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Wang Y, Wu J, Shao T, Su D, Ma X, Yu Z, Li N. PROGNOSTIC IMPLICATIONS OF CHANGES IN PLATELET TRAJECTORIES IN PATIENTS WITH SEPSIS: A RETROSPECTIVE ANALYSIS USING THE MEDICAL INFORMATION MART FOR INTENSIVE CARE IV DATABASE. Shock 2025; 63:371-378. [PMID: 39450919 DOI: 10.1097/shk.0000000000002493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
ABSTRACT Objective: Patients with sepsis often experience reductions or increases in platelet counts, but the implications of these temporal patterns on prognosis remain unclear. The aim of this study was to investigate the impact of changes in platelet trajectories on the clinical prognosis of sepsis. Methods: This study was a retrospective analysis using data from the Medical Information Mart for Intensive Care IV database. Patients with sepsis were identified from the database, and their platelet trajectories were categorized into four distinct models based on the changes in platelet counts over a period of 14 days after diagnosis of sepsis. The effect of these trajectories on patient prognosis was subsequently evaluated. Results: A total of 15,250 patients with sepsis were included to construct a model, and the following four distinct platelet count trajectories were identified: normal platelet levels (phenotype 1); persistently low platelet levels (phenotype 2); gradually increasing platelet levels exceeding the normal range (phenotype 3); and consistently significantly elevated platelet levels (phenotype 4). Statistically significant differences were found in the 28-day mortality, in-hospital mortality, and 90-day mortality among the four phenotypes. Multivariate regression analysis showed that compared to the group with normal platelet levels (phenotype 1), the group with persistently low platelet levels (phenotype 2) had higher in-hospital mortality (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 1.16-1.54), 28-day mortality (OR = 1.69, 95% CI: 1.47-1.94), and 90-day mortality (OR = 1.50, 95% CI: 1.32-1.69). There was no difference in in-hospital mortality between phenotypes 3 and 4 compared to phenotype 1, although phenotype 4 showed an increase in 28-day mortality ( P < 0.05), and phenotype 3 showed a decreasing trend in 90-day mortality ( P < 0.05). The results of inverse probability weighting adjusted by regression were basically consistent with the above findings, except that there was no statistical difference in 28-day mortality between phenotype 4 and phenotype 1. In the subgroups based on age, weight, and antiplatelet drugs or therapies, there was an interaction between platelet levels and these factors. Conclusions: In patients with sepsis, a decrease in platelet count is associated with increased mortality, while a moderate increase in platelet count can reduce 90-day mortality. However, for patients with persistently elevated platelet counts, caution is advised when using antiplatelet drugs or therapies, as it may increase mortality.
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Affiliation(s)
- Yingxin Wang
- Department of Critical Care Medicine, Affiliated Hospital of Hebei University, BaoDing, China
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Rapszky GA, Do To UN, Kiss VE, Kói T, Walter A, Gergő D, Meznerics FA, Rakovics M, Váncsa S, Kemény LV, Csupor D, Hegyi P, Filbin MR, Varga C, Fenyves BG. Rapid molecular assays versus blood culture for bloodstream infections: a systematic review and meta-analysis. EClinicalMedicine 2025; 79:103028. [PMID: 39968206 PMCID: PMC11833021 DOI: 10.1016/j.eclinm.2024.103028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 12/07/2024] [Accepted: 12/12/2024] [Indexed: 02/20/2025] Open
Abstract
Background Timely management of sepsis with early targeted antimicrobial therapy improves patient outcomes. Rapid molecular assays (RMAs) have emerged, enabling the detection of bloodstream infection (BSI) with a shorter turnaround time than blood cultures (BCs). The accuracy of several RMAs has not been comprehensively reviewed. We aimed to identify commercial RMAs reported in the literature and evaluate their diagnostic performance compared to BC. Methods A systematic review and meta-analysis was conducted, covering MEDLINE, Cochrane Library, Embase, and Web of Science from inception to September 23, 2024. Eligible studies included patients with suspected or documented BSI, tested with both an RMA (turnaround time of ≤12 h, targeting ≥20 pathogens) and BC. Non-original research articles and animal studies were excluded. The primary outcomes were pooled sensitivity and specificity of RMAs for pathogen detection compared to BC. Bivariate analysis was used to produce summary receiver operating characteristic plots and diagnostic metric measures stratified by different units of analysis (sample versus patient), RMA types, and patient populations. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) tools. The study was registered with PROSPERO, CRD42022377280. Findings A total of 63,916 articles were identified, of which 104 were included in the qualitative synthesis and 75 in the quantitative synthesis, covering 17,952 samples and 11,393 patients analyzed separately. Eleven RMAs were identified, with four included in the RMA-based subgroup analysis (LightCycler SeptiFast Test MGRADE®, IRIDICA BAC BSI assay, SepsiTest, MagicPlex Sepsis Test) and five additional ones in the pooled analysis (UMD-SelectNA, VYOO®, MicrobScan assay, MicrobScan-Kairos24/7, REBA Sepsis-ID test). Two RMAs were included in the qualitative synthesis only (InfectID-BSI, Pilot Gene Technology droplet digital polymerase chain reaction). Pooled specificity of RMAs was higher (0.858, 95% confidence interval (CI) 0.830-0.883) than sensitivity (0.659, 95% CI 0.594-0.719) by patient. Sensitivities varied by RMA type from 0.492 (95% CI 0.390-0.594, MagicPlex Sepsis Test) to 0.783 (95% CI 0.662-0.870, IRIDICA BAC BSI assay) by patient. Specificities varied more by patient population, ranging from 0.811 (95% CI 0.716-0.879) in the intensive care population to 0.892 (95% CI 0.838-0.930) in the emergency department population, by patient. Similar metrics were observed when the analysis was done by sample. Risk of bias was judged to be high in all included articles. Interpretation Despite their shorter turnaround time, low sensitivity means RMAs cannot replace BCs. However, our data indicate that RMAs may have value as an add-on test by increasing pathogen detection rates. Higher-sensitivity RMAs are needed which could possibly be achieved by expanding pathogen coverage and increasing blood sample volumes. High-quality implementation studies and standardized reporting are required to assess the clinical advantages of RMAs. Funding Centre for Translational Medicine, Semmelweis University.
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Affiliation(s)
- Gabriella Anna Rapszky
- Department of Emergency Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Uyen Nguyen Do To
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- András Pető Faculty, Semmelweis University, Budapest, Hungary
| | | | - Tamás Kói
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Budapest University of Technology and Economics, Department of Stochastics, Budapest, Hungary
| | - Anna Walter
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Dorottya Gergő
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
| | - Fanni Adél Meznerics
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary
| | - Márton Rakovics
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Eötvös Loránd University, Faculty of Social Sciences, Department of Statistics, Budapest, Hungary
| | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Lajos Vince Kemény
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary
- Department of Physiology, Semmelweis University, Budapest, Hungary
- HCEMM-SU, Translational Dermatology Research Group, Semmelweis University, Budapest, Hungary
| | - Dezső Csupor
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Michael R. Filbin
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Emergency Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Csaba Varga
- Department of Emergency Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Bánk G. Fenyves
- Department of Emergency Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Molecular Biology, Semmelweis University, Budapest, Hungary
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Li J, Xiao F, Lin B, Huang Z, Wu M, Ma H, Dou R, Song X, Wang Z, Cai C, Guan X, Xu J, Xiang FL. Ferrostatin-1 improves acute sepsis-induced cardiomyopathy via inhibiting neutrophil infiltration through impaired chemokine axis. Front Cell Dev Biol 2024; 12:1510232. [PMID: 39726718 PMCID: PMC11669711 DOI: 10.3389/fcell.2024.1510232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 11/29/2024] [Indexed: 12/28/2024] Open
Abstract
Introduction Sepsis-induced cardiomyopathy is a common complication of sepsis and is associated with higher mortality. To date, effective diagnostic and management strategies are still lacking. Recent studies suggest that ferroptosis plays a critical role in sepsis-induced cardiomyopathy and ferroptosis inhibitor Ferrostatin-1 (Fer-1) improved cardiac dysfunction and survival in lipopolysaccharide (LPS) induced endotoxemia. However, the effects of Fer-1 in cardiac dysfunction in the early stages of cecal ligation and puncture (CLP) induced sepsis remains unclear. Our study aims to elucidate the role of Fer-1 in the acute phase of peritonitis sepsis induced cardiac injury. Methods and Results CLP was used to induce peritonitis sepsis in mice. Pretreatment of ferroptosis inhibitor ferrostatin-1 (Fer-1) was used in the in vivo models. Survival was monitored for 48h. Cardiac function and histology were analyzed 6h after surgery. We found that ejection fraction (EF) remained normal at 6h after CLP, but the contractility detected by cardiac muscle strain analysis was significantly reduced, along with increased immune cell infiltration. Pretreating the CLP mice with 5 mg/kg Fer-1 significantly reduced mortality. At 6h after CLP, ferroptosis key regulator Gpx4, cardiac iron and malonaldehyde (MDA) did not change, but ferroptosis marker gene expression increased. Fer-1 treatment showed beneficial effects in cardiac function, less myocardial inflammatory cytokine expression and significantly inhibited immune cells, especially neutrophil infiltration in the heart. Consistently, expression of neutrophil associated chemokines (Ccrl2, Cxcl2, Cxcl3 and Cxcl5) as well as extracellular matrix (ECM) degradation enzymes (Adamts1, Adamts4, Adamts9 and Mmp8) significantly decreased in Fer-1 pre-treated CLP heart. Conclusion and Discussion Our findings suggest that Fer-1 inhibits neutrophil infiltration in early sepsis by disrupting the chemokine axis, highlighting its potential as a therapeutic option to manage acute immune overactivation in early stages of sepsis-induced cardiomyopathy.
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Affiliation(s)
- Jialin Li
- Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Institute of Precision Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fang Xiao
- Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Institute of Precision Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bingsen Lin
- Institute of Precision Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Anesthesia, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhilei Huang
- Institute of Precision Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mingyue Wu
- Institute of Precision Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Huan Ma
- Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ruoxu Dou
- Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaodong Song
- Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhongxing Wang
- Department of Anesthesia, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Changjie Cai
- Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiangdong Guan
- Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jie Xu
- Institute of Precision Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China
| | - Fu-Li Xiang
- Institute of Precision Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- NHC Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China
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Lee R, Al Rifaie R, Subedi K, Coletti C. Comparative Analysis of Bacteremic and Non-bacteremic Sepsis: A Retrospective Study. Cureus 2024; 16:e76418. [PMID: 39872553 PMCID: PMC11770239 DOI: 10.7759/cureus.76418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2024] [Indexed: 01/30/2025] Open
Abstract
INTRODUCTION Sepsis remains a prevalent critical illness encountered in emergency departments and intensive care units (ICU), with culture-negative sepsis constituting 30-60% of cases. The effect of culture type on treatment and outcomes remains unclear, and conflicting evidence exists regarding disparities between Gram-positive and Gram-negative infections. OBJECTIVE To further describe and compare characteristics and outcomes of culture-positive versus culture-negative sepsis. DESIGN, SETTING AND PARTICIPANTS This retrospective cohort study included 1375 patients admitted to the ICU of a single tertiary care hospital between 2016 and 2019 with a diagnosis of sepsis or septic shock. Patients who did not meet the screening criteria, lacked drawn or documented cultures, or had documented non-bacterial infections, were excluded. MAIN OUTCOMES AND MEASURES The primary outcome was disease severity and secondary outcomes included in-hospital mortality and duration of hospital and ICU stay. The principal and secondary exposure variables were blood culture status (positive vs. negative) and Gram staining (positive vs. negative), respectively. RESULTS Overall, 943 patients (68.5%) were culture-negative and 432 (31.5%) were culture-positive. Gram-positive bacteria were isolated from 178 patients, Gram-negative bacteria from 199 patients, and both from 55 patients. Culture-positive patients demonstrated an almost two-fold higher likelihood of requiring vasopressors (adjusted odds ratio (OR): 1.98), a higher incidence of stress-dose steroid administration (adjusted OR, 1.68), and higher resuscitative fluid administration at six and 72 hours than culture-negative patients. No significant between-group differences emerged in the ICU or hospital length of stay, or mortality. No significant variations were observed when comparing Gram-positive and Gram-negative bacteremia. CONCLUSION Although significant differences in illness severity existed between blood culture-negative and blood culture-positive patients with sepsis, patient-oriented secondary outcomes did not exhibit significant between-group differences. These results indicate that clinicians should not be reassured by the lack of proven bacteremia in patients with suspected sepsis, given similar outcomes.
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Affiliation(s)
- Ryan Lee
- Emergency Medicine, Christiana Care Health System, Newark, USA
- Pulmonary and Critical Care Medicine, University of Maryland Medical Center, Baltimore, USA
| | - Rawaa Al Rifaie
- Emergency Medicine, Christiana Care Health System, Newark, USA
| | - Keshab Subedi
- Biostatistics, Christiana Care Health System, Newark, USA
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Wang K, Lu D, Wang F. Subphenotypes of platelet count trajectories in sepsis from multi-center ICU data. Sci Rep 2024; 14:20187. [PMID: 39215039 PMCID: PMC11364765 DOI: 10.1038/s41598-024-71186-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024] Open
Abstract
Although thrombocytopenia on admission to the ICU is associated with increased in-hospital mortality in septic patients, the role of longitudinally measured platelet counts, which are dynamically changing, is unclear. We aimed to identify patterns of dynamic platelet count trajectories and evaluate their association with outcomes and thrombocytopenia in septic patients. We tested the longitudinal platelet trajectory patterns of sepsis patients within the first four days of ICU admission in the MIMIC-IV database and their association with 28-day mortality, and independently validated our findings in the eICU-CRD database. Statistical methods used included multivariate regression, propensity score analysis, doubly robust estimation, gradient boosting model, and inverse probability weighting to ensure the robustness of our findings. A total of 22,866 septic patients were included in our study. The trajectory analysis categorizes patients into ascending (AS), stable (ST), or descending (DS) patterns. The risk of 28-day mortality was increased in the DS patients (OR = 2.464, 95%CI 1.895-3.203, p < 0.001) and ST patients (OR = 1.302, 95%CI 1.067-1.589, p = 0.009) compared to AS patients. The AS patients had lower ICU length of stay (2.36 vs. 4.32, p < 0.001) and 28-day maximum SOFA scores (5.00 vs. 6.00, p < 0.001) than the DS patients, but had more ventilator-free days within 28 days than the DS group (26.00 vs. 24.00, p < 0.001). The mediating effect of thrombocytopenia was significant (p < 0.001 for the average causal mediation effect (ACME)). Longitudinal platelet trajectory was associated with risk-adjusted 28-day mortality among patients with sepsis and was proportionally mediated through thrombocytopenia.
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Affiliation(s)
- Kai Wang
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China
| | - Dufu Lu
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China
| | - Fang Wang
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
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Zhang Z, Tan XJ, Shi HQ, Zhang H, Li JB, Liao XL. Bibliometric study of sepsis-associated liver injury from 2000 to 2023. World J Gastroenterol 2024; 30:3609-3624. [PMID: 39193568 PMCID: PMC11346150 DOI: 10.3748/wjg.v30.i30.3609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 06/28/2024] [Accepted: 07/16/2024] [Indexed: 08/08/2024] Open
Abstract
BACKGROUND Sepsis-associated liver injury (SLI) is a severe and prevalent complication of sepsis. AIM To explore the literature on SLI via a bibliometric approach. METHODS Reviews and articles correlated with SLI published from January 1, 2000 to October 28, 2023 were searched from the Web of Science Core Collection. Then, the searched data were analyzed using VOSviewer, CiteSpace, and R language. RESULTS There were 787 publications involved in this paper, comprising 745 articles and 42 reviews. China, the United States, and Germany are the primary publication sources in this area. Studies related to SLI primarily focused on mechanisms of pathogenesis, as evidenced by analyzing keywords, references, and the counting of original research. These studies mainly involved tumor necrosis factor alpha, inflammation, oxidative stress, and nuclear factor-kappa B. CONCLUSION There is significant growth in the research on SLI. Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms. According to the analyzed literature, the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.
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Affiliation(s)
- Zheng Zhang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Jiao Tan
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hai-Qing Shi
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Zhang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian-Bo Li
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xue-Lian Liao
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Critical Care Medicine, West China Tianfu Hospital of Sichuan University, Chengdu 610200, Sichuan Province, China
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Zhang Z, Tan XJ, Shi HQ, Zhang H, Li JB, Liao XL. Bibliometric study of sepsis-associated liver injury from 2000 to 2023. World J Gastroenterol 2024; 30:3610-3625. [DOI: 10.3748/wjg.v30.i30.3610] [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: 03/13/2024] [Revised: 06/28/2024] [Accepted: 07/16/2024] [Indexed: 08/08/2024] Open
Abstract
BACKGROUND Sepsis-associated liver injury (SLI) is a severe and prevalent complication of sepsis.
AIM To explore the literature on SLI via a bibliometric approach.
METHODS Reviews and articles correlated with SLI published from January 1, 2000 to October 28, 2023 were searched from the Web of Science Core Collection. Then, the searched data were analyzed using VOSviewer, CiteSpace, and R language.
RESULTS There were 787 publications involved in this paper, comprising 745 articles and 42 reviews. China, the United States, and Germany are the primary publication sources in this area. Studies related to SLI primarily focused on mechanisms of pathogenesis, as evidenced by analyzing keywords, references, and the counting of original research. These studies mainly involved tumor necrosis factor alpha, inflammation, oxidative stress, and nuclear factor-kappa B.
CONCLUSION There is significant growth in the research on SLI. Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms. According to the analyzed literature, the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.
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Affiliation(s)
- Zheng Zhang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Jiao Tan
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hai-Qing Shi
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Zhang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian-Bo Li
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xue-Lian Liao
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Critical Care Medicine, West China Tianfu Hospital of Sichuan University, Chengdu 610200, Sichuan Province, China
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Jouffroy R, Fabre T, Gilbert B, Travers S, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Gueye P. Association between prehospital ROX index with 30-day mortality among septic shock. Eur J Med Res 2024; 29:304. [PMID: 38822441 PMCID: PMC11141059 DOI: 10.1186/s40001-024-01902-8] [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: 03/18/2024] [Accepted: 05/24/2024] [Indexed: 06/03/2024] Open
Abstract
PURPOSE Respiratory dysfunction is one of the most frequent symptoms observed during sepsis reflecting hypoxemia and/or acidosis that may be assessed by the ROX index (ratio of oxygen saturation by pulse oximetry/fraction of inspired oxygen to respiratory rate). This study aimed to describe the relationship between the prehospital ROX index and 30-day mortality rate among septic shock patients cared for in the prehospital setting by a mobile intensive care unit (MICU). METHODS From May 2016 to December 2021, 530 septic shock patients cared for by a prehospital MICU were retrospectively analysed. Initial ROX index value was calculated at the first contact with MICU. A Cox regression analysis after propensity score matching was performed to assess the relationship between 30-day mortality rate and a ROX index ≤ 10. RESULTS Pulmonary, digestive and urinary sepsis were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality reached 31%. Cox regression analysis showed a significant association between 30-day mortality and a ROX index ≤ 10: adjusted hazard ratio of 1.54 [1.08-2.31], p < 0.05. CONCLUSIONS During the prehospital stage of septic shock patients cared for by a MICU, ROX index is significantly associated with 30-day mortality. A prehospital ROX ≤ 10 value is associated with a 1.5-fold 30-day mortality rate increase. Prospective studies are needed to confirm the ability of prehospital ROX to predict sepsis outcome since the prehospital setting.
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Affiliation(s)
- Romain Jouffroy
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique - Hôpitaux de Paris, 9 avenue Charles De Gaulle, 92100, Boulogne-Billancourt, France.
- U1018 INSERM, Centre de Recherche en Epidémiologie et Santé des Populations, Paris Saclay University, Gif-sur-Yvette, France.
- EA 7329, Institut de Recherche Médicale et d'Épidémiologie du Sport, Institut National du Sport, de l'Expertise et de la Performance, Paris, France.
| | - Tristan Fabre
- SAMU 972, Centre Hospitalier Universitaire de Martinique, Fort-de-France Martinique, France
- EA 7525, University of the Antilles, French West Indies, France
| | - Basile Gilbert
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | | | - Emmanuel Bloch-Laine
- Emergency Department, Cochin Hospital, Paris, France
- Emergency Department, SMUR, Hôtel Dieu Hospital, Paris, France
| | - Patrick Ecollan
- Intensive Care Unit, SMUR, Pitie Salpêtriere Hospital, 47 Boulevard de l'Hôpital, 75013, Paris, France
| | | | - Vincent Bounes
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | - Benoît Vivien
- SAMU de Paris, Service d'Anesthésie Réanimation, Hôpital Universitaire Necker - Enfants Malades, Assistance Publique - Hôpitaux de Paris, Université Paris Cité, Paris, France
| | - Papa Gueye
- SAMU 972, Centre Hospitalier Universitaire de Martinique, Fort-de-France Martinique, France
- EA 7525, University of the Antilles, French West Indies, France
- UR5_3 PC2E Pathologie Cardiaque, Toxicité Environnementale et Envenimations, Université des Antilles, Pointe-à-Pitre, France
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Makkar D, Gakhar D, Mishra V, Rakha A. Fine Tuning Mesenchymal Stromal Cells - Code For Mitigating Kidney Diseases. Stem Cell Rev Rep 2024; 20:738-754. [PMID: 38334884 DOI: 10.1007/s12015-024-10684-9] [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] [Accepted: 01/18/2024] [Indexed: 02/10/2024]
Abstract
Kidney Disease (KD), has a high global prevalence and accounts for one of the most prominent causes of morbidity and mortality in the twenty-first century. Despite the advances in our understanding of its pathophysiology, the only available therapy options are dialysis and kidney transplantation. Mesenchymal stem cells (MSCs) have proven to be a viable choice for KD therapy due to their antiapoptotic, immunomodulatory, antioxidative, and pro-angiogenic activities. However, the low engraftment, low survival rate, diminished paracrine ability, and delayed delivery of MSCs are the major causes of the low clinical efficacy. A number of preconditioning regimens are being tested to increase the therapeutic capabilities of MSCs. In this review, we highlight the various strategies to prime MSCs and their protective effects in kidney diseases.
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Affiliation(s)
- Diksha Makkar
- Department of Translational and Regenerative Medicine, PGIMER, Chandigarh, 160012, India
| | - Diksha Gakhar
- Department of Translational and Regenerative Medicine, PGIMER, Chandigarh, 160012, India
| | - Vinod Mishra
- Department of Translational and Regenerative Medicine, PGIMER, Chandigarh, 160012, India
| | - Aruna Rakha
- Department of Translational and Regenerative Medicine, PGIMER, Chandigarh, 160012, India.
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10
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Lu N, Qin H, Meng Z, Yu Y, Gao Q, Cheng Z, Liu C, Hu J. Inhibiting apoptosis and GSDME-mediated pyroptosis attenuates hepatic injury in septic mice. Arch Biochem Biophys 2024; 754:109923. [PMID: 38408533 DOI: 10.1016/j.abb.2024.109923] [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: 09/13/2023] [Revised: 02/01/2024] [Accepted: 02/03/2024] [Indexed: 02/28/2024]
Abstract
BACKGROUND Sepsis is characterized by severe inflammation and organ dysfunction resulting from a dysregulated organismal response to infection. Although pyroptosis has been presumably shown to be a major cause of multiple organ failure and septic death, whether gasdermin E (GSDME)-mediated pyroptosis occurs in septic liver injury and whether inhibiting apoptosis and GSDME-mediated pyroptosis can attenuate septic liver injury remain unclear. This study investigated the role of apoptosis and GSDME-mediated pyroptosis in septic liver injury. METHODS Adult male C57BL/6 mice were randomly divided into four groups: sham, cecal ligation puncture (CLP), CLP + Z-DEVD-FMK (a caspase-3 inhibitor, 5 mg/kg), and CLP + Ac-DMLD-CMK (a GSDME inhibitor, 5 mg/kg). Sepsis severity was assessed using the murine sepsis score (MSS). Hepatic tissue damage was observed by the hematoxylin-eosin staining method, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the levels of malondialdehyde (MDA), the concentrations of interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured according to the related kits, and the changes in the hepatic tissue reactive oxygen species (ROS) levels were detected by immunofluorescence (IF). The protein expression levels of cleaved caspase-3, GSDME-N, IL-1β, B-cell lymphoma-2 (Bcl-2), cytochrome C (Cyt-c), and acetaldehyde dehydrogenase 2 (ALDH2) were detected using western blotting. GSDME expression was detected by immunohistochemistry. RESULTS Compared with the Sham group, CLP mice showed high sepsis scores and obvious liver damage. However, in the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups, the sepsis scores were reduced and liver injury was alleviated. Compared with the Sham group, the serum ALT and AST activities, MDA and ROS levels, and IL-1β and TNF-α concentrations were increased in the CLP group, as well as the protein expression of cleaved caspase-3, GSDME-N, IL-1β, Cyt-c, and GSDME positive cells (P < 0.05). However, the expression levels of Bcl-2 and ALDH2 protein were decreased (P < 0.05). Compared with the CLP group, the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups showed low sepsis scores, ALT and AST activities, MDA and ROS levels, decreased IL-1β and TNF-α concentrations, and decreased expression of cleaved caspase-3, GSDME-N, IL-1β protein expression, and GSDME positive cells (P < 0.05). The expression levels of Bcl-2 and ALDH2 protein were increased (P < 0.05). CONCLUSION Apoptosis and GSDME-mediated pyroptosis are involved in the development of sepsis-induced hepatic injury. Inhibition of apoptosis and GSDME-mediated pyroptosis attenuates injury. ALDH2 plays a protective role by inhibiting apoptosis and pyroptosis.
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Affiliation(s)
- Na Lu
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, PR China; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, PR China; Clinical Research Center for Respiratory Disease (tumor) in Anhui Province, PR China.
| | - Hongqian Qin
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, PR China; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, PR China; Clinical Research Center for Respiratory Disease (tumor) in Anhui Province, PR China.
| | - Zhaofei Meng
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, PR China; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, PR China; Clinical Research Center for Respiratory Disease (tumor) in Anhui Province, PR China.
| | - Ying Yu
- Department of Physiology, Bengbu Medical University, Bengbu, 233000, Anhui, PR China.
| | - Qin Gao
- Department of Physiology, Bengbu Medical University, Bengbu, 233000, Anhui, PR China.
| | - Zhipeng Cheng
- School of Clinical Medicine, Bengbu Medical University, Bengbu, 233000, Anhui, PR China
| | - Chuanmiao Liu
- National Clinical Research Center for Infectious Diseases, 287 Changhuai Road, Bengbu, 233004, Anhui, PR China.
| | - Junfeng Hu
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical University, PR China; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, PR China; Clinical Research Center for Respiratory Disease (tumor) in Anhui Province, PR China.
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11
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Mollura M, Chicco D, Paglialonga A, Barbieri R. Identifying prognostic factors for survival in intensive care unit patients with SIRS or sepsis by machine learning analysis on electronic health records. PLOS DIGITAL HEALTH 2024; 3:e0000459. [PMID: 38489347 PMCID: PMC10942078 DOI: 10.1371/journal.pdig.0000459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 02/05/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND Systemic inflammatory response syndrome (SIRS) and sepsis are the most common causes of in-hospital death. However, the characteristics associated with the improvement in the patient conditions during the ICU stay were not fully elucidated for each population as well as the possible differences between the two. GOAL The aim of this study is to highlight the differences between the prognostic clinical features for the survival of patients diagnosed with SIRS and those of patients diagnosed with sepsis by using a multi-variable predictive modeling approach with a reduced set of easily available measurements collected at the admission to the intensive care unit (ICU). METHODS Data were collected from 1,257 patients (816 non-sepsis SIRS and 441 sepsis) admitted to the ICU. We compared the performance of five machine learning models in predicting patient survival. Matthews correlation coefficient (MCC) was used to evaluate model performances and feature importance, and by applying Monte Carlo stratified Cross-Validation. RESULTS Extreme Gradient Boosting (MCC = 0.489) and Logistic Regression (MCC = 0.533) achieved the highest results for SIRS and sepsis cohorts, respectively. In order of importance, APACHE II, mean platelet volume (MPV), eosinophil counts (EoC), and C-reactive protein (CRP) showed higher importance for predicting sepsis patient survival, whereas, SOFA, APACHE II, platelet counts (PLTC), and CRP obtained higher importance in the SIRS cohort. CONCLUSION By using complete blood count parameters as predictors of ICU patient survival, machine learning models can accurately predict the survival of SIRS and sepsis ICU patients. Interestingly, feature importance highlights the role of CRP and APACHE II in both SIRS and sepsis populations. In addition, MPV and EoC are shown to be important features for the sepsis population only, whereas SOFA and PLTC have higher importance for SIRS patients.
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Affiliation(s)
- Maximiliano Mollura
- Dipartimento di Elettronica Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy
| | - Davide Chicco
- Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Dipartimento di Informatica Sistemistica e Comunicazione, Università di Milano-Bicocca, Milan, Italy
| | - Alessia Paglialonga
- CNR-Istituto di Elettronica e di Ingegneria dell’Informazione e delle Telecomunicazioni (CNR-IEIIT), Milan, Italy
| | - Riccardo Barbieri
- Dipartimento di Elettronica Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy
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12
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Giamarellos-Bourboulis EJ, Aschenbrenner AC, Bauer M, Bock C, Calandra T, Gat-Viks I, Kyriazopoulou E, Lupse M, Monneret G, Pickkers P, Schultze JL, van der Poll T, van de Veerdonk FL, Vlaar APJ, Weis S, Wiersinga WJ, Netea MG. The pathophysiology of sepsis and precision-medicine-based immunotherapy. Nat Immunol 2024; 25:19-28. [PMID: 38168953 DOI: 10.1038/s41590-023-01660-5] [Citation(s) in RCA: 102] [Impact Index Per Article: 102.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 09/21/2023] [Indexed: 01/05/2024]
Abstract
Sepsis remains a major cause of morbidity and mortality in both low- and high-income countries. Antibiotic therapy and supportive care have significantly improved survival following sepsis in the twentieth century, but further progress has been challenging. Immunotherapy trials for sepsis, mainly aimed at suppressing the immune response, from the 1990s and 2000s, have largely failed, in part owing to unresolved patient heterogeneity in the underlying immune disbalance. The past decade has brought the promise to break this blockade through technological developments based on omics-based technologies and systems medicine that can provide a much larger data space to describe in greater detail the immune endotypes in sepsis. Patient stratification opens new avenues towards precision medicine approaches that aim to apply immunotherapies to sepsis, on the basis of precise biomarkers and molecular mechanisms defining specific immune endotypes. This approach has the potential to lead to the establishment of immunotherapy as a successful pillar in the treatment of sepsis for future generations.
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Affiliation(s)
- Evangelos J Giamarellos-Bourboulis
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
- Hellenic Institute for the Study of Sepsis, Athens, Greece
| | - Anna C Aschenbrenner
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
| | - Michael Bauer
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University, Jena, Germany
| | - Christoph Bock
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
- Medical University of Vienna, Institute of Artificial Intelligence, Center for Medical Data Science, Vienna, Austria
| | - Thierry Calandra
- Service of Immunology and Allergy and Center of Human Immunology Lausanne, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Irit Gat-Viks
- The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Evdoxia Kyriazopoulou
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
- Hellenic Institute for the Study of Sepsis, Athens, Greece
| | - Mihaela Lupse
- Infectious Diseases Hospital, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - Guillaume Monneret
- Joint Research Unit HCL-bioMérieux, EA 7426 'Pathophysiology of Injury-Induced Immunosuppression' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon, bioMérieux), Lyon, France
- Immunology Laboratory, Edouard Herriot Hospital - Hospices Civils de Lyon, Lyon, France
| | - Peter Pickkers
- Department of Intensive Care, Radboud University Medical Center, Nijmegen, The Netherlands
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Joachim L Schultze
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- PRECISE Platform for Single Cell Genomics and Epigenomics, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and the University of Bonn, Bonn, Germany
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
| | - Tom van der Poll
- Division of Infectious Diseases, Amsterdam University Medical Centers (Amsterdam UMC), Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, The Netherlands
| | - Frank L van de Veerdonk
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Alexander P J Vlaar
- Department of Intensive Care and Laboratory of Experimental Intensive Care and Anesthesiology L.E.C.A. Amsterdam Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Sebastian Weis
- Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller University, Jena, Germany
- Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute-HKI, Jena, Germany
| | - W Joost Wiersinga
- Division of Infectious Diseases, Amsterdam University Medical Centers (Amsterdam UMC), Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Amsterdam, The Netherlands
| | - Mihai G Netea
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
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13
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Leonhardt J, Dorresteijn MJ, Neugebauer S, Mihaylov D, Kunze J, Rubio I, Hohberger FS, Leonhardt S, Kiehntopf M, Stahl K, Bode C, David S, Wagener FADTG, Pickkers P, Bauer M. Immunosuppressive effects of circulating bile acids in human endotoxemia and septic shock: patients with liver failure are at risk. Crit Care 2023; 27:372. [PMID: 37759239 PMCID: PMC10523742 DOI: 10.1186/s13054-023-04620-5] [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: 05/16/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Sepsis-induced immunosuppression is a frequent cause of opportunistic infections and death in critically ill patients. A better understanding of the underlying mechanisms is needed to develop targeted therapies. Circulating bile acids with immunosuppressive effects were recently identified in critically ill patients. These bile acids activate the monocyte G-protein coupled receptor TGR5, thereby inducing profound innate immune dysfunction. Whether these mechanisms contribute to immunosuppression and disease severity in sepsis is unknown. The aim of this study was to determine if immunosuppressive bile acids are present in endotoxemia and septic shock and, if so, which patients are particularly at risk. METHODS To induce experimental endotoxemia in humans, ten healthy volunteers received 2 ng/kg E. coli lipopolysaccharide (LPS). Circulating bile acids were profiled before and after LPS administration. Furthermore, 48 patients with early (shock onset within < 24 h) and severe septic shock (norepinephrine dose > 0.4 μg/kg/min) and 48 healthy age- and sex-matched controls were analyzed for circulating bile acids. To screen for immunosuppressive effects of circulating bile acids, the capability to induce TGR5 activation was computed for each individual bile acid profile by a recently published formula. RESULTS Although experimental endotoxemia as well as septic shock led to significant increases in total bile acids compared to controls, this increase was mild in most cases. By contrast, there was a marked and significant increase in circulating bile acids in septic shock patients with severe liver failure compared to healthy controls (61.8 µmol/L vs. 2.8 µmol/L, p = 0.0016). Circulating bile acids in these patients were capable to induce immunosuppression, as indicated by a significant increase in TGR5 activation by circulating bile acids (20.4% in severe liver failure vs. 2.8% in healthy controls, p = 0.0139). CONCLUSIONS Circulating bile acids capable of inducing immunosuppression are present in septic shock patients with severe liver failure. Future studies should examine whether modulation of bile acid metabolism can improve the clinical course and outcome of sepsis in these patients.
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Affiliation(s)
- Julia Leonhardt
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), Jena, Germany.
- Center for Sepsis Control and Care (CSCC), Jena University Hospital-Friedrich Schiller University, Jena, Germany.
| | - Mirrin J Dorresteijn
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
- Department of Intensive Care Medicine, Alrijne Hospital, Leiderdorp, the Netherlands
| | - Sophie Neugebauer
- Institute of Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), Jena, Germany
| | - Diana Mihaylov
- Institute of Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), Jena, Germany
| | - Julia Kunze
- Institute of Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), Jena, Germany
| | - Ignacio Rubio
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), Jena, Germany
- Center for Sepsis Control and Care (CSCC), Jena University Hospital-Friedrich Schiller University, Jena, Germany
| | - Frank-Stephan Hohberger
- Department of Oral and Maxillofacial Surgery and Plastic Surgery, Jena University Hospital, Jena, Germany
| | - Silke Leonhardt
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - Michael Kiehntopf
- Center for Sepsis Control and Care (CSCC), Jena University Hospital-Friedrich Schiller University, Jena, Germany
- Institute of Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), Jena, Germany
| | - Klaus Stahl
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Christian Bode
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland
- Department of Nephrology, Hannover Medical School, Hannover, Germany
| | - Frank A D T G Wagener
- Department of Dentistry-Orthodontics and Craniofacial Biology, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Peter Pickkers
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Michael Bauer
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Member of the Leibniz Center for Photonics in Infection Research (LPI), Jena, Germany
- Center for Sepsis Control and Care (CSCC), Jena University Hospital-Friedrich Schiller University, Jena, Germany
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14
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Holler JG, Jensen JUS, Engsig FN, Bestle MH, Lindegaard B, Rasmussen JH, Bundgaard H, Nielsen FE, Iversen KK, Larsen JJ, Holzknecht BJ, Boel J, Sivapalan P, Itenov TS. Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018-2021. Clin Epidemiol 2023; 15:939-955. [PMID: 37700929 PMCID: PMC10493095 DOI: 10.2147/clep.s413403] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 07/21/2023] [Indexed: 09/14/2023] Open
Abstract
Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.
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Affiliation(s)
- Jon Gitz Holler
- Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark
| | - Jens Ulrik Stæhr Jensen
- Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- PERSIMUNE & CHIP: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Frederik Neess Engsig
- Department of Emergency Medicine, Copenhagen University Hospital – Amager and Hvidovre, Copenhagen, Denmark
| | - Morten H Bestle
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Anesthesia and Intensive Care Medicine, Copenhagen University Hospital – North Zealand, Hilleroed, Denmark
| | - Birgitte Lindegaard
- Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Centre for Physical Activity, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Jens Henning Rasmussen
- Department of Emergency Medicine, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Henning Bundgaard
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Cardiology, The Capital Region’s Unit of Inherited Cardiac Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Finn Erland Nielsen
- Department of Emergency Medicine, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Kasper Karmark Iversen
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Emergency Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
| | - Jesper Juul Larsen
- Department of Emergency Medicine, Copenhagen University Hospital - North Zealand, Hilleroed, Denmark
| | - Barbara Juliane Holzknecht
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Microbiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
| | - Jonas Boel
- Department of Clinical Microbiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- Copenhagen University Hospital - Capital Region Pharmacy, Copenhagen, Denmark
| | - Pradeesh Sivapalan
- Department of Medicine, Section of Respiratory Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Theis Skovsgaard Itenov
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Anesthesiology and Intensive Care Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
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15
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Jouffroy R, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Gueye P. Prehospital pulse pressure and mortality of septic shock patients cared for by a mobile intensive care unit. BMC Emerg Med 2023; 23:97. [PMID: 37626302 PMCID: PMC10464421 DOI: 10.1186/s12873-023-00864-0] [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: 03/20/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND Septic shock medical treatment relies on a bundle of care including antibiotic therapy and hemodynamic optimisation. Hemodynamic optimisation consists of fluid expansion and norepinephrine administration aiming to optimise cardiac output to reach a mean arterial pressure of 65mmHg. In the prehospital setting, direct cardiac output assessment is difficult because of the lack of invasive and non-invasive devices. This study aims to assess the relationship between 30-day mortality and (i) initial pulse pressure (iPP) as (ii) pulse pressure variation (dPP) during the prehospital stage among patients cared for SS by a prehospital mobile intensive care unit (MICU). METHODS From May 09th, 2016 to December 02nd, 2021, septic shock patients requiring MICU intervention were retrospectively analysed. iPP was calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the first contact between the patient and the MICU team prior to any treatment and, dPP as the difference between the final PP (the difference between SBP and DBP at the end of the prehospital stage) and iPP divided by prehospital duration. To consider cofounders, the propensity score method was used to assess the relationship between (i) iPP < 40mmHg, (ii) positive dPP and 30-day mortality. RESULTS Among the 530 patients analysed, pulmonary, digestive, and urinary infections were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality rate reached 31%. Cox regression analysis showed an association between 30-day mortality and (i) iPP < 40mmHg; aHR of 1.61 [1.03-2.51], and (ii) a positive dPP; aHR of 0.56 [0.36-0.88]. CONCLUSION The current study reports an association between 30-day mortality rate and iPP < 40mmHg and a positive dPP among septic shock patients cared for by a prehospital MICU. A negative dPP could be helpful to identify septic shock with higher risk of poor outcome despite prehospital hemodynamic optimization.
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Affiliation(s)
- Romain Jouffroy
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique Hôpitaux Paris and Paris Saclay University, 9 avenue Charles De Gaulle, Boulogne-Billancourt, 92100, France.
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique - Hôpitaux Paris, Paris, France.
- Centre de recherche en Epidémiologie et Santé des Populations - U1018 INSERM, Paris Saclay University, Villejuif, France.
- Institut de Recherche bioMédicale et d'Epidémiologie du Sport - EA7329, INSEP - Paris University, Paris, France.
- EA 7525 Université des Antilles, Fort de France, France.
| | - Basile Gilbert
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | | | - Emmanuel Bloch-Laine
- Emergency Department, Cochin Hospital, Paris, France
- Emergency Department, SMUR, Hôtel Dieu Hospital - Assistance Publique - Hôpitaux Paris, Paris, France
| | - Patrick Ecollan
- Intensive Care Unit, SMUR, Pitie Salpêtriere Hospital, 47 Boulevard de l'Hôpital, Paris - Assistance Publique - Hôpitaux Paris, Paris, 75013, France
| | - Josiane Boularan
- SAMU 31, Centre Hospitalier Intercommunal Castres-Mazamet, Castres, France
| | - Vincent Bounes
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | - Benoit Vivien
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique - Hôpitaux Paris, Paris, France
| | - Papa Gueye
- EA 7525 Université des Antilles, Fort de France, France
- SAMU 972, Centre Hospitalier Universitaire de Martinique, Fort-de-France Martinique, France
- EA 7525 University of the Antilles, Martinique, France
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16
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Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Brück LM, Hoffmann U, Bertsch T, Weiß C, Akin I, Behnes M. Diagnostic and prognostic value of the AST/ALT ratio in patients with sepsis and septic shock. Scand J Gastroenterol 2023; 58:392-402. [PMID: 36259154 DOI: 10.1080/00365521.2022.2131331] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The study investigates the diagnostic and prognostic value of the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in patients with sepsis and septic shock. Limited data regarding the prognostic value of the AST/ALT ratio in patients suffering from sepsis or septic shock is available. METHODS Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from day of disease onset (day 1), day 2, 3, 5 and 7. First, the diagnostic value of the AST/ALT ratio was tested for septic shock compared to sepsis. Second, the prognostic value of the AST/ALT ratio was tested for 30-d all-cause mortality. Statistical analyses included univariable t-test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. RESULTS A total of 289 patients were included, of which 55% had sepsis and 45% septic shock. The overall rate of all-cause mortality at 30 d was 53%. With an area under the curve (AUC) of 0.651 on day 1 and 0.794 on day 7, the AST/ALT ratio revealed moderate but better diagnostic discrimination of septic shock compared to bilirubin. Furthermore, the AST/ALT ratio was able to discriminate 30-d all-cause mortality (AUC = 0.624; 95% CI 0.559 - 0.689; p = 0.001). Patients with an AST/ALT ratio above the median (>1.8) had higher rates of 30-d all-cause mortality compared to lower values (mortality rate 63 vs. 43%; log-rank p = 0.001), even after multivariable adjustment (HR = 1.703; 95% CI 1.182 - 2.453; p = 0.004) and propensity score matching. CONCLUSIONS The AST/ALT was a reliable diagnostic tool for the diagnosis of septic shock as well as a reliable tool to predict 30-d all-cause mortality in patients suffering from sepsis and septic shock.
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Affiliation(s)
- Tobias Schupp
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Kathrin Weidner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Jonas Rusnak
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Schanas Jawhar
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Jan Forner
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Floriana Dulatahu
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Lea Marie Brück
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Ursula Hoffmann
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Thomas Bertsch
- Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany
| | - Christel Weiß
- Department of Statistical Analysis, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany
| | - Ibrahim Akin
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Michael Behnes
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany
- European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheim, Mannheim, Germany
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17
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Li X, Yin Z, Yan W, Wang M, Xue L, Zhou Q, Sun Y. Baseline red blood cell distribution width and perforin, dynamic levels of interleukin 6 and lactate are predictors of mortality in patients with sepsis. J Clin Lab Anal 2023; 37:e24838. [PMID: 36631067 PMCID: PMC9978088 DOI: 10.1002/jcla.24838] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/07/2022] [Accepted: 12/30/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Sepsis is a critical illness often encountered in the intensive care unit. However, prognostic biomarkers for sepsis have limited sensitivity. This study aimed to identify more sensitive predictors of mortality through repeated monitoring of laboratory parameters. METHODS Patients with sepsis (Sepsis 3.0 criteria met) were recruited and divided into the survivor and nonsurvivor groups after 28 days. Data on blood biochemistry, lymphocyte subsets, and cytokines were obtained on the first and seventh hospitalization days. Univariate and multivariate Cox regression analyses were performed to explore the correlation between these variables and patient mortality. RESULTS Forty patients with sepsis were included. The mortality rate was 37.5%. Red blood cell distribution width-standard deviation (RDWSD) (hazard ratio [HR] = 1.107 [95% CI: 1.005-1.219], p = 0.040) and perforin level (HR = 1.001 [95% CI: 1-1.003], p = 0.035) on the first day, as well as lactate (HR = 112.064 [95% CI: 2.192-5729.629], p = 0.019) and interleukin 6 (IL-6) (HR = 1.005 [95% CI: 1.001-1.008], p = 0.014) levels on the seventh day, were independent risk factors of mortality. If the patients were divided into two groups based on RDWSD (normal: n = 31; increased: n = 9), the Kaplan-Meier curves showed that the group with increased RDWSD had a lower survival (p = 0.025). CONCLUSION Baseline RDWSD and perforin, along with dynamic IL-6 and lactate levels, were independent predictors of mortality in patients with sepsis.
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Affiliation(s)
- Xin Li
- Department of Respiratory and Critical Care MedicinePeking University Third HospitalBeijingChina
| | - Zhongnan Yin
- Institute of Medical Innovation and ResearchPeking University Third HospitalBeijingChina
- Biobank, Peking University Third HospitalBeijingChina
| | - Wei Yan
- Department of Respiratory and Critical Care MedicinePeking University Third HospitalBeijingChina
| | - Meng Wang
- Department of Respiratory and Critical Care MedicinePeking University Third HospitalBeijingChina
| | - Lixiang Xue
- Institute of Medical Innovation and ResearchPeking University Third HospitalBeijingChina
- Biobank, Peking University Third HospitalBeijingChina
| | - Qingtao Zhou
- Department of Respiratory and Critical Care MedicinePeking University Third HospitalBeijingChina
| | - Yongchang Sun
- Department of Respiratory and Critical Care MedicinePeking University Third HospitalBeijingChina
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18
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Low-Dose Colchicine Attenuates Sepsis-Induced Liver Injury: A Novel Method for Alleviating Systemic Inflammation. Inflammation 2023; 46:963-974. [PMID: 36656466 DOI: 10.1007/s10753-023-01783-9] [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: 08/09/2022] [Revised: 01/06/2023] [Accepted: 01/09/2023] [Indexed: 01/20/2023]
Abstract
Sepsis is a significant public health challenge. The immune system underlies the pathogenesis of the disease. The liver is both an active player and a target organ in sepsis. Targeting the gut immune system using low-dose colchicine is an attractive method for alleviating systemic inflammation in sepsis without inducing immunosuppression. The present study aimed to determine the use of low-dose colchicine in LPS-induced sepsis in mice. C67B mice were injected intraperitoneal with LPS to induce sepsis. The treatment group received 0.02 mg/kg colchicine daily by gavage. Short and extended models were performed, lasting 3 and 5 days, respectively. We followed the mice for biochemical markers of end-organ injury, blood counts, cytokine levels, and liver pathology and conducted proteomic studies on liver samples. Targeting the gut immune system using low-dose colchicine improved mice's well-being measured by the murine sepsis score. Treatment alleviated the liver injury in septic mice, manifested by a significant decrease in their liver enzyme levels, including ALT, AST, and LDH. Treatment exerted a trend to reduce creatinine levels. Low-dose colchicine improved liver pathology, reduced inflammation, and reduced the pro-inflammatory cytokine TNFα and IL1-β levels. A liver proteomic analysis revealed low-dose colchicine down-regulated sepsis-related proteins, alpha-1 antitrypsin, and serine dehydratase. Targeting the gut immune system using low-dose colchicine attenuated liver injury in LPS-induced sepsis, reducing the pro-inflammatory cytokine levels. Low-dose colchicine provides a safe method for immunomodulation for multiple inflammatory disorders.
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19
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Hu T, Yao W, Li Y, Liu Y. Interaction of acute heart failure and acute kidney injury on in-hospital mortality of critically ill patients with sepsis: A retrospective observational study. PLoS One 2023; 18:e0282842. [PMID: 36888602 PMCID: PMC9994701 DOI: 10.1371/journal.pone.0282842] [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: 11/11/2022] [Accepted: 02/23/2023] [Indexed: 03/09/2023] Open
Abstract
BACKGROUND The present study aimed to evaluate the synergistic impact of acute heart failure (AHF) and acute kidney injury (AKI) on in-hospital mortality in critically ill patients with sepsis. METHODS We undertook a retrospective, observational analysis using data acquired from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD). The effects of AKI and AHF on in-hospital mortality were examined using a Cox proportional hazards model. Additive interactions were analyzed using the relative extra risk attributable to interaction. RESULTS A total of 33,184 patients were eventually included, comprising 20,626 patients in the training cohort collected from the MIMIC-IV database and 12,558 patients in the validation cohort extracted from the eICU-CRD database. After multivariate Cox analysis, the independent variables for in-hospital mortality included: AHF only (HR:1.20, 95% CI:1.02-1.41, P = 0.005), AKI only (HR:2.10, 95% CI:1.91-2.31, P < 0.001), and both AHF and AKI (HR:3.80, 95%CI:13.40-4.24, P < 0.001). The relative excess risk owing to interaction was 1.49 (95% CI:1.14-1.87), the attributable percentage due to interaction was 0.39 (95%CI:0.31-0.46), and the synergy index was 2.15 (95%CI:1.75-2.63), demonstrated AHF and AKI had a strong synergic impact on in-hospital mortality. And the findings in the validation cohort indicated identical conclusions to the training cohort. CONCLUSION Our data demonstrated a synergistic relationship of AHF and AKI on in-hospital mortality in critically unwell patients with sepsis.
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Affiliation(s)
- Tianyang Hu
- Precision Medicine Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wanjun Yao
- Department of Anesthesiology, Wuhan No.1 Hospital, 430030, Wuhan, Hubei, China
| | - Yu Li
- Department of Nephrology, Chongqing Bishan District People’s Hospital (Bishan Hospital Affiliated to Chongqing Medical University), Chongqing, China
| | - Yanan Liu
- Department of Nephrology, Rheumatology and Immunology, Jiulongpo District People’s Hospital, Chongqing, China
- * E-mail:
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20
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Zhang X, Li S, Luo H, He S, Yang H, Li L, Tian T, Han Q, Ye J, Huang C, Liu A, Jiang Y. Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach. Signal Transduct Target Ther 2022; 7:245. [PMID: 35871689 PMCID: PMC9309159 DOI: 10.1038/s41392-022-01035-6] [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: 12/27/2021] [Revised: 04/06/2022] [Accepted: 05/18/2022] [Indexed: 11/11/2022] Open
Abstract
Effectively killing pathogenic bacteria is key for the treatment of sepsis. Although various anti-infective drugs have been used for the treatment of sepsis, the therapeutic effect is largely limited by the lack of a specific bacterium-targeting delivery system. This study aimed to develop antibacterial peptides that specifically target pathogenic bacteria for the treatment of sepsis. The lethal bacterial strain Escherichia coli MSI001 was isolated from mice of a cecal ligation and puncture (CLP) model and was used as a target to screen bacterial binding heptapeptides through an integrative bioinformatics approach based on phage display technology and high-throughput sequencing (HTS). Heptapeptides binding to E. coli MSI001 with high affinity were acquired after normalization by the heptapeptide frequency of the library. A representative heptapeptide VTKLGSL (VTK) was selected for fusion with the antibacterial peptide LL-37 to construct the specific-targeting antibacterial peptide VTK-LL37. We found that, in comparison with LL37, VTK-LL37 showed prominent bacteriostatic activity and an inhibitive effect on biofilm formation in vitro. In vivo experiments demonstrated that VTK-LL37 significantly inhibited bacterial growth, reduced HMGB1 expression, alleviated lesions of vital organs and improved the survival of mice subjected to CLP modeling. Furthermore, membrane DEGP and DEGQ were identified as VTK-binding proteins by proteomic methods. This study provides a novel strategy for targeted pathogen killing, which is helpful for the treatment of sepsis in the era of precise medicine.
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21
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Ling L, Mui OOY, Laupland KB, Lefrant JY, Roberts JA, Gopalan PD, Lipman J, Joynt GM. Scoping review on diagnostic criteria and investigative approach in sepsis of unknown origin in critically ill patients. J Intensive Care 2022; 10:44. [PMID: 36089642 PMCID: PMC9465866 DOI: 10.1186/s40560-022-00633-4] [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: 07/13/2022] [Accepted: 08/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Up to 11% of critically ill patients with sepsis have an unknown source, where the pathogen and site of infection are unclear. The aim of this scoping review is to document currently reported diagnostic criteria of sepsis of unknown origin (SUO) and identify the types and breadth of existing evidence supporting diagnostic processes to identify the infection source in critically ill patients with suspected SUO. METHODS A literature search of Embase, MEDLINE and PubMed for published studies from 1910 to August 19, 2021 addressing the topic of SUO was performed. Study type, country of origin according to World Bank classification, diagnostic criteria of sepsis of unknown origin, and investigative approaches were extracted from the studies. RESULTS From an initial 722 studies, 89 unique publications fulfilled the inclusion and exclusion criteria and were included for full text review. The most common publication type was case report/series 45/89 (51%). Only 10/89 (11%) of studies provided a diagnostic criteria of SUO, but a universally accepted diagnostic criterion was not identified. The included studies discussed 30/89 (34%) history, 23/89 (26%) examination, 57/89 (64%) imaging, microbiology 39/89 (44%), and special tests 32/89 (36%) as part of the diagnostic processes in patients with SUO. CONCLUSIONS Universally accepted diagnostic criteria for SUO was not found. Prospective studies on investigative processes in critically ill patients managed as SUO across different healthcare settings are needed to understand the epidemiology and inform the diagnostic criteria required to diagnose SUO.
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Affiliation(s)
- Lowell Ling
- Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, SAR, China.
| | - Oliver Oi Yat Mui
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Kevin B Laupland
- Department of Intensive Care Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
- Queensland University of Technology (QUT), Brisbane, QLD, Australia
| | - Jean-Yves Lefrant
- UR-UM103 IMAGINE, University of Montpellier, Division of Anesthesia Critical Care, Pain and Emergency Medicine, Nîmes University Hospital, Montpellier, France
| | - Jason A Roberts
- UR-UM103 IMAGINE, University of Montpellier, Division of Anesthesia Critical Care, Pain and Emergency Medicine, Nîmes University Hospital, Montpellier, France
- University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Australia
- Department of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Pragasan Dean Gopalan
- Discipline of Anaesthesiology & Critical Care, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
| | - Jeffrey Lipman
- Department of Intensive Care Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
- UR-UM103 IMAGINE, University of Montpellier, Division of Anesthesia Critical Care, Pain and Emergency Medicine, Nîmes University Hospital, Montpellier, France
- University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Australia
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Gavin M Joynt
- Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, SAR, China
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22
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IL-1R1 blockade attenuates liver injury through inhibiting the recruitment of myeloid-derived suppressor cells in sepsis. Biochem Biophys Res Commun 2022; 620:21-28. [DOI: 10.1016/j.bbrc.2022.06.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/08/2022] [Accepted: 06/10/2022] [Indexed: 11/23/2022]
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23
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Spectroscopy detects skeletal muscle microvascular dysfunction during onset of sepsis in a rat fecal peritonitis model. Sci Rep 2022; 12:6339. [PMID: 35428849 PMCID: PMC9012880 DOI: 10.1038/s41598-022-10208-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 03/15/2022] [Indexed: 01/20/2023] Open
Abstract
Sepsis is a dysregulated host inflammatory response to infection potentially leading to life-threatening organ dysfunction. The objectives of this study were to determine whether early microvascular dysfunction (MVD) in skeletal muscle can be detected as dynamic changes in microvascular hemoglobin (MVHb) levels using spectroscopy and whether MVD precedes organ histopathology in septic peritonitis. Skeletal muscle of male Sprague-Dawley rats was prepared for intravital microscopy. After intraperitoneal injection of fecal slurry or saline, microscopy and spectroscopy recordings were taken for 6 h. Capillary red blood cell (RBC) dynamics and SO2 were quantified from digitized microscopy frames and MVHb levels were derived from spectroscopy data. Capillary RBC dynamics were significantly decreased by 4 h after peritoneal infection and preceded macrohemodynamic changes. At the same time, low-frequency oscillations in MVHb levels exhibited a significant increase in Power in parts of the muscle and resembled oscillations in RBC dynamics and SO2. After completion of microscopy, tissues were collected. Histopathological alterations were not observed in livers, kidneys, brains, or muscles 6 h after induction of peritonitis. The findings of this study show that, in our rat model of sepsis, MVD occurs before detectable organ histopathology and includes ~ 30-s oscillations in MVHb. Our work highlights MVHb oscillations as one of the indicators of MVD onset and provides a foundation for the use of non-invasive spectroscopy to continuously monitor MVD in septic patients.
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24
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Cointe S, Vallier L, Esnault P, Dacos M, Bonifay A, Macagno N, Harti Souab K, Chareyre C, Judicone C, Frankel D, Robert S, Hraiech S, Alessi MC, Poncelet P, Albanese J, Dignat-George F, Lacroix R. Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock. Blood 2022; 139:2377-2391. [PMID: 35026004 PMCID: PMC11022829 DOI: 10.1182/blood.2021013328] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 12/16/2021] [Indexed: 11/20/2022] Open
Abstract
Microvesicles (MVs) have previously been shown to exert profibrinolytic capacity, which is increased in patients with septic shock (SS) with a favorable outcome. We, therefore, hypothesized that the plasmin generation capacity (PGC) could confer to MVs a protective effect supported by their capacity to lyse a thrombus, and we investigated the mechanisms involved. Using an MV-PGC kinetic assay, ELISA, and flow cytometry, we found that granulocyte MVs (Gran-MVs) from SS patients display a heterogeneous PGC profile driven by the uPA (urokinase)/uPAR system. In vitro, these MVs lyse a thrombus according to their MV-PGC levels in a uPA/uPAR-dependent manner, as shown in a fluorescent clot lysis test and a lysis front retraction assay. Fibrinolytic activators conveyed by MVs contribute to approximately 30% of the plasma plasminogenolytic capacity of SS patients. In a murine model of SS, the injection of high PGC Gran-MVs significantly improved mouse survival and reduced the number of thrombi in vital organs. This was associated with a modification of the mouse coagulation and fibrinolysis properties toward a more fibrinolytic profile. Interestingly, mouse survival was not improved when soluble uPA was injected. Finally, using a multiplex array on plasma from SS patients, we found that neutrophil elastase correlates with the effect of high-PGC-capacity plasma and modulates the Gran-MV plasmin generation capacity by cleaving uPA-PAI-1 complexes. In conclusion, we show that the high PGC level displayed by Gran-MVs reduces thrombus formation and improves survival, conferring to Gran-MVs a protective role in a murine model of sepsis.
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Affiliation(s)
- Sylvie Cointe
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
- Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France
| | - Loris Vallier
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
| | - Pierre Esnault
- Intensive Care Unit, Sainte Anne Military Hospital, Toulon, France
| | - Mathilde Dacos
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
| | - Amandine Bonifay
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
| | - Nicolas Macagno
- Department of Pathology and Neuropathology, CHU Timone, APHM, Marseille, France
- Aix-Marseille University, INSERM, MMG, Marseille, France
| | | | - Corinne Chareyre
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
| | | | - Diane Frankel
- Department of Cell Biology, Aix-Marseille University, APHM, INSERM, MMG, CHU Timone, APHM, Marseille, France
| | - Stéphane Robert
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
| | - Sami Hraiech
- Intensive Care Unit, APHM, CHU Nord, CEReSS-Center for Studies and Research on Health Services and Quality of Life EA3279, Aix-Marseille University, Marseille, France
| | - Marie-Christine Alessi
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
- Department of Hematology, CHU La Timone, APHM, Marseille, France
| | | | | | - Françoise Dignat-George
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
- Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France
| | - Romaric Lacroix
- Aix-Marseille University, C2VN, INSERM 1263, INRA 1260, Marseille, France
- Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France
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25
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Jouffroy R, Hajjar A, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Gueye PN. Prehospital norepinephrine administration reduces 30-day mortality among septic shock patients. BMC Infect Dis 2022; 22:345. [PMID: 35387608 PMCID: PMC8988327 DOI: 10.1186/s12879-022-07337-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 02/21/2022] [Indexed: 11/23/2022] Open
Abstract
Background Despite differences in time of sepsis recognition, recent studies support that early initiation of norepinephrine in patients with septic shock (SS) improves outcome without an increase in adverse effects. This study aims to investigate the relationship between 30-day mortality in patients with SS and prehospital norepinephrine infusion in order to reach a mean blood pressure (MAP) > 65 mmHg at the end of the prehospital stage. Methods From April 06th, 2016 to December 31th, 2020, patients with SS requiring prehospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To consider cofounders, the propensity score method was used to assess the relationship between prehospital norepinephrine administration in order to reach a MAP > 65 mmHg at the end of the prehospital stage and 30-day mortality.
Results Four hundred and seventy-eight patients were retrospectively analysed, among which 309 patients (65%) were male. The mean age was 69 ± 15 years. Pulmonary, digestive, and urinary infections were suspected among 44%, 24% and 17% patients, respectively. One third of patients (n = 143) received prehospital norepinephrine administration with a median dose of 1.0 [0.5–2.0] mg h−1, among which 84 (69%) were alive and 38 (31%) were deceased on day 30 after hospital-admission. 30-day overall mortality was 30%. Cox regression analysis after the propensity score showed a significant association between prehospital norepinephrine administration and 30-day mortality, with an adjusted hazard ratio of 0.42 [0.25–0.70], p < 10–3. Multivariate logistic regression of IPTW retrieved a significant decrease of 30-day mortality among the prehospital norepinephrine group: ORa = 0.75 [0.70–0.79], p < 10–3.
Conclusion In this study, we report that prehospital norepinephrine infusion in order to reach a MAP > 65 mmHg at the end of the prehospital stage is associated with a decrease in 30-day mortality in patients with SS cared for by a MICU in the prehospital setting. Further prospective studies are needed to confirm that very early norepinephrine infusion decreases septic shock mortality.
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Affiliation(s)
- Romain Jouffroy
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique Hôpitaux Paris and Paris Saclay University, 9 avenue Charles de Gaulle, 92100, Boulogne-Billancourt, France. .,Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique, Hôpitaux Paris, Paris, France. .,Centre de Recherche en Epidémiologie et Santé des Populations, U1018 INSERM, Paris Saclay University, Paris, France. .,Institut de Recherche bioMédicale et d'Epidémiologie du Sport, EA7329, INSEP, Paris University, Paris, France. .,EA 7525 Université des Antilles, Pointe-à-Pitre, France.
| | - Adèle Hajjar
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique Hôpitaux Paris and Paris Saclay University, 9 avenue Charles de Gaulle, 92100, Boulogne-Billancourt, France
| | - Basile Gilbert
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | | | - Emmanuel Bloch-Laine
- Emergency Department, Cochin Hospital, Paris, France.,Emergency Department, SMUR, Hôtel Dieu Hospital, Assistance Publique, Hôpitaux Paris, Paris, France
| | - Patrick Ecollan
- Intensive Care Unit, SMUR, Pitie Salpêtriere Hospital, Assistance Publique, Hôpitaux Paris, 47 Boulevard de l'Hôpital, 75013, Paris, France
| | - Josiane Boularan
- SAMU 31, Centre Hospitalier Intercommunal Castres-Mazamet, Castres, France
| | - Vincent Bounes
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | - Benoit Vivien
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique, Hôpitaux Paris, Paris, France
| | - Papa-Ngalgou Gueye
- EA 7525 Université des Antilles, Pointe-à-Pitre, France.,SAMU 972 University Hospital of Martinique, Fort-de-France, Martinique, France
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26
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Baïsse A, Daix T, Hernandez Padilla AC, Jeannet R, Barraud O, Dalmay F, François B, Vignon P, Lafon T. High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia. BMC Infect Dis 2022; 22:295. [PMID: 35346082 PMCID: PMC8960225 DOI: 10.1186/s12879-022-07295-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 03/14/2022] [Indexed: 11/23/2022] Open
Abstract
Background In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia. Methods This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count < 0.5 G/L) were studied. Patients with hematological or oncological diseases, HIV infection, hepato-cellular deficiency, immunosuppression, or patients over 85 years old were excluded. Diagnoses of infection were validated by an independent adjudication committee. The association between various parameters and infection was assessed using a multivariate logistic regression analysis. Results Of 953 patients admitted to the ED with severe lymphopenia, 245 were studied (148 men; mean age: 63 ± 19 years). Infection was confirmed in 159 patients (65%) (bacterial: 60%, viral: 30%, other: 10%). Only 61 patients (25%) were referred to the ED for a suspected infection. In the univariate analysis, SIRS criteria (OR: 5.39; 95%CI: 3.04–9.70; p < 0.001) and temperature ≥ 38.3 °C (OR: 10.95; 95%CI: 5.39–22.26; p < 0.001) were strongly associate with infection. In the multivariate analysis, only SIRS criteria (OR: 2.4; 95%CI: 1.48–3.9; p < 0.01) and fever (OR: 3.35; 95%CI: 1.26–8.93; p = 0.016) were independently associated with infection. Conclusions The prevalence of underlying infection is high in patients admitted to the ED with lymphopenia, irrespective of the reason for admission. Whether lymphopenia could constitute a valuable marker of underlying infection in this clinical setting remains to be confirmed prospectively in larger cohorts. Trial registration: No registration required as this is a retrospective study. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07295-5.
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27
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Song H, Zhang X, Zhai R, Liang H, Song G, Yuan Y, Xu Y, Yan Y, Qiu L, Sun T. Metformin attenuated sepsis-associated liver injury and inflammatory response in aged mice. Bioengineered 2022; 13:4598-4609. [PMID: 35156512 PMCID: PMC8973864 DOI: 10.1080/21655979.2022.2036305] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/24/2022] [Accepted: 01/25/2022] [Indexed: 12/14/2022] Open
Abstract
Sepsis-associated liver injury is with poor survival in intensive care units. Metformin is well known for its therapeutic effects; however, its impact on treating liver injury due to sepsis remains poorly understood. This study investigated the therapeutic effects of metformin on aged mice suffering from sepsis-associated liver injury. Male C57BL/6 J mice aged (18-19 months) were divided into 3 groups: 1) intraperitoneal injection of sterile normal saline (C group), 12.5 mg/kg lipopolysaccharide (LPS) to induce sepsis-associated liver injury (LPS group), and 25 mg/kg metformin (MET) at 1 h after LPS injection (MET group). After 24 h, blood samples and liver tissue were collected for biochemical analysis. Histological assays revealed significantly elevated inflammatory infiltration and apoptosis in the liver, while metformin was found to relieve these aberrant features. The percentage of apoptotic cells decreased after metformin treatment (P < 0.05). Additionally, MET group had significantly reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to the LPS group (P < 0.05). Furthermore, in the MET group, the mRNA levels of chemokines and inflammatory factors, TNF-α, IL-6, caspase-1, decreased markedly (P < 0.05). Metformin notably reversed the decreased phosphorylated AMP-activated protein kinase (p-AMPK) and PGC-1α expressions in the liver of septic rats. Metformin also inhibited PDK1, HIF-1α expression, including downstream inflammatory mediators, HMGB1 and TNF-α. Metformin attenuated inflammation and liver injury in septic aged mice. Most importantly, we report the effect of metformin on liver injury via the AMPK-PGC1α axis in septic aged mice for the first time.
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Affiliation(s)
- Heng Song
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Xiaojuan Zhang
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
| | - Ruiqing Zhai
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Huoyan Liang
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Gaofei Song
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yangyang Yuan
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
| | - Yanan Xu
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
| | - Yan Yan
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
| | - Lingxiao Qiu
- Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tongwen Sun
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
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28
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Zhu C, Wang DQ, Zi H, Huang Q, Gu JM, Li LY, Guo XP, Li F, Fang C, Li XD, Zeng XT. Epidemiological trends of urinary tract infections, urolithiasis and benign prostatic hyperplasia in 203 countries and territories from 1990 to 2019. Mil Med Res 2021; 8:64. [PMID: 34879880 PMCID: PMC8656041 DOI: 10.1186/s40779-021-00359-8] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 11/15/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Urinary tract infections (UTI), urolithiasis, and benign prostatic hyperplasia (BPH) are three of the most common nonmalignant conditions in urology. However, there is still a lack of comprehensive and updated epidemiological data. This study aimed to investigate the disease burden of UTI, urolithiasis, and BPH in 203 countries and territories from 1990 to 2019. METHODS Data were extracted from the Global Burden of Disease 2019, including incident cases, deaths, disability-adjusted life-years (DALYs) and corresponding age-standardized rate (ASR) from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to evaluate the trends of ASR. The associations between disease burden and social development degrees were analyzed using a sociodemographic index (SDI). RESULTS Compared with 1990, the incident cases of UTI, urolithiasis, and BPH increased by 60.40%, 48.57%, and 105.70% in 2019, respectively. The age-standardized incidence rate (ASIR) of UTI increased (EAPC = 0.08), while urolithiasis (EAPC = - 0.83) and BPH (EAPC = - 0.03) decreased from 1990 to 2019. In 2019, the age-standardized mortality rate (ASMR) of UTI and urolithiasis were 3.13/100,000 and 0.17/100,000, respectively. BPH had the largest increase (110.56%) in DALYs in the past three decades, followed by UTI (68.89%) and urolithiasis (16.95%). The burden of UTI was mainly concentrated in South Asia and Tropical Latin America, while the burden of urolithiasis and BPH was recorded in Asia and Eastern Europe. Moreover, the ASIR and SDI of urolithiasis in high-SDI regions from 1990 to 2019 were negatively correlated, while the opposite trend was seen in low-SDI regions. In 2019, the ASIR of UTI in females was 3.59 times that of males, while the ASIR of urolithiasis in males was 1.96 times higher than that in females. The incidence was highest in the 30-34, 55-59, and 65-69 age groups among the UTI, urolithiasis, and BPH groups, respectively. CONCLUSION Over the past three decades, the disease burden has increased for UTI but decreased for urolithiasis and BPH. The allocation of medical resources should be based more on the epidemiological characteristics and geographical distribution of diseases.
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Affiliation(s)
- Cong Zhu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Dan-Qi Wang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Hao Zi
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Qiao Huang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Department of Evidence-Based Medicine and Clinical Epidemiology, Second School of Clinical Medicine, Wuhan University, Wuhan, 430071, Hubei, China
| | - Jia-Min Gu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Lu-Yao Li
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Xing-Pei Guo
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Institutes of Evidence-Based Medicine and Knowledge Translation, Henan University, Kaifeng, 475000, Henan, China
| | - Fei Li
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.,Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Cheng Fang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
| | - Xiao-Dong Li
- Institutes of Evidence-Based Medicine and Knowledge Translation, Henan University, Kaifeng, 475000, Henan, China. .,Department of Urology, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China.
| | - Xian-Tao Zeng
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. .,Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. .,Department of Evidence-Based Medicine and Clinical Epidemiology, Second School of Clinical Medicine, Wuhan University, Wuhan, 430071, Hubei, China.
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29
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Plasma IgM Levels Differentiate between Survivors and Non-Survivors of Culture-Positive and Culture-Negative Sepsis and SIRS: A Pilot Study. J Clin Med 2021; 10:jcm10225391. [PMID: 34830673 PMCID: PMC8626001 DOI: 10.3390/jcm10225391] [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: 09/11/2021] [Revised: 11/10/2021] [Accepted: 11/15/2021] [Indexed: 11/17/2022] Open
Abstract
Immunoglobulin IgM is important for controlling viral and bacterial infections, and low immunoglobulin levels have been found in sepsis. There is a clear need to stratify sepsis patients according to the presence of an invading organism, compared to no organism identified, and SIRS patients, where organ dysfunction is a result of a non-infective process. The aim of this pilot study in a small cohort of patients with sepsis was to evaluate the association between IgM plasma levels and survival in 47 patients with sepsis and 11 patients diagnosed with organ failure without the identification of a pathogen (SIRS). Patients were admitted to the intensive care unit (ICU) at The Royal Glamorgan Hospital, Llantrisant, UK between 2010 and 2014. We found that low IgM levels were associated with sepsis, but not SIRS. IgM levels did not differ significantly for culture-positive (CP) compared with culture-negative (CN, no organism found) sepsis samples. Kaplan–Meier analysis was used to compare survival curves according to IgM levels, with no significant difference. We observed significantly higher survival in the CP samples when comparing with CN. Cut-off value for IgM (266 μg/mL) for diagnosis of sepsis patients was determined using receiver operator characteristic (ROC) curves with 70% sensitivity, 69% specificity and 92% negative predictive values (NPV), respectively. The corresponding area under the curve (AUC) for the discrimination of sepsis patients was AUC = 0.73, and in a subgroup analysis of CP was AUC = 0.77 and for CN was AUC = 0.79. We confirm IgM as a good diagnostic marker of sepsis. These findings indicate a difference in the pathology between culture-positive versus negative sepsis, SIRS and survival. This indicates that IgM is likely relevant to pathology, because of its role in the early immune response against pathogens, the potentially protective role of natural IgM antibodies, and supports its application in immunoglobulin therapy.
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30
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Biswas S, Soneja M, Makkar N, Farooqui FA, Roy A, Kumar A, Nischal N, Biswas A, Wig N, Sood R, Sreenivas V. N-terminal pro-brain natriuretic peptide is an independent predictor of mortality in patients with sepsis. J Investig Med 2021; 70:369-375. [PMID: 34702775 DOI: 10.1136/jim-2021-002017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2021] [Indexed: 11/04/2022]
Abstract
This study aims to evaluate the role of cardiac enzymes N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin-I (CTnI) as predictors of outcomes in patients with sepsis.78 cases with a diagnosis of sepsis were enrolled over a 2-year period. Baseline demographic, Acute Physiology and Chronic Health Evaluation-II (APACHE-II), Simplified Acute Physiology Score-II (SAPS-II), hematologic and biochemical parameters were noted. Serum NT-proBNP and CTnI were evaluated at 24 and 72 hours of admission along with echocardiography. Patients were prospectively followed up until death or discharge.Mean APACHE-II score was 19.8±9.6 and SAPS-II was 44.8±17.2. Survival rate in the study was 47.5% (36 of 78 patients). NT-proBNP was significantly higher in non-survivors with values over 4300 pg/mL at 24 hours and 5229 pg/mL at 72 hours associated with poor outcomes (p<0.05). CTnI was higher among non-survivors than in survivors, but the difference was not significant. APACHE-II score combined with NT-proBNP predicted a poor outcome in 51.2% cases compared with 14.6% cases with APACHE-II alone (p<0.05), while SAPS-II combined with NT-proBNP predicted a poor outcome in 53.6% cases as compared with 9.6% cases with SAPS-II alone (p<0.05). SAPS-II greater than 45 and NT-proBNP values at 72 hours were independent predictors of mortality in patients with sepsis.NT-proBNP is an independent predictor of mortality in patients with sepsis and its combination with APACHE-II and SAPS-II improves the predictive values of the scoring systems.
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Affiliation(s)
- Sagnik Biswas
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Manish Soneja
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Nayani Makkar
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Faraz Ahmed Farooqui
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Ambuj Roy
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Arvind Kumar
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Neeraj Nischal
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Ashutosh Biswas
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Naveet Wig
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Rita Sood
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
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31
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Sever IH, Ozkul B, Erisik Tanriover D, Ozkul O, Elgormus CS, Gur SG, Sogut I, Uyanikgil Y, Cetin EO, Erbas O. Protective effect of oxytocin through its anti-inflammatory and antioxidant role in a model of sepsis-induced acute lung injury: Demonstrated by CT and histological findings. Exp Lung Res 2021; 47:426-435. [PMID: 34665057 DOI: 10.1080/01902148.2021.1992808] [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: 10/20/2022]
Abstract
Although several studies demonstrate the anti-inflammatory effect of oxytocin in different pathophysiological processes, there are limited data describing the impact of oxytocin on acute respiratory distress syndrome (ARDS). We aimed to elucidate the protective effect of oxytocin in ARDS with histopathological evaluation and radiological imaging in addition to biochemical markers. Fecal intraperitoneal injection procedure (FIP) was performed on 24 of 32 rats included in the study for creating a sepsis model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 8), untreated septic group [was operated (FIP) and received no treatment, n = 8], placebo group (FIP, treated with 10 ml/kg of saline at once, n = 8), and treated group (FIP, treated with 0.1 mg/kg of oxytocin at once, n = 8). Chest CT was performed for all rats 20 hours after the procedure and density of the lungs were measured manually by using HU. All animals were sacrificed for histopathological examination of lung damage and blood samples were collected for biochemical analysis. Plasma malondialdehyde (MDA), lactic acid (LA), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL 1-β) levels were significantly increased in the placebo (FIP + saline) and the untreated (FIP) groups, and plasma levels of all biomarkers were reversed by oxytocin. Further, the density of the lung parenchyma (Hounsfield unit) on CT images and the histopathological lung damage score values were closer to the control group in the oxytocin-treated group compared to the placebo group. Our findings suggested that oxytocin could exert anti-inflammatory, antioxidant and protective effects in FIP-induced ARDS.
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Affiliation(s)
- I H Sever
- Department of Radiology, Demiroğlu Bilim University, Istanbul, Turkey
| | - B Ozkul
- Department of Radiology, Istanbul Atlas University, Istanbul, Turkey
| | - D Erisik Tanriover
- Department of Histology and Embryology, Ege University, Faculty of Medicine, Izmir, Turkey
| | - O Ozkul
- Medical Oncology, Bagcilar Research and Training Hospital, Istanbul, Turkey
| | - C S Elgormus
- Department of Emergency Medicine, Istanbul Atlas University, Istanbul, Turkey
| | - S G Gur
- Department of Radiology, Demiroğlu Bilim University, Istanbul, Turkey
| | - I Sogut
- Department of Biochemistry, Demiroğlu Bilim University, Istanbul, Turkey
| | - Y Uyanikgil
- Department of Histology and Embryology, Ege University, Faculty of Medicine, Izmir, Turkey
| | - E O Cetin
- Department of Pharmaceutical Technology, Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Ege University, Izmir, Turkey
| | - O Erbas
- Department of Physiology, Demiroğlu Bilim University, Istanbul, Turkey
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32
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Peng M, Deng F, Qi D, Hu Z, Zhang L. The Hyperbilirubinemia and Potential Predictors Influence on Long-Term Outcomes in Sepsis: A Population-Based Propensity Score-Matched Study. Front Med (Lausanne) 2021; 8:713917. [PMID: 34604255 PMCID: PMC8484885 DOI: 10.3389/fmed.2021.713917] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 08/16/2021] [Indexed: 01/20/2023] Open
Abstract
Objective: Although hyperbilirubinemia has been associated with mortality in patients who are critically ill, yet no clinical studies dissect the effect of dynamic change of hyperbilirubinemia on long-term septic prognosis. The study aims to investigate the specific stages of hyperbilirubinemia and potential risk factors on long-term outcomes in patients with sepsis. Methods: In this retrospective observational cohort study, patients with sepsis, without previous chronic liver diseases, were identified from the Medical Information Mart for the Intensive Care III MIMIC-III database. We used propensity scores (PS) to adjust the baseline differences in septic patients with hyperbilirubinemia or not. The multivariate Cox was employed to investigate the predictors that influence a clinical outcome in sepsis. Results: Of 2,784 patients with sepsis, hyperbilirubinemia occurred in 544 patients (19.5%). After PS matching, a survival curve demonstrated that patients with sepsis with the new onset of total bilirubin (TBIL) levels more than or equal to 5 mg/dl survived at significantly lower rates than those with TBIL levels <5 mg/dl. Multivariate Cox hazard analysis showed that patients with TBIL at more than or equal to 5 mg/dl during sepsis exhibit 1.608 times (95% CI: 1.228-2.106) higher risk of 1-year mortality than those with TBIL levels <5 mg/dl. Also, age above 65 years old, preexisting malignancy, a respiratory rate above 30 beats/min at admission, serum parameters levels within 24-h admission, containing international normalized ratio (INR) above 1.5, platelet <50*10∧9/L, lactate above 4 mmol/L, and bicarbonate <22 or above 29 mmol/L are the independent risk factors for long-term mortality of patients with sepsis. Conclusions: After PS matching, serum TBIL levels at more than or equal to 5 mg/dl during hospitality are associated with increased long-term mortality for patients with sepsis. This study may provide clinicians with some cutoff values for early intervention, which may improve the prognosis of patients with sepsis.
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Affiliation(s)
- Milin Peng
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Fuxing Deng
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Desheng Qi
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.,Department of Emergency, Xiangya Hospital, Central South University, Changsha, China
| | - Zhonghua Hu
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Institute of Molecular Precision Medicine, Central South University, Changsha, China
| | - Lina Zhang
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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33
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Zha YF, Xie J, Ding P, Zhu CL, Li P, Zhao ZZ, Li YH, Wang JF. Senkyunolide I protect against lung injury via inhibiting formation of neutrophil extracellular trap in a murine model of cecal ligation and puncture. Int Immunopharmacol 2021; 99:107922. [PMID: 34224996 DOI: 10.1016/j.intimp.2021.107922] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/16/2021] [Accepted: 06/22/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Senkyunolide I (SEI), a component of a Chinese herb named Ligusticum Chuanxiong hort, which is included in the formulation of Xuebijing Injection, a medication used to treat sepsis in China. Our previous study showed that SEI was protective against sepsis-associated encephalopathy and the present study was performed to investigate the role of SEI in sepsis-induced lung injury in a murine model of cecal ligation and puncture (CLP). METHODS SEI (36 mg/kg in 200 μl) or vehicle was administered immediately after CLP surgery. The lung injury was assessed 24 h later by histopathological tests, protein concentration in the bronchoalveolar lavage fluid (BALF), neutrophil recruitment in the lung tissue (myeloperoxidase fluorescence, MPO), pro-inflammatory cytokines and oxidative responses. Platelet activation was detected by CD42d/GP5 immunofluorescence and neutrophil extracellular trap (NET) were determined by immunofluorescence assays and enzyme linked immunosorbent assay (ELISA) of MPO-DNA. In vitro experiments were performed to detect the level of MPO-DNA complex released by SEI-treated neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA) or co-cultured with platelets from CLP mice. RESULTS SEI administration relieved the injury degree in CLP mice according to the histopathological tests (P < 0.05 compared with DMSO + CLP group). Protein level in the BALF and neutrophil infiltration were remarkably reduced by SEI after CLP surgery (P < 0.05 compared with DMSO + CLP group). TNF-α, IL-1β and IL-6 were decreased in the plasma and lung tissues from CLP mice treated with SEI (P < 0.05 compared with DMSO + CLP group). The phosphorylation of JNK, ERK, p38 and p65 were all inhibited by SEI (P < 0.05 compared with DMSO + CLP group). Immunofluorescence of MPO showed that neutrophil number was significantly lower in SEI treated CLP mice than in vehicle treated CLP mice (P < 0.05). The CD42d/GP5 staining suggested that platelet activation was significantly reduced and the NET level in the lung tissue and plasma was greatly attenuated by SEI treatment (P < 0.05 compared with DMSO + CLP group). In vitro experiments showed that the MPO-DNA level stimulated by PMA was significantly reduced by SEI treatment (P < 0.05 compared with DMSO treatment). Co-culture neutrophils with platelets from CLP mice resulted in higher level of MPO-DNA complex, while SEI partly reversed such effects of platelet on NET formation. CONCLUSIONS SEI was protective against lung injury induced by CLP in mice. The NET formation was significantly reduced by SEI treatment, which might be involved in the mechanism of the protective effect.
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Affiliation(s)
- Yi-Feng Zha
- Department of Anesthesiology, Huashan Hospital North, Fudan University, Shanghai 201906, China
| | - Jian Xie
- Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Peng Ding
- Department of Anesthesiology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Cheng-Long Zhu
- Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Peng Li
- Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Zhen-Zhen Zhao
- Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Yong-Hua Li
- Department of Anesthesiology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
| | - Jia-Feng Wang
- Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
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Cao L, Xiao M, Wan Y, Zhang C, Gao X, Chen X, Zheng X, Xiao X, Yang M, Zhang Y. Epidemiology and Mortality of Sepsis in Intensive Care Units in Prefecture-Level Cities in Sichuan, China: A Prospective Multicenter Study. Med Sci Monit 2021; 27:e932227. [PMID: 34504051 PMCID: PMC8439121 DOI: 10.12659/msm.932227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Studies on the epidemiology of sepsis in intensive care units (ICUs) of prefecture-level hospitals in China are rare. This study aimed to investigate the epidemiological characteristics and mortality risk factors of sepsis in ICUs of tertiary hospitals in Sichuan, China. MATERIAL AND METHODS In this prospective, multicenter, observational study, patients admitted to the ICU of 7 tertiary hospitals in Sichuan (China) between October 10, 2017 and January 9, 2018 were screened for sepsis using the Sepsis-3 criteria. Patients with sepsis were included. RESULTS Of the 1604 patients screened for sepsis, 294 (18.3%) had sepsis, and 140 (47.6%) had septic shock. Of these, 169 (57.5%) died. Multivariable analysis showed that central nervous system dysfunction (odds ratio [OR]=2.59, 95% confidence interval [CI]: 1.15-5.84, P=0.022), lowest blood phosphorus level (OR=2.56, 95% CI: 1.21-5.44, P=0.014), highest lactate level (OR=1.20, 95% CI: 1.10-1.32, P<0.001), 24-h Acute Physiologic Assessment and Chronic Health Evaluation-II (APACHE-II) score (OR=1.08, 95% CI: 1.03-1.13, P=0.002), and lung infection (OR=2.57, 95% CI: 1.30-5.09, P=0.007) were independently associated with mortality in patients with sepsis. CONCLUSIONS The prevalence and mortality rates of sepsis are high in tertiary hospital ICUs in Sichuan, China. The APACHE-II score on day 1 after diagnosis, acute central nervous system dysfunction, lowest blood phosphorus, high serum lactate, and lung infection were independent risk factors of mortality in patients with sepsis.
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Affiliation(s)
- Lianghai Cao
- Department of Critical Care Medicine, Second People's Hospital of Yibin City, Yibin, Sichuan, China (mainland)
| | - Min Xiao
- Department of Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China (mainland)
| | - Yong Wan
- Department of Anesthesiology, North Sichuan Medical College, Nanchong, Sichuan, China (mainland)
| | - Chaogui Zhang
- Department of Critical Care Medicine, Second People's Hospital of Yibin City, Yibin, Sichuan, China (mainland)
| | - Xiaofeng Gao
- Department of Preventive Medicine, North Sichuan Medical College, Nanchong, Sichuan, China (mainland)
| | - Xuemei Chen
- Department of Critical Care Medicine, West China-Guang'an Hospital, Sichuan University, Guangan, Sichuan, China (mainland)
| | - Xiangde Zheng
- Department of Critical Care Medicine, Dazhou Central Hospital, Dazhou, Sichuan, China (mainland)
| | - Xianhua Xiao
- Department of Critical Care Medicine, Second People's Hospital of Neijiang City, Neijiang, Sichuan, China (mainland)
| | - Mingquan Yang
- Department of Critical Care Medicine, First People's Hospital of Zigong City, Zigong, Sichuan, China (mainland)
| | - Yuanhua Zhang
- Department of Critical Care Medicine, First People's Hospital of Yibin City, Yibin, Sichuan, China (mainland)
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Kumar R, Tripathi AS, Sharma N, Singh G, Mohapatra L. Is Regular Probiotic Practice Safe for Management of Sepsis? Chin J Integr Med 2021; 28:185-192. [PMID: 34268649 DOI: 10.1007/s11655-021-3334-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2020] [Indexed: 12/28/2022]
Abstract
For decades, the gut has been thought to play an important role in sepsis pathogenesis. Sepsis is a serious life-threatening, chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit patients. Probiotics have dual roles in polymicrobial sepsis i.e. probiotics may induce sepsis in many cases and may prevent its prognosis in many cases. Experimental evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor, interleukin-10 (IL-10), IL-6, etc., in septicemia. In addition, probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in septicemia. On contrary, probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced inflammation. Importantly, in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing it. This review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.
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Affiliation(s)
- Rishabh Kumar
- Department of Pharmacology, ISF College of Pharmacy, Moga (Punjab), India
| | - Alok Shiomurti Tripathi
- Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Lucknow (UP), India.
| | - Nidhi Sharma
- Department of Pharmacology, ISF College of Pharmacy, Moga (Punjab), India
| | - Gaaminepreet Singh
- Department of Pharmacology, ISF College of Pharmacy, Moga (Punjab), India
| | - Lucy Mohapatra
- Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Lucknow (UP), India
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Impact of Cardiovascular Failure in Intensive CareUnit-Acquired Pneumonia: A Single-Center, Prospective Study. Antibiotics (Basel) 2021; 10:antibiotics10070798. [PMID: 34209181 PMCID: PMC8300830 DOI: 10.3390/antibiotics10070798] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/21/2021] [Accepted: 06/24/2021] [Indexed: 01/20/2023] Open
Abstract
Background: Cardiovascular failure (CVF) may complicate intensive care unit-acquired pneumonia (ICUAP) and radically alters the empirical treatment of this condition. The aim of this study was to determine the impact of CVF on outcome in patients with ICUAP. Methods: A prospective, single-center, observational study was conducted in six medical and surgical ICUs at a University Hospital. CVS was defined as a score of 3 or more on the cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score. At the onset of ICUAP, CVF was reported as absent, transient (if lasting ≤ 3 days) or persistent (>3 days). The primary outcome was 90-day mortality modelled through a Cox regression analysis. Secondary outcomes were 28-day mortality, hospital mortality, ICU length of stay (LOS) and hospital LOS. Results: 358 patients were enrolled: 203 (57%) without CVF, 82 (23%) with transient CVF, and 73 (20%) with persistent CVF. Patients with transient and persistent CVF were more severely ill and presented higher inflammatory response than those without CVF. Despite having similar severity and aetiology, the persistent CVF group more frequently received inadequate initial antibiotic treatment and presented more treatment failures than the transient CVF group. In the persistent CVF group, at day 3, a bacterial superinfection was more frequently detected. The 90-day mortality was significantly higher in the persistent CVF group (62%). The 28-day mortality rates for patients without CVF, with transient and with persistent CVF were 19, 35 and 41% respectively and ICU mortality was 60, 38 and 19% respectively. In the multivariate analysis chronic pulmonary conditions, lack of Pa02/FiO2 improvement at day 3, pulmonary superinfection at day 3 and persistent CVF were independently associated with 90-day mortality in ICUAP patients. Conclusions: Persistent CVF has a significant impact on the outcome of patients with ICUAP. Patients at risk from persistent CVF should be promptly recognized to optimize treatment and outcomes.
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Hausfater P, Robert Boter N, Morales Indiano C, Cancella de Abreu M, Marin AM, Pernet J, Quesada D, Castro I, Careaga D, Arock M, Tejidor L, Velly L. Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study. Crit Care 2021; 25:227. [PMID: 34193208 PMCID: PMC8247285 DOI: 10.1186/s13054-021-03622-5] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/31/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP). METHODS Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP). RESULTS A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI]. CONCLUSIONS MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).
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Affiliation(s)
- Pierre Hausfater
- Emergency Department, Hôpital Pitié-Salpêtrière, APHP-Sorbonne Université, 83 Boulevard de l'hôpital, 75651, Paris Cedex 13, France.
- Sorbonne Université, GRC-14 BIOSFAST, Paris, France.
- UMR INSERM 1166, IHU ICAN, Sorbonne Université, Paris, France.
| | - Neus Robert Boter
- Emergency Department, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
- Universitat Autònoma de Barcelona, Badalona, Spain
| | - Cristian Morales Indiano
- Universitat Autònoma de Barcelona, Badalona, Spain
- Laboratory Medicine Department, Laboratori Clinic Metropolitana Nord, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
| | - Marta Cancella de Abreu
- Emergency Department, Hôpital Pitié-Salpêtrière, APHP-Sorbonne Université, 83 Boulevard de l'hôpital, 75651, Paris Cedex 13, France
- Sorbonne Université, GRC-14 BIOSFAST, Paris, France
| | - Adria Mendoza Marin
- Emergency Department, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
- Universitat Autònoma de Barcelona, Badalona, Spain
| | - Julie Pernet
- Emergency Department, Hôpital Pitié-Salpêtrière, APHP-Sorbonne Université, 83 Boulevard de l'hôpital, 75651, Paris Cedex 13, France
| | - Dolores Quesada
- Universitat Autònoma de Barcelona, Badalona, Spain
- Microbiology Department, Laboratori Clinic Metropolitana Nord, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
| | | | | | - Michel Arock
- Biochemisty and Emergency Biology Department, Hôpital Pitié-Salpêtrière, APHP-Sorbonne Université, Paris, France
| | | | - Laetitia Velly
- Emergency Department, Hôpital Pitié-Salpêtrière, APHP-Sorbonne Université, 83 Boulevard de l'hôpital, 75651, Paris Cedex 13, France
- Sorbonne Université, GRC-14 BIOSFAST, Paris, France
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Alves B, Jouffroy R. [A central role for the home care nurse in the assessment of the severity of sepsis]. SOINS; LA REVUE DE REFERENCE INFIRMIERE 2021; 66:11-13. [PMID: 34187646 DOI: 10.1016/s0038-0814(21)00155-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
En 2016, la conférence de consensus Sepsis 3 a mis en avant le score Quick Sepsis-related Organ Failure Assessment en complément du raisonnement clinique paramédical pour évaluer la sévérité et le risque de mortalité du sepsis À l'hôpital, ce score permet de dépister précocement le sepsis à risque d'évolution défavorable Sa mise en œuvre par les infirmiers à domicile devrait permettre de réduire la morbi-mortalité du sepsis, soulignant le rôle essentiel de ces professionnels dans l'activation de la chaîne de survie du sepsis.
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Affiliation(s)
- Barbara Alves
- Service d'anesthésie-réanimation, Samu de Paris, Assistance publique-Hôpitaux de Paris, hôpital Necker-Enfants malades, 149 rue de Sèvres, 75015 Paris, France
| | - Romain Jouffroy
- Service d'anesthésie-réanimation, Samu de Paris, Assistance publique-Hôpitaux de Paris, hôpital Necker-Enfants malades, 149 rue de Sèvres, 75015 Paris, France; Service de médecine intensive réanimation, hôpital Ambroise-Paré, 9 avenue Charles-de-Gaulle, 92100 Boulogne-Billancourt, France; Centre de recherche en épidémiologie et santé des populations, U1018 Inserm équipe 5, université Paris Saclay, hopital Ambroise-Paré, 9 avenue Charles-de-Gaulle 92100 Boulogne Billancourt, France.
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Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome. Crit Care Med 2021; 48:e391-e399. [PMID: 32187077 DOI: 10.1097/ccm.0000000000004285] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome. DESIGN Prospective phase I clinical trial. SETTING Medical center in Kaohsiung, Taiwan. PATIENTS Moderate-to-severe acute respiratory distress syndrome with a PaO2/FIO2 ratio less than 200. INTERVENTIONS Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 10 cells/kg), the next three patients with intermediate dose (5.0 × 10 cells/kg), and the final three patients with high dose (1.0 × 10 cells/kg) between December 2017 and August 2019. MEASUREMENTS AND MAIN RESULTS Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14CD33/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14CD33+) and mesenchymal stem cell markers (CD26+CD45-/CD29+CD45-/CD34+CD45-/CD44+CD45-/CD73+CD45-/CD90+CD45-/CD105+CD45-/CD26+CD45-) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cell/Cytotoxity-T-cell/Regulatory-T-cell) were notably increased (p for trend < 0.001) after cell infusion. CONCLUSIONS The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.
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Jouffroy R, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Bounes V, Boularan J, Léguillier T, Gueye-Ngalgou P, Vivien B. Impact of Prehospital Antibiotic Therapy on Septic Shock Mortality. PREHOSP EMERG CARE 2021; 25:317-324. [PMID: 32352890 DOI: 10.1080/10903127.2020.1763532] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 04/28/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Septic shock (SS) is associated with high morbidity and mortality rate. Early antibiotic therapy administration in septic patients was shown to reduce mortality but its impact on mortality in a prehospital setting is still under debate. To clarify this point, we performed a retrospective analysis on patients with septic shock who received antibiotics in a prehospital setting. Methods: From April 15th, 2017 to March 1st, 2020, patients with septic shock requiring Mobile Intensive Care Unit (MICU) intervention were retrospectively analyzed to assess the impact of prehospital antibiotic therapy administration on a 30-day mortality. Results: Three-hundred-eight patients with septic shock requiring MICU intervention in the prehospital setting were analyzed. The mean age of the study population was 70 ± 15 years. Presumed origin of SS was mainly pulmonary (44%), digestive (21%) or urinary (19%) infection. Overall 30-day mortality was 29%. Ninety-eight (32%) patients received antibiotic therapy. Using Cox regression analysis, we showed that prehospital antibiotic therapy significantly reduces 30-day mortality for patients with septic shock (hazard ratio = 0.56, 95%CI [0.35-0.89], p = 0.016). Conclusion: In this retrospective study, prehospital antibiotic therapy reduces 30-day mortality of septic shock patients cared for by MICU. Further studies will be needed to confirm the beneficial effect of prehospital antibiotic therapy in association or not with prehospital hemodynamic optimization to improve the survival of septic shock patients.
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Lu Z, Zhang J, Hong J, Wu J, Liu Y, Xiao W, Hua T, Yang M. Development of a Nomogram to Predict 28-Day Mortality of Patients With Sepsis-Induced Coagulopathy: An Analysis of the MIMIC-III Database. Front Med (Lausanne) 2021; 8:661710. [PMID: 33889591 PMCID: PMC8056034 DOI: 10.3389/fmed.2021.661710] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 03/04/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Sepsis-induced coagulopathy (SIC) is a common cause for inducing poor prognosis of critically ill patients in intensive care unit (ICU). However, currently there are no tools specifically designed for assessing short-term mortality in SIC patients. This study aimed to develop a practical nomogram to predict the risk of 28-day mortality in SIC patients. Methods: In this retrospective cohort study, we extracted patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis was defined based on Sepsis 3.0 criteria and SIC based on Toshiaki Iba's criteria. Kaplan–Meier curves were plotted to compare the short survival time between SIC and non-SIC patients. Afterward, only SIC cohort was randomly divided into training or validation set. We employed univariate logistic regression and stepwise multivariate analysis to select predictive features. The proposed nomogram was developed based on multivariate logistic regression model, and the discrimination and calibration were verified by internal validation. We then compared model discrimination with other traditional severity scores and machine learning models. Results: 9432 sepsis patients in MIMIC III were enrolled, in which 3280 (34.8%) patients were diagnosed as SIC during the first ICU admission. SIC was independently associated with the 7- and 28-day mortality of ICU patients. K–M curve indicated a significant difference in 7-day (Log-Rank: P < 0.001 and P = 0.017) and 28-day survival (Log-Rank: P < 0.001 and P < 0.001) between SIC and non-SIC groups whether the propensity score match (PSM) was balanced or not. For nomogram development, a total of thirteen variables of 3,280 SIC patients were enrolled. When predicted the risk of 28-day mortality, the nomogram performed a good discrimination in training and validation sets (AUROC: 0.78 and 0.81). The AUROC values were 0.80, 0.81, 0.71, 0.70, 0.74, and 0.60 for random forest, support vector machine, sequential organ failure assessment (SOFA) score, logistic organ dysfunction score (LODS), simplified acute physiology II score (SAPS II) and SIC score, respectively, in validation set. And the nomogram calibration slope was 0.91, the Brier value was 0.15. As presented by the decision curve analyses, the nomogram always obtained more net benefit when compared with other severity scores. Conclusions: SIC is independently related to the short-term mortality of ICU patients. The nomogram achieved an optimal prediction of 28-day mortality in SIC patient, which can lead to a better prognostics assessment. However, the discriminative ability of the nomogram requires validation in external cohorts to further improve generalizability.
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Affiliation(s)
- Zongqing Lu
- The 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jin Zhang
- The 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jianchao Hong
- The 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jiatian Wu
- The 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yu Liu
- Key Laboratory of Intelligent Computing & Signal Processing, Ministry of Education, Anhui University, Hefei, China
| | - Wenyan Xiao
- The 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Tianfeng Hua
- The 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Min Yang
- The 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
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Abstract
Introduction: Sepsis is a life-threatening organ dysfunction that is caused by a dysregulated host response to the infection. Urosepsis contributes up to 25% of all sepsis cases. An important part of the management of urosepsis is to rule out possible surgical causes such as urolithiasis, obstructive uropathy, or abscess formation along the urogenital tract. Objective: The aim of this study is to look at whether urological conditions and recent urological surgery contribute significantly to all patients admitted with urosepsis. Methods: A total of 2679 urine cultures and 654 blood cultures performed in Connolly Hospital Emergency Department were reviewed between 2016 and 2018. Patients were included if they had a matching urine culture and blood culture performed within 24 hours of admission. A retrospective chart review was performed for all patients included in the study. Results: Our study included 85 patients admitted with urosepsis between 2016 and 2018. The average age was 70.3 years (21–100 years), in which 61% (n = 52) of patients were female, 18% (n = 16) had a long-term indwelling catheter, 11.8% (n = 10) were admitted as urosepsis with a urological condition. The most common urological condition predisposing patients to urosepsis in this study was bladder outlet obstruction secondary to benign prostatic hyperplasia. A total of 4.7% (n = 4) of patients died during their admission. The complications as a result of urosepsis included a prostatic abscess, a psoas abscess, an ileus, an infected cyst, and 1 case of emphysematous pyelonephritis. Conclusion: In this study, the majority of patients admitted with urosepsis did not have an underlying urological condition or recent urological instrumentation. Clinicians should be aware of potential complications as a result of a urosepsis.
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Prehospital hemodynamic optimisation is associated with a 30-day mortality decrease in patients with septic shock. Am J Emerg Med 2021; 45:105-111. [PMID: 33684866 DOI: 10.1016/j.ajem.2021.02.060] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 02/01/2021] [Accepted: 02/24/2021] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Septic shock (SS) is characterized by low blood pressure resulting in organ failure and poor prognosis. Among SS treatments, in hospital studies reported a beneficial effect of early hemodynamic resuscitation on mortality rate. This study aims to investigate the relationship between prehospital hemodynamic optimisation and 30-day mortality in patients with SS. METHODS From April 6th, 2016 to December 31th, 2019, patients with SS requiring prehospital Mobile Intensive Care Unit intervention (mICU) were included. Prehospital hemodynamic optimisation was defined as a arterial blood pressure of >65 mmHg, or >75 mmHg if previous hypertension history, at the end of the prehospital stage. RESULTS Three hundred thirty-seven patients were retrospectively analysed. The mean age was 69 ± 15 years, and 226 patients (67%) were male. One hundred and thirty-six patients (40%) had previous hypertension history. Pulmonary, digestive and urinary infections were the suspected cause of the SS in respectively 46%, 23% and 15% of the cases. 30-day overall mortality was 30%. Prehospital hemodynamic optimisation was complete for 204 patients (61%). Cox regression analysis reports a significant association between prehospital hemodynamic optimisation and 30-day mortality (HRa = 0.52 95%CI [0.31-0.86], p = 0.01). CONCLUSION In this study, we report that prehospital hemodynamic optimisation is associated with a decrease in 30-day mortality in patients with SS cared for by a mICU in the prehospital setting. An individualized mean arterial pressure target, based on previous hypertension history, may be considered from the prehospital stage of SS resuscitation.
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Lin J, Gu C, Zhang S, Tian L, Ren K, Cao Z, Han X. Sites and Causes of Infection in Patients with Sepsis-Associated Liver Dysfunction: A Population Study from the Medical Information Mart for Intensive Care III. Med Sci Monit 2021; 27:e928928. [PMID: 33638975 PMCID: PMC7927361 DOI: 10.12659/msm.928928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 12/17/2020] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Little is known about the relationship between the site of infection, type of pathogen, and the occurrence of sepsis-associated liver dysfunction (SALD). This population study aimed to identify the sites and types of infection in SALD patients. MATERIAL AND METHODS We conducted a retrospective observational study using the Medical Information Mart for Intensive Care III. Patients with sepsis were divided into a SALD group and a control group. We evaluated the effect of the location of culture-positive specimens and the distribution of pathogens on the occurrence of SALD and then compared the clinical outcomes. RESULTS A total of 14 596 admissions were included, and the incidence of SALD was 11.96%. Positive bile culture (odds ratio [OR] 7.450, P<0.001), peritoneal fluid culture (OR 3.616, P<0.001), and blood culture (OR 1.957, P<0.001) were correlated with the occurrence of SALD. Infection with Enterococcus faecium (OR 3.065, P<0.001), Bacteroides fragilis (OR 2.061, P<0.001), Klebsiella oxytoca (OR 2.066, P<0.001), Enterobacter aerogenes (OR 1.92, P=0.001), and Aspergillus fumigatus (OR 2.144, P=0.001) were correlated with the occurrence of SALD. The Intensive Care Unit mortality and hospital mortality were higher in the SALD group than in the control group (24.7% vs 9.0%, P<0.001; 34.2% vs 13.8%, P<0.001, respectively). CONCLUSIONS SALD should be considered for patients with sepsis whose infection site is the biliary system, abdominal cavity, or blood and the pathogen is Enterococcus faecium, B. fragilis, K. oxytoca, Enterobacter aerogenes, or A. fumigatus. When SALD occurs in patients with sepsis, the above infection sites and pathogens should be considered first.
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Affiliation(s)
- Jinfeng Lin
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, P.R. China
| | - Chunfeng Gu
- Ctrip Infrastructure Service, Trip.com Group Ltd., Nantong, Jiangsu, P.R. China
| | - Suyan Zhang
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, P.R. China
| | - Lijun Tian
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, P.R. China
| | - Ke Ren
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, P.R. China
| | - Zhilong Cao
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, P.R. China
| | - Xudong Han
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, P.R. China
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45
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Wang M, Jiang L, Zhu B, Li W, Du B, Kang Y, Weng L, Qin T, Ma X, Zhu D, Wang Y, Zhan Q, Duan M, Li W, Sun B, Cao X, Ai Y, Li T, Zhu X, Jia J, Zhou J, He Y, Xi X. The Prevalence, Risk Factors, and Outcomes of Sepsis in Critically Ill Patients in China: A Multicenter Prospective Cohort Study. Front Med (Lausanne) 2020; 7:593808. [PMID: 33392219 PMCID: PMC7774866 DOI: 10.3389/fmed.2020.593808] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 11/16/2020] [Indexed: 02/05/2023] Open
Abstract
Background: Sepsis is a main cause of morbidity and mortality in critically ill patients. The epidemiology of sepsis in high-income countries is well-known, but information on sepsis in middle- or low-income countries is still deficient, especially in China. The purpose of this study was to explore the prevalence, characteristics, risk factors, treatment, and outcomes of sepsis in critically ill patients in tertiary hospitals in China. Methods: A multicenter prospective observational cohort study was performed with consecutively collected data from adults who stayed in any intensive care unit (ICU) for at least 24 h; data were collected from 1 January 2014 to 31 August 2015, and patients were followed until death or discharge from the hospital. Results: A total of 4,910 patients were enrolled in the study. Of these, 2,086 (42.5%) presented with sepsis or septic shock on admission to the ICU or within the first 48 h after admission to the ICU. ICU mortality was higher in patients with sepsis (13.1%) and septic shock (39.0%) and varied according to geographical region. Acinetobacter, Pseudomonas, and Staphylococcus infections were associated with increased ICU mortality. In addition, age, Acute Physiology, and Chronic Health Evaluation II (APACHE II) scores, pre-existing cardiovascular diseases, malignant tumors, renal replacement therapy (RRT), and septic shock were independent risk factors for mortality in patients with sepsis. The prompt administration of antibiotics (OR 0.65, 95% CI 0.46-0.92) and 30 mL/kg of initial fluid resuscitation during the first 3 h (OR 0.43, 95% CI 0.30-0.63) improved the outcome in patients with septic shock. Conclusions: Sepsis was common and was associated with a high mortality rate in critically ill patients in tertiary hospitals in China. The prompt administration of antibiotics and 30 mL/kg fluid resuscitation decreased the risk of mortality.
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Affiliation(s)
- Meiping Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.,Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Li Jiang
- Department of Critical Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Bo Zhu
- Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Wen Li
- Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Bin Du
- Medical Intensive Care Unit, Peking Union Medical College Hospital, Beijing, China
| | - Yan Kang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Li Weng
- Medical Intensive Care Unit, Peking Union Medical College Hospital, Beijing, China
| | - Tiehe Qin
- Department of Critical Care Medicine, Guangdong Geriatric Institute, Guangdong General Hospital, Guangdong, China
| | - Xiaochun Ma
- Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Duming Zhu
- Surgical Intensive Care Unit, Department of Anaesthesiology, ZhongShan Hospital, FuDan University, Shanghai, China
| | - Yushan Wang
- Intensive Care Unit, The First Hospital of Jilin University, Changchun, China
| | - Qingyuan Zhan
- Department of Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Meili Duan
- Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wenxiong Li
- Surgical Intensive Care Unit, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Bing Sun
- Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xiangyuan Cao
- Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Ningxia, China
| | - Yuhang Ai
- Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Tong Li
- Department of Critical Care Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xi Zhu
- Department of Critical Care Medicine, Peking University Third Hospital, Beijing, China
| | - Jianguo Jia
- Surgical Intensive Care Unit, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jianxin Zhou
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yan He
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Xiuming Xi
- Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China
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Zhou Z, Feng T, Xie Y, Zhang X, Du J, Tian R, Qian B, Wang R. Prognosis and rescue therapy for sepsis-related severe thrombocytopenia in critically ill patients. Cytokine 2020; 136:155227. [PMID: 32810784 DOI: 10.1016/j.cyto.2020.155227] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 07/19/2020] [Accepted: 07/30/2020] [Indexed: 12/20/2022]
Abstract
Sepsis is the most common critical disease with high mortality in intensive care unit. Platelet count (PC) frequently altered in sepsis patients and implicated in the pathogenesis of multi-organ failure. It is also worth mentioning that thrombocytopenia was closely associated with poor outcomes in sepsis patients. However, whether drug intervention aimed at correcting thrombocytopenia would improve the prognosis of sepsis patients and which kind of sepsis patients could benefit from this therapy is still unclear. This study aims to explore the effect of severe thrombocytopenia on the prognosis of sepsis and the impact of a platelet-elevating drug (recombinant human thrombopoietin, rhTPO) for these sepsis patients. In this study, we included 249 sepsis patients diagnosed by sepsis 3.0, and these patients were classified into the three groups based on PC: normal (PC ≥ 100 × 109/L), mild-moderate thrombocytopenia (50 × 109/L ≤ PC < 100 × 109/L), and severe thrombocytopenia (PC < 50 × 109/L). We found that patients with severe thrombocytopenia had more blood transfusion, shorter days free from organ support, and worse outcomes as compared with the normal group. However, there was no significant difference between normal and mild-moderate thrombocytopenia groups. Furthermore, a subgroup analysis showed that rescue therapy with rhTPO could rapidly lead to a recovery of the PC, prolong days free from organ support, increase survival days, and reduce the 28-day mortality in sepsis patients with severe thrombocytopenia. These results suggested that sepsis patients with severe thrombocytopenia, not mild-moderate thrombocytopenia, had a poorer prognosis. RhTPO, probably as effective rescue therapy, could quickly recover PC and improve the prognosis in these sepsis patients.
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Affiliation(s)
- Zhigang Zhou
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Tienan Feng
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yun Xie
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Xiaoyan Zhang
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Jiang Du
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Rui Tian
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Biyun Qian
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ruilan Wang
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
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Sun J, Zhang J, Wang X, Ji F, Ronco C, Tian J, Yin Y. Gut-liver crosstalk in sepsis-induced liver injury. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2020; 24:614. [PMID: 33076940 PMCID: PMC7574296 DOI: 10.1186/s13054-020-03327-1] [Citation(s) in RCA: 133] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 10/05/2020] [Indexed: 02/07/2023]
Abstract
Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury.
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Affiliation(s)
- Jian Sun
- Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, China.,International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy
| | - Jingxiao Zhang
- Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, China.,International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy
| | - Xiangfeng Wang
- Department of Pharmacy, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Fuxi Ji
- Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, China
| | - Claudio Ronco
- International Renal Research Institute of Vicenza (IRRIV), Vicenza, Italy.,Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy
| | - Jiakun Tian
- Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, China.
| | - Yongjie Yin
- Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, China.
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Prehospital lactate clearance is associated with reduced mortality in patients with septic shock. Am J Emerg Med 2020; 46:367-373. [PMID: 33097320 DOI: 10.1016/j.ajem.2020.10.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 09/28/2020] [Accepted: 10/07/2020] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Assessment of disease severity in patients with septic shock (SS) is crucial in determining optimal level of care. In both pre- and in-hospital settings, blood lactate measurement is broadly used in combination with the clinical evaluation of patients as the clinical picture alone is not sufficient for assessing disease severity and outcomes. METHODS From 15th April 2017 to 15th April 2019, patients with SS requiring prehospital mobile Intensive Care Unit intervention (mICU) were prospectively included in this observational study. Prehospital blood lactate clearance was estimated by the difference between prehospital (time of first contact between the patients and the mICU prior to any treatment) and in-hospital (at hospital admission) blood lactate levels divided by prehospital blood lactate. RESULTS Among the 185 patients included in this study, lactate measurement was missing for six (3%) in the prehospital setting and for four (2%) at hospital admission, thus 175 (95%) were analysed for prehospital blood lactate clearance (mean age 70 ± 14 years). Pulmonary, digestive and urinary infections were probably the cause of the SS in respectively 56%, 22% and 10% of the cases. The 30-day overall mortality was 32%. Mean prehospital blood lactate clearance was significantly different between patients who died and those who survived (respectively 0.41 ± 2.50 mmol.l-1 vs 1.65 ± 2.88 mmol.l-1, p = 0.007). Cox regression analysis showed that 30-day mortality was associated with prehospital blood lactate clearance > 10% (HRa [CI95] = 0.49 [0.26-0.92], p = 0.028) and prehospital blood lactate clearance < 10% (HRa [CI95] = 2.04 [1.08-3.84], p = 0.028). CONCLUSION A prehospital blood lactate clearance < 10% is associated with 30-day mortality increase in patients with SS handled by the prehospital mICU. Further studies will be needed to evaluate if prehospital blood lactate clearance alone or combined with clinical scores could affected the triage decision-making process for those patients.
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Pre-Hospital Lactatemia Predicts 30-Day Mortality in Patients with Septic Shock-Preliminary Results from the LAPHSUS Study. J Clin Med 2020; 9:jcm9103290. [PMID: 33066337 PMCID: PMC7602068 DOI: 10.3390/jcm9103290] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 09/27/2020] [Accepted: 09/30/2020] [Indexed: 12/29/2022] Open
Abstract
Background: Assessment of disease severity in patients with septic shock (SS) is crucial in determining optimal level of care. In both pre- and in-hospital settings, the clinical picture alone is not sufficient for assessing disease severity and outcomes. Because blood lactate level is included in the clinical criteria of SS it should be considered to improve the assessment of its severity. This study aims to investigate the relationship between pre-hospital blood lactate level and 30-day mortality in patients with SS. Methods: From 15 April 2017 to 15 April 2019, patients with SS requiring pre-hospital Mobile Intensive Care Unit intervention (MICU) were prospectively included in the LAPHSUS study, an observational, non-randomized controlled study. Pre-hospital blood lactate levels were measured at the time of first contact between the patients and the MICU. Results: Among the 183 patients with septic shock requiring action by the MICU drawn at random from LAPHSUS study patients, six (3%) were lost to follow-up on the 30th day and thus 177 (97%) were analyzed for blood lactate levels (mean age 70 ± 14 years). Pulmonary, urinary and digestive infections were probably the cause of the SS in respectively 58%, 21% and 11% of the cases. The 30-day overall mortality was 32%. Mean pre-hospital lactatemia was significantly different between patients who died and those who survived (respectively 7.1 ± 4.0 mmol/L vs. 5.9 ± 3.5 mmol/L, p < 10−3). Using Cox regression analysis adjusted for potential confounders we showed that a pre-hospital blood lactate level ≥ 4 mmol/L significantly predicted 30-day mortality in patients with SS (adjusted hazard ratio = 2.37, 95%CI (1.01–5.57), p = 0.04). Conclusion: In this study, we showed that pre-hospital lactatemia predicts 30-day mortality in patients with septic shock handled by the MICU. Further studies will be needed to evaluate if pre-hospital lactatemia alone or combined with clinical scores could affect the triage decision-making process for those patients.
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50
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Van de Louw A, Twomey K, Habecker N, Rakszawski K. Prevalence of acute liver dysfunction and impact on outcome in critically ill patients with hematological malignancies: a single-center retrospective cohort study. Ann Hematol 2020; 100:229-237. [PMID: 32918593 DOI: 10.1007/s00277-020-04197-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 07/20/2020] [Indexed: 12/20/2022]
Abstract
Patients with hematological malignancies (HM) often require ICU admission, and acute respiratory or renal failure are then independent risk factors for mortality. Data are scarce on acute liver dysfunction (ALD), despite HM patients cumulating risk factors. The objective of this retrospective cohort study was to assess the prevalence of ALD in critically ill HM patients and its impact on outcome. Data of all patients with HM admitted to the medical ICU between 2008 and 2018 were extracted from electronic medical records. ALD was defined by ALT > 165 U/L, AST > 230 U/L, or total bilirubin > 4 mg/dL. Univariate and multivariate logistic regressions were used to analyze hospital mortality. Charts of survivors with ALD were reviewed to assess impact of ALD on subsequent anti-cancer treatment. We included 971 patients (60% male), age 64 (54-72) years, of whom 196 (20%) developed ALD. ALD patients were younger, more frequently had liver cirrhosis or acute leukemia, and had increased severity of illness and vital organ support needs. ALD was associated with hospital mortality in univariate (OR 4.14, 95% CI 2.95-5.80, p < 0.001) and multivariate analysis (OR 1.86, 95% CI 1.07-3.24, p = 0.03). Hospital mortality was 46% in ALD patients; among 106 survivors, a third of patients requiring therapy received it as previously planned, and half of the patients were alive at 1 year. In summary, in a large population of critically ill patients with hematological malignancies, 20% developed ALD, which was an independent risk factor for hospital mortality and occasionally altered further anti-cancer treatment.
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Affiliation(s)
- Andry Van de Louw
- Division of Pulmonary and Critical Care Medicine, Penn State Health Hershey Medical Center, 500 University Dr., Hershey, PA, 17033, USA.
| | - Kathleen Twomey
- Division of Pulmonary and Critical Care Medicine, Penn State Health Hershey Medical Center, 500 University Dr., Hershey, PA, 17033, USA
| | - Nicholas Habecker
- Division of Pulmonary and Critical Care Medicine, Penn State Health Hershey Medical Center, 500 University Dr., Hershey, PA, 17033, USA
| | - Kevin Rakszawski
- Division of Hematology and Oncology, Penn State Health Hershey Medical Center, 500 University Dr, Hershey, PA, 17033, USA
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