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4. Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Author

Wahlster, Sarah, Sharma, Monisha, Taran, Shaurya, Town, James A, Stevens, Robert D, Cinotti, Raphaël, Asehoune, Karim, Pelosi, Paolo, Robba, Chiara, Paër-Sélim Abback, Anaïs Codorniu, Giuseppe Citerio, Vittoria Ludovica Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Jessica Giuseppina Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Denise Battaglini, Patrick Biston, Mohamed Fathi Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter van Vliet, Benjamin Marcel Gerretsen, Iris Xochitl Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, Wytze J Vermeijden, Alexander Daniel Cornet, Sergio Reyes Inurrigarro, Rafael Cirino Lara Domínguez, Maria Mercedes Bellini, Maria Milagros Gomez Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Roberto Carlos Miranda-Ackerman, Francisco José Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Hana Basheer Yahya, Ala Khaled, Mohamed Ghula, Cracchiolo Neville Andrea, Palma Maria Daniela, Cristian Deana, Luigi Vetrugno, Manuel J Rivera Chavez, Rocio Mendoza Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu van der Jagt, Job van Steenkiste, Hazem Ahmed, Alexander Edward Coombs, Jessie Welbourne, Ana Alicia Velarde Pineda, Víctor Hugo Nubert Castillo, Mohammed A Azab, Ahmed Y Azzam, David Michael Paul van Meenen, Gilberto Adrian Gasca, Alfredo Arellano, Forttino Galicia-Espinosa, José Carlos García-Ramos, Ghanshyam Yadav, Amarendra Kumar Jha, Vincent Robert-Edan, Pierre-Andre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal, Yashbir Deewan, Syed Tariq Reza, Md Mozaffer Hossain, Christos Papadas, Vasiliki Chantziara, Chrysanthi Sklavou, Yannick Hourmant, Nicolas Grillot, Romain Pirracchio, Abdelraouf Akkari, Mohamed Abdelaty, Ahmed Hashim, Yoann Launey, Elodie Masseret, Sigismond Lasocki, Soizic Gergaud, Nicolas Mouclier, Sulekha Saxena, Avinash Agrawal, Shakti Bedanta Mishra, Samir Samal, Julio Cesar Mijangos, Mattias Haënggi, Mohan Gurjar, Marcus J Schultz, Callum Kaye, Daniela Agustin Godoy, Pablo Alvarez, Aikaterini Ioakeimidou, Yoshitoyo Ueno, Rafael Badenes, Abdurrahmaan Ali Suei Elbuzidi, Michaël Piagnerelli, Muhammed Elhadi, Jean Catherine Digitale, Nicholas Fong, Ricardo Campos Cerda, Norma de la Torre Peredo, Wahlster, S, Sharma, M, Taran, S, Town, J, Stevens, R, Cinotti, R, Asehoune, K, Pelosi, P, Robba, C, Abback, P, Codorniu, A, Citerio, G, Sala, V, Astuto, M, Tringali, E, Alampi, D, Rocco, M, Maugeri, J, Bellissima, A, Filippini, M, Lazzeri, N, Cortegiani, A, Ippolito, M, Battaglini, D, Biston, P, Al-Gharyani, M, Chabanne, R, Astier, L, Soyer, B, Gaugain, S, Zimmerli, A, Pietsch, U, Filipovic, M, Brandi, G, Bicciato, G, Serrano, A, Monleon, B, van Vliet, P, Gerretsen, B, Ortiz-Macias, I, Oto, J, Enomoto, N, Matsuda, T, Masui, N, Garcon, P, Zarka, J, Vermeijden, W, Cornet, A, Inurrigarro, S, Dominguez, R, Bellini, M, Gomez Haedo, M, Lamot, L, Orquera, J, Biais, M, Georges, D, Baronia, A, Miranda-Ackerman, R, Barbosa-Camacho, F, Porter, J, Lopez-Morales, M, Geeraerts, T, Compagnon, B, Perez-Torres, D, Prol-Silva, E, Yahya, H, Khaled, A, Ghula, M, Andrea, C, Daniela, P, Deana, C, Vetrugno, L, Chavez, M, Trujillo, R, Legros, V, Brochet, B, Huet, O, Geslain, M, van der Jagt, M, van Steenkiste, J, Ahmed, H, Coombs, A, Welbourne, J, Velarde Pineda, A, Nubert Castillo, V, Azab, M, Azzam, A, van Meenen, D, Gasca, G, Arellano, A, Galicia-Espinosa, F, Garcia-Ramos, J, Yadav, G, Jha, A, Robert-Edan, V, Rodie-Talbere, P, Jain, G, Panda, S, Agarwal, S, Deewan, Y, Reza, S, Hossain, M, Papadas, C, Chantziara, V, Sklavou, C, Hourmant, Y, Grillot, N, Pirracchio, R, Akkari, A, Abdelaty, M, Hashim, A, Launey, Y, Masseret, E, Lasocki, S, Gergaud, S, Mouclier, N, Saxena, S, Agrawal, A, Mishra, S, Samal, S, Mijangos, J, Haenggi, M, Gurjar, M, Schultz, M, Kaye, C, Godoy, D, Alvarez, P, Ioakeimidou, A, Ueno, Y, Badenes, R, Suei Elbuzidi, A, Piagnerelli, M, Elhadi, M, Digitale, J, Fong, N, Cerda, R, de la Torre Peredo, N, Wahlster, Sarah, Sharma, Monisha, Taran, Shaurya, Town, James A, Stevens, Robert D, Cinotti, Raphaël, Asehoune, Karim, Pelosi, Paolo, Robba, Chiara, and Paër-Sélim Abback, Anaïs Codorniu, Giuseppe Citerio, Vittoria Ludovica Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Jessica Giuseppina Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Denise Battaglini, Patrick Biston, Mohamed Fathi Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter van Vliet, Benjamin Marcel Gerretsen, Iris Xochitl Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, Wytze J Vermeijden, Alexander Daniel Cornet, Sergio Reyes Inurrigarro, Rafael Cirino Lara Domínguez, Maria Mercedes Bellini, Maria Milagros Gomez Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Roberto Carlos Miranda-Ackerman, Francisco José Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Hana Basheer Yahya, Ala Khaled, Mohamed Ghula, Cracchiolo Neville Andrea, Palma Maria Daniela, Cristian Deana, Luigi Vetrugno, Manuel J Rivera Chavez, Rocio Mendoza Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu van der Jagt, Job van Steenkiste, Hazem Ahmed, Alexander Edward Coombs, Jessie Welbourne, Ana Alicia Velarde Pineda, Víctor Hugo Nubert Castillo, Mohammed A Azab, Ahmed Y Azzam, David Michael Paul van Meenen, Gilberto Adrian Gasca, Alfredo Arellano, Forttino Galicia-Espinosa, José Carlos García-Ramos, Ghanshyam Yadav, Amarendra Kumar Jha, Vincent Robert-Edan, Pierre-Andre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal, Yashbir Deewan, Gilberto Adrian Gasca, Alfredo Arellano, Syed Tariq Reza, Md Mozaffer Hossain, Christos Papadas, Vasiliki Chantziara, Chrysanthi Sklavou, Yannick Hourmant, Nicolas Grillot, Job van Steenkiste, Mathieu van der Jagt, Romain Pirracchio, Abdelraouf Akkari, Mohamed Abdelaty, Ahmed Hashim, Yoann Launey, Elodie Masseret, Sigismond Lasocki, Soizic Gergaud, Nicolas Mouclier, Sulekha Saxena, Avinash Agrawal, Shakti Bedanta Mishra, Samir Samal, Julio Cesar Mijangos, Mattias Haënggi, Mohan Gurjar, Marcus J Schultz, Callum Kaye, Daniela Agustin Godoy, Pablo Alvarez, Aikaterini Ioakeimidou, Yoshitoyo Ueno, Rafael Badenes, Abdurrahmaan Ali Suei Elbuzidi, Michaël Piagnerelli, Muhammed Elhadi, Syed Tariq Reza, Jean Catherine Digitale, Nicholas Fong, Ricardo Campos Cerda, Norma de la Torre Peredo

Subjects
Mechanical power, Mechanical ventilation, Traumatic brain injury, Acute respiratory distress syndrome, Acute ischemic stroke, Acute brain injury, Intracranial hemorrhage, Subarachnoid hemorrhage
Abstract

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9J/min [IQR 9.2-15.1], 13J/min [IQR 10-17], and 14J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9J/min, aRR at 17J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation.

Published
2023

5. Extubation in neurocritical care patients: the ENIO international prospective study

Author

Cinotti, Raphaël, Mijangos, Julio Cesar, Pelosi, Paolo, Haenggi, Matthias, Gurjar, Mohan, Schultz, Marcus J., Kaye, Callum, Godoy, Daniel Agustin, Alvarez, Pablo, Ioakeimidou, Aikaterini, Ueno, Yoshitoyo, Badenes, Rafael, Suei Elbuzidi, Abdurrahmaan Ali, Piagnerelli, Michaël, Elhadi, Muhammed, Reza, Syed Tariq, Azab, Mohammed Atef, McCredie, Victoria, Stevens, Robert D., Digitale, Jean Catherine, Fong, Nicholas, Asehnoune, Karim, Abback, Paër-sélim, Codorniu, Anaïs, Citerio, Giuseppe, Sala, Vittoria Ludovica, Astuto, Marinella, Tringali, Eleonora, Alampi, Daniela, Rocco, Monica, Maugeri, Jessica Giuseppina, Bellissima, Agrippino, Filippini, Matteo, Lazzeri, Nicoletta, Cortegiani, Andrea, Ippolito, Mariachiara, Robba, Chiara, Battaglini, Denise, Biston, Patrick, Al-Gharyani, Mohamed Fathi, Chabanne, Russell, Astier, Léo, Soyer, Benjamin, Gaugain, Samuel, Zimmerli, Alice, Pietsch, Urs, Filipovic, Miodrag, Brandi, Giovanna, Bicciato, Giulio, Serrano, Ainhoa, Monleon, Berta, van Vliet, Peter, Gerretsen, Benjamin Marcel, Ortiz-Macias, Iris Xochitl, Oto, Jun, Enomoto, Noriya, Matsuda, Tomomichi, Masui, Nobutaka, Garçon, Pierre, Zarka, Jonathan, Vermeijden, Wytze J., Cornet, Alexander Daniel, Inurrigarro, Sergio Reyes, Domínguez, Rafael Cirino Lara, Bellini, Maria Mercedes, Haedo, Maria Milagros Gomez, Lamot, Laura, Orquera, Jose, Biais, Matthieu, Georges, Delphine, Baronia, Arvind, Miranda-Ackerman, Roberto Carlos, Barbosa-Camacho, Francisco José, Porter, John, Lopez-Morales, Miguel, Geeraerts, Thomas, Compagnon, Baptiste, Pérez-Torres, David, Prol-Silva, Estefanía, Yahya, Hana Basheer, Khaled, Ala, Ghula, Mohamed, Andrea, Cracchiolo Neville, Daniela, Palma Maria, Deana, Cristian, Vetrugno, Luigi, Chavez, Manuel J. Rivera, Trujillo, Rocio Mendoza, Legros, Vincent, Brochet, Benjamin, Huet, Olivier, Geslain, Marie, van der Jagt, Mathieu, van Steenkiste, Job, Ahmed, Hazem, Coombs, Alexander Edward, Welbourne, Jessie, Pineda, Ana Alicia Velarde, Castillo, Víctor Hugo Nubert, Azab, Mohammed A., Azzam, Ahmed Y., van Meenen, David Michael Paul, Gasca, Gilberto Adrian, Arellano, Alfredo, Galicia-Espinosa, Forttino, García-Ramos, José Carlos, Yadav, Ghanshyam, Jha, Amarendra Kumar, Robert-Edan, Vincent, Rodie-Talbere, Pierre-Andre, Jain, Gaurav, Panda, Sagarika, Agarwal, Sonika, Deewan, Yashbir, Hossain, Md. Mozaffer, Papadas, Christos, Chantziara, Vasiliki, Sklavou, Chrysanthi, Hourmant, Yannick, Grillot, Nicolas, Pirracchio, Romain, Akkari, Abdelraouf, Abdelaty, Mohamed, Hashim, Ahmed, Launey, Yoann, Masseret, Elodie, Lasocki, Sigismond, Gergaud, Soizic, Mouclier, Nicolas, Saxena, Sulekha, Agrawal, Avinash, Mishra, Shakti Bedanta, Samal, Samir, Cinotti, R, Mijangos, J, Pelosi, P, Haenggi, M, Gurjar, M, Schultz, M, Kaye, C, Godoy, D, Alvarez, P, Ioakeimidou, A, Ueno, Y, Badenes, R, Suei Elbuzidi, A, Piagnerelli, M, Elhadi, M, Reza, S, Azab, M, Mccredie, V, Stevens, R, Digitale, J, Fong, N, Asehnoune, K, Abback, P, Codorniu, A, Citerio, G, Sala, V, Astuto, M, Tringali, E, Alampi, D, Rocco, M, Maugeri, J, Bellissima, A, Filippini, M, Lazzeri, N, Cortegiani, A, Ippolito, M, Robba, C, Battaglini, D, Biston, P, Al-Gharyani, M, Chabanne, R, Astier, L, Soyer, B, Gaugain, S, Zimmerli, A, Pietsch, U, Filipovic, M, Brandi, G, Bicciato, G, Serrano, A, Monleon, B, van Vliet, P, Gerretsen, B, Ortiz-Macias, I, Oto, J, Enomoto, N, Matsuda, T, Masui, N, Garcon, P, Zarka, J, Vermeijden, W, Cornet, A, Inurrigarro, S, Dominguez, R, Bellini, M, Haedo, M, Lamot, L, Orquera, J, Biais, M, Georges, D, Baronia, A, Miranda-Ackerman, R, Barbosa-Camacho, F, Porter, J, Lopez-Morales, M, Geeraerts, T, Compagnon, B, Perez-Torres, D, Prol-Silva, E, Yahya, H, Khaled, A, Ghula, M, Andrea, C, Daniela, P, Deana, C, Vetrugno, L, Chavez, M, Trujillo, R, Legros, V, Brochet, B, Huet, O, Geslain, M, van der Jagt, M, van Steenkiste, J, Ahmed, H, Coombs, A, Welbourne, J, Pineda, A, Castillo, V, Azzam, A, van Meenen, D, Gasca, G, Arellano, A, Galicia-Espinosa, F, Garcia-Ramos, J, Yadav, G, Jha, A, Robert-Edan, V, Rodie-Talbere, P, Jain, G, Panda, S, Agarwal, S, Deewan, Y, Hossain, M, Papadas, C, Chantziara, V, Sklavou, C, Hourmant, Y, Grillot, N, Pirracchio, R, Akkari, A, Abdelaty, M, Hashim, A, Launey, Y, Masseret, E, Lasocki, S, Gergaud, S, Mouclier, N, Saxena, S, Agrawal, A, Mishra, S, Samal, S, Cinotti, Raphaël, Mijangos, Julio Cesar, Pelosi, Paolo, Haenggi, Matthia, Gurjar, Mohan, Schultz, Marcus J., Kaye, Callum, Godoy, Daniel Agustin, Alvarez, Pablo, Ioakeimidou, Aikaterini, Ueno, Yoshitoyo, Badenes, Rafael, Suei Elbuzidi, Abdurrahmaan Ali, Piagnerelli, Michaël, Elhadi, Muhammed, Reza, Syed Tariq, Azab, Mohammed Atef, McCredie, Victoria, Stevens, Robert D., Digitale, Jean Catherine, Fong, Nichola, Asehnoune, Karim, Abback, Paër-sélim, Codorniu, Anaï, Citerio, Giuseppe, Sala, Vittoria Ludovica, Astuto, Marinella, Tringali, Eleonora, Alampi, Daniela, Rocco, Monica, Maugeri, Jessica Giuseppina, Bellissima, Agrippino, Filippini, Matteo, Lazzeri, Nicoletta, Cortegiani, Andrea, Ippolito, Mariachiara, Robba, Chiara, Battaglini, Denise, Biston, Patrick, Al-Gharyani, Mohamed Fathi, Chabanne, Russell, Astier, Léo, Soyer, Benjamin, Gaugain, Samuel, Zimmerli, Alice, Pietsch, Ur, Filipovic, Miodrag, Brandi, Giovanna, Bicciato, Giulio, Serrano, Ainhoa, Monleon, Berta, van Vliet, Peter, Gerretsen, Benjamin Marcel, Ortiz-Macias, Iris Xochitl, Oto, Jun, Enomoto, Noriya, Matsuda, Tomomichi, Masui, Nobutaka, Garçon, Pierre, Zarka, Jonathan, Vermeijden, Wytze J., Cornet, Alexander Daniel, Inurrigarro, Sergio Reye, Domínguez, Rafael Cirino Lara, Bellini, Maria Mercede, Haedo, Maria Milagros Gomez, Lamot, Laura, Orquera, Jose, Biais, Matthieu, Georges, Delphine, Baronia, Arvind, Miranda-Ackerman, Roberto Carlo, Barbosa-Camacho, Francisco José, Porter, John, Lopez-Morales, Miguel, Geeraerts, Thoma, Compagnon, Baptiste, Pérez-Torres, David, Prol-Silva, Estefanía, Yahya, Hana Basheer, Khaled, Ala, Ghula, Mohamed, Andrea, Cracchiolo Neville, Daniela, Palma Maria, Deana, Cristian, Vetrugno, Luigi, Chavez, Manuel J. Rivera, Trujillo, Rocio Mendoza, Legros, Vincent, Brochet, Benjamin, Huet, Olivier, Geslain, Marie, van der Jagt, Mathieu, van Steenkiste, Job, Ahmed, Hazem, Coombs, Alexander Edward, Welbourne, Jessie, Pineda, Ana Alicia Velarde, Castillo, Víctor Hugo Nubert, Azab, Mohammed A., Azzam, Ahmed Y., van Meenen, David Michael Paul, Gasca, Gilberto Adrian, Arellano, Alfredo, Galicia-Espinosa, Forttino, García-Ramos, José Carlo, Yadav, Ghanshyam, Jha, Amarendra Kumar, Robert-Edan, Vincent, Rodie-Talbere, Pierre-Andre, Jain, Gaurav, Panda, Sagarika, Agarwal, Sonika, Deewan, Yashbir, Hossain, Md. Mozaffer, Papadas, Christo, Chantziara, Vasiliki, Sklavou, Chrysanthi, Hourmant, Yannick, Grillot, Nicola, Pirracchio, Romain, Akkari, Abdelraouf, Abdelaty, Mohamed, Hashim, Ahmed, Launey, Yoann, Masseret, Elodie, Lasocki, Sigismond, Gergaud, Soizic, Mouclier, Nicola, Saxena, Sulekha, Agrawal, Avinash, Mishra, Shakti Bedanta, Samal, Samir, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, ACS - Diabetes & metabolism, and ACS - Microcirculation

Subjects
Intensive Care Units, Tracheostomy, Traumatic brain injury, Extubation, Airway Extubation, Humans, Prospective Studies, Brain injury, Critical Care and Intensive Care Medicine, Intra-cranial haemorrhage, Respiration, Artificial
Abstract

Purpose: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. Methods: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. Results: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71–0.87] and 0.71 CI95 [0.61–0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7–21] vs 6 [3–11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). Conclusions: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.

Published
2022

6. Role of serum complement C3 and C4 on kidney outcomes in IgA nephropathy.

Author

Tringali E, Vetrano D, Tondolo F, Maritati F, Fabbrizio B, Pasquinelli G, Provenzano M, La Manna G, and Baraldi O

Subjects
Humans, Male, Female, Adult, Retrospective Studies, Prognosis, Middle Aged, Disease Progression, Glomerular Filtration Rate, Renal Insufficiency, Chronic blood, Biomarkers blood, Kidney pathology, Kidney physiopathology, Glomerulonephritis, IGA blood, Complement C3 metabolism, Complement C3 analysis, Complement C4 metabolism, Complement C4 analysis
Abstract

IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients., (© 2024. The Author(s).)

Published
2024
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7. Improving Kidney Disease Care: One Giant Leap for Nephrology.

Author

Provenzano M, Hu L, Tringali E, Senatore M, Talarico R, Di Dio M, Ruotolo C, La Manna G, Garofalo C, and Zaza G

Abstract

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence have prompted the development and implementation of novel drugs in clinical practice with the aim of treating the 'specific cause' of kidney disease (including chronic kidney disease, glomerular disease, and genetic kidney disorders) and the main immunological complications following kidney transplantation. Herein, we provide an overview of the principal emerging drug classes with proved efficacy in the context of the aforementioned clinical conditions. This can represent a simplified guide for clinical nephrologists to remind them of the vast and heterogeneous armamentarium of drugs that should be used in the present and the future to improve the management of patients suffering from kidney disease.

Published
2024
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8. Hypertension in Cardiovascular and Kidney Disease: Recent Trends - Treating Two Diseases as One.

Author

De Pascalis A, Tomassetti A, Vetrano D, Tringali E, Di Lullo L, Napoli M, La Manna G, and Cianciolo G

Subjects
Humans, Antihypertensive Agents therapeutic use, Blood Pressure physiology, Glomerular Filtration Rate physiology, Risk Factors, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic physiopathology, Hypertension complications, Hypertension physiopathology, Hypertension drug therapy, Cardiovascular Diseases complications, Disease Progression
Abstract

Background: Hypertension and chronic kidney disease (CKD) are closely interlinked pathophysiologic states, such that high blood pressure (BP) is an independent risk factor for disease progression in both adult and pediatric patients with kidney disorders and progressive decline in kidney function can conversely lead to worsening BP control., Summary: Hypertension in CKD is not only associated with GFR loss, but increases cardiovascular risk, which is the leading source of mortality and morbidity in this population. Given this complex relationship between hypertension, CKD, and CVD, an optimal management of BP in CKD is mandatory to break an established vicious pathophysiological cycle that leads to adverse outcomes., Key Messages: New promising molecules for the treatment of CKD, with interesting mechanisms, particularly regarding their pathophysiological interactions with arterial hypertension, are available or under development and in the very next future they may change the way we treat high BP in CKD patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Published
2024
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9. Fabry Disease Nephropathy: Histological Changes With Nonclassical Mutations and Genetic Variants of Unknown Significance.

Author

Santostefano M, Cappuccilli M, Gibertoni D, Fabbrizio B, Malvi D, Demetri M, Capelli I, Tringali E, Papa V, Biagini E, Cenacchi G, Galdi A, Donadio V, Liguori R, Zoli G, La Manna G, and Pasquinelli G

Abstract

Rationale & Objective: Fabry disease (FD) is an X-linked genetic disorder that causes lysosomal storage of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its derivative globotriaosylsphingosine (lyso-Gb3), with multiorgan dysfunction including chronic kidney disease. Affected individuals may be carriers of gene variants that are of uncertain significance (GVUS). We describe kidney pathology at the early stages of FD-related kidney disease to gain insights into its association with GVUS and sex., Study Design: Single-center, case series., Setting & Participants: Thirty-five consecutively biopsied patients (aged 48.1±15.4 years, 22 females) from among 64 patients with genetically diagnosed FD. Biopsies were retrospectively screened using the International Study Group of Fabry Nephropathy Scoring System., Observations: Genetic mutation type, p.N215S and D313Y, sex, age, estimated glomerular filtration rate (eGFR), plasma lyso-Gb3 (pLyso-Gb3) levels, and histological parameters, including Gb3 deposits were recorded. Genetic analyses showed mostly missense mutations, p.N215S variant in 15, and the "benign polymorphism" D313Y in 4 of the biopsied patients. Morphological lesions were similar for men and women except for interstitial fibrosis and arteriolar hyalinosis being more common in men. Early in their clinical course, patients with normal/mild albuminuria had podocyte, tubular, and peritubular capillary vacuoles/inclusions, and evidence of chronicity, i.e., glomerulosclerosis, interstitial fibrosis, tubular atrophy. These findings appeared to be associated with pLyso-Gb3, eGFR, and age., Limitations: Retrospective design and inclusion of outpatients partially based on family pedigree., Conclusions: In early stages of kidney disease in the setting of FD, numerous histological abnormalities are present. These observations suggest that kidney biopsies early in FD may reveal activity of kidney involvement that may inform clinical management., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Published
2023
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10. Anti-Inflammatory Approach in Chronic Dialysis Patients with SARS-CoV-2: ATA or PMMA Dialyzers?

Author

Donati G, Gasperoni L, Napoli M, Scrivo A, Zappulo F, Abenavoli C, Hu L, Angelini A, Di Nunzio M, Tringali E, Cingolani A, Marchegiani BC, Rigotti A, and La Manna G

Subjects
Humans, SARS-CoV-2, Prospective Studies, Dialysis, Interleukin-6, Renal Dialysis, C-Reactive Protein, Anti-Inflammatory Agents, Membranes, Artificial, Polymethyl Methacrylate, COVID-19
Abstract

Introduction: High-flux hemodialysis membranes may modulate the cytokine storm of SARS-CoV-2, but their impact on chronic hemodialysis (CHD) patients is unknown. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers and clinical outcomes in CHD patients with SARS-CoV-2., Methods: A prospective, observational study on CHD patients with SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021. Pre- and postdialysis C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) were determined at each session. Patients who underwent on-line hemodiafiltration (OLHDF) with a PMMA dialyzer were compared with those treated with OLHDF with a ATA dialyzer. The primary endpoint was the differences in the reduction ratio per session (RR) of CRP, PCT, IL-6, and IL-6 RR >25%., Results: We consecutively enrolled 74 CHD patients with COVID-19, 48 were treated with ATA membrane, and 26 with PMMA. Median IL-6 RR was higher in the ATA group compared to PMMA (17.08%, IQR -9.0 to 40.0 vs. 2.95%, IQR -34.63 to 27.32). Median CRP RR was 7.77% (IQR 2.47-13.77) in the ATA group versus 4.8% (IQR -2.65 to 11.38) in the PMMA group (p = 0.0017). Median PCT-RR% was 77.38% (IQR 70.92-82.97) in ATA group versus 54.59% (IQR 42.62-63.16) in the PMMA group (p < 0.0001). A multiple logistic regression analysis with IL-6 RR >25% as the outcome including the membrane employed, pre-dialysis IL-6, CRP, PCT, and ferritin showed that ATA led to a higher probability to reach the outcome (OR 1.891, 95% CI 1.273-2.840, p = 0.0018) while higher CRP favors the risk of lower IL-6 RR values (OR 0.910, 95% CI 0.868-0.949, p ≤ 0.0001)., Conclusions: In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile, regarding IL-6 RR, compared to PMMA., (© 2022 S. Karger AG, Basel.)

Published
2023
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