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Miao S, Liu Y, Li M, Yan J. Clinical subtypes identification and feature recognition of sepsis leukocyte trajectories based on machine learning. Sci Rep 2025; 15:12291. [PMID: 40210965 PMCID: PMC11986166 DOI: 10.1038/s41598-025-96718-9] [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: 11/16/2024] [Accepted: 03/31/2025] [Indexed: 04/12/2025] Open
Abstract
Sepsis is a highly variable condition, and tracking leukocyte patterns may offer insights for tailored treatment and prognosis. We used the MIMIC-IV database to analyze patients diagnosed with Sepsis-3 within 24 h of ICU admission. Latent class mixed models (LCMM) were applied to leukocyte trajectories to identify sepsis subtypes. The primary outcome was 28-day all-cause mortality, with secondary outcomes including the need for life-support therapies. Associations between leukocyte trajectories and outcomes were assessed using multivariate regression, and findings were externally validated with the eICU database. Use the XGBoost model to identify baseline characteristics of high-risk mortality sepsis subgroups for predicting subgroup allocation upon patient admission to the ICU, and apply the SHAP method to interpret the contributing variables of the model. Among 7410 sepsis patients, eight distinct leukocyte trajectory subtypes were identified. Among those subtypes, patients with persistently high leukocyte levels had the poorest prognosis (HR 3.00; 95% CI 2.48-3.62) and a significantly greater need for life-support therapies; Patients with persistently low white blood cell levels had a higher risk of death (HR 1.68; 95% CI 1.24-2.27) but were less likely to receive invasive mechanical ventilation. Incorporating early ICU baseline variables into an XGBoost algorithm enables effective prediction of high-mortality risk subgroups (AUC > 0.8). SHAP method reveals distinct early clinical characteristics between hyperinflammatory subtypes (class 4, 7, and 8) and the hypoinflammatory subtype (class 1). In ICU-admitted sepsis patients, eight leukocyte trajectories are identified, which is the key independent predictors of prognosis, separating from single leukocyte measurements. High-mortality risk subgroups exhibit distinct clinical characteristics at ICU admission, providing valuable insights for their prediction and personalized early intervention.
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Affiliation(s)
- ShengHui Miao
- The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, 322000, China
| | - YiJing Liu
- Department of Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, 310053, Zhejiang, China
| | - Min Li
- The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, 322000, China
| | - Jing Yan
- Zhejiang Hospital, Zhejiang University School of Medicine, Lingyin Road 12, Hangzhou, 310013, Zhejiang, China.
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Vujaklija Brajkovic A, Kosuta I, Batur L, Sundalic S, Medic M, Vujevic A, Bielen L, Babel J. Patients admitted in the intensive care unit after solid organ or bone marrow transplantation: Retrospective cohort study. World J Transplant 2025; 15:98975. [PMID: 40104198 PMCID: PMC11612888 DOI: 10.5500/wjt.v15.i1.98975] [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: 07/11/2024] [Revised: 09/27/2024] [Accepted: 10/25/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) revolutionized the survival and quality of life of patients with malignant diseases, various immunologic, and metabolic disorders or those associated with a significant impairment in a patient's quality of life. AIM To investigate admission causes and treatment outcomes of patients after SOT or HSCT treated in a medical intensive care unit (ICU). METHODS We conducted a single-center, retrospective epidemiological study in the medical ICU at the University Hospital Centre Zagreb, Croatia covering the period from January 1, 2018 to December 31, 2023. RESULTS The study included 91 patients with either SOT [28 patients (30.8%)] or HSCT [63 patients (69.2%)]. The median age was 56 (43.2-64.7) years, and 60.4% of the patients were male. Patients with SOT had more comorbidities than patients after HSCT [χ² (5, n = 141) = 18.513, P < 0.001]. Sepsis and septic shock were the most frequent reasons for admission, followed by acute respiratory insufficiency in patients following HSCT. Survival rate significantly differed between SOT and HSCT [χ² (1, n = 91) = 21.767, P < 0.001]. ICU survival was 57% in the SOT and 12.7 % in the HSCT group. The need for mechanical ventilation [χ² (1, n = 91) = 17.081, P < 0.001] and vasopressor therapy [χ² (1, n = 91) = 36.803, P < 0.001] was associated with survival. The necessity for acute renal replacement therapy did not influence patients' survival [χ² (1, n = 91) = 0.376, P = 0.54]. In the subgroup of patients with infection, 90% had septic shock, and the majority had positive microbiological samples, mostly Gram-negative bacteria. The ICU survival of patients with sepsis/septic shock cumulatively was 15%. The survival of SOT patients with sepsis/shock was 45%. CONCLUSION Patients with SOT or HSCT are frequently admitted to the ICU due to sepsis and septic shock. Despite advancements in critical care, the mortality rate of patients with refractory septic shock and multiorgan failure in this patient population is extremely high. Early recognition and timely ICU admittance might improve the outcome of patients, especially after HSCT.
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Affiliation(s)
- Ana Vujaklija Brajkovic
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Iva Kosuta
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Lucija Batur
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Sara Sundalic
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Marijana Medic
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Andro Vujevic
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Luka Bielen
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Jaksa Babel
- Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
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Yang H, Li J, Zhang C, Sierra AP, Shen B. Predictive model for daily risk alerts in sepsis patients in the ICU: visualization and clinical analysis of risk indicators. PRECISION CLINICAL MEDICINE 2025; 8:pbaf003. [PMID: 40041421 PMCID: PMC11878768 DOI: 10.1093/pcmedi/pbaf003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 03/06/2025] Open
Abstract
This study introduces a novel Transformer-based time-series framework designed to revolutionize risk stratification in Intensive Care Units (ICUs) by predicting patient outcomes with high temporal precision. Leveraging sequential data from the eICU database, our two-stage architecture dynamically captures evolving health trajectories throughout a patient's ICU stay, enabling real-time identification of high-risk individuals and actionable insights for personalized interventions. The model demonstrated exceptional predictive power, achieving a progressive AUC increase from 0.87 (±0.021) on admission day to 0.92 (±0.009) by day 5, reflecting its capacity to assimilate longitudinal physiological patterns. Rigorous external validation across geographically diverse cohorts-including an 81.8% accuracy on Chinese sepsis data (AUC=0.73) and 76.56% accuracy on MIMIC-IV-3.1 (AUC=0.84)-confirmed robust generalizability. Crucially, SHAP-derived temporal heatmaps unveiled mortality-associated feature dynamics over time, bridging the gap between model predictions and clinically interpretable biomarkers. These findings establish a new paradigm for ICU prognostics, where data-driven temporal modeling synergizes with clinician expertise to optimize triage, reduce diagnostic latency, and ultimately improve survival outcomes in critical care.
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Affiliation(s)
- Hao Yang
- Information Center, West China Hospital of Sichuan University, Chengdu 610041, China
- Department of Computer Science and Information Technologies, Research Center for Information and Communications Technologies, University of A Coruña, Biomedical Research Institute of a Coruña, A Coruña 15071, Spain
| | - Jiaxi Li
- Department of Clinical Laboratory Medicine, Jinniu Maternity and Child Health Hospital of Chengdu, Chengdu 610031, China
| | - Chi Zhang
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Alejandro Pazos Sierra
- Department of Computer Science and Information Technologies, Research Center for Information and Communications Technologies, University of A Coruña, Biomedical Research Institute of a Coruña, A Coruña 15071, Spain
| | - Bairong Shen
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
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Dargent A, Bourredjem A, Jacquier M, Bohe J, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock: α2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS): A Double-Blind Randomized Controlled Pilot Trial. Crit Care Med 2025; 53:00003246-990000000-00485. [PMID: 40019329 PMCID: PMC11952692 DOI: 10.1097/ccm.0000000000006608] [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] [Indexed: 03/01/2025]
Abstract
OBJECTIVES Increasing evidence has suggested the benefits of dexmedetomidine in patients with sepsis. Dexmedetomidine may increase vasopressor sensitivity, which may be of interest in the setting of refractory septic shock. The α2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS) pilot study aimed to evaluate the effect of dexmedetomidine on the vasopressor response in patients with refractory septic shock. DESIGN This study was a multicenter, randomized, placebo-controlled, double-blind pilot trial. SETTING The study was conducted in 5 ICUs in France. PATIENTS Inclusion criteria were septic shock (Sepsis-3 definition) and norepinephrine requirement greater than or equal to 0.25 µg/kg/min (0.5 µg/kg/min of norepinephrine tartrate) with persistent circulatory failure (defined by lactate > 2 mmol/L, oliguria, or skin mottling) and invasive mechanical ventilation. INTERVENTIONS The arterial pressure response to phenylephrine was measured before starting the treatment (0 hr), at 6 hours (primary outcome), and 12 hours. In the treatment arm, dexmedetomidine was given at a fixed dose of 1 µg/kg/hr. MEASUREMENTS AND MAIN RESULTS Inclusions were stopped early because of higher mortality in the dexmedetomidine arm. Thirty-two patients of the 36 planned were included. Response to phenylephrine at 6 hours was lower in the dexmedetomidine group than in the placebo group (1.26 ± 0.23 vs. 1.45 ± 0.26; p = 0.048), although this difference was also observed at baseline (p = 0.029). There were no significant differences between the groups in terms of cumulative norepinephrine dose, lactatemia, Sequential Organ Failure Assessment score, fluid balance, ventilation-free days, or occurrence of bradycardia. Mortality on day 3 was higher in the dexmedetomidine group than in the placebo group, with a difference that diminished and was no longer significant on 30 and 90 days. CONCLUSIONS Patients in the dexmedetomidine arm had a significantly lower response to phenylephrine at all study times including baseline, which might have contributed to higher early mortality in the dexmedetomidine arm and preclude to conclude on dexmedetomidine efficacy in refractory septic shock. However, heart rate was not decreased in the dexmedetomidine arm.
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Affiliation(s)
- Auguste Dargent
- Anesthesia and Critical Care Department, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France
- APCSe Laboratory, VetAgro Sup UPSP 2016.A101, Marcy-l’Étoile, France
| | - Abderrahmane Bourredjem
- INSERM, Université de Bourgogne, CIC 1432, Module Epidémiologique Clinique, CHU Dijon Bourgogne, Dijon, France
| | | | - Julien Bohe
- Anesthesia and Critical Care Department, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France
| | - Laurent Argaud
- Medical Intensive Care Department, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | - Bruno Levy
- Medical Intensive Care Department, CHU Nancy Brabois, Nancy, France
- INSERM U1116, Institut du Cœur et des Vaisseaux, Groupe Choc, équipe 2, Faculté de Médecine, Nancy-Brabois, France
| | - Isabelle Fournel
- INSERM, Université de Bourgogne, CIC 1432, Module Epidémiologique Clinique, CHU Dijon Bourgogne, Dijon, France
| | | | - Julio Badie
- Critical Care Department, Hôpital Nord Franche-Comté, Trévenans, France
| | | | - Jean-Pierre Quenot
- Medical Intensive Care Department, CHU Dijon, Dijon, France
- INSERM UMR1231, LabEx LipSTIC Research Unit (Lipness team), Bourgogne-Franche Comté University, Dijon, France
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Xu DJ, Wang GT, Zhong Q. Extracellular matrix gene set and microRNA network in intestinal ischemia-reperfusion injury: Insights from RNA sequencing for diagnosis and therapy. World J Gastrointest Surg 2025; 17:100034. [DOI: 10.4240/wjgs.v17.i2.100034] [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: 08/05/2024] [Revised: 11/26/2024] [Accepted: 12/06/2024] [Indexed: 01/22/2025] Open
Abstract
Intestinal ischemia-reperfusion injury (IIRI) is a complex and severe pathophysiological process characterized by oxidative stress, inflammation, and apoptosis. In recent years, the critical roles of extracellular matrix (ECM) genes and microRNAs (miRNAs) in IIRI have garnered widespread attention. This review aims to systematically summarize the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI. First, we review the molecular mechanisms of IIRI, focusing on the dual role of the ECM in tissue injury and repair processes. The expression changes and functions of ECM components such as collagen, elastin, and matrix metalloproteinases during IIRI progression are deeply analyzed. Second, we systematically summarize the regulatory roles of miRNAs in IIRI, particularly the mechanisms and functions of miRNAs such as miR-125b and miR-200a in regulating inflammation, apoptosis, and ECM remodeling. Additionally, this review discusses potential diagnostic biomarkers and treatment strategies based on ECM genes and miRNAs. We extensively evaluate the prospects of miRNA-targeted therapy and ECM component modulation in preventing and treating IIRI, emphasizing the clinical translational potential of these emerging therapies. In conclusion, the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI provides new directions for further research, necessitating additional clinical and basic studies to validate and expand these findings for improving clinical outcomes in IIRI patients.
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Affiliation(s)
- Dao-Jian Xu
- Department of Emergency Medicine, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, China
| | - Guo-Tao Wang
- Department of Emergency Medicine, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, China
| | - Qiang Zhong
- Department of Emergency Medicine, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang Province, China
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Liu G, Zheng S, He J, Zhang ZM, Wu R, Yu Y, Fu H, Han L, Zhu H, Xu Y, Shao H, Yan H, Chen T, Shen X. An Easy and Quick Risk-Stratified Early Forewarning Model for Septic Shock in the Intensive Care Unit: Development, Validation, and Interpretation Study. J Med Internet Res 2025; 27:e58779. [PMID: 39913913 PMCID: PMC11843061 DOI: 10.2196/58779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 11/09/2024] [Accepted: 12/19/2024] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Septic shock (SS) is a syndrome with high mortality. Early forewarning and diagnosis of SS, which are critical in reducing mortality, are still challenging in clinical management. OBJECTIVE We propose a simple and fast risk-stratified forewarning model for SS to help physicians recognize patients in time. Moreover, further insights can be gained from the application of the model to improve our understanding of SS. METHODS A total of 5125 patients with sepsis from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were divided into training, validation, and test sets. In addition, 2180 patients with sepsis from the eICU Collaborative Research Database (eICU) were used as an external validation set. We developed a simplified risk-stratified early forewarning model for SS based on the weight of evidence and logistic regression, which was compared with multi-feature complex models, and clinical characteristics among risk groups were evaluated. RESULTS Using only vital signs and rapid arterial blood gas test features according to feature importance, we constructed the Septic Shock Risk Predictor (SORP), with an area under the curve (AUC) of 0.9458 in the test set, which is only slightly lower than that of the optimal multi-feature complex model (0.9651). A median forewarning time of 13 hours was calculated for SS patients. 4 distinct risk groups (high, medium, low, and ultralow) were identified by the SORP 6 hours before onset, and the incidence rates of SS in the 4 risk groups in the postonset interval were 88.6% (433/489), 34.5% (262/760), 2.5% (67/2707), and 0.3% (4/1301), respectively. The severity increased significantly with increasing risk in both clinical features and survival. Clustering analysis demonstrated a high similarity of pathophysiological characteristics between the high-risk patients without SS diagnosis (NS_HR) and the SS patients, while a significantly worse overall survival was shown in NS_HR patients. On further exploring the characteristics of the treatment and comorbidities of the NS_HR group, these patients demonstrated a significantly higher incidence of mean blood pressure <65 mmHg, significantly lower vasopressor use and infused volume, and more severe renal dysfunction. The above findings were further validated by multicenter eICU data. CONCLUSIONS The SORP demonstrated accurate forewarning and a reliable risk stratification capability. Among patients forewarned as high risk, similar pathophysiological phenotypes and high mortality were observed in both those subsequently diagnosed as having SS and those without such a diagnosis. NS_HR patients, overlooked by the Sepsis-3 definition, may provide further insights into the pathophysiological processes of SS onset and help to complement its diagnosis and precise management. The importance of precise fluid resuscitation management in SS patients with renal dysfunction is further highlighted. For convenience, an online service for the SORP has been provided.
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Affiliation(s)
- Guanghao Liu
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Shixiang Zheng
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- Department of Critical Care Medicine, Union Hospital of Fujian Medical University, Fuzhou, China
| | - Jun He
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Zi-Mei Zhang
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Ruoqiong Wu
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
| | - Yingying Yu
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
| | - Hao Fu
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
| | - Li Han
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
| | - Haibo Zhu
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Yichang Xu
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- School of Medical Imaging, Fujian Medical University, Fuzhou, China
| | - Huaguo Shao
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
| | - Haidan Yan
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Ting Chen
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- Department of Computer Science and Technology, Institute of Artificial Intelligence, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing, China
| | - Xiaopei Shen
- Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou, China
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
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Liu G, Wu R, He J, Xu Y, Han L, Yu Y, Zhu H, Guo Y, Fu H, Chen T, Zheng S, Shen X. Clinical phenotyping of septic shock with latent profile analysis: A retrospective multicenter study. J Crit Care 2025; 85:154932. [PMID: 39432929 DOI: 10.1016/j.jcrc.2024.154932] [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: 05/18/2024] [Revised: 09/16/2024] [Accepted: 10/08/2024] [Indexed: 10/23/2024]
Abstract
BACKGROUND Septic shock (SS) is a highly fatal and heterogeneous syndrome. Identifying distinct clinical phenotypes provides valuable insights into the underlying pathophysiological mechanisms and may help to propose precise clinical management strategies. METHODS Latent profile analysis (LPA), a model-based unsupervised method, was used for phenotyping in the MIMIC cohort, and the model was externally independently validated in the eICU and AUMC cohorts. RESULTS Three phenotypes, labeled phenotype I, II, and III, were derived. These phenotypes varied in demographics, clinical features, comorbidities, patterns of organ dysfunction, organ support, and prognosis. Phenotype I, characterized by the most severe organ dysfunction (especially liver), the youngest age, and the highest BMI, had the highest mortality (p < 0.001). Phenotype II, with moderate mortality, was characterized by severe renal injury. In contrast, phenotype III, associated with the oldest age and the fewest comorbidities, exhibited significantly lower mortality. Phenotype I patients had the steepest survival curves and demonstrated an ultra-high risk of death, particularly within the first few days after SS onset. CONCLUSIONS The individualized identification of phenotypes is well suited to clinical practice. The three SS phenotypes differed significantly in pathophysiological and clinical outcomes, which are crucial for informing management decisions and prognosis.
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Affiliation(s)
- Guanghao Liu
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou 350122, China
| | - Ruoqiong Wu
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China
| | - Jun He
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China
| | - Yichang Xu
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China
| | - Li Han
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China
| | - Yingying Yu
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China
| | - Haibo Zhu
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou 350122, China
| | - Yehan Guo
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; School of Medical Imaging, Fujian Medical University, Fuzhou 350122, China
| | - Hao Fu
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China
| | - Ting Chen
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Department of Computer Science and Technology & Institute of Artificial Intelligence & BNRist, Tsinghua University, Beijing 100084, China.
| | - Shixiang Zheng
- Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Department of Critical Care Medicine, Union Hospital of Fujian Medical University, Fuzhou 350001, China.
| | - Xiaopei Shen
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; Fujian Key Laboratory of Medical Bioinformatics, Institute of Precision Medicine, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou 350122, China; Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; School of Medical Imaging, Fujian Medical University, Fuzhou 350122, China.
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Goto A, Ishikawa K, Komiya K. A systematic review of factors associated with poor prognosis despite appropriate antibiotics usage for pneumonia. Respir Investig 2024; 62:1215-1219. [PMID: 39504760 DOI: 10.1016/j.resinv.2024.10.012] [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: 08/22/2024] [Revised: 10/16/2024] [Accepted: 10/31/2024] [Indexed: 11/08/2024]
Abstract
Treatment with appropriate antibiotics does not seem to be associated with prognosis among elderly patients with pneumonia. Identifying factors associated with poor prognosis despite the use of appropriate antibiotics might help withhold aggressive antibiotic treatment in patients with pneumonia. This systematic review aims to identify the risk factors associated with unfavored outcomes despite using appropriate antibiotics for pneumonia. The PubMed database was searched for studies focusing on appropriate antibiotic use in patients with pneumonia (assessed on Aug 7, 2024). Appropriate antibiotics were defined as those sensitive to microorganisms isolated from patients. The risk of bias was evaluated using the Risk of Bias Assessment tool for nonrandomized Studies utilized for controlled observational studies. A total of 1563 studies were identified from the database, and eight observational studies were included in this review: ventilator-associated pneumonia (n = 4), community-onset pneumonia (n = 2), P. aeruginosa pneumonia (n = 1), and S. maltophilia pneumonia (n = 1). Advanced age was the most commonly evaluated factor associated with mortality. Additionally, high severity scores were related to the unfavored outcomes even after treatment with appropriate antibiotics. Advanced age and high severity scores may be associated with increased mortality despite appropriate antibiotic usage for pneumonia. Broad-spectrum antibiotics might not be indicated in elderly pneumonia patients with high severity status who do not wish to receive aggressive antibiotic treatments.
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Affiliation(s)
- Akihiko Goto
- Department of Respiratory Medicine, Oita Medical Center, 2-11-45 Yokota, Oita, 870-0263, Japan; Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.
| | - Kentaro Ishikawa
- Department of Respiratory Medicine, Oita Medical Center, 2-11-45 Yokota, Oita, 870-0263, Japan.
| | - Kosaku Komiya
- Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.
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9
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Ding B, Zhang Y, Wu Y, Li Y. Analysis of the epidemiology and clinical characteristics of Epstein-Barr virus infection. J Med Virol 2024; 96:e29960. [PMID: 39380297 DOI: 10.1002/jmv.29960] [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: 05/17/2024] [Revised: 08/28/2024] [Accepted: 09/28/2024] [Indexed: 10/10/2024]
Abstract
The Epstein-Barr virus (EBV) is responsible for a spectrum of human diseases and demonstrates a considerable prevalence among various populations. Advances in molecular epidemiological research have enhanced our comprehension of EBV-related pathologies. In this study, our objective was to examine the epidemiological profile and clinical features of EBV infection in Chongqing, China. We enrolled patients suspected of EBV-related diseases who were admitted to the First Affiliated Hospital of Chongqing Medical University between May 2013 and November 2022. Inclusion criteria were based on those who underwent EBV-specific immunofluorescence or plasma EBV-DNA testing. Among 13 584 inpatients, the overall seropositivity rates for EBNA-1-IgG, EBV-VCA-IgM, EBV-EA-IgG, EBV-EA-IgA, EBV-VCA-IgA, and EBV-DNA were 91.89%, 7.22%, 18.00%, 16.19%, 30.78%, and 18.00%, respectively. The seropositivity rate for EBNA-1-IgG steadily increased with age. The seropositivity rate for VCA-IgM, an indicator of acute EBV infection, was highest in patients aged 11-20 years at 26.41%, decreasing to 2%-6% in older patients. Additionally, among 205 outpatients, the EBV-DNA positivity rate was 14.15%. In 3670 individuals from health check-up centers, the seropositivity rates for EBV-EA-IgA and EBV-VCA-IgA were 11.96% and 28.09%, respectively, and the EBV-DNA positivity rate was 11.92%, all of which were lower than those in inpatients. Among the 762 EBV-DNA positive inpatients, adults aged 31-40 years were the least affected, with a seropositivity rate of 12.00%, which increased with age. The most common diseases associated with primary EBV infection were infectious mononucleosis (IM) (35.49%), followed by EBV infection (14.15%) and pneumonia (7.19%). The most common diseases associated with EBV reactivation were pneumonia (16.80%), nasopharyngeal carcinoma (NPC) (11.02%), and autoimmune diseases (7.04%). Patients with hemophagocytic lymphohistiocytosis (HLH) had the highest viral load, significantly higher than those with NPC, pneumonia, and liver cirrhosis. This large-scale retrospective study explores the epidemiological characteristics and disease spectrum of EBV infection across all age groups. The findings contribute to the improvement of diagnostic and management strategies for EBV infection.
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Affiliation(s)
- Beining Ding
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Youyu Zhang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yilin Wu
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yongguo Li
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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张 舒, 赵 星, 杨 伟. [Bacterial Blocking and Repair of Intestinal Defects With Well-Alighed Lamellar MXene/Polyvinyl Alcohol Hydrogels Prepared by Bidirectional Freezing Method]. SICHUAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF SICHUAN UNIVERSITY. MEDICAL SCIENCE EDITION 2024; 55:838-844. [PMID: 39170025 PMCID: PMC11334287 DOI: 10.12182/20240760103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Indexed: 08/23/2024]
Abstract
Objective To explore the bacterial blocking effect of oriented multilayer MXene/polyvinyl alcohol (PVA) nanocomposite hydrogels and their effect on the repair of intestinal defects. Methods MXene/PVA nanocomposite hydrogels were prepared using the traditional freezing method and the bidirectional freezing ice template method. The structures of the different hydrogels were observed using scanning electron microscopy (SEM) and micro-CT reconstruction. The rheological properties of the hydrogels were measured using a dynamic rheometer, and their mechanical properties were assessed using a universal testing machine. The burst pressure of the hydrogels was determined through burst experiments, and bacterial colony growth was observed by the osmosis method to assess the bacteria blocking ability of the hydrogels in vitro. A rat model of cecal perforation was established, and the hydrogels were used for intestinal repair. Gram staining was performed to observe in vivo the bacterial blocking ability of the hydrogels, HE staining was performed to observe the intestinal inflammation, and CD31 and CD68 immunofluorescence staining and proliferating cell nuclear antigen (PCNA) staining were performed to observe the repair effect of the hydrogels on intestinal defects. Results SEM and micro-CT reconstruction revealed that the hydrogel prepared by the traditional freezing method exhibited a random porous structure, while the hydrogel prepared by the bidirectional freezing method showed an oriented multilayer structure. Rheological and tensile tests indicated that the oriented hydrogel had superior mechanical properties, and the burst pressure of the oriented multilayer hydrogel was as high as 27 kPa, significantly higher than that of the non-oriented hydrogel (P<0.001). Bacterial colony growth was observed by the osmosis method and it was found that, compared with the non-oriented hydrogel, the oriented multilayer hydrogel could effectively prevent the infiltration of Escherichia coli and Staphylococcus aureus in vitro. Gram staining results showed that the oriented multilayer hydrogel could effectively block intestinal bacteria from entering the abdominal cavity in vivo. HE staining results showed that the oriented multilayer hydrogel could effectively reduce intestinal inflammation in vivo. CD31 and CD68 immunofluorescence staining and PCNA staining results showed that the oriented multilayer hydrogel had a repairing effect on intestinal defects in vivo. Conclusion The oriented multilayer hydrogel prepared by bidirectional freezing effectively prevents bacterial infiltration and reduces intestinal inflammation.
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Affiliation(s)
- 舒婷 张
- 四川大学高分子科学与工程学院 （成都 610065）College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China
| | - 星 赵
- 四川大学高分子科学与工程学院 （成都 610065）College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China
| | - 伟 杨
- 四川大学高分子科学与工程学院 （成都 610065）College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China
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11
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Singhal A, Dubey S, Khan S, Tiwari R, Das S, Ahmad R. Neutrophil-to-Lymphocyte Ratio and Procalcitonin in Sepsis Patients: Do They Have Any Prognostic Significance? Cureus 2024; 16:e62360. [PMID: 39006695 PMCID: PMC11246564 DOI: 10.7759/cureus.62360] [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] [Accepted: 06/14/2024] [Indexed: 07/16/2024] Open
Abstract
INTRODUCTION Biomarkers like white blood cells, C-reactive protein, procalcitonin, and interleukin-1 are used in patients with sepsis for early diagnosis, differentiating various infections, making decisions to start antibiotics and evaluate their response, and to prognosticate morbidity and mortality. Despite the availability of these biomarkers, the prognosis of patients with sepsis in the ICU remains poor. Hence, this study was carried out to test the efficacy of procalcitonin and neutrophil-to-lymphocyte ratio (NLR) to prognosticate mortality and morbidity in terms of incidence of organ dysfunction and length of ICU stay in sepsis patients. METHODS In this prospective observational study, we measured NLR and procalcitonin at days one, three, and seven of sepsis patients and divided them into four groups: low NLR and high procalcitonin (LNHP), high NLR and high procalcitonin (HNHP), high NLR and low procalcitonin (HNLP), and low NLR and low procalcitonin (LNLP). Mortality at 28 days was noted as the primary outcome. RESULTS Out of 85 patients included in the study, five were lost to follow-up. Although no statistically significant difference was found in the primary outcome between all four groups, regression analysis showed that rising NLR and procalcitonin values were associated with a significant increase in mortality. CONCLUSION Serial values of NLR and procalcitonin are more important in predicting severity in comparison to a single value at presentation and can be used as a prognostic marker in sepsis patients.
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Affiliation(s)
- Akash Singhal
- Critical Care Medicine, Max Super Speciality Hospital, Lucknow, Lucknow, IND
| | - Shruti Dubey
- Emergency Medicine, LN Medical College and Research Center, Bhopal, IND
| | - Shehtaj Khan
- Emergency Medicine, LN Medical College and Research Center, Bhopal, IND
| | - Reshma Tiwari
- Critical Care Medicine, Artemis Hospital, Bhopal, IND
| | - Saurabh Das
- Critical Care Medicine, Max Super Speciality Hospital, Shalimar Bagh, New Delhi, IND
| | - Reyaz Ahmad
- Pediatric Surgery, All India Institute of Medical Sciences, Bhopal, IND
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12
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Messina JM, Luo M, Hossan MS, Gadelrab HA, Yang X, John A, Wilmore JR, Luo J. Unveiling cytokine charge disparity as a potential mechanism for immune regulation. Cytokine Growth Factor Rev 2024; 77:1-14. [PMID: 38184374 PMCID: PMC11923798 DOI: 10.1016/j.cytogfr.2023.12.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/21/2023] [Accepted: 12/22/2023] [Indexed: 01/08/2024]
Abstract
Cytokines are small signaling proteins that regulate the immune responses to infection and tissue damage. Surface charges of cytokines determine their in vivo fate in immune regulation, e.g., half-life and distribution. The overall negative charges in the extracellular microenvironment and the acidosis during inflammation and infection may differentially impact cytokines with different surface charges for fine-tuned immune regulation via controlling tissue residential properties. However, the trend and role of cytokine surface charges has yet to be elucidated in the literature. Interestingly, we have observed that most pro-inflammatory cytokines have a negative charge, while most anti-inflammatory cytokines and chemokines have a positive charge. In this review, we extensively examined the surface charges of all cytokines and chemokines, summarized the pharmacokinetics and tissue adhesion of major cytokines, and analyzed the link of surface charge with cytokine biodistribution, activation, and function in immune regulation. Additionally, we identified that the general trend of charge disparity between pro- and anti-inflammatory cytokines represents a unique opportunity to develop precise immune modulation approaches, which can be applied to many inflammation-associated diseases including solid tumors, chronic wounds, infection, and sepsis.
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Affiliation(s)
- Jennifer M Messina
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States
| | - Minghao Luo
- Department of Clinical Medicine, 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Md Shanewaz Hossan
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States
| | - Hadil A Gadelrab
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States
| | - Xiguang Yang
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States
| | - Anna John
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States
| | - Joel R Wilmore
- Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Upstate Sepsis Interdisciplinary Research Center, State University of New York Upstate Medical University, Syracuse, NY 13210, United States
| | - Juntao Luo
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Upstate Cancer Center, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Upstate Sepsis Interdisciplinary Research Center, State University of New York Upstate Medical University, Syracuse, NY 13210, United States.
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13
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Girardis M, Coloretti I, Antonelli M, Berlot G, Busani S, Cortegiani A, De Pascale G, De Rosa FG, De Rosa S, Donadello K, Donati A, Forfori F, Giannella M, Grasselli G, Montrucchio G, Oliva A, Pasero D, Piazza O, Romagnoli S, Tascini C, Viaggi B, Tumbarello M, Viale P. Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2024; 4:28. [PMID: 38689337 PMCID: PMC11059820 DOI: 10.1186/s44158-024-00165-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 04/18/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. METHODS A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. RESULTS The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. CONCLUSIONS Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.
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Affiliation(s)
- Massimo Girardis
- Anesthesia and Intensive Care Medicine, Policlinico Di Modena, University of Modena and Reggio Emilia, Modena, Italy.
| | - Irene Coloretti
- Anesthesia and Intensive Care Medicine, Policlinico Di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Massimo Antonelli
- Dipartimento Di Scienze Biotecnologiche Di Base, Cliniche Intensivologiche E Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Dell'Emergenza, Anestesiologiche E Della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giorgio Berlot
- Anesthesia and Intensive Care, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
| | - Stefano Busani
- Anesthesia and Intensive Care Medicine, Policlinico Di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Andrea Cortegiani
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy
- Department of Anaesthesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, Palermo, Italy
| | - Gennaro De Pascale
- Dipartimento Di Scienze Biotecnologiche Di Base, Cliniche Intensivologiche E Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Dell'Emergenza, Anestesiologiche E Della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | | | - Silvia De Rosa
- Anesthesia and Intensive Care, Santa Chiara Regional Hospital, APSS, Trento, Italy
| | - Katia Donadello
- Department of Surgery, Dentistry, Ginaecology and Paediatrics, University of Verona, and Anesthesia and Intensive Care Unit B, University Hospital Integrated Trust of Verona, Verona, Italy
| | - Abele Donati
- Anesthesia and Intensive Care, Azienda Ospedaliero Universitaria Delle Marche, Ancona, Italy
| | - Francesco Forfori
- Anesthesia and Intensive Care, Anesthesia and Resuscitation Department, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Maddalena Giannella
- Department of Medical and Surgical Sciences Infectious Diseases Unit, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giacomo Grasselli
- Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Giorgia Montrucchio
- Department of Surgical Sciences, Departement of Anesthesia, Resuscitation and Emergency Torino, University of Turin, Turin, Italy
| | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Daniela Pasero
- Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
| | - Ornella Piazza
- University Hospital "San Giovanni Di Dio E Ruggi d'Aragona", Salerno, Italy
| | - Stefano Romagnoli
- Department of Health Science, Department of Anesthesia and Intensive Care, University of Florence, Careggi University Hospital, Florence, Italy
| | - Carlo Tascini
- Department of Medicine (DAME), Infectious Diseases Clinic, University of Udine, Udine, Italy
| | - Bruno Viaggi
- Anesthesia and Intensive Care, Careggi University Hospital, Florence, Italy
| | - Mario Tumbarello
- Infectious and Tropical Diseases Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences Infectious Diseases Unit, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
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Petramala L, Milito C, Sarlo F, Servello A, Circosta F, Marino L, Sardella G, Trapani P, D'aguanno G, Cimo' A, Galardo G, Letizia C. Clinical impact of transient lymphopenia. Clin Exp Med 2024; 24:77. [PMID: 38630321 PMCID: PMC11023980 DOI: 10.1007/s10238-024-01340-0] [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: 01/23/2024] [Accepted: 03/27/2024] [Indexed: 04/19/2024]
Abstract
Transient or persistent immunosuppression is a known risk factor for morbidity and mortality in critically ill patients. Aim of the present study is to evaluate the lymphopenia in patients admitted to the Emergency Unit of AOU Policlinico Umberto I, to investigate its prevalence at admission and the persistence during hospitalization until discharge. Possible correlations were evaluated between lymphopenia, diagnosis of admission, comorbidities and chronic treatments. In this study, 240 patients (142 men; 98 female; mean age 75.1 ± 15.1) were enrolled. Patients were divided into two groups according to the lymphocytes count at hospital admission, namely "Group A" with lymphopenia and "Group B" with values in the normal range. Moreover, the patients in group A were distinguished in relation to the regression or persistence of the lymphopenia assessed at the time of hospital discharge (Group A1: persistence; Group A2: normalization). Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; and none differences were observed regarding gender. Prevalence of lymphopenia at admission was 57%; Group A showed higher mean age and percentage of patients over 65 years of age; no differences were observed regarding gender. All subsets of the lymphocytes (CD4+, CD8+, NK) were equally reduced. Persistent lymphopenia was found in 19% of patients. Lymphopenia should be valued at the time of hospital admission as a factor influencing the prognosis, the management and the treatment of these patients.
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Affiliation(s)
- Luigi Petramala
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Cinzia Milito
- Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Francesca Sarlo
- UOC Chimica, Biochimica E Biologia Molecolare Clinica, Fondazione Policlinico Universitario A. Gemelli I.R.C.C.S, Rome, Italy
| | - Adriana Servello
- Emergency Medicine Unit, Department of Emergency-Acceptance, Critical Areas and Trauma, Policlinico "Umberto I", Rome, Italy
| | - Francesco Circosta
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
- General Surgery Unit, ICOT Hospital, Latina, Italy
| | - Luca Marino
- Emergency Medicine Unit, Department of Emergency-Acceptance, Critical Areas and Trauma, Policlinico "Umberto I", Rome, Italy.
- Department of Mechanical and Aerospace Engineering, "Sapienza" University of Rome, Rome, Italy.
| | - Germano Sardella
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
- General Surgery Unit, ICOT Hospital, Latina, Italy
| | - Piero Trapani
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
- General Surgery Unit, ICOT Hospital, Latina, Italy
| | - Giulio D'aguanno
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
- General Surgery Unit, ICOT Hospital, Latina, Italy
| | - Antonino Cimo'
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
- General Surgery Unit, ICOT Hospital, Latina, Italy
| | - Gioacchino Galardo
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
- General Surgery Unit, ICOT Hospital, Latina, Italy
| | - Claudio Letizia
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
- General Surgery Unit, ICOT Hospital, Latina, Italy
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15
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Kikuchi K, Kazuma S, Masuda Y. Improvement in ICU Mortality From Sepsis Associated With Recuperation From Septic Multiple-Organ Failure: A Retrospective, Single-Center, Cohort Study. Cureus 2024; 16:e57118. [PMID: 38681321 PMCID: PMC11055621 DOI: 10.7759/cureus.57118] [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] [Accepted: 03/28/2024] [Indexed: 05/01/2024] Open
Abstract
BACKGROUND Although mortality due to sepsis has decreased in recent decades, there are few studies on the timing of death during ICU stay. Characteristics of patients related to changes over the years of ICU death and changes in the timing of ICU death will provide new insights for future sepsis management. METHODS This was a single-center, retrospective study. Patients admitted to the ICU for sepsis between 2005 and 2019 were included in the study. The study period was divided into three five-year intervals, and the timing of death in the ICU was divided into early-stage (1-3 ICU days), mid-stage (4-14 ICU days), and late-stage (15 or more ICU days). Patient characteristics related to ICU death at three five-year intervals and the timing of death were evaluated. RESULTS ICU mortality for sepsis has decreased over time (2005-2009, 30.2%; 2010-2014, 21.0%; 2015-2019, 12.1%; p<0.01). In the timing of death, only mid-stage mortality decreased. Multiple-organ failure (OR, 4.53; 95% CI, 2.79-7.48) and hematological malignancies (OR, 2.48; 95% CI, 1.19-5.07) were associated with ICU mortality over entire study periods. Only multiple-organ failure was associated with ICU mortality at the five-year intervals (OR, 5.94; 95% CI, 2.73-13.7 for 2005-2009; OR, 4.01; 95% CI, 1.82-9.31 for 2010-2014; OR, 2.58; 95% CI, 1.05-6.59 for 2015-2019). Mid-stage mortality of multiple-organ failure decreased (2005-2009, 12.8%; 2010-2014, 7.6%; 2015-2019, 1.6%; p=0.02). However, early- and late-stage mortality of multiple-organ failure did not change. CONCLUSIONS Improvement in mid-stage mortality in septic patients with multiple-organ failure can contribute to the improvement of overall ICU mortality in patients with sepsis.
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Affiliation(s)
- Kenichiro Kikuchi
- Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, JPN
| | - Satoshi Kazuma
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
| | - Yoshiki Masuda
- Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, JPN
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Mazlan MZ, Ghazali AG, Omar M, Yaacob NM, Nik Mohamad NA, Hassan MH, Wan Muhd Shukeri WF. Predictors of Treatment Failure and Mortality among Patients with Septic Shock Treated with Meropenem in the Intensive Care Unit. Malays J Med Sci 2024; 31:76-90. [PMID: 38456106 PMCID: PMC10917586 DOI: 10.21315/mjms2024.31.1.7] [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: 12/04/2022] [Accepted: 05/11/2023] [Indexed: 03/09/2024] Open
Abstract
Background The aim of the study was to determine the predictors of meropenem treatment failure and mortality in the Intensive Care Unit (ICU). Methods This was a retrospective study, involving sepsis and septic shock patients who were admitted to the ICU and received intravenous meropenem. Treatment failure is defined as evidence of non-resolved fever, non-reduced total white cell (TWC), non-reduced C-reactive protein (CRP), subsequent culture negative and death in ICU. Results An Acute Physiology and Chronic Health Evaluation II (APACHE II) and duration of antibiotic treatment less than 5 days were associated with treatment failure with adjusted OR = 1.24 (95% CI: 1.15, 1.33; P < 0.001), OR = 65.43 (95% CI: 21.70, 197.23; P < 0.001). A higher risk of mortality was observed with higher APACHE and Sequential Organ Failure Assessment (SOFA) scores, initiating antibiotics > 72 h of sepsis, duration of antibiotic treatment less than 5 days and meropenem with renal adjustment dose with an adjusted OR = 1.21 (95% CI: 1.12, 1.30; P < 0.001), adjusted OR = 1.23 (95% CI: 1.08, 1.41; P < 0.001), adjusted OR = 6.38 (95% CI: 1.67, 24.50; P = 0.007), adjusted OR = 0.03 (95% CI: 0.01, 0.14; P < 0.001), adjusted OR = 0.30 (95% CI: 0.14, 0.64; P = 0.002). Conclusion A total of 50 (14.12%) patients had a treatment failure with meropenem with 120 (48.02%) ICU mortality. The predictors of meropenem failure are higher APACHE score and shorter duration of meropenem treatment. The high APACHE, high SOFA score, initiating antibiotics more than 72 h of sepsis, shorter duration of treatment and meropenem with renal adjustment dose were predictors of mortality.
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Affiliation(s)
- Mohd Zulfakar Mazlan
- Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia
| | - Amar Ghassani Ghazali
- Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia
| | - Mahamarowi Omar
- Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia
| | - Najib Majdi Yaacob
- Unit of Biostatistics and Research Methodology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nik Abdullah Nik Mohamad
- Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia
| | - Mohamad Hasyizan Hassan
- Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia
| | - Wan Fadzlina Wan Muhd Shukeri
- Department of Anaesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Department of Anaesthesiology and Intensive Care, Hospital Universiti Sains Malaysia, Kelantan, Malaysia
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Wang Z, Wang M, Lin M, Wei P. The immunomodulatory effects of metformin in LPS-induced macrophages: an in vitro study. Inflamm Res 2024; 73:175-181. [PMID: 38091014 DOI: 10.1007/s00011-023-01827-8] [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: 07/28/2023] [Revised: 11/17/2023] [Accepted: 11/23/2023] [Indexed: 01/31/2024] Open
Abstract
OBJECTIVE The study aimed to explore the immunomodulatory effects of clinically relevant concentrations of metformin on macrophages during sepsis, which is characterized by an initial hyperinflammatory phase followed by a period of immunosuppression. METHODS: We employed the RAW 264.7 mouse macrophage cell line as an in vitro model to induce inflammatory responses and immune suppression through primary and secondary stimulation by lipopolysaccharide (LPS). The cells were exposed to clinically relevant concentrations of metformin, and their responses were gauged through cytotoxicity assays, enzyme-linked immunosorbent assay for cytokine quantification, and assessments of intracellular reactive oxygen species (ROS) production. Moreover, to probe the role of AMPK in mediating the effects of metformin, we conducted an AMP-activated protein kinase (AMPK) activity assay and knocked down AMPK using siRNA. RESULTS: Our study revealed that clinically relevant concentrations of metformin considerably decreased the LPS-induced secretion of tumor necrosis factor-α and interleukin-6, which indicates the suppression of the initial hyperinflammatory response. Furthermore, metformin prevented LPS-induced immunosuppression. Notably, these immunomodulatory effects of metformin were not mediated by the activation of the AMPK pathway, as evidenced by the unaltered AMPK activity and siRNA experiments. The modulation of intracellular ROS levels emerged as the critical mechanism underlying the inhibition of hyperinflammation and impediment of immunosuppression by metformin. CONCLUSION A certain therapeutic dose of metformin inhibited hyperinflammatory responses and alleviated immunosuppression in LPS-induced macrophages through the bidirectional modulation of intracellular ROS generation.
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Affiliation(s)
- Zhiyong Wang
- Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Min Wang
- Department of Pharmaceutics, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Mao Lin
- Department of Physiology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Pei Wei
- Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China.
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Suri TM, Hadda V, Ali S, Chopra A, Khan MA, Singh J, Ghosh T, Mittal S, Tiwari P, Madan K, Mohan A, Guleria R. Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study. J Intensive Care Med 2024; 39:125-135. [PMID: 37554063 PMCID: PMC7615840 DOI: 10.1177/08850666231193962] [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] [Indexed: 08/10/2023]
Abstract
INTRODUCTION The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. METHODS We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. RESULTS A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. CONCLUSIONS None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.
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Affiliation(s)
- Tejas Menon Suri
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Vijay Hadda
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Shadab Ali
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Anita Chopra
- Department of Laboratory Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Maroof Ahmad Khan
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Jay Singh
- Department of Laboratory Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Tamoghna Ghosh
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Mittal
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Pawan Tiwari
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Karan Madan
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Anant Mohan
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Randeep Guleria
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
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Jacquet-Lagrèze M, Pernollet A, Kattan E, Ait-Oufella H, Chesnel D, Ruste M, Schweizer R, Allaouchiche B, Hernandez G, Fellahi JL. Prognostic value of capillary refill time in adult patients: a systematic review with meta-analysis. Crit Care 2023; 27:473. [PMID: 38042855 PMCID: PMC10693708 DOI: 10.1186/s13054-023-04751-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 11/19/2023] [Indexed: 12/04/2023] Open
Abstract
PURPOSE Acute circulatory failure leads to tissue hypoperfusion. Capillary refill time (CRT) has been widely studied, but its predictive value remains debated. We conducted a meta-analysis to assess the ability of CRT to predict death or adverse events in a context at risk or confirmed acute circulatory failure in adults. METHOD MEDLINE, EMBASE, and Google scholar databases were screened for relevant studies. The pooled area under the ROC curve (AUC ROC), sensitivity, specificity, threshold, and diagnostic odds ratio using a random-effects model were determined. The primary analysis was the ability of abnormal CRT to predict death in patients with acute circulatory failure. Secondary analysis included the ability of CRT to predict death or adverse events in patients at risk or with confirmed acute circulatory failure, the comparison with lactate, and the identification of explanatory factors associated with better accuracy. RESULTS A total of 60,656 patients in 23 studies were included. Concerning the primary analysis, the pooled AUC ROC of 13 studies was 0.66 (95%CI [0.59; 0.76]), and pooled sensitivity was 54% (95%CI [43; 64]). The pooled specificity was 72% (95%CI [55; 84]). The pooled diagnostic odds ratio was 3.4 (95%CI [1.4; 8.3]). Concerning the secondary analysis, the pooled AUC ROC of 23 studies was 0.69 (95%CI [0.65; 0.74]). The prognostic value of CRT compared to lactate was not significantly different. High-quality CRT was associated with a greater accuracy. CONCLUSION CRT poorly predicted death and adverse events in patients at risk or established acute circulatory failure. Its accuracy is greater when high-quality CRT measurement is performed.
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Affiliation(s)
- Matthias Jacquet-Lagrèze
- Service d'anesthésie-Réanimation, Hôpital Cardiologique Louis Pradel, 59 Bd Pinel, 69500, Hospices Civils de LyonBron, France.
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373, Lyon Cedex 08, France.
- CarMeN Laboratoire, Inserm UMR 1060, Université Claude Bernard, Lyon 1, Lyon, France.
| | - Aymeric Pernollet
- Service d'anesthésie-Réanimation, Hôpital Cardiologique Louis Pradel, 59 Bd Pinel, 69500, Hospices Civils de LyonBron, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373, Lyon Cedex 08, France
| | - Eduardo Kattan
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- The Latin American Intensive Care Network (LIVEN), Santiago, Chile
| | - Hafid Ait-Oufella
- Hôpital Saint-Antoine, Service de Médecine Intensive-Réanimation, Sorbonne Université, Paris, France
| | - Delphine Chesnel
- Service d'anesthésie-Réanimation, Hôpital Cardiologique Louis Pradel, 59 Bd Pinel, 69500, Hospices Civils de LyonBron, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373, Lyon Cedex 08, France
| | - Martin Ruste
- Service d'anesthésie-Réanimation, Hôpital Cardiologique Louis Pradel, 59 Bd Pinel, 69500, Hospices Civils de LyonBron, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373, Lyon Cedex 08, France
- CarMeN Laboratoire, Inserm UMR 1060, Université Claude Bernard, Lyon 1, Lyon, France
| | - Rémi Schweizer
- Service d'anesthésie-Réanimation, Hôpital Cardiologique Louis Pradel, 59 Bd Pinel, 69500, Hospices Civils de LyonBron, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373, Lyon Cedex 08, France
| | - Bernard Allaouchiche
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373, Lyon Cedex 08, France
- Service d'anesthésie-Réanimation, Hôpital Lyon Sud, Hospices Civils de Lyon, 165 Chem. du Grand Revoyet, 69495, Pierre-Bénite, France
| | - Glenn Hernandez
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- The Latin American Intensive Care Network (LIVEN), Santiago, Chile
| | - Jean-Luc Fellahi
- Service d'anesthésie-Réanimation, Hôpital Cardiologique Louis Pradel, 59 Bd Pinel, 69500, Hospices Civils de LyonBron, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8, Avenue Rockefeller, 69373, Lyon Cedex 08, France
- CarMeN Laboratoire, Inserm UMR 1060, Université Claude Bernard, Lyon 1, Lyon, France
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Pham HM, Nguyen DLM, Duong MC, Phan XT, Tran LT, Trang DHT, Pham TTN. Neutrophil CD64-a prognostic marker of sepsis in intensive care unit: a prospective cohort study. Front Med (Lausanne) 2023; 10:1251221. [PMID: 37746077 PMCID: PMC10514672 DOI: 10.3389/fmed.2023.1251221] [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: 07/01/2023] [Accepted: 08/29/2023] [Indexed: 09/26/2023] Open
Abstract
Background Little is known about the prognostic ability of nCD64 in critically ill patients. This study aimed to assess the prognostic values of nCD64 in adult ICU patients with sepsis. Methods A prospective cohort study was conducted at the ICU of Cho Ray Hospital in Vietnam between January 2019 to September 2020. All newly admitted 86 septic patients diagnosed based on sepsis-3 criteria were included. An evaluation of nCD64 was performed at admission (T0) and 48 h thereafter (T48). Delta nCD64 (nCD64 T48 - nCD64 T0), %delta nCD64 [(nCD64 T48 - nCD64 T0)/nCD64 T0 x 100%], APACHE II and SOFA scores were calculated and examined. Serum procalcitonin levels and white blood cell counts were documented. Spearman's rank correlation coefficient was used to test the correlation between nCD64 and severity scores. Receiver-operating characteristic (ROC) curve was performed to evaluate the predictive efficacy of the sepsis parameters. Results Patients with septic shock had significantly higher nCD64 levels than septic patients [3,568 (2,589; 5,999) vs. 1,514 (1,416;2,542) molecules/cell, p < 0.001]. nCD64 T0 and SOFA scores had a moderately positive linear correlation (R = 0.31, p = 0.004). In the survivor group, nCD64 levels significantly decreased within the first 48 h of admission (p < 0.001), while this trend was not statistically significant in the non-survivor group (p = 0.866). The area under the ROC curve (AUC) value of %delta nCD64 combined with APACHE II score (0.81) was higher than that of any other parameter alone or in combination with each other. Conclusion The nCD64 index may serve as a valuable biomarker for predicting the course of sepsis. Monitoring changes in nCD64 during the initial 48 h of admission can aid in predicting the prognosis of septic patients. The use of a combination of the trends of nCD64 index in the first 48 h with APACHE II score would further enhance the predictive accuracy. More studies with longer follow-ups are needed to fully understand the implications of serial trend and kinetics of nCD64 in septic patients.
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Affiliation(s)
- Huy Minh Pham
- Department of Emergency and Critical Care, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Intensive Care Unit, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | | | - Minh Cuong Duong
- School of Population Health, University of New South Wales, Sydney, NSW, Australia
| | - Xuan Thi Phan
- Intensive Care Unit, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Linh Thanh Tran
- Intensive Care Unit, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | | | - Thao Thi Ngoc Pham
- Department of Emergency and Critical Care, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Intensive Care Unit, Cho Ray Hospital, Ho Chi Minh City, Vietnam
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21
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Lyons NB, Proctor KG. Are the Outcomes of a Pig Endotoxemia Model Applicable to Human Sepsis? Crit Care Med 2023; 51:1102-1104. [PMID: 37439647 DOI: 10.1097/ccm.0000000000005904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Affiliation(s)
- Nicole B Lyons
- Both authors: Division of Trauma, Burns, and Surgical Critical Care, Daughtry Family, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL
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22
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Lima MR, Silva D. Septic cardiomyopathy: A narrative review. Rev Port Cardiol 2023; 42:471-481. [PMID: 36893835 DOI: 10.1016/j.repc.2021.05.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 03/03/2021] [Accepted: 05/01/2021] [Indexed: 03/09/2023] Open
Abstract
Sepsis is a systemic inflammatory response syndrome of suspected or documented infectious origin, whose outcome is multiorgan failure. Sepsis-induced myocardial dysfunction (SIMD), present in more than 50% of septic patients, is characterized by (i) left ventricular (LV) dilatation with normal or low filling pressure, (ii) right and/or LV (systolic and/or diastolic) dysfunction and (iii) reversibility. Since the first definition proposed by Parker et al. in 1984, attempts have been made to define SIMD. Many parameters are used to assess cardiac function in septic patients, sometimes making it more difficult to measure due to the intrinsic hemodynamical changes in this condition. Nevertheless, with advanced echocardiographic techniques, such as speckle tracking analysis, it is possible to diagnose and assess systolic and diastolic dysfunction, even in the earliest stages of sepsis. Cardiac magnetic resonance imaging brings new insights into the reversibility of this condition. Many uncertainties still remain regarding the mechanisms, characteristics, treatment and even prognosis of this condition. There are also inconsistent conclusions from studies, therefore this review attempts to summarize our current knowledge of SIMD.
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Affiliation(s)
- Maria Rita Lima
- Internal Medicine Department, Egas Moniz Hospital, Lisbon Ocidental Hospital Center, Lisbon, Portugal.
| | - Doroteia Silva
- Intensive Care Department, Santa Maria University Hospital, Lisbon North Hospital Center, Lisbon, Portugal; CCUL, Lisbon Academic Medical Center, Faculty of Medicine of Lisbon, Lisbon, Portugal
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23
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Li L, Shi X, Xiong M, Kong K, Chen Z, Zhou S, Zeng Z, An S, Xu B. Dexmedetomidine only regimen for long-term sedation is associated with reduced vasopressor requirements in septic shock patients: A retrospective cohort study from MIMIC-IV database. Front Med (Lausanne) 2023; 10:1107251. [PMID: 36923011 PMCID: PMC10010261 DOI: 10.3389/fmed.2023.1107251] [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: 11/24/2022] [Accepted: 02/03/2023] [Indexed: 03/02/2023] Open
Abstract
Background Previous studies have shown that dexmedetomidine (DEX) may be associated with reduced vasopressor requirements in septic shock patients, however, long-term DEX-only sedation in reducing vasopressor requirements is still controversial. Methods A retrospective study was conducted among patients with septic shock on mechanical ventilation using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was the ratio of norepinephrine equivalent dose to mean arterial pressure (NEq/MAP) in the first 72 h after DEX or other sedatives for sedation. The secondary outcomes were key organ function parameters, 28-day mortality, and 90-day mortality. Univariate, propensity score matching (PSM), and generalized linear mixed model (GLMM) analyses were performed. Results DEX was associated with decreased NEq/MAP in the first 72 h (difference = 0.05, 95% CI = -0.02-0.08, p = 0.002) after adjusting for confounders in the GLMM analysis. The DEX group was also associated with a lower heart rate, cardiac output (CO), lactate level, aspartate transaminase (AST) level, and higher PaO2/FiO2 ratio (p < 0.0125). Moreover, DEX only sedation was associated with reduced 90-day mortality (OR = 0.60, 95% CI = 0.37-0.94, p = 0.030). Conclusion DEX may be associated with decreased vasopressor requirements, improved AST and PaO2/FiO2 levels, and reduced 90-day mortality in patients with septic shock, which warrants further study.
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Affiliation(s)
- Lulan Li
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLA, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaotong Shi
- Department of Biostatistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, Guangdong, China
| | - Ming Xiong
- Department of Anesthesiology & Peri-Operative Medicine, New Jersey Medical School, Rutgers, United States
| | - Karen Kong
- Department of Anesthesiology & Peri-Operative Medicine, New Jersey Medical School, Rutgers, United States
| | - Zhongqing Chen
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shiyu Zhou
- Department of Biostatistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, Guangdong, China
| | - Zhenhua Zeng
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shengli An
- Department of Biostatistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, Guangdong, China
| | - Bo Xu
- Department of Anesthesiology, General Hospital of Southern Theatre Command of PLA, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
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Maamar A, Guillot P, Joussellin V, Delamaire F, Painvin B, Bichon A, de la Jartre OB, Mauget M, Lesouhaitier M, Tadié JM, Terzi N, Gacouin A. Moderate to severe ARDS: COVID-19 patients compared to influenza patients for ventilator parameters and mortality. ERJ Open Res 2023; 9:00554-2022. [PMID: 37041986 PMCID: PMC9885245 DOI: 10.1183/23120541.00554-2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 12/21/2022] [Indexed: 01/27/2023] Open
Abstract
BackgroundThis study aimed to compare ventilatory parameters recorded the first days of ARDS, and mortality at day 60 between COVID-19 and influenza ARDS patients with PaO2/FiO2≤150 mmHg.MethodsWe compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure (DP), respiratory system compliance (CRs), ventilator ratio (VR), corrected minute ventilation (VEcorr), and surrogate of mechanical power [index=(4×DP)+respiratory rate] were calculated from day1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed.ResultsOn day 1 of ARDS, COVID-19 patients had significantly higher PaO2/FiO2ratio (median [IQR], 97 mmHg [79–129]versus83 [62.2–114]), p=0.001), and lower DP (13 cmH20 [11–16.0]versus14 [12.0–16.7], p=0.01), VR (2.08 [1.73–2.49versus2.52 [1.97–3.03], p<0.001), VEcorr (12.7 L·mn−1[10.2–14.9]versus14.9 [11.6–18.6], p<0.001), index (80 [70–89]versus84 [75–94], p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5 repeated values of PaO2/FiO2ratio, PaCO2, VR and VEcorr differed significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29%versus21.7%, p=0.43).ConclusionsVentilation was more impaired in influenza than in COVID-19 ARDS patients the first day of ARDS with important overlap of values. However, mortality at day 60 did not differ significantly in the matched population.
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Chen Z, Liu X, Shou C, Yang W, Yu J. Advances in the diagnosis of non-occlusive mesenteric ischemia and challenges in intra-abdominal sepsis patients: a narrative review. PeerJ 2023; 11:e15307. [PMID: 37128207 PMCID: PMC10148637 DOI: 10.7717/peerj.15307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 04/06/2023] [Indexed: 05/03/2023] Open
Abstract
Non-occlusive mesenteric ischemia (NOMI) is a type of acute mesenteric ischemia (AMI) with a high mortality rate mainly because of a delayed or misdiagnosis. Intra-abdominal sepsis is one of the risk factors for developing NOMI, and its presence makes early diagnosis much more difficult. An increase in routine abdominal surgeries carries a corresponding risk of abdominal infection, which is a complication that should not be overlooked. It is critical that physicians are aware of the possibility for intestinal necrosis in abdominal sepsis patients due to the poor survival rate of NOMI. This review aims to summarize advances in the diagnosis of NOMI, and focuses on the diagnostic challenges of mesenteric ischemia in patients with intra-abdominal sepsis.
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Nüse B, Holland T, Rauh M, Gerlach RG, Mattner J. L-arginine metabolism as pivotal interface of mutual host-microbe interactions in the gut. Gut Microbes 2023; 15:2222961. [PMID: 37358082 PMCID: PMC10294761 DOI: 10.1080/19490976.2023.2222961] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 06/05/2023] [Indexed: 06/27/2023] Open
Abstract
L-arginine (L-arg) is a versatile amino acid and a central intestinal metabolite in mammalian and microbial organisms. Thus, L-arg participates as precursor of multiple metabolic pathways in the regulation of cell division and growth. It also serves as a source of carbon, nitrogen, and energy or as a substrate for protein synthesis. Consequently, L-arg can simultaneously modify mammalian immune functions, intraluminal metabolism, intestinal microbiota, and microbial pathogenesis. While dietary intake, protein turnover or de novo synthesis usually supply L-arg in sufficient amounts, the expression of several key enzymes of L-arg metabolism can change rapidly and dramatically following inflammation, sepsis, or injury. Consequently, the availability of L-arg can be restricted due to increased catabolism, transforming L-arg into an essential amino acid. Here, we review the enzymatic pathways of L-arg metabolism in microbial and mammalian cells and their role in immune function, intraluminal metabolism, colonization resistance, and microbial pathogenesis in the gut.
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Affiliation(s)
- Björn Nüse
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Tim Holland
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Manfred Rauh
- Department of Pediatrics and Adolescent Medicine, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Roman G. Gerlach
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Jochen Mattner
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany
- Medical Immunology Campus Erlangen, FAUErlangen-Nürnberg, Erlangen, Germany
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Bourcier S, Ulmann G, Jamme M, Savary G, Paul M, Benghanem S, Lavillegrand JR, Schmidt M, Luyt CE, Maury E, Combes A, Pène F, Neveux N, Cariou A. A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study. Ann Intensive Care 2022; 12:113. [PMID: 36527517 PMCID: PMC9759607 DOI: 10.1186/s13613-022-01092-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis. METHODS We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria. RESULTS Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70-0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50-86], specificity of 85% [55-98], a negative predictive value of 58% [36-93] and a positive predictive value 90% [67-96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12-0.75], p = 0.01). CONCLUSION In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.
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Affiliation(s)
- Simon Bourcier
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France ,grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France
| | - Guillaume Ulmann
- grid.5842.b0000 0001 2171 2558Clinical Chemistry Department, AP-HP Centre, Hôpital Cochin, Université de Paris, Paris, France ,grid.5842.b0000 0001 2171 2558EA 4466 PRETRAM, Faculty of Pharmacy, Université de Paris, Paris, France
| | - Matthieu Jamme
- grid.418433.90000 0000 8804 2678Réanimation Polyvalente, Hôpital Privé de l’Ouest Parisien, Ramsay Générale de Santé, Trappes, France ,grid.12832.3a0000 0001 2323 0229INSERM U1018, Centre de Recherche en Epidémiologie et Santé des Populations, Team 5 (EpReC, Renal and Cardiovascular Epidemiology), Université Versailles Saint-Quentin, Villejuif, France
| | - Guillaume Savary
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Marine Paul
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Sarah Benghanem
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Jean-Rémi Lavillegrand
- grid.50550.350000 0001 2175 4109AP-HP, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Médecine Intensive Réanimation, Paris, France
| | - Matthieu Schmidt
- grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France ,grid.462844.80000 0001 2308 1657INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France
| | - Charles-Edouard Luyt
- grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France ,grid.462844.80000 0001 2308 1657INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France
| | - Eric Maury
- grid.50550.350000 0001 2175 4109AP-HP, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Médecine Intensive Réanimation, Paris, France
| | - Alain Combes
- grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France ,grid.462844.80000 0001 2308 1657INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France
| | - Frédéric Pène
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Nathalie Neveux
- grid.5842.b0000 0001 2171 2558Clinical Chemistry Department, AP-HP Centre, Hôpital Cochin, Université de Paris, Paris, France ,grid.5842.b0000 0001 2171 2558EA 4466 PRETRAM, Faculty of Pharmacy, Université de Paris, Paris, France
| | - Alain Cariou
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
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Oruganti S, Evans J, Cromarty T, Javaid A, Roland D. Identification of sepsis in paediatric emergency departments: A scoping review. Acta Paediatr 2022; 111:2262-2277. [PMID: 36053116 PMCID: PMC9826118 DOI: 10.1111/apa.16536] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/04/2022] [Accepted: 09/01/2022] [Indexed: 01/11/2023]
Abstract
AIM Sepsis is an acute illness associated with significant morbidity and mortality. Early detection and time-sensitive management of sepsis has been shown to improve outcomes. We report the results of a scoping review to explore methods evaluated for the identification of sepsis in children presenting to emergency departments. METHODS A systematic literature search was carried out on two databases, Medline and Web of Science, to identify relevant studies published from 1990 to 2022. Data were extracted for age groups including study design, reference standard used for comparison, sepsis identification method evaluated and study quality. RESULTS A total of 89 studies were identified from the literature search. There was significant heterogeneity in the age groups including study design and reference standards used for evaluating the performance of the sepsis identification methods. There has been a substantial increase in the number of published studies in the last 2 years. CONCLUSION Our scoping review identifies marked heterogeneity in approaches to identifying sepsis but demonstrates a recent focus of research on patient outcomes. Using appropriate core outcome sets, developing reference standards, monitoring sepsis prevalence via registries and continuously monitoring process measures will provide robust evidence to identify the best performing identification tools and the impact they have on patient-orientated outcomes.
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Affiliation(s)
- Sivakumar Oruganti
- Noah's Ark Children's Hospital for WalesCardiffUK
- Cardiff UniversityCardiffUK
| | - Jordan Evans
- Paediatric Emergency DepartmentUniversity Hospital of WalesCardiffUK
| | - Thomas Cromarty
- Paediatric Emergency DepartmentUniversity Hospital of WalesCardiffUK
| | - Assim Javaid
- Cardiff UniversityCardiffUK
- Paediatric Emergency DepartmentUniversity Hospital of WalesCardiffUK
| | - Damian Roland
- Leicester Academic (PEMLA) groupLeicester Royal InfirmaryLeicesterUK
- SAPPHIRE group Health SciencesLeicester UniversityLeicesterUK
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29
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Wang C, Xu H, Gao R, Leng F, Huo F, Li Y, Liu S, Xu M, Bai J. CD19 +CD24 hiCD38 hi regulatory B cells deficiency revealed severity and poor prognosis in patients with sepsis. BMC Immunol 2022; 23:54. [PMID: 36357845 PMCID: PMC9648441 DOI: 10.1186/s12865-022-00528-x] [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: 03/24/2022] [Accepted: 10/20/2022] [Indexed: 11/12/2022] Open
Abstract
Background Sepsis still remains a major challenge in intensive care medicine with unacceptably high mortality among patients with septic shock. Due to current limitations of human CD19+CD24hiCD38hi Breg cells (Bregs) studies among sepsis, here, we tried to evaluate Bregs in severity and prognostic value in patients with sepsis. Methods Peripheral blood from 58 patients with sepsis and 22 healthy controls was analyzed using flow cytometry to evaluate the frequency and number of Bregs. All cases were divided into non-survived or survived group after 28 days followed up. Spearman's correlation analysis was performed on Bregs frequency and clinical indices. The area under the curve was acquired using the receiver operating characteristic analysis to assess the sensitivity and specificity of Bregs for outcome of sepsis. Survival curve analysis and binary logistic regression were applied to estimate the value of Bregs in prognosis among cases with sepsis. Results Sepsis patients had decreased proportions and number of Bregs. Sepsis patients with low frequency of Bregs were associated with an increased risk of septic shock. Bregs frequency is inversely associated with lactate, SOFA, and APACHE II and positively correlated with Tregs frequency. Low levels of Bregs closely correlated with septic outcomes. Numbers of Bregs were prediction factors for poor prognosis. Conclusions Frequency and number of Bregs decreased, and Bregs deficiency revealed poor prognosis in patients with sepsis. Supplementary Information The online version contains supplementary material available at 10.1186/s12865-022-00528-x.
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Affiliation(s)
- Chunmei Wang
- grid.89957.3a0000 0000 9255 8984Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Nanjing Medical University, Nanjing, 211166 Jiangsu Province China ,grid.24516.340000000123704535Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120 China
| | - Huihui Xu
- grid.9227.e0000000119573309Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China ,grid.410726.60000 0004 1797 8419University of Chinese Academy of Sciences, Beijing, China
| | - Rui Gao
- grid.452252.60000 0004 8342 692XDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Jining Medical University, Jining, 272067 Shandong Province China
| | - Fengying Leng
- grid.24516.340000000123704535Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120 China
| | - Fangjie Huo
- Department of Respiratory Medicine, Xi’an No. 4 Hospital, Xi’an, 710004 Shanxi Province China
| | - Yinzhen Li
- grid.24516.340000000123704535Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120 China ,grid.24516.340000000123704535Medical School, Tongji University, Shanghai, 200120 China
| | - Siting Liu
- grid.24516.340000000123704535Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120 China
| | - Mingzheng Xu
- grid.24516.340000000123704535Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120 China
| | - Jianwen Bai
- grid.89957.3a0000 0000 9255 8984Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Nanjing Medical University, Nanjing, 211166 Jiangsu Province China ,grid.24516.340000000123704535Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120 China
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30
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Bala M, Catena F, Kashuk J, De Simone B, Gomes CA, Weber D, Sartelli M, Coccolini F, Kluger Y, Abu-Zidan FM, Picetti E, Ansaloni L, Augustin G, Biffl WL, Ceresoli M, Chiara O, Chiarugi M, Coimbra R, Cui Y, Damaskos D, Di Saverio S, Galante JM, Khokha V, Kirkpatrick AW, Inaba K, Leppäniemi A, Litvin A, Peitzman AB, Shelat VG, Sugrue M, Tolonen M, Rizoli S, Sall I, Beka SG, Di Carlo I, Ten Broek R, Mircea C, Tebala G, Pisano M, van Goor H, Maier RV, Jeekel H, Civil I, Hecker A, Tan E, Soreide K, Lee MJ, Wani I, Bonavina L, Malangoni MA, Koike K, Velmahos GC, Fraga GP, Fette A, de'Angelis N, Balogh ZJ, Scalea TM, Sganga G, Kelly MD, Khan J, Stahel PF, Moore EE. Acute mesenteric ischemia: updated guidelines of the World Society of Emergency Surgery. World J Emerg Surg 2022; 17:54. [PMID: 36261857 PMCID: PMC9580452 DOI: 10.1186/s13017-022-00443-x] [Citation(s) in RCA: 123] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 06/17/2022] [Indexed: 02/08/2023] Open
Abstract
Acute mesenteric ischemia (AMI) is a group of diseases characterized by an interruption of the blood supply to varying portions of the intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process may progress to life-threatening intestinal necrosis. The incidence is low, estimated at 0.09-0.2% of all acute surgical admissions, but increases with age. Although the entity is an uncommon cause of abdominal pain, diligence is required because if untreated, mortality remains in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques is evolving and provides new treatment options. Lastly, a focused multidisciplinary approach based on early diagnosis and individualized treatment is essential. Thus, we believe that updated guidelines from World Society of Emergency Surgery are warranted, in order to provide the most recent and practical recommendations for diagnosis and treatment of AMI.
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Affiliation(s)
- Miklosh Bala
- Director of Acute Care Surgery and Trauma Unit, Department of General Surgery, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem Kiriat Hadassah, POB 12000, 91120, Jerusalem, Israel.
| | - Fausto Catena
- General and Emergency Surgery Department, Bufalini Hospital, Cesena, Italy
| | - Jeffry Kashuk
- Tel Aviv Sackler School of Medicine, Tel Aviv, Israel
| | - Belinda De Simone
- Department of General, Digestive and Metabolic Minimally Invasive Surgery, Centre Hospitalier Intercommunal De Poissy/St Germain en Laye, Poissy, France
| | - Carlos Augusto Gomes
- Department of Surgery, Faculdade de Ciências Médicas e da Saúde de Juiz de Fora, Hospital Universitário Terezinha de Jesus, Juiz de Fora, Brazil
| | - Dieter Weber
- Department of General Surgery, Royal Perth Hospital, The University of Western Australia, Perth, Australia
| | | | - Federico Coccolini
- Department of General, Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy
| | - Yoram Kluger
- Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - Fikri M Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
| | - Edoardo Picetti
- Department of Anesthesia and Intensive Care, Azienda Ospedaliero-Universitaria Parma, Parma, Italy
| | - Luca Ansaloni
- Department of Surgery, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Goran Augustin
- Department of Surgery, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Walter L Biffl
- Division of Trauma/Acute Care Surgery, Scripps Clinic Medical Group, La Jolla, CA, USA
| | - Marco Ceresoli
- Emergency and General Surgery Department, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Osvaldo Chiara
- Emergency Department, Niguarda Ca'Granda Hospital, Milan, Italy
| | - Massimo Chiarugi
- Department of General, Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy
| | - Raul Coimbra
- CECORC Research Center, Riverside University Health System, Loma Linda University, Loma Linda, USA
| | - Yunfeng Cui
- Department of Surgery, Nankai Clinical School of Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China
| | | | - Salomone Di Saverio
- General Surgery Department Hospital of San Benedetto del Tronto, Marche region, Italy
| | - Joseph M Galante
- Division of Trauma and Acute Care Surgery, Department of Surgery, University of California Davis, Sacramento, CA, USA
| | - Vladimir Khokha
- Department of Emergency Surgery, City Hospital, Mozyr, Belarus
| | - Andrew W Kirkpatrick
- General, Acute Care, Abdominal Wall Reconstruction, and Trauma Surgery, Foothills Medical Centre, Calgary, AB, Canada
| | - Kenji Inaba
- Division of Trauma and Surgical Critical Care, Department of Surgery, University of Southern California, Los Angeles, CA, USA
| | - Ari Leppäniemi
- Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Andrey Litvin
- Department of Surgical Disciplines, Regional Clinical Hospital, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
| | - Andrew B Peitzman
- Department of Surgery, University of Pittsburgh School of Medicine, UPMC-Presbyterian, Pittsburgh, USA
| | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Novena, Singapore
| | - Michael Sugrue
- Donegal Clinical Research Academy Emergency Surgery Outcome Project, Letterkenny University Hospital, Donegal, Ireland
| | - Matti Tolonen
- Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Sandro Rizoli
- Surgery Department, Section of Trauma Surgery, Hamad General Hospital (HGH), Doha, Qatar
| | - Ibrahima Sall
- General Surgery Department, Military Teaching Hospital, Dakar, Senegal
| | | | - Isidoro Di Carlo
- Department of Surgical Sciences and Advanced Technologies, General Surgery Cannizzaro Hospital, University of Catania, Catania, Italy
| | - Richard Ten Broek
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Chirika Mircea
- Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
| | - Giovanni Tebala
- Department of Digestive and Emergency Surgery, S.Maria Hospital Trust, Terni, Italy
| | - Michele Pisano
- General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Harry van Goor
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ronald V Maier
- Harborview Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Hans Jeekel
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Ian Civil
- Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Andreas Hecker
- Emergency Medicine Department of General and Thoracic Surgery, University Hospital of Giessen, Giessen, Germany
| | - Edward Tan
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Kjetil Soreide
- HPB Unit, Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Matthew J Lee
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | | | - Luigi Bonavina
- Department of Surgery, IRCCS Policlinico San Donato, University of Milano, Milano, Italy
| | - Mark A Malangoni
- Case Western Reserve University School of Medicine, Cleveland, USA
| | | | - George C Velmahos
- Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston, PA, USA
| | - Gustavo P Fraga
- Division of Trauma Surgery, School of Medical Sciences, University of Campinas (Unicamp), Campinas, Brazil
| | - Andreas Fette
- Pediatric Surgery, Children's Care Center, SRH Klinikum Suhl, Suhl, Thueringen, Germany
| | - Nicola de'Angelis
- Unit of Digestive and HPB Surgery, Faculty of Medicine, University of Paris, Paris, France
| | - Zsolt J Balogh
- John Hunter Hospital and University of Newcastle, Newcastle, NSW, Australia
| | - Thomas M Scalea
- Cowley Shock Trauma Center at the University of Maryland, Baltimore, MD, USA
| | - Gabriele Sganga
- Emergency Surgery and Trauma, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Michael D Kelly
- Department of General Surgery, Albury Hospital, Albury, Australia
| | - Jim Khan
- University of Portsmouth, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Philip F Stahel
- College of Osteopathic Medicine, Rocky Vista University, Parker, CO, USA
| | - Ernest E Moore
- Ernest E Moore Shock Trauma Center at Denver Health, University of Colorado, Denver, CO, USA
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Mezgebu TA, Sibhat MM, Getnet MT, Gebeyehu KT, Chane WZ, Getahun EM, Habtamu AS, Asmare HB, Ambaw MM. Risk factors of early mortality among COVID-19 deceased patients in Addis Ababa COVID-19 care centers, Ethiopia. PLoS One 2022; 17:e0275131. [PMID: 36166445 PMCID: PMC9514640 DOI: 10.1371/journal.pone.0275131] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 09/10/2022] [Indexed: 01/09/2023] Open
Abstract
Background Severe acute respiratory syndrome coronavirus-2 is a global health care problem with high mortality. Despite early mortality seeming alarming, data regarding factors that lead to increased early mortality of COVID 19 patients is not well-documented yet. The objective of this study was to identify the risk factors of early mortality in patients with confirmed COVID-19 infections. Methodology A case-control study design was employed. With this, a total of 261 COVID-19 deceased recordings were reviewed. The cases of the study were recordings of patients deceased within three days of intensive care unit admission whereas, the rest 187 were recordings of patients who died after three days of admission. Data were collected using an extraction checklist, entered into Epi data version 4.4.2.2, and analyzed by SPSS version 25. After the description, binary logistic regression was run to conduct bivariate and multivariable analyses. Finally, statistical significance was declared at p-value <0.05, and an adjusted odds ratio with a 95% confidence interval was used to report the strength of association. Result The analysis was performed on 261 (87 cases and 174 controls) recordings. About 62.5% of the participants were aged above 65 years and two-thirds were males. The presence of cardiovascular disease (AOR = 4.79, with 95%CI: 1.73, 13.27) and bronchial-asthma (AOR = 6.57; 95% CI: 1.39, 31.13) were found to have a statistically significant association with early mortality. The existence of complications from COVID-19 (AOR = 0.22; 95% CI: 0.07, 0.74) and previous history of COVID-19 infection (AOR = 0.17, 95% CI: 0.04, 0.69) were associated with decreased risk of early mortality. Conclusions Having cardiovascular diseases and bronchial asthma was associated with an increased risk of early mortality. Conversely, the presence of intensive care unit complications and previous history of COVID-19 infection were associated with decreased risk of early mortality.
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Affiliation(s)
- Taye Ashine Mezgebu
- Schools of Nursing, College of Health Science and Medicine, Wachemo University, Hosanna, Ethiopia
- * E-mail:
| | | | - Melsew Tsegaw Getnet
- Saint Paul’s Hospital Millennium Medical College, Millennium COVID-19 Care Center, Addis Ababa, Ethiopia
| | | | - Wuletaw Zewde Chane
- Saint Paul’s Hospital Millennium Medical College, Millennium COVID-19 Care Center, Addis Ababa, Ethiopia
| | - Edmialem Mesfin Getahun
- Saint Paul’s Hospital Millennium Medical College, Millennium COVID-19 Care Center, Addis Ababa, Ethiopia
| | - Asaminew Sane Habtamu
- School of Nursing, College of Health Science and Medicine, Jimma University, Jimma, Ethiopia
| | - Hailu Beyene Asmare
- School of Nursing, College of Health Science and Medicine, Wolaita Sodo University, Sodo, Ethiopia
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32
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Warr D, Rivera T, Romeo M. Case report: Non-occlusive mesenteric ischemia in the setting of sildenafil use. Am J Emerg Med 2022; 62:148.e1-148.e3. [PMID: 36137848 DOI: 10.1016/j.ajem.2022.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/25/2022] [Accepted: 09/08/2022] [Indexed: 11/25/2022] Open
Abstract
Acute mesenteric ischemia (AMI) is a condition that results from a sudden decline in blood flow through the mesenteric vessels that has a high morbidity and mortality. Non-occlusive AMI often presents in critically ill, hypotensive patients that suffer from decreased organ perfusion. Here we describe a case of non-occlusive acute mesenteric ischemia in the setting of transient hypotension precipitated by sildenafil. The patient required rapid fluid resuscitation in the emergency department. He did not require surgical intervention and was able to be discharged home with resolution of symptoms after a 7-day inpatient stay.
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Affiliation(s)
- Dillon Warr
- PGY2 Emergency Medicine, Temple University Hospital, United States of America.
| | - Troy Rivera
- Fellow Critical Care Medicine, Cooper University Health Care, United States of America
| | - Michelle Romeo
- Assistant Professor Emergency Medicine, Lewis Katz School of Medicine at Temple University, United States of America
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33
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Antoni AC, Pylaeva E, Budeus B, Jablonska J, Klein-Hitpaß L, Dudda M, Flohé SB. TLR2-induced CD8+ T-cell deactivation shapes dendritic cell differentiation in the bone marrow during sepsis. Front Immunol 2022; 13:945409. [PMID: 36148245 PMCID: PMC9488929 DOI: 10.3389/fimmu.2022.945409] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/15/2022] [Indexed: 11/17/2022] Open
Abstract
Sepsis is associated with profound immune dysregulation that increases the risk for life-threatening secondary infections: Dendritic cells (DCs) undergo functional reprogramming due to yet unknown changes during differentiation in the bone marrow (BM). In parallel, lymphopenia and exhaustion of T lymphocytes interfere with antigen-specific adaptive immunity. We hypothesized that there exists a link between T cells and the modulation of DC differentiation in the BM during murine polymicrobial sepsis. Sepsis was induced by cecal ligation and puncture (CLP), a model for human bacterial sepsis. At different time points after CLP, the BM and spleen were analyzed in terms of T-cell subpopulations, activation, and Interferon (IFN)-γ synthesis as well as the number of pre-DCs. BM-derived DCs were generated in vitro. We observed that naïve and virtual memory CD8+ T cells, but not CD4+ T cells, were activated in an antigen-independent manner and accumulated in the BM early after CLP, whereas lymphopenia was evident in the spleen. The number of pre-DCs strongly declined during acute sepsis in the BM and almost recovered by day 4 after CLP, which required the presence of CD8+ T cells. Adoptive transfer experiments and in vitro studies with purified T cells revealed that Toll-like receptor 2 (TLR2) signaling in CD8+ T cells suppressed their capacity to secrete IFN-γ and was sufficient to change the transcriptome of the BM during sepsis. Moreover, the diminished IFN-γ production of CD8+ T cells favored the differentiation of DCs with increased production of the immune-activating cytokine Interleukin (IL)-12. These data identify a novel role of CD8+ T cells in the BM during sepsis as they sense TLR2 ligands and control the number and function of de novo differentiating DCs.
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Affiliation(s)
- Anne-Charlotte Antoni
- Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Ekaterina Pylaeva
- Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Bettina Budeus
- Institute of Cell Biology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Jadwiga Jablonska
- Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Ludger Klein-Hitpaß
- Institute of Cell Biology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Marcel Dudda
- Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Stefanie B. Flohé
- Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- *Correspondence: Stefanie B. Flohé,
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Bick A, Buys W, Engler A, Madel R, Atia M, Faro F, Westendorf AM, Limmer A, Buer J, Herbstreit F, Kirschning CJ, Peters J. Immune hyporeactivity to bacteria and multiple TLR-ligands, yet no response to checkpoint inhibition in patients just after meeting Sepsis-3 criteria. PLoS One 2022; 17:e0273247. [PMID: 35981050 PMCID: PMC9387870 DOI: 10.1371/journal.pone.0273247] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 08/03/2022] [Indexed: 11/18/2022] Open
Abstract
Rationale
The immune profile of sepsis patients is incompletely understood and hyperinflammation and hypoinflammation may occur concurrently or sequentially. Immune checkpoint inhibition (ICI) may counter hypoinflammation but effects are uncertain. We tested the reactivity of septic whole blood to bacteria, Toll-like receptor (TLR) ligands and to ICI.
Methods
Whole blood assays of 61 patients’ samples within 24h of meeting sepsis-3 criteria and 12 age and sex-matched healthy volunteers. Measurements included pattern/danger-associated molecular pattern (P/DAMP), cytokine concentrations at baseline and in response to TLR 2, 4, and 7/8 ligands, heat-inactivated Staphylococcus aureus or Escherichia coli, E.coli lipopolysaccharide (LPS), concentration of soluble and cellular immune checkpoint molecules, and cytokine concentrations in response to ICI directed against programmed-death receptor 1 (PD1), PD1-ligand 1, or cytotoxic T-lymphocyte antigen 4, both in the absence and presence of LPS.
Main results
In sepsis, concentrations of P/DAMPs and inflammatory cytokines were increased and the latter increased further upon incubation ex vivo. However, cytokine responses to TLR 2, 4, and 7/8 ligands, heat-inactivated S. aureus or E. coli, and E. coli LPS were all depressed. Depression of the response to LPS was associated with increased in-hospital mortality. Despite increased PD-1 expression on monocytes and T-cells, and monocyte CTLA-4 expression, however, addition of corresponding checkpoint inhibitors to assays failed to increase inflammatory cytokine concentrations in the absence and presence of LPS.
Conclusion
Patients first meeting Sepsis-3 criteria reveal 1) depressed responses to multiple TLR-ligands, bacteria, and bacterial LPS, despite concomitant inflammation, but 2) no response to immune checkpoint inhibition.
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Affiliation(s)
- Alexandra Bick
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
| | - Willem Buys
- Universität Duisburg-Essen, Essen, Germany
- * E-mail:
| | - Andrea Engler
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
| | | | - Mazen Atia
- Universität Duisburg-Essen, Essen, Germany
| | | | - Astrid M. Westendorf
- Institut für Medizinische Mikrobiologie, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
| | - Andreas Limmer
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
| | - Jan Buer
- Institut für Medizinische Mikrobiologie, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
| | - Frank Herbstreit
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
| | - Carsten J. Kirschning
- Institut für Medizinische Mikrobiologie, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
| | - Jürgen Peters
- Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg Essen & Universitätsklinikum Essen, Essen, Germany
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Dargent A, Bourredjem A, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study). Front Med (Lausanne) 2022; 9:968274. [PMID: 36017005 PMCID: PMC9395682 DOI: 10.3389/fmed.2022.968274] [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: 06/13/2022] [Accepted: 07/20/2022] [Indexed: 11/19/2022] Open
Abstract
Introduction Refractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial. Methods This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5μg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee “Sud-Est VI” (2019-000726-22) and patients will be included after informed consent. Discussion The present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients. Trial registration Registered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.
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Affiliation(s)
- Auguste Dargent
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation, Lyon, France
- APCSe VetAgro Sup UPSP 2016.A101, Marcy l'Etoile, France
- *Correspondence: Auguste Dargent
| | - Abderrahmane Bourredjem
- INSERM, CIC 1432, Module Epidémiologie Clinique, Dijon, France
- CHU Dijon-Bourgogne, Centre d'Investigation Clinique, Épidémiologie Clinique/essais Cliniques, Dijon, France
| | - Laurent Argaud
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation, Lyon, France
- Université de Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Est, Lyon, France
| | - Bruno Levy
- Service de Réanimation Médicale, Centre Hospitalier Universitaire Nancy Brabois, Nancy, France
- Institut du Cœur et des Vaisseaux, Groupe Choc, équipe 2, Inserm U1116, Faculté de Médecine, Nancy-Brabois, France
| | - Isabelle Fournel
- INSERM, CIC 1432, Module Epidémiologie Clinique, Dijon, France
- CHU Dijon-Bourgogne, Centre d'Investigation Clinique, Épidémiologie Clinique/essais Cliniques, Dijon, France
| | - Amélie Cransac
- Department of Pharmacy, Dijon University Hospital, Dijon, France
- LNC-UMR1231, University of Burgundy and Franche-Comté, Dijon, France
| | - Julio Badie
- Hôpital Nord Franche-Comté, Service de Médecine Intensive-Réanimation, Trévenans, France
| | - Luc Quintin
- Hôpital d'instruction des armées Desgenettes, Lyon, France
| | - Jean-Pierre Quenot
- LNC-UMR1231, University of Burgundy and Franche-Comté, Dijon, France
- Service de Médecine Intensive Réanimation, CHU Dijon, Dijon, France
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Poole J, Ray D. The Role of Circadian Clock Genes in Critical Illness: The Potential Role of Translational Clock Gene Therapies for Targeting Inflammation, Mitochondrial Function, and Muscle Mass in Intensive Care. J Biol Rhythms 2022; 37:385-402. [PMID: 35880253 PMCID: PMC9326790 DOI: 10.1177/07487304221092727] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The Earth's 24-h planetary rotation, with predictable light and heat cycles, has driven profound evolutionary adaptation, with prominent impacts on physiological mechanisms important for surviving critical illness. Pathways of interest include inflammation, mitochondrial function, energy metabolism, hypoxic signaling, apoptosis, and defenses against reactive oxygen species. Regulation of these by the cellular circadian clock (BMAL-1 and its network) has an important influence on pulmonary inflammation; ventilator-associated lung injury; septic shock; brain injury, including vasospasm; and overall mortality in both animals and humans. Whether it is cytokines, the inflammasome, or mitochondrial biogenesis, circadian medicine represents exciting opportunities for translational therapy in intensive care, which is currently lacking. Circadian medicine also represents a link to metabolic determinants of outcome, such as diabetes and cardiovascular disease. More than ever, we are appreciating the problem of circadian desynchrony in intensive care. This review explores the rationale and evidence for the importance of the circadian clock in surviving critical illness.
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Affiliation(s)
- Joanna Poole
- Anaesthetics and Critical Care, Gloucestershire Royal Hospital, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
| | - David Ray
- NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.,Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
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Pieroni M, Olier I, Ortega-Martorell S, Johnston BW, Welters ID. In-Hospital Mortality of Sepsis Differs Depending on the Origin of Infection: An Investigation of Predisposing Factors. Front Med (Lausanne) 2022; 9:915224. [PMID: 35911394 PMCID: PMC9326002 DOI: 10.3389/fmed.2022.915224] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 06/20/2022] [Indexed: 11/18/2022] Open
Abstract
Sepsis is a heterogeneous syndrome characterized by a variety of clinical features. Analysis of large clinical datasets may serve to define groups of sepsis with different risks of adverse outcomes. Clinical experience supports the concept that prognosis, treatment, severity, and time course of sepsis vary depending on the source of infection. We analyzed a large publicly available database to test this hypothesis. In addition, we developed prognostic models for the three main types of sepsis: pulmonary, urinary, and abdominal sepsis. We used logistic regression using routinely available clinical data for mortality prediction in each of these groups. The data was extracted from the eICU collaborative research database, a multi-center intensive care unit with over 200,000 admissions. Sepsis cohorts were defined using admission diagnosis codes. We used univariate and multivariate analyses to establish factors relevant for outcome prediction in all three cohorts of sepsis (pulmonary, urinary and abdominal). For logistic regression, input variables were automatically selected using a sequential forward search algorithm over 10 dataset instances. Receiver operator characteristics were generated for each model and compared with established prognostication tools (APACHE IV and SOFA). A total of 3,958 sepsis admissions were included in the analysis. Sepsis in-hospital mortality differed depending on the cause of infection: abdominal 18.93%, pulmonary 19.27%, and renal 12.81%. Higher average heart rate was associated with increased mortality risk. Increased average Mean Arterial Pressure (MAP) showed a reduced mortality risk across all sepsis groups. Results from the LR models found significant factors that were relevant for specific sepsis groups. Our models outperformed APACHE IV and SOFA scores with AUC between 0.63 and 0.74. Predictive power decreased over time, with the best results achieved for data extracted for the first 24 h of admission. Mortality varied significantly between the three sepsis groups. We also demonstrate that factors of importance show considerable heterogeneity depending on the source of infection. The factors influencing in-hospital mortality vary depending on the source of sepsis which may explain why most sepsis trials have failed to identify an effective treatment. The source of infection should be considered when considering mortality risk. Planning of sepsis treatment trials may benefit from risk stratification based on the source of infection.
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Affiliation(s)
- Mark Pieroni
- School of Computer Science and Mathematics, Liverpool John Moores University, Liverpool, United Kingdom
- Liverpool Centre for Cardiovascular Science, Liverpool, United Kingdom
| | - Ivan Olier
- School of Computer Science and Mathematics, Liverpool John Moores University, Liverpool, United Kingdom
- Liverpool Centre for Cardiovascular Science, Liverpool, United Kingdom
| | - Sandra Ortega-Martorell
- School of Computer Science and Mathematics, Liverpool John Moores University, Liverpool, United Kingdom
- Liverpool Centre for Cardiovascular Science, Liverpool, United Kingdom
| | - Brian W Johnston
- Liverpool Centre for Cardiovascular Science, Liverpool, United Kingdom
- Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
- Liverpool University Hospitals National Health Service (NHS) Foundation Trust, Liverpool, United Kingdom
| | - Ingeborg D Welters
- Liverpool Centre for Cardiovascular Science, Liverpool, United Kingdom
- Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
- Liverpool University Hospitals National Health Service (NHS) Foundation Trust, Liverpool, United Kingdom
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38
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Wen X, Xie B, Yuan S, Zhang J. The "Self-Sacrifice" of ImmuneCells in Sepsis. Front Immunol 2022; 13:833479. [PMID: 35572571 PMCID: PMC9099213 DOI: 10.3389/fimmu.2022.833479] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 04/05/2022] [Indexed: 12/15/2022] Open
Abstract
Sepsis is a life-threatening organ dysfunction caused by the host’s malfunctioning response to infection. Due to its high mortality rate and medical cost, sepsis remains one of the world’s most intractable diseases. In the early stage of sepsis, the over-activated immune system and a cascade of inflammation are usually accompanied by immunosuppression. The core pathogenesis of sepsis is the maladjustment of the host’s innate and adaptive immune response. Many immune cells are involved in this process, including neutrophils, mononuclear/macrophages and lymphocytes. The immune cells recognize pathogens, devour pathogens and release cytokines to recruit or activate other cells in direct or indirect manner. Pyroptosis, immune cell-extracellular traps formation and autophagy are several novel forms of cell death that are different from apoptosis, which play essential roles in the progress of sepsis. Immune cells can initiate “self-sacrifice” through the above three forms of cell death to protect or kill pathogens. However, the exact roles and mechanisms of the self-sacrifice in the immune cells in sepsis are not fully elucidated. This paper mainly analyzes the self-sacrifice of several representative immune cells in the forms of pyroptosis, immune cell-extracellular traps formation and autophagy to reveal the specific roles they play in the occurrence and progression of sepsis, also to provide inspiration and references for further investigation of the roles and mechanisms of self-sacrifice of immune cells in the sepsis in the future, meanwhile, through this work, we hope to bring inspiration to clinical work.
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Affiliation(s)
- Xiaoyue Wen
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bing Xie
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiying Yuan
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiancheng Zhang
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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39
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Sepsis prediction in intensive care unit based on genetic feature optimization and stacked deep ensemble learning. Neural Comput Appl 2022. [DOI: 10.1007/s00521-021-06631-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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40
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Gao YL, Yao Y, Zhang X, Chen F, Meng XL, Chen XS, Wang CL, Liu YC, Tian X, Shou ST, Chai YF. Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis? Front Immunol 2022; 13:829210. [PMID: 35281010 PMCID: PMC8914284 DOI: 10.3389/fimmu.2022.829210] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 02/07/2022] [Indexed: 12/12/2022] Open
Abstract
Sepsis is a syndrome characterized by life-threatening organ dysfunction caused by the dysregulated host response to an infection. Sepsis, especially septic shock and multiple organ dysfunction is a medical emergency associated with high morbidity, high mortality, and prolonged after-effects. Over the past 20 years, regulatory T cells (Tregs) have been a key topic of focus in all stages of sepsis research. Tregs play a controversial role in sepsis based on their heterogeneous characteristics, complex organ/tissue-specific patterns in the host, the multi-dimensional heterogeneous syndrome of sepsis, the different types of pathogenic microbiology, and even different types of laboratory research models and clinical research methods. In the context of sepsis, Tregs may be considered both angels and demons. We propose that the symptoms and signs of sepsis can be attenuated by regulating Tregs. This review summarizes the controversial roles and Treg checkpoints in sepsis.
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Affiliation(s)
- Yu-lei Gao
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
- *Correspondence: Yan-fen Chai, ; Yu-lei Gao,
| | - Ying Yao
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiang Zhang
- Department of Emergency Medicine, Rizhao People’s Hospital of Shandong Province, Rizhao, China
| | - Fang Chen
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiang-long Meng
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin-sen Chen
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Chao-lan Wang
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Yan-cun Liu
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin Tian
- Department of Medical Research, Beijing Qiansong Technology Development Company, Beijing, China
| | - Song-tao Shou
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Yan-fen Chai
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
- *Correspondence: Yan-fen Chai, ; Yu-lei Gao,
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Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction. Proc Natl Acad Sci U S A 2022; 119:2115139119. [PMID: 35173051 PMCID: PMC8872724 DOI: 10.1073/pnas.2115139119] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2021] [Indexed: 12/13/2022] Open
Abstract
Since sepsis induces a sustained immunosuppression responsible for secondary infections acquisition and late mortality, restoring immune function would result in a better outcome. Given the role of arginine deficiency in T cell dysfunction, the evaluation of restoring arginine availability in sepsis has to be explored. Using an animal model of sepsis, we demonstrated that increasing arginine availability enhanced mitochondrial T cell function and decreased sepsis-induced immunosuppression. Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.
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Reaven MS, Rozario NL, McCarter MSJ, Heffner AC. Incidence and risk factors associated with early death in patients with emergency department septic shock. Acute Crit Care 2022; 37:193-201. [PMID: 35172528 PMCID: PMC9184973 DOI: 10.4266/acc.2021.00857] [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: 06/23/2021] [Accepted: 11/08/2021] [Indexed: 11/30/2022] Open
Abstract
Background Limited research has explored early mortality among patients presenting with septic shock. The objective of this study was to determine the incidence and factors associated with early death following emergency department (ED) presentation of septic shock. Methods A prospective registry of patients enrolled in an ED septic shock clinical pathway was used to identify patients. Patients were compared across demographic, comorbid, clinical, and treatment variables by death within 72 hours of ED presentation. Results Among the sample of 2,414 patients, overall hospital mortality was 20.6%. Among patients who died in the hospital, mean and median time from ED presentation to death were 4.96 days and 2.28 days, respectively. Death at 24, 48, and 72 hours occurred in 5.5%, 9.5%, and 11.5% of patients, respectively. Multivariate regression analysis demonstrated that the following factors were independently associated with early mortality: age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03–1.05), malignancy (OR, 1.53; 95% CI, 1.11–2.11), pneumonia (OR, 1.39; 95% CI, 1.02–1.88), urinary tract infection (OR, 0.63; 95% CI, 0.44–0.89), first shock index (OR, 1.85; 95% CI, 1.27–2.70), early vasopressor use (OR, 2.16; 95% CI, 1.60–2.92), initial international normalized ratio (OR, 1.14; 95% CI, 1.07–1.27), initial albumin (OR, 0.55; 95% CI, 0.44–0.69), and first serum lactate (OR, 1.21; 95% CI, 1.16–1.26). Conclusions Adult septic shock patients experience a high rate of early mortality within 72 hours of ED arrival. Recognizable clinical factors may aid the identification of patients at risk of early death.
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Mezzaroba AL, Larangeira AS, Morakami FK, Junior JJ, Vieira AA, Costa MM, Kaneshima FM, Chiquetti G, Colonheze UE, Brunello GC, Cardoso LT, Matsuo T, Grion CM. Evaluation of time to death after admission to an intensive care unit and factors associated with mortality: A retrospective longitudinal study. Int J Crit Illn Inj Sci 2022; 12:121-126. [PMID: 36506928 PMCID: PMC9728075 DOI: 10.4103/ijciis.ijciis_98_21] [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: 11/23/2021] [Revised: 01/14/2022] [Accepted: 01/26/2022] [Indexed: 12/15/2022] Open
Abstract
Background Among nonsurvivors admitted to the intensive care unit (ICU), some present early mortality while other patients, despite having a favorable evolution regarding the initial disease, die later due to complications related to hospitalization. This study aims to identify factors associated with the time until death after admission to an ICU of a university hospital. Methods Retrospective longitudinal study that included adult patients admitted to the ICU between January 1, 2008, and December 31, 2017. Nonsurviving patients were divided into groups according to the length of time from admission to the ICU until death: Early (0-5 days), intermediate (6-28 days), and late (>28 days). Patients were considered septic if they had this diagnosis on admission to the ICU. Simple linear regression analysis was performed to evaluate the association between time to death over the years of the study. Multivariate cox regression was used to assess risk factors for the outcome in the ICU. Results In total, 6596 patients were analyzed. Mortality rate was 32.9% in the ICU. Most deaths occurred in the early (42.8%) and intermediate periods (47.9%). Patients with three or more dysfunctions on admission were more likely to die early (P < 0.001). The diagnosis of sepsis was associated with a higher mortality rate. The multivariate analysis identified age >60 years (hazard ratio [HR] 1.009), male (HR 1.192), mechanical ventilation (HR 1.476), dialysis (HR 2.297), and sequential organ failure assessment >6 (HR 1.319) as risk factors for mortality. Conclusion We found a higher proportion of early and intermediate deaths in the study period. The presence of three or more organ dysfunctions at ICU admission was associated with early death. The diagnosis of sepsis evident on ICU admission was associated with higher mortality.
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Affiliation(s)
- Ana Luiza Mezzaroba
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | | | - Fernanda K. Morakami
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Jair Jesus Junior
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Amanda A. Vieira
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Marina M. Costa
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Fernanda M. Kaneshima
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Giovana Chiquetti
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Ulisses E. Colonheze
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | | | - Lucienne T.Q. Cardoso
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Tiemi Matsuo
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil
| | - Cintia M.C. Grion
- Department of Clinical Medicine, Universidade Estadual De Londrina, Londrina, Brazil,Address for correspondence: Prof. Cintia M. C. Grion, Divisão De Terapia Intensive, Rua Robert Koch 60, Vila Operária, Londrina 86038-440, Paraná, Brazil. E-mail:
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Aletreby W, Mady A, Al-Odat M, Balshi A, Mady A, Al-Odat A, Elshayeb A, Mostafa A, Abd Elsalam S, Odchigue K. Early versus late DNR orders and its predictors in a Saudi Arabian ICU: A descriptive study. SAUDI JOURNAL OF MEDICINE AND MEDICAL SCIENCES 2022; 10:192-197. [PMID: 36247060 PMCID: PMC9555038 DOI: 10.4103/sjmms.sjmms_141_22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/24/2022] [Accepted: 06/22/2022] [Indexed: 11/04/2022] Open
Abstract
Background Objective: Methods: Results: Conclusion:
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Magrupov BA, Sharipova VK, Ubaydullaeva VU, Vervekina TA, Alimov AK, Rashidov DZ, Karimov AA, Kochetov VE. [Comparison of the final clinical and autopsy detected diagnoses in sepsis]. Arkh Patol 2022; 84:38-44. [PMID: 35880598 DOI: 10.17116/patol20228404138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
UNLABELLED With sepsis, more than a third of patients die, while the immediate causes of death may remain unknown. Autopsy largely helps to establish them. OBJECTIVE Identification of discrepancies in the final clinical and autopsy detected diagnoses in patients with sepsis who died in the surgical intensive care unit. MATERIAL AND METHODS 107 cases of patients with sepsis who died in the Department of Surgical Resuscitation of the Republican Scientific Center for Emergency Medical Care in 2020-2021 were studied. Autopsy was performed in 60 (56%) of the deceased. The autopsy was performed within 24 hours after the death was pronounced. The final clinical and pathoanatomic diagnoses were compared in accordance with the International Goldman System and the Russian Classification of categories of diagnosis discrepancies. RESULTS As a result of autopsies, 3 (5%) of the deceased had a discrepancy in the diagnoses of class I and 14 (23%) - class II according to the International Goldman System. During his lifetime, diseases or their complications were not recognized in 17 (28%) cases, mainly acute myocardial infarction of type 2 (3 cases) and liver abscesses (3 cases). CONCLUSION A pathoanatomic autopsy is a modern and important diagnostic tool that can clarify the causes of death.
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Affiliation(s)
- B A Magrupov
- Center for the Development of Professional Qualifications of Medical Workers, Tashkent, Republic of Uzbekistan
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
| | - V Kh Sharipova
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
| | - V U Ubaydullaeva
- Center for the Development of Professional Qualifications of Medical Workers, Tashkent, Republic of Uzbekistan
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
| | - T A Vervekina
- Center for the Development of Professional Qualifications of Medical Workers, Tashkent, Republic of Uzbekistan
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
| | - A Kh Alimov
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
| | - D Z Rashidov
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
| | - A A Karimov
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
| | - V E Kochetov
- Republican Scientific Center for Emergency Medical Care, Tashkent, Republic of Uzbekistan
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Watanabe S, Liu K, Morita Y, Kanaya T, Naito Y, Suzuki S, Hasegawa Y. Effects of Mobilization among Critically Ill Patients in the Intensive Care Unit: A Single-center Retrospective Study. Prog Rehabil Med 2022; 7:20220013. [PMID: 35415279 PMCID: PMC8938413 DOI: 10.2490/prm.20220013] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 02/04/2022] [Indexed: 11/09/2022] Open
Abstract
Objectives: This study investigated the effect of early mobilization [EM; physical rehabilitation
with the intensity needed to sit on the edge of the bed started within 5 days of
intensive care unit (ICU) admission] in relation to improvements in gait independence
and other clinical outcomes. Methods: This retrospective single-center study evaluated patients aged at least 18 years who
stayed in the ICU for at least 48 h and were categorized into EM and late mobilization
(LM; physical rehabilitation started more than 5 days after ICU admission) groups.
Outcomes were compared after adjusting for 20 background factors by propensity score
matching and inverse probability of treatment weighting. The primary outcome was
independent gait at discharge. The secondary outcomes were medical costs, 90-day
survival, and durations of ICU and hospital stays. Results: Of 177 patients, 85 and 92 were enrolled in the EM and LM groups, respectively.
Propensity score matching created 37 patient pairs. There was no significant difference
in the 90-day survival rate (P=0.308) or medical costs (P=0.054), whereas independent
gait at discharge (P=0.025) and duration of hospital stay (P=0.013) differed
significantly. Multivariate logistic regression analysis showed that EM was
independently associated with independent gait at discharge (P=0.011) and duration of
hospital stay (P=0.010) but was not associated with 90-day survival (odds ratio: 2.64,
95% confidence interval: 0.67–13.12, P=0.169). Conclusions: Early mobilization in the ICU did not affect 90-day survival and did not lower medical
costs but was associated with independent gait at discharge and shorter hospital
stays.
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Affiliation(s)
- Shinichi Watanabe
- Department of Rehabilitation Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan
| | - Keibun Liu
- Critical Care Research Group, The Prince Charles Hospital, Chermside, Australia
| | - Yasunari Morita
- Department of Critical Care Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan
| | - Takahiro Kanaya
- Department of Rehabilitation Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan
| | - Yuji Naito
- Department of Rehabilitation Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan
| | - Shuichi Suzuki
- Department of Critical Care Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan
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Pape T, Hunkemöller AM, Kümpers P, Haller H, David S, Stahl K. Targeting the "sweet spot" in septic shock - A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2. Matrix Biol Plus 2021; 12:100095. [PMID: 34917926 PMCID: PMC8669377 DOI: 10.1016/j.mbplus.2021.100095] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/20/2021] [Accepted: 11/23/2021] [Indexed: 12/23/2022] Open
Abstract
Sepsis is a life-threatening syndrome caused by a pathological host response to an infection that eventually, if uncontrolled, leads to septic shock and ultimately, death. In sepsis, a massive aggregation of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) cause a cytokine storm. The endothelial glycocalyx (eGC) is a gel like layer on the luminal side of the endothelium that consists of proteoglycans, glycosaminoglycans (GAG) and plasma proteins. It is synthesized by endothelial cells and plays an active role in the regulation of inflammation, permeability, and coagulation. In sepsis, early and profound injury of the eGC is observed and circulating eGC components correlate directly with clinical severity and outcome. The activity of the heparan sulfate (HS) specific glucuronidase Heparanase-1 (Hpa-1) is elevated in sepsis, resulting in shedding of heparan sulfate (HS), a main GAG of the eGC. HS induces endothelial barrier breakdown and accelerates systemic inflammation. Lipopolysaccharide (LPS), a PAMP mainly found on the surface of gram-negative bacteria, activates TLR-4, which results in cytokine production and further activation of Hpa-1. Hpa-1 shed HS fragments act as DAMPs themselves, leading to a vicious cycle of inflammation and end-organ dysfunction such as septic cardiomyopathy and encephalopathy. Recently, Hpa-1's natural antagonist, Heparanase-2 (Hpa-2) has been identified. It has no intrinsic enzymatic activity but instead acts by reducing inflammation. Hpa-2 levels are reduced in septic mice and patients, leading to an acquired imbalance of Hpa-1 and Hpa-2 paving the road towards a therapeutic intervention. Recently, the synthetic antimicrobial peptide 19-2.5 was described as a promising therapy protecting the eGC by inhibition of Hpa-1 activity and HS shed fragments in animal studies. However, a recombinant Hpa-2 therapy does not exist to the present time. Therapeutic plasma exchange (TPE), a modality already tested in clinical practice, effectively removes injurious mediators, e.g., Hpa-1, while replacing depleted protective molecules, e.g., Hpa-2. In critically ill patients with septic shock, TPE restores the physiological Hpa-1/Hpa-2 ratio and attenuates eGC breakdown. TPE results in a significant improvement in hemodynamic instability including reduced vasopressor requirement. Although promising, further studies are needed to determine the therapeutic impact of TPE in septic shock.
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Affiliation(s)
- Thorben Pape
- Division of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
| | - Anna Maria Hunkemöller
- Department of Medicine, Division of General Internal and Emergency Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
| | - Philipp Kümpers
- Department of Medicine, Division of General Internal and Emergency Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
| | - Hermann Haller
- Division of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
| | - Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Klaus Stahl
- Division of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.,Division of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
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Hortová-Kohoutková M, De Zuani M, Lázničková P, Bendíčková K, Mrkva O, Andrejčinová I, Mýtniková A, Polanský O, Kočí K, Tomášková V, Šrámek V, Helán M, Frič J. Polymorphonuclear Cells Show Features of Dysfunctional Activation During Fatal Sepsis. Front Immunol 2021; 12:741484. [PMID: 34966382 PMCID: PMC8710474 DOI: 10.3389/fimmu.2021.741484] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 11/24/2021] [Indexed: 12/29/2022] Open
Abstract
Sepsis and septic shock remain leading causes of morbidity and mortality for patients in the intensive care unit. During the early phase, immune cells produce various cytokines leading to prompt activation of the immune system. Polymorphonuclear leukocytes (PMNs) respond to different signals producing inflammatory factors and executing their antimicrobial mechanisms, resulting in the engulfment and elimination of invading pathogens. However, excessive activation caused by various inflammatory signals produced during sepsis progression can lead to the alteration of PMN signaling and subsequent defects in their functionality. Here, we analyzed samples from 34 patients in septic shock, focusing on PMNs gene expression and proteome changes associated with septic shock. We revealed that, compared to those patients who survived longer than five days, PMNs from patients who had fulminant sepsis were characterized by a dysfunctional hyper-activation, show altered metabolism, and recent exit from the cell cycle and signs of cellular lifespan. We believe that this multi-omics approach, although limited, pinpoints the alterations in PMNs' functionality, which may be rescued by targeted treatments.
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Affiliation(s)
| | - Marco De Zuani
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Petra Lázničková
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
- Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Kamila Bendíčková
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Ondřej Mrkva
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Ivana Andrejčinová
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
- Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Alexandra Mýtniková
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Ondřej Polanský
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Kamila Kočí
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Veronika Tomášková
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Vladimír Šrámek
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Martin Helán
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Jan Frič
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
- Department of Modern Immunotherapy, Institute of Hematology and Blood Transfusion, Prague, Czechia
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Vallés J, Diaz E, Carles Oliva J, Martínez M, Navas A, Mesquida J, Gruartmoner G, de Haro C, Mestre J, Guía C, Rodriguez A, Ochagavía A. Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control. Med Intensiva 2021; 45:541-551. [PMID: 34839885 DOI: 10.1016/j.medine.2020.05.013] [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: 03/02/2020] [Accepted: 05/16/2020] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To evaluate the incidence and risk factors for early mortality (EM) in the ICU in patients with community-acquired septic shock (CASS). DESIGN A retrospective cohort study of patients with CASS admitted to the ICU (2003-2016). SETTING ICU at a University Hospital in Spain. PATIENTS All consecutive patients admitted to the ICU with CASS. INTERVENTIONS None. MAIN VARIABLES OF INTEREST CASS was defined according to the Sepsis-3 definitions. EM were defined as occurring within of 72h following ICU admission. A multinomial logistic regression analysis was performed to identify the risk factors associated with early deaths. RESULTS During the study period, 625 patients met the Sepsis-3 criteria and admitted with CASS. 14.4% of all patients died within the first 72h. Of 161 patients who died in the ICU, 90 (55.9%) died within the first 72h. The percentage of early and late mortality did not vary significantly during the study period. The need and adequacy of source control were significantly lower in patients with EM. In the multivariate analysis, ARDS, non-respiratory infections, bacteremia and severity at admission were variables independently associated with EM. The only factor that decreased EM was adequate source control in patients with infections amenable to source control. CONCLUSIONS The incidence of EM has remained stable over time, which means that more than half of the patients who die from CASS do so within the first 72h. Infections where adequate source control can be performed have lower EM.
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Affiliation(s)
- J Vallés
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain.
| | - E Diaz
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - J Carles Oliva
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - M Martínez
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - A Navas
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - J Mesquida
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - G Gruartmoner
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - C de Haro
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - J Mestre
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - C Guía
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - A Rodriguez
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - A Ochagavía
- Critical Care Department, Fundació Parc Taulí, Hospital Universitari Parc Taulí, Sabadell, Spain
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Mandai S, Ando F, Mori T, Susa K, Iimori S, Naito S, Sohara E, Uchida S, Fushimi K, Rai T. Burden of kidney disease on the discrepancy between reasons for hospital admission and death: An observational cohort study. PLoS One 2021; 16:e0258846. [PMID: 34731197 PMCID: PMC8565775 DOI: 10.1371/journal.pone.0258846] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/07/2021] [Indexed: 12/30/2022] Open
Abstract
Background Physicians have long noted a substantial discrepancy between the reasons for hospital admission and ultimate causes of death, particularly among older adults or patients with complex underlying diseases. However, objective data on this phenomenon are lacking. We aimed to examine the risk of in-hospital death caused by a reason other than the original reason for hospitalization and its association with underlying kidney disease in a nationwide inpatient database. Methods In this retrospective cohort study, we studied 639,556 Japanese adults who died in the hospital from 2012 to 2015, using data from Japan’s Diagnosis Procedure Combination database. We analyzed the discrepancy rate between reasons for hospital admission and death and associated factors using the International Classification of Diseases, 10th Revision (ICD-10) diagnostic codes and seven related categories. Results Among non-chronic kidney disease (CKD) (590,551), CKD (24,708), and end-stage kidney disease (ESKD) (24,297) patients, the median age was 77 years (interquartile range [IQR]: 67–84 years), 83 years (IQR: 75–88), and 75 years (IQR: 67–81), and 25.7%, 30.3%, and 41.6% died from a reason other than the original reason for hospitalization, respectively. Multivariate logistic regression analyses determined CKD/ESKD as the predominant risk factor for this discrepancy, rather than older age, male sex, obesity, and other comorbidities. Sankey diagrams that presented diagnostic changes from hospital admission to death revealed multiple wider segments connecting to different disease classifications, particularly to congestive and septic death in CKD and ESKD patients, respectively. Death owing to another disease classification led to an increase in the median length of hospital stay by 5–7 days and to a 1.3-–1.4-fold increase in medical costs across the populations. Conclusions A substantial proportion of patients with CKD and ESKD died during hospitalization for a reason other than their original reason for admission, leading to increased length of hospital stay and cost.
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Affiliation(s)
- Shintaro Mandai
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
- * E-mail: (SM); (TM)
| | - Fumiaki Ando
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Takayasu Mori
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Koichiro Susa
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Soichiro Iimori
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Shotaro Naito
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Eisei Sohara
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Shinichi Uchida
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | - Tatemitsu Rai
- Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
- * E-mail: (SM); (TM)
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