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4. Racial and ethnic minority participants in clinical trials of acute respiratory distress syndrome

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Papoutsi, Eleni, Kremmydas, Panagiotis, Tsolaki, Vasiliki, Kyriakoudi, Anna, Routsi, Christina, Kotanidou, Anastasia, and Siempos, Ilias I.

Subjects
United States. National Heart, Lung and Blood Institute, Health aspects, Mortality -- Greece -- United Kingdom -- India -- Asia, Clinical trials -- Health aspects, Respiratory distress syndrome -- Health aspects, Native Americans -- Health aspects, Adult respiratory distress syndrome -- Health aspects, Acute respiratory distress syndrome -- Health aspects
Abstract

Author(s): Eleni Papoutsi [sup.1], Panagiotis Kremmydas [sup.1], Vasiliki Tsolaki [sup.2], Anna Kyriakoudi [sup.3], Christina Routsi [sup.1], Anastasia Kotanidou [sup.1], Ilias I. Siempos [sup.1] [sup.4] Author Affiliations: (1) First Department of [...], Purpose There is growing interest in improving the inclusiveness of racial and ethnic minority participants in trials of acute respiratory distress syndrome (ARDS). With our study we aimed to examine temporal trends of representation and mortality of racial and ethnic minority participants in randomized controlled trials of ARDS. Methods We performed a secondary analysis of eight ARDS Network and PETAL Network therapeutic clinical trials, published between 2000 and 2019. We classified race/ethnicity into 'White', 'Black', 'Hispanic', or 'Other' (including Asian, American Indian or Alaskan Native, Native Hawaiian, or other Pacific Islander participants). Results Of 5375 participants with ARDS, 1634 (30.4%) were Black, Hispanic, or Other race participants. Representation of racial and ethnic minority participants in trials did not change significantly over time (p = 0.257). However, among participants with moderate to severe ARDS (i.e., partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 150), the difference in mortality between racial and ethnic minority participants and White participants decreased over time. In the five most recent trials, including 2923 participants with ARDS, there were no statistically significant differences in mortality between racial/ethnic groups, even after adjusting for potential confounders. In these five most recent trials, mortality was 31% for White, 31.9% for Black, 30.3% for Hispanic, and 37.1% for Other race participants (p = 0.633). Conclusion Representation of racial and ethnic minority participants in ARDS trials from North America, published between 2000 and 2019, did not change over time. Black and Hispanic participants with ARDS may have similar mortality as White participants within trials.

Published
2023
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5. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

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Hermine, Olivier, Mariette, Xavier, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Resche-Rigon, Matthieu, Tharaux, Pierre-Louis, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Porcher, Raphaël, Pourchet-Martinez, Valerie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Raked, Nabil, Mameri, Lakhdar, Montlahuc, Claire, Biard, Lucie, Alary, St.phanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Charreteur, Robin, Dupre, Céline, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Pavy, Stephan, Nocturne, Gaétane, Bitoun, Samuel, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stephane, Baudry, Elodie, Verny, Christiane, Lefevre, Edouard, Zaidan, Mohamad, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Grimaldi, Lamiae, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Soléne, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Le Tiec, Clotilde, Verstuyft, Céline, Roques, Anne-Marie, Georgin-Lavialle, Sophie, Senet, Patricia, Pialoux, Gilles, Soria, Angele, Parrot, Antoine, François, Helene, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadege, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefévre, Guillaume, Gottenberg, Jacques-Eric, Hansmann, Yves, Blanc, Frédéric, Ohlmann-Caillard, Sophie, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurelien, Heger, Bob, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Mertes, Paul-Michel, Noll, Eric, Oberlin, Mathieu, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Weill, François, Meyer, Nicolas, Andres, Emmanuel, Demonsant, Eric, Tayebi, Hakim, Nisand, Gabriel, Brin, Stéphane, Sublon, Cédric, Becker, Guillaume, Hutt, Anne, Martin, Tristan, Bayer, Sophie, Metzger, Catherine, Mekinian, Arsene, Abisror, Noémie, Adedjouma, Amir, Bollens, Diane, Bonneton, Marion, Bourcicaux, Nathalie, Bourrier, Anne, Thibault Chiarabiani, Maria Chauchard, Chopin, Doroth.e, Cohen, Jonathan, Devred, Ines, Donadille, Bruno, Fain, Olivier, Hariri, Geoffrey, Jachiet, Vincent, Ingliz, Patrick, Garnier, Marc, Gatfosse, Marc, Ghrenassia, Etienne, Gobert, Delphine, Krause le Garrec, Jessica, Landman, Cecilia, Lavillegrand, Jean Remy, Lefebvre, Benedicte, Mahevas, Thibault, Mazerand, Sandie, Meynard, Jean Luc, Morgand, Marjolaine, Ouaz.ne, Zineb, Pacanowski, Jerome, Riviere, S.bastien, Seksik, Philippe, Sokol, Harry, Soliman, Heithem, Valin, Nadia, Urbina, Thomas, McAvoy, Chloé, Miranda, Maria Pereira, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Nguyen, Anne Daguenel, Girault, Elise, Mayala-Kanda, Cl.mentine, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Pennet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Denis, Jesuthasan, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Val.rie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, Xavier, Ghosn, Jade, Bachelard, Antoine, Rachline, Anne, Isernia, Valentina, Bao-chau, Phung, Vallois, Dorothée, Sautereau, Aurelie, Neukrich, Catherine, Dossier, Antoine, Borie, Raphaël, Crestani, Bruno, Ducrocq, Gregory, Steg, Philippe Gabriel, Dieude, Philippe, Papo, Thomas, Marcault, Estelle, Chaudhry, Marhaba, Da Silveira, Charléne, Metois, Annabelle, Mahenni, Ismahan, Meziani, Meriam, Nilusmas, Cyndie, Le Gac, Sylvie, Ndiaye, Awa, Louni, Fran.oise, Chansombat, Malikhone, Julia, Zelie, Chalal, Solaya, Chalal, Lynda, Kramer, Laura, Le Grand, Jeniffer, Ouifiya, Kafif, Piquard, Valentine, Tubiana, Sarah, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anais, Zarrouk, Virginie, de Lastours, Victoire, Uzzan, Matthieu, Gamany, Naura, Claveirole, Agathe, Navid, Alexandre, Fouque, Tiffanie, Cohen, Yonathan, Lupo, Maya, Gilles, Constance, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, de Castro, Nathalie, Clément, Melissa, Darmon, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lenglin, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asma, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Lebras, Karine Celli, Chabert, Julien, Djaghout, Lamia, Fauvaux, Catherine, Jegu, Anne Lise, Kozakiewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madelaine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, Sène, Damien, Burlacu, Ruxandra, Chousterman, Benjamin, Mégarbanne, Bruno, Richette, Pascal, Riveline, Jean-Pierre, Frazier, Aline, Vicaut, Eric, Berton, Laure, Hadjam, Tassadit, Vazquez-Ibarra, Miguel Alejandro, Jourdaine, Clément, Tran, Olivia, Jouis, Véronique, Jacob, Aude, Smati, Julie, Renaud, Stéphane, Pernin, Claire, Suarez, Lydia, Semerano, Luca, Abad, Sébastien, nainous, Ruben B., Bonnet, Nicolas, Comparon, Celine, Cohen, Yves, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Gille, Thomas, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Nunes, Hilario, Oziel, Johanna, Roulot, Dominique, Sese, Lucile, ClaireTantet, Uzunhan, Yurdagul, Bloch-Queyrat, Coralie, Levy, Vincent, Messani, Fadhila, Rahaoui, Mohammed, Petit, Myléne, Brahmi, Sabrina, Rathoin, Vanessa, Rigal, Marthe, Costedoat-Chalumeau, Nathalie, Luong, Liem Binh, Hamou, Zakaria Ait, Benghanem, Sarah, Blanche, Philippe, Carlier, Nicolas, Chaigne, Benjamin, Gauzit, Remy, Joumaa, Hassan, Jozwiak, Mathieu, Lachétre, Marie, Lafoeste, Hélène, Launay, Odie, Legendre, Paul, Marey, Jonathan, Morbieu, Caroline, Palmieri, Lola-Jade, Szwebel, Tali-Anne, Abdoul, Hendy, Bruneau, Alexandra, Beclin-Clabaux, Audrey, Larrieu, Charly, Montanari, Pierre, Dufour, Eric, Clarke, Ada, Le Bourlout, Catherine, Marin, Nathalie, Menage, Nathalie, Saleh-Mghir, Samira, Cisse, Mamadou Salif, Cheref, Kahina, Guerin, Corinne, Zerbit, Jérémie, Michel, Marc, Gallien, Sébastien, Crickx, Etienne, Le Vavasseur, Benjamin, Kempf, Emmanuelle, Jaffal, Karim, Vindrios, William, Oniszczuk, Julie, Guillaud, Constance, Lim, Pascal, Fois, Elena, Melica, Giovanna, Matignon, Marie, Jalabert, Maud, Lelièvre, Jean-Daniel, Schmitz, David, Bourhis, Marion, Belazouz, Sylia, Languille, Laetitia, Boucle, Caroline, Cita, Nelly, Didier, Agnés, Froura, Fahem, Ledudal, Katia, Sadaoui, Thiziri, Thiemele, Alaki, Le Febvre De Bailly, Delphine, Verlinde, Muriel Carvhalo, Mayaux, Julien, Cacoub, Patrice, Saadoun, David, Vautier, Mathieu, Bugaut, Héléne, Benveniste, Olivier, Allenbach, Yves, Leroux, Gaëlle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Chloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Goncalo, Ferfar, Yasmina, Corvol, Jean-Christophe, Louapre, C.line, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aicha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sebastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Charbonnier, Fanny, Aguilar, Claire, Alby-Laurent, Fanny, Burger, Carole, Campos-Vega, Clara, Chavarot, Nathalie, Fournier, Benjamin, Rouzaud, Claire, Vimpére, Damien, Elie, Caroline, Bakouboula, Prissile, Choupeaux, Laure, Granville, Sophie, Issorat, Elodie, Broissand, Christine, Alyanakian, Marie-Alexandra, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Héléne, Duclos-vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Kounis, Ilias, Tamazirt, Sonia, Rudant, Eric, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Christophe, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Netzer, Florence, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Héléne, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Chan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Marquis, Eric, Benoit, Philippe, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Helene, Mourad, Jean-Jacques, Sacco, Emmanuelle, Renet, Sophie, Ader, F., Yazdanpanah, Y., Mentre, F., Peiffer-Smadja, N., Lescure, F.X., Poissy, J., Bouadma, L., Timsit, J.F., Lina, B., Morfin-Sherpa, F., Bouscambert, M., Gaymard, A., Peytavin, G., Abel, L., Guedj, J., Andrejak, C., Burdet, C., Laouenan, C., Belhadi, D., Dupont, A., Alfaiate, T., Basli, B., Chair, A., Laribi, S., Level, J., Schneider, M., Tellier, M.C., Dechanet, A., Costagliola, D., Terrier, B., Ohana, M., Couffin-Cadiergues, S., Esperou, H., Delmas, C., Saillard, J., Fougerou, C., Moinot, L., Wittkop, L., Cagnot, C., Le Mestre, S., Lebrasseur-Longuet, D., Petrov-Sanchez, V., Diallo, A., Mercier, N., Icard, V., Leveau, B., Tubiana, S., Hamze, B., Gelley, A., Noret, M., D’Ortenzio, E., Puechal, O., Semaille, C., Welte, T., Paiva, J.A., Halanova, M., Kieny, M.P., Balssa, E., Birkle, C., Gibowski, S., Landry, E., Le Goff, A., Moachon, L., Moins, C., Wadouachi, L., Paul, C., Levier, A., Bougon, D., Djossou, F., Epelboin, L., Dellamonica, J., Marquette, C.H., Robert, C., Gibot, S., Senneville, E., Jean-Michel, V., Zerbib, Y., Chirouze, C., Boyer, A., Cazanave, C., Gruson, D., Malvy, D., Andreu, P., Quenot, J.P., Terzi, N., Faure, K., Chabartier, C., Le Moing, V., Klouche, K., Ferry, T., F, Valour, Gaborit, B., Canet, E., Le Turnier, P., Boutoille, D., Bani-Sadr, F., Benezit, F., Revest, M., Cameli, C., Caro, A., Um Tegue, MJ Ngo, Le Tulzo, Y., Laviolle, B., Laine, F., Thiery, G., Meziani, F., Hansmann, Y., Oulehri, W., Tacquard, C., Vardon-Bounes, F., Riu-Poulenc, B., Murris-Espin, M., Bernard, L., Garot, D., Hinschberger, O., Martinot, M., Bruel, C., Pilmis, B., Bouchaud, O., Loubet, P., Roger, C., Monnet, X., Figueiredo, S., Godard, V., Mira, J.P., Lachatre, M., Kerneis, S., Aboab, J., Sayre, N., Crockett, F., Lebeaux, D., Buffet, A., Diehl, J.L., Fayol, A., Hulot, J.S., Livrozet, M., Dessap, A Mekontso, Ficko, C., Stefan, F., Le Pavec, J., Mayaux, J., Ait-Oufella, H., Molina, J.M., Pialoux, G., Fartoukh, M., Textoris, J., Brossard, M., Essat, A., Netzer, E., Riault, Y., Ghislain, M., Beniguel, L., Genin, M., Gouichiche, L., Betard, C., Belkhir, L., Altdorfer, A., Centro, V Fraipont, Braz, S., Ribeiro, JM Ferreira, Alburqueque, R Roncon, Berna, M., Alexandre, M., Lamprecht, B., Egle, A., Greil, R., Joannidis, M., Patterson, Thomas F., Ponce, Philip O., Taylor, Barbara S., Patterson, Jan E., Bowling, Jason E., Javeri, Heta, Kalil, Andre C., Larson, LuAnn, Hewlett, Angela, Mehta, Aneesh K., Rouphael, Nadine G., Saklawi, Youssef, Scanlon, Nicholas, Traenkner, Jessica J., Trible, Ronald P., Jr., Walter, Emmanuel B., Ivey, Noel, Holland, Thomas L., Ruiz-Palacios, Guillermo M., Ponce de León, Alfredo, Rajme, Sandra, Hsieh, Lanny, Amin, Alpesh N., Watanabe, Miki, Lee, Helen S., Kline, Susan, Billings, Joanne, Noren, Brooke, Kim, Hyun, Bold, Tyler D., Tapson, Victor, Grein, Jonathan, Sutterwala, Fayyaz, Iovine, Nicole, Beattie, Lars K., Wakeman, Rebecca Murray, Shaw, Matthew, Jain, Mamta K., Mocherla, Satish, Meisner, Jessica, Luque, Amneris, Sweeney, Daniel A., Benson, Constance A., Ali, Farhana, Atmar, Robert L., El Sahly, Hana M., Whitaker, Jennifer, Falsey, Ann R., Branche, Angela R., Rozario, Cheryl, Pineda, Justino Regalado, Martinez-Orozco, José Arturo, Lye, David Chien, Ong, Sean WX., Chia, Po Ying, Young, Barnaby E., Sandkovsky, Uriel, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Cantos, Valeria D., Kelley, Colleen F., Rebolledo Esteinou, Paulina A., Kandiah, Sheetal, Doernberg, Sarah B., Crouch, Pierre-Cedric B., Jang, Hannah, Luetkemeyer, Anne F., Dwyer, Jay, Cohen, Stuart H., Thompson, George R., 3rd, Nguyen, Hien H., Finberg, Robert W., Wang, Jennifer P., Perez-Velazquez, Juan, Wessolossky, Mireya, Jackson, Patrick E.H., Bell, Taison D., West, Miranda J., Taiwo, Babafemi, Krueger, Karen, Perez, Johnny, Pearson, Triniece, Paules, Catharine I., Julian, Kathleen G., Ahmad, Danish, Hajduczok, Alexander G., Arguinchona, Henry, Arguinchona, Christa, Erdmann, Nathaniel, Goepfert, Paul, Ahuja, Neera, Frank, Maria G., Wyles, David, Young, Heather, Oh, Myoung-don, Park, Wan Beom, Kang, Chang Kyung, Marconi, Vincent, Moanna, Abeer, Cribbs, Sushma, Harrison, Telisha, Kim, Eu Suk, Jung, Jongtak, Song, Kyoung-Ho, Kim, Hong Bin, Tan, Seow Yen, Shafi, Humaira, Chien, Jaime, Fong, Raymond KC., Murray, Daniel D., Lundgren, Jens, Nielsen, Henrik, Jensen, Tomas, Zingman, Barry S., Grossberg, Robert, Riska, Paul F., Yang, Otto O., Ahn, Jenny, Arias, Rubi, Rapaka, Rekha R., Hauser, Naomi, Campbell, James D., Short, William R., Tebas, Pablo, Baron, Jillian T., McLellan, Susan L.F., Blanton, Lucas S., Seashore, Justin B., Creech, C. Buddy, Rice, Todd W., Walker, Shannon, Thomsen, Isaac P., Lopez de Castilla, Diego, Van Winkle, Jason W., Riedo, Francis X., Pada, Surinder Kaur, Wang, Alvin DY., Lin, Li, Harkins, Michelle, Mertz, Gregory, Sosa, Nestor, Ann Chai, Louis Yi, Tambyah, Paul Anantharajah, Tham, Sai Meng, Archuleta, Sophia, Yan, Gabriel, Lindholm, David A., Markelz, Ana Elizabeth, Mende, Katrin, Mularski, Richard, Hohmann, Elizabeth, Torres-Soto, Mariam, Jilg, Nikolaus, Maves, Ryan C., Utz, Gregory C., George, Sarah L., Hoft, Daniel F., Brien, James D., Paredes, Roger, Mateu, Lourdes, Loste, Cora, Kumar, Princy, Thornton, Sarah, Mohanraj, Sharmila, Hynes, Noreen A., Sauer, Lauren M., Colombo, Christopher J., Schofield, Christina, Colombo, Rhonda E., Chambers, Susan E., Novak, Richard M., Wendrow, Andrea, Gupta, Samir K., Lee, Tida, Lalani, Tahaniyat, Holodniy, Mark, Chary, Aarthi, Huprikar, Nikhil, Ganesan, Anuradha, Ohmagari, Norio, Mikami, Ayako, Price, D. Ashley, Duncan, Christopher J.A., Dierberg, Kerry, Neumann, Henry J., Taylor, Stephanie N., Lacour, Alisha, Masri, Najy, Swiatlo, Edwin, Widmer, Kyle, Neaton, James D., Bessesen, Mary, Stephens, David S., Burgess, Timothy H., Uyeki, Timothy M., Walker, Robert, Marks, G. Lynn, Osinusi, Anu, Cao, Huyen, Cardoso, Anabela, de Bono, Stephanie, Schlichting, Douglas E., Chung, Kevin K., Ferreira, Jennifer L., Green, Michelle, Makowski, Mat, Wierzbicki, Michael R., Conrad, Tom M., El-Khorazaty, Jill Ann, Hill, Heather, Bonnett, Tyler, Gettinger, Nikki, Engel, Theresa, Lewis, Teri, Wang, Jing, Beigel, John H., Tomashek, Kay M., Ghazaryan, Varduhi, Beresnev, Tatiana, Nayak, Seema, Dodd, Lori E., Dempsey, Walla, Nomicos, Effie, Lee, Marina, Pikaart-Tautges, Rhonda, Elsafy, Mohamed, Jurao, Robert, Koo, Hyung, Proschan, Michael, Yokum, Tammy, Arega, Janice, Florese, Ruth, Voell, Jocelyn D., Davey, Richard, Serrano, Ruth C., Wiley, Zanthia, Phadke, Varun K., Goepfert, Paul A., Gomez, Carlos A., Sofarelli, Theresa A., Certain, Laura, Imlay, Hannah N., Wolfe, Cameron R., Ko, Emily R., Engemann, John J., Felix, Nora Bautista, Wan, Claire R., Elmor, Sammy T., Bristow, Laurel R., Harkins, Michelle S., Iovine, Nicole M., Elie-Turenne, Marie-Carmelle, Tapson, Victor F., Choe, Pyoeng Gyun, Mularski, Richard A., Rhie, Kevin S., Hussein, Rezhan H., Ince, Dilek, Winokur, Patricia L., Takasaki, Jin, Saito, Sho, McConnell, Kimberly, Wyles, David L., Sarcone, Ellen, Grimes, Kevin A., Perez, Katherine, Janak, Charles, Whitaker, Jennifer A., Rebolledo, Paulina A., Gharbin, John, Lambert, Allison A., Zea, Diego F., Bainbridge, Emma, Hostler, David C., Hostler, Jordanna M., Shahan, Brian T., Ling, Evelyn, Go, Minjoung, Hubbard, Fleesie A., Chakrabarty, Melony, Laguio-Vila, Maryrose, Walsh, Edward E., Guirgis, Faheem, Marconi, Vincent C., Madar, Christian, Borgetti, Scott A., Levine, Corri, Nock, Joy, Candiotti, Keith, Rozman, Julia, Dangond, Fernando, Hyvert, Yann, Seitzinger, Andrea, Cross, Kaitlyn, Pettibone, Stephanie, Nayak, Seema U., Deye, Gregory A., Siempos, Ilias I., Belhadi, Drifa, Veiga, Viviane Cordeiro, Cavalcanti, Alexandre Biasi, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta A., and Kotanidou, Anastasia

Published
2024
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15. Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study

Author

Gavrielatou, Evdokia, Vaporidi, Katerina, Tsolaki, Vasiliki, Tserlikakis, Nikos, Zakynthinos, George E., Papoutsi, Eleni, Maragkuti, Aikaterini, Mantelou, Athina G., Karayiannis, Dimitrios, Mastora, Zafeiria, Georgopoulos, Dimitris, Zakynthinos, Epaminondas, Routsi, Christina, Zakynthinos, Spyros G., Schenck, Edward J., Kotanidou, Anastasia, and Siempos, Ilias I.

Published
2022
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16. Association Between Baseline Driving Pressure and Mortality in Very Old Patients with Acute Respiratory Distress Syndrome.

Author

Papoutsi, Eleni, Gkirgkiris, Konstantinos, Tsolaki, Vasiliki, Andrianopoulos, Ioannis, Pontikis, Konstantinos, Vaporidi, Katerina, Gkoufas, Spyridon, Kyriakopoulou, Magdalini, Kyriakoudi, Anna, Paramythiotou, Elisabeth, Kaimakamis, Evangelos, Bostantzoglou, Clementine, Bitzani, Militsa, Daganou, Mary, Koulouras, Vasilios, Kondili, Eumorfia, Koutsoukou, Antonia, Dimopoulou, Ioanna, Kotanidou, Anastasia, and Siempos, Ilias I.

Subjects
ADULT respiratory distress syndrome, RESPIRATORY organs, OLDER patients, LOGISTIC regression analysis, OCTOGENARIANS
Abstract

Rationale: Because of the effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age. Objectives: We endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (⩾80 yr), patients. Methods: We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). We tested our hypothesis in a second, independent, national cohort ("Hellenic cohort"). We performed both binary logistic and Cox regression analyses including the interaction term between age (as a continuous variable) and driving pressure at baseline (i.e., the day of trial enrollment) as the predictor and 90-day mortality as the dependent variable. Measurements and Main Results: On the basis of data from 4,567 patients with ARDS included in the ARDSNet cohort, we found that the effect of driving pressure on mortality depended on age (P = 0.01 for the interaction between age as a continuous variable and driving pressure). The difference in driving pressure between survivors and nonsurvivors significantly changed across the adult lifespan (P < 0.01). In both cohorts, a driving pressure threshold of 11 cm H2O was associated with mortality in very old patients. Conclusions: Data from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on the mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Retraction: UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis

Author

Moon, Jong-Seok, Lee, Seonmin, Park, Mi-Ae, Siempos, Ilias I., Haslip, Maria, Lee, Patty J., Yun, Mijin, Kim, Chun K., Howrylak, Judie, Ryter, Stefan W., Nakahira, Kiichi, and Choi, Augustine M.K.

Abstract

Jong-Seok Moon, Seonmin Lee, Mi-Ae Park, Ilias I. Siempos, Maria Haslip, Patty J. Lee, Mijin Yun, Chun K. Kim, Judie Howrylak, Stefan W. Ryter, Kiichi Nakahira, and Augustine M.K. Choi [...]

Published
2023
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19. Mechanical ventilation in patients with acute brain injury: recommendations of the European Society of Intensive Care Medicine consensus

Author

Robba, Chiara, Poole, Daniele, McNett, Molly, Asehnoune, Karim, Bösel, Julian, Bruder, Nicolas, Chieregato, Arturo, Cinotti, Raphael, Duranteau, Jacques, Einav, Sharon, Ercole, Ari, Ferguson, Niall, Guerin, Claude, Siempos, Ilias I., Kurtz, Pedro, Juffermans, Nicole P., Mancebo, Jordi, Mascia, Luciana, McCredie, Victoria, Nin, Nicolas, Oddo, Mauro, Pelosi, Paolo, Rabinstein, Alejandro A., Neto, Ary Serpa, Seder, David B., Skrifvars, Markus B., Suarez, Jose I., Taccone, Fabio Silvio, van der Jagt, Mathieu, Citerio, Giuseppe, and Stevens, Robert D.

Published
2020
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26. Early Mortality in Clinical Trials of Acute Respiratory Distress Syndrome.

Author

Giannakoulis, Vassilis G., Schenck, Edward J., Papoutsi, Eleni, Price, David R., Villar, Jesús, Sarwath, Hina, Schmidt, Frank, Thompson, B. Taylor, Choi, Augustine M. K., and Siempos, Ilias I.

Subjects
ADULT respiratory distress syndrome, CLINICAL trials, LACTOSE intolerance
Abstract

The article focuses on early mortality among patients with acute respiratory distress syndrome (ARDS) within the context of randomized controlled trials. It hypothesizes that early deaths, occurring within 3 days of randomization, exhibit distinct baseline characteristics, clinical trajectories, and proteomic profiles compared to late deaths. It highlight potential biomarkers associated with early mortality in ARDS, providing insights for prognosis and therapeutic strategies.

Published
2024
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31. Drug-overdose associated acute hypoxemic respiratory failure: A secondary analysis.

Author

Gkirgkiris, Konstantinos, Papoutsi, Eleni, Athanasiou, Nikolaos, Gκoufas, Spyridon, and Siempos, Ilias I.

Subjects
ADULT respiratory distress syndrome, DRUG overdose, SECONDARY analysis
Abstract

INTRODUCTION: The majority of fatal drug overdose cases are due to acute hypoxemic respiratory failure (AHRF). We examined whether AHRF associated with drug overdose has distinct features from AHRF associated with other risk factors. METHODS: We performed a secondary analysis of patient-level data from the LOTUS FRUIT study, a multicenter, prospective, observational study conducted by the PETAL Network. We classified patients with AHRF into the 'drugoverdose associated AHRF' (when PETAL investigators listed drug overdose as a risk factor of AHRF) versus the 'non-drug-overdose associated AHRF' group. To assess the association between drug overdose and 28-day mortality, we used a Cox proportional hazards regression analysis, both unadjusted and adjusted, and a mediation analysis. RESULTS: Of the 1280 patients with AHRF, 48 (3.8%) had drug-overdose associated AHRF. They were younger (42.0 vs 60.0 years), more likely to develop rapidly improving AHRF (50.0% vs 24.5%) and had lower unadjusted mortality than patients with non-drug-overdose associated AHRF (16.7% vs 34.4.%) (hazard ratio, HR=0.450; 95% CI: 0.223-0.905). However, after adjustment, drug overdose was no longer associated with lower mortality (adjusted hazard ratio, AHR=0.584; 95% CI: 0.288-1.185). Also, in mediation analysis, lower unadjusted mortality among patients with drug-overdose AHRF was significantly mediated by the development of rapidly improving AHRF (p<0.001 for the average causal mediation effect). CONCLUSIONS: Patients with drug-overdose associated AHRF were younger and had lower unadjusted mortality than patients with non-drug-overdose associated AHRF. However, this difference in mortality seemed to be due to confounders, such as age, and to be mediated by the development of rapidly improving AHRF. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Right atrial strain during prone ventilation in acute respiratory distress syndrome.

Author

Kalogeris, Aimilianos N., Ntaidou, Theodora K., Koroneos, Apostolos, Kotanidou, Anastasia, and Siempos, Ilias I.

Subjects
ADULT respiratory distress syndrome, SPECKLE tracking echocardiography, ECHOCARDIOGRAPHY, PULMONARY artery catheters, VENTILATION
Abstract

Although prone ventilation is widely used in acute respiratory distress syndrome (ARDS), its effects on right heart function, assessed by state-of-the-art echocardiography, are not well studied. We report the effect of prone ventilation on right atrial strain in severe ARDS after optimization of lung recruitment and hemodynamics using esophageal pressure and pulmonary artery catheter measurements, respectively. A 66-year-old obese man with ischemic heart failure was intubated due to ARDS. Before, during and after his first prone session, pulmonary, hemodynamic and echocardiographic (using twodimensional transthoracic speckle tracking echocardiography) parameters were measured. Prone ventilation sustainably improved lung recruitment and right atrial strain. Combining detailed physiological and advanced echocardiographic assessment provides insights into the effect of prone ventilation in ARDS. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Association Between Vaccination Status and Mortality Among Intubated Patients With COVID-19–Related Acute Respiratory Distress Syndrome

Author

Grapsa, Eirini, primary, Adamos, Georgios, additional, Andrianopoulos, Ioannis, additional, Tsolaki, Vasiliki, additional, Giannakoulis, Vassilis G., additional, Karavidas, Nikitas, additional, Giannopoulou, Vassiliki, additional, Sarri, Katerina, additional, Mizi, Eleftheria, additional, Gavrielatou, Evdokia, additional, Papathanakos, Georgios, additional, Mantzarlis, Konstantinos D., additional, Mastora, Zafeiria, additional, Magira, Eleni, additional, Koulouras, Vasilios, additional, Kotanidou, Anastasia, additional, and Siempos, Ilias I., additional

Published
2022
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39. Older adults with severe coronavirus disease 2019 admitted to intensive care unit: prevalence, characteristics and risk factors for mortality

Author

KOKKORIS, Stelios, primary, GKOUFA, Aikaterini, additional, MANETA, Eleni, additional, DOUMAS, Georgios, additional, MIZI, Eleftheria, additional, GEORGAKOPOULOU, Vassiliki E., additional, SIGALA, Ioanna, additional, DIMA, Efthymia, additional, PAPACHATZAKIS, Ioannis, additional, NTAIDOU, Theodora K., additional, MARKAKI, Vassiliki, additional, TSIMARAS, Michail, additional, KREMMYDAS, Panagiotis, additional, SAMARKOS, Michail, additional, SIEMPOS, Ilias I., additional, VASILEIADIS, Ioannis, additional, KOTANIDOU, Anastasia, additional, ZAKYNTHINOS, Spyros, additional, BENETOS, Athanase, additional, and ROUTSI, Christina, additional

Published
2022
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40. Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice

Author

Cloonan, Suzanne M., Glass, Kimberly, Laucho-Contreras, Maria E., Bhashyam, Abhiram R., Cervo, Morgan, Pabon, Maria A., Konrad, Csaba, Polverino, Francesca, Siempos, Ilias I., Perez, Elizabeth, Mizumura, Kenji, Ghosh, Manik C., Parameswaran, Harikrishnan, Williams, Niamh C., Rooney, Kristen T., Chen, Zhi-Hua, Goldklang, Monica P., Yuan, Guo-Cheng, Moore, Stephen C., Demeo, Dawn L., Rouault, Tracey A., D'Armiento, Jeanine M., Schon, Eric A., Manfredi, Giovanni, Quackenbush, John, Mahmood, Ashfaq, Silverman, Edwin K., Owen, Caroline A., and Choi, &.Augustine M.K.

Subjects
Care and treatment, Genetic aspects, Patient outcomes, Methods, Health aspects, Cigarette smoke -- Health aspects, Emphysema -- Genetic aspects -- Care and treatment, Molecular targeted therapy -- Methods -- Patient outcomes, Chelation therapy -- Methods -- Patient outcomes, Bronchitis -- Analysis -- Genetic aspects -- Care and treatment, Emphysema, Pulmonary -- Genetic aspects -- Care and treatment
Abstract

COPD presents as a complex, debilitating lung disease that encompasses a variety of clinical and pathologic phenotypes ranging from airway inflammation (chronic bronchitis) to destruction of lung tissue (emphysema) and [...], Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element-binding protein 2 (IRP2) as an important COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RNA immunoprecipitation followed by sequencing (RIP-seq), RNA sequencing (RNA-seq), and gene expression and functional enrichment clustering analysis, we identified Irp2 as a regulator of mitochondrial function in the lungs of mice. Irp2 increased mitochondrial iron loading and levels of cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice, which had higher mitochondrial iron loading, showed impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas mice deficient in the synthesis of cytochrome c oxidase, which have reduced COX, were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-induced impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeuticition for the mitochondrial-iron axis in COPD.

Published
2016
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42. Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis

Author

Gavrielatou, Evdokia Xourgia, Eleni Xixi, Nikoleta A. and Mantelou, Athina G. Ischaki, Eleni Kanavou, Aggeliki and Zervakis, Dimitris Routsi, Christina Kotanidou, Anastasia and Siempos, Ilias I. and Gavrielatou, Evdokia Xourgia, Eleni Xixi, Nikoleta A. and Mantelou, Athina G. Ischaki, Eleni Kanavou, Aggeliki and Zervakis, Dimitris Routsi, Christina Kotanidou, Anastasia and Siempos, Ilias I.

Abstract

Background: Whether vitamin C provides any benefit when administered in critically ill patients, including those with coronavirus disease (COVID-19), is controversial. We endeavored to estimate the effect of administration of vitamin C on clinical outcomes of critically ill patients with COVID-19 by performing an observational study and subsequent meta-analysis.& nbsp;Methods: Firstly, we conducted an observational study of critically ill patients with laboratory-confirmed COVID-19 who consecutively underwent invasive mechanical ventilation in an academic intensive care unit (ICU) during the second pandemic wave. We compared all-cause mortality of patients receiving vitamin C ( “vitamin C “ group) or not ( “control “ group) on top of standard-of-care. Subsequently, we systematically searched PubMed and CENTRAL for relevant studies, which reported on all-cause mortality (primary outcome) and/or morbidity of critically ill patients with COVID-19 receiving vitamin C or not treatment. Pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO.& nbsp;Results: In the observational study, baseline characteristics were comparable between the two groups. Mortality was 20.0% (2/10) in the vitamin C group vs. 47.6% (49/103; p = 0.11) in the control group. Subsequently, the meta-analysis included 11 studies (6 observational; five randomized controlled trials) enrolling 1,807 critically ill patients with COVID-19. Mortality of patients receiving vitamin C on top of standard-of-care was not lower than patients receiving standard-of-care alone (25.8 vs. 34.7%; RR 0.85, 95% CI 0.57-1.26; p = 0.42).& nbsp;Conclusions: After combining results of our observational cohort with those of relevant studies into a meta-analysis of data from 1,807 patients, we found that administration vitamin C as opposed to standard-of-care alone might not be associated with lower of mortality among criti

Published
2022

43. Abnormal Right Ventricular Free Wall Strain Prior to Prone Ventilation May Be Associated With Worse Outcome of Patients With COVID-19-Associated Acute Respiratory Distress Syndrome.

Author

Temperikidis, Prodromos Koroneos, Apostolos Xourgia, Eleni Kotanidou, Anastasia Siempos, Ilias I. and Temperikidis, Prodromos Koroneos, Apostolos Xourgia, Eleni Kotanidou, Anastasia Siempos, Ilias I.

Abstract

We investigated the effect of prone ventilation on right ventricular (RV) function of intubated patients with COVID-19-associated acute respiratory distress syndrome by measuring both conventional RV functional variables (namely, tricuspid annular peak systolic velocity, tricuspid annular plane systolic excursion, and fractional area change) and right ventricular free wall strain (RVFWS) using transthoracic speckle-tracking echocardiography at baseline (before prone positioning), 18 hours after prone positioning, and 1 hour after supine repositioning. We found that transthoracic echocardiography was feasible in a considerable proportion (nine patients, 75% of our cohort) of patients undergoing prone ventilation. Also, abnormal as opposed to normal RVFWS values (in the absence of conventional variables of RV dysfunction) at baseline were associated with higher mortality (100% vs 20%; p = 0.048). Finally, we found that, among patients without acute cor pulmonale or conventional markers of RV dysfunction, one session of prone ventilation may not affect right myocardial strain.

Published
2022

45. Additional file 1 of Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study

Author

Gavrielatou, Evdokia, Vaporidi, Katerina, Tsolaki, Vasiliki, Tserlikakis, Nikos, Zakynthinos, George E., Papoutsi, Eleni, Maragkuti, Aikaterini, Mantelou, Athina G., Karayiannis, Dimitrios, Mastora, Zafeiria, Georgopoulos, Dimitris, Zakynthinos, Epaminondas, Routsi, Christina, Zakynthinos, Spyros G., Schenck, Edward J., Kotanidou, Anastasia, and Siempos, Ilias I.

Subjects
respiratory tract diseases
Abstract

Additional file 1: Table 1. Baseline characteristics, lung mechanics and outcomes of included patients across the three participating study sites. Figure S1. Distribution of scores of Sequential Organ Failure Assessment (SOFA) on the day of intubation among the three study sites. Figure S2. Distribution of partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) values on the day of intubation (calculated after intubation) among the three study sites. Table S2. Univariable and multiple variable regression analysis to isolate the contribution of age, modified SOFA score on the day of intubation and study site (independent variables) to the ICU-mortality (dependent variable). Table S3. Univariable and multiple variable regression analysis to isolate the contribution of PaO2:FiO2, FiO2 and driving pressure on the day of intubation (independent variables) to the development of persistent severe ARDS (dependent variable). Table S4. Univariable and multiple variable regression analysis to isolate the contribution of age, modified SOFA score on the day of intubation and change in PaO2:FiO2 from day of intubation to the first day following intubation (independent variables) to the ICU-mortality (dependent variable). Table S5. Characteristics and outcomes of patients hospitalized in Crete with ARDS related to COVID-19 versus influenza. Table S6. Characteristics and outcomes of patients with rapidly improving ARDS due to pneumonia related or not to COVID-19.

Published
2022
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46. UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis

Author

Moon, Jong-Seok, Lee, Seonmin, Park, Mi-Ae, Siempos, Ilias I., Haslip, Maria, Lee, Patty J., Yun, Mijin, Kim, Chun K., Howrylak, Judie, Ryter, Stefan W., Nakahira, Kiichi, and Choi, Augustine M.K.

Subjects
Development and progression, Genetic aspects, Properties, Lipid synthesis -- Genetic aspects, Cellular proteins -- Properties, Sepsis -- Genetic aspects -- Development and progression, Immune response -- Genetic aspects, Lipids -- Synthesis
Abstract

Introduction Sepsis remains the leading cause of death in the medical intensive care unit (MICU) (1). Although inflammatory responses are important for host defense against invading microbes, excessive inflammation in [...], Cellular lipid metabolism has been linked to Immune responses; however, the precise mechanisms by which de novo fatty add synthesis can regulate inflammatory responses remain unclear. The NLRP3 inflammasome serves as a platform for caspase-1-dependent maturation and secretion of proinflammatory cytokines. Here, we demonstrated that the mitochondrial uncoupling protein-2 (UCP2) regulates NLRP3-mediated caspase-1 activation through the stimulation of lipid synthesis in macrophages. UCP2-deficient mice displayed improved survival in a mouse model of polymicrobial sepsis. Moreover, UCP2 expression was increased in human sepsis. Consistently, UCP2-deficient mice displayed impaired lipid synthesis and decreased production of IL-1β and IL-18 in response to LPS challenge. In macrophages, UCP2 deficiency suppressed NLRP3-mediated caspase-1 activation and NLRP3 expression associated with inhibition of lipid synthesis. In UCP2- deficient macrophages, inhibition of lipid synthesis resulted from the downregulation of fatty acid synthase (FASN), a key regulator of fatty acid synthesis. FASN inhibition by shRNA and treatment with the chemical inhibitors C75 and cerulenin suppressed NLRP3-mediated caspase-1 activation and inhibited NLRP3 and pro-IL-1β gene expression in macrophages. In conclusion, our results suggest that UCP2 regulates the NLRP3 inflammasome by inducing the lipid synthesis pathway in macrophages. These results identify UCP2 as a potential therapeutic target in inflammatory diseases such as sepsis.

Published
2015
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