starch [HES], albumin)-induced or crystalloid (Ringer's acetate)-induced dilutional coagulopathy was analysed using rotational thromboelastometry (ROTEM®) and standard laboratory tests. The following experimental conditions were analysed in vitro: whole blood, 60% dilution (40% blood and 60% diluent) ± 50 or 100 mg/kg–1 fibryga® or Haemocomplettan®, respectively. Results: Dilution with either diluent resulted in prolonged clotting time (CT) in an extrinsic activated test (CTEXTEM) and decreased maximum clot firmness (MCFFIBTEM) as expressed, e.g., by gelatine: (59.5 s [62/54.8] vs. 95 s [102.8/86.8]; p < 0.001 and 14 mm [16/10.5] vs. 3 mm [4–3]; p < 0.001). Substitution after 60% dilution with HES resulted in no difference between the preparations, except for shorter thrombin time with fibryga® (14 s [15/14] vs. 18 s [18.8/17]; p = 0.0093; low dose). CTEXTEM was higher with Haemocomplettan® in a gelatine-induced dilution (51 s [54.5/47.5] vs. 63 s [71/60.3]; p = 0.0202; low dose) whereas thrombin time was lower with fibryga® (19.5 s [20.8/19] vs. 27 s [29/25.3]; p = 0.0017). In dilution with albumin, differences in CTEXTEM (69 s [76.5/66] vs. 56 s [57/53.3]; p = 0.0114; low dose) and thrombin time (18 s [18/17] vs. 24.5 s [25.8/24]; p = 0.0202; low dose) were seen. In dilution with crystalloid solution, again differences in CTEXTEM (53.5 s [57.8/53] vs. 45 s [47/43]; p = 0.035; low dose) and thrombin time (17 s [17/16] vs. 23.5 s [24/23]; p = 0.0014; low dose) were seen. Fibrinogen levels were more increased by high-dose substitution of both preparations. Conclusion: Based on this data it can be stated that both fibryga® and Haemocomplettan® had the same performance in our in vitro model except for CTEXTEM and thrombin time. [ABSTRACT FROM AUTHOR]

Published
2020
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21. Hypoxia inducible factor-1 alpha and prolinhydroxlase 2 polymorphisms in patients with severe sepsis : a prospective observational trial

Author

Höcker, Annika, Rabeling, Miriam, Bick, Alexandra, Cox, Linda, Kreuzer, Maximiliane, Engler, Andrea, Walstein, Kai, Bachmann, Hagen Sjard, Jöckel, Karl-Heinz, Eisele, Lewin, Adamzik, Michael, Peters, Jürgen, and Schäfer, Simon T.

Subjects
Hypoxia inducible factor, Genetic variants, Anesthesiology and Pain Medicine, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Pharmakogenetik, Sepsis, Medizin, ddc:61, HIF, ddc:610, Polymorphism, Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Anästhesiologie und Intensivmedizin, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Medizinische Informatik, Biometrie und Epidemiologie
Abstract

Background Hypoxia-inducible-factor-1α (HIF-1α) and HIF-1 degrading prolyl-hydroxylases (PHD) are key regulators of the hypoxic-inflammatory response. Functionally active genetic variants in the HIF-1α (C/T; Single Nucleotide Polymorphism (SNP) rs11549465) and the PHD2 gene (EGLN1; C/T; SNP rs516651 and T/C; SNP rs480902) are associated with altered HIF-1α mRNA nuclear translocation and an altered adaptation to hypoxia. Furthermore, the HIF system is important in surviving inflammatory disorders and sepsis. Thus, we tested the hypotheses, that SNPs in the HIF-1α or PHD2 genes are (1) common in Caucasians, with 2) the HIF-1α genetic variant being associated with an altered HIF-1α mRNA expression; and 3) independent risk factors for 30-day mortality in severe sepsis. Methods After ethics approval, 128 septic patients (Caucasian descent) were included prospectively within 24 h after first diagnosing sepsis. Patients characteristics and severity of illness (simplified acute physiology score II), genotypes (Taqman assay), and their influence on leukocyte HIF-1α-mRNA-expression (Real-Time PCR) and 30-day mortality were determined. Results Frequencies were 0.8 % for homozygous HIF-1α TT-carriers (CT 17.6 %; CC 81.6 %), 2.5 % for homozygous PHD2 SNP rs516651 TT-allele carriers (CT 17.5 % and CC 80 %), and 9.4 % for homozygous PHD2 SNP rs480902 TT-allele carriers (CT 34.4 % and CC 56.3 %). While HIF-1α T-allele carriers had a borderline decrease in HIF-1α-mRNA-expression (p = 0.06) neither HIF-1α nor PHD2 SNPs were (independent) risk factors for 30-day mortality. Conclusions Genetic variants in HIF-1α and PHD2 genes exist in Caucasians but do not appear to alter 30-day mortality in sepsis.

Published
2016

22. Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils

Author

Völlger, Lena, Akong-Moore, Kathryn, Cox, Linda, Goldmann, Oliver, Wang, Yanming, Schäfer, Simon T, Naim, Hassan Y, Nizet, Victor, von Köckritz-Blickwede, Maren, and Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.

Subjects
Medizin
Abstract

OA gold Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial components (histones, antimicrobial peptides and proteases) are deployed and mediate immobilization of microbes. Here we describe an effect of iron chelation on the phenotype of NET formation. Iron-chelating agent desferrioxamine (DFO) showed a modest but significant induction of NETs by freshly isolated human neutrophils as visualized and quantified by immunocytochemistry against histone–DNA complexes. Further analyses revealed that NET induction by iron chelation required NADPH-dependent production of reactive oxygen species (ROS) as well as protease and peptidyl-arginine-deiminase 4 (PAD4) activities, three key mechanistic pathways previously linked to NET formation. Our results demonstrate that iron chelation by DFO contributes to the formation of NETs and suggest a target for pharmacological manipulation of NET activity.

Published
2016

24. Mitochondrial DNA

Author

Schäfer, Simon T., primary, Franken, Lars, additional, Adamzik, Michael, additional, Schumak, Beatrix, additional, Scherag, André, additional, Engler, Andrea, additional, Schönborn, Niels, additional, Walden, Jennifer, additional, Koch, Susanne, additional, Baba, Hideo A., additional, Steinmann, Jörg, additional, Westendorf, Astrid M., additional, Fandrey, Joachim, additional, Bieber, Thomas, additional, Kurts, Christian, additional, Frede, Stilla, additional, Peters, Jürgen, additional, and Limmer, Andreas, additional

Published
2016
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25. Hypoxia inducible factor-1 alpha and prolinhydroxlase 2 polymorphisms in patients with severe sepsis: a prospective observational trial

Author

Höcker, Annika, primary, Rabeling, Miriam, additional, Bick, Alexandra, additional, Cox, Linda, additional, Kreuzer, Maximiliane, additional, Engler, Andrea, additional, Walstein, Kai, additional, Bachmann, Hagen S., additional, Jöckel, Karl-Heinz, additional, Eisele, Lewin, additional, Adamzik, Michael, additional, Peters, Jürgen, additional, and Schäfer, Simon T., additional

Published
2015
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26. Hypoxia Inducible Factor-2Alpha and Prolinhydroxylase 2 Polymorphisms in Patients with Acute Respiratory Distress Syndrome (ARDS).

Author

Dötsch, Annika, Eisele, Lewin, Rabeling, Miriam, Rump, Katharina, Walstein, Kai, Bick, Alexandra, Cox, Linda, Engler, Andrea, Bachmann, Hagen S., Jöckel, Karl-Heinz, Adamzik, Michael, Peters, Jürgen, and Schäfer, Simon T.

Subjects
ADULT respiratory distress syndrome treatment, ADULT respiratory distress syndrome, HYPOXEMIA, GENETIC polymorphisms, HUMAN genetic variation, PATIENTS
Abstract

Hypoxia-inducible-factor-2α (HIF-2α) and HIF-2 degrading prolyl-hydroxylases (PHD) are key regulators of adaptive hypoxic responses i.e., in acute respiratory distress syndrome (ARDS). Specifically, functionally active genetic variants of HIF-2α (single nucleotide polymorphism (SNP) [ch2:46441523(hg18)]) and PHD2 (C/T; SNP rs516651 and T/C; SNP rs480902) are associated with improved adaptation to hypoxia i.e., in high-altitude residents. However, little is known about these SNPs' prevalence in Caucasians and impact on ARDS-outcome. Thus, we tested the hypotheses that in Caucasian ARDS patients SNPs in HIF-2α or PHD2 genes are (1) common, and (2) independent risk factors for 30-day mortality. After ethics-committee approval, 272 ARDS patients were prospectively included, genotyped for PHD2 (Taqman SNP Genotyping Assay) and HIF-2α-polymorphism (restriction digest + agarose-gel visualization), and genotype dependent 30-day mortality was analyzed using Kaplan-Meier-plots and multivariate Cox-regression analyses. Frequencies were 99.62% for homozygous HIF-2a CC-carriers (CG: 0.38%; GG: 0%), 2.3% for homozygous PHD2 SNP rs516651 TT-carriers (CT: 18.9%; CC: 78.8%), and 3.7% for homozygous PHD2 SNP rs480902 TT-carriers (CT: 43.9%; CC: 52.4%). PHD2 rs516651 TT-genotype in ARDS was independently associated with a 3.34 times greater mortality risk (OR 3.34, CI 1.09-10.22; p = 0.034) within 30-days, whereas the other SNPs had no significant impact (p = ns). The homozygous HIF-2α GG-genotype was not present in our Caucasian ARDS cohort; however PHD2 SNPs exist in Caucasians, and PHD2 rs516651 TT-genotype was associated with an increased 30-day mortality suggesting a relevance for adaptive responses in ARDS. [ABSTRACT FROM AUTHOR]

Published
2017
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27. Hydrocortisone Fails to Abolish NF-κB1 Protein Nuclear Translocation in Deletion Allele Carriers of the NFKB1 Promoter Polymorphism (-94ins/delATTG) and Is Associated with Increased 30-Day Mortality in Septic Shock

Author

Schäfer, Simon T., primary, Gessner, Sophia, additional, Scherag, André, additional, Rump, Katharina, additional, Frey, Ulrich H., additional, Siffert, Winfried, additional, Westendorf, Astrid M., additional, Steinmann, Jörg, additional, Peters, Jürgen, additional, and Adamzik, Michael, additional

Published
2014
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30. Mitochondrial DNA: An Endogenous Trigger for Immune Paralysis.

Author

Schäfer, Simon T., Franken, Lars, Adamzik, Michael, Schumak, Beatrix, Scherag, André, Engler, Andrea, Schönborn, Niels, Walden, Jennifer, Koch, Susanne, Baba, Hideo A., Steinmann, Jörg, Westendorf, Astrid M., Fandrey, Joachim, Bieber, Thomas, Kurts, Christian, Frede, Stilla, Peters, Jürgen, and Limmer, Andreas

Subjects
*ANIMALS, *BIOLOGICAL models, *CATASTROPHIC illness, *DNA, *FLOW cytometry, *IMMUNITY, *INFLAMMATION, *LONGITUDINAL method, *MICE, *POLYMERASE chain reaction, *SEPSIS
Abstract

Background: Critically ill patients are at high risk to suffer from sepsis, even in the absence of an initial infectious source, but the molecular mechanisms for their increased sepsis susceptibility, including a suppressed immune system, remain unclear. Although microbes and pathogen-associated molecular pattern are accepted inducers of sepsis and septic immunosuppression, the role of endogenous Toll-like receptor (TLR) ligands, such as mitochondrial DNA (mtDNA), in altering the immune response is unknown.Methods: Mitochondrial DNA serum concentrations of the mitochondrial genes D-Loop and adenosine triphosphatase 6 were determined (quantitative polymerase chain reaction) in 165 septic patients and 50 healthy volunteers. Furthermore, cytotoxic T-cell activity was analyzed in wild-type and TLR9 knockout mice, with/without previous mtDNA administration, followed by injection of an ovalbumin-expressing adenoviral vector.Results: Mitochondrial DNA serum concentrations were increased in septic patients (adenosine triphosphatase 6, 123-fold; D-Loop, 76-fold, P < 0.0001) compared with volunteers. Furthermore, a single mtDNA injection caused profound, TLR9-dependent immunosuppression of adaptive T-cell cytotoxicity in wild-type but not in TLR9 knockout mice and evoked various immunosuppressive mechanisms including the destruction of the splenic microstructure, deletion of cross-presenting dendritic cells, and up-regulation of programmed cell death ligand 1 and indoleamine 2,3-dioxygenase. Several of these findings in mice were mirrored in septic patients, and mtDNA concentrations were associated with an increased 30-day mortality.Conclusions: The findings of this study imply that mtDNA, an endogenous danger associated molecular pattern, is a hitherto unknown inducer of septic immunoparalysis and one possible link between initial inflammation and subsequent immunosuppression in critically ill patients. [ABSTRACT FROM AUTHOR]

Published
2016
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35. Hydrocortisone Fails to Abolish NF-κB1 Protein Nuclear Translocation in Deletion Allele Carriers of the NFKB1 Promoter Polymorphism (-94ins/delATTG) and Is Associated with Increased 30-Day Mortality in Septic Shock.

Author

Schäfer, Simon T., Gessner, Sophia, Scherag, André, Rump, Katharina, Frey, Ulrich H., Siffert, Winfried, Westendorf, Astrid M., Steinmann, Jörg, Peters, Jürgen, and Adamzik, Michael

Subjects
*SEPTIC shock, *MORTALITY, *HYDROCORTISONE, *NF-kappa B, *CHROMOSOMAL translocation, *DELETION mutation, *PROMOTERS (Genetics), *GENETIC polymorphisms
Abstract

Background: Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Methods: Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Results: Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Conclusion: Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is associated with markedly increased 30-day-mortality only in such carriers. Accordingly, previous heterogeneous results regarding the benefit of hydrocortisone in septic shock may be reconciled by genetic variation of the NFKB1 promoter polymorphism. [ABSTRACT FROM AUTHOR]

Published
2014
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36. DARBEPOETIN , A LONG-ACTING ERYTHROPOEITIN DERIVATE, DOES NOT ALTER LPS EVOKED MYOCARDIAL DEPRESSION AND GENE EXPRESSION OF BAX, BCL-XS, BCL-XL, BCL-2, AND TNF-

Author

Brendt, Peter, Frey, Ulrich, Adamzik, Michael, Schäfer, Simon T, and Peters, Jürgen

Abstract

Darbepoetin (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127B8; 10 mg/kg, i.p.). Darbepoetin or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (−64.6 ± 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P< 0,01), but this effect was not attenuated by DA pretreatment or DA treatment. LPS administration increased gene expression of Bcl-Xs, Bax, and TNF-, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

Published
2009
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37. Peri-interventional outcome study in the elderly in Europe A 30-day prospective cohort study

Author

Ana Sekulic, Selene Martinez Perez, Danny Feike Hoogma, GÖKHAN KILINÇ, Marc Danguy des Déserts, Evangelia Samara, AYSE HIZAL, Nicolai Goettel, Martin Scharffenberg, Sofia Fernandes, Jose Ignacio García-Sánchez, Tobias Kammerer, Marc Moritz Berger, Florian Piekarski, CEREN AYGÜN MUÇUOĞLU, PATRICIA PIÑEIRO OTERO, Angel Becerra, Aurelio Rodriguez-Perez, Ülkü Ceren Köksoy, Jakob Wittenstein, Lars Lundstrøm, Diana Zamudio Penko, Hans-Joerg Gillmann, Dianne De Korte-de Boer, Jose miguel Marcos-vidal, Sebastian Ziemann, Tournoy, Jos, Kowark, Ana, Rossaint, Rolf, Matot, Idit, Nickel, Frank, Grau Torradeflot, Laura, Coburn, Mark, Berger, Marc, Farcher, Helmut, Opperer, Mathias, Adriaensens, Ine, Saldien, Vera, Berghmans, Johan, Van Hove, Sofie, Rex, Steffen, Beran, Maud, Eerdekens, Gert-Jan, Mesotten, Dieter, Timmers, Maxim, Vandermeulen, Elly, De Bruyne, Ann, De Hert, Stefan, De Ruyter, Hendrik, Van Belleghem, Vincent, Boscart, Isabelle, Steinmetz, Jacob, De Corte, Wouter, Desmet, Matthias, Missant, Carlo, Carlier, Stefaan, Castelain, Charlotte, Demeyer, Caroline, Vandenbossche, Carl, Detienne, Hans, Devroe, Sarah, Dewinter, Geertrui, Hoogma, Danny, Huygens, Christel, Meeusen, Roselien, Van de Velde, Marc, Lebrun, Christophe, Poels, Stéphanie, Soetens, Filiep, Fenger-Eriksen, Christian, Alanoglu, Zekeriyya, Draegert, Christina, Santos, Sofia Gaspar, Soelling, Christine, Andersen, Gertrud, Dalsø, Sille M., Haderslev, Pernille, Rasmussen, Vibe M., Vester-Andersen, Morten, Sommer, Tine G., Berger, Marc M., Kirkegaard, Johan, Lundstrøm, Lars H., Olesen, Christian M., Paramanathan, Sansu, Jensen, Lisbet Tokkesdal, Knudsen, Halfdan H., Schmidt, Jens C., Stehen, Nick P., Dupont, Hervé, Herbinet, Clément, Falières, Xavier, Lorne, Emmanuel, Mahjoub, Yazine, Ntouba, Alexandre, Fritsch, Marine, Garcia, Manuela, Lasocki, Sigismond, Petit Phan, Jonathan, Lieutaud, Thomas, Bonneric, Laura, Boselli, Emmanuel, Goettel, Nicolai, Gaillet, Maxime, des Déserts, Marc Danguy, Montelescaut, Etienne, Lamblin, Antoine, Muller, Violaine, Lagrange, Celine, Le Moal, Charlene, Robert, Alain, Staikowsky, Frederik, Lebas, Benoit, Kartalov, Andrijan, Lebuffe, Gilles, Garot, Matthias, Beuvelot, Johanne, Dejour, David, Deligne, Emmanuel, Desebbe, Olivier, Delannoy, Bertand, Gignoux, Benoit, Guillaud, Olivier, Nloga, Joseph, Katsanoulas, Konstantinos, Prunier-Bossion, Florence, Sibellas, Franck, Abraham, Paul, Bidon, Cyril, Rimmele, Thomas, Bruge-Ansel, Marie-Hélène, Friggeri, Arnaud, Lukaszewicz, Anne-Claire, Dziadzko, Mikhail, Leone, Marc, Rückbeil, Marcia V., Kenig, Jakub, Meresse, Zoe, Pastene, Bruno, Odin, Isabelle, Bonnal, Aurelien, Bouic, Nicolas, Trinh Duc, Pierre, Pillant, Thomas, Riboulet, Fabien, Degoul, Samuel, Saumier, Nicolas, Khoronenko, Victoria, Wasilewski, Marion, Asehnoune, Karim, Roquilly, Antoine, Glasman, Pauline, Puybasset, Louis, Garnier, Fanny, Verdonk, Franck, Samama, Charles M., Towa, Line, Blet, Alice, Barrau, Stéphanie, Boisson, Matthieu, Debaene, Bertrand, Frasca, Denis, Imzi, Nadia, Delvaux, Bernard, Huynh, Davy, Maupain, Olivier, Mercadal, Luc, Zanoun, Nabil, Macharadze, Tamar, de Baene, Armelle, Boulay-Maninovsky, Catherine, Fernandes, Olivier, Giltaire, Agathe, Gomis, Philippe, Malinovsky, Jean-Marc, Romain, François-Xavier, Calmelet, Astrid, Dupont, Ségolène, Gouraud, David, Milenovic, Miodrag, Millet, Sophie, Simonneau, Frédéric, Charret, Francoise, Couturier, Charlène, Lanoiselée, Julien, Lornage, Estelle, Mallard, Jeremy, Milati, Ryan, Passot, Sylvie, Vallier, Sylvain, Molliex, Serge, Agavriloaia, Mihaela L., Badoux, Quentin, Lewandowski, Mehdi, Mermet, Yanis, Michel, Denis, Kiskira, Olga, Adjavon, Sherifa, Dumans, Virginie, Le Guen, Morgan, Josserand, Julien, Órfão, Rosário, Ma, Sabrina, Castanera, Jeremy, Massiera, Benjamin, Petua, Philippe, Bounes-Vardon, Fanny, Bosc, Gaëlle, Bosch, Laëtitia, Clermond, Edouard, Ferre, Fabrice, Labaste, François, Soro, Marina, Martin, Charlotte, Menut, Rémi, Minville, Vincent, Srairi, Mohamed, Tarasi, Maria, Varin, Florent, Grüßer, Linda, Stefan, Mihai, Van Waesberghe, Julia, Ziemann, Sebastian, Bergmann, Lars, Nowak, Hartmuth, Oprea, Günther, Rump, Katharina, Unterberg, Matthias, Vogelsang, Heike, Klutzny, Mitja, Neumann, Claudia, Sungur, Zerrin, Soehle, Martin, Wittmann, Maria, Scharffenberg, Martin, Wittenstein, Jakob, Hinterberg, Jonas, Kienbaum, Peter, Lurati-Buse, Giovanna, Schäfer, Maximilian, Lindau, Simone, Hilgers, Ralf-Dieter, Szakmany, Tamas, Meybohm, Patrick, Gillmann, Hans-Joerg, Piekarski, Florian, Kaufhold, Theresa A., Koppert, Wolfgang, Leffler, Andreas, Reiffen, Hans-Peter, Rudolph, Diana, Starke, Henning, Stueber, Thomas, Baños, Victoria, Bischoff, Petra, Haberecht, Heinz, Plehn, Heiko, Bauer, Michael, Kortgen, Andreas, Sponholz, Christoph, Krüger, Uwe, Müller-Esch, Sabine, Otto, Mareike, Rempf, Christian, Rodriguez, Mireia, Schmidt, Christian, Schumacher, Dunja, Blazek, Juliane, Büttner, Christin, Leibeling, Andrea, Rüsch, Dirk, Wulf, Hinnerk, Burow, Karsten, El-Hilali, Eugen A., Greke, Christian, Martinez, Selene, Großmann, Paul, Kluth, Mario, Schulz, Regina, Dridi, Sofiane, Popovska, Ivana, Brenes, Andrés, Ranft, Andreas, Feddersen, Pia, Gerstmeyer, Dominik, Fthenakis, Philippe, Saller, Thomas, Schneider, Gerhard, Miketta, Dirk, von Dossow, Vera, Groene, Philipp, Höchter, Dominik, Hofmann-Kiefer, Klaus, Kammerer, Tobias, Kamrath, Malte, Schaefer, Simon T., Schäfer, Simon T., Tomasi, Roland, Wiedemann, Tobias, Zeuzem-Lampert, Catharina, Zwissler, Bernhard, Braune, Stephan, Brune, Mona, Gurlit, Simone, Hemping-Bovenkerk, André, Möllmann, Michael, Santamaria, Mario, Schirwitz, Leonie M., Meersch, Melanie, Zarbock, Alexander, Guenther, Ulf, Decker, Stefanie, Drexler, Berthold, Hipp, Silvia, Hofmann, Pascal, Müller, Markus, Roth, Judith, Seiß, Miriam, Adam, Christian, Schwartges, Ingo, Kranke, Peter, Chloropoulou, Pelagia, Andreeva, Antonia, Dimakopoulou, Antonia, Douma, Amalia, Gregoriadou, Iphigeneia, Koutsouli, Evelina, Mendrinou, Konstantina, Mavrommati, Eirini, Stathopoulos, Anastasios, Batistaki, Chrysanthi, Matsota, Paraskevi, Kalopita, Konstantina, Skandalou, Vasiliki, Balanika, Marina, Papathanakos, Georgios, Tzimas, Petros, Ketikidou, Evgenia, Vachlioti, Anastasia, Kiamiloglou, Bioulent, Nikouli, Evangelia, Arnaoutoglou, Eleni, Kolonia, Konstantina, Laou, Eleni, Stamoulis, Konstantinos, Vlachakis, Epaminondas, Bilotta, Federico, Karpetas, Georgios, Lianou, Ioanna, Spyraki, Maria, Tatani, Irini, Panagiotou, Eleni, Samara, Evangelia, Kolesnikova, Anna, Sifaki, Freideriki, Zarzava, Eirini, Bampzelis, Athanasios, Georgopoulou, Eleni, Christidou, Eleni, Tsaousi, Georgia, Nastou, Maria, Ioannidis, Orestis, Dolzenko, Eugene, Geleve, Georgia, Logotheti, Eleni, Yfantidis, Fotios, Lee, Peter, Rajamanickam, Senbagam, Ramaswamy, Shanmuga, Switzer, Timothy, Das Punshi, Gurmukh, Srinivasan, Karthikeyan, Gilmartin, Michael, Morris, Osmond, Buchman, Immanuel, Gozal, Yaacov, Merissat, Amar, Peled, Reut, Willner, Dafna, Chariski, Hila A., Eidelman, Leonid A., Livne, Michal Y., Mangoubi, Eitan, Berkenstadt, Haim, Orlcin, Dina, Yahav-Shafir, Dana, Aharonov, Rita, Cattan, Anat, Felman, Lior, Refaeli-Awin, Einat, Steinberg, Yohai, Zabeeda, Wisam, Kuzmanovska, Biljana, Naumovski, Filip, Toleska, Marija, Sivevski, Atanas, Andriessen, Anouk, Kortekaas, Minke, Buhre, Wolfgang, Van Gorp, Roos, de Korte-de Boer, Dianne, Smit-Fun, Valerie, Theunissen, Maurice, Droger, Mirjam, van den Enden, Toine, Koopman, Seppe, Marsman, Marije, van Schaik, Eva, Azenha, Marta, Lanzaro, Camile, Borrego, Andreia, Branquinho, Pedro, Fernandes, Sofia, Laires, Miguel, de Noronha, Denise, Ferraz, Inês, Pires, Ana, Silva, Joana, Corneci, Dan, Oprea, Oana, Zahiu, Stefan-Vladimir, Tomescu, Dana R., Grintescu, Ioana M., Filipescu, Daniela, Stefanescu, Elena, Vazenin, Andrey, Baskakov, Danil, Tipisev, Dmitry, Kozlova, Ksenia, Marinkovic, Olivera, Sekulic, Ana, Rajkovic, Marija, Djukanovic, Marija, Nikolic, Jovanka, Sreckovic, Svetlana, Stojanovic, Marina, Ladjevic, Nebojsa, Jovicic, Jelena, Unic-Stojanovic, Dragana, Bollheimer, Leo C., Stosic, Biljana, Bulasevic, Aleksandra, Espinosa-Moreno, Alma M., García-Sánchez, Jose I., Martín-Vaquerizo, Beatriz, Morandeira-Rivas, Clara, Zamudio, Diana, Guadalupe, Nerea, Herranz, Gracia, Baute, Javier, Madrona, Vanesa, de Jose, Roser, Miralles, Jordi, Merten, Alfred, Muñoz, Rolando, Delgado, Anabel, Cruz, Patricia, Moral, Victoria, Blesa, Aleix Carmona, Espejo, Sara, Grau Torredeflot, Laura, Fernández, Alejandro Romero, Sanabra, Maria, Pujol, Pere Serra, Alvira Uribe, Maria J., Perez, Astrid Alvarez, Brunetto, Espedito, Fernández, Carmen, Castelli, Federica, Aguirre, Jorge Gonzalez, Villar, Adriana Herivas, Rojas, Guido Munoz, Montero, Natalia, González, Víctor Baladrón, Becerra-Bolaños, Ángel, Rodríguez-Pérez, Aurelio, Santana-Ortega, Luis, Suárez-Romero, Vanessa, Torres-Machí, María L., Ferrero de Paz, Javier, Marcos-Vidal, Jose M., Garcia, Ana Martín, García, María Merino, Diaz, Consuelo Rego, Santiago, Ana Crespo, Laso, Lourdes Ferreira, Solores, Felix Lobato, Burgos, Alba, Calvo, Alberto, Fernández, Ignacio, Garutti, Ignacio, Higuero, Fernando, Martinez, David, Piñeiro, Patricia, Carazo, Sonia Expósito, Hernández, Rosa Méndez, Rodríguez, Mar Orts, Rueda, Fernando Ramasco, Abad-Motos, Ane, Ripollés-Melchor, Javier, López, Carmen Pastor, Charco, Pedro, Perez-Palao, Sara, Sancho-Iñigo, Laura, Segura, Nasara, Utrera, Esther, Albinarrate, Ania, Fondarella, Ana M., Gallego-Ligorit, Lucia, Torrijos, Luisa Lacosta, Bandschapp, Oliver, Blum, Andrea A., Seeberger, Esther, Steiner, Luzius A., Thomann, Alessandra E., Frei, Seraina, Hoehn, Susan, Baenziger, Bertram, Capaldo, Giuliana, Christ, Daniel, Doerig, Ramon, Hodel, Daniel, Weiss, Andreas, Witt, Lukas, Schumacher, Philippe, Siebing, Dirk A., Akbuz, Seyma Orcan, Bengisun, Zuleyha Kazak, Kazbek, Baturay K., Koksoy, Ulku C., Terzi, Engin Z., Yilmaz, Hakan, Alkis, Neslihan, Turhan, Sanem Cakar, Meco, Basak C., Hajiyeva, Konul, Guclu, Cigdem Yildirim, Ergil, Jülide, Ceran, Emine Unal, Ozcelik, Menekse, Bülent, Atik, Gökhan, Kilinc, Saracoglu, Kemal T., Kir, Bunyamin, Koltka, Kemalettin, Sivrikoz, Nükhet, Dincer, Pelin Corman, Canbolat, Nur, Kudsioglu, Turkan, Aydin, Gaye, Mucuoglu, Ceren Aygün, Inal, Duriye G., Kucukguclu, Semih, Egilmez, Ayse I., Kozanhan, Betul, Yildiz, Munise, Pinar, Hüseyin U., Erdivanlı, Başar, Hızal, Ayşe, Karagöz, Emre, Kazdal, Hızır, Özdemir, Abdullah, Tas Tuna, Ayca, Gulgun, Gamze, Oleg, Dolya, Hoeft, Andreas, MUMC+: MA Anesthesiologie (3), RS: MHeNs - R3 - Neuroscience, and MUMC+: MA Anesthesiologie (9)

Subjects
Aged, 80 and over, Male, Patient, Frailty, Preoperative assessment, Surgical outcomes, Europe, Hospitalization, Older, Anesthesiology and Pain Medicine, Outcome Assessment, Health Care, Humans, Female, Surgery, Prospective Studies, Derivation, Mortality, Aged
Abstract

OBJECTIVES The aim of this study was to describe the 30-day mortality rate of patients aged 80 years and older undergoing surgical and nonsurgical procedures under anaesthesia in Europe and to identify risk factors associated with mortality. DESIGN A prospective cohort study. SETTING European multicentre study, performed from October 2017 to December 2018. Centres committed to a 30-day recruitment period within the study period. PATIENTS Nine thousand four hundred and ninety-seven consecutively recruited patients aged 80 years and older undergoing any kind of surgical or nonsurgical procedures under anaesthesia. MAIN OUTCOME MEASURES The primary outcome was all-cause mortality within 30 days after procedure described by Kaplan–Meier curves with 95% CI. Risk factors for 30-day mortality were analysed using a Cox regression model with 14 fixed effects and a random centre effect. RESULTS Data for 9497 patients (median age, 83.0 years; 52.8% women) from 177 academic and nonacademic hospitals in 20 countries were analysed. Patients presented with multimorbidity (77%), frailty (14%) and at least partial functional dependence (38%). The estimated 30-day mortality rate was 4.2% (95% CI 3.8 to 4.7). Among others, independent risk factors for 30-day mortality were multimorbidity, hazard ratio 1.87 (95% CI 1.26 to 2.78), frailty, hazard ratio 2.63 (95% CI 2.10 to 3.30), and limited mobility, hazard ratio 2.19 (95% CI 1.24 to 3.86). The majority of deaths (76%) occurred in hospital. Mortality risk for unplanned ICU admission was higher, hazard ratio 3.57 (95% CI 2.38 to 5.26) than for planned ICU admission, hazard ratio 1.92 (95% CI 1.47 to 2.50). Compared with other studies, the in-hospital complication rates of 17.4 and 3.9% after discharge were low. Admission to a unit with geriatric care within 30 days after the intervention was associated with a better survival within the first 10 days. CONCLUSIONS The estimated 30-day mortality rate of 4.2% was lower than expected in this vulnerable population. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03152734, https://clinicaltrials.gov. ispartof: European Journal Of Anaesthesiology vol:39 issue:3 pages:198-209 ispartof: location:England status: published

Published
2022
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38. Acute Exercise in Hypobaric Hypoxia Attenuates Endothelial Shedding in Subjects Unacclimatized to High Altitudes.

Author

Kröpfl JM, Kammerer T, Faihs V, Gruber HJ, Stutz J, Rehm M, Stelzer I, Schäfer ST, and Spengler CM

Abstract

Travel of unacclimatized subjects to a high altitude has been growing in popularity. Changes in endothelial shedding [circulating endothelial cells (ECs)] and hematopoietic stem and progenitor cells (CPCs) during physical exercise in hypobaric hypoxia, however, are not well understood. We investigated the change in ECs and CPCs when exposed to high altitude, after acute exercise therein, and after an overnight stay in hypobaric hypoxia in 11 healthy unacclimatized subjects. Blood withdrawal was done at baseline (520 m a.s.l.; baseline), after passive ascent to 3,883 m a.s.l. (arrival), after acute physical exercise (±400 m, postexercise) and after an overnight stay at 3,883 m a.s.l. (24 h). Mature blood cells, ECs, and CPCs were assessed by a hematology analyzer and flow cytometry, respectively. The presence of matrix metalloproteinases (MMPs), their activity, and hematopoietic cytokines were assessed in serum and plasma. EC and CPC concentrations significantly decreased after exercise ( p = 0.019, p = 0.007, respectively). CPCs remained low until the next morning (24 h, p = 0.002), while EC concentrations returned back to baseline. MMP-9 decreased at arrival ( p = 0.021), stayed low postexercise ( p = 0.033), and returned to baseline at 24 h ( p = 0.035 to postexercise). MMP-activity did not change throughout the study. Circulating MMP-9 concentrations, but not MMP-activity, were associated with EC concentrations ( r rm = 0.48, p = 0.010). CPC concentrations were not linked to hematopoietic cytokines. Acute exercise at high altitude attenuated endothelial shedding, but did not enhance regenerative CPCs. Results were not linked to endothelial matrix remodeling or CPC mobilization. These results provide information to better understand the endothelium and immature immune system during an active, short-term sojourn at high altitude., (Copyright © 2020 Kröpfl, Kammerer, Faihs, Gruber, Stutz, Rehm, Stelzer, Schäfer and Spengler.)

Published
2020
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39. Darbepoetin alpha, a long-acting erythropoeitin derivate, does not alter LPS evoked myocardial depression and gene expression of Bax, Bcl-Xs, Bcl-XL, Bcl-2, and TNF-alpha.

Author

Brendt P, Frey U, Adamzik M, Schäfer ST, and Peters J

Subjects
Animals, Apoptosis drug effects, Cardiomyopathies chemically induced, Cardiomyopathies metabolism, Cardiomyopathies pathology, Darbepoetin alfa, Drug Resistance drug effects, Erythropoietin pharmacology, Male, Myocardium pathology, Rats, Rats, Inbred Lew, Sepsis chemically induced, Sepsis pathology, Ventricular Function, Left drug effects, Erythropoietin analogs & derivatives, Gene Expression Regulation drug effects, Hematinics pharmacology, Lipopolysaccharides toxicity, Myocardium metabolism, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Sepsis metabolism, Tumor Necrosis Factor-alpha biosynthesis, bcl-2-Associated X Protein biosynthesis, bcl-X Protein biosynthesis
Abstract

Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P < 0,01), but this effect was not attenuated by DA pretreatment or DA treatment. LPS administration increased gene expression of Bcl-Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

Published
2009
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