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

Author

Siempos, Ilias, Kalil, Andre, Belhadi, Drifa, Veiga, Viviane, Cavalcanti, Alexandre, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta, Kotanidou, Anastasia, Hermine, Olivier, Porcher, Raphaël, and Mariette, Xavier

Subjects
Acute hypoxemic respiratory failure, Acute respiratory distress syndrome, Cancer, Critically ill, Pneumonia
Abstract

BACKGROUND: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. METHODS: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). FINDINGS: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61-1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64-1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09-0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. INTERPRETATION: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. FUNDING: Hellenic Foundation for Research and Innovation.

Published
2024

5. Effect of Early Versus Delayed Tracheostomy Strategy on Functional Outcome of Patients With Severe Traumatic Brain Injury: A Target Trial Emulation

Author

Vassilis G. Giannakoulis, MD, Georgios Psychogios, MD, PhD, Christina Routsi, MD, PhD, Ioanna Dimopoulou, MD, PhD, and Ilias I. Siempos, MD, DSc

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Optimal timing of tracheostomy in severe traumatic brain injury (TBI) is unknown due to lack of clinical trials. We emulated a target trial to estimate the effect of early vs. delayed tracheostomy strategy on functional outcome of patients with severe TBI. DESIGN:. Target trial emulation using 1:1 balanced risk-set matching. SETTING:. North American hospitals participating in the TBI Hypertonic Saline randomized controlled trial of the Resuscitation Outcomes Consortium. PATIENTS:. The prematching population consisted of patients with TBI and admission Glasgow Coma Scale less than or equal to 8, who were alive and on mechanical ventilation on the fourth day following trial enrollment, and stayed in the ICU for at least 5 days. Patients with absolute indication for tracheostomy and patients who died during the first 28 days with a decision to withdraw care were excluded. INTERVENTIONS:. We matched patients who received tracheostomy at a certain timepoint (early group) with patients who had not received tracheostomy at the same timepoint but were at-risk of tracheostomy in the future (delayed group). The primary outcome was a poor 6-month functional outcome, defined as Glasgow Outcome Scale-Extended less than or equal to 4. MEASUREMENTS AND MAIN RESULTS:. Out of 1282 patients available for analysis, 275 comprised the prematching population, with 75 pairs being created postmatching. Median time of tracheostomy differed significantly in the early vs. the delayed group (7.0 d [6.0–10.0 d] vs. 12.0 d [9.8–18.3 d]; p < 0.001). Only 40% of patients in the delayed group received tracheostomy. There was no statistically significant difference between groups regarding poor 6-month functional outcome (early: 68.0% vs. delayed: 72.0%; p = 0.593). CONCLUSIONS:. In a target trial emulation, early as opposed to delayed tracheostomy strategy was not associated with differences in 6-month functional outcome following severe TBI. Considering the limitations of target trial emulations, delaying tracheostomy through a “watchful waiting” approach may be appropriate.

Published
2024
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6. Racial and ethnic minority participants in clinical trials of acute respiratory distress syndrome

Author

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

Author

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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8. Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

Author

Patsouris Efstratios, Agrogiannis George, Kopterides Petros, Metaxas Eugenios I, Siempos Ilias I, Kapetanakis Theodoros, Lazaris Andreas C, Stravodimos Konstantinos G, Roussos Charis, and Armaganidis Apostolos

Subjects
Anesthesiology, RD78.3-87.3
Abstract

Abstract Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI). Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001). Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

Published
2011
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13. Dysregulated Coagulation and Fibrinolysis Are Present in Patients Admitted to the Emergency Department with Acute Hypoxemic Respiratory Failure: A Prospective Study

Author

Chrysi Keskinidou, Alice Georgia Vassiliou, Elena Papoutsi, Edison Jahaj, Ioanna Dimopoulou, Ilias Siempos, and Anastasia Kotanidou

Subjects
AHRF, plasminogen, sEPCR, coagulation, fibrinolysis, endothelium, Biology (General), QH301-705.5
Abstract

Acute hypoxemic respiratory failure (AHRF) is defined as acute and progressive, and patients are at a greater risk of developing acute respiratory distress syndrome (ARDS). Until now, most studies have focused on prognostic and diagnostic biomarkers in ARDS. Since there is evidence supporting a connection between dysregulated coagulant and fibrinolytic pathways in ARDS progression, it is plausible that this dysregulation also exists in AHRF. The aim of this study was to explore whether levels of soluble endothelial protein C receptor (sEPCR) and plasminogen differentiate patients admitted to the emergency department (ED) with AHRF. sEPCR and plasminogen levels were measured in 130 AHRF patients upon ED presentation by ELISA. Our results demonstrated that patients presenting to the ED with AHRF had elevated levels of sEPCR and plasminogen. It seems that dysregulation of coagulation and fibrinolysis occur in the early stages of respiratory failure requiring hospitalisation. Further research is needed to fully comprehend the contribution of sEPCR and plasminogen in AHRF.

Published
2024
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21. 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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22. 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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25. 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. Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis

Author

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

Subjects
acute respiratory distress syndrome, acute respiratory failure, pneumonia, mechanical ventilation, intensive care unit, coronavirus, Medicine (General), R5-920
Abstract

BackgroundWhether 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.MethodsFirstly, 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.ResultsIn 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).ConclusionsAfter 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 critically ill patients with COVID-19. Additional evidence is anticipated from relevant large randomized controlled trials which are currently underway.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42021276655.

Published
2022
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27. 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

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

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
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
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29. Evaluation of Albumin Kinetics in Critically Ill Patients With Coronavirus Disease 2019 Compared to Those With Sepsis-Induced Acute Respiratory Distress Syndrome

Author

Chang Su, PhD, Katherine L. Hoffman, MS, Zhenxing Xu, PhD, Elizabeth Sanchez, MD, Ilias I. Siempos, MD, Dsc, John S. Harrington, MD, Alexandra C. Racanelli, MD, PhD, Maria Plataki, MD, PhD, Fei Wang, PhD, and Edward J. Schenck, MD, MS

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. This report aims to characterize the kinetics of serum albumin in critically ill patients with coronavirus disease 2019 compared with critically ill patients with sepsis-induced acute respiratory distress syndrome. DESIGN:. Retrospective analysis. SETTING:. We analyzed two critically ill cohorts, one with coronavirus disease 2019 and another with sepsis-induced acute respiratory distress syndrome, treated in the New York Presbyterian Hospital-Weill Cornell Medical Center. PATIENTS:. Adult patients in the coronavirus disease 2019 cohort, diagnosed through reverse transcriptase-polymerase chain reaction assays performed on nasopharyngeal swabs, were admitted from March 3, 2020, to July 10, 2020. Adult patients in the sepsis-induced acute respiratory distress syndrome cohort, defined by Sepsis III criteria receipt of invasive mechanical ventilation and a Pao2/Fio2 ratio less than 300 were admitted from December 12, 2006, to February 26, 2019. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We evaluated serial serum albumin levels within 30 days after ICU admission in each cohort. We then examined the albumin progression trajectories, aligned at ICU admission time to test the relationship at a similar point in disease progression, in survivors and nonsurvivors. Albumin trajectory in all critically ill coronavirus disease 2019 patients show two distinct phases: phase I (deterioration) showing rapid albumin loss and phase II (recovery) showing albumin stabilization or improvement. Meanwhile, albumin recovery predicted clinical improvement in critical coronavirus disease 2019. In addition, we found a deterioration and recovery trends in survivors in the sepsis-induced acute respiratory distress syndrome cohort but did not find such two-phase trend in nonsurvivors. CONCLUSIONS:. The changes in albumin associated with coronavirus disease 2019 associated respiratory failure are transient compared with sepsis-associated acute respiratory distress syndrome and highlight the potential for recovery following a protracted course of severe coronavirus disease 2019.

Published
2021
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30. Fewer Intubations but Higher Mortality Among Intubated Coronavirus Disease 2019 Patients During the Second Than the First Wave

Author

Christina Routsi, MD, PhD, Stelios Kokkoris, MD, PhD, Ilias Siempos, MD, PhD, Eleni Magira, MD, PhD, Anastasia Kotanidou, MD, PhD, and Spyros Zakynthinos, MD, PhD

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Since changes in pharmacological treatments for severely ill patients with coronavirus disease 2019 have been incorporated into clinical practice, both by their use (corticosteroids and remdesivir) and by stopping them (e.g., hydroxychloroquine), we sought to compare the rate of intubation and mortality of intubated patients in our ICUs between the first and second waves of the pandemic. DESIGN:. Single-center, observational. SETTING:. Four coronavirus disease 2019 designated ICUs at an urban Greek teaching hospital. PATIENTS:. All adult patients with coronavirus disease 2019 consecutively admitted to ICU during the first (n = 50) and second (n = 212) waves of the pandemic. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The percentage of intubated ICU patients dropped from 82% during the first wave to 66% during the second wave (p = 0.042). However, the absolute number of intubated ICU patients was lower during the first than the second wave (41 vs 140 patients). ICU or hospital mortality of intubated patients increased from 39% during the first wave to 60% during the second wave (p = 0.028). The binary logistic regression for hospital mortality as the dependent variable in intubated patients and covariates the age, Acute Physiology and Chronic Health Evaluation II score, cardiovascular comorbidity, lactate, positive end-expiratory pressure, Sequential Organ Failure Assessment score, and wave, distinguished only Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.40 with 95% CI, 1.14—1.72; p = 0.001) as the sole independent predictor of hospital mortality. CONCLUSIONS:. Pharmacological adaptations and other measures may have led to fewer intubations over time. However, these changes do not seem to be translated into improved outcomes of intubated patients. Perhaps the same change in the use of drugs and protocols that could cause fewer intubations of ICU patients might be a reason of increased mortality in those patients who are eventually intubated. Furthermore, the relative staff inexperience and overall increase in patients’ comorbidities during the second wave could have contributed to increased Acute Physiology and Chronic Health Evaluation II score and mortality of intubated patients.

Published
2021
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37. 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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41. The combination of inspiratory muscle training and high-flow nasal cannula oxygen therapy for promoting weaning outcomes in difficult-to-wean patients: protocol for a randomised controlled trial

Author

Irini Patsaki, Anna Christakou, Emmanouel Papadopoulos, Martha Katartzi, Alexandros Kouvarakos, Ilias Siempos, Dimitris Tsimouris, Anastasia Skoura, Antonina Xatzimina, Sotirios Malachias, Νikolaos Koulouris, Eirini Grammatopoulou, Spiros Zakinthinos, and Eleni Ischaki

Subjects
Medicine
Abstract

Background According to the literature, 20–30% of intubated patients are difficult to wean off mechanical ventilation and have a prolonged intensive care unit (ICU) stay with detrimental effects on muscle strength, functional ability and quality of life. Inspiratory muscle training (IMT) via a threshold device has been proposed as an effective exercise for minimising the effects of mechanical ventilation on respiratory muscles of critically ill patients with prolonged weaning. In addition, high-flow nasal cannula (HFNC) oxygen has been proved to provide efficient support for both high- and low-risk patients after extubation, thus preventing re-intubation. Material and methods A randomised controlled trial was designed to assess the efficacy of combining IMT and HFNC as therapeutic strategies for patients with high risk for weaning failure. Once patients with prognostic factors of difficult weaning are awake, ventilated with support settings and cooperative, they will be randomised to one of the two following study groups: intervention group (IMT and HFNC) and control group (IMT and Venturi mask). IMT will start as soon as possible. Each allocated oxygen delivery device will be applied immediately after extubation. IMT intervention will continue until patients' discharge from ICU. The primary outcome is the rate of weaning failure. Secondary outcomes are maximal inspiratory and expiratory strength, endurance of respiratory muscles, global muscle strength, functional ability and quality of life along with duration of ventilation (days) and ICU and hospital length of stay. Conclusion The present study could significantly contribute to knowledge of how best to treat patients with difficult weaning and high risk of re-intubation.

Published
2020
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45. Plasma surfactant protein-D as a diagnostic biomarker for acute respiratory distress syndrome: validation in US and Korean cohorts

Author

Jinkyeong Park, Maria Pabon, Augustine M. K. Choi, Ilias I. Siempos, Laura E. Fredenburgh, Rebecca M. Baron, Kyeongman Jeon, Chi Ryang Chung, Jeong Hoon Yang, Chi-Min Park, and Gee Young Suh

Subjects
Acute lung injury, Critical illness, Pulmonary surfactant-associated protein D, Respiratory distress syndrome, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Acute respiratory distress syndrome (ARDS) is potentially underrecognized by clinicians. Early recognition and subsequent optimal treatment of patients with ARDS may be facilitated by usage of biomarkers. Surfactant protein D (SP-D), a marker of alveolar epithelial injury, has been proposed as a potentially useful biomarker for diagnosis of ARDS in a few studies. We tried to validate the performance of plasma SP-D levels for diagnosis of ARDS. Methods We conducted a retrospective analysis using data from three (two in USA and one in Korea) prospective biobank cohorts involving 407 critically ill patients admitted to medical intensive care unit (ICU). A propensity score matched analysis (patients with versus without ARDS, matched 1:1) was carried out using significant variables from multiple logistic regression. The diagnostic accuracy of plasma SP-D as a diagnostic marker of ARDS was assessed by receiver operating characteristic curve analysis. Results Out of the 407 subjects included in this study, 39 (10%) patients fulfilled ARDS criteria. Patients with ARDS had higher SP-D levels in plasma (p

Published
2017
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46. Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials.

Author

Elizabeth Sanchez, David R Price, Kuei-Pin Chung, Clara Oromendia, Augustine M K Choi, Edward J Schenck, and Ilias I Siempos

Subjects
Medicine, Science
Abstract

BackgroundAcute respiratory distress syndrome (ARDS) is heterogeneous. As an indication of the heterogeneity of ARDS, there are patients whose syndrome improves rapidly (i.e., within 24 hours), others whose hypoxemia improves gradually and still others whose severe hypoxemia persists for several days. The latter group of patients with persistent severe ARDS poses challenges to clinicians. We attempted to assess the baseline characteristics and outcomes of persistent severe ARDS and to identify which variables are useful to predict it.MethodsA secondary analysis of patient-level data from the ALTA, EDEN and SAILS ARDSNet clinical trials was conducted. We defined persistent severe ARDS as a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) of equal to or less than 100 mmHg on the second study day following enrollment. Regularized logistic regression with an L1 penalty [Least Absolute Shrinkage and Selection Operator (LASSO)] techniques were used to identify predictive variables of persistent severe ARDS.ResultsOf the 1531 individuals with ARDS alive on the second study day after enrollment, 232 (15%) had persistent severe ARDS. Of the latter, 100 (43%) individuals had mild or moderate hypoxemia at baseline. Usage of vasopressors was greater [144/232 (62%) versus 623/1299 (48%); pConclusionsPatients with persistent severe ARDS have distinct baseline characteristics and poor prognosis. Identifying such patients at enrollment may be useful for the prognostic enrichment of trials.

Published
2020
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48. Association between Vaccination Status and Mortality among Intubated Patients with COVID-19-Related Acute Respiratory Distress Syndrome

Author

Siempos, I.I. Grapsa, E. Adamos, G. Andrianopoulos, I. Tsolaki, V. Giannakoulis, V.G. Karavidas, N. Giannopoulou, V. Sarri, K. Mizi, E. Gavrielatou, E. Papathanakos, G. Mantzarlis, K.D. Mastora, Z. Magira, E. Koulouras, V. Kotanidou, A. Siempos, I.I. and Siempos, I.I. Grapsa, E. Adamos, G. Andrianopoulos, I. Tsolaki, V. Giannakoulis, V.G. Karavidas, N. Giannopoulou, V. Sarri, K. Mizi, E. Gavrielatou, E. Papathanakos, G. Mantzarlis, K.D. Mastora, Z. Magira, E. Koulouras, V. Kotanidou, A. Siempos, I.I.

Abstract

Importance: Although vaccination substantially reduces the risk of severe COVID-19, it is yet unknown whether vaccinated patients who develop COVID-19 and require invasive mechanical ventilation have lower mortality than controls. Objective: To examine the association between COVID-19 vaccination status and mortality among critically ill patients who require invasive mechanical ventilation owing to acute respiratory distress syndrome (ARDS) related to COVID-19. Design, Setting, and Participants: This multicenter cohort study was performed between June 7, 2021, and February 1, 2022, among 265 consecutive adult patients with COVID-19 in academic intensive care units who underwent invasive mechanical ventilation owing to ARDS. Exposures: Patients in the full vaccination group had completed the primary COVID-19 vaccination series more than 14 days but less than 5 months prior to intubation. This time threshold was chosen because guidelines from the US Centers for Disease Control and Prevention recommend a booster dose beyond that time. The remaining patients (ie, those who were unvaccinated, partially vaccinated, or fully vaccinated <14 days or >5 months before intubation) comprised the control group. Main Outcomes and Measures: The primary outcome was time from intubation to all-cause intensive care unit mortality. A Cox proportional hazards regression model including vaccination status, age, comorbid conditions, and baseline Sequential Organ Failure Assessment score on the day of intubation was used. Results: A total of 265 intubated patients (170 men [64.2%]; median age, 66.0 years [IQR, 58.0-76.0 years]; 26 [9.8%] in the full vaccination group) were included in the study. A total of 20 patients (76.9%) in the full vaccination group received the BNT162b2 vaccine, and the remaining 6 (23.1%) received the ChAdOx1 nCoV-19 vaccine. Patients in the full vaccination group were older (median age, 72.5 years [IQR, 62.8-80.0 years] vs 66.0 years [IQR, 57.0-75.0 years])

Published
2022

49. Comparison of qSOFA and SIRS for predicting adverse outcomes of patients with suspicion of sepsis outside the intensive care unit

Author

Eli J. Finkelsztein, Daniel S. Jones, Kevin C. Ma, Maria A. Pabón, Tatiana Delgado, Kiichi Nakahira, John E. Arbo, David A. Berlin, Edward J. Schenck, Augustine M. K. Choi, and Ilias I. Siempos

Subjects
Infection, Critical care, Organ failure, Severe sepsis, Mortality, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Task Force recently introduced a new clinical score termed quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) for identification of patients at risk of sepsis outside the intensive care unit (ICU). We attempted to compare the discriminatory capacity of the qSOFA versus the Systemic Inflammatory Response Syndrome (SIRS) score for predicting mortality, ICU-free days, and organ dysfunction-free days in patients with suspicion of infection outside the ICU. Methods The Weill Cornell Medicine Registry and Biobank of Critically Ill Patients is an ongoing cohort of critically ill patients, for whom biological samples and clinical information (including vital signs before and during ICU hospitalization) are prospectively collected. Using such information, qSOFA and SIRS scores outside the ICU (specifically, within 8 hours before ICU admission) were calculated. This study population was therefore comprised of patients in the emergency department or the hospital wards who had suspected infection, were subsequently admitted to the medical ICU and were included in the Registry and Biobank. Results One hundred fifty-two patients (67% from the emergency department) were included in this study. Sixty-seven percent had positive cultures and 19% died in the hospital. Discrimination of in-hospital mortality using qSOFA [area under the receiver operating characteristic curve (AUC), 0.74; 95% confidence intervals (CI), 0.66–0.81] was significantly greater compared with SIRS criteria (AUC, 0.59; 95% CI, 0.51–0.67; p = 0.03). The qSOFA performed better than SIRS regarding discrimination for ICU-free days (p = 0.04), but not for ventilator-free days (p = 0.19), any organ dysfunction-free days (p = 0.13), or renal dysfunction-free days (p = 0.17). Conclusions In patients with suspected infection who eventually required admission to the ICU, qSOFA calculated before their ICU admission had greater accuracy than SIRS for predicting mortality and ICU-free days. However, it may be less clear whether qSOFA is also better than SIRS criteria for predicting ventilator free-days and organ dysfunction-free days. These findings may help clinicians gain further insight into the usefulness of qSOFA.

Published
2017
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50. Effect of Different Early Oxygenation Levels on Clinical Outcomes of Patients Presenting in the Emergency Department With Severe Traumatic Brain Injury

Author

Vrettou, C.S. Giannakoulis, V.G. Gallos, P. Kotanidou, A. Siempos, I.I. and Vrettou, C.S. Giannakoulis, V.G. Gallos, P. Kotanidou, A. Siempos, I.I.

Abstract

Study objective: Despite the almost universal administration of supplemental oxygen in patients presenting in the emergency department (ED) with severe traumatic brain injury, optimal early oxygenation levels are unknown. Therefore, we aimed to examine the effect of different early oxygenation levels on the clinical outcomes of patients presenting in the emergency department with severe traumatic brain injury. Methods: We performed a secondary analysis of the Resuscitation Outcomes Consortium Traumatic Brain Injury Hypertonic Saline randomized controlled trial by including patients with Glasgow Coma Scale ≤8. Early oxygenation levels were assessed by the worst value of arterial partial pressure of oxygen (PaO2) during the first 4 hours of presentation in the emergency department. The primary outcome was 6-month neurologic status, as assessed by the Extended Glasgow Outcome Scale. A binary logistic regression was utilized, and an odds ratio (OR) with 95% (95% confidence intervals) was calculated. Results: A total of 910 patients were included. In unadjusted (crude) analysis, a PaO2 of 101 to 250 mmHg (OR, 0.59 [0.38 to 0.91]), or 251 to 400 mmHg (OR, 0.53 [0.34 to 0.83]) or ≥401 mmHg (OR, 0.31 [0.20 to 0.49]) was less likely to be associated with poor neurologic status when compared with a PaO2 of ≤100 mmHg. This was also the case for adjusted analyses (including age, pupillary reactivity, and Revised Trauma Score). Conclusion: High oxygenation levels as early as the first 4 hours of presentation in the emergency department may not be adversely associated with the long-term neurologic status of patients with severe traumatic brain injury. Therefore, during the early phase of trauma, clinicians may focus on stabilizing patients while giving low priority to the titration of oxygenation levels. © 2022 American College of Emergency Physicians

Published
2023

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