Acute and Critical Care

Original Articles

Pulmonary
Relationship between positive end-expiratory pressure levels, central venous pressure, systemic inflammation and acute renal failure in critically ill ventilated COVID-19 patients: a monocenter retrospective study in France: Pierre Basse, Louis Morisson, Romain Barthélémy, Nathan Julian, Manuel Kindermans, Magalie Collet, Benjamin Huot, Etienne Gayat, Alexandre Mebazaa, Benjamin G. Chousterman; Acute Crit Care. 2023;38(2):172-181. Published online May 25, 2023; DOI: https://doi.org/10.4266/acc.2022.01494

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Background
The role of positive pressure ventilation, central venous pressure (CVP) and inflammation on the occurrence of acute kidney injury (AKI) have been poorly described in mechanically ventilated patient secondary to coronavirus disease 2019 (COVID-19).
Methods
This was a monocenter retrospective cohort study of consecutive ventilated COVID-19 patients admitted in a French surgical intensive care unit between March 2020 and July 2020. Worsening renal function (WRF) was defined as development of a new AKI or a persistent AKI during the 5 days after mechanical ventilation initiation. We studied the association between WRF and ventilatory parameters including positive end-expiratory pressure (PEEP), CVP, and leukocytes count.
Results
Fifty-seven patients were included, 12 (21%) presented WRF. Daily PEEP, 5 days mean PEEP and daily CVP values were not associated with occurrence of WRF. 5 days mean CVP was higher in the WRF group compared to patients without WRF (median [IQR], 12 mm Hg [11-13] vs. 10 mm Hg [9–12]; P=0.03). Multivariate models with adjustment on leukocytes and Simplified Acute Physiology Score (SAPS) II confirmed the association between CVP value and risk of WRF (odd ratio, 1.97; 95% confidence interval, 1.12–4.33). Leukocytes count was also associated with occurrence of WRF in the WRF group (14 G/L [11–18]) and the no-WRF group (9 G/L [8–11]) (P=0.002).
Conclusions
In mechanically ventilated COVID-19 patients, PEEP levels did not appear to influence occurrence of WRF. High CVP levels and leukocytes count are associated with risk of WRF.

Citations

Citations to this article as recorded by

Early Driving Pressure Is Associated with Major Adverse Kidney Events at 30 Days in ARDS Patients with SARS-CoV-2
Gustavo Casas-Aparicio, Adrián E. Caballero-Islas, Antonio León-Ortiz, David Escamilla-Illescas, Yovanna Rueda-Escobedo, Carlos Ascención-López, Diana Hernández-Quino, Aimee Flores-Vargas, Jesús Sosa-Chombo, Abraham Tolentino-de La Mora, Ana Saucedo-Prune
Journal of Clinical Medicine.2025; 14(8): 2783. CrossRef
PEEP-AKI-COVID ICU: Effect of positive end-expiratory pressure on acute kidney injury development in patients with COVID-19-associated acute respiratory distress syndrome: an ancillary analysis of the COVID-ICU study
Léo Poirot, Lionel Tchatat Wangueu, Isaure Breteau, Matthieu Petit, Matthieu Schmidt, Florent Bavozet, Alain Mercat, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Arthur Pavot, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dre
Journal of Intensive Care.2025;[Epub] CrossRef
Bidirectional pressure: a mini review of ventilator-lung-kidney interactions
Avnee Kumar, Katie Epler, Sean DeWolf, Laura Barnes, Mark Hepokoski
Frontiers in Physiology.2024;[Epub] CrossRef
Renal venous flow in different regions of the kidney are different and reflecting different etiologies of venous reflux disorders in septic acute kidney injury: a prospective cohort study
Rongping Chen, Hui Lian, Hua Zhao, Xiaoting Wang
Intensive Care Medicine Experimental.2024;[Epub] CrossRef

Neurology
Cytokine profiles in intensive care unit delirium: Ryan J. Smith, Christian Lachner, Vijay P. Singh, Shubham Trivedi, Biswajit Khatua, Rodrigo Cartin-Ceba; Acute Crit Care. 2022;37(3):415-428. Published online June 20, 2022; DOI: https://doi.org/10.4266/acc.2021.01508

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Abstract PDF

Background
Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery.
Methods
This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020. Delirium was identified using the validated confusion assessment method for the ICU. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. Serums samples were collected within 12 hours of ICU admission and cytokine levels were measured.
Results
The following proinflammatory cytokines were elevated in our delirium population: tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, C-C motif ligand (CCL) 2, CCL3, C-X-C motif chemokine ligand (CXCL)1, CXCL10, IL-8, IL-1 receptor antagonist, and IL-10. Analysis of relative cytokine levels in those patients that developed delirium in the setting of sepsis, COVID-19, and recent surgery showed elevations of CCL2, CXCL10, and TNF-α in both the sepsis and COVID-19 group in comparison to the postsurgical population. In the postsurgical group, granulocyte colony-stimulating factor was elevated and CXCL10 was decreased relative to the opposing groups.
Conclusions
We identify several cytokines and precipitating factors known to be associated with delirium. However, our study suggests that the cytokine profile associated with delirium is variable and contingent upon delirium precipitating factors.

Citations

Citations to this article as recorded by

Sleep fragmentation, impaired glymphatic clearance, and long-term cognitive impairment after critical illness
Fawaz Alshammari, Samantha A. Keil, Mary Elizabeth Wilcox
Critical Care Science.2026;[Epub] CrossRef
Neurological Complications in Intensive Care Units: From Delirium to Long-Term Cognitive Dysfunction—A Narrative Review
Mateusz Szczupak, Jacek Kobak, Jolanta Wierzchowska, Amelia Dąbrowska, Wioletta Mędrzycka-Dąbrowska, Sabina Krupa-Nurcek
Journal of Clinical Medicine.2026; 15(7): 2478. CrossRef
Postoperative Delirium After Cardiac Surgery: Psychiatric Vulnerability, Biological Mechanisms, and Prevention Strategies
Vasileios Leivaditis, Anastasios Sepetis, Francesk Mulita, Athanasios Papatriantafyllou, Sofoklis Mitsos, Periklis Tomos, Konstantinos Grapatsas, Ejona Shaska, Elias Liolis, Efstratios Koletsis, Nikolaos Baikoussis
Medical Sciences.2026; 14(2): 176. CrossRef
Blood-based biomarkers and delirium in critically ill adults in the ICU: a systematic review
Julie Kathrine Ryberg Sankel, Naia Bech Cranø, Pär Ingemar Johansson, Lars Peter Kloster Andersen
Intensive Care Medicine Experimental.2026;[Epub] CrossRef
Decoding the delirium proteome: linking clinical vulnerabilities to acute brain dysfunction
Xiaoxiao Wang, Kaixi Liu, Xiangyang Guo, Nan Li, Zhengqian Li, Lewis A Lipsitz
The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences.2026;[Epub] CrossRef
Post-liver transplantation delirium: Pathogenesis, risk factors, clinical management, and future directions
Kai Wang, Heng Cui, Yudong Zhang, Mingmei Jiang, Qingxiang Xu, Hongrang Chen
Liver Transplantation.2026;[Epub] CrossRef
Postoperative sepsis-associated neurocognitive disorder: mechanisms, predictive strategies, and treatment approaches
Zijing Gao, Zhenyu Xu
Frontiers in Medicine.2025;[Epub] CrossRef
Association between albumin-corrected anion gap and delirium in acute pancreatitis: insights from the MIMIC-IV database
Yuanshuo Ge, Youran Ma, Peng Lv, Junhao Ren, Zhe Wang, Cheng Zhang
BMC Gastroenterology.2025;[Epub] CrossRef
Unravelling the complex inflammatory landscape of COVID-19 infection: a pathway to biomarkers identification in infection-associated delirium in the ICU
Tristan Born, Matthieu Perreau, Pierre-Paul Axisa, Craig Fenwick, Andrea Pinto, Nawfel Ben-Hamouda, Andrea O. Rossetti, Renaud Du Pasquier, Jean-Daniel Chiche, Raphaël Bernard-Valnet
Intensive Care Medicine Experimental.2025;[Epub] CrossRef
Incidence and Factors Associated With Confusional Syndrome (Delirium) in Hospitalized Patients With Severe SARS-CoV-2 Pneumonia in the Intensive Care Unit of a Latin American University Hospital
Felipe Botero-Rodriguez, Juan Sebastian Insignares Hernandez, Paola Garcia Martinez, Luis Carlos Triana Moreno, Williams Cervera Cadena, Juan Carlos Paredes Marin, Daniel Solarte-Bothe, Laura Muñoz Rodriguez, Juan David Junco, Juan Ricardo Cuenca, Gabriel
Revista Colombiana de Psiquiatría.2025;[Epub] CrossRef
Association of postoperative delirium with serum and cerebrospinal fluid proteomic profiles: a prospective cohort study in older hip fracture patients
Lucía Lozano-Vicario, Ángel Javier Muñoz-Vázquez, Robinson Ramírez-Vélez, Arkaitz Galbete-Jiménez, Joaquín Fernández-Irigoyen, Enrique Santamaría, Bernardo Abel Cedeno-Veloz, Fabricio Zambom-Ferraresi, Barbara C. Van Munster, José Ramón Ortiz-Gómez, Ángel
GeroScience.2024; 46(3): 3235. CrossRef
Association of peripheral B cells and delirium: combined single-cell sequencing and Mendelian randomization analysis
Siyou Tan, Sining Pan, Lai Wei, Wenyan Chen, Bingbing Pan, Gaoyin Kong, Jing Chen, Yubo Xie
Frontiers in Neurology.2024;[Epub] CrossRef
Delirium in the ICU: how much do we know? A narrative review
Si Bo Liu, Hong Yu Wu, Mei Li Duan, Rong Li Yang, Chen Hua Ji, Jin Jie Liu, Hongtao Zhao
Annals of Medicine.2024;[Epub] CrossRef
Brain injury biomarkers do not predict delirium in acutely ill older patients: a prospective cohort study
Júlio César Garcia de Alencar, Flávia Barreto Garcez, Agnes Araujo Sardinha Pinto, Lucas Oliveira Junqueira e Silva, Lucas de Moraes Soler, Shirley Steffany Muñoz Fernandez, Victor Van Vaisberg, Luz Marina Gomez Gomez, Sandra Maria Lima Ribeiro, Thiago Ju
Scientific Reports.2023;[Epub] CrossRef
Systemic interleukin-6 inhibition ameliorates acute neuropsychiatric phenotypes in a murine model of acute lung injury
Faizan Anwar, Nicklaus A. Sparrow, Mohammad Harun Rashid, Gena Guidry, Michael M. Gezalian, Eric J. Ley, Maya Koronyo-Hamaoui, Itai Danovitch, E. Wesley Ely, S. Ananth Karumanchi, Shouri Lahiri
Critical Care.2022;[Epub] CrossRef

Review Article

Basic Science and Research
Two-photon intravital imaging of leukocyte migration during inflammation in the respiratory system: Young Min Kim, Soi Jeong, Young Ho Choe, Young-Min Hyun; Acute Crit Care. 2019;34(2):101-107. Published online May 31, 2019; DOI: https://doi.org/10.4266/acc.2019.00542

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Abstract PDF

Two-photon intravital imaging is a powerful method by which researchers are able to directly observe biological phenomena in live organisms. Researchers in various biomedical research fields have applied two-photon imaging to a variety of target organs by utilizing this technology’s ability to penetrate to significant depths with minimal phototoxicity. The mouse respiratory system in inflammation models is a good example, as two-photon intravital imaging can provide insights as to how the immune system is activated in response to inflammation within the respiratory system. Inflammation models can be generated via influenza viral, bacterial, or lipopolysaccharide injection. To exteriorize the lungs or trachea, thoracotomy or tracheotomy is performed, respectively; the appropriate combination of inflammation induction and organ exposure is selected depending on the study purpose. On the other hand, visualizing the movement of leukocytes is also an important component; to this end, immune cell populations of interest are either labeled via the genetic attachment of fluorescent proteins or stained with antibodies or dyes. With the proper selection of methods at each step, twophoton intravital imaging can yield visual evidence regarding immune responses to inflammation.

Citations

Citations to this article as recorded by

CCR5-mediated dynamic maintenance of resident memory T cells in the respiratory tract
Tiange Shao, Jiacheng Yao, Shiyue Hou, Jianbin Wang, Hai Qi
Science China Life Sciences.2025; 68(8): 2431. CrossRef
Live-Cell Imaging Quantifies Changes in Function and Metabolic NADH Autofluorescence During Macrophage-Mediated Phagocytosis of Tumor Cells
Shelby N. Bess, Matthew J. Igoe, Timothy J. Muldoon
Immunological Investigations.2024; 53(2): 210. CrossRef
Regional specialization within the mammalian respiratory immune system
David P. Hoytema van Konijnenburg, Peter A. Nigrovic, Ivan Zanoni
Trends in Immunology.2024; 45(11): 871. CrossRef
Integration of immune cells in organs-on-chips: a tutorial
Lisette Van Os, Britta Engelhardt, Olivier T. Guenat
Frontiers in Bioengineering and Biotechnology.2023;[Epub] CrossRef
Intravital Imaging of Pulmonary Immune Response in Inflammation and Infection
Nazli Alizadeh-Tabrizi, Stefan Hall, Christian Lehmann
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Probe-based intravital microscopy: filling the gap between in vivo imaging and tissue sample microscopy in basic research and clinical applications
Katrien Van Dyck, Eliane Vanhoffelen, Jonas Yserbyt, Patrick Van Dijck, Marco Erreni, Sophie Hernot, Greetje Vande Velde
Journal of Physics: Photonics.2021; 3(3): 032003. CrossRef

Original Articles

Basic Science and Research
Anti-inflammatory Role of Mesenchymal Stem Cells in an Acute Lung Injury Mouse Model: Jin Won Huh, Won Young Kim, Yun Young Park, Chae-Man Lim, Younsuck Koh, Mi-Jung Kim, Sang-Bum Hong; Acute Crit Care. 2018;33(3):154-161. Published online August 31, 2018; DOI: https://doi.org/10.4266/acc.2018.00619

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Abstract PDF Supplementary Material

Background
Mesenchymal stem cells (MSCs) attenuate injury in various lung injury models through paracrine effects. We hypothesized that intratracheal transplantation of allogenic MSCs could attenuate lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, mediated by anti-inflammatory responses.
Methods
Six-week-old male mice were randomized to either the control or the ALI group. ALI was induced by intratracheal LPS instillation. Four hours after LPS instillation, MSCs or phosphate-buffered saline was randomly intratracheally administered. Neutrophil count and protein concentration in bronchoalveolar lavage fluid (BALF); lung histology; levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein-2; and the expression of proliferation cell nuclear antigen (PCNA), caspase-3, and caspase-9 were evaluated at 48 hours after injury.
Results
Treatment with MSCs attenuated lung injury in ALI mice by decreasing protein level and neutrophil recruitment into the BALF and improving the histologic change. MSCs also decreased the protein levels of proinflammatory cytokines including IL-1β, IL-6, and TNF-α, but had little effect on the protein expression of PCNA, caspase-3, and caspase-9.
Conclusions
Intratracheal injection of bone marrow-derived allogenic MSCs attenuates LPSinduced ALI via immunomodulatory effects.

Citations

Citations to this article as recorded by

Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model
Mahtab Golmohammadi, Mohammad Hasan Sheikhha, Fatemeh Ganji, Ali Shirani, Mahmood Barati, Seyed Mehdi Kalantar, Seyed Mohammad Amin Haramshahi, Nushin Karkuki Osguei, Ali Samadikuchaksaraei
Scientific Reports.2025;[Epub] CrossRef
Mesenchymal stem cell‐mediated mitochondrial transfer regulates the fate of B lymphocytes
Veronika Somova, Natalie Jaborova, Bianka Porubska, Daniel Vasek, Natalie Fikarova, Martin Prevorovsky, Zuzana Nahacka, Jiri Neuzil, Magdalena Krulova
European Journal of Clinical Investigation.2025;[Epub] CrossRef
Effect of Acute Lung Injury (ALI) Induced by Lipopolysaccharide (LPS) on the Pulmonary Pharmacokinetics of an Antibody
Shweta Jogi, Dhaval K. Shah
Antibodies.2025; 14(2): 33. CrossRef
The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats
Georgios Geropoulos, Kyriakos Psarras, Maria Papaioannou, Vasileios Geropoulos, Argyri Niti, Christina Nikolaidou, Georgios Koimtzis, Nikolaos Symeonidis, Efstathios T. Pavlidis, Georgios Koliakos, Theodoros E. Pavlidis, Ioannis Galanis
Journal of Personalized Medicine.2024; 14(1): 121. CrossRef
Mesenchymal stem cells suppress inflammation by downregulating interleukin-6 expression in intestinal perforation animal model
Eko Setiawan, Agung Putra, Dimas Irfan Nabih, Shafira Zahra Ovaditya, Rheza Rizaldy
Annals of Medicine & Surgery.2024; 86(10): 5776. CrossRef
Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice
Youngheon Park, Jimin Jang, Jooyeon Lee, Hyosin Baek, Jaehyun Park, Sang-Ryul Cha, Se Bi Lee, Sunghun Na, Jae-Woo Kwon, Seok-Ho Hong, Se-Ran Yang
International Journal of Stem Cells.2023; 16(2): 191. CrossRef
Mesenchymal stem cells and their derived exosomes to combat Covid–19
Maryam Yousefi Dehbidi, Nima Goodarzi, Mohammad H. Azhdari, Mohammad Doroudian
Reviews in Medical Virology.2022;[Epub] CrossRef
Stem Cell‐based therapies for COVID‐19‐related acute respiratory distress syndrome
Hoi Wa Ngai, Dae Hong Kim, Mohamed Hammad, Margarita Gutova, Karen Aboody, Christopher D. Cox
Journal of Cellular and Molecular Medicine.2022; 26(9): 2483. CrossRef
Development of a physiomimetic model of acute respiratory distress syndrome by using ECM hydrogels and organ-on-a-chip devices
Esther Marhuenda, Alvaro Villarino, Maria Narciso, Linda Elowsson, Isaac Almendros, Gunilla Westergren-Thorsson, Ramon Farré, Núria Gavara, Jorge Otero
Frontiers in Pharmacology.2022;[Epub] CrossRef
Advances in mesenchymal stromal cell therapy for acute lung injury/acute respiratory distress syndrome
Chang Liu, Kun Xiao, Lixin Xie
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Auxiliary role of mesenchymal stem cells as regenerative medicine soldiers to attenuate inflammatory processes of severe acute respiratory infections caused by COVID-19
Peyvand Parhizkar Roudsari, Sepideh Alavi-Moghadam, Moloud Payab, Forough Azam Sayahpour, Hamid Reza Aghayan, Parisa Goodarzi, Fereshteh Mohamadi-jahani, Bagher Larijani, Babak Arjmand
Cell and Tissue Banking.2020; 21(3): 405. CrossRef
The Role of MSC Therapy in Attenuating the Damaging Effects of the Cytokine Storm Induced by COVID-19 on the Heart and Cardiovascular System
Georgina M. Ellison-Hughes, Liam Colley, Katie A. O'Brien, Kirsty A. Roberts, Thomas A. Agbaedeng, Mark D. Ross
Frontiers in Cardiovascular Medicine.2020;[Epub] CrossRef

The Utility of Serum Procalcitonin Levels in the Management of Systemic Inflammatory Response Syndrome in the Emergency Department: Kyung Hye Park, Kang Hyun Lee, Kyoung Chul Cha, Hyun Kim, Sung Oh Hwang; Korean J Crit Care Med. 2012;27(1):10-15.; DOI: https://doi.org/10.4266/kjccm.2012.27.1.10

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Abstract PDF: BACKGROUND
The aim of this study was to investigate whether obtaining serum procalcitonin (PCT) levels in patients with systemic inflammatory response syndrome (SIRS) helps the differential diagnosis between sepsis and non-sepsis and predicts disease severity in the emergency department (ED).
METHODS
This prospective study enrolled 132 consecutive adult patients with SIRS who visited the ED. Serum C-reactive protein (CRP) levels and serum PCT levels were compared between sepsis and non-sepsis groups upon ED admission. Sequential Organ Failure Assessment (SOFA), Multiple Organ Dysfunction Score (MODS), and Acute Physiology and Chronic Health Evaluation (APACHE) III scores were calculated, and their correlations with CRP and PCT levels were evaluated. The PCT and CRP levels were assessed to predict sepsis in terms of comparing receiver operating characteristic (ROC) curves.
RESULTS
Eighty patients were included in the sepsis group. The levels of PCT and CRP in the sepsis group were significantly higher. In the sepsis group, the initial serum PCT correlated with the SOFA and MODS scores, and this also correlated in the non-sepsis group, but CRP did not. No differences were found when the PCT and CRP ROCs were compared.
CONCLUSIONS
Correlation between PCT and severity in the non-sepsis group is considered to be clinically meaningless because of low levels. Additionally, PCT levels had similar diagnostic value for sepsis as CRP levels. PCT is recommended for prediction of severity in sepsis patients in ED, but not for differential diagnosis between sepsis and non-sepsis.

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