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Cai L, Dou X, Dong W, Zou K, Zhang L, Hong H, Zhang X, Liu J, Tian D, Wu X, Zhang J. Serum RIPK1, Acute Lung Injury, and Outcomes in Severe Traumatic Brain Injury: A Multicenter Prospective Study. Ther Clin Risk Manag 2025; 21:385-405. [PMID: 40129517 PMCID: PMC11932039 DOI: 10.2147/tcrm.s502775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 03/06/2025] [Indexed: 03/26/2025] Open
Abstract
Background Receptor-interacting protein kinase-1 (RIPK1), a regulator of necroptosis, is involved in acute brain injury and acute lung injury (ALI). Here, serum RIPK1 levels were measured after severe traumatic brain injury (sTBI), with an endeavor to unveil its prognostic implications and mediation effects of ALI. Methods In this multicenter prospective study, serum RIPK1 levels were gauged in 100 healthy individuals and 158 sTBI patients in need of decompressive craniectomy for brain herniation. The collected materials encompassed the Glasgow Coma Scale (GCS), pupil enlargement status, basal cisternal shapes, ALI, etc. The extended Glasgow outcome scale (GOSE) was employed for estimating neurological impairments at posttraumatic 180-day mark. Multifactorial analytical methods were applied to assess relevancies. Results Patients, as opposed to controls, had markedly raised serum RIPK1 levels, with the even substantially higher levels in those with lower GCS scores, bilateral pupil enlargement or obliterated basal cisterns. Using restricted cubic spline, RIPK1 levels were linearly related to occurrent risks of the four outcome variables of interest, that is 180-day death, overall survival, poor prognosis (GOSE scores 1-4) and ALI. RIPK1 levels independently predicted these outcome variables. RIPK1 levels had noninteractional effects with age, sex, hypertension, diabetes, smoking and alcohol habits in terms of its association with these outcome variables. RIPK1 levels exhibited high discriminatory efficiency for these outcome variables under the receiver operating characteristic curve. RIPK1 levels, via partial mediation by ALI, were associated with death and poor prognosis of patients. Conclusion Elevated serum RIPK1 levels of patients with sTBI may be highly related to trauma severity, and risks of poor outcomes and ALI; and ALI partially explains the links between serum RIPK1 levels, death and poor prognosis, substantializing serum RIPK1 as a serological prognostic predictor of good prospect in sTBI.
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Affiliation(s)
- Liang Cai
- Department of Neurosurgery, The second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China
| | - Xianghong Dou
- Department of Neurology, Donghai County People’s Hospital, Lianyungang, Jiangsu, 222300, People’s Republic of China
| | - Wensheng Dong
- Department of Neurosurgery, The second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China
| | - Kangqin Zou
- Department of Neurosurgery, The second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China
| | - Lixin Zhang
- Department of Neurosurgery, The Hangzhou Ninth People’s Hospital, Hangzhou, Zhejiang, 311225, People’s Republic of China
| | - Huayong Hong
- Department of Neurosurgery, The Hangzhou Ninth People’s Hospital, Hangzhou, Zhejiang, 311225, People’s Republic of China
| | - Xiaole Zhang
- Department of Neurosurgery, The Hangzhou Ninth People’s Hospital, Hangzhou, Zhejiang, 311225, People’s Republic of China
| | - Jin Liu
- Department of Neurosurgery, The Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Da Tian
- Department of Neurosurgery, The Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Xiaoyu Wu
- Department of Neurosurgery, The Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Jianhua Zhang
- Department of Neurosurgery, The second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China
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Ma W, Tang S, Yao P, Zhou T, Niu Q, Liu P, Tang S, Chen Y, Gan L, Cao Y. Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies. Signal Transduct Target Ther 2025; 10:75. [PMID: 40050633 PMCID: PMC11885678 DOI: 10.1038/s41392-025-02127-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 12/27/2024] [Accepted: 12/27/2024] [Indexed: 03/09/2025] Open
Abstract
In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases. Over the past seven decades, our understanding of the pathology and clinical characteristics of ARDS has evolved significantly, yet it remains an area of active research and discovery. ARDS is highly heterogeneous, including diverse pathological causes, clinical presentations, and treatment responses, presenting a significant challenge for clinicians and researchers. In this review, we comprehensively discuss the latest advancements in ARDS research, focusing on its heterogeneity, pathophysiological mechanisms, and emerging therapeutic approaches, such as cellular therapy, immunotherapy, and targeted therapy. Moreover, we also examine the pathological characteristics of COVID-19-related ARDS and discuss the corresponding therapeutic approaches. In the face of challenges posed by ARDS heterogeneity, recent advancements offer hope for improved patient outcomes. Further research is essential to translate these findings into effective clinical interventions and personalized treatment approaches for ARDS, ultimately leading to better outcomes for patients suffering from ARDS.
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Affiliation(s)
- Wen Ma
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
- Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, China
| | - Songling Tang
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Peng Yao
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Tingyuan Zhou
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
- Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, China
| | - Qingsheng Niu
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Peng Liu
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Shiyuan Tang
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yao Chen
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lu Gan
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.
| | - Yu Cao
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.
- Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, China.
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An L, Shao R, Hang C, Wang X, Zhang L, Cui H, Yu J, Shan Z, Tang Z. Monocyte programmed death-ligand 1 upregulation in early post-out-of-hospital cardiac arrest is associated with increased risk of acute respiratory distress syndrome. Resusc Plus 2024; 20:100822. [PMID: 39559732 PMCID: PMC11570934 DOI: 10.1016/j.resplu.2024.100822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 10/28/2024] [Accepted: 10/28/2024] [Indexed: 11/20/2024] Open
Abstract
Background Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Acute respiratory distress syndrome (ARDS) is a common condition in OHCA patients. We investigated the relationship between the expression of programmed death-1 (PD-1) related molecules and the development and prognosis of ARDS. Methods Between January 2021 and December 2023, post-resuscitated patients were screened for eligibility in the study. PD-1 related molecules expression was measured by flow cytometry at 48 h of admission in patients with OHCA. The prognostic variables were the development of ARDS during hospitalization and the 28-day patient mortality rate. We analyzed the relationship between the expression of PD-1-related molecules and the development of secondary ARDS in OHCA patients, and assessed the correlation of this expression with the prognosis of ARDS patients. Results In total, 107 consecutive OHCA patients were enrolled in this study. The median age of the enrolled patients was 60 years, with an age range of 53 to 67 years, and 71 % were male. Among the cardiac arrest patients, 44.8 % had a cardiac etiology, 30.8 % were witnessed, 17.8 % received bystander CPR, and 66.4 % had an initial rhythm of asystole. Our results showed that only monocyte ligand programmed death ligand-1 (PD-L1) expression was significantly elevated in the ARDS group of OHCA patients (P < 0.001). Among patients with ARDS, the expression of PD-L1 on monocytes in non-survivors was significantly higher than in survivors (P < 0.05). The Receiver operating characteristic curves analysis demonstrates that monocyte PD-L1 expression has predictive potential for the development and prognosis of ARDS. Multivariate logistic regression analysis showed that monocyte PD-L1 expression was an independent predictor of mortality in OHCA patients with ARDS. Conclusions This study indicates that patients with increased PD-L1 on monocytes after OHCA may be more likely to develop ARDS. The expression of PD-L1 on monocytes was an independent predictive factor for the incidence of ARDS and mortality rate in OHCA patients.
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Affiliation(s)
- Le An
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Rui Shao
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Chenchen Hang
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Xingsheng Wang
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Luying Zhang
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Hao Cui
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Jingfei Yu
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Zhenyu Shan
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Ziren Tang
- Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
- Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing 100020, China
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Cave C, Samano D, Sharma AM, Dickinson J, Salomon J, Mahapatra S. Acute respiratory distress syndrome: A review of ARDS across the life course. J Investig Med 2024; 72:798-818. [PMID: 39092841 DOI: 10.1177/10815589241270612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Acute respiratory distress syndrome (ARDS) is a multifactorial, inflammatory lung disease with significant morbidity and mortality that predominantly requires supportive care in its management. Although initially described in adult patients, the diagnostic definitions for ARDS have evolved over time to accurately describe this disease process in pediatric and, more recently, neonatal patients. The management of ARDS in each age demographic has converged in the application of lung-protective ventilatory strategies to mitigate the primary disease process and prevent its exacerbation by limiting ventilator-induced lung injury. However, differences arise in the preferred ventilatory strategies or adjunctive pulmonary therapies used to mitigate each type of ARDS. In this review, we compare and contrast the epidemiology, common etiologies, pathophysiology, diagnostic criteria, and outcomes of ARDS across the lifespan. Additionally, we discuss in detail the different management strategies used for each subtype of ARDS and spotlight how these strategies were applied to mitigate poor outcomes during the COVID-19 pandemic. This review is geared toward both clinicians and clinician-scientists as it not only summarizes the latest information on disease pathogenesis and patient management in ARDS across the lifespan but also highlights knowledge gaps for further investigative efforts. We conclude by projecting how future studies can fill these gaps in research and what improvements may be envisioned in the management of NARDS and PARDS based on the current breadth of literature on adult ARDS treatment strategies.
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Affiliation(s)
- Caleb Cave
- Division of Neonatology, and Division of Pulmonology, Department of Pediatrics, Children's Hospital and Medical Center, Omaha, University of Nebraska Medical Center, Omaha, NE, USA
| | - Dannielle Samano
- Division of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Abhineet M Sharma
- Division of Neonatology, and Division of Pulmonology, Department of Pediatrics, Children's Hospital and Medical Center, Omaha, University of Nebraska Medical Center, Omaha, NE, USA
| | - John Dickinson
- Division of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Jeffrey Salomon
- Division of Critical Care Medicine, Department of Pediatrics, Children's Hospital and Medical Center, Omaha, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sidharth Mahapatra
- Division of Critical Care Medicine, Department of Pediatrics, Children's Hospital and Medical Center, Omaha, University of Nebraska Medical Center, Omaha, NE, USA
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Wick KD, Ware LB, Matthay MA. Acute respiratory distress syndrome. BMJ 2024; 387:e076612. [PMID: 39467606 DOI: 10.1136/bmj-2023-076612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/30/2024]
Abstract
The understanding of acute respiratory distress syndrome (ARDS) has evolved greatly since it was first described in a 1967 case series, with several subsequent updates to the definition of the syndrome. Basic science advances and clinical trials have provided insight into the mechanisms of lung injury in ARDS and led to reduced mortality through comprehensive critical care interventions. This review summarizes the current understanding of the epidemiology, pathophysiology, and management of ARDS. Key highlights include a recommended new global definition of ARDS and updated guidelines for managing ARDS on a backbone of established interventions such as low tidal volume ventilation, prone positioning, and a conservative fluid strategy. Future priorities for investigation of ARDS are also highlighted.
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Affiliation(s)
- Katherine D Wick
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Lorraine B Ware
- Departments of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael A Matthay
- Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, CA, USA
- Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA
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Tunstead C, Volkova E, Dunbar H, Hawthorne IJ, Bell A, Crowe L, Masterson JC, Dos Santos CC, McNicholas B, Laffey JG, English K. The ARDS microenvironment enhances MSC-induced repair via VEGF in experimental acute lung inflammation. Mol Ther 2024; 32:3422-3432. [PMID: 39108095 PMCID: PMC11489539 DOI: 10.1016/j.ymthe.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 06/10/2024] [Accepted: 08/02/2024] [Indexed: 08/19/2024] Open
Abstract
Clinical trials investigating the potential of mesenchymal stromal cells (MSCs) for the treatment of inflammatory diseases, such as acute respiratory distress syndrome (ARDS), have been disappointing, with less than 50% of patients responding to treatment. Licensed MSCs show enhanced therapeutic efficacy in response to cytokine-mediated activation signals. There are two distinct sub-phenotypes of ARDS: hypo- and hyper-inflammatory. We hypothesized that pre-licensing MSCs in a hyper-inflammatory ARDS environment would enhance their therapeutic efficacy in acute lung inflammation (ALI). Serum samples from patients with ARDS were segregated into hypo- and hyper-inflammatory categories based on interleukin (IL)-6 levels. MSCs were licensed with pooled serum from patients with hypo- or hyper-inflammatory ARDS or healthy serum controls. Our findings show that hyper-inflammatory ARDS pre-licensed MSC conditioned medium (MSC-CMHyper) led to a significant enrichment in tight junction expression and enhanced barrier integrity in lung epithelial cells in vitro and in vivo in a vascular endothelial growth factor (VEGF)-dependent manner. Importantly, while both MSC-CMHypo and MSC-CMHyper significantly reduced IL-6 and tumor necrosis factor alpha (TNF-α) levels in the bronchoalveolar lavage fluid (BALF) of lipopolysaccharide (LPS)-induced ALI mice, only MSC-CMHyper significantly reduced lung permeability and overall clinical outcomes including weight loss and clinical score. Thus, the hypo- and hyper-inflammatory ARDS environments may differentially influence MSC cytoprotective and immunomodulatory functions.
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Affiliation(s)
- Courteney Tunstead
- Cellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland
| | - Evelina Volkova
- Cellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland
| | - Hazel Dunbar
- Cellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland
| | - Ian J Hawthorne
- Cellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland
| | - Alison Bell
- Anesthesia and Intensive Care Medicine, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland; Anesthesia and Intensive Care Medicine, Galway University Hospitals, Saolta University Hospitals Groups, Galway, Ireland
| | - Louise Crowe
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland; Allergy, Inflammation & Remodelling Research Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland
| | - Joanne C Masterson
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland; Allergy, Inflammation & Remodelling Research Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland
| | - Claudia C Dos Santos
- Keenan Research Centre for Biomedical Research, St. Michael's Hospital, Toronto, ON, Canada
| | - Bairbre McNicholas
- Anesthesia and Intensive Care Medicine, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland; Anesthesia and Intensive Care Medicine, Galway University Hospitals, Saolta University Hospitals Groups, Galway, Ireland
| | - John G Laffey
- Anesthesia and Intensive Care Medicine, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland; Anesthesia and Intensive Care Medicine, Galway University Hospitals, Saolta University Hospitals Groups, Galway, Ireland
| | - Karen English
- Cellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland.
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Lin S, Yan J, Wang W, Luo L. STAT3-Mediated Ferroptosis is Involved in Sepsis-Associated Acute Respiratory Distress Syndrome. Inflammation 2024; 47:1204-1219. [PMID: 38236387 DOI: 10.1007/s10753-024-01970-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 01/04/2024] [Accepted: 01/06/2024] [Indexed: 01/19/2024]
Abstract
Sepsis-induced acute respiratory distress syndrome (ARDS) poses a grave danger to life, resulting from sepsis-induced multi-organ failure. Although ferroptosis, a form of iron-dependent lipid peroxidative cell death, has been associated with sepsis-induced ARDS, the specific mechanisms are not fully understood. In this study, we utilized WGCNA, PPI, friends analysis, and six machine learning techniques (Lasso, SVM, RFB, XGBoost, AdaBoost, and LightGBM) to pinpoint STAT3 as a potential diagnostic marker. A significant increase in monocyte and neutrophil levels was observed in patients with sepsis-induced ARDS, as revealed by immune infiltration analyses, when compared to controls. Moreover, there was a positive correlation between STAT3 expression and the level of infiltration. Single-cell analysis uncovered a notable disparity in B-cell expression between sepsis and sepsis-induced ARDS. Furthermore, in vitro experiments using LPS-treated human bronchial epithelial cells (BEAS-2B) and THP1 cells demonstrated a significant increase in STAT3 phosphorylation expression. Additionally, the inhibition of STAT3 phosphorylation by Stattic effectively prevented LPS-induced ferroptosis in both BEAS-2B and THP1 cells. This indicates that the activation of STAT3 phosphorylation promotes ferroptosis in human bronchial epithelial cells in response to LPS. In summary, this research has discovered and confirmed STAT3 as a potential biomarker for the diagnosis and treatment of sepsis-induced ARDS.
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Affiliation(s)
- Shanshan Lin
- The Marine Biomedical Research Institute, The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Jiayu Yan
- The Marine Biomedical Research Institute, The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Wenjian Wang
- The Marine Biomedical Research Institute, The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China
| | - Lianxiang Luo
- The Marine Biomedical Research Institute, The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
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Han J, Zhang X, Cai M, Tian F, Xu Y, Chen H, He W, Zhang J, Tian H. TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis. Chin Med J (Engl) 2024; 137:1592-1602. [PMID: 38644799 PMCID: PMC11230828 DOI: 10.1097/cm9.0000000000003105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Indexed: 04/23/2024] Open
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI. METHODS TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t -test. RESULTS TSPO- KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO -KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO -KO cells. CONCLUSION TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.
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Affiliation(s)
- Jingyi Han
- Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
| | - Xue Zhang
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
| | - Menghua Cai
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
- Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy, Changzhou, Jiangsu 213000, China
| | - Feng Tian
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
| | - Yi Xu
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
- Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy, Changzhou, Jiangsu 213000, China
| | - Hui Chen
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
- Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy, Changzhou, Jiangsu 213000, China
- Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Wei He
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
- Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy, Changzhou, Jiangsu 213000, China
| | - Jianmin Zhang
- CAMS Key Laboratory of T Cell and Immunotherapy, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, China
- Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy, Changzhou, Jiangsu 213000, China
- Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Hui Tian
- Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
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Kaimakamis E, Kotoulas S, Tzimou M, Karachristos C, Giannaki C, Kilintzis V, Stefanopoulos L, Chatzis E, Beredimas N, Rocha B, Pessoa D, Paiva RP, Maglaveras N, Bitzani M. Back to the future: the novel art of digital auscultation applied in a prospective observational study of critically ill Covid-19 patients. Pneumonia (Nathan) 2024; 16:9. [PMID: 38835101 DOI: 10.1186/s41479-024-00131-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 03/27/2024] [Indexed: 06/06/2024] Open
Abstract
BACKGROUND The Covid-19 pandemic has caused immense pressure on Intensive Care Units (ICU). In patients with severe ARDS due to Covid-19, respiratory mechanics are important for determining the severity of lung damage. Lung auscultation could not be used during the pandemic despite its merit. The main objective of this study was to investigate associations between lung auscultatory sound features and lung mechanical properties, length of stay (LOS) and survival, in adults with severe Covid-19 ARDS. METHODS Consecutive patients admitted to a large ICU between 2020 and 2021 (n = 173) were included. Digital stethoscopes obtained auscultatory sounds and stored them in an on-line database for replay and further processing using advanced AI techniques. Correlation and regression analysis explored relationships between digital auscultation findings and lung mechanics or the ICU outcome. The resulting annotated lung sounds database is also publicly available as supplementary material. RESULTS The presence of squawks was associated with the ICU LOS, outcome and 90-day mortality. Other features (age, SOFA score & oxygenation index upon admission, minimum crackle entropy) had significant impact on outcome. Additional features affecting the 90-d survival were age and mean crackle entropy. Multivariate logistic regression showed that survival was affected by age, baseline SOFA, baseline oxygenation index and minimum crackle entropy. CONCLUSIONS Respiratory mechanics were associated with various adventitious sounds, whereas the lung sound analytics and the presence of certain adventitious sounds correlated with the ICU outcome and the 90-d survival. Spectral features of crackles sounds can serve as prognostic factors for survival, highlighting the importance of digital auscultation.
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Affiliation(s)
- Evangelos Kaimakamis
- 1st Intensive Care Unit, "G. Papanikolaou" General Hospital, Exochi Thessalonikis, 57010, Greece.
| | - Serafeim Kotoulas
- 1st Intensive Care Unit, "G. Papanikolaou" General Hospital, Exochi Thessalonikis, 57010, Greece
| | - Myrto Tzimou
- 1st Intensive Care Unit, "G. Papanikolaou" General Hospital, Exochi Thessalonikis, 57010, Greece
| | - Christos Karachristos
- 1st Intensive Care Unit, "G. Papanikolaou" General Hospital, Exochi Thessalonikis, 57010, Greece
| | - Chrysavgi Giannaki
- 1st Intensive Care Unit, "G. Papanikolaou" General Hospital, Exochi Thessalonikis, 57010, Greece
| | - Vassileios Kilintzis
- Lab of Computing, Medical Informatics and Biomedical Imaging Technologies, The Medical School, Aristotle University, Thessaloniki, Greece
- 2nd Department of Obstetrics and Gynecology, The Medical School, Thessaloniki, 54124, Greece
| | - Leandros Stefanopoulos
- Lab of Computing, Medical Informatics and Biomedical Imaging Technologies, The Medical School, Aristotle University, Thessaloniki, Greece
- 2nd Department of Obstetrics and Gynecology, The Medical School, Thessaloniki, 54124, Greece
| | - Evangelos Chatzis
- Lab of Computing, Medical Informatics and Biomedical Imaging Technologies, The Medical School, Aristotle University, Thessaloniki, Greece
| | - Nikolaos Beredimas
- Lab of Computing, Medical Informatics and Biomedical Imaging Technologies, The Medical School, Aristotle University, Thessaloniki, Greece
| | - Bruno Rocha
- Centre for Informatics and Systems of the University of Coimbra, Department of Informatics Engineering, University of Coimbra, LASI, Coimbra, Portugal
| | - Diogo Pessoa
- Centre for Informatics and Systems of the University of Coimbra, Department of Informatics Engineering, University of Coimbra, LASI, Coimbra, Portugal
| | - Rui Pedro Paiva
- Centre for Informatics and Systems of the University of Coimbra, Department of Informatics Engineering, University of Coimbra, LASI, Coimbra, Portugal
| | - Nicos Maglaveras
- 2nd Department of Obstetrics and Gynecology, The Medical School, Thessaloniki, 54124, Greece
| | - Militsa Bitzani
- 1st Intensive Care Unit, "G. Papanikolaou" General Hospital, Exochi Thessalonikis, 57010, Greece
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10
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Dong J, Liu W, Liu W, Wen Y, Liu Q, Wang H, Xiang G, Liu Y, Hao H. Acute lung injury: a view from the perspective of necroptosis. Inflamm Res 2024; 73:997-1018. [PMID: 38615296 DOI: 10.1007/s00011-024-01879-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/23/2024] [Accepted: 03/31/2024] [Indexed: 04/15/2024] Open
Abstract
BACKGROUND ALI/ARDS is a syndrome of acute onset characterized by progressive hypoxemia and noncardiogenic pulmonary edema as the primary clinical manifestations. Necroptosis is a form of programmed cell necrosis that is precisely regulated by molecular signals. This process is characterized by organelle swelling and membrane rupture, is highly immunogenic, involves extensive crosstalk with various cellular stress mechanisms, and is significantly implicated in the onset and progression of ALI/ARDS. METHODS The current body of literature on necroptosis and ALI/ARDS was thoroughly reviewed. Initially, an overview of the molecular mechanism of necroptosis was provided, followed by an examination of its interactions with apoptosis, pyroptosis, autophagy, ferroptosis, PANOptosis, and NETosis. Subsequently, the involvement of necroptosis in various stages of ALI/ARDS progression was delineated. Lastly, drugs targeting necroptosis, biomarkers, and current obstacles were presented. CONCLUSION Necroptosis plays an important role in the progression of ALI/ARDS. However, since ALI/ARDS is a clinical syndrome caused by a variety of mechanisms, we emphasize that while focusing on necroptosis, it may be more beneficial to treat ALI/ARDS by collaborating with other mechanisms.
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Affiliation(s)
- Jinyan Dong
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China
| | - Weihong Liu
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China
| | - Wenli Liu
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China
| | - Yuqi Wen
- Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China
| | - Qingkuo Liu
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China
| | - Hongtao Wang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China
| | - Guohan Xiang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China
| | - Yang Liu
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China.
| | - Hao Hao
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, China.
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11
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Ziaka M, Exadaktylos A. Exploring the lung-gut direction of the gut-lung axis in patients with ARDS. Crit Care 2024; 28:179. [PMID: 38802959 PMCID: PMC11131229 DOI: 10.1186/s13054-024-04966-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/22/2024] [Indexed: 05/29/2024] Open
Abstract
Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements in treatment perspectives, ARDS still carries a high mortality rate, often due to systemic inflammatory responses leading to multiple organ dysfunction syndrome (MODS). Indeed, the deterioration and associated mortality in patients with acute lung injury (LI)/ARDS is believed to originate alongside respiratory failure mainly from the involvement of extrapulmonary organs, a consequence of the complex interaction between initial inflammatory cascades related to the primary event and ongoing mechanical ventilation-induced injury resulting in multiple organ failure (MOF) and potentially death. Even though recent research has increasingly highlighted the role of the gastrointestinal tract in this process, the pathophysiology of gut dysfunction in patients with ARDS remains mainly underexplored. This review aims to elucidate the complex interplay between lung and gut in patients with LI/ARDS. We will examine various factors, including systemic inflammation, epithelial barrier dysfunction, the effects of mechanical ventilation (MV), hypercapnia, and gut dysbiosis. Understanding these factors and their interaction may provide valuable insights into the pathophysiology of ARDS and potential therapeutic strategies to improve patient outcomes.
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Affiliation(s)
- Mairi Ziaka
- Clinic of Geriatric Medicine, Center of Geriatric Medicine and Rehabilitation, Kantonsspital Baselland, Bruderholz, Switzerland.
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
| | - Aristomenis Exadaktylos
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
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12
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Cui XQ, Zhang LW, Zhao P, Feng JJ. Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation. World J Clin Cases 2024; 12:2542-2550. [PMID: 38817218 PMCID: PMC11135438 DOI: 10.12998/wjcc.v12.i15.2542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/24/2024] [Accepted: 03/28/2024] [Indexed: 05/14/2024] Open
Abstract
BACKGROUND The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants. Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4''-O-isovaleryltransferase gene (ist) from streptomyces thermotoleran. Carrimycin has good antibacterial and antiviral effects. However, no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia (SP) after solid organ transplantation. AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment. METHODS In March 2022, ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022. When the condition was critical and difficult to control with other drugs, carrimycin was administered. These ten patients' clinical features and treatment protocols were retrospectively analyzed, and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated. RESULTS All ten patients were included in the analysis. Regarding etiological agent detection, there were three cases of fungal pneumonia, two cases of bacterial pneumonia, two cases of Pneumocystis pneumonia, and three cases of mixed infections. After treatment with carrimycin, the disease in seven patients significantly improved, the course of the disease was significantly shortened, fever was quickly controlled, chest computed tomography was significantly improved, and oxygenation was significantly improved. Finally, the patients were discharged after curing. One patient died of acute respiratory distress syndrome, and two patients discontinued treatment. CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.
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Affiliation(s)
- Xian-Quan Cui
- Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Lu-Wei Zhang
- Department of Blood Purification, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Peng Zhao
- Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Jing-Jing Feng
- Department of Blood Purification, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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13
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Chiumello D, Fioccola A. Recent advances in cardiorespiratory monitoring in acute respiratory distress syndrome patients. J Intensive Care 2024; 12:17. [PMID: 38706001 PMCID: PMC11070081 DOI: 10.1186/s40560-024-00727-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 04/04/2024] [Indexed: 05/07/2024] Open
Abstract
BACKGROUND Recent advances on cardiorespiratory monitoring applied in ARDS patients undergoing invasive mechanical ventilation and noninvasive ventilatory support are available in the literature and may have potential prognostic implication in ARDS treatment. MAIN BODY The measurement of oxygen saturation by pulse oximetry is a valid, low-cost, noninvasive alternative for assessing arterial oxygenation. Caution must be taken in patients with darker skin pigmentation, who may experience a greater incidence of occult hypoxemia. Dead space surrogates, which are easy to calculate, have important prognostic implications. The mechanical power, which can be automatically computed by intensive care ventilators, is an important parameter correlated with ventilator-induced lung injury and outcome. In patients undergoing noninvasive ventilatory support, the use of esophageal pressure can measure inspiratory effort, avoiding possible delays in endotracheal intubation. Fluid responsiveness can also be evaluated using dynamic indices in patients ventilated at low tidal volumes (< 8 mL/kg). In patients ventilated at high levels of positive end expiratory pressure (PEEP), the PEEP test represents a valid alternative to passive leg raising. There is growing evidence on alternative parameters for evaluating fluid responsiveness, such as central venous oxygen saturation variations, inferior vena cava diameter variations and capillary refill time. CONCLUSION Careful cardiorespiratory monitoring in patients affected by ARDS is crucial to improve prognosis and to tailor treatment via mechanical ventilatory support.
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Affiliation(s)
- Davide Chiumello
- Department of Health Sciences, University of Milan, Milan, Italy.
- Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital Milan, Via Di Rudinì 9, Milan, Italy.
- Coordinated Research Center on Respiratory Failure, University of Milan, Milan, Italy.
| | - Antonio Fioccola
- Department of Health Sciences, University of Milan, Milan, Italy
- Department of Health Sciences, University of Florence, Florence, Italy
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14
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Gramstad LE. [About the Norwegian translation of ‘acute respiratory distress syndrome’]. TIDSSKRIFT FOR DEN NORSKE LEGEFORENING 2024; 144:24-0134. [PMID: 38651713 DOI: 10.4045/tidsskr.24.0134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2024] Open
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15
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Dicle Y, Aydin E, Seker U. Investigation of the protective activity of baicalein on the lungs via regulation of various cellular responses in rats exposed to experimental sepsis. Toxicol Res (Camb) 2024; 13:tfad112. [PMID: 38178997 PMCID: PMC10762668 DOI: 10.1093/toxres/tfad112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 10/27/2023] [Accepted: 11/20/2023] [Indexed: 01/06/2024] Open
Abstract
Backgrounds In the present study, a cecal ligation and puncture (CLP)-induced experimental sepsis rat model was used to explore the effects of baicalein on inflammatory cytokine levels and oxidative stress as well as the possible regulatory role of nuclear factor-kappa B (NF-κB). Methods For that purpose, 42 Wistar albino rats were equally divided into control, sham, sepsis, B50 + S, B100 + S, S + B50, and S + B100 groups. The B50 + S and B100 + S groups received baicalein before the induction of sepsis, while the S + B50 and S + B100 groups received baicalein afterwards. Experimental sepsis in related groups is generated through ligation of cecum and a puncture in cecal wall. Serum samples were used for tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) analyses, and tissue Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione (GSH), IL-6, and NF-κB levels were measured. Results Compared to the control group, there were significantly increases in the serum TNF-α, IL-6, tissue MDA, and NF-κB levels and decreases in the tissue SOD and GSH levels in the septic group (P < 0.05). Compared to the septic group, inflammation and oxidative stress were reduced in the baicalein-treated groups. Although all of the pre- and post-treatment protocols alleviated inflammation and oxidative stress to varying degrees, pre-treatment with 100 mg/kg was the most successful. Conclusions Findings of this study indicated that baicalein has the potential to reduce sepsis-related oxidative stress and inflammation in the lungs and that pathological outcomes could be regulated via NF-κB transcription factor activity.
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Affiliation(s)
- Yalcin Dicle
- Department of Medical Microbiology, Faculty of Medicine, Mardin Artuklu University, 47200, Mardin, Türkiye
| | - Elif Aydin
- Tavsanli Vocational School of Health Services, Kutahya Health Sciences University, 43300, Kutahya, Türkiye
| | - Ugur Seker
- Department of Histology and Embryology, Faculty of Medicine, Mardin Artuklu University, 47200, Mardin, Türkiye
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16
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Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, Calfee CS, Combes A, Daniel BM, Ferguson ND, Gong MN, Gotts JE, Herridge MS, Laffey JG, Liu KD, Machado FR, Martin TR, McAuley DF, Mercat A, Moss M, Mularski RA, Pesenti A, Qiu H, Ramakrishnan N, Ranieri VM, Riviello ED, Rubin E, Slutsky AS, Thompson BT, Twagirumugabe T, Ware LB, Wick KD. A New Global Definition of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2024; 209:37-47. [PMID: 37487152 PMCID: PMC10870872 DOI: 10.1164/rccm.202303-0558ws] [Citation(s) in RCA: 234] [Impact Index Per Article: 234.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 07/24/2023] [Indexed: 07/26/2023] Open
Abstract
Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.
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Affiliation(s)
- Michael A. Matthay
- Department of Medicine
- Department of Anesthesia
- Cardiovascular Research Institute, and
| | - Yaseen Arabi
- King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | | | - Gordon Bernard
- Division of Allergy, Pulmonary, and Critical Care Medicine, Center for Lung Research, and
| | | | - Laurent J. Brochard
- Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Carolyn S. Calfee
- Department of Medicine
- Department of Anesthesia
- Cardiovascular Research Institute, and
| | - Alain Combes
- Médecine Intensive – Réanimation, Sorbonne Université, APHP Hôpital Pitié-Salpêtrière, Paris, France
| | - Brian M. Daniel
- Respiratory Therapy, University of California, San Francisco, San Francisco, California
| | - Niall D. Ferguson
- Interdepartmental Division of Critical Care Medicine and
- Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Michelle N. Gong
- Department of Medicine, Montefiore Medical Center, Bronx, New York
| | - Jeffrey E. Gotts
- Kaiser Permanente San Francisco Medical Center, San Francisco, California
| | | | - John G. Laffey
- Anesthesia, University Hospital Galway, University of Galway, Galway, Ireland
| | | | - Flavia R. Machado
- Intensive Care Department, Hospital São Paulo, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Thomas R. Martin
- Department of Medicine, University of Washington, Seattle, Washington
| | - Danny F. McAuley
- Centre for Experimental Medicine, Queen’s University Belfast, Belfast, United Kingdom
| | - Alain Mercat
- Medical ICU, Angers University Hospital, Angers, France
| | - Marc Moss
- Department of Medicine, University of Colorado Denver, Aurora, Colorado
| | | | - Antonio Pesenti
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Haibo Qiu
- Critical Care Medicine, Zhongda Hospital, Nanjing, China
| | | | - V. Marco Ranieri
- Emergency and Intensive Care Medicine, Alma Mater Studorium University of Bologna, Bologna, Italy
| | - Elisabeth D. Riviello
- Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | | | - Arthur S. Slutsky
- Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
| | - B. Taylor Thompson
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Theogene Twagirumugabe
- Department of Anesthesia, Critical Care, and Emergency Medicine, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda; and
| | - Lorraine B. Ware
- Department of Medicine, Vanderbilt University, Nashville, Tennessee
| | - Katherine D. Wick
- Department of Medicine, University of California, Davis, Davis, California
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17
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Mehri A, Sotoodeh Ghorbani S, Farhadi-Babadi K, Rahimi E, Barati Z, Taherpour N, Izadi N, Shahbazi F, Mokhayeri Y, Seifi A, Fallah S, Feyzi R, Etemed K, Hashemi Nazari SS. Risk Factors Associated with Severity and Death from COVID-19 in Iran: A Systematic Review and Meta-Analysis Study. J Intensive Care Med 2023; 38:825-837. [PMID: 36976873 PMCID: PMC10051011 DOI: 10.1177/08850666231166344] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 03/09/2023] [Accepted: 03/03/2023] [Indexed: 03/30/2023]
Abstract
Objectives: This study aims to investigate the risk factors associated with severity and death from COVID-19 through a systematic review and meta-analysis of the published documents in Iran. Methods: A systematic search was performed based on all articles indexed in Scopus, Embase, Web of Science (WOS), PubMed, and Google Scholar in English and Scientific Information Database (SID) and Iranian Research Institute for Information Science and Technology (IRA)NDOC indexes in Persian. To assess quality, we used the Newcastle Ottawa Scale. Publication bias was assessed using Egger's tests. Forest plots were used for a graphical description of the results. We used HRs, and ORs reported for the association between risk factors and COVID-19 severity and death. Results: Sixty-nine studies were included in the meta-analysis, of which 62 and 13 had assessed risk factors for death and severity, respectively. The results showed a significant association between death from COVID-19 and age, male gender, diabetes, hypertension, cardiovascular disease (CVD), cerebrovascular disease, chronic kidney disease (CKD), Headache, and Dyspnea. We observed a significant association between increased white blood cell (WBC), decreased Lymphocyte, increased blood urea nitrogen (BUN), increased creatinine, vitamin D deficiency, and death from COVID-19. There was only a significant relationship between CVD and disease severity. Conclusion: It is recommended that the predictive risk factors of COVID-19 severity and death mentioned in this study to be used for therapeutic and health interventions, to update clinical guidelines and determine patients' prognoses.
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Affiliation(s)
- Ahmad Mehri
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sahar Sotoodeh Ghorbani
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kosar Farhadi-Babadi
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elham Rahimi
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Barati
- Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Niloufar Taherpour
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Prevention of Cardiovascular Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Izadi
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Shahbazi
- Department of Epidemiology, School of Health, Hamadan University of Medical Sciences Hamadan, Iran
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Yaser Mokhayeri
- Department of Infectious Disease, School of Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Seifi
- Health Management and Social Development Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Saeid Fallah
- Department of Epidemiology, School of Public Health and Safety, Prevention of Cardiovascular Disease Research Center, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rezvan Feyzi
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Koorosh Etemed
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Saeed Hashemi Nazari
- Department of Epidemiology, School of Public Health and Safety, Prevention of Cardiovascular Disease Research Center, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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18
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Ragel EJ, Harris LK, Campbell RA. Acute respiratory distress syndrome: potential of therapeutic interventions effective in treating progression from COVID-19 to treat progression from other illnesses-a systematic review. BMJ Open Respir Res 2023; 10:e001525. [PMID: 37657844 PMCID: PMC10476125 DOI: 10.1136/bmjresp-2022-001525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 08/04/2023] [Indexed: 09/03/2023] Open
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) is the most severe form of lung injury, rendering gaseous exchange insufficient, leading to respiratory failure. Despite over 50 years of research on the treatment of ARDS when developed from illnesses such as sepsis and pneumonia, mortality remains high, and no robust pharmacological treatments exist. The progression of SARS-CoV-2 infections to ARDS during the recent global pandemic led to a surge in the number of clinical trials on the condition. Understandably, this explosion in new research focused on COVID-19 ARDS (CARDS) rather than ARDS when developed from other illnesses, yet differences in pathology between the two conditions mean that optimal treatment for them may be distinct. AIM The aim of the present work is to assess whether new therapeutic interventions that have been developed for the treatment of CARDS may also hold strong potential in the treatment of ARDS when developed from other illnesses. The study objectives are achieved through a systematic review of clinical trials. RESULTS The COVID-19 pandemic led to the identification of various therapeutic interventions for CARDS, some but not all of which are optimal for the management of ARDS. Interventions more suited to CARDS pathology include antithrombotics and biologic agents, such as cytokine inhibitors. Cell-based therapies, on the other hand, show promise in the treatment of both conditions, attributed to their broad mechanisms of action and the overlap in the clinical manifestations of the conditions. A shift towards personalised treatments for both CARDS and ARDS, as reflected through the increasing use of biologics, is also evident. CONCLUSIONS As ongoing CARDS clinical trials progress, their findings are likely to have important implications that alter the management of ARDS in patients that develop the condition from illnesses other than COVID-19 in the future.
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Affiliation(s)
- Emma J Ragel
- Division of Pharmacy and Optometry, University of Manchester, Manchester, UK
| | - Lynda K Harris
- Division of Pharmacy and Optometry, University of Manchester, Manchester, UK
- Maternal and Fetal Health Research Centre, University of Manchester, Manchester, UK
- 3St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK
- Olson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Richard A Campbell
- Division of Pharmacy and Optometry, University of Manchester, Manchester, UK
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19
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Song Y, Gou Y, Gao J, Chen D, Zhang H, Zhao W, Qian F, Xu A, Shen Y. Lomerizine attenuates LPS-induced acute lung injury by inhibiting the macrophage activation through reducing Ca 2+ influx. Front Pharmacol 2023; 14:1236469. [PMID: 37693893 PMCID: PMC10484514 DOI: 10.3389/fphar.2023.1236469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 08/14/2023] [Indexed: 09/12/2023] Open
Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening lung diseases with high mortality rates, predominantly attributable to acute and severe pulmonary inflammation. Lomerizine (LMZ) is a calcium channel blocker previously used in preventing and treating migraine. Here, we found that LMZ inhibited inflammatory responses and lung pathological injury by reducing pulmonary edema, neutrophil infiltration and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-induced ALI mice. In vitro experiments, upon treating with LMZ, the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was attenuated in macrophages. The phosphorylation of p38 MAPK, ERK1/2, JNK, and NF-κB p65 was inhibited after LMZ treatment. Furthermore, LPS-induced Ca2+ influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca2+ channel agonist Bay K8644 (BK) could restore cytokine generation. In conclusion, our study demonstrated that LMZ alleviates LPS-induced ALI and is a potential agent for treating ALI/ARDS.
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Affiliation(s)
- Yunduan Song
- Department of Respiratory and Critical Care Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
- Department of Clinical Laboratory, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yusen Gou
- Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Jiameng Gao
- Department of Respiratory and Critical Care Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Dongxin Chen
- Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Haibo Zhang
- Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Wenjuan Zhao
- Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Feng Qian
- Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Ajing Xu
- Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yao Shen
- Department of Respiratory and Critical Care Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
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20
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Braksator M, Jachymek M, Witkiewicz K, Witkiewicz W, Peregud-Pogorzelska M, Kotfis K, Kaźmierczak J, Brykczyński M. The Impact of Left Ventricular Diastolic Dysfunction on Respiratory Adverse Events in Cardiac Surgery Patients-An Observational Prospective Single-Center Study. J Clin Med 2023; 12:4960. [PMID: 37568361 PMCID: PMC10419440 DOI: 10.3390/jcm12154960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 07/20/2023] [Accepted: 07/24/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Left ventricular diastolic dysfunction (LV DD) is the most dominant cause of heart failure with preserved ejection fraction (HFpEF) worldwide. This pathological condition may contribute to postcapillary pulmonary hypertension (pcPH) development. Hypoxemia, often observed in pcPH, may significantly negatively impact the course of hospitalization in patients after cardiac surgery. The aim of our study was to investigate the impact of LV DD on the frequency of postoperative respiratory adverse events (RAE) in patients undergoing Coronary Artery Bypass Grafting (CABG). METHODS The left ventricular (LV) diastolic function was assessed in 56 consecutive patients admitted for CABG. We investigated the relationship between LV DD and postoperative respiratory adverse events (RAE) in groups with normal LV diastolic function and LV DD stage I, II, and III. RESULTS Left ventricular diastolic dysfunction stage I was observed in 11 patients (19.6%) and LV DD stage II or III in 19 patients (33.9%). Arterial blood partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) index during postoperative mechanical ventilation was significantly lower in LV DD stage II or III than in the group with normal LV diastolic function. Patients with DD stage II or III had a higher occurrence of postoperative pneumonia than the group with normal LV diastolic function. CONCLUSIONS Left ventricular diastolic dysfunction is widespread in cardiac surgery patients and is an independent risk factor for lower minimal PaO2/FiO2 index during mechanical ventilation and higher occurrence of pneumonia.
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Affiliation(s)
- Marta Braksator
- Department of Cardiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (M.B.); (M.J.); (W.W.); (M.P.-P.); (J.K.)
| | - Magdalena Jachymek
- Department of Cardiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (M.B.); (M.J.); (W.W.); (M.P.-P.); (J.K.)
| | - Karina Witkiewicz
- Department of Pulmonology, Pomeranian Medical University, 70-204 Szczecin, Poland;
| | - Wojciech Witkiewicz
- Department of Cardiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (M.B.); (M.J.); (W.W.); (M.P.-P.); (J.K.)
| | - Małgorzata Peregud-Pogorzelska
- Department of Cardiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (M.B.); (M.J.); (W.W.); (M.P.-P.); (J.K.)
| | - Katarzyna Kotfis
- Department of Anaesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University, 70-111 Szczecin, Poland
| | - Jarosław Kaźmierczak
- Department of Cardiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (M.B.); (M.J.); (W.W.); (M.P.-P.); (J.K.)
| | - Mirosław Brykczyński
- Department of Cardiac Surgery, University of Zielona Góra, 65-417 Zielona Góra, Poland;
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21
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Grasselli G, Calfee CS, Camporota L, Poole D, Amato MBP, Antonelli M, Arabi YM, Baroncelli F, Beitler JR, Bellani G, Bellingan G, Blackwood B, Bos LDJ, Brochard L, Brodie D, Burns KEA, Combes A, D'Arrigo S, De Backer D, Demoule A, Einav S, Fan E, Ferguson ND, Frat JP, Gattinoni L, Guérin C, Herridge MS, Hodgson C, Hough CL, Jaber S, Juffermans NP, Karagiannidis C, Kesecioglu J, Kwizera A, Laffey JG, Mancebo J, Matthay MA, McAuley DF, Mercat A, Meyer NJ, Moss M, Munshi L, Myatra SN, Ng Gong M, Papazian L, Patel BK, Pellegrini M, Perner A, Pesenti A, Piquilloud L, Qiu H, Ranieri MV, Riviello E, Slutsky AS, Stapleton RD, Summers C, Thompson TB, Valente Barbas CS, Villar J, Ware LB, Weiss B, Zampieri FG, Azoulay E, Cecconi M. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies. Intensive Care Med 2023; 49:727-759. [PMID: 37326646 PMCID: PMC10354163 DOI: 10.1007/s00134-023-07050-7] [Citation(s) in RCA: 345] [Impact Index Per Article: 172.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 03/24/2023] [Indexed: 06/17/2023]
Abstract
The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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Affiliation(s)
- Giacomo Grasselli
- Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
| | - Carolyn S Calfee
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Luigi Camporota
- Department of Adult Critical Care, Guy's and St Thomas' NHS Foundation Trust, London, UK
- Centre for Human and Applied Physiological Sciences, King's College London, London, UK
| | - Daniele Poole
- Operative Unit of Anesthesia and Intensive Care, S. Martino Hospital, Belluno, Italy
| | | | - Massimo Antonelli
- Department of Anesthesiology Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| | - Yaseen M Arabi
- Intensive Care Department, Ministry of the National Guard - Health Affairs, Riyadh, Kingdom of Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Francesca Baroncelli
- Department of Anesthesia and Intensive Care, San Giovanni Bosco Hospital, Torino, Italy
| | - Jeremy R Beitler
- Center for Acute Respiratory Failure and Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University, New York, NY, USA
| | - Giacomo Bellani
- Centre for Medical Sciences - CISMed, University of Trento, Trento, Italy
- Department of Anesthesia and Intensive Care, Santa Chiara Hospital, APSS Trento, Trento, Italy
| | - Geoff Bellingan
- Intensive Care Medicine, University College London, NIHR University College London Hospitals Biomedical Research Centre, London, UK
| | - Bronagh Blackwood
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Lieuwe D J Bos
- Intensive Care, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Laurent Brochard
- Keenan Research Center, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Canada
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
| | - Daniel Brodie
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Karen E A Burns
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
- Department of Medicine, Division of Critical Care, Unity Health Toronto - Saint Michael's Hospital, Toronto, Canada
- Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
| | - Alain Combes
- Sorbonne Université, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, F-75013, Paris, France
- Service de Médecine Intensive-Réanimation, Institut de Cardiologie, APHP Sorbonne Université Hôpital Pitié-Salpêtrière, F-75013, Paris, France
| | - Sonia D'Arrigo
- Department of Anesthesiology Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Daniel De Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Alexandre Demoule
- Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France
- AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, site Pitié-Salpêtrière, Service de Médecine Intensive - Réanimation (Département R3S), Paris, France
| | - Sharon Einav
- Shaare Zedek Medical Center and Hebrew University Faculty of Medicine, Jerusalem, Israel
| | - Eddy Fan
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
| | - Niall D Ferguson
- Department of Medicine, Division of Respirology and Critical Care, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada
- Departments of Medicine and Physiology, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| | - Jean-Pierre Frat
- CHU De Poitiers, Médecine Intensive Réanimation, Poitiers, France
- INSERM, CIC-1402, IS-ALIVE, Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers, France
| | - Luciano Gattinoni
- Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany
| | - Claude Guérin
- University of Lyon, Lyon, France
- Institut Mondor de Recherches Biomédicales, INSERM 955 CNRS 7200, Créteil, France
| | - Margaret S Herridge
- Critical Care and Respiratory Medicine, University Health Network, Toronto General Research Institute, Institute of Medical Sciences, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
| | - Carol Hodgson
- The Australian and New Zealand Intensive Care Research Center, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- Department of Intensive Care, Alfred Health, Melbourne, Australia
| | - Catherine L Hough
- Division of Pulmonary, Allergy and Critical Care Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Samir Jaber
- Anesthesia and Critical Care Department (DAR-B), Saint Eloi Teaching Hospital, University of Montpellier, Research Unit: PhyMedExp, INSERM U-1046, CNRS, 34295, Montpellier, France
| | - Nicole P Juffermans
- Laboratory of Translational Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Christian Karagiannidis
- Department of Pneumology and Critical Care Medicine, Cologne-Merheim Hospital, ARDS and ECMO Centre, Kliniken Der Stadt Köln gGmbH, Witten/Herdecke University Hospital, Cologne, Germany
| | - Jozef Kesecioglu
- Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Arthur Kwizera
- Makerere University College of Health Sciences, School of Medicine, Department of Anesthesia and Intensive Care, Kampala, Uganda
| | - John G Laffey
- Anesthesia and Intensive Care Medicine, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland
- Anesthesia and Intensive Care Medicine, Galway University Hospitals, Saolta University Hospitals Groups, Galway, Ireland
| | - Jordi Mancebo
- Intensive Care Department, Hospital Universitari de La Santa Creu I Sant Pau, Barcelona, Spain
| | - Michael A Matthay
- Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA
| | - Daniel F McAuley
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
- Regional Intensive Care Unit, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK
| | - Alain Mercat
- Département de Médecine Intensive Réanimation, CHU d'Angers, Université d'Angers, Angers, France
| | - Nuala J Meyer
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Marc Moss
- Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, School of Medicine, Aurora, CO, USA
| | - Laveena Munshi
- Interdepartmental Division of Critical Care Medicine, Sinai Health System, University of Toronto, Toronto, Canada
| | - Sheila N Myatra
- Department of Anesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Michelle Ng Gong
- Division of Pulmonary and Critical Care Medicine, Montefiore Medical Center, Bronx, New York, NY, USA
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY, USA
| | - Laurent Papazian
- Bastia General Hospital Intensive Care Unit, Bastia, France
- Aix-Marseille University, Faculté de Médecine, Marseille, France
| | - Bhakti K Patel
- Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Mariangela Pellegrini
- Anesthesia and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Anders Perner
- Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Antonio Pesenti
- Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Lise Piquilloud
- Adult Intensive Care Unit, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Haibo Qiu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009, China
| | - Marco V Ranieri
- Alma Mater Studiorum - Università di Bologna, Bologna, Italy
- Anesthesia and Intensive Care Medicine, IRCCS Policlinico di Sant'Orsola, Bologna, Italy
| | - Elisabeth Riviello
- Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Arthur S Slutsky
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
- Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada
| | - Renee D Stapleton
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA
| | - Charlotte Summers
- Department of Medicine, University of Cambridge Medical School, Cambridge, UK
| | - Taylor B Thompson
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Carmen S Valente Barbas
- University of São Paulo Medical School, São Paulo, Brazil
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Jesús Villar
- Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
- Research Unit, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
| | - Lorraine B Ware
- Departments of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Björn Weiss
- Department of Anesthesiology and Intensive Care Medicine (CCM CVK), Charitè - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
| | - Fernando G Zampieri
- Academic Research Organization, Albert Einstein Hospital, São Paulo, Brazil
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Elie Azoulay
- Médecine Intensive et Réanimation, APHP, Hôpital Saint-Louis, Paris Cité University, Paris, France
| | - Maurizio Cecconi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Anesthesia and Intensive Care Medicine, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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22
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Laake JH, Aslam TN, Barratt-Due A, Løwhagen B, Pischke SE, Tønnessen TI, Wisløff-Aase K, Aasmundstad TA. [ARDS or acute respiratory failure syndrome?]. TIDSSKRIFT FOR DEN NORSKE LEGEFORENING 2023; 143:23-0402. [PMID: 37376931 DOI: 10.4045/tidsskr.23.0402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2023] Open
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23
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Lim MJ, Lakshminrusimha S, Hedriana H, Albertson T. Pregnancy and Severe ARDS with COVID-19: Epidemiology, Diagnosis, Outcomes and Treatment. Semin Fetal Neonatal Med 2023; 28:101426. [PMID: 36964118 PMCID: PMC9990893 DOI: 10.1016/j.siny.2023.101426] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
Pregnancy-related acute respiratory distress syndrome (ARDS) is fast becoming a growing and clinically relevant subgroup of ARDS amidst global outbreaks of various viral respiratory pathogens that include H1N1-influenza, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and the most recent COVID-19 pandemic. Pregnancy is a risk factor for severe viral-induced ARDS and commonly associated with poor maternal and fetal outcomes including fetal growth-restriction, preterm birth, and spontaneous abortion. Physiologic changes of pregnancy further compounded by mechanical and immunologic alterations are theorized to impact the development of ARDS from viral pneumonia. The COVID-19 sub-phenotype of ARDS share overlapping molecular features of maternal pathogenicity of pregnancy with respect to immune-dysregulation and endothelial/microvascular injury (i.e., preeclampsia) that may in part explain a trend toward poor maternal and fetal outcomes seen with severe COVID-19 maternal infections. To date, current ARDS diagnostic criteria and treatment management fail to include and consider physiologic adaptations that are unique to maternal physiology of pregnancy and consideration of maternal-fetal interactions. Treatment focused on lung-protective ventilation strategies have been shown to improve clinical outcomes in adults with ARDS but may have adverse maternal-fetal interactions when applied in pregnancy-related ARDS. No specific pharmacotherapy has been identified to improve outcomes in pregnancy with ARDS. Adjunctive therapies aimed at immune-modulation and anti-viral treatment with COVID-19 infection during pregnancy have been reported but data in regard to its efficacy and safety is currently lacking.
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Affiliation(s)
- Michelle J Lim
- UC Davis School of Medicine, UC Davis Children's Hospital, Department of Pediatrics, Division of Critical Care and Neonatology, Sacramento, CA, USA.
| | - Satyan Lakshminrusimha
- UC Davis School of Medicine, UC Davis Children's Hospital, Department of Pediatrics, Division of Critical Care and Neonatology, Sacramento, CA, USA
| | - Herman Hedriana
- UC Davis School of Medicine, UC Davis Medical Center, Department of Obstetrics and Gynecology, Sacramento, CA, USA
| | - Timothy Albertson
- UC Davis School of Medicine, UC Davis Medical Center, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Sacramento, CA, USA
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24
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Lin KC, Fang WF, Sung PH, Huang KT, Chiang JY, Chen YL, Huang CR, Li YC, Lee MS, Yip HK. Early and Dose-Dependent Xenogeneic Mesenchymal Stem Cell Therapy Improved Outcomes in Acute Respiratory Distress Syndrome Rodent Through Ameliorating Inflammation, Oxidative Stress, and Immune Reaction. Cell Transplant 2023; 32:9636897231190178. [PMID: 37592717 PMCID: PMC10469224 DOI: 10.1177/09636897231190178] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 06/29/2023] [Accepted: 07/11/2023] [Indexed: 08/19/2023] Open
Abstract
This study tested whether human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) treatment effectively protected the rat lung against acute respiratory distress syndrome (ARDS) injury, and benefits of early and dose-dependent treatment. Rat pulmonary epithelial cell line L2 (PECL2) were categorized into G1 (PECL2), G2 (PECL2 + healthy rat lung-derived extraction/50 mg/ml co-cultured for 24 h), G3 (PECL2 + ARDS rat lung-derived extraction/50 mg/ml co-cultured for 24 h), and G4 (condition as G3 + HUCDMSCs/1 × 105/co-cultured for 24 h). The result showed that the protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IkB/NF-κB/IL-1β/TNF-α), oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/JNKs/JUN/cytosolic-cytochrome-C/cyclophilin-D/DRP1), and cell-apoptotic/fibrotic (cleaved-caspase 3/cleaved-PARP/TGF-β/p-Smad3) biomarkers were significantly increased in G3 than in G1/G2 and were significantly reversed in G4 (all P < 0.001), but they were similar between G1/G2. Adult male rats (n = 42) were equally categorized into group 1 (normal control), group 2 (ARDS only), group 3 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 3 h after 48 h ARDS induction (i.e., early treatment)], group 4 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 24 h after 48 h ARDS induction (late treatment)], and group 5 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 3 h/24 h after-48 h ARDS induction (dose-dependent treatment)]. By day 5 after ARDS induction, the SaO2%/immune regulatory T cells were highest in group 1, lowest in group 2, significantly lower in group 4 than in groups 3/5, and significantly lower in group 3 than in group 5, whereas the circulatory/bronchioalveolar lavage fluid inflammatory cells (CD11b-c+/LyG6+/MPO+)/circulatory immune cells (CD3-C4+/CD3-CD8+)/lung-leakage-albumin level/lung injury score/lung protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IκB-β/p-NF-κB/IL-1β/TNF-α)/fibrotic (p-SMad3/TGF-β), apoptosis (mitochondrial-Bax/cleaved-caspase-3)/oxidative-cell-stress (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/p-JNKs/p-cJUN)/mitochondrial damaged (cyclophilin-D/DRP1/cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of SaO2% among the groups (all P < 0.0001). Early administration was superior to and two-dose counterpart was even more superior to late HUCDMSCs treatment for protecting the lung against ARDS injury.
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Affiliation(s)
- Kun-Chen Lin
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
| | - Wen-Feng Fang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
| | - Pei-Hsun Sung
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, R. O. C
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, R. O. C
| | - Kuo-Tung Huang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
| | - John Y. Chiang
- Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, R. O. C
- Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, R. O. C
| | - Yi-Ling Chen
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, R. O. C
| | - Chi-Ruei Huang
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, R. O. C
| | - Yi-Chen Li
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
| | | | - Hon-Kan Yip
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, R. O. C
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, R. O. C
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, R. O. C
- Department of Nursing, Asia University, Taichung, R. O. C
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, R. O. C
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, R. O. C
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Xu D, Yang F, Chen J, Zhu T, Wang F, Xiao Y, Liang Z, Bi L, Huang G, Jiang Z, Shan H, Li D. Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury. Acta Pharm Sin B 2022; 13:2124-2137. [DOI: 10.1016/j.apsb.2022.12.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/11/2022] [Accepted: 12/15/2022] [Indexed: 12/29/2022] Open
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Wick KD, Matthay MA, Ware LB. Pulse oximetry for the diagnosis and management of acute respiratory distress syndrome. THE LANCET. RESPIRATORY MEDICINE 2022; 10:1086-1098. [PMID: 36049490 PMCID: PMC9423770 DOI: 10.1016/s2213-2600(22)00058-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 01/30/2022] [Accepted: 02/10/2022] [Indexed: 02/07/2023]
Abstract
The diagnosis of acute respiratory distress syndrome (ARDS) traditionally requires calculation of the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) using arterial blood, which can be costly and is not possible in many resource-limited settings. By contrast, pulse oximetry is continuously available, accurate, inexpensive, and non-invasive. Pulse oximetry-based indices, such as the ratio of pulse-oximetric oxygen saturation to FiO2 (SpO2/FiO2), have been validated in clinical studies for the diagnosis and risk stratification of patients with ARDS. Limitations of the SpO2/FiO2 ratio include reduced accuracy in poor perfusion states or above oxygen saturations of 97%, and the potential for reduced accuracy in patients with darker skin pigmentation. Application of pulse oximetry to the diagnosis and management of ARDS, including formal adoption of the SpO2/FiO2 ratio as an alternative to PaO2/FiO2 to meet the diagnostic criterion for hypoxaemia in ARDS, could facilitate increased and earlier recognition of ARDS worldwide to advance both clinical practice and research.
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Affiliation(s)
- Katherine D Wick
- Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, CA, USA
| | - Michael A Matthay
- Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, CA, USA
| | - Lorraine B Ware
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine and Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
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Lv Z, Duan S, Zhou M, Gu M, Li S, Wang Y, Xia Q, Xu D, Mao Y, Dong W, Jiang L. Mouse Bone Marrow Mesenchymal Stem Cells Inhibit Sepsis-Induced Lung Injury in Mice via Exosomal SAA1. Mol Pharm 2022; 19:4254-4263. [PMID: 36173129 DOI: 10.1021/acs.molpharmaceut.2c00542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Sepsis is a global disease burden, and approximately 40% of cases develop acute lung injury (ALI). Bone marrow mesenchymal stromal cells (BMSCs) and their exosomes are widely used in treating a variety of diseases including sepsis. As an acute phase protein, serum amyloid A1 (SAA1) regulates inflammation and immunity. However, the role of SAA1 in BMSCs-exosomes in septic lung injury remains to be elucidated. Exosomes derived from serum and BMSCs were isolated by ultracentrifugation. SAA1 was silenced or overexpressed in mouse BMSCs using lentiviral plasmids, containing either SAA1-targeting short interfering RNAs or SAA1 cDNA. Sepsis was induced by cecal ligation and puncture (CLP). LPS was used to induce ALI in mice. Mouse alveolar macrophages were isolated by flow cytometry. Levels of SAA1, endotoxin, TNF-α, and IL-6 were measured using commercial kits. LPS internalization was monitored by immunostaining. RT-qPCR or immunoblots were performed to test gene and protein expressions. Serum exosomes of patients with sepsis-induced lung injury had significantly higher levels of SAA1, endotoxin, TNF-α, and IL-6. Overexpression of SAA1 in BMSCs inhibited CLP- or LPS-induced lung injury and decreased CLP- or LPS-induced endotoxin, TNF-α, and IL-6 levels. Administration of the SAA1 blocking peptide was found to partially inhibit SAA1-induced LPS internalization by mouse alveolar macrophages and reverse the protective effect of SAA1. In conclusion, BMSCs inhibit sepsis-induced lung injury through exosomal SAA1. These results highlight the importance of BMSCs, exosomes, and SAA1, which may provide novel directions for the treatment of septic lung injury.
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Affiliation(s)
- Zhou Lv
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Shuxian Duan
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Miao Zhou
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Minglu Gu
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Siyuan Li
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Yan Wang
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Qin Xia
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Dunfeng Xu
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Yanfei Mao
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Wenwen Dong
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Lai Jiang
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai 200092, China
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Wick KD, Aggarwal NR, Curley MAQ, Fowler AA, Jaber S, Kostrubiec M, Lassau N, Laterre PF, Lebreton G, Levitt JE, Mebazaa A, Rubin E, Sinha P, Ware LB, Matthay MA. Opportunities for improved clinical trial designs in acute respiratory distress syndrome. THE LANCET. RESPIRATORY MEDICINE 2022; 10:916-924. [PMID: 36057279 DOI: 10.1016/s2213-2600(22)00294-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 07/02/2022] [Accepted: 07/19/2022] [Indexed: 02/08/2023]
Abstract
The acute respiratory distress syndrome (ARDS) is a common critical illness syndrome with high morbidity and mortality. There are no proven pharmacological therapies for ARDS. The current definition of ARDS is based on shared clinical characteristics but does not capture the heterogeneity in clinical risk factors, imaging characteristics, physiology, timing of onset and trajectory, and biology of the syndrome. There is increasing interest within the ARDS clinical trialist community to design clinical trials that reduce heterogeneity in the trial population. This effort must be balanced with ongoing work to craft an inclusive, global definition of ARDS, with important implications for trial design. Ultimately, the two aims-to design trials that are applicable to the diverse global ARDS population while also advancing opportunities to identify targetable traits-should coexist. In this Personal View, we recommend two primary strategies to improve future ARDS trials: the development of new methods to target treatable traits in clinical trial populations, and improvements in the representativeness of ARDS trials, with the inclusion of global populations. We emphasise that these two strategies are complementary. We also discuss how a proposed expansion of the definition of ARDS could affect the future of clinical trials.
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Affiliation(s)
- Katherine D Wick
- Cardiovascular Research Institute, University of California, San Francisco, CA, USA
| | - Neil R Aggarwal
- Division of Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado, Aurora, CO, USA; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Martha A Q Curley
- Department of Family and Community Health, School of Nursing, University of Pennsylvania, Philadelphia, PA, USA
| | - Alpha A Fowler
- Division of Pulmonary Disease and Critical Care, Virginia Commonwealth University, Richmond, VA, USA
| | - Samir Jaber
- University Hospital, CHU de Montpellier Hôpital Saint Eloi, Intensive Care Unit and Transplantation, Department of Anesthesiology DAR B, Montpellier, France
| | - Maciej Kostrubiec
- Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - Nathalie Lassau
- Department of Imaging, Gustave Roussy, Université Paris Saclay, Villejuif, France; Biomaps, UMR1281 INSERM, CEA, CNRS, Université Paris Saclay, Villejuif, France
| | - Pierre François Laterre
- Intensive Care Medicine, Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium
| | - Guillaume Lebreton
- Institute of Cardiometabolism and Nutrition, Inserm, UMRS 1166-ICAN, Sorbonne University, Paris, France; Cardiac Surgery Service, Institute of Cardiology, AP-HP, Sorbonne University, Paris, France
| | - Joseph E Levitt
- Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, USA
| | - Alexandre Mebazaa
- Department of Anesthesiology and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals, Paris, France
| | | | - Pratik Sinha
- Department of Anesthesiology, Washington University in St Louis, St Louis, MO, USA
| | - Lorraine B Ware
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael A Matthay
- Cardiovascular Research Institute, University of California, San Francisco, CA, USA; Departments of Medicine and Anesthesia, University of California, San Francisco, CA, USA.
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Bowcock EM, Mclean A. Bedside assessment of left atrial pressure in critical care: a multifaceted gem. Crit Care 2022; 26:247. [PMID: 35964098 PMCID: PMC9375940 DOI: 10.1186/s13054-022-04115-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 07/31/2022] [Indexed: 11/23/2022] Open
Abstract
Evaluating left atrial pressure (LAP) solely from the left ventricular preload perspective is a restrained approach. Accurate assessment of LAP is particularly relevant when pulmonary congestion and/or right heart dysfunction are present since it is the pressure most closely related to pulmonary venous pressure and thus pulmonary haemodynamic load. Amalgamation of LAP measurement into assessment of the ‘transpulmonary circuit’ may have a particular role in differentiating cardiac failure phenotypes in critical care. Most of the literature in this area involves cardiology patients, and gaps of knowledge in application to the bedside of the critically ill patient remain significant. Explored in this review is an overview of left atrial physiology, invasive and non-invasive methods of LAP measurement and their potential clinical application.
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Zhan B, Shen J. Mitochondria and their potential role in acute lung injury (Review). Exp Ther Med 2022; 24:479. [PMID: 35761815 PMCID: PMC9214601 DOI: 10.3892/etm.2022.11406] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 05/16/2022] [Indexed: 11/06/2022] Open
Affiliation(s)
- Biao Zhan
- Center of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
| | - Jie Shen
- Center of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China
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Abstract
Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence-supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-suggests that the current syndrome-based framework of critical illness should be reconsidered. Here we discuss recent findings from basic science and clinical research in critical care and explore how these might inform a new conceptual model of critical illness. De-emphasizing syndromes, we focus on the underlying biological changes that underpin critical illness states and that may be amenable to treatment. We hypothesize that such an approach will accelerate critical care research, leading to a richer understanding of the pathobiology of critical illness and of the key determinants of patient outcomes. This, in turn, will support the design of more effective clinical trials and inform a more precise and more effective practice at the bedside.
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Laake JH, Småstuen MC, Møller MH, Larsson A, Aslam TN, Hofsø K, Pham T, Fan E, Bellani G, Laffey JG. Patient characteristics, management and outcomes in a Nordic subset of the "large observational study to understand the global impact of severe acute respiratory failure" (LUNG SAFE) study. Acta Anaesthesiol Scand 2022; 66:684-695. [PMID: 35398892 PMCID: PMC9322410 DOI: 10.1111/aas.14069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 02/07/2022] [Accepted: 03/28/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The "Large observational study to understand the global impact of severe acute respiratory failure" (LUNG SAFE) study described the worldwide epidemiology and management of patients with acute hypoxaemic respiratory failure (AHRF). Here, we present the Nordic subset of data from the LUNG SAFE cohort. METHODS We extracted LUNG SAFE data for adults fulfilling criteria for AHRF in intensive care units (ICU) in Denmark, Norway and Sweden, including demographics, co-morbidities, clinical assessment and management characteristics, 90-day survival and length-of-stay (LOS). We analysed ICU LOS with linear regression, and associations between risk factors and mortality were quantified using Cox regression. RESULTS We included 192 patients, with a median age of 64 years (IQR 55, 72), and a male-to-female ratio of 2:1. The majority had one or more co-morbidities, and clinicians identified pneumonia as the primary cause of respiratory failure in 56% and acute respiratory distress syndrome (ARDS) in 21%. Median ICU LOS and duration of invasive mechanical ventilation (IMV) were 5 and 3 days. Tidal volumes (TV) were frequently larger than that supported by evidence and IMV allowing for spontaneous ventilation was common. Younger age, co-morbidity, surgical admission and ARDS were associated with ICU LOS. Sixty-one patients (32%) were dead at 90 days. Age and a non-surgical cause of admission were associated with death. CONCLUSIONS In this subset of LUNG SAFE, ARDS was often not recognised in patients with AHRF and management frequently deviated from evidence-based practices. ICU LOS was generally short, and mortality was attributable to known risk factors.
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Affiliation(s)
- Jon Henrik Laake
- Department of Anaesthesiology and Intensive Care Medicine, Division of Emergencies and Critical Care, Rikshospitalet Medical Centre Oslo University Hospital Oslo Norway
- Department of Research and Development, Division of Emergencies and Critical Care Oslo University Hospital Oslo Norway
| | - Milada Cvancarova Småstuen
- Faculty of Health Sciences, Department of Nursing and Health Promotion Oslo Metropolitan University Oslo Norway
| | - Morten Hylander Møller
- Department of Intensive Care Rigshospitalet, University of Copenhagen Copenhagen Denmark
- Collaboration for Research in Intensive Care Copenhagen Denmark
| | - Anders Larsson
- Department of Surgical Sciences, Anaesthesiology and Intensive Care Uppsala University Hospital Uppsala Sweden
| | - Tayyba Naz Aslam
- Department of Anaesthesiology and Intensive Care Medicine, Division of Emergencies and Critical Care, Rikshospitalet Medical Centre Oslo University Hospital Oslo Norway
- Department of Research and Development, Division of Emergencies and Critical Care Oslo University Hospital Oslo Norway
| | - Kristin Hofsø
- Department of Research and Development, Division of Emergencies and Critical Care Oslo University Hospital Oslo Norway
- Lovisenberg Diaconal University College Oslo Norway
| | - Tài Pham
- Service de médecine intensive‐réanimation, AP‐HP, Hôpital de Bicêtre Hôpitaux Universitaires Paris‐Saclay Le Kremlin‐Bicêtre France
- Université Paris‐Saclay, UVSQ, Univ. Paris‐Sud, Inserm U1018, Equipe d'Epidémiologie respiratoire intégrative, CESP Villejuif France
| | - Eddy Fan
- Interdepartmental Division of Critical Care Medicine and the Institute of Health Policy, Management and Evaluation University of Toronto Toronto Canada
| | - Giacomo Bellani
- Department of Medicine and Surgery University of Milan‐Bicocca and Department of Emercengy, ASST Monza Monza Italy
| | - John G. Laffey
- School of Medicine, National University of Ireland Galway and Dept of Anaesthesia and Intensive Care Medicine Galway University Hospitals Galway Ireland
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Lee SH, Shin MH, Leem AY, Lee SH, Chung KS, Kim YS, Park MS. NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model. Respir Res 2022; 23:73. [PMID: 35346198 PMCID: PMC8962540 DOI: 10.1186/s12931-022-01992-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
Background For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model. Methods Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 μL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined. Results Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p < 0.01) and EphA2 KO with HTV group (p < 0.001) compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p < 0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p < 0.001). In patients with respiratory disease, NOX4 and EphA2 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit. Conclusion In the VILI model with high tidal volume, NOX4 KO, EphA2 KO or monoclonal antibodies attenuated the VILI. NOX4 and EphA2 levels were significantly higher in patients with pneumonia and especially in mechanical ventilated in the ICU. Inhibition of Nox4 is a potential therapeutic target for the prevention and reduction of VILI. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-022-01992-0.
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Affiliation(s)
- Sang Hoon Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Mi Hwa Shin
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Ah Young Leem
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Su Hwan Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Kyung Soo Chung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Young Sam Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Moo Suk Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
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Leow EH, Wong JJM, Mok YH, Hornik CP, Ng YH, Lee JH. Fluid overload in children with pediatric acute respiratory distress syndrome: A retrospective cohort study. Pediatr Pulmonol 2022; 57:300-307. [PMID: 34633156 DOI: 10.1002/ppul.25720] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/29/2021] [Accepted: 10/08/2021] [Indexed: 01/22/2023]
Abstract
OBJECTIVES To assess the association of cumulative fluid overload (FO) up to 14 days from the diagnosis of pediatric acute respiratory syndrome (PARDS) with pediatric intensive care unit (PICU) mortality, 28-day mechanical ventilation free days (VFD), and 28-day intensive care unit free days (IFD). We hypothesized that fluid overload, even beyond the acute period, would be associated with increased morbidity and mortality. METHODS We conducted a retrospective cohort study of PARDS patients admitted to PICU from 2009 to 2015. For repeated admissions, we considered the admission with the highest oxygenation index (OI). Daily FO (%) was calculated as (intake - output)/weight at PICU admission × 100. Peak cumulative FO (CFO) was the highest CFO from the diagnosis of PARDS to Day 14 or to PICU discharge or mortality, whichever was earliest. Rate to peak CFO was the peak CFO divided by the number of days to reach that highest CFO. The association of FO with mortality, VFD and IFD were analyzed with logistic and linear regression models, with the following covariates: Pediatric Index of Mortality 2 score, PARDS severity, and the presence of acute kidney injury (AKI). RESULTS There were 165 patients included in this study, with a mortality rate of 45.5% (75/165), median age 3.2 years (interquartile range [IQR] 0.7-9.9) and OI 15.8 (IQR 9.5-27.9). Seventy-three (44.2%) patients had severe PARDS and 64 (38.8%) had AKI. AKI (aOR [adjusted odds ratio] 3.19, 95% CI [confidence interval] 1.43-7.09, p = 0.004) and rate to peak cumulative FO (aOR 1.23, 95% CI 1.07-1.42, p = 0.004) were associated with mortality. AKI and peak cumulative FO were associated with decreased VFD and IFD. CONCLUSION The rate to peak CFO over the first 14 days of PARDS was associated with mortality and peak CFO was associated with decreased VFD and IFD.
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Affiliation(s)
- Esther H Leow
- Department of Paediatric Nephrology, KK Women's and Children's Hospital, Singapore
| | - Judith J-M Wong
- Department of Pediatric Subspecialties, Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore.,Duke-NUS Medical School, Singapore
| | - Yee H Mok
- Department of Pediatric Subspecialties, Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore
| | - Christoph P Hornik
- Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.,Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Yong H Ng
- Department of Paediatric Nephrology, KK Women's and Children's Hospital, Singapore
| | - Jan H Lee
- Department of Pediatric Subspecialties, Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore.,Duke-NUS Medical School, Singapore
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Imtiaz K, Jodeh W, Sudekum D, DiGiovine B, Hecht J. The Use of Inhaled Epoprostenol for Acute Respiratory Distress Syndrome Secondary Due To COVID-19: a Case Series. J Crit Care Med (Targu Mures) 2022; 8:33-40. [PMID: 35274053 PMCID: PMC8852286 DOI: 10.2478/jccm-2021-0037] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 09/27/2021] [Indexed: 01/08/2023] Open
Abstract
Introduction Inhaled epoprostenol (iEpo) is a pulmonary vasodilator used to treat refractory respiratory failure, including that caused by Coronavirus 2019 (COVID-19) pneumonia. Aim of Study To describe the experience at three teaching hospitals using iEpo for severe respiratory failure due to COVID-19 and evaluate its efficacy in improving oxygenation. Methods Fifteen patients were included who received iEpo, had confirmed COVID-19 and had an arterial blood gas measurement in the 12 hours before and 24 hours after iEpo initiation. Results Eleven patients received prone ventilation before iEpo (73.3%), and six (40%) were paralyzed. The partial pressure of arterial oxygen to fraction of inspired oxygen (P/F ratio) improved from 95.7 mmHg to 118.9 mmHg (p=0.279) following iEpo initiation. In the nine patients with severe ARDS, the mean P/F ratio improved from 66.1 mmHg to 95.7 mmHg (p=0.317). Ultimately, four patients (26.7%) were extubated after an average of 9.9 days post-initiation. Conclusions The findings demonstrated a trend towards improvement in oxygenation in critically ill COVID-19 patients. Although limited by the small sample size, the results of this case series portend further investigation into the role of iEpo for severe respiratory failure associated with COVID-19.
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Affiliation(s)
- Komal Imtiaz
- University of Texas at Houston, Houston, TX, USA
| | - Wade Jodeh
- St Joseph Mercy Ann Arbor. Ann Arbor, MI, USA
| | | | | | - Jason Hecht
- St Joseph Mercy Ann Arbor. Ann Arbor, MI, USA
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Abstract
Acute Respiratory Distress Syndrome is a familiar and destructive clinical condition characterized by progressive, swift and impaired pulmonary state. It leads to mortality if not managed in a timely manner. Recently the role of imbalanced macrophage polarization has been reported in ARDS. Macrophages are known for their heterogeneity and plasticity. Under different microenvironmental stimuli, they (M0) can switch between classically activated macrophage (M1) and alternatively activated (M2) states. This switch is regulated by several signaling pathways and epigenetic changes. In this review, the importance of macrophage M1 and M2 has been discussed in the arena of ARDS citing the phase-wise impact of macrophage polarization. This will provide a further understanding of the molecular mechanism involved in ARDS and will help in developing novel therapeutic targets. Various biomarkers that are currently used concerning this pathophysiological feature have also been summarized.
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Molaei E, Molaei A, Hayes AW, Karimi G. Resolvin D1, therapeutic target in acute respiratory distress syndrome. Eur J Pharmacol 2021; 911:174527. [PMID: 34582846 PMCID: PMC8464084 DOI: 10.1016/j.ejphar.2021.174527] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/09/2021] [Accepted: 09/23/2021] [Indexed: 12/25/2022]
Abstract
Acute lung injury (ALI), or its more severe form, acute respiratory distress syndrome (ARDS), is a disease with high mortality and is a serious challenge facing the World Health Organization because there is no specific treatment. The excessive and prolonged immune response is the hallmark of this disorder, so modulating and regulating inflammation plays an important role in its prevention and treatment. Resolvin D1 (RvD1) as a specialized pro-resolving mediator has the potential to suppress the expression of inflammatory cytokines and to facilitate the production of antioxidant proteins by stimulating lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2). These changes limit the invasion of immune cells into the lung tissue, inhibit coagulation, and enhance cell protection against oxidative stress (OS). In particular, this biomolecule reduces the generation of reactive oxygen species (ROS) by blocking the activation of inflammatory transcription factors, especially nuclear factor-κB (NF-κB), and accelerating the synthesis of antioxidant compounds such as heme oxygenase 1 (HO-1) and superoxide dismutase (SOD). Therefore, the destruction and dysfunction of important cell components such as cytoplasmic membrane, mitochondria, Na+/k + adenosine triphosphatase (ATPase) and proteins involved in the phagocytic activity of scavenger macrophages are attenuated. Numerous studies on the effect of RvD1 over inflammation using animal models revealed that Rvs have both anti-inflammatory and pro-resolving capabilities and therefore, might have potential therapeutic value in treating ALI. Here, we review the current knowledge on the classification, biosynthesis, receptors, mechanisms of action, and role of Rvs in ALI/ARDS.
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Affiliation(s)
- Emad Molaei
- Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Molaei
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A Wallace Hayes
- University of South Florida College of Public Health, Tampa, FL, USA
| | - Gholamreza Karimi
- Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacodynamics and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Guo B, Peng Y, Gu Y, Zhong Y, Su C, Liu L, Chai D, Song T, Zhao N, Yan X, Xu T. Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells' maturation and function. Open Life Sci 2021; 16:1064-1081. [PMID: 34676301 PMCID: PMC8483064 DOI: 10.1515/biol-2021-0110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/10/2021] [Accepted: 08/16/2021] [Indexed: 11/20/2022] Open
Abstract
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe syndrome lacking efficient therapy and resulting in high morbidity and mortality. Although resveratrol (RES), a natural phytoalexin, has been reported to protect the ALI by suppressing the inflammatory response, the detailed mechanism of how RES affected the immune system is poorly studied. Pulmonary conventional dendritic cells (cDCs) are critically involved in the pathogenesis of inflammatory lung diseases including ALI. In this study, we aimed to investigate the protective role of RES via pulmonary cDCs in lipopolysaccharide (LPS)-induced ALI mice. Murine ALI model was established by intratracheally challenging with 5 mg/kg LPS. We found that RES pretreatment could mitigate LPS-induced ALI. Additionally, proinflammatory-skewed cytokines decreased whereas anti-inflammatory-related cytokines increased in bronchoalveolar lavage fluid by RES pretreatment. Mechanistically, RES regulated pulmonary cDCs' maturation and function, exhibiting lower level of CD80, CD86, major histocompatibility complex (MHC) II expression, and IL-10 secretion in ALI mice. Furthermore, RES modulated the balance between proinflammation and anti-inflammation of cDCs. Moreover, in vitro RES pretreatment regulated the maturation and function of bone marrow derived dendritic cells (BMDCs). Finally, the adoptive transfer of RES-pretreated BMDCs enhanced recovery of ALI. Thus, these data might further extend our understanding of a protective role of RES in regulating pulmonary cDCs against ALI.
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Affiliation(s)
- Bingnan Guo
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Yigen Peng
- Department of Emergency Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, China
| | - Yuting Gu
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Yi Zhong
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Chenglei Su
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Lin Liu
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Dafei Chai
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
| | - Tengfei Song
- The Feinstein Institute for Medical Research, Manhasset, NY 11030, New York, United States
| | - Ningjun Zhao
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Xianliang Yan
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Tie Xu
- Jiangsu Institute of Health Emergency, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
- Department of Emergency Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, China
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Abstract
The acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality in the intensive care unit. Improving outcomes depends on not only evidence-based care once ARDS has already developed but also preventing ARDS incidence. Several environmental exposures have now been shown to increase the risk of ARDS and related adverse outcomes. How environmental factors impact the risk of developing ARDS is a growing and important field of research that should inform the care of individual patients as well as public health policy.
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Affiliation(s)
- Katherine D Wick
- Department of Anesthesia, University of California, San Francisco, 513 Parnassus Avenue, HSE 760, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA
| | - Michael A Matthay
- Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, M-917, San Francisco, CA 94143, USA; Department of Anesthesia, University of California, San Francisco, 505 Parnassus Avenue, M-917, San Francisco, CA 94143, USA.
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Meije Y, Duarte-Borges A, Sanz X, Clemente M, Ribera A, Ortega L, González-Pérez R, Cid R, Pareja J, Cantero I, Ariño M, Sagués T, LLaberia J, Ayestarán A, Fernández-Hidalgo N, Candás-Estébanez B. Long-term outcomes of patients following hospitalization for coronavirus disease 2019: a prospective observational study. Clin Microbiol Infect 2021; 27:1151-1157. [PMID: 33901667 PMCID: PMC8062910 DOI: 10.1016/j.cmi.2021.04.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/31/2021] [Accepted: 04/06/2021] [Indexed: 12/29/2022]
Abstract
OBJECTIVES Few data are available regarding follow up of patients with coronavirus disease 2019 (COVID-19) after their discharge. We aim to describe the long-term outcomes of survivors of hospitalization for COVID-19 followed up first at an outpatient facility and subsequently by telephone. METHODS Observational prospective study conducted at a tertiary general hospital. Clinical and radiological progression was assessed and data were recorded on a standardized reporting form. Patients were divided into three groups according to Pao2/Fio2 at hospitalization: Pao2/Fio2 >300, Pao2/Fio2 300-200 and Pao2/Fio2 <200. A logistic multivariate regression model was performed to identify factors associated with persistence of symptoms. RESULTS For facility follow up, 302 individuals were enrolled. Median follow up was 45 days after discharge; 78% (228/294) of patients had COVID-19-related symptoms (53% asthenia, 56% respiratory symptoms) and 40% (122/302) had residual pulmonary radiographic lesions. Pao2/Fio2 <200 was an independent predictor of persistent dyspnoea (OR 1.87, 95% CI 1.38-2.52, p < 0.0001). Pao2/Fio2 >300 was associated with resolution of chest radiographic lesions (OR 0.56, 95% CI 0.42-0.74, p < 0.0001). Fifty per cent of patients required specific medical follow up after the first consultation and were transferred to another physician. A total of 294 patients were contacted for telephone follow up after a median follow-up time of 7 months. Fifty per cent of patients (147/294) still presented symptoms and 49% (145/294) had psychological disorders. Asthenia was identified in 27% (78/294) and dyspnoea in 10% (28/294) of patients independently of Pao2/Fio2. CONCLUSIONS Patients with COVID-19 require long-term follow up because of the persistence of symptoms; patients with low Pao2/Fio2 during the acute illness require special attention.
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Affiliation(s)
- Yolanda Meije
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Joint Commission for Infectious Disease Management, Control & Prevention, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain.
| | - Alejandra Duarte-Borges
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Joint Commission for Infectious Disease Management, Control & Prevention, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Xavier Sanz
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Mercedes Clemente
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Alba Ribera
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Joint Commission for Infectious Disease Management, Control & Prevention, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Lucía Ortega
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Ruth González-Pérez
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Roser Cid
- Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Júlia Pareja
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Irene Cantero
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Miquel Ariño
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Teresa Sagués
- Infectious Disease Unit - Internal Medicine Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Jaume LLaberia
- Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Joint Commission for Infectious Disease Management, Control & Prevention, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Microbiology Unit, Clinical Laboratory Department. Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Ana Ayestarán
- Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Joint Commission for Infectious Disease Management, Control & Prevention, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Pharmacy Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
| | - Nuria Fernández-Hidalgo
- Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain
| | - Beatriz Candás-Estébanez
- Multidisciplinary COVID-Team, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain; Biochemistry Unit, Clinical Laboratory Department, Hospital de Barcelona, Societat Cooperativa d'Instal·lacions Assistencials Sanitàries (SCIAS), Barcelona, Spain
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Prkachin Y. The Reign of the Ventilator: Acute Respiratory Distress Syndrome, COVID-19, and Technological Imperatives in Intensive Care. Ann Intern Med 2021; 174:1145-1150. [PMID: 33939486 PMCID: PMC8112582 DOI: 10.7326/m21-0270] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
In the early phase of the COVID-19 pandemic, a dispute arose as to whether the disease caused a typical or atypical version of acute respiratory distress syndrome (ARDS). This essay recounts the emergence of ARDS and places it in the context of the technological transformation of modern hospital care-particularly the emergence of intensive care after the 1952 Copenhagen polio epidemic. The polio epidemic seemed to show the value of manual positive-pressure ventilation, leading to the proliferation of mechanical ventilators and the expansion of intensive care units in the 1960s. This created the conditions of possibility for ARDS to be described and institutionalized within modern intensive care. Yet the centrality of the ventilator to descriptions and definitions of ARDS quickly made it difficult to conceive of the disorder outside the framework of mechanical ventilation and blood gas levels, or to acknowledge the degree to which the ventilator was a source of iatrogenic injury and complications. Moreover, the imperative to understand and treat ARDS with mechanical ventilation set the stage for the early confusion about whether patients with COVID-19 should receive mechanical ventilation. This history offers many crucial lessons about how new technologies can lead to new and valuable therapies but can also subtly shape and constrain medical thinking. Moreover, ventilators not only changed how respiratory disorders were conceived; they also brought new forms of respiratory illness into existence.
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Wilkins D, Lane AS, Orde SR. Audit of low tidal volume ventilation in patients with hypoxic respiratory failure in a tertiary Australian intensive care unit. Anaesth Intensive Care 2021; 49:301-308. [PMID: 34324389 DOI: 10.1177/0310057x21993132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
A low tidal volume ventilation (LTVV) strategy improves outcomes in patients with acute respiratory distress syndrome (ARDS). Subsequently, a LTVV strategy has become the standard of care for patients receiving mechanical ventilation. This strategy is poorly adhered to within intensive care units (ICUs). A retrospective analysis was conducted of prescribed tidal volumes in mechanically ventilated patients with hypoxic respiratory failure between April 2013 and March 2017. Data collection included the establishment of a new data-entry box for patient height in March 2016, aimed at assisting the calculation of LTVV. We reviewed 836 ICU admissions, comprising 19,884 hours of ventilation. A total of 92% of admissions lacked patient height recording. When height was recorded, 54% of hours of ventilation were LTVV adherent. Non-LTVV hours for both groups involved higher tidal volumes (38%) rather than lower tidal volumes (8%). Non-LTVV-adherent hours were significantly (P<0.001) more likely to be associated with patient mortality than LTVV-adherent hours were. For all hours of ventilation, mean tidal volume before March 2016 was significantly higher (496 (standard deviation (SD) 101) ml, compared to after March 2016 (451 (SD 107) ml, P<0.001, 95% confidence interval for true difference in means 42 to 48 ml). However, this trend gradually reversed over time. There was a clinician preference for multiples of 50 ml. There was poor adherence to LTVV strategy in patients with hypoxic respiratory failure, which was associated with an increase in patient mortality. An electronic medical record intervention was successful in producing change, but this was not sustainable over time. Clinician ventilation prescribing habits were based on numerical simplicity rather than evidence-based practice.
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Affiliation(s)
- David Wilkins
- Sydney Medical School, The University of Sydney, Sydney, Australia
| | - Andrew S Lane
- Sydney Medical School, The University of Sydney, Sydney, Australia.,Intensive Care Unit, Nepean Hospital, Penrith, Australia
| | - Sam R Orde
- Intensive Care Unit, Nepean Hospital, Penrith, Australia
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Wick KD, Leligdowicz A, Zhuo H, Ware LB, Matthay MA. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight 2021; 6:148983. [PMID: 33974564 PMCID: PMC8262503 DOI: 10.1172/jci.insight.148983] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/05/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Whether airspace biomarkers add value to plasma biomarkers in studying acute respiratory distress syndrome (ARDS) is not well understood. Mesenchymal stromal cells (MSCs) are an investigational therapy for ARDS, and airspace biomarkers may provide mechanistic evidence for MSCs’ impact in patients with ARDS. METHODS We carried out a nested cohort study within a phase 2a safety trial of treatment with allogeneic MSCs for moderate-to-severe ARDS. Nonbronchoscopic bronchoalveolar lavage and plasma samples were collected 48 hours after study drug infusion. Airspace and plasma biomarker concentrations were compared between the MSC (n = 17) and placebo (n = 10) treatment arms, and correlation between the two compartments was tested. Airspace biomarkers were also tested for associations with clinical and radiographic outcomes. RESULTS Compared with placebo, MSC treatment significantly reduced airspace total protein, angiopoietin-2 (Ang-2), IL-6, and soluble TNF receptor-1 concentrations. Plasma biomarkers did not differ between groups. Each 10-fold increase in airspace Ang-2 was independently associated with 6.7 fewer days alive and free of mechanical ventilation (95% CI, –12.3 to –1.0, P = 0.023), and each 10-fold increase in airspace receptor for advanced glycation end-products (RAGE) was independently associated with a 6.6-point increase in day 3 radiographic assessment of lung edema score (95% CI, 2.4 to 10.8, P = 0.004). CONCLUSION MSCs reduced biological evidence of lung injury in patients with ARDS. Biomarkers from the airspaces provide additional value for studying pathogenesis, treatment effects, and outcomes in ARDS. TRIAL REGISTRATION ClinicalTrials.gov NCT02097641. FUNDING National Heart, Lung, and Blood Institute.
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Affiliation(s)
- Katherine D Wick
- Departments of Medicine and Anesthesia and.,Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA
| | - Aleksandra Leligdowicz
- Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA.,Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Hanjing Zhuo
- Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA
| | - Lorraine B Ware
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and.,Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Michael A Matthay
- Departments of Medicine and Anesthesia and.,Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA
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Kim BK, Kim S, Kim CY, Kim YJ, Lee SH, Cha JH, Kim JH. Predictive Role of Lung Injury Prediction Score in the Development of Acute Respiratory Distress Syndrome in Korea. Yonsei Med J 2021; 62:417-423. [PMID: 33908212 PMCID: PMC8084702 DOI: 10.3349/ymj.2021.62.5.417] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 01/14/2021] [Accepted: 03/04/2021] [Indexed: 12/29/2022] Open
Abstract
PURPOSE Early recognition and therapeutic intervention are important in patients at high risk of acute respiratory distress syndrome (ARDS). The lung injury prediction score (LIPS) has been used to predict ARDS development; however, it was developed based on the previous definition of ARDS. We investigated the predictive role of LIPS in ARDS development according to its Berlin definition in the Korean population. MATERIALS AND METHODS This was a retrospective study that enrolled adult patients admitted to the intensive care unit (ICU) at a single university-affiliated hospital in Korea from September 1, 2018, to August 31, 2019. LIPS at the time of ICU admission and the development of ARDS were evaluated. RESULTS Of the 548 enrolled patients, 33 (6.0%) fulfilled the Berlin ARDS definition. The LIPS for non-ARDS and ARDS groups were 4.96±3.05 and 8.53±2.45, respectively (p<0.001); it was significantly associated with ARDS development (odds ratio 1.48, 95% confidence interval, 1.29-1.69; p<0.001). LIPS >6 predicted the development of ARDS with a sensitivity of 84.8% and a specificity of 67.2% [area under the curve (AUC)=0.82]. A modified LIPS model adjusted for age and severity at ICU admission predicted ICU mortality in patients with ARDS (AUC=0.80), but not in those without ARDS (AUC=0.54). CONCLUSION LIPS predicted the development of ARDS as diagnosed by the Berlin definition in the Korean population. LIPS provides useful information for managing patients with ARDS.
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Affiliation(s)
- Beong Ki Kim
- Division of Pulmonology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Sua Kim
- Department of Critical Care Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Chi Young Kim
- Division of Pulmonology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Yu Jin Kim
- Division of Pulmonology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Seung Heon Lee
- Division of Pulmonology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Jae Hyung Cha
- Medical Science Research Center, Korea University Ansan Hospital, Ansan, Korea
| | - Je Hyeong Kim
- Division of Pulmonology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
- Department of Critical Care Medicine, Korea University Ansan Hospital, Ansan, Korea.
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Tiba MH, McCracken BM, Leander DC, Colmenero CI, Nemzek JA, Sjoding MW, Konopka KE, Flott TL, VanEpps JS, Daniels RC, Ward KR, Stringer KA, Dickson RP. A novel swine model of the acute respiratory distress syndrome using clinically relevant injury exposures. Physiol Rep 2021; 9:e14871. [PMID: 33991456 PMCID: PMC8123544 DOI: 10.14814/phy2.14871] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 04/17/2021] [Indexed: 12/18/2022] Open
Abstract
To date, existing animal models of the acute respiratory distress syndrome (ARDS) have failed to translate preclinical discoveries into effective pharmacotherapy or diagnostic biomarkers. To address this translational gap, we developed a high-fidelity swine model of ARDS utilizing clinically relevant lung injury exposures. Fourteen male swine were anesthetized, mechanically ventilated, and surgically instrumented for hemodynamic monitoring, blood, and tissue sampling. Animals were allocated to one of three groups: (1) Indirect lung injury only: animals were inoculated by direct injection of Escherichia coli into the kidney parenchyma, provoking systemic inflammation and distributive shock physiology; (2) Direct lung injury only: animals received volutrauma, hyperoxia, and bronchoscope-delivered gastric particles; (3) Combined indirect and direct lung injury: animals were administered both above-described indirect and direct lung injury exposures. Animals were monitored for up to 12 h, with serial collection of physiologic data, blood samples, and radiographic imaging. Lung tissue was acquired postmortem for pathological examination. In contrast to indirect lung injury only and direct lung injury only groups, animals in the combined indirect and direct lung injury group exhibited all of the physiological, radiographic, and histopathologic hallmarks of human ARDS: impaired gas exchange (mean PaO2 /FiO2 ratio 124.8 ± 63.8), diffuse bilateral opacities on chest radiographs, and extensive pathologic evidence of diffuse alveolar damage. Our novel porcine model of ARDS, built on clinically relevant lung injury exposures, faithfully recapitulates the physiologic, radiographic, and histopathologic features of human ARDS and fills a crucial gap in the translational study of human lung injury.
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Affiliation(s)
- Mohamad H. Tiba
- Department of Emergency MedicineUniversity of MichiganAnn ArborMIUSA
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
| | - Brendan M. McCracken
- Department of Emergency MedicineUniversity of MichiganAnn ArborMIUSA
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
| | - Danielle C. Leander
- Department of Emergency MedicineUniversity of MichiganAnn ArborMIUSA
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
| | - Carmen I. Colmenero
- Department of Emergency MedicineUniversity of MichiganAnn ArborMIUSA
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
| | - Jean A. Nemzek
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Unit of Laboratory Animal MedicineUniversity of MichiganAnn ArborMIUSA
| | - Michael W. Sjoding
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Division of Pulmonary and Critical Care MedicineDepartment of Internal MedicineUniversity of MichiganAnn ArborMIUSA
- Institute for Healthcare Policy and InnovationUniversity of MichiganAnn ArborMIUSA
- Department of Computational Medicine and BioinformaticsUniversity of MichiganAnn ArborMIUSA
| | - Kristine E. Konopka
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Department of PathologyUniversity of MichiganAnn ArborMIUSA
| | - Thomas L. Flott
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Department of Clinical PharmacyCollege of PharmacyUniversity of MichiganAnn ArborMIUSA
| | - J. Scott VanEpps
- Department of Emergency MedicineUniversity of MichiganAnn ArborMIUSA
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Department of Biomedical EngineeringUniversity of MichiganAnn ArborMIUSA
- Biointerfaces InstituteUniversity of MichiganAnn ArborMIUSA
| | - Rodney C. Daniels
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Department of Biomedical EngineeringUniversity of MichiganAnn ArborMIUSA
- Department of PediatricsPediatric Critical Care MedicineUniversity of MichiganAnn ArborMIUSA
| | - Kevin R. Ward
- Department of Emergency MedicineUniversity of MichiganAnn ArborMIUSA
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Department of Biomedical EngineeringUniversity of MichiganAnn ArborMIUSA
| | - Kathleen A. Stringer
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Division of Pulmonary and Critical Care MedicineDepartment of Internal MedicineUniversity of MichiganAnn ArborMIUSA
- Department of Clinical PharmacyCollege of PharmacyUniversity of MichiganAnn ArborMIUSA
| | - Robert P. Dickson
- Michigan Center for Integrative Research in Critical CareUniversity of MichiganAnn ArborMIUSA
- Division of Pulmonary and Critical Care MedicineDepartment of Internal MedicineUniversity of MichiganAnn ArborMIUSA
- Department of Microbiology & ImmunologyUniversity of MichiganAnn ArborMIUSA
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Sayed M, Riaño D, Villar J. Novel criteria to classify ARDS severity using a machine learning approach. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2021; 25:150. [PMID: 33879214 PMCID: PMC8056190 DOI: 10.1186/s13054-021-03566-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 04/05/2021] [Indexed: 12/15/2022]
Abstract
Background Usually, arterial oxygenation in patients with the acute respiratory distress syndrome (ARDS) improves substantially by increasing the level of positive end-expiratory pressure (PEEP). Herein, we are proposing a novel variable [PaO2/(FiO2xPEEP) or P/FPE] for PEEP ≥ 5 to address Berlin’s definition gap for ARDS severity by using machine learning (ML) approaches. Methods We examined P/FPE values delimiting the boundaries of mild, moderate, and severe ARDS. We applied ML to predict ARDS severity after onset over time by comparing current Berlin PaO2/FiO2 criteria with P/FPE under three different scenarios. We extracted clinical data from the first 3 ICU days after ARDS onset (N = 2738, 1519, and 1341 patients, respectively) from MIMIC-III database according to Berlin criteria for severity. Then, we used the multicenter database eICU (2014–2015) and extracted data from the first 3 ICU days after ARDS onset (N = 5153, 2981, and 2326 patients, respectively). Disease progression in each database was tracked along those 3 ICU days to assess ARDS severity. Three robust ML classification techniques were implemented using Python 3.7 (LightGBM, RF, and XGBoost) for predicting ARDS severity over time. Results P/FPE ratio outperformed PaO2/FiO2 ratio in all ML models for predicting ARDS severity after onset over time (MIMIC-III: AUC 0.711–0.788 and CORR 0.376–0.566; eICU: AUC 0.734–0.873 and CORR 0.511–0.745). Conclusions The novel P/FPE ratio to assess ARDS severity after onset over time is markedly better than current PaO2/FiO2 criteria. The use of P/FPE could help to manage ARDS patients with a more precise therapeutic regimen for each ARDS category of severity. Supplementary Information The online version contains supplementary material available at 10.1186/s13054-021-03566-w.
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Affiliation(s)
- Mohammed Sayed
- Banzai Research Group On Artificial Intelligence, Department of Computer Engineering, Universitat Rovira I Virgili, Av Paisos Catalans 26, 43007, Tarragona, Spain.
| | - David Riaño
- Banzai Research Group On Artificial Intelligence, Department of Computer Engineering, Universitat Rovira I Virgili, Av Paisos Catalans 26, 43007, Tarragona, Spain.
| | - Jesús Villar
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. .,Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr Negrín, Barranco de la Ballena s/n, 4th Floor -South Wing, 35019, Las Palmas de Gran Canaria, Spain. .,Keenan Research Center for Biomedical Science at the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada.
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Ho K, Gordon J, Litzenberg KT, Exline MC, Englert JA, Herman DD. Cancer Is an Independent Risk Factor for Acute Respiratory Distress Syndrome in Critically Ill Patients: A Single Center Retrospective Cohort Study. J Intensive Care Med 2021; 37:385-392. [PMID: 33779386 DOI: 10.1177/08850666211005422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Acute Respiratory Distress Syndrome (ARDS) is a frequent cause of respiratory failure in intensive care unit (ICU) patients and results in significant morbidity and mortality. ARDS often develops as a result of a local or systemic inflammatory insult. Cancer can lead to systemic inflammation but whether cancer is an independent risk factor for developing ARDS is unknown. We hypothesized that critically ill cancer patients admitted to the ICU were at increased risk for the diagnosis of ARDS. METHODS Retrospective cohort study of critically ill patients admitted between July 2017 and December 2018 at an academic medical center in Columbus, Ohio. The primary outcome was the association of patients with malignancy and the diagnosis of ARDS in a multivariable logistic regression model with covariables selected a priori informed through the construction of a directed acyclic graph. RESULTS 412 ARDS cases were identified with 166 of those patients having active cancer. There was an association between cancer and ARDS, with an odds ratio (OR) of 1.55 (95% CI 1.26-1.92, P < 0.001). When adjusted for our pre-specified confounding variables, the association remained statistically significant (OR 1.57, 95% CI 1.15-2.13, P = 0.004). In an unadjusted pre-specified subgroup analysis, hematologic malignancy (OR 1.81, 95% CI 1.30-2.53, P < 0.001) was associated with increased odds of developing ARDS while non-metastatic solid tumors (OR 0.51, 95% CI 0.31-0.85, P = 0.01) had statistically significant negative association. Cancer patients with ARDS had a significantly higher ICU (70.5% vs 39.8%, P < 0.001) and hospital (72.9% vs 40.7%, P < 0.001) mortality compared to ARDS patients without active malignancy. CONCLUSION In this single center retrospective cohort study, cancer was found to be an independent risk factor for the diagnosis of ARDS in critically ill patients. To our knowledge, we are the first report an independent association between cancer and ARDS in critically ill patients.
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Affiliation(s)
- Kevin Ho
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Joshua Gordon
- Division of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Kevin T Litzenberg
- Division of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Matthew C Exline
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Joshua A Englert
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Derrick D Herman
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Guo J, Zhu J, Wang Q, Wang J, Jia Y. Comparative Efficacy of Seven Kinds of Chinese Medicine Injections in Acute Lung Injury and Acute Respiratory Distress Syndrome: A Network Meta-analysis of Randomized Controlled Trials. Front Pharmacol 2021; 12:627751. [PMID: 33767627 PMCID: PMC7985440 DOI: 10.3389/fphar.2021.627751] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/28/2021] [Indexed: 01/01/2023] Open
Abstract
Background: Chinese medicine injection is wildly used in Acute Lung Injury and Acute respiratory distress syndrome (ALI/ARDS) treatment. However, what kinds of CMIs are more effective in the ALI/ARDS treatment is uncertain. Objectives: Compare the efficacy of different CMIs to identify the optimal one for the therapy of ALI/ARDS patients. Data sources: We searched the data up to April 30, 2020 from MEDLINE, EMBASE, The Cochrane Library, Web of Science, the China Science Journal Citation Report (VIP database), WanFang and the China National Knowledge Infrastructure Study selection: Randomized Clinical Trials assessed at least one of the following outcomes: mortality, Oxygenation Index, length of ICU stay, mechanical ventilation duration, APACHEⅡ score, SOFA score and Murray score, for adult patients of ALI/ADRS. Eligible Studies should also use CMIs as complementary therapies in addition to the standard treatment. Data extraction and synthesis: Two reviewers independently assessed the data. Then, we used a Bayesian random-effects network meta-analysis for data synthesis. Results: Twenty-six studies were selected (involved 2073 participants). Seven kinds of CMIs were evaluated. Compared with standard treatment, Xuebijing is associated with lower mortality. Tanreqing and Xuebijing have the best effect on improving the Oxygenation Index. Huangqi, Danshen, Tanreqing and Xuebijing can significantly reduce the APACHE II score (Huangqi works better than Xuebijing). Huangqi and Xuebijing have the best effect on reducing mechanical ventilation duration and Murray score, while Xuebijing has the best effect on shortening the length of ICU stay. Conclusions: As adjuvant drugs, Xuebijing, Tanreqing and Huangqi show certain effects on treating ALI/ARDS in different aspects.
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Affiliation(s)
- Jie Guo
- Department of Internal Medicine of TCM, The First Clinical Medical College, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Chinese Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Jia Zhu
- Department of Respiratory medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Qian Wang
- Department of Respiratory medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Juan Wang
- Department of Internal Medicine of TCM, The First Clinical Medical College, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Intensive Medicine, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Yaodan Jia
- Environmental science, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
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Effectiveness of Glucocorticoids in Acute Respiratory Distress Syndrome: An Umbrella Review. Crit Care Res Pract 2021. [DOI: 10.1155/2021/7068762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Objectives. Acute respiratory distress syndrome is a very challenging condition that is associated with high morbidity and mortality. This review was intended to evaluate evidence on the effectiveness of glucocorticoid treatment for acute respiratory distress syndrome. Method. A comprehensive search strategy was conducted on PubMed/Medline, Cochrane Library, Science Direct, and LILACS. Data extraction was carried out by two independent reviewers using a customized checklist. The quality of each systematic review was assessed by two independent reviewers using an AMSTAR tool, and the overall quality of evidence was generated with online GRADEpro GDT software for primary and secondary outcomes. Results. The umbrella review included nine systematic reviews and meta-analysis and one narrative review with 8491 participants. The methodological quality of the included studies was moderate-to-high quality. The overall quality of evidence and recommendations varied form high to very low. Conclusion. There is high-to-moderate quality evidence that early low-dose prolonged glucocorticoid therapy reduces mortality in ARDS. However, randomized controlled trials with large sample sizes to address ventilator-free days, the incidence of infection, and other glucocorticoid-associated adverse events are required as the quality of evidence for these secondary outcomes which were low to very low. Registration. This umbrella review was registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42019130539).
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Yamanoğlu A, Celebi Yamanoğlu NG. Bedside ultrasound in the management of critically ill patients; Echocardiographic signs of acute respiratory distress syndrome and pulmonary embolism can be very similar, and lung ultrasound can act as a key: A case report. JOURNAL OF CLINICAL ULTRASOUND : JCU 2021; 49:159-163. [PMID: 32856315 DOI: 10.1002/jcu.22910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 05/26/2020] [Accepted: 08/04/2020] [Indexed: 06/11/2023]
Abstract
Right-sided heart failure (RHF) diagnosed at point-of-care-ultrasonography examination of critical patients may reveal an acute disease, such as pulmonary embolism (PE), requiring emergency thrombolytic treatment. However, acute respiratory distress syndrome (ARDS) and PE leading to acute RHF may exhibit very similar echocardiographic features. We report the case of a 27-year-old pregnant woman diagnosed with ARDS due to septic abortion, and in whom ARDS mimicked PE both clinically and on echocardiography. Such similarity may lead to inappropriate administration of thrombolytic therapy and/or delay the correct treatment. Lung ultrasonography may help avoiding this pitfall.
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Affiliation(s)
- Adnan Yamanoğlu
- Department of Emergency Medicine, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
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