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3. GCN5-dependent acetylation of HIV-1 integrase enhances viral integration

Author

Albanese Alberto, Allouch Awatef, Tozzini Valentina, Di Fenza Armida, Di Primio Cristina, Gutierrez Maria, Liverani Vania, Valentini Paola, Terreni Mariaelena, Giacca Mauro, and Cereseto Anna

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background An essential event during the replication cycle of HIV-1 is the integration of the reverse transcribed viral DNA into the host cellular genome. Our former report revealed that HIV-1 integrase (IN), the enzyme that catalyzes the integration reaction, is positively regulated by acetylation mediated by the histone acetyltransferase (HAT) p300. Results In this study we demonstrate that another cellular HAT, GCN5, acetylates IN leading to enhanced 3'-end processing and strand transfer activities. GCN5 participates in the integration step of HIV-1 replication cycle as demonstrated by the reduced infectivity, due to inefficient provirus formation, in GCN5 knockdown cells. Within the C-terminal domain of IN, four lysines (K258, K264, K266, and K273) are targeted by GCN5 acetylation, three of which (K264, K266, and K273) are also modified by p300. Replication analysis of HIV-1 clones carrying substitutions at the IN lysines acetylated by both GCN5 and p300, or exclusively by GCN5, demonstrated that these residues are required for efficient viral integration. In addition, a comparative analysis of the replication efficiencies of the IN triple- and quadruple-mutant viruses revealed that even though the lysines targeted by both GCN5 and p300 are required for efficient virus integration, the residue exclusively modified by GCN5 (K258) does not affect this process. Conclusions The results presented here further demonstrate the relevance of IN post-translational modification by acetylation, which results from the catalytic activities of multiple HATs during the viral replication cycle. Finally, this study contributes to clarifying the recent debate raised on the role of IN acetylated lysines during HIV-1 infection.

Published
2010
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5. Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study

Author

Anstey, Matthew, Colica, Sandra, Brewster, David, Simpson, Shannon, Regli, Adrian, O'Grady, Ross, Litton, Edward, Ferrier, Janet, Bartholdy, Roland, Tabah, Alexis, Bowen, David, Rowley, Rebecca, Gatward, Jonathan, Alonso, Julio, Varkey, Sneha, Palaniswamy, Vijayanand, Chimunda, Timothy, Reza, Syed T., Hossain, Mozaffer, Islam, Motiul, Hamid, Tarikul, Parotto, Matteo, Ajami, Samareh, Steel, Andrew, Del Sorbo, Lorenzo, Goffi, Alberto, Randall, Ian, Adhikari, Neill K.J., Mehesry, Tasneem H., Vera, Maria M., Bugedo, Guillermo, Labarca, Gonzalo, Silva, Monica, Ma, Wuhua, Li, Yongxing, Wu, Jiayan, Wu, Lun, Radivojević, Renata Curić, Matas, Marijana, Ivančan, Višnja, Pavlek, Mario, Mihaljević, Slobodan, Jumić, Aleksandra, Moguš, Mate, Tucić, Iva, Michalek, Pavel, Flaksa, Marek, Aguirre-Bermeo, Hernan, Tirape-Castro, Hugo, García Aguilera, Maria F., Montenegro, Diana Alvarez, Tutillo, Diego Morocho, Tutillo León, Jose A., Winiszewski, Hadrien, Piton, Gael, Aissaoui, Nadia, Augy, Jean-Loup, Champigneulle, Benoit, Zlotnik, Diane, Muller, Grégoire, Jacquier, Sophie, Hraiech, Sami, Guervilly, Christophe, Plantefeve, Gaetan, Contou, Damien, Ricard, Jean Damien, Besset, Sebastien, Colin, Gwenhael, Pouplet, Caroline, Mirouse, Adrien, Azoulay, Elie, Boissier, Florence, Frat, Jean-Pierre, Mercier, Emmanuelle, Salmon-Gandonnière, Charlotte, Lascarrou, Jean-Baptiste, Martin, Maelle, Ferre, Alexis, Legriel, Stephane, Bruel, Cedric, Philippard, Francois, Zarka, Jonathan, Chemouni, Frank, Hamzaoui, Olfa, Sztrymf, Benjamin, Brunin, Yannick, Pili-Floury, Sébastien, Constantin, Jean-Michel, Godet, Thomas, Maraffi, Tommaso, Dessap, Armand Mekontso, Jozwiak, Mathieu, Marin, Nathalie, Guitton, Christophe, Chudeau, Nicolas, Gros, Alexandre, Boyer, Alexandre, Papandreou, Eleni, Petsiou, Athanasia, Papanikolaou, Metaxia, Kyparissi, Aikaterini, Tileli, Maria, Makris, Alexandros, Tsiftsis, Dimitrios, El-Fellah, Nadia, Karametos, Ilias, Nakou, Evi, Chalkias, Athanasios, Arnaoutoglou, Eleni, Katsoulis, Panagiotis, Pouriki, Sofia, Vagdatli, Kyriaki, Dimitropoulou, Aikaterini, Kothekar, Amol, Baliga, Nishanth, Korula, Sara V., Philip, Sam, Singh, Lalit, Agrawal, Nipun, Jeswani, Deepak, Jeswani, Deepti, Jha, Simant, Singh, Nitesh, Bhattacharyya, Mahuya, Das, Amit, Kuragayala, Swarna D., Kesavarapu, Subba R., Shah, Bhagyesh, Kaushik, Shuchi, Sunil, Nilu, Gnanadurai, Kingsly, Singh, Atul K., Singh, Dinesh K., Khunteta, Sudhir, Gupta, Kulbhusahn, Sanyal, Rhik, Midya, Abhirup, Tyagi, Vijay N., Bendre, Prashant, Prashant, Kumar, Chaurasia, Satish, Mishra, Prasanna, Dash, Sampat, Sundrani, Omprakash, Lalwani, Jaya, Jain, Nikhilesh, Agrawal, Kehari, Ray, Banambar, Meher, Ranjan, Saravanabavan, Lakshmikanthcharan, Munusamy, Satheesh, Gupta, Manish, Ahmad, Meraj, Gopalakrishna, Kadarapura N., Suparna, Bharadwaj, Surath, Manimala R., Munta, Kartik, Jagiasi, Bharat, Srivastava, Anand, Sahu, Samir, Mrinal, Sircar, Kumar, Singh Sujeet, Shah, Mehul, Patel, Mayur, Bamane, Shrirang, Narkhede, Amit, Chawla, Rajesh, Chawla, Aakanksha, Maheshwarappa, Harish Mallapura, Manjunath, Ramya Ballekatte, Rahmani, Lua, Laffey, John G., Rona, Roberto, Benini, Annalisa, Russotto, Vincenzo, Rundo, Annalisa, Luzi, Annalisa, Esposito, Clelia, Nespoli, Moana R., Pradella, Andrea, Lungu, Ramona, Baccari, Laura, Chiumiento, Fernando, Mariano, Karim, Cotoia, Antonella, De Rosa, Silvia, Boni, Elisa, Palmese, Salvatore, Gammaldi, Renato, Spadaro, Savino, Santoro, Lida, Cracchiolo, Andrea N., Palma, Daniela M., Pinciroli, Riccardo, Giovannini, Ilaria, Calamai, Italo, Spina, Rosario, Cappellini, Iacopo, Tutino, Lorenzo, Bellissima, Agrippino, Maugeri, Jessica G., Riva, Ivano, Fabretti, Fabrizio, Brazzi, Luca, Sales, Gabriele, Montrucchio, Giorgia, Orsello, Alberto, Costamagna, Andrea, Canavosio, Federico G., Pelagalli, Lorella, Marcelli, Maria E., Cortegiani, Andrea, Tramarin, Jacopo, Musso, Stefania, Tarantino, Stefano, Di Giacinto, Ida, Licciardi, Anna L., Montini, Luca, De Pascale, Gennaro, Giacomucci, Angelo, Russo, Pierpaolo, Longhini, Federico, Garofalo, Eugenio, Ferluga, Massimo, Moro, Valeria, Cascella, Marco, Di Caprio, Barbara, Di Fenza, Raffaele, Nespoli, Francesca, Bassini, Ospedale E., Muttini, Stefano, Pezzi, Angelo, Elhadi, Muhammed, Ghula, Mohamed, Ahmed, Hazem Abdelkarem, Khaled, Ala, Elhadi, Ahmed, Alhadi, Abdulmueti, Mazlan, Mohd Z., Wan Hassan, Wan Mohd N., Hasan, Shahnaz, Jamaluddin, Muhamad F.H., Samat, Noryani Mohd, Ismail, Muhamad A., Alias, Anita, Hwa, Ngu Pei, Irtiza, Ismail Nahla, Khalidah, Hapiz, Kiok, Lee Chew, Nordin, Norbaniza Mohd, Wan Ismail, Wan N., Ali, Mohd N., Sánchez-Hurtado, Luis, Toledo-Salinas, Otoniel, Landaverde, Antonio, Sosa, Miguel A., Gonzalez, Mayra Martinez, Lopez Nava, Claudia L., San Juan Roman, Nandyelly, Gonzalez, Maria, Espinoza, Missael, González, Daira, Flores, Fernando, Pantoja Leal, Jesus N., Loza Gallardo, Luis R., Young, Paul, Mistry, Ravi, Browne, Alexander, Crone, Petra, Chandwani, Juhi, Hossein, Sazzad, Koul, Salman S., Aman, Rubina, Ali, Syed M., Akhtar, Shazia N., Jankowski, Milosz, Bielanski, Piotr, Mudyna, Wojciech, Franczyk, Pawel, Galkin, Piotr, Skowronski, Lukasz, Gaszynski, Tomasz, Piegat, Mariusz, Catorze, Nuno, Pinto, Marcia, Leonor, Tiago, Fernandes, Marco, Campos, Patricia, Aragão, Irene, Costa, Paulo F., Franco, Daniela G., Basto, Marta, Nogueira, Carla, Cunha, Rui P., Costa, Vasco, Lomivorotov, Vladimir, Nikitenko, Artem, Belsky, Vladislav, Furman, Mikhail, Magomedov, Marat, Baturova, Vera, Karelov, Alexey, Marova, Nadezhda, Almekhlafi, Ghaleb, Alghamdi, Adnan, Maseda, Emilio, Suarez de la Rica, Alejandro, Gonzalez, Jesus Flores, Ruiz, Miryam Pérez, Roca, Oriol, Santafe, Manel, Fernandez, Gemma Goma, Escudero-Acha, Patricia, González-Castro, Alejandro, Agvald-Öhman, Christina, Broman, Lina, Spangfors, Martin, Hannesdottir, Katrin, Persson, Elin, Rosell, Jon, Sperber, Jesper, Ohlsson, Annika, Von Seth, Magnus, Pedrotti, Niccolò, Wahlstrom, Carl, Meirik, Maria, Bandert, Anna, Krog, Ditte, Kuo, Lu-Cheng, Shin, Ming-Hann, Chien, Jung-Yien, Ku, Shih-Chi, Ruan, Sheng-Yuan, Huang, Chun-Kai, Yeh, Yu-Chang, Chao, Anne, Wang, Kuo-Chuan, Chiu, Ching-Tang, Lee, Chien-Chang, Chou, Nai-Kuan, Szakmany, Tamas, Jones, Benjamin, Jones, Laura, Della Torre, Valentina, Sinah, Ayush, Quayle, Alice, Cheetham, Olivia, Syed, Yadullah, Mensah, Kwabena, Edmunds, Christopher, Kaye, Callum T., Bauer, Philippe R., Odeyemi, Yewande E., Nates, Joseph, Laserna, Andres, Mosier, Jarrod, Hypes, Cameron, Gottesman, Eric, Mastroianni, Fiore, Fein, Daniel G., Zhao, Dawn, Fonseca Fuentes, Xavier E., Gallo de Moraes, Alice, Sandefur, Benjamin J., Khan, Akram, Matos, Dubier, Kaufman, David A., Lehr, Andrew, Bigatello, Luca, Bonney, Iwona, Lascarrou, Jean Baptiste, Tassistro, Elena, Antolini, Laura, Bauer, Philippe, Szułdrzyński, Konstanty, Camporota, Luigi, Putensen, Christian, Pelosi, Paolo, Sorbello, Massimiliano, Higgs, Andy, Greif, Robert, Grasselli, Giacomo, Valsecchi, Maria G., Fumagalli, Roberto, Foti, Giuseppe, Caironi, Pietro, Bellani, Giacomo, and Myatra, Sheila N.

Published
2023
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6. Pronation Reveals a Heterogeneous Response of Global and Regional Respiratory Mechanics in Patients With Acute Hypoxemic Respiratory Failure

Author

Caio C.A. Morais, PhD, Glasiele Alcala, PhD, Roberta R. De Santis Santiago, MD, Carlo Valsecchi, MD, Eduardo Diaz, BS, Hatus Wanderley, MS, Bijan Safaee Fakhr, MD, Raffaele Di Fenza, MD, Stefano Gianni, MD, Sara Foote, BS, Marvin G. Chang, MD, Edward A. Bittner, MD, Ryan W. Carroll, MD, Eduardo L.V. Costa, MD, Marcelo B.P. Amato, MD, and Lorenzo Berra, MD

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

OBJECTIVES:. Experimental models suggest that prone position and positive end-expiratory pressure (PEEP) homogenize ventral–dorsal ventilation distribution and regional respiratory compliance. However, this response still needs confirmation on humans. Therefore, this study aimed to assess the changes in global and regional respiratory mechanics in supine and prone positions over a range of PEEP levels in acute respiratory distress syndrome (ARDS) patients. DESIGN:. A prospective cohort study. PATIENTS:. Twenty-two intubated patients with ARDS caused by COVID-19 pneumonia. INTERVENTIONS:. Electrical impedance tomography and esophageal manometry were applied during PEEP titrations from 20 cm H2O to 6 cm H2O in supine and prone positions. MEASUREMENTS:. Global respiratory system compliance (Crs), chest wall compliance, regional lung compliance, ventilation distribution in supine and prone positions. MAIN RESULTS:. Compared with supine position, the maximum level of Crs changed after prone position in 59% of ARDS patients (n = 13), of which the Crs decreased in 32% (n = 7) and increased in 27% (n = 6). To reach maximum Crs after pronation, PEEP was changed in 45% of the patients by at least 4 cm H2O. After pronation, the ventilation and compliance of the dorsal region did not consistently change in the entire sample of patients, increasing specifically in a subgroup of patients who showed a positive change in Crs when transitioning from supine to prone position. These combined changes in ventilation and compliance suggest dorsal recruitment postpronation. In addition, the subgroup with increased Crs postpronation demonstrated the most pronounced difference between dorsal and ventral ventilation distribution from supine to prone position (p = 0.01), indicating heterogeneous ventilation distribution in prone position. CONCLUSIONS:. Prone position modifies global respiratory compliance in most patients with ARDS. Only a subgroup of patients with a positive change in Crs postpronation presented a consistent improvement in dorsal ventilation and compliance. These data suggest that the response to pronation on global and regional mechanics can vary among ARDS patients, with some patients presenting more dorsal lung recruitment than others.

Published
2023
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7. Patient hesitancy in perioperative clinical trial enrollment during the COVID-19 pandemic.

Author

Josue D Chirinos, Isabella S Turco, Raffaele Di Fenza, Stefano Gianni, Grant M Larson, Joseph F Swingle, Oluwaseun Akeju, and Lorenzo Berra

Subjects
Medicine, Science
Abstract

The COVID-19 pandemic has caused tremendous disruptions to non-COVID-19 clinical research. However, there has been little investigation on how patients themselves have responded to clinical trial recruitment during the COVID-19 pandemic. To investigate the effect of the COVID-19 pandemic on rates of patient consent to enrollment into non-COVID-19 clinical trials, we carried out a cross-sectional study using data from the Nitric Oxide/Acute Kidney Injury (NO/AKI) and Minimizing ICU Neurological Dysfunction with Dexmedetomidine-Induced Sleep (MINDDS) trials. All patients eligible for the NO/AKI or MINDDS trials who came to the hospital for cardiac surgery and were approached to gain consent to enrollment were included in the current study. We defined "Before COVID-19" as the time between the start of the relevant clinical trial and the date when efforts toward that clinical trial were deescalated by the hospital due to COVID-19. We defined "During COVID-19" as the time between trial de-escalation and trial completion. 5,015 patients were screened for eligibility. 3,851 were excluded, and 1,434 were approached to gain consent to enrollment. The rate of consent to enrollment was 64% in the "Before COVID-19" group and 45% in the "During COVID-19" group (n = 1,334, P

Published
2023
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9. Programmed Deviations of Ribosomes From Standard Decoding in Archaea

Author

Federica De Lise, Andrea Strazzulli, Roberta Iacono, Nicola Curci, Mauro Di Fenza, Luisa Maurelli, Marco Moracci, and Beatrice Cobucci-Ponzano

Subjects
alpha-fucosidase, recoding, frameshifting, pyrrolysine, selenocysteine, archaea, Microbiology, QR1-502
Abstract

Genetic code decoding, initially considered to be universal and immutable, is now known to be flexible. In fact, in specific genes, ribosomes deviate from the standard translational rules in a programmed way, a phenomenon globally termed recoding. Translational recoding, which has been found in all domains of life, includes a group of events occurring during gene translation, namely stop codon readthrough, programmed ± 1 frameshifting, and ribosome bypassing. These events regulate protein expression at translational level and their mechanisms are well known and characterized in viruses, bacteria and eukaryotes. In this review we summarize the current state-of-the-art of recoding in the third domain of life. In Archaea, it was demonstrated and extensively studied that translational recoding regulates the decoding of the 21st and the 22nd amino acids selenocysteine and pyrrolysine, respectively, and only one case of programmed –1 frameshifting has been reported so far in Saccharolobus solfataricus P2. However, further putative events of translational recoding have been hypothesized in other archaeal species, but not extensively studied and confirmed yet. Although this phenomenon could have some implication for the physiology and adaptation of life in extreme environments, this field is still underexplored and genes whose expression could be regulated by recoding are still poorly characterized. The study of these recoding episodes in Archaea is urgently needed.

Published
2021
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10. Pronation Reveals a Heterogeneous Response of Global and Regional Respiratory Mechanics in Patients With Acute Hypoxemic Respiratory Failure

Author

Morais, Caio C.A., primary, Alcala, Glasiele, additional, De Santis Santiago, Roberta R., additional, Valsecchi, Carlo, additional, Diaz, Eduardo, additional, Wanderley, Hatus, additional, Fakhr, Bijan Safaee, additional, Di Fenza, Raffaele, additional, Gianni, Stefano, additional, Foote, Sara, additional, Chang, Marvin G., additional, Bittner, Edward A., additional, Carroll, Ryan W., additional, Costa, Eduardo L.V., additional, Amato, Marcelo B.P., additional, and Berra, Lorenzo, additional

Published
2023
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11. High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure due to COVID-19: A Multicenter Phase 2 Trial

Author

Di Fenza, Raffaele, primary, Shetty, Naman S, additional, Gianni, Stefano, additional, Parcha, Vibhu, additional, Giammatteo, Valentina, additional, Safaee Fakhr, Bijan, additional, Tornberg, Daniel, additional, Wall, Olof, additional, Harbut, Piotr, additional, Lai, Peggy S., additional, Li, Jonathan Z., additional, Paganoni, Sabrina, additional, Cenci, Stefano, additional, Mueller, Ariel L., additional, Houle, Timothy T., additional, Akeju, Oluwaseun, additional, Bittner, Edward A, additional, Bose, Somnath, additional, Scott, Louie K, additional, Carroll, Ryan W., additional, Ichinose, Fumito, additional, Hedenstierna, Magnus, additional, Arora, Pankaj, additional, and Berra, Lorenzo, additional

Published
2023
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13. High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19)

Author

Safaee Fakhr, Bijan, Wiegand, Steffen B., Pinciroli, Riccardo, Gianni, Stefano, Morais, Caio C. A., Ikeda, Takamitsu, Miyazaki, Yusuke, Marutani, Eizo, Di Fenza, Raffaele, Larson, Grant M., Parcha, Vibhu, Gibson, Lauren E., Chang, Marvin G., Arora, Pankaj, Carroll, Ryan W., Kacmarek, Robert M., Ichinose, Fumito, Barth, William H., Jr, Kaimal, Anjali, Hohmann, Elizabeth L., Zapol, Warren M., and Berra, Lorenzo

Published
2020
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14. High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial.

Author

Di Fenza, Raffaele, Shetty, Naman S., Gianni, Stefano, Parcha, Vibhu, Giammatteo, Valentina, Fakhr, Bijan Safaee, Tornberg, Daniel, Wall, Olof, Harbut, Piotr, Lai, Peggy S., Li, Jonathan Z., Paganoni, Sabrina, Cenci, Stefano, Mueller, Ariel L., Houle, Timothy T., Akeju, Oluwaseun, Bittner, Edward A., Bose, Somnath, Scott, Louie K., and Carroll, Ryan W.

Abstract

Rationale: The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives: The primary outcome was the change in arterial oxygenation (PaO2/FIO2) at 48 hours. The secondary outcomes included: time to reach a PaO2/FIO2 .300mmHg for at least 24 hours, the proportion of participants with a PaO2/FIO2 .300mmHg at 28 days, and survival at 28 and at 90 days. Methods: Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo). Measurements and Main Results: A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FIO2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2/FIO2 .300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2/FIO2 .300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. Conclusions: The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FIO2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Xyloglucan Oligosaccharides Hydrolysis by Exo-Acting Glycoside Hydrolases from Hyperthermophilic Microorganism Saccharolobus solfataricus

Author

Nicola Curci, Andrea Strazzulli, Roberta Iacono, Federica De Lise, Luisa Maurelli, Mauro Di Fenza, Beatrice Cobucci-Ponzano, and Marco Moracci

Subjects
glycoside hydrolases, Saccharolobus solfataricus, xyloglucan, polysaccharide degradation, archaea, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

In the field of biocatalysis and the development of a bio-based economy, hemicellulases have attracted great interest for various applications in industrial processes. However, the study of the catalytic activity of the lignocellulose-degrading enzymes needs to be improved to achieve the efficient hydrolysis of plant biomasses. In this framework, hemicellulases from hyperthermophilic archaea show interesting features as biocatalysts and provide many advantages in industrial applications thanks to their stability in the harsh conditions encountered during the pretreatment process. However, the hemicellulases from archaea are less studied compared to their bacterial counterpart, and the activity of most of them has been barely tested on natural substrates. Here, we investigated the hydrolysis of xyloglucan oligosaccharides from two different plants by using, both synergistically and individually, three glycoside hydrolases from Saccharolobus solfataricus: a GH1 β-gluco-/β-galactosidase, a α-fucosidase belonging to GH29, and a α-xylosidase from GH31. The results showed that the three enzymes were able to release monosaccharides from xyloglucan oligosaccharides after incubation at 65 °C. The concerted actions of β-gluco-/β-galactosidase and the α-xylosidase on both xyloglucan oligosaccharides have been observed, while the α-fucosidase was capable of releasing all α-linked fucose units from xyloglucan from apple pomace, representing the first GH29 enzyme belonging to subfamily A that is active on xyloglucan.

Published
2021
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19. Europe needs a strong, explicit policy in support of Industrial Biotechnology to accelerate sustainable transitions and avoid its demise

Author

O'Donohue, Michael, Martins Dos Santos, Vitor, Ancelin, Marie, Di Fenza, Mauro, and Penttilä, Merja

Abstract

This policy note is the second one produced by IBISBA. It briefly describes international developments in the field of industrial biotechnology and alerts on the fact that Europe risks to lose its competitive edge.

Published
2023
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21. High-Dose Nitric Oxide From Pressurized Cylinders and Nitric Oxide Produced by an Electric Generator From Air

Author

Stefano Gianni, Raffaele Di Fenza, Caio C. A. Morais, Ariel Mueller, Fumito Ichinose, Bijan Safaee Fakhr, Binglan Yu, Warren M. Zapol, Lorenzo Berra, and Ryan W. Carroll

Subjects
Pulmonary and Respiratory Medicine, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Pilot Projects, Nitric Oxide, Critical Care and Intensive Care Medicine, Methemoglobinemia, Methemoglobin, Nitric oxide, chemistry.chemical_compound, Administration, Inhalation, Heart rate, medicine, Humans, Nitrogen dioxide, Adverse effect, Original Research, SARS-CoV-2, business.industry, COVID-19, General Medicine, medicine.disease, chemistry, Oxygen Saturation, Anesthesia, Breathing, business
Abstract

BACKGROUND: High-dose (≥ 80 ppm) inhaled nitric oxide (INO) has antimicrobial effects. We designed a trial to test the preventive effects of high-dose NO on coronavirus disease 2019 (COVID-19) in health care providers working with patients with COVID-19. The study was interrupted prematurely due to the introduction of COVID-19 vaccines for health care professionals. We thereby present data on safety and feasibility of breathing 160 ppm NO using 2 different NO sources, namely pressurized nitrogen/NO cylinders (INO) and electric NO (eNO) generators. METHODS: NO gas was inhaled at 160 ppm in air for 15 min twice daily, before and after each work shift, over 14 d by health care providers (NCT04312243). During NO administration, vital signs were continuously monitored. Safety was assessed by measuring transcutaneous methemoglobinemia (SpMet) and the inhaled nitrogen dioxide (NO(2)) concentration. RESULTS: Twelve healthy health care professionals received a collective total of 185 administrations of high-dose NO (160 ppm) for 15 min twice daily. One-hundred and seventy-one doses were delivered by INO and 14 doses by eNO. During NO administration, SpMet increased similarly in both groups (P = .82). Methemoglobin decreased in all subjects at 5 min after discontinuing NO administration. Inhaled NO(2) concentrations remained between 0.70 ppm (0.63–0.79) and 0.75 ppm (0.67–0.83) in the INO group and between 0.74 ppm (0.68–0.78) and 0.88 ppm (0.70–0.93) in the eNO group. During NO administration, peripheral oxygen saturation and heart rate did not change. No adverse events occurred. CONCLUSIONS: This pilot study testing high-dose INO (160 ppm) for 15 min twice daily using eNO seems feasible and similarly safe when compared with INO.

Published
2021

22. High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19)

Author

Riccardo Pinciroli, Fumito Ichinose, Steffen B Wiegand, Grant Larson, William H. Barth, Caio C. A. Morais, Marvin G. Chang, Lauren E. Gibson, Robert M. Kacmarek, Vibhu Parcha, Pankaj Arora, Elizabeth L. Hohmann, Eizo Marutani, Raffaele Di Fenza, Warren M. Zapol, Bijan Safaee Fakhr, Lorenzo Berra, Yusuke Miyazaki, Anjali J Kaimal, Ryan W. Carroll, Stefano Gianni, Takamitsu Ikeda, Safaee Fakhr, B, Wiegand, S, Pinciroli, R, Gianni, S, Morais, C, Ikeda, T, Miyazaki, Y, Marutani, E, Di Fenza, R, Larson, G, Parcha, V, Gibson, L, Chang, M, Arora, P, Carroll, R, Kacmarek, R, Ichinose, F, Barth, W, Kaimal, A, Hohmann, E, Zapol, W, and Berra, L

Subjects
Massachusett, Pneumonia, Viral, Nitric Oxide, Tachypnea, Hypoxemia, Nitric oxide, Betacoronavirus, chemistry.chemical_compound, Pregnancy, Obstetrics and Gynaecology, Administration, Inhalation, Humans, Medicine, Pregnancy Complications, Infectious, Pandemics, Betacoronaviru, Pandemic, Inhalation, Coronavirus Infection, SARS-CoV-2, business.industry, COVID-19, Obstetrics and Gynecology, Oxygenation, medicine.disease, Pneumonia, Treatment Outcome, Massachusetts, Respiratory failure, chemistry, Procedures and Instruments, Anesthesia, Pregnancy Complications, Infectiou, Female, Contents, medicine.symptom, Coronavirus Infections, business, Human
Abstract

High-dose nitric oxide is a novel treatment associated with improved oxygenation and decreased tachypnea in pregnant patients with severe coronavirus disease 2019 (COVID-19)., BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160–200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

Published
2020

23. The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data.

Author

Gautier Koscielny, Gagarine Yaikhom, Vivek Iyer, Terrence F. Meehan, Hugh Morgan, Julian Atienza-Herrero, Andrew Blake 0003, Chao-Kung Chen, Richard Easty, Armida Di Fenza, Tanja Fiegel, Mark Grifiths, Alan Horne, Natasha A. Karp, Natalja Kurbatova, Jeremy C. Mason, Peter Matthews, Darren J. Oakley, Asfand Qazi, Jack Regnart, Ahmad Retha, Luis A. Santos, Duncan J. Sneddon, Jonathan Warren, Henrik Westerberg, Robert J. Wilson, David G. Melvin, Damian Smedley, Steve D. M. Brown, Paul Flicek, William C. Skarnes, Ann-Marie Mallon, and Helen E. Parkinson

Published
2014
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24. Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial

Author

Mauri, T, Foti, G, Fornari, C, Grasselli, G, Pinciroli, R, Lovisari, F, Tubiolo, D, Volta, C, Spadaro, S, Rona, R, Rondelli, E, Navalesi, P, Garofalo, E, Knafelj, R, Gorjup, V, Colombo, R, Cortegiani, A, Zhou, J, D'Andrea, R, Calamai, I, Gonzalez, A, Roca, O, Grieco, D, Jovaisa, T, Bampalis, D, Becher, T, Battaglini, D, Ge, H, Luz, M, Constantin, J, Ranieri, M, Guerin, C, Mancebo, J, Pelosi, P, Fumagalli, R, Brochard, L, Pesenti, A, Papoff, A, Di Fenza, R, Gianni, S, Spinelli, E, Lissoni, A, Abbruzzese, C, Bronco, A, Villa, S, Russotto, V, Iachi, A, Ball, L, Patroniti, N, Spina, R, Giuntini, R, Peruzzi, S, Menga, L, Fossali, T, Castelli, A, Ottolina, D, Garcia-De-Acilu, M, Santafe, M, Schadler, D, Weiler, N, Carvajal, E, Calvo, C, Neou, E, Wang, Y, Zhou, Y, Longhini, F, Bruni, A, Leonardi, M, Gregoretti, C, Ippolito, M, Milazzo, Z, Querci, L, Ranieri, S, Insom, G, Berden, J, Noc, M, Mikuz, U, Arzenton, M, Lazzeri, M, Villa, A, Barreto, B, Rios, M, Gusmao-Flores, D, Phull, M, Barnes, T, Musarat, H, Conti, S, Mauri T., Foti G., Fornari C., Grasselli G., Pinciroli R., Lovisari F., Tubiolo D., Volta C. A., Spadaro S., Rona R., Rondelli E., Navalesi P., Garofalo E., Knafelj R., Gorjup V., Colombo R., Cortegiani A., Zhou J. -X., D'Andrea R., Calamai I., Gonzalez A. V., Roca O., Grieco D. L., Jovaisa T., Bampalis D., Becher T., Battaglini D., Ge H., Luz M., Constantin J. -M., Ranieri M., Guerin C., Mancebo J., Pelosi P., Fumagalli R., Brochard L., Pesenti A., Papoff A., Di Fenza R., Gianni S., Spinelli E., Lissoni A., Abbruzzese C., Bronco A., Villa S., Russotto V., Iachi A., Ball L., Patroniti N., Spina R., Giuntini R., Peruzzi S., Menga L. S., Fossali T., Castelli A., Ottolina D., Garcia-De-Acilu M., Santafe M., Schadler D., Weiler N., Carvajal E. R., Calvo C. P., Neou E., Wang Y. -M., Zhou Y. -M., Longhini F., Bruni A., Leonardi M., Gregoretti C., Ippolito M., Milazzo Z., Querci L., Ranieri S., Insom G., Berden J., Noc M., Mikuz U., Arzenton M., Lazzeri M., Villa A., Barreto B. B., Rios M. N. O., Gusmao-Flores D., Phull M., Barnes T., Musarat H., Conti S., Mauri, T, Foti, G, Fornari, C, Grasselli, G, Pinciroli, R, Lovisari, F, Tubiolo, D, Volta, C, Spadaro, S, Rona, R, Rondelli, E, Navalesi, P, Garofalo, E, Knafelj, R, Gorjup, V, Colombo, R, Cortegiani, A, Zhou, J, D'Andrea, R, Calamai, I, Gonzalez, A, Roca, O, Grieco, D, Jovaisa, T, Bampalis, D, Becher, T, Battaglini, D, Ge, H, Luz, M, Constantin, J, Ranieri, M, Guerin, C, Mancebo, J, Pelosi, P, Fumagalli, R, Brochard, L, Pesenti, A, Papoff, A, Di Fenza, R, Gianni, S, Spinelli, E, Lissoni, A, Abbruzzese, C, Bronco, A, Villa, S, Russotto, V, Iachi, A, Ball, L, Patroniti, N, Spina, R, Giuntini, R, Peruzzi, S, Menga, L, Fossali, T, Castelli, A, Ottolina, D, Garcia-De-Acilu, M, Santafe, M, Schadler, D, Weiler, N, Carvajal, E, Calvo, C, Neou, E, Wang, Y, Zhou, Y, Longhini, F, Bruni, A, Leonardi, M, Gregoretti, C, Ippolito, M, Milazzo, Z, Querci, L, Ranieri, S, Insom, G, Berden, J, Noc, M, Mikuz, U, Arzenton, M, Lazzeri, M, Villa, A, Barreto, B, Rios, M, Gusmao-Flores, D, Phull, M, Barnes, T, Musarat, H, Conti, S, Mauri T., Foti G., Fornari C., Grasselli G., Pinciroli R., Lovisari F., Tubiolo D., Volta C. A., Spadaro S., Rona R., Rondelli E., Navalesi P., Garofalo E., Knafelj R., Gorjup V., Colombo R., Cortegiani A., Zhou J. -X., D'Andrea R., Calamai I., Gonzalez A. V., Roca O., Grieco D. L., Jovaisa T., Bampalis D., Becher T., Battaglini D., Ge H., Luz M., Constantin J. -M., Ranieri M., Guerin C., Mancebo J., Pelosi P., Fumagalli R., Brochard L., Pesenti A., Papoff A., Di Fenza R., Gianni S., Spinelli E., Lissoni A., Abbruzzese C., Bronco A., Villa S., Russotto V., Iachi A., Ball L., Patroniti N., Spina R., Giuntini R., Peruzzi S., Menga L. S., Fossali T., Castelli A., Ottolina D., Garcia-De-Acilu M., Santafe M., Schadler D., Weiler N., Carvajal E. R., Calvo C. P., Neou E., Wang Y. -M., Zhou Y. -M., Longhini F., Bruni A., Leonardi M., Gregoretti C., Ippolito M., Milazzo Z., Querci L., Ranieri S., Insom G., Berden J., Noc M., Mikuz U., Arzenton M., Lazzeri M., Villa A., Barreto B. B., Rios M. N. O., Gusmao-Flores D., Phull M., Barnes T., Musarat H., and Conti S.

Abstract

Background: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. Research Question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study Design and Methods: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. Results: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, –7%; 95% CI, –18% to 4%; P =. 015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P =. 852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P =. 337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P =. 300) for the sigh vs no-sigh group. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.

Published
2021

25. Transcriptomic response of maize primary roots to low temperatures at seedling emergence

Author

Mauro Di Fenza, Bridget Hogg, Jim Grant, and Susanne Barth

Subjects
Maize, Cold stress, Chilling tolerance, Transcriptome, Roots, Low temperature, Medicine, Biology (General), QH301-705.5
Abstract

Background Maize (Zea mays) is a C4 tropical cereal and its adaptation to temperate climates can be problematic due to low soil temperatures at early stages of establishment. Methods In the current study we have firstly investigated the physiological response of twelve maize varieties, from a chilling condition adapted gene pool, to sub-optimal growth temperature during seedling emergence. To identify transcriptomic markers of cold tolerance in already adapted maize genotypes, temperature conditions were set below the optimal growth range in both control and low temperature groups. The conditions were as follows; control (18 °C for 16 h and 12 °C for 8 h) and low temperature (12 °C for 16 h and 6 °C for 8 h). Four genotypes were identified from the condition adapted gene pool with significant contrasting chilling tolerance. Results Picker and PR39B29 were the more cold-tolerant lines and Fergus and Codisco were the less cold-tolerant lines. These four varieties were subjected to microarray analysis to identify differentially expressed genes under chilling conditions. Exposure to low temperature during establishment in the maize varieties Picker, PR39B29, Fergus and Codisco, was reflected at the transcriptomic level in the varieties Picker and PR39B29. No significant changes in expression were observed in Fergus and Codisco following chilling stress. A total number of 64 genes were differentially expressed in the two chilling tolerant varieties. These two varieties exhibited contrasting transcriptomic profiles, in which only four genes overlapped. Discussion We observed that maize varieties possessing an enhanced root growth ratio under low temperature were more tolerant, which could be an early and inexpensive measure for germplasm screening under controlled conditions. We have identified novel cold inducible genes in an already adapted maize breeding gene pool. This illustrates that further varietal selection for enhanced chilling tolerance is possible in an already preselected gene pool.

Published
2017
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26. Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS

Author

Tommaso Mauri, Giuseppe Foti, Carla Fornari, Giacomo Grasselli, Riccardo Pinciroli, Federica Lovisari, Daniela Tubiolo, Carlo Alberto Volta, Savino Spadaro, Roberto Rona, Egle Rondelli, Paolo Navalesi, Eugenio Garofalo, Rihard Knafelj, Vojka Gorjup, Riccardo Colombo, Andrea Cortegiani, Jian-Xin Zhou, Rocco D’Andrea, Italo Calamai, Ánxela Vidal González, Oriol Roca, Domenico Luca Grieco, Tomas Jovaisa, Dimitrios Bampalis, Tobias Becher, Denise Battaglini, Huiqing Ge, Mariana Luz, Jean-Michel Constantin, Marco Ranieri, Claude Guerin, Jordi Mancebo, Paolo Pelosi, Roberto Fumagalli, Laurent Brochard, Antonio Pesenti, null Plug working group of ESICM, Alessandra Papoff, Raffaele Di Fenza, Stefano Gianni, Elena Spinelli, Alfredo Lissoni, Chiara Abbruzzese, Alfio Bronco, Silvia Villa, Vincenzo Russotto, Arianna Iachi, Lorenzo Ball, Nicolò Patroniti, Rosario Spina, Romano Giuntini, Simone Peruzzi, Luca Salvatore Menga, Tommaso Fossali, Antonio Castelli, Davide Ottolina, Marina García-de-Acilu, Manel Santafè, Dirk Schädler, Norbert Weiler, Emilia Rosas Carvajal, César Pérez Calvo, Evangelia Neou, Yu-Mei Wang, Yi-Min Zhou, Federico Longhini, Andrea Bruni, Mariacristina Leonardi, Cesare Gregoretti, Mariachiara Ippolito, Zelia Milazzo, Lorenzo Querci, Serena Ranieri, Giulia Insom, Jernej Berden, Marko Noc, Ursa Mikuz, Matteo Arzenton, Marta Lazzeri, Arianna Villa, Bruna Brandão Barreto, Marcos Nogueira Oliveira Rios, Dimitri Gusmao-Flores, Mandeep Phull, Tom Barnes, Hussain Musarat, and Sara Conti

Subjects
Pulmonary and Respiratory Medicine, ARDS, business.industry, Pressure support ventilation, Critical Care and Intensive Care Medicine, medicine.disease, Spontaneous breathing trial, law.invention, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Randomized controlled trial, law, Anesthesia, Breathing, Medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Respiratory minute volume, Positive end-expiratory pressure, Tidal volume
Abstract

Background Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. Research Question Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study Design and Methods We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. Results Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, –7%; 95% CI, –18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. Interpretation Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. Trial Registry ClinicalTrials.gov ; No.: NCT03201263 ; URL: www.clinicaltrials.gov

Published
2021

27. High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial

Author

Roberta De Santis Santiago, Maddalena Teggia Droghi, Jacopo Fumagalli, Francesco Marrazzo, Gaetano Florio, Luigi G. Grassi, Susimeire Gomes, Caio C. A. Morais, Ozires P. S. Ramos, Maurizio Bottiroli, Riccardo Pinciroli, David A. Imber, Aranya Bagchi, Kenneth Shelton, Abraham Sonny, Edward A. Bittner, Marcelo B. P. Amato, Robert M. Kacmarek, Lorenzo Berra, Adriana Sayuri Hirota, Daniela Davis Madureira Iope, Carolina Eimi Kajiyama, Andrea Fonseca, Otilia Batista, Silvia Cristina Leopoldino, Carlo Valsecchi, Erick Leon, Kathryn Hibbert, Charles C. Hardin, Kim Connelly, Daniel Fisher, Grant Michael Larson, Emanuele Vassena, Raffaele Di Fenza, Stefano Gianni, Bijan Safaee Fakhr, Jeanine Wiener-Kronish, and Brian Kavanagh

Subjects
Pulmonary and Respiratory Medicine, obesity, medicine.medical_specialty, ARDS, Critical Care, medicine.medical_treatment, Hemodynamics, Atelectasis, mechanical ventilation, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, intrathoracic pressure, Internal medicine, medicine.artery, Tidal Volume, medicine, Humans, 030212 general & internal medicine, Mechanical ventilation, Respiratory Distress Syndrome, Lung, business.industry, Original Articles, acute respiratory distress syndrome, respiratory system, medicine.disease, Respiration, Artificial, medicine.anatomical_structure, 030228 respiratory system, Pulmonary artery, Breathing, Vascular resistance, Cardiology, business
Abstract

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension. Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6). Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7–10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and V./Q. matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13–4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2–0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15–6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the V./Q. ratio. Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure. Clinical trial registered with www.clinicaltrials.gov (NCT 02503241).

Published
2021

28. Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness

Author

Raffaele Di Fenza, Lauren E. Gibson, Marvin G. Chang, Jayashree Kalpathy-Cramer, Min Lang, Fumito Ichinose, Brent P. Little, Pankaj Arora, Ariel Mueller, Martin Capriles, Matthew D. Li, Lorenzo Berra, and Edward A. Bittner

Subjects
Adult, Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Critical Illness, Heart Ventricles, Ventricular Dysfunction, Right, Strain (injury), Acute respiratory distress, 030204 cardiovascular system & hematology, right ventricle, Critical Care and Intensive Care Medicine, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, strain, Internal medicine, Severity of illness, Medicine, Humans, In patient, 030212 general & internal medicine, Original Research, Aged, Randomized Controlled Trials as Topic, Respiratory illness, cardiac dysfunction, business.industry, COVID-19, acute respiratory distress syndrome, Middle Aged, medicine.disease, Respiration, Artificial, Ventricular Function, Right, Female, business, Respiratory Insufficiency
Abstract

Background: Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients. Methods: We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism. Results: Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = −0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings. Conclusions: RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage. Trial Registration: National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393

Published
2021

29. SAFETY AND EFFICACY OF INHALED HIGH-DOSE NITRIC OXIDE IN NON-INTUBATED PATIENTS WITH COVID-19 PNEUMONIA

Author

SAFAEE FAKHR, B., primary, DI FENZA, R., additional, GIANNI, S., additional, WIEGAND, S., additional, MIYAZAKI, Y., additional, ARAUJO MORAIS, C., additional, GIBSON, L., additional, CHANG, M., additional, MUELLER, A., additional, RODRIGUEZ-LOPEZ, J., additional, ACKMAN, J., additional, ARORA, P., additional, SCOTT, L., additional, BLOCH, D., additional, ZAPOL, W., additional, CARROLL, R., additional, ICHINOSE, F., additional, and BERRA, L., additional

Published
2022
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30. High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19)

Author

Safaee Fakhr, B, Wiegand, S, Pinciroli, R, Gianni, S, Morais, C, Ikeda, T, Miyazaki, Y, Marutani, E, Di Fenza, R, Larson, G, Parcha, V, Gibson, L, Chang, M, Arora, P, Carroll, R, Kacmarek, R, Ichinose, F, Barth, W, Kaimal, A, Hohmann, E, Zapol, W, Berra, L, Safaee Fakhr B., Wiegand S. B., Pinciroli R., Gianni S., Morais C. C. A., Ikeda T., Miyazaki Y., Marutani E., Di Fenza R., Larson G. M., Parcha V., Gibson L. E., Chang M. G., Arora P., Carroll R. W., Kacmarek R. M., Ichinose F., Barth W. H., Kaimal A., Hohmann E. L., Zapol W. M., Berra L., Safaee Fakhr, B, Wiegand, S, Pinciroli, R, Gianni, S, Morais, C, Ikeda, T, Miyazaki, Y, Marutani, E, Di Fenza, R, Larson, G, Parcha, V, Gibson, L, Chang, M, Arora, P, Carroll, R, Kacmarek, R, Ichinose, F, Barth, W, Kaimal, A, Hohmann, E, Zapol, W, Berra, L, Safaee Fakhr B., Wiegand S. B., Pinciroli R., Gianni S., Morais C. C. A., Ikeda T., Miyazaki Y., Marutani E., Di Fenza R., Larson G. M., Parcha V., Gibson L. E., Chang M. G., Arora P., Carroll R. W., Kacmarek R. M., Ichinose F., Barth W. H., Kaimal A., Hohmann E. L., Zapol W. M., and Berra L.

Abstract

BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160-200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160-200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

Published
2020

31. Bedside monitoring of lung perfusion by electrical impedance tomography in the time of COVID-19

Author

Safaee Fakhr, B, Araujo Morais, C, De Santis Santiago, R, Di Fenza, R, Gibson, L, Restrepo, P, Chang, M, Bittner, E, Pinciroli, R, Fintelmann, F, Kacmarek, R, Berra, L, Safaee Fakhr B., Araujo Morais C. C., De Santis Santiago R. R., Di Fenza R., Gibson L. E., Restrepo P. A., Chang M. G., Bittner E. A., Pinciroli R., Fintelmann F. J., Kacmarek R. M., Berra L., Safaee Fakhr, B, Araujo Morais, C, De Santis Santiago, R, Di Fenza, R, Gibson, L, Restrepo, P, Chang, M, Bittner, E, Pinciroli, R, Fintelmann, F, Kacmarek, R, Berra, L, Safaee Fakhr B., Araujo Morais C. C., De Santis Santiago R. R., Di Fenza R., Gibson L. E., Restrepo P. A., Chang M. G., Bittner E. A., Pinciroli R., Fintelmann F. J., Kacmarek R. M., and Berra L.

Published
2020

32. Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds

Author

Raffaele, Di Fenza, Binglan, Yu, Ryan W, Carroll, and Lorenzo, Berra

Subjects
Luminescence, Nitrates, General Immunology and Microbiology, General Chemical Engineering, General Neuroscience, Luminescent Measurements, Nitric Oxide, Nitrites, General Biochemistry, Genetics and Molecular Biology
Abstract

Nitric oxide (NO) activity in vivo is the combined results of its direct effects, the action of its derivatives generated from NO autoxidation, and the effects of nitrosated compounds. Measuring NO metabolites is essential to studying NO activity both at vascular levels and in other tissues, especially in the experimental settings where exogenous NO is administered. Ozone-based chemiluminescence assays allow precise measurements of NO and NO metabolites in both fluids (including plasma, tissue homogenates, cell cultures) and gas mixtures (e.g., exhaled breath). NO reacts with ozone to generate nitrogen dioxide in an excited state. The consequent light emission allows photodetection and the generation of an electric signal reflecting the NO content of the sample. Aliquots from the same sample can be used to measure specific NO metabolites, such as nitrate, nitrite, S-nitrosothiols, and iron-nitrosyl complexes. In addition, NO consumed by cell-free hemoglobin is also quantified with chemiluminescence analysis. An illustration of all these techniques is provided.

Published
2022

33. Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial

Author

Mauri T., Foti G., Fornari C., Grasselli G., Pinciroli R., Lovisari F., Tubiolo D., Volta C. A., Spadaro S., Rona R., Rondelli E., Navalesi P., Garofalo E., Knafelj R., Gorjup V., Colombo R., Cortegiani A., Zhou J. -X., D'Andrea R., Calamai I., Gonzalez A. V., Roca O., Grieco D. L., Jovaisa T., Bampalis D., Becher T., Battaglini D., Ge H., Luz M., Constantin J. -M., Ranieri M., Guerin C., Mancebo J., Pelosi P., Fumagalli R., Brochard L., Pesenti A., Papoff A., Di Fenza R., Gianni S., Spinelli E., Lissoni A., Abbruzzese C., Bronco A., Villa S., Russotto V., Iachi A., Ball L., Patroniti N., Spina R., Giuntini R., Peruzzi S., Menga L. S., Fossali T., Castelli A., Ottolina D., Garcia-De-Acilu M., Santafe M., Schadler D., Weiler N., Carvajal E. R., Calvo C. P., Neou E., Wang Y. -M., Zhou Y. -M., Longhini F., Bruni A., Leonardi M., Gregoretti C., Ippolito M., Milazzo Z., Querci L., Ranieri S., Insom G., Berden J., Noc M., Mikuz U., Arzenton M., Lazzeri M., Villa A., Barreto B. B., Rios M. N. O., Gusmao-Flores D., Phull M., Barnes T., Musarat H., Conti S., Mauri, Tommaso, Foti, Giuseppe, Fornari, Carla, Grasselli, Giacomo, Pinciroli, Riccardo, Lovisari, Federica, Tubiolo, Daniela, Volta, Carlo Alberto, Spadaro, Savino, Rona, Roberto, Rondelli, Egle, Navalesi, Paolo, Garofalo, Eugenio, Knafelj, Rihard, Gorjup, Vojka, Colombo, Riccardo, Cortegiani, Andrea, Zhou, Jian-Xin, D'Andrea, Rocco, Calamai, Italo, González, Ánxela Vidal, Roca, Oriol, Grieco, Domenico Luca, Jovaisa, Toma, Bampalis, Dimitrio, Becher, Tobia, Battaglini, Denise, Ge, Huiqing, Luz, Mariana, Constantin, Jean-Michel, Ranieri, Marco, Guerin, Claude, Mancebo, Jordi, Pelosi, Paolo, Fumagalli, Roberto, Brochard, Laurent, Pesenti, Antonio, PROTECTION collaborators: Alessandra Papoff, Raffaele Di Fenza, Stefano Gianni, Elena Spinelli, Alfredo Lissoni, Chiara Abbruzzese, Alfio Bronco, Silvia Villa, Vincenzo Russotto, Arianna Iachi, Lorenzo Ball, Nicolò Patroniti, Rosario Spina, Romano Giuntini, Simone Peruzzi, Luca Salvatore Menga, Tommaso Fossali, Antonio Castelli, Davide Ottolina, Marina García-de-Acilu, Manel Santafè, Dirk Schädler, Norbert Weiler, Emilia Rosas Carvajal, César Pérez Calvo, Evangelia Neou, Yu-Mei Wang, Yi-Min Zhou, Federico Longhini, Andrea Bruni, Mariacristina Leonardi, Cesare Gregoretti, Mariachiara Ippolito, Zelia Milazzo, Lorenzo Querci, Serena Ranieri, Giulia Insom, Jernej Berden, Marko Noc, Ursa Mikuz, Matteo Arzenton, Marta Lazzeri, Arianna Villa, Bruna Brandão Barreto, Marcos Nogueira Oliveira Rios, Dimitri Gusmao-Flores, Mandeep Phull, Tom Barnes, Hussain Musarat, Sara Conti, Mauri, T, Foti, G, Fornari, C, Grasselli, G, Pinciroli, R, Lovisari, F, Tubiolo, D, Volta, C, Spadaro, S, Rona, R, Rondelli, E, Navalesi, P, Garofalo, E, Knafelj, R, Gorjup, V, Colombo, R, Cortegiani, A, Zhou, J, D'Andrea, R, Calamai, I, Gonzalez, A, Roca, O, Grieco, D, Jovaisa, T, Bampalis, D, Becher, T, Battaglini, D, Ge, H, Luz, M, Constantin, J, Ranieri, M, Guerin, C, Mancebo, J, Pelosi, P, Fumagalli, R, Brochard, L, Pesenti, A, Papoff, A, Di Fenza, R, Gianni, S, Spinelli, E, Lissoni, A, Abbruzzese, C, Bronco, A, Villa, S, Russotto, V, Iachi, A, Ball, L, Patroniti, N, Spina, R, Giuntini, R, Peruzzi, S, Menga, L, Fossali, T, Castelli, A, Ottolina, D, Garcia-De-Acilu, M, Santafe, M, Schadler, D, Weiler, N, Carvajal, E, Calvo, C, Neou, E, Wang, Y, Zhou, Y, Longhini, F, Bruni, A, Leonardi, M, Gregoretti, C, Ippolito, M, Milazzo, Z, Querci, L, Ranieri, S, Insom, G, Berden, J, Noc, M, Mikuz, U, Arzenton, M, Lazzeri, M, Villa, A, Barreto, B, Rios, M, Gusmao-Flores, D, Phull, M, Barnes, T, Musarat, H, and Conti, S

Subjects
pressure support, ventilation, sigh, ARDS, mechanical ventilation, feasibility
Abstract

Background: Sigh is a cyclic brief recruitment manoeuvre: previous physiological studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity and increase release of surfactant. Research question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study design and methods: We conducted a multi-center non-inferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome undergoing PSV. Patients were randomized to the No Sigh group and treated by PSV alone, or to the Sigh group, treated by PSV plus sigh (increase of airway pressure to 30 cmH2Ofor 3 seconds once per minute) until day 28 or death or successful spontaneous breathing trial. The primary endpoint of the study was feasibility, assessed as non-inferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiological parameters in the first week from randomization, 28-day mortality and ventilator-free days. Results: Two-hundred fifty-eight patients (31% women; median age 65 [54-75] years) were enrolled. In the Sigh group, 23% of patients failed to remain on assisted ventilation vs. 30% in the No Sigh group (absolute difference -7%, 95%CI -18% to 4%; p=0.015 for non-inferiority). Adverse events occurred in 12% vs. 13% in Sigh vs. No Sigh (p=0.852). Oxygenation was improved while tidal volume, respiratory rate and corrected minute ventilation were lower over the first 7 days from randomization in Sigh vs. No Sigh. There was no significant difference in terms of mortality (16% vs. 21%, p=0.342) and ventilator-free days (22 [7-26] vs. 22 [3-25] days, p=0.300) for Sigh vs. No Sigh. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.

Published
2020

34. A mouse informatics platform for phenotypic and translational discovery

Author

Ring, Natalie, Meehan, Terrence F., Blake, Andrew, Brown, James, Chen, Chao-Kung, Conte, Nathalie, Di Fenza, Armida, Fiegel, Tanja, Horner, Neil, Jacobsen, Julius O. B., Karp, Natasha, Lawson, Thomas, Mason, Jeremy C., Matthews, Peter, Morgan, Hugh, Relac, Mike, Santos, Luis, Smedley, Damian, Sneddon, Duncan, Pengelly, Alice, Tudose, Ilinca, Warren, Jonathan W. G., Westerberg, Henrik, Yaikhom, Gagarine, Parkinson, Helen, and Mallon, Ann-Marie

Published
2015
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35. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics

Author

Hrabě de Angelis, Martin, Nicholson, George, Selloum, Mohammed, White, Jacqueline K, Morgan, Hugh, Ramirez-Solis, Ramiro, Sorg, Tania, Wells, Sara, Fuchs, Helmut, Fray, Martin, Adams, David J, Adams, Niels C, Adler, Thure, Aguilar-Pimentel, Antonio, Ali-Hadji, Dalila, Amann, Gregory, André, Philippe, Atkins, Sarah, Auburtin, Aurelie, Ayadi, Abdel, Becker, Julien, Becker, Lore, Bedu, Elodie, Bekeredjian, Raffi, Birling, Marie-Christine, Blake, Andrew, Bottomley, Joanna, Bowl, Michael R, Brault, Véronique, Busch, Dirk H, Bussell, James N, Calzada-Wack, Julia, Cater, Heather, Champy, Marie-France, Charles, Philippe, Chevalier, Claire, Chiani, Francesco, Codner, Gemma F, Combe, Roy, Cox, Roger, Dalloneau, Emilie, Dierich, André, Di Fenza, Armida, Doe, Brendan, Duchon, Arnaud, Eickelberg, Oliver, Esapa, Chris T, Fertak, Lahcen El, Feigel, Tanja, Emelyanova, Irina, Estabel, Jeanne, Favor, Jack, Flenniken, Ann, Gambadoro, Alessia, Garrett, Lilian, Gates, Hilary, Gerdin, Anna-Karin, Gkoutos, George, Greenaway, Simon, Glasl, Lisa, Goetz, Patrice, Da Cruz, Isabelle Goncalves, Götz, Alexander, Graw, Jochen, Guimond, Alain, Hans, Wolfgang, Hicks, Geoff, Hölter, Sabine M, Höfler, Heinz, Hancock, John M, Hoehndorf, Robert, Hough, Tertius, Houghton, Richard, Hurt, Anja, Ivandic, Boris, Jacobs, Hughes, Jacquot, Sylvie, Jones, Nora, Karp, Natasha A, Katus, Hugo A, Kitchen, Sharon, Klein-Rodewald, Tanja, Klingenspor, Martin, Klopstock, Thomas, Lalanne, Valerie, Leblanc, Sophie, Lengger, Christoph, le Marchand, Elise, Ludwig, Tonia, Lux, Aline, McKerlie, Colin, Maier, Holger, Mandel, Jean-Louis, Marschall, Susan, Mark, Manuel, Melvin, David G, Meziane, Hamid, Micklich, Kateryna, Mittelhauser, Christophe, Monassier, Laurent, Moulaert, David, Muller, Stéphanie, Naton, Beatrix, Neff, Frauke, Nolan, Patrick M, Nutter, Lauryl M J, Ollert, Markus, Pavlovic, Guillaume, Pellegata, Natalia S, Peter, Emilie, Petit-Demoulière, Benoit, Pickard, Amanda, Podrini, Christine, Potter, Paul, Pouilly, Laurent, Puk, Oliver, Richardson, David, Rousseau, Stephane, Quintanilla-Fend, Leticia, Quwailid, Mohamed M, Racz, Ildiko, Rathkolb, Birgit, Riet, Fabrice, Rossant, Janet, Roux, Michel, Rozman, Jan, Ryder, Edward, Salisbury, Jennifer, Santos, Luis, Schäble, Karl-Heinz, Schiller, Evelyn, Schrewe, Anja, Schulz, Holger, Steinkamp, Ralf, Simon, Michelle, Stewart, Michelle, Stöger, Claudia, Stöger, Tobias, Sun, Minxuan, Sunter, David, Teboul, Lydia, Tilly, Isabelle, Tocchini-Valentini, Glauco P, Tost, Monica, Treise, Irina, Vasseur, Laurent, Velot, Emilie, Vogt-Weisenhorn, Daniela, Wagner, Christelle, Walling, Alison, Wattenhofer-Donze, Marie, Weber, Bruno, Wendling, Olivia, Westerberg, Henrik, Willershäuser, Monja, Wolf, Eckhard, Wolter, Anne, Wood, Joe, Wurst, Wolfgang, Yildirim, Ali Önder, Zeh, Ramona, Zimmer, Andreas, Zimprich, Annemarie, Holmes, Chris, Steel, Karen P, Herault, Yann, Gailus-Durner, Valérie, Mallon, Ann-Marie, and Brown, Steve D M

Published
2015
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38. Xyloglucan Oligosaccharides Hydrolysis by Exo-Acting Glycoside Hydrolases from Hyperthermophilic Microorganism Saccharolobus solfataricus

Author

Andrea Strazzulli, Beatrice Cobucci-Ponzano, Roberta Iacono, Federica De Lise, Luisa Maurelli, Marco Moracci, Mauro Di Fenza, Nicola Curci, Curci, N., Strazzulli, A., Iacono, R., De Lise, F., Maurelli, L., Di Fenza, M., Cobucci-ponzano, B., and Moracci, M.

Subjects
0301 basic medicine, Glycoside Hydrolase, Saccharolobus solfataricu, Oligosaccharides, Fucose, Oligosaccharide, lcsh:Chemistry, chemistry.chemical_compound, xyloglucan, Saccharolobus solfataricus, Tamarindus, Glycoside hydrolase, Glucans, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, biology, Chemistry, Hydrolysis, Temperature, General Medicine, Recombinant Protein, Glucan, Recombinant Proteins, Computer Science Applications, Xyloglucan, Xylosidases, Biochemistry, Seeds, Sulfolobus solfataricus, Xylans, Tamarindu, archaea, 030106 microbiology, Article, Catalysis, Inorganic Chemistry, Xylan, 03 medical and health sciences, polysaccharide degradation, Monosaccharide, Physical and Theoretical Chemistry, Molecular Biology, Seed, Organic Chemistry, Sulfolobus solfataricu, biology.organism_classification, Hydrolysi, 030104 developmental biology, Enzyme, lcsh:Biology (General), lcsh:QD1-999, Biocatalysis, glycoside hydrolases, Archaea
Abstract

In the field of biocatalysis and the development of a bio-based economy, hemicellulases have attracted great interest for various applications in industrial processes. However, the study of the catalytic activity of the lignocellulose-degrading enzymes needs to be improved to achieve the efficient hydrolysis of plant biomasses. In this framework, hemicellulases from hyperthermophilic archaea show interesting features as biocatalysts and provide many advantages in industrial applications thanks to their stability in the harsh conditions encountered during the pretreatment process. However, the hemicellulases from archaea are less studied compared to their bacterial counterpart, and the activity of most of them has been barely tested on natural substrates. Here, we investigated the hydrolysis of xyloglucan oligosaccharides from two different plants by using, both synergistically and individually, three glycoside hydrolases from Saccharolobus solfataricus: a GH1 β-gluco-/β-galactosidase, a α-fucosidase belonging to GH29, and a α-xylosidase from GH31. The results showed that the three enzymes were able to release monosaccharides from xyloglucan oligosaccharides after incubation at 65 °C. The concerted actions of β-gluco-/β-galactosidase and the α-xylosidase on both xyloglucan oligosaccharides have been observed, while the α-fucosidase was capable of releasing all α-linked fucose units from xyloglucan from apple pomace, representing the first GH29 enzyme belonging to subfamily A that is active on xyloglucan.

Published
2021

40. Reply to Mezidi et al.: Assessment of Airway Closure and Expiratory Airflow Limitation to Set Positive End-Expiratory Pressure in Morbidly Obese Patients with Acute Respiratory Distress Syndrome

Author

Lorenzo Berra, Raffaele Di Fenza, David A. Imber, Caio C. A. Morais, Robert M. Kacmarek, Aditi Balakrishna, Roberta R. De Santis Santiago, and Pankaj Arora

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pulmonary Atelectasis, Respiratory Distress Syndrome, business.industry, Swine, Hemodynamics, Shock, Acute respiratory distress, Morbidly obese, Critical Care and Intensive Care Medicine, Obesity, Morbid, Expiratory Airflow, Positive-Pressure Respiration, Internal medicine, Correspondence, medicine, Cardiology, Animals, Humans, Obesity, business, Pulmonary Ventilation, Positive end-expiratory pressure, Airway closure
Published
2021

41. Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries

Author

Russotto V., Myatra S. N., Laffey J. G., Tassistro E., Antolini L., Bauer P., Lascarrou J. B., Szuldrzynski K., Camporota L., Pelosi P., Sorbello M., Higgs A., Greif R., Putensen C., Agvald-Ohman C., Chalkias A., Bokums K., Brewster D., Rossi E., Fumagalli R., Pesenti A., Foti G., Bellani G., Hazem Abdelkarem Ahmed, Neill K J Adhikari, Kehari Agrawal, Nipun Agrawal, Hernan Aguirre-Bermeo, Christina Agvald-Öhman, Meraj Ahmad, Samareh Ajami, Shazia N Akhtar, Adnan Alghamdi, Abdulmueti Alhadi, Syed M Ali, Mohd N Ali, Anita Alias, Ghaleb Almekhlafi, Julio Alonso, Diana Alvarez Montenegro, Rubina Aman, Matthew Anstey, Irene Aragão, Eleni Arnaoutoglou, Elie Azoulay, Laura Baccari, Nishanth Baliga, Ramya Ballekatte Manjunath, Shrirang Bamane, Anna Bandert, Roland Bartholdy, Marta Basto, Vera Baturova, Philippe R Bauer, Agrippino Bellissima, Vladislav Belsky, Prashant Bendre, Annalisa Benini, Sebastien Besset, Mahuya Bhattacharyya, Piotr Bielanski, Luca Bigatello, Florence Boissier, Kristaps Bokums, Elisa Boni, Iwona Bonney, David Bowen, Alexandre Boyer, Luca Brazzi, David Brewster, Lina Broman, Alexander Browne, Cedric Bruel, Yannick Brunin, Guillermo Bugedo, Italo Calamai, Patricia Campos, Federico G Canavosio, Iacopo Cappellini, Marco Cascella, Nuno Catorze, Athanasios Chalkias, Benoit Champigneulle, Juhi Chandwani, Anne Chao, Satish Chaurasia, Rajesh Chawla, Aakanksha Chawla, Olivia Cheetham, Frank Chemouni, Lee Chew Kiok, Jung-Yien Chien, Timothy Chimunda, Ching-Tang Chiu, Fernando Chiumiento, Nai-Kuan Chou, Nicolas Chudeau, Sandra Colica, Gwenhael Colin, Jean-Michel Constantin, Damien Contou, Andrea Cortegiani, Paulo F Costa, Vasco Costa, Andrea Costamagna, Antonella Cotoia, Andrea N Cracchiolo, Petra Crone, Rui P Cunha, Renata Curić Radivojević, Amit Das, Sampat Dash, Gennaro De Pascale, Silvia De Rosa, Lorenzo Del Sorbo, Valentina Della Torre, Barbara Di Caprio, Raffaele Di Fenza, Ida Di Giacinto, Aikaterini Dimitropoulou, Marcel Dudda, Christopher Edmunds, Stefan F Ehrentraut, Nadia El-Fellah, Muhammed Elhadi, Ahmed Elhadi, Patricia Escudero-Acha, Missael Espinoza, Clelia Esposito, Fabrizio Fabretti, Daniel G Fein, Massimo Ferluga, Marco Fernandes, Alexis Ferre, Janet Ferrier, Marek Flaksa, Fernando Flores, Jesus Flores Gonzalez, Xavier E Fonseca Fuentes, Roland Francis, Daniela G Franco, Pawel Franczyk, Jean-Pierre Frat, Mikhail Furman, Maurizio Fusari, Piotr Galkin, Alice Gallo de Moraes, Renato Gammaldi, Maria F García Aguilera, Eugenio Garofalo, Tomasz Gaszynski, Jonathan Gatward, Mohamed Ghula, Angelo Giacomucci, Ilaria Giovannini, Kingsly Gnanadurai, Thomas Godet, Alberto Goffi, Gemma Goma Fernandez, Maria Gonzalez, Daira González, Alejandro González-Castro, Kadarapura N Gopalakrishna, Eric Gottesman, Alexandre Gros, Christophe Guervilly, Christophe Guitton, Manish Gupta, Kulbhusahn Gupta, Tarikul Hamid, Olfa Hamzaoui, Katrin Hannesdottir, Shahnaz Hasan, Mozaffer Hossain, Sazzad Hossein, Sami Hraiech, Chun-Kai Huang, Cameron Hypes, Soad Imhmed Alkhumsi, Motiul Islam, Muhamad A Ismail, Višnja Ivančan, Sophie Jacquier, Bharat Jagiasi, Nikhilesh Jain, Muhamad Fadhil Hadi Jamaluddin, Milosz Jankowski, Deepak Jeswani, Deepti Jeswani, Simant Jha, Laura Jones, Benjamin Jones, Mathieu Jozwiak, Aleksandra Jumić, Oliver Kamp, Ilias Karametos, Alexey Karelov, Panagiotis Katsoulis, David A Kaufman, Shuchi Kaushik, Callum T Kaye, Subba R Kesavarapu, Ala Khaled, Hapiz Khalidah, Akram Khan, Sudhir Khunteta, Detlef Kindgen-Milles, Sara V Korula, Amol Kothekar, Salman S Koul, Ditte Krog, Shih-Chi Ku, Mira Kuellmar, Lu-Cheng Kuo, Swarna D Kuragayala, Aikaterini Kyparissi, Gonzalo Labarca, John G Laffey, Jaya Lalwani, Antonio Landaverde, Jean-Baptiste Lascarrou, Andres Laserna, Chien-Chang Lee, Stephane Legriel, Andrew Lehr, Tiago Leonor, Yongxing Li, Anna Lisa Licciardi, Edward Litton, Vladimir Lomivorotov, Federico Longhini, Claudia L Lopez Nava, Luis R Loza Gallardo, Ramona Lungu, Annalisa Luzi, Wuhua Ma, Marat Magomedov, Alexandros Makris, Harish Mallapura Maheshwarappa, Tommaso Maraffi, Maria E Marcelli, Karim Mariano, Nathalie Marin, Nadezhda Marova, Maelle Martin, Mayra Martinez Gonzalez, Emilio Maseda, Fiore Mastroianni, Marijana Matas, Dubier Matos, Jessica G Maugeri, Mohd Z Mazlan, Melanie Meersch, Ranjan Meher, Tasneem H Mehesry, Maria Meirik, Armand Mekontso Dessap, Kwabena Mensah, Emmanuelle Mercier, Pavel Michalek, Abhirup Midya, Slobodan Mihaljević, Adrien Mirouse, Prasanna Mishra, Ravi Mistry, Mate Moguš, Norbaniza Mohd Nordin, Noryani Mohd Samat, Luca Montini, Giorgia Montrucchio, Valeria Moro, Diego Morocho Tutillo, Jarrod Mosier, Sircar Mrinal, Wojciech Mudyna, Grégoire Muller, Kartik Munta, Satheesh Munusamy, Stefania Musso, Stefano Muttini, Ismail Nahla Irtiza, Evi Nakou, Amit Narkhede, Joseph Nates, Moana R Nespoli, Francesca Nespoli, Artem Nikitenko, Carla Nogueira, Ross O'Grady, Yewande E Odeyemi, Annika Ohlsson, Alberto Orsello, Vijayanand Palaniswamy, Daniela M Palma, Salvatore Palmese, Jesus N Pantoja Leal, Eleni Papandreou, Metaxia Papanikolaou, Matteo Parotto, Mayur Patel, Mario Pavlek, Niccolò Pedrotti, Ngu Pei Hwa, Lorella Pelagalli, Miryam Pérez Ruiz, Elin Persson, Athanasia Petsiou, Angelo Pezzi, Sam Philip, Francois Philippard, Mariusz Piegat, Sébastien Pili-Floury, Riccardo Pinciroli, Marcia Pinto, Gael Piton, Gaetan Plantefeve, Caroline Pouplet, Sofia Pouriki, Andrea Pradella, Kumar Prashant, Christian Putensen, Alice Quayle, Lua Rahmani, Ian Randall, Banambar Ray, Adrian Regli, Syed T Reza, Jean Damien Ricard, Ivano Riva, Oriol Roca, Roberto Rona, Jon Rosell, Rebecca Rowley, Sheng-Yuan Ruan, Kay Rumschuessel, Annalisa Rundo, Pierpaolo Russo, Vincenzo Russotto, Samir Sahu, Gabriele Sales, Charlotte Salmon-Gandonnière, Nandyelly San Juan Roman, Luis Sánchez-Hurtado, Benjamin J Sandefur, Manel Santafe, Lida Santoro, Rhik Sanyal, Lakshmikanthcharan Saravanabavan, Bhagyesh Shah, Mehul Shah, Ming-Hann Shin, Monica Silva, Shannon Simpson, Ayush Sinah, Atul K Singh, Dinesh K Singh, Nitesh Singh, Lalit Singh, Lukasz Skowronski, Miguel A Sosa, Savino Spadaro, Martin Spangfors, Jesper Sperber, Rosario Spina, Anand Srivastava, Andrew Steel, Alejandro Suarez de la Rica, Singh Sujeet Kumar, Omprakash Sundrani, Nilu Sunil, Bharadwaj Suparna, Manimala R Surath, Yadullah Syed, Tamas Szakmany, Benjamin Sztrymf, Alexis Tabah, Stefano Tarantino, Maria Tileli, Hugo Tirape-Castro, Otoniel Toledo-Salinas, Jacopo Tramarin, Dimitrios Tsiftsis, Iva Tucić, Jose A Tutillo León, Lorenzo Tutino, Vijay N Tyagi, Kyriaki Vagdatli, Sneha Varkey, Maria M Vera, Magnus Von Seth, Carl Wahlstrom, Wan Mohd N Wan Hassan, Wan N Wan Ismail, Kuo-Chuan Wang, Hadrien Winiszewski, Jiayan Wu, Lun Wu, Yu-Chang Yeh, Paul Young, Gianluca Zani, Jonathan Zarka, Dawn Zhao, Diane Zlotnik, Russotto, V, Myatra, S, Laffey, J, Tassistro, E, Antolini, L, Bauer, P, Lascarrou, J, Szuldrzynski, K, Camporota, L, Pelosi, P, Sorbello, M, Higgs, A, Greif, R, Putensen, C, Agvald-Öhman, C, Chalkias, A, Bokums, K, Brewster, D, Rossi, E, Fumagalli, R, Pesenti, A, Foti, G, Bellani, G, Russotto V., Myatra S.N., Laffey J.G., Tassistro E., Antolini L., Bauer P., Lascarrou J.B., Szuldrzynski K., Camporota L., Pelosi P., Sorbello M., Higgs A., Greif R., Putensen C., Agvald-Ohman C., Chalkias A., Bokums K., Brewster D., Rossi E., Fumagalli R., Pesenti A., Foti G., Bellani G., and Hazem Abdelkarem Ahmed, Neill K J Adhikari, Kehari Agrawal, Nipun Agrawal, Hernan Aguirre-Bermeo, Christina Agvald-Öhman, Meraj Ahmad, Samareh Ajami, Shazia N Akhtar, Adnan Alghamdi, Abdulmueti Alhadi, Syed M Ali, Mohd N Ali, Anita Alias, Ghaleb Almekhlafi, Julio Alonso, Diana Alvarez Montenegro, Rubina Aman, Matthew Anstey, Irene Aragão, Eleni Arnaoutoglou, Elie Azoulay, Laura Baccari, Nishanth Baliga, Ramya Ballekatte Manjunath, Shrirang Bamane, Anna Bandert, Roland Bartholdy, Marta Basto, Vera Baturova, Philippe R Bauer, Agrippino Bellissima, Vladislav Belsky, Prashant Bendre, Annalisa Benini, Sebastien Besset, Mahuya Bhattacharyya, Piotr Bielanski, Luca Bigatello, Florence Boissier, Kristaps Bokums, Elisa Boni, Iwona Bonney, David Bowen, Alexandre Boyer, Luca Brazzi, David Brewster, Lina Broman, Alexander Browne, Cedric Bruel, Yannick Brunin, Guillermo Bugedo, Italo Calamai, Patricia Campos, Federico G Canavosio, Iacopo Cappellini, Marco Cascella, Nuno Catorze, Athanasios Chalkias, Benoit Champigneulle, Juhi Chandwani, Anne Chao, Satish Chaurasia, Rajesh Chawla, Aakanksha Chawla, Olivia Cheetham, Frank Chemouni, Lee Chew Kiok, Jung-Yien Chien, Timothy Chimunda, Ching-Tang Chiu, Fernando Chiumiento, Nai-Kuan Chou, Nicolas Chudeau, Sandra Colica, Gwenhael Colin, Jean-Michel Constantin, Damien Contou, Andrea Cortegiani, Paulo F Costa, Vasco Costa, Andrea Costamagna, Antonella Cotoia, Andrea N Cracchiolo, Petra Crone, Rui P Cunha, Renata Curić Radivojević, Amit Das, Sampat Dash, Gennaro De Pascale, Silvia De Rosa, Lorenzo Del Sorbo, Valentina Della Torre, Barbara Di Caprio, Raffaele Di Fenza, Ida Di Giacinto, Aikaterini Dimitropoulou, Marcel Dudda, Christopher Edmunds, Stefan F Ehrentraut, Nadia El-Fellah, Muhammed Elhadi, Ahmed Elhadi, Patricia Escudero-Acha, Missael Espinoza, Clelia Esposito, Fabrizio Fabretti, Daniel G Fein, Massimo Ferluga, Marco Fernandes, Alexis Ferre, Janet Ferrier, Marek Flaksa, Fernando Flores, Jesus Flores Gonzalez, Xavier E Fonseca Fuentes, Roland Francis, Daniela G Franco, Pawel Franczyk, Jean-Pierre Frat, Mikhail Furman, Maurizio Fusari, Piotr Galkin, Alice Gallo de Moraes, Renato Gammaldi, Maria F García Aguilera, Eugenio Garofalo, Tomasz Gaszynski, Jonathan Gatward, Mohamed Ghula, Angelo Giacomucci, Ilaria Giovannini, Kingsly Gnanadurai, Thomas Godet, Alberto Goffi, Gemma Goma Fernandez, Maria Gonzalez, Daira González, Alejandro González-Castro, Kadarapura N Gopalakrishna, Eric Gottesman, Alexandre Gros, Christophe Guervilly, Christophe Guitton, Manish Gupta, Kulbhusahn Gupta, Tarikul Hamid, Olfa Hamzaoui, Katrin Hannesdottir, Shahnaz Hasan, Mozaffer Hossain, Sazzad Hossein, Sami Hraiech, Chun-Kai Huang, Cameron Hypes, Soad Imhmed Alkhumsi, Motiul Islam, Muhamad A Ismail, Višnja Ivančan, Sophie Jacquier, Bharat Jagiasi, Nikhilesh Jain, Muhamad Fadhil Hadi Jamaluddin, Milosz Jankowski, Deepak Jeswani, Deepti Jeswani, Simant Jha, Laura Jones, Benjamin Jones, Mathieu Jozwiak, Aleksandra Jumić, Oliver Kamp, Ilias Karametos, Alexey Karelov, Panagiotis Katsoulis, David A Kaufman, Shuchi Kaushik, Callum T Kaye, Subba R Kesavarapu, Ala Khaled, Hapiz Khalidah, Akram Khan, Sudhir Khunteta, Detlef Kindgen-Milles, Sara V Korula, Amol Kothekar, Salman S Koul, Ditte Krog, Shih-Chi Ku, Mira Kuellmar, Lu-Cheng Kuo, Swarna D Kuragayala, Aikaterini Kyparissi, Gonzalo Labarca, John G Laffey, Jaya Lalwani, Antonio Landaverde, Jean-Baptiste Lascarrou, Andres Laserna, Chien-Chang Lee, Stephane Legriel, Andrew Lehr, Tiago Leonor, Yongxing Li, Anna Lisa Licciardi, Edward Litton, Vladimir Lomivorotov, Federico Longhini, Claudia L Lopez Nava, Luis R Loza Gallardo, Ramona Lungu, Annalisa Luzi, Wuhua Ma, Marat Magomedov, Alexandros Makris, Harish Mallapura Maheshwarappa, Tommaso Maraffi, Maria E Marcelli, Karim Mariano, Nathalie Marin, Nadezhda Marova, Maelle Martin, Mayra Martinez Gonzalez, Emilio Maseda, Fiore Mastroianni, Marijana Matas, Dubier Matos, Jessica G Maugeri, Mohd Z Mazlan, Melanie Meersch, Ranjan Meher, Tasneem H Mehesry, Maria Meirik, Armand Mekontso Dessap, Kwabena Mensah, Emmanuelle Mercier, Pavel Michalek, Abhirup Midya, Slobodan Mihaljević, Adrien Mirouse, Prasanna Mishra, Ravi Mistry, Mate Moguš, Norbaniza Mohd Nordin, Noryani Mohd Samat, Luca Montini, Giorgia Montrucchio, Valeria Moro, Diego Morocho Tutillo, Jarrod Mosier, Sircar Mrinal, Wojciech Mudyna, Grégoire Muller, Kartik Munta, Satheesh Munusamy, Stefania Musso, Stefano Muttini, Ismail Nahla Irtiza, Evi Nakou, Amit Narkhede, Joseph Nates, Moana R Nespoli, Francesca Nespoli, Artem Nikitenko, Carla Nogueira, Ross O'Grady, Yewande E Odeyemi, Annika Ohlsson, Alberto Orsello, Vijayanand Palaniswamy, Daniela M Palma, Salvatore Palmese, Jesus N Pantoja Leal, Eleni Papandreou, Metaxia Papanikolaou, Matteo Parotto, Mayur Patel, Mario Pavlek, Niccolò Pedrotti, Ngu Pei Hwa, Lorella Pelagalli, Miryam Pérez Ruiz, Elin Persson, Athanasia Petsiou, Angelo Pezzi, Sam Philip, Francois Philippard, Mariusz Piegat, Sébastien Pili-Floury, Riccardo Pinciroli, Marcia Pinto, Gael Piton, Gaetan Plantefeve, Caroline Pouplet, Sofia Pouriki, Andrea Pradella, Kumar Prashant, Christian Putensen, Alice Quayle, Lua Rahmani, Ian Randall, Banambar Ray, Adrian Regli, Syed T Reza, Jean Damien Ricard, Ivano Riva, Oriol Roca, Roberto Rona, Jon Rosell, Rebecca Rowley, Sheng-Yuan Ruan, Kay Rumschuessel, Annalisa Rundo, Pierpaolo Russo, Vincenzo Russotto, Samir Sahu, Gabriele Sales, Charlotte Salmon-Gandonnière, Nandyelly San Juan Roman, Luis Sánchez-Hurtado, Benjamin J Sandefur, Manel Santafe, Lida Santoro, Rhik Sanyal, Lakshmikanthcharan Saravanabavan, Bhagyesh Shah, Mehul Shah, Ming-Hann Shin, Monica Silva, Shannon Simpson, Ayush Sinah, Atul K Singh, Dinesh K Singh, Nitesh Singh, Lalit Singh, Lukasz Skowronski, Miguel A Sosa, Savino Spadaro, Martin Spangfors, Jesper Sperber, Rosario Spina, Anand Srivastava, Andrew Steel, Alejandro Suarez de la Rica, Singh Sujeet Kumar, Omprakash Sundrani, Nilu Sunil, Bharadwaj Suparna, Manimala R Surath, Yadullah Syed, Tamas Szakmany, Benjamin Sztrymf, Alexis Tabah, Stefano Tarantino, Maria Tileli, Hugo Tirape-Castro, Otoniel Toledo-Salinas, Jacopo Tramarin, Dimitrios Tsiftsis, Iva Tucić, Jose A Tutillo León, Lorenzo Tutino, Vijay N Tyagi, Kyriaki Vagdatli, Sneha Varkey, Maria M Vera, Magnus Von Seth, Carl Wahlstrom, Wan Mohd N Wan Hassan, Wan N Wan Ismail, Kuo-Chuan Wang, Hadrien Winiszewski, Jiayan Wu, Lun Wu, Yu-Chang Yeh, Paul Young, Gianluca Zani, Jonathan Zarka, Dawn Zhao, Diane Zlotnik

Subjects
Male, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, Aged, Female, Heart Arrest, Humans, Hypotension, Hypoxia, Intensive Care Units, Intubation, Intratracheal, Logistic Models, Medical Errors, Middle Aged, Prospective Studies, Respiration, Artificial, Respiratory Insufficiency, Vasoconstrictor Agents, 01 natural sciences, NO, tracheal intubation, adverse peri-intubation events, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Medicine, Intubation, Intubation, Critical Care, 030212 general & internal medicine, 0101 mathematics, 610 Medicine & health, Prospective cohort study, business.industry, Respiration, 010102 general mathematics, Tracheal intubation, General Medicine, Intratracheal, Intubation procedure, Respiratory failure, Artificial, Emergency medicine, Airway management, business
Abstract

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation

Published
2021

42. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia

Author

Safaee Fakhr, Bijan, primary, Di Fenza, Raffaele, additional, Gianni, Stefano, additional, Wiegand, Steffen B., additional, Miyazaki, Yusuke, additional, Araujo Morais, Caio C., additional, Gibson, Lauren E., additional, Chang, Marvin G., additional, Mueller, Ariel L., additional, Rodriguez-Lopez, Josanna M., additional, Ackman, Jeanne B., additional, Arora, Pankaj, additional, Scott, Louie K., additional, Bloch, Donald B., additional, Zapol, Warren M., additional, Carroll, Ryan W., additional, Ichinose, Fumito, additional, Berra, Lorenzo, additional, Marutani, Eizo, additional, Ikeda, Takamitsu, additional, Parcha, Vibhu, additional, Corman, Benjamin, additional, Larson, Grant, additional, Delgado, Eduardo Diaz, additional, Wanderley, Hatus V., additional, Hutchinson, Kimberley, additional, Caskey, Elizabeth I., additional, Capriles, Martin, additional, Traeger, Lisa, additional, Fischbach, Anna, additional, Grange, Robert M.H., additional, Hibbert, Kathryn, additional, Lai, Peggy S., additional, Akeju, Oluwaseun, additional, Pinciroli, Riccardo, additional, Harris, Stuart N., additional, Bittner, Edward A., additional, Greene, Reginald E., additional, and Kacmarek, Robert M., additional

Published
2021
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44. Bedside monitoring of lung perfusion by electrical impedance tomography in the time of COVID-19

Author

Raffaele Di Fenza, Bijan Safaee Fakhr, Paula A. Restrepo, Caio C. A. Morais, Florian J. Fintelmann, Riccardo Pinciroli, Roberta R. De Santis Santiago, Lauren E. Gibson, Edward A. Bittner, Robert M. Kacmarek, Lorenzo Berra, Marvin G. Chang, Safaee Fakhr, B, Araujo Morais, C, De Santis Santiago, R, Di Fenza, R, Gibson, L, Restrepo, P, Chang, M, Bittner, E, Pinciroli, R, Fintelmann, F, Kacmarek, R, and Berra, L

Subjects
2019-20 coronavirus outbreak, medicine.medical_specialty, lung perfusion, pulmonary embolism, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mechanical ventilation, Article, Internal medicine, medicine, Electrical impedance tomography, Mechanical ventilation, biology, business.industry, COVID-19, Lung perfusion, biology.organism_classification, medicine.disease, Pulmonary embolism, Anesthesiology and Pain Medicine, ventilation/perfusion matching, Cardiology, business, Betacoronavirus, electrical impedance tomography
Published
2020

45. A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects

Author

Dianna Robinson, Stefano Gianni, Warren M. Zapol, Anna Fischbach, Ryan W. Carroll, Lorenzo Berra, Caio C. A. Morais, Raffaele Di Fenza, Riccardo Pinciroli, Bijan Safaee Fakhr, and Lisa Traeger

Subjects
medicine.medical_specialty, Critical Care, Coronavirus disease 2019 (COVID-19), General Chemical Engineering, Nitric Oxide, General Biochemistry, Genetics and Molecular Biology, Nitric oxide, law.invention, chemistry.chemical_compound, law, Administration, Inhalation, Humans, Medicine, Nitrogen dioxide, Respiratory Protective Devices, Intensive care medicine, High concentration, Ventilators, Mechanical, General Immunology and Microbiology, Inhalation, SARS-CoV-2, business.industry, General Neuroscience, Intensive care unit, COVID-19 Drug Treatment, Intensive Care Units, chemistry, Nitric oxide gas, Breathing, business
Abstract

Nitric Oxide (NO) is administered as gas for inhalation to induce selective pulmonary vasodilation. It is a safe therapy, with few potential risks even if administered at high concentration. Inhaled NO gas is routinely used to increase systemic oxygenation in different disease conditions. The administration of high concentrations of NO also exerts a virucidal effect in vitro. Owing to its favorable pharmacodynamic and safety profiles, the familiarity in its use by critical care providers, and the potential for a direct virucidal effect, NO is clinically used in patients with coronavirus disease-2019 (COVID-19). Nevertheless, no device is currently available to easily administer inhaled NO at concentrations higher than 80 parts per million (ppm) at various inspired oxygen fractions, without the need for dedicated, heavy, and costly equipment. The development of a reliable, safe, inexpensive, lightweight, and ventilator-free solution is crucial, particularly for the early treatment of non-intubated patients outside of the intensive care unit (ICU) and in a limited-resource scenario. To overcome such a barrier, a simple system for the non-invasive NO gas administration up to 250 ppm was developed using standard consumables and a scavenging chamber. The method has been proven safe and reliable in delivering a specified NO concentration while limiting nitrogen dioxide levels. This paper aims to provide clinicians and researchers with the necessary information on how to assemble or adapt such a system for research purposes or clinical use in COVID-19 or other diseases in which NO administration might be beneficial.

Published
2021

48. Veno‐venous extracorporeal blood phototherapy increases the rate of carbon monoxide (CO) elimination in CO‐poisoned pigs

Author

Fischbach, Anna, primary, Wiegand, Steffen B., additional, Zazzeron, Luca, additional, Traeger, Lisa, additional, di Fenza, Raffaele, additional, Bagchi, Aranya, additional, Farinelli, William A., additional, Franco, Walfre, additional, Korupolu, Sandeep, additional, Arens, Jutta, additional, Grassi, Luigi, additional, Zadek, Francesco, additional, Bloch, Donald B., additional, Rox Anderson, R., additional, and Zapol, Warren M., additional

Published
2021
Full Text
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50. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia

Author

Bijan Safaee Fakhr, Raffaele Di Fenza, Stefano Gianni, Steffen B. Wiegand, Yusuke Miyazaki, Caio C. Araujo Morais, Lauren E. Gibson, Marvin G. Chang, Ariel L. Mueller, Josanna M. Rodriguez-Lopez, Jeanne B. Ackman, Pankaj Arora, Louie K. Scott, Donald B. Bloch, Warren M. Zapol, Ryan W. Carroll, Fumito Ichinose, Lorenzo Berra, Eizo Marutani, Takamitsu Ikeda, Vibhu Parcha, Benjamin Corman, Grant Larson, Eduardo Diaz Delgado, Hatus V. Wanderley, Kimberley Hutchinson, Elizabeth I. Caskey, Martin Capriles, Lisa Traeger, Anna Fischbach, Robert M.H. Grange, Kathryn Hibbert, Peggy S. Lai, Oluwaseun Akeju, Riccardo Pinciroli, Stuart N. Harris, Edward A. Bittner, Reginald E. Greene, and Robert M. Kacmarek

Subjects
Cancer Research, Respiratory rate, Physiology, medicine.medical_treatment, Viral pneumonia, Clinical Biochemistry, Pneumonia, Viral, Biochemistry, Hypoxemia, Interquartile range, Administration, Inhalation, medicine, Humans, Respiratory system, Adverse effect, Mechanical ventilation, Dose-Response Relationship, Drug, business.industry, Respiration, COVID-19, Regular Article, Nitric oxide, medicine.disease, COVID-19 Drug Treatment, Hospitalization, Pneumonia, Anesthesia, Breathing, medicine.symptom, business
Abstract

Background Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). Methods This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. Results Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4–8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. Conclusions In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

Published
2021

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