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Xi F, Teng R, Xiong B, Wang D, Zheng N, Cheng J, Dong W, Huang X, Wang X, Tan S. Low sarcopenia index predicts intra-abdominal infection in patients with abdominal trauma. Nutrition 2025; 133:112695. [PMID: 39970767 DOI: 10.1016/j.nut.2025.112695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 01/14/2025] [Accepted: 01/22/2025] [Indexed: 02/21/2025]
Abstract
OBJECTIVES Prediction of intra-abdominal infection (IAI) in patients with abdominal trauma is crucial, yet reliable predictive indicators are currently lacking. The sarcopenia index (SI) is a readily available indicator of clinical outcomes in several diseases that holds diagnostic and prognostic value. The aim of this study is to assess the predictive value of SI for IAI in patients with abdominal trauma. METHODS This retrospective cohort study enrolled patients with abdominal trauma. Multivariable logistic analyses were used to identify independent factors of IAI. We divided patients into 2 groups based on sex. The receiver operating characteristic (ROC) curve was used to evaluate the performance of SI in predicting IAI. Then, based on the cut-off values of the SI established for males and females, we stratified patients into high and low-IAI risk groups to compare clinical outcomes. Spearman correlation analysis was used for correlation analysis. RESULTS A total of 378 participants with abdominal trauma were included. Multivariable logistic analyses identified SI as an independent risk factor for IAI in both males [odds ratio (OR): 0.82, 95% confidence interval (CI): 0.74-0.90, P < 0.001] and females (OR: 0.68, 95% CI: 0.51-0.91, P = 0.009). The area under the ROC curve for SI in predicting IAI was 0.712 for males and 0.733 for females, with optimal cut-off values of 81.430 for males and 57.907 for females. Furthermore, SI showed significant correlations with the length of hospital stay (P = 0.003) and hospital costs (P = 0.042). CONCLUSIONS SI was identified as an independent risk factor for IAI in patients with abdominal trauma, offering predictive value for both genders. SI correlates with poor clinical outcomes. This might provide new ideas and theoretical guidance for diagnosing and treating IAI.
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Affiliation(s)
- Fengchan Xi
- Department of Intensive Care Unit, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, Jiangsu, China; Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Ran Teng
- Department of Intensive Care Unit, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, Jiangsu, China
| | - Bing Xiong
- Department of Radiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Di Wang
- Department of Intensive Care Unit, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, Jiangsu, China
| | - Nan Zheng
- Department of Intensive Care Unit, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, Jiangsu, China
| | - Jinghui Cheng
- Department of Intensive Care Unit, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, Jiangsu, China
| | - Wei Dong
- Department of Intensive Care Unit, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, Jiangsu, China
| | - Xinwei Huang
- Department of Intensive Care Unit, Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, Jiangsu, China
| | - Xiling Wang
- Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, China.
| | - Shanjun Tan
- Department of General Surgery/Shanghai Clinical Nutrition Research Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Shi MQ, Chen J, Ji FH, Zhou H, Peng K, Wang J, Fan CL, Wang X, Wang Y. Prognostic impact of hypernatremia for septic shock patients in the intensive care unit. World J Clin Cases 2025; 13:95430. [PMID: 40051797 PMCID: PMC11612684 DOI: 10.12998/wjcc.v13.i7.95430] [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: 04/10/2024] [Revised: 10/04/2024] [Accepted: 11/13/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Hypernatremia represents a significant electrolyte imbalance associated with numerous adverse outcomes, particularly in cases of intensive care unit (ICU)-acquired hypernatremia (IAH). Nevertheless, its relevance in patients with septic shock remains uncertain. AIM To identify independent risk factors and their predictive efficacy for IAH to improve outcomes in patients with septic shock. METHODS In the present retrospective single-center study, a cohort of 157 septic shock patients with concurrent hypernatremia in the ICU at The First Affiliated Hospital of Soochow University, between August 1, 2018, and May 31, 2023, were analyzed. Patients were categorized based on the timing of hypernatremia occurrence into the IAH group (n = 62), the non-IAH group (n = 41), and the normonatremia group (n = 54). RESULTS In the present study, there was a significant association between the high serum sodium concentrations, excessive persistent inflammation, immunosuppression and catabolism syndrome and chronic critical illness, while rapid recovery had an apparent association with normonatremia. Moreover, multivariable analyses revealed the following independent risk factors for IAH: Total urinary output over the preceding three days [odds ratio (OR) = 1.09; 95%CI: 1.02-1.17; P = 0.014], enteral nutrition (EN) sodium content of 500 mg (OR = 2.93; 95%CI: 1.13-7.60; P = 0.027), and EN sodium content of 670 mg (OR = 6.19; 95%CI: 1.75-21.98; P = 0.005) were positively correlated with the development of IAH. Notably, the area under the curve for total urinary output over the preceding three days was 0.800 (95%CI: 0.678-0.922, P = 0.001). Furthermore, maximum serum sodium levels, the duration of hypernatremia, and varying sodium correction rates were significantly associated with 28-day in-hospital mortality in septic shock patients (P < 0.05). CONCLUSION The present findings illustrate that elevated serum sodium level was significantly associated with a poor prognosis in septic shock patients in the ICU. It is highly recommended that hypernatremia be considered a potentially important prognostic indicator for the outcome of septic shock.
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Affiliation(s)
- Mai-Qing Shi
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Jun Chen
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Fu-Hai Ji
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Hao Zhou
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Ke Peng
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Jun Wang
- Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Chun-Lei Fan
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Xu Wang
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Yang Wang
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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López-Cruz I, García-Giménez JL, Madrazo M, García-Guallarte J, Piles L, Pallardó FV, Artero A. Epigenome-wide DNA methylation profiling in septic and non-septic patients with similar infections: potential use as sepsis biomarkers. Front Cell Infect Microbiol 2025; 14:1532417. [PMID: 39926115 PMCID: PMC11802815 DOI: 10.3389/fcimb.2024.1532417] [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: 11/21/2024] [Accepted: 12/31/2024] [Indexed: 02/11/2025] Open
Abstract
Introduction Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis. Methods A prospective case-control study was conducted to compare DNA methylation profiles between patients with community-acquired sepsis and matched controls who had similar infections but did not develop sepsis. Whole blood samples from these patients were analyzed using the Infinium MethylationEPIC v2.0 kit, enabling genome-wide methylation analysis. Selected genes with differential methylation were validated by pyrosequencing. Results Significant differential DNA methylation patterns were identified between septic and non-septic individuals uising. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction. The most prominent findings include the hypomethylation of immune-related genes (SERPINA1, AZU1, MPO, and SLX4), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels. Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858). Discussion Our results underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.
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Affiliation(s)
- Ian López-Cruz
- Department of Internal Medicine, Dr. Peset University Hospital, Valencia, Spain
- Department of Medicine, Faculty of Medicine & Dentistry, University of Valencia, Valencia, Spain
| | - José Luis García-Giménez
- Department of Physiology, Faculty of Medicine & Dentistry, University of Valencia, Valencia, Spain
- INCLIVA Biomedical Research Institute, Valencia, Spain
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
| | - Manuel Madrazo
- Department of Internal Medicine, Dr. Peset University Hospital, Valencia, Spain
- Department of Medicine, Faculty of Medicine & Dentistry, University of Valencia, Valencia, Spain
| | | | - Laura Piles
- Department of Internal Medicine, Dr. Peset University Hospital, Valencia, Spain
| | - Federico V. Pallardó
- Department of Physiology, Faculty of Medicine & Dentistry, University of Valencia, Valencia, Spain
- INCLIVA Biomedical Research Institute, Valencia, Spain
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
| | - Arturo Artero
- Department of Internal Medicine, Dr. Peset University Hospital, Valencia, Spain
- Department of Medicine, Faculty of Medicine & Dentistry, University of Valencia, Valencia, Spain
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Ohbe H, Satoh K, Totoki T, Tanikawa A, Shirasaki K, Kuribayashi Y, Tamura M, Takatani Y, Ishikura H, Nakamura K. Definitions, epidemiology, and outcomes of persistent/chronic critical illness: a scoping review for translation to clinical practice. Crit Care 2024; 28:435. [PMID: 39731183 PMCID: PMC11681689 DOI: 10.1186/s13054-024-05215-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 12/14/2024] [Indexed: 12/29/2024] Open
Abstract
BACKGROUND Medical advances in intensive care units (ICUs) have resulted in the emergence of a new patient population-those who survive the initial acute phase of critical illness, but require prolonged ICU stays and develop chronic critical symptoms. This condition, often termed Persistent Critical Illness (PerCI) or Chronic Critical Illness (CCI), remains poorly understood and inconsistently reported across studies, resulting in a lack of clinical practice use. This scoping review aims to systematically review and synthesize the existing literature on PerCI/CCI, with a focus on definitions, epidemiology, and outcomes for its translation to clinical practice. METHODS A scoping review was conducted using MEDLINE and Scopus, adhering to the PRISMA-ScR guidelines. Peer-reviewed original research articles published until May 31, 2024 that described adult PerCI/CCI in their definitions of patient populations, covariates, and outcomes were included. Data on definitions, epidemiology, and outcomes were extracted by a data charting process from eligible studies and synthesized. RESULTS Ninety-nine studies met the inclusion criteria. Of these studies, 64 used the term CCI, 18 used PerCI, and 17 used other terms. CCI definitions showed greater variability, while PerCI definitions remained relatively consistent, with an ICU stay ≥ 14 days for CCI and ≥ 10 days for PerCI being the most common. A meta-analysis of the prevalence of PerCI/CCI among the denominators of "all ICU patients", "sepsis", "trauma", and "COVID-19" showed 11% (95% confidence interval 10-12%), 28% (22-34%), 24% (15-33%), and 35% (20-50%), respectively. A meta-analysis of in-hospital mortality was 27% (26-29%) and that of one-year mortality was 45% (32-58%). Meta-analyses of the prevalence of CCI and PerCI showed 17% (16-18%) and 18% (16-20%), respectively, and those for in-hospital mortality were 28% (26-30%) and 26% (24-29%), respectively. Functional outcomes were generally poor, with many survivors requiring long-term care. CONCLUSIONS This scoping review synthesized many studies on PerCI/CCI, highlighting the serious impact of PerCI/CCI on patients' long-term outcomes. The results obtained underscore the need for consistent terminology with high-quality research for PerCI/CCI. The results obtained provide important information to be used in discussions with patients and families regarding prognosis and care options.
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Affiliation(s)
- Hiroyuki Ohbe
- Department of Emergency and Critical Care Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Kasumi Satoh
- Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan
| | - Takaaki Totoki
- Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan
| | - Atsushi Tanikawa
- Department of Emergency and Critical Care Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Kasumi Shirasaki
- Department of Emergency and Critical Care Medicine, St. Luke's International Hospital, 9-1 Akashicho, Chuo-ku, Tokyo, 104-8560, Japan
- Department of Emergency and Disaster Medicine, Kanazawa University Hospital, 13, 1-1 Takara-Machi, Kanazawa 920-8640, Aoba-ku, Sendai, 980-8574, Japan
| | - Yoshihide Kuribayashi
- Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasamacho, Yufu, Oita, 879-5593, Japan
| | - Miku Tamura
- Department of Pharmacy, Funabashi Municipal Medical Center, 1-21-1 Kanasugi, Funabashi city, Chiba, Japan
| | - Yudai Takatani
- Department of Primary Care and Emergency Medicine, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hiroyasu Ishikura
- Department of Emergency and Critical Care Center, Rakuwakai Otowa Hospital, 2 Otowachinji-cho, Yamashina-ku, Kyoto, 607-8062, Japan
| | - Kensuke Nakamura
- Department of Critical Care Medicine, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
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Graziani E Sousa A, Godoi A, Florêncio de Mesquita C, Prajiante Bertolino E, Canizares Quisiguina SI, Mazzola Poli de Figueiredo S. Irrigation with fibrinolytic agents versus saline for percutaneous drainage of abdominal abscesses: A meta-analysis with trial sequential analysis of randomized trials. World J Surg 2024; 48:2629-2636. [PMID: 39425743 DOI: 10.1002/wjs.12377] [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: 06/29/2024] [Accepted: 10/07/2024] [Indexed: 10/21/2024]
Abstract
INTRODUCTION Fibrinolytic agents (FA) activate the fibrinolytic system, converting plasminogen into plasmin to break down fibrin. Their use for irrigation of abdominal abscesses is debated, and this meta-analysis evaluates their efficacy. METHODS We searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing FA and saline in percutaneous drainage of abdominal abscesses. Outcomes included length of hospitalization, duration of drainage, and drainage volume. We pooled mean differences (MD) and 95% confidence intervals (CI) using a random-effects model. We also performed a trial sequential analysis (TSA). RESULTS We included six RCTs encompassing 299 patients. In the overall analysis, FA increased drainage volume (MD 104.25 mL; 95% CI 35.72-172.77 mL; p = 0.003; I2 = 0%). In children, saline reduced hospitalization duration (MD -1.26 days; 95% CI -1.98 to -0.55 days; p = 0.0006; I2 = 0%), whereas FA increased drainage volume (MD 84.66 mL; 95% CI 5.77-153.54 mL; p = 0.04; I2 = 0%). In adults, FA significantly reduced hospitalization duration (MD -11.12 days; 95% CI -15.16 to -7.08 days; p < 0.00001; I2 = 0%) and duration of drainage (MD -6.53 days; 95% CI -9.25 to -3.81 days; p < 0.00001; I2 = 0%) while increasing drainage volume (MD 164.47 mL; 95% CI 26.16-302.78 mL; p = 0.02; I2 = 0%). On TSA, the required information size was achieved only for the adult subgroup's hospitalization and drainage duration. CONCLUSION In adults, FA reduce hospitalization and drainage duration and increase drainage volume. In children, saline seems more effective in reducing hospitalization duration, while FA increase drainage volume. These findings underscore the need for age-specific treatments and further research, especially in the pediatric population.
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Affiliation(s)
| | - Amanda Godoi
- Cardiff University School of Medicine, Cardiff, Wales, UK
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Tanioka N, Kuwahara M, Maeda H, Edo N, Nokubo Y, Shimizu S, Akimori T, Seo S. Usefulness of laparoscopic surgery for colorectal perforation: a single-center retrospective cohort study. Surg Today 2024; 54:1301-1308. [PMID: 38918215 DOI: 10.1007/s00595-024-02886-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 03/17/2024] [Indexed: 06/27/2024]
Abstract
PURPOSE This study aimed to determine the safety and efficacy of laparoscopic surgery in patients with colorectal perforation owing to a significant lack of evidence in this field. METHODS This retrospective cohort study analyzed the data of 70 patients who underwent emergency surgery for colorectal perforations between January 2017 and December 2023. The surgical outcomes of the patients who underwent open and laparoscopic surgeries were statistically compared. The primary endpoints were postoperative mortality and complications. The secondary endpoints included blood loss, surgical time, length of hospital stay, and 1-year overall survival. RESULTS Overall, 28 patients underwent open surgery and 42 underwent laparoscopic surgery. No significant difference was noted in the postoperative mortality or overall rate of severe complications between the two groups. The incidence of superficial and deep incisional surgical site infection was lower in the laparoscopic surgery group (35.7% vs. 0.0%, p < 0.001), while the surgical time was significantly longer in the laparoscopic group (175.6 ± 92.2 min vs. 290.0 ± 102.3 min, p < 0.001). No significant differences were found in blood loss, length of hospital stay, or 1-year overall survival. CONCLUSIONS Laparoscopic surgery for colorectal perforation markedly reduced superficial and deep incisional surgical site infection, with no substantial difference in mortality or severe complications.
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Affiliation(s)
- Nobuhisa Tanioka
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City, Kochi, 788-0785, Japan
| | - Michio Kuwahara
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City, Kochi, 788-0785, Japan.
| | - Hiromichi Maeda
- Department of Surgery, Kochi Medical School Hospital, Kochi University, Kohasu, Oko-Cho, Nankoku, Kochi, 783-8505, Japan
| | - Naoki Edo
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City, Kochi, 788-0785, Japan
| | - Yuzuko Nokubo
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City, Kochi, 788-0785, Japan
| | - Shigeto Shimizu
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City, Kochi, 788-0785, Japan
| | - Toyokazu Akimori
- Department of Surgery, Hata Kenmin Hospital, 3-1 Yoshina, Yamanacho, Sukumo-City, Kochi, 788-0785, Japan
| | - Satoru Seo
- Department of Surgery, Kochi Medical School Hospital, Kochi University, Kohasu, Oko-Cho, Nankoku, Kochi, 783-8505, Japan
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Paiva JA, Rello J, Eckmann C, Antonelli M, Arvaniti K, Koulenti D, Papathanakos G, Dimopoulos G, Deschepper M, Blot S. Intra-abdominal infection and sepsis in immunocompromised intensive care unit patients: Disease expression, microbial aetiology, and clinical outcomes. Eur J Intern Med 2024; 129:100-110. [PMID: 39079800 DOI: 10.1016/j.ejim.2024.07.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 06/24/2024] [Accepted: 07/16/2024] [Indexed: 11/05/2024]
Abstract
We compared epidemiology of intra-abdominal infection (IAI) between immunocompromised and non-immunocompromised ICU patients and identified risk factors for mortality. We performed a secondary analysis on the "AbSeS" database, a prospective, observational study with IAI patients from 309 ICUs in 42 countries. Immunocompromised status was defined as either neutropenia or prolonged corticosteroids use, chemotherapy or radiotherapy in the past year, bone marrow or solid organ transplantation, congenital immunodeficiency, or immunosuppressive drugs use. Mortality was defined as ICU mortality at any time or 28-day mortality for those discharged earlier. Associations with mortality were assessed by logistic regression. The cohort included 2589 patients of which 239 immunocompromised (9.2 %), most with secondary peritonitis. Among immunocompromised patients, biliary tract infections were less frequent, typhlitis more frequent, and IAIs were more frequently healthcare-associated or early-onset hospital-acquired compared with immunocompetent patients. No difference existed in grade of anatomical disruption, disease severity, organ failure, pathogens, and resistance patterns. Septic shock was significantly more frequent in the immunocompromised population. Mortality was similar in both groups (31.1% vs. 28.9 %; p = 0.468). Immunocompromise was not a risk factor for mortality (OR 0.98, 95 % CI 0.66-1.43). Independent risk factors for mortality among immunocompromised patients included septic shock at presentation (OR 6.64, 95 % CI 1.27-55.72), and unsuccessful source control with persistent inflammation (OR 5.48, 95 % CI 2.29-12.57). In immunocompromised ICU patients with IAI, short-term mortality was similar to immunocompetent patients, despite the former presented more frequently with septic shock, and septic shock and persistent inflammation after source control were independent risk factors for death.
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Affiliation(s)
- José-Artur Paiva
- Intensive Care Department, Centro Hospitalar Universitario S. Joao, Faculty of Medicine, University of Porto, Portugal; Grupo Infecao e Sepsis, Portugal
| | - Jordi Rello
- Nimes University Hospital, University of Montpellier, Nimes, France; Ciberes and Vall d'Hebron Institute of Research, Barcelona, Spain
| | - Christian Eckmann
- Department of General, Visceral and Thoracic Surgery, Klinikum Hannoversch-Muenden, Goettingen University, Germany
| | - Massimo Antonelli
- Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy
| | - Kostoula Arvaniti
- Intensive Care Unit, Papageorgiou University Affiliated Hospital, Thessaloníki, Greece
| | - Despoina Koulenti
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia; Department of Critical Care, King's College Hospital NHS Foundation Trust, London, UK
| | - Georgios Papathanakos
- Department of Intensive Care Medicine, University Hospital of Ioannina, Ioannina, Greece
| | - George Dimopoulos
- 3rd Department of Critical Care, "EVGENIDIO" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Mieke Deschepper
- Data Science Institute, Ghent University Hospital, Ghent, Belgium
| | - Stijn Blot
- Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
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Price AD, Becker ER, Barrios EL, Mazer MB, McGonagill PW, Bergmann CB, Goodman MD, Gould RW, Rao M, Polcz VE, Kucaba TA, Walton AH, Miles S, Xu J, Liang M, Loftus TJ, Efron PA, Remy KE, Brakenridge SC, Badovinac VP, Griffith TS, Moldawer LL, Hotchkiss RS, Caldwell CC. Surviving septic patients endotyped with a functional assay demonstrate active immune responses. Front Immunol 2024; 15:1418613. [PMID: 39469706 PMCID: PMC11513262 DOI: 10.3389/fimmu.2024.1418613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 09/24/2024] [Indexed: 10/30/2024] Open
Abstract
Introduction Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients. Methods This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an 'immunocompetent', 'immunosuppressed endotype', and two 'mixed' endotypes. Results Whole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. 'Immunocompetent' endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the 'immunosuppressed' endotype. Similarly, 'immunocompetent' endotype patients on day 4 had a higher in-hospital survival compared to the 'immunosuppressed' endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality. Conclusions Increased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early 'immunocompetent' endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.
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Affiliation(s)
- Adam D. Price
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Ellen R. Becker
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Evan L. Barrios
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Monty B. Mazer
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Patrick W. McGonagill
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Christian B. Bergmann
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Michael D. Goodman
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Robert W. Gould
- Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Mahil Rao
- Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Valerie E. Polcz
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Tamara A. Kucaba
- Department of Urology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Andrew H. Walton
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Sydney Miles
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Julie Xu
- Department of Urology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Muxuan Liang
- Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL, United States
| | - Tyler J. Loftus
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Philip A. Efron
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Kenneth E. Remy
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Scott C. Brakenridge
- Department of Surgery, Harborview Medical Center, University of Washington School of Medicine, Seattle, WA, United States
| | - Vladimir P. Badovinac
- Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
- Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Thomas S. Griffith
- Department of Urology, University of Minnesota Medical School, Minneapolis, MN, United States
- Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, United States
- Minneapolis VA Healthcare System, Minneapolis, MN, United States
| | - Lyle L. Moldawer
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Richard S. Hotchkiss
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Charles C. Caldwell
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States
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9
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Xu D, Lu Y, Wang Y, Li F. The obesity paradox and 90 day mortality in chronic critically ill patients: a cohort study using a large clinical database. Eur J Med Res 2024; 29:392. [PMID: 39075583 PMCID: PMC11285416 DOI: 10.1186/s40001-024-01962-w] [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: 02/10/2024] [Accepted: 07/04/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND This study investigates the obesity paradox, where obesity is linked to lower mortality in certain patient groups, focusing on its impact on long-term mortality in chronic critically ill (CCI) patients. METHODS We retrospectively analyzed CCI patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database's Intensive Care Unit, categorizing them into six groups based on Body Mass Index (BMI). Using stepwise multivariable Cox regression and restricted cubic spline models, we examined the association between BMI and 90 day mortality, accounting for confounding variables through subgroup analyses. RESULTS The study included 1996 CCI patients, revealing a 90 day mortality of 34.12%. Overweight and obese patients exhibited significantly lower mortality compared to normal-weight individuals. Adjusted analysis showed lower mortality risks in overweight and obese groups (HRs 0.60 to 0.72, p < 0.001). The cubic spline model indicated a negative correlation between BMI and 90 day mortality, with subgroup analyses highlighting interactions with age. CONCLUSION Our findings confirm the obesity paradox in CCI patients, especially among the elderly (65-85 years) and very elderly (≥ 85 years). The results suggest a beneficial association of higher BMI in older CCI patients, though caution is advised for those under 45.
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Affiliation(s)
- Danyu Xu
- Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Yan Lu
- Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Yan Wang
- Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Feng Li
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
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10
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Likhvantsev VV, Berikashvili LB, Yadgarov MY, Yakovlev AA, Kuzovlev AN. The Tri-Steps Model of Critical Conditions in Intensive Care: Introducing a New Paradigm for Chronic Critical Illness. J Clin Med 2024; 13:3683. [PMID: 38999249 PMCID: PMC11242724 DOI: 10.3390/jcm13133683] [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] [Received: 05/03/2024] [Revised: 06/15/2024] [Accepted: 06/20/2024] [Indexed: 07/14/2024] Open
Abstract
Background: The prevailing model for understanding chronic critical illness is a biphasic model, suggesting phases of acute and chronic critical conditions. A major challenge within this model is the difficulty in determining the timing of the process chronicity. It is likely that the triad of symptoms (inflammation, catabolism, and immunosuppression [ICIS]) could be associated with this particular point. We aimed to explore the impact of the symptom triad (inflammation, catabolism, immunosuppression) on the outcomes of patients hospitalized in intensive care units (ICUs). Methods: The eICU-CRD database with 200,859 ICU admissions was analyzed. Adult patients with the ICIS triad, identified by elevated CRP (>20 mg/L), reduced albumin (<30 g/L), and low lymphocyte counts (<0.8 × 109/L), were included. The cumulative risk of developing ICIS was assessed using the Nelson-Aalen estimator. Results: This retrospective cohort study included 894 patients (485 males, 54%), with 60 (6.7%) developing ICIS. The cumulative risk of ICIS by day 21 was 22.5%, with incidence peaks on days 2-3 and 10-12 after ICU admission. Patients with the ICIS triad had a 2.5-fold higher mortality risk (p = 0.009) and double the likelihood of using vasopressors (p = 0.008). The triad onset day did not significantly affect mortality (p = 0.104). Patients with ICIS also experienced extended hospital (p = 0.041) and ICU stays (p < 0.001). Conclusions: The symptom triad (inflammation, catabolism, immunosuppression) during hospitalization increases mortality risk by 2.5 times (p = 0.009) and reflects the chronicity of the critical condition. Identifying two incidence peaks allows the proposal of a new Tri-steps model of chronic critical illness with acute, extended, and chronic phases.
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Affiliation(s)
- Valery V Likhvantsev
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow 107031, Russia
| | - Levan B Berikashvili
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow 107031, Russia
| | - Mikhail Ya Yadgarov
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow 107031, Russia
| | - Alexey A Yakovlev
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow 107031, Russia
| | - Artem N Kuzovlev
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow 107031, Russia
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11
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Amati AL, Ebert R, Maier L, Panah AK, Schwandner T, Sander M, Reichert M, Grau V, Petzoldt S, Hecker A. Reduced preoperative serum choline esterase levels and fecal peritoneal contamination as potential predictors for the leakage of intestinal sutures after source control in secondary peritonitis. World J Emerg Surg 2024; 19:21. [PMID: 38840189 PMCID: PMC11151556 DOI: 10.1186/s13017-024-00550-x] [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: 04/25/2024] [Accepted: 05/29/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND The high rate of stoma placement during emergency laparotomy for secondary peritonitis is a paradigm in need of change in the current fast-track surgical setting. Despite growing evidence for the feasibility of primary bowel reconstruction in a peritonitic environment, little data substantiate a surgeons' choice between a stoma and an anastomosis. The aim of this retrospective analysis is to identify pre- and intraoperative parameters that predict the leakage risk for enteric sutures placed during source control surgery (SCS) for secondary peritonitis. METHODS Between January 2014 and December 2020, 497 patients underwent SCS for secondary peritonitis, of whom 187 received a primary reconstruction of the lower gastro-intestinal tract without a diverting stoma. In 47 (25.1%) patients postoperative leakage of the enteric sutures was directly confirmed during revision surgery or by computed tomography. Quantifiable predictors of intestinal suture outcome were detected by multivariate analysis. RESULTS Length of intensive care, in-hospital mortality and failure of release to the initial home environment were significantly higher in patients with enteric suture leakage following SCS compared to patients with intact anastomoses (p < 0.0001, p = 0.0026 and p =0.0009, respectively). Reduced serum choline esterase (sCHE) levels and a high extent of peritonitis were identified as independent risk factors for insufficiency of enteric sutures placed during emergency laparotomy. CONCLUSIONS A preoperative sCHE < 4.5 kU/L and generalized fecal peritonitis associate with a significantly higher incidence of enteric suture insufficiency after primary reconstruction of the lower gastro-intestinal tract in a peritonitic abdomen. These parameters may guide surgeons when choosing the optimal surgical procedure in the emergency setting.
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Affiliation(s)
- A L Amati
- Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany.
| | - R Ebert
- Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany
| | - L Maier
- Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany
| | - A K Panah
- Department of General, Visceral and Transplant Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - T Schwandner
- Department of General and Visceral Surgery, Asklepios Clinic Lich, Goethestrasse 4, 35423, Lich, Germany
| | - M Sander
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany
| | - M Reichert
- Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany
| | - V Grau
- Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany
| | - S Petzoldt
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany
| | - A Hecker
- Department of General, Visceral, Thoracic and Transplant Surgery, University Hospital of Giessen, Justus-Liebig University Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany
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12
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Chung KP, Su JY, Wang YF, Budiarto BR, Yeh YC, Cheng JC, Keng LT, Chen YJ, Lu YT, Juan YH, Nakahira K, Ruan SY, Chien JY, Chang HT, Jerng JS, Huang YT, Chen SY, Yu CJ. Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness. Front Immunol 2024; 15:1334882. [PMID: 38426112 PMCID: PMC10902670 DOI: 10.3389/fimmu.2024.1334882] [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: 11/08/2023] [Accepted: 01/10/2024] [Indexed: 03/02/2024] Open
Abstract
Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.
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Affiliation(s)
- Kuei-Pin Chung
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jia-Ying Su
- Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan
| | - Yi-Fu Wang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Bugi Ratno Budiarto
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
- Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan
| | - Yu-Chang Yeh
- Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jui-Chen Cheng
- Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan
| | - Li-Ta Keng
- Department of Internal Medicine, National Taiwan University Hospital, Hsinchu, Taiwan
| | - Yi-Jung Chen
- Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ya-Ting Lu
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Yi-Hsiu Juan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kiichi Nakahira
- Department of Pharmacology, Nara Medical University, Kashihara, Nara, Japan
| | - Sheng-Yuan Ruan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jung-Yien Chien
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hou-Tai Chang
- Department of Critical Care Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan
- Department of Industrial Engineering and Management, Yuan Ze University, Taoyuan, Taiwan
| | - Jih-Shuin Jerng
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Tsung Huang
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - Shih-Yu Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Chong-Jen Yu
- Department of Internal Medicine, National Taiwan University Hospital, Hsinchu, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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13
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Barrios EL, Mazer MB, McGonagill PW, Bergmann CB, Goodman MD, Gould RW, Rao M, Polcz VE, Davis RJ, Del Toro DE, Dirain ML, Dram A, Hale LO, Heidarian M, Kim CY, Kucaba TA, Lanz JP, McCray AE, Meszaros S, Miles S, Nelson CR, Rocha IL, Silva EE, Ungaro RF, Walton AH, Xu J, Zeumer-Spataro L, Drewry AM, Liang M, Bible LE, Loftus TJ, Turnbull IR, Efron PA, Remy KE, Brakenridge SC, Badovinac VP, Griffith TS, Moldawer LL, Hotchkiss RS, Caldwell CC. Adverse outcomes and an immunosuppressed endotype in septic patients with reduced IFN-γ ELISpot. JCI Insight 2024; 9:e175785. [PMID: 38100268 PMCID: PMC10906237 DOI: 10.1172/jci.insight.175785] [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: 09/26/2023] [Accepted: 11/30/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUNDSepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting clinical outcomes and immunological endotyping of septic patients generally relies on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.METHODSAn ex vivo whole-blood enzyme-linked immunosorbent spot (ELISpot) assay for cellular production of interferon γ (IFN-γ) was evaluated in 107 septic and 68 nonseptic patients from 5 academic health centers using blood samples collected on days 1, 4, and 7 following ICU admission.RESULTSCompared with 46 healthy participants, unstimulated and stimulated whole-blood IFN-γ expression was either increased or unchanged, respectively, in septic and nonseptic ICU patients. However, in septic patients who did not survive 180 days, stimulated whole-blood IFN-γ expression was significantly reduced on ICU days 1, 4, and 7 (all P < 0.05), due to both significant reductions in total number of IFN-γ-producing cells and amount of IFN-γ produced per cell (all P < 0.05). Importantly, IFN-γ total expression on days 1 and 4 after admission could discriminate 180-day mortality better than absolute lymphocyte count (ALC), IL-6, and procalcitonin. Septic patients with low IFN-γ expression were older and had lower ALCs and higher soluble PD-L1 and IL-10 concentrations, consistent with an immunosuppressed endotype.CONCLUSIONSA whole-blood IFN-γ ELISpot assay can both identify septic patients at increased risk of late mortality and identify immunosuppressed septic patients.TRIAL REGISTRYN/A.FUNDINGThis prospective, observational, multicenter clinical study was directly supported by National Institute of General Medical Sciences grant R01 GM-139046, including a supplement (R01 GM-139046-03S1) from 2022 to 2024.
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Affiliation(s)
- Evan L. Barrios
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Monty B. Mazer
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Patrick W. McGonagill
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Christian B. Bergmann
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- University Hospital Ulm, Clinic for Trauma Surgery, Hand, Plastic, and Reconstructive Surgery Albert-Einstein-Allee 23, Ulm, Germany
| | - Michael D. Goodman
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Robert W. Gould
- Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Mahil Rao
- Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Valerie E. Polcz
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Ruth J. Davis
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Drew E. Del Toro
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Marvin L.S. Dirain
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Alexandra Dram
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Lucas O. Hale
- Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Mohammad Heidarian
- Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Caleb Y. Kim
- Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Tamara A. Kucaba
- Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Jennifer P. Lanz
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Ashley E. McCray
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Sandra Meszaros
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Sydney Miles
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Candace R. Nelson
- Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Ivanna L. Rocha
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Elvia E. Silva
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Ricardo F. Ungaro
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Andrew H. Walton
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Julie Xu
- Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Leilani Zeumer-Spataro
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Anne M. Drewry
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Muxuan Liang
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
- Department of Biostatistics, University of Florida College of Public Health and Health Professions and the University of Florida College of Medicine, Gainesville, Florida, USA
| | - Letitia E. Bible
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Tyler J. Loftus
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Isaiah R. Turnbull
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Philip A. Efron
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Kenneth E. Remy
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Scott C. Brakenridge
- Department of Surgery, Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington, USA
| | - Vladimir P. Badovinac
- Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Experimental Pathology PhD Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Thomas S. Griffith
- Department of Urology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
- Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
- Minneapolis VA Healthcare System, Minneapolis, Minnesota, USA
| | - Lyle L. Moldawer
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Richard S. Hotchkiss
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Charles C. Caldwell
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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14
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Efron PA, Brakenridge SC, Mohr AM, Barrios EL, Polcz VE, Anton S, Ozrazgat-Baslanti T, Bihorac A, Guirgis F, Loftus TJ, Rosenthal M, Leeuwenburgh C, Mankowski R, Moldawer LL, Moore FA. The persistent inflammation, immunosuppression, and catabolism syndrome 10 years later. J Trauma Acute Care Surg 2023; 95:790-799. [PMID: 37561664 PMCID: PMC10615691 DOI: 10.1097/ta.0000000000004087] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
With the implementation of new intensive care unit (ICU) therapies in the 1970s, multiple organ failure (MOF) emerged as a fulminant inflammatory phenotype leading to early ICU death. Over the ensuing decades, with fundamental advances in care, this syndrome has evolved into a lingering phenotype of chronic critical illness (CCI) leading to indolent late post-hospital discharge death. In 2012, the University of Florida (UF) Sepsis Critical Illness Research Center (SCIRC) coined the term Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) to provide a mechanistic framework to study CCI in surgical patients. This was followed by a decade of research into PICS-CCI in surgical ICU patients in order to define the epidemiology, dysregulated immunity, and long-term outcomes after sepsis. Other focused studies were performed in trauma ICU patients and emergency department sepsis patients. Early deaths were surprisingly low (4%); 63% experienced rapid recovery. Unfortunately, 33% progressed to CCI, of which 79% had a poor post-discharge disposition and 41% were dead within one year. These patients had biomarker evidence of PICS, and these biomarkers enhanced clinical prediction models for dismal one-year outcomes. Emergency myelopoiesis appears to play a central role in the observed persistent immune dysregulation that characterizes PICS-CCI. Older patients were especially vulnerable. Disturbingly, over half of the older CCI patients were dead within one year and older CCI survivors remained severely disabled. Although CCI is less frequent (20%) after major trauma, PICS appears to be a valid concept. This review will specifically detail the epidemiology of CCI, PICS biomarkers, effect of site of infection, acute kidney injury, effect on older patients, dysfunctional high-density lipoproteins, sarcopenia/cachexia, emergency myelopoiesis, dysregulated erythropoiesis, and potential therapeutic interventions. A review of UF SCIRC’s research efforts characterizing CCI, PICS biomarkers, effect of site of infection, acute kidney injury, effects on older patients, dysfunctional high-density lipoproteins, sarcopenia/cachexia, emergency myelopoiesis, and dysregulated erythropoiesis.
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Affiliation(s)
- Philip A Efron
- From the Department of Surgery and Anesthesiology (P.A.E., A.M.M., M.R.), University of Florida, Gainesville, Florida, Department of Surgery (S.C.B.), University of Washington, Seattle, Washington; Department of Surgery (E.L.B., V.E.P., T.J.L., L.L.M., F.A.M.), Department of Physiology and Aging (S.A., C.L., R.M.), Department of Medicine (T.O.-B., A.B.), University of Florida, Gainesville; and Department of Emergency Medicine (F.G.), University of Florida, Jacksonville, Florida
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15
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Barrios EA, Mazer MB, McGonagill P, Bergmann CB, Goodman MD, Gould R, Rao M, Polcz V, Davis R, Del Toro D, Dirain M, Dram A, Hale L, Heidarian M, Kucaba TA, Lanz JP, McCray A, Meszaros S, Miles S, Nelson C, Rocha I, Silva EE, Ungaro R, Walton A, Xu J, Zeumer-Spataro L, Drewry A, Liang M, Bible LE, Loftus T, Turnbull I, Efron PA, Remy KE, Brakenridge S, Badovinac VP, Griffith TS, Moldawer LL, Hotchkiss RS, Caldwell CC. Adverse Long-Term Outcomes and an Immune Suppressed Endotype in Sepsis Patients with Reduced Interferon-γELISpot: A Multicenter, Prospective Observational Study. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.09.13.23295360. [PMID: 37745385 PMCID: PMC10516075 DOI: 10.1101/2023.09.13.23295360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
BACKGROUND Sepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting clinical outcomes and immunological endotyping of septic patients has generally relied on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision. METHODS An ex vivo whole blood enzyme-linked immunosorbent (ELISpot) assay for cellular production of interferon-γ (IFN-γ) was evaluated in 107 septic and 68 non-septic patients from five academic health centers using blood samples collected on days 1, 4 and 7 following ICU admission. RESULTS Compared with 46 healthy subjects, unstimulated and stimulated whole blood IFNγ expression were either increased or unchanged, respectively, in septic and nonseptic ICU patients. However, in septic patients who did not survive 180 days, stimulated whole blood IFNγ expression was significantly reduced on ICU days 1, 4 and 7 (all p<0.05), due to both significant reductions in total number of IFNγ producing cells and amount of IFNγ produced per cell (all p<0.05). Importantly, IFNγ total expression on day 1 and 4 after admission could discriminate 180-day mortality better than absolute lymphocyte count (ALC), IL-6 and procalcitonin. Septic patients with low IFNγ expression were older and had lower ALC and higher sPD-L1 and IL-10 concentrations, consistent with an immune suppressed endotype. CONCLUSIONS A whole blood IFNγ ELISpot assay can both identify septic patients at increased risk of late mortality, and identify immune-suppressed, sepsis patients.
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Best A, Harvey C, Minton C. Experiences of families of prolonged critical illness survivors that are discharged home: An integrative review of the literature. Nurs Crit Care 2023. [DOI: 10.1111/nicc.12886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Amy Best
- School of Nursing Massey University Wellington New Zealand
- Intensive Care Unit Wellington Regional Hospital Wellington New Zealand
| | - Clare Harvey
- School of Nursing Massey University Wellington New Zealand
| | - Claire Minton
- School of Nursing Massey University Palmerston North New Zealand
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Chen X, Chen M, Yang Y, Xu C, Lu H, Xu Y, Li X, Wei Y, Zhu Z, Ding Y, Yu W. LIPOPOLYSACCHARIDE-PRECONDITIONED MESENCHYMAL STEM CELL TRANSPLANTATION ATTENUATES CRITICAL PERSISTENT INFLAMMATION IMMUNE SUPPRESSION AND CATABOLISM SYNDROME IN MICE. Shock 2022; 58:417-425. [PMID: 36155397 DOI: 10.1097/shk.0000000000001993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
ABSTRACT Background: Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is associated with high mortality and high health care costs, and there is currently no effective target treatment. Mesenchymal stem cells (MSCs) possess multipotent immunomodulatory properties. LPS-preconditioned type 1 MSCs (MSC1s) are potentially beneficial for PIICS treatment because of their proinflammatory, anti-infective, and healing properties. Here, we investigated the therapeutic efficacy and mechanisms of action of MSC1s in PIICS. Methods: We previously optimized a reaggravated PIICS mouse model, which was used in this study. PIICS mice were subjected to cecal ligation and puncture on day 1 and LPS injection on day 11. Subsequently, the mice were treated with or without MSC1s. Animal survival and phenotypes, along with the levels of catabolism, inflammation, and immunosuppression, were evaluated. MSC1s were cocultured with CD8 + T cells in vitro , and inflammatory cytokine levels and CD8 + T-cell function were assessed. Results: MSC1 transplantation alleviated weight loss and muscle wasting, inhibited catabolism and inflammation, and considerably improved the proportion and function of CD8 + T cells in the PIICS mice. After coculture with MSC1s, the expression levels of CD107a and interferon γ increased, whereas the expression level of programmed death 1 decreased significantly in CD8 + T cells. MSC1s also promoted proinflammatory cytokine secretion and reduced the concentration of soluble PD-L1 in vitro . Conclusions: MSC1s can protect mice against critical PIICS, partly by enhancing CD8 + T-cell function. Therefore, MSC1 transplantation is a novel therapeutic candidate for PIICS.
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Affiliation(s)
- Xiancheng Chen
- Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Ming Chen
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Yang Yang
- Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Can Xu
- Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Huimin Lu
- Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Yali Xu
- Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Xiaojing Li
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yu Wei
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhanghua Zhu
- Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Yitao Ding
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Wenkui Yu
- Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
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Yamashita T, Street JM, Halasa BC, Naito Y, Tsuji T, Tsuji N, Hayase N, Yuen PST, Star RA. The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis. PLoS One 2022; 17:e0271667. [PMID: 35951593 PMCID: PMC9371331 DOI: 10.1371/journal.pone.0271667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 07/06/2022] [Indexed: 11/19/2022] Open
Abstract
Sepsis, a life-threatening organ dysfunction, results from dysregulated host responses to infection and still has a high incidence and mortality. Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established. We evaluated the effect of continuous intravenous norepinephrine infusion in a septic cecal ligation and puncture (CLP) mouse model, evaluating systemic hemodynamics and body temperature post-hoc. CLP surgery significantly decreased mean arterial blood pressure (MAP), heart rate, and body temperature within six hours. Continuous norepinephrine infusion (NE+, n = 12) started at the time of CLP surgery significantly increased MAP at 24 and 30 hours and heart rate at 6, 18, 24, and 30 hours after CLP vs CLP alone (NE-, n = 12). However, addition of norepinephrine did not improve survival rate (NE+ n = 34, NE- n = 31). Early (6 hours or earlier, when the animal became visibly sick) MAP did not predict 7-day mortality. However, heart rates at 3 and at 6 hours after CLP/norepinephrine (NE+) were highly predictive of mortality, as also been found in one clinical study. We conclude that limited hemodynamic support can be provided in a mouse sepsis model. We propose that heart rate can be used to stratify severity of illness in rodent preclinical studies of sepsis therapeutics.
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Affiliation(s)
- Tetsushi Yamashita
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Jonathan M. Street
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Brianna C. Halasa
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Yoshitaka Naito
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Takayuki Tsuji
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Naoko Tsuji
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Naoki Hayase
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Peter S. T. Yuen
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
- * E-mail:
| | - Robert A. Star
- Renal Diagnostics and Therapeutics Unit, NIDDK, NIH, Bethesda, Maryland, United States of America
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Wu YC, Wong LT, Wu CL, Chao WC. The association between culture positivity and long-term mortality in critically ill surgical patients. J Intensive Care 2021; 9:66. [PMID: 34702345 PMCID: PMC8546784 DOI: 10.1186/s40560-021-00576-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 09/19/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The long-term outcome is an essential issue in critically ill patients, and the identification of early determinant is needed for risk stratification of the long-term outcome. In the present study, we investigate the association between culture positivity during admission and long-term outcome in critically ill surgical patients. METHODS We linked the 2015-2019 critical care database at Taichung Veterans General Hospital with the nationwide death registration files in Taiwan. We described the long-term mortality and proportion of culture positivity among enrolled subjects. We used a log-rank test to estimate survival curves between patients with and without positive cultures and a multivariable Cox proportional hazards regression model to determine hazard ratio (HR) and 95% confidence interval (CI). RESULTS A total of 6748 critically ill patients were enrolled, and 32.5% (2196/6749) of them died during the follow-up period, with the overall follow-up duration was 1.8 ± 1.4 years. We found that 31.4% (2122/6748) of critically ill patients had at least one positive culture during the index admission, and the number of patients with positive culture in the blood, respiratory tract, urinary tract, skin and soft tissue and abdomen were 417, 1702, 554, 194 and 139, respectively. We found that a positive culture from any sites was independently associated with high long-term mortality (aHR 1.579, 95% CI 1.422-1.754) after adjusting relevant covariates, including age, sex, body-mass index, comorbidities, severity score, shock, early fluid overload, receiving mechanical ventilation and the need of renal replacement therapy for critical illness. CONCLUSIONS We linked two databases to identify that a positive culture during admission was independently correlated with increased long-term mortality in critically ill surgical patients. Our findings highlight the need for vigilance among patients with a positive culture during admission, and more studies are warranted to validate our findings and to clarify underlying mechanisms.
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Affiliation(s)
- Yu-Cheng Wu
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Li-Ting Wong
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chieh-Liang Wu
- Department of Critical Care Medicine, Taichung Veterans General Hospital, No, 1650, Section 4, Taiwan Boulevard, Xitun District, 40705, Taichung, Taiwan.,Department of Computer Science, Tunghai University, Taichung, Taiwan.,Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan.,Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan
| | - Wen-Cheng Chao
- Department of Critical Care Medicine, Taichung Veterans General Hospital, No, 1650, Section 4, Taiwan Boulevard, Xitun District, 40705, Taichung, Taiwan. .,Department of Computer Science, Tunghai University, Taichung, Taiwan. .,Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan. .,Artificial Intelligence Studio, Taichung Veterans General Hospital, Taichung, Taiwan.
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20
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Sartelli M, Coccolini F, Kluger Y, Agastra E, Abu-Zidan FM, Abbas AES, Ansaloni L, Adesunkanmi AK, Atanasov B, Augustin G, Bala M, Baraket O, Baral S, Biffl WL, Boermeester MA, Ceresoli M, Cerutti E, Chiara O, Cicuttin E, Chiarugi M, Coimbra R, Colak E, Corsi D, Cortese F, Cui Y, Damaskos D, de’ Angelis N, Delibegovic S, Demetrashvili Z, De Simone B, de Jonge SW, Dhingra S, Di Bella S, Di Marzo F, Di Saverio S, Dogjani A, Duane TM, Enani MA, Fugazzola P, Galante JM, Gachabayov M, Ghnnam W, Gkiokas G, Gomes CA, Griffiths EA, Hardcastle TC, Hecker A, Herzog T, Kabir SMU, Karamarkovic A, Khokha V, Kim PK, Kim JI, Kirkpatrick AW, Kong V, Koshy RM, Kryvoruchko IA, Inaba K, Isik A, Iskandar K, Ivatury R, Labricciosa FM, Lee YY, Leppäniemi A, Litvin A, Luppi D, Machain GM, Maier RV, Marinis A, Marmorale C, Marwah S, Mesina C, Moore EE, Moore FA, Negoi I, Olaoye I, Ordoñez CA, Ouadii M, Peitzman AB, Perrone G, Pikoulis M, Pintar T, Pipitone G, Podda M, Raşa K, Ribeiro J, Rodrigues G, Rubio-Perez I, Sall I, Sato N, Sawyer RG, Segovia Lohse H, Sganga G, Shelat VG, Stephens I, Sugrue M, Tarasconi A, Tochie JN, Tolonen M, Tomadze G, et alSartelli M, Coccolini F, Kluger Y, Agastra E, Abu-Zidan FM, Abbas AES, Ansaloni L, Adesunkanmi AK, Atanasov B, Augustin G, Bala M, Baraket O, Baral S, Biffl WL, Boermeester MA, Ceresoli M, Cerutti E, Chiara O, Cicuttin E, Chiarugi M, Coimbra R, Colak E, Corsi D, Cortese F, Cui Y, Damaskos D, de’ Angelis N, Delibegovic S, Demetrashvili Z, De Simone B, de Jonge SW, Dhingra S, Di Bella S, Di Marzo F, Di Saverio S, Dogjani A, Duane TM, Enani MA, Fugazzola P, Galante JM, Gachabayov M, Ghnnam W, Gkiokas G, Gomes CA, Griffiths EA, Hardcastle TC, Hecker A, Herzog T, Kabir SMU, Karamarkovic A, Khokha V, Kim PK, Kim JI, Kirkpatrick AW, Kong V, Koshy RM, Kryvoruchko IA, Inaba K, Isik A, Iskandar K, Ivatury R, Labricciosa FM, Lee YY, Leppäniemi A, Litvin A, Luppi D, Machain GM, Maier RV, Marinis A, Marmorale C, Marwah S, Mesina C, Moore EE, Moore FA, Negoi I, Olaoye I, Ordoñez CA, Ouadii M, Peitzman AB, Perrone G, Pikoulis M, Pintar T, Pipitone G, Podda M, Raşa K, Ribeiro J, Rodrigues G, Rubio-Perez I, Sall I, Sato N, Sawyer RG, Segovia Lohse H, Sganga G, Shelat VG, Stephens I, Sugrue M, Tarasconi A, Tochie JN, Tolonen M, Tomadze G, Ulrych J, Vereczkei A, Viaggi B, Gurioli C, Casella C, Pagani L, Baiocchi GL, Catena F. WSES/GAIS/SIS-E/WSIS/AAST global clinical pathways for patients with intra-abdominal infections. World J Emerg Surg 2021; 16:49. [PMID: 34563232 PMCID: PMC8467193 DOI: 10.1186/s13017-021-00387-8] [Show More Authors] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 08/05/2021] [Indexed: 02/08/2023] Open
Abstract
Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.
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Affiliation(s)
- Massimo Sartelli
- Department of Surgery Department of Surgery, Macerata Hospital, Macerata, Italy
| | - 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
| | - Ervis Agastra
- General Surgery Department, Regional Hospital of Durres, Durres, Albania
| | - Fikri M. Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates
| | - Ashraf El Sayed Abbas
- Department of General and Emergency Surgery Faculty of Medicine, Mansoura University Hospital, Mansoura, Egypt
| | - Luca Ansaloni
- Department of Surgery, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Abdulrashid Kayode Adesunkanmi
- Department of Surgery, Faculty of Clinical Sciences, College of Health Sciences, Obafemi Awolowo University, Osun State, Ile-Ife, Nigeria
| | - Boyko Atanasov
- Department of General Surgery, Medical University of Plovdiv, UMHAT Eurohospital, Plovdiv, Bulgaria
| | - Goran Augustin
- Department of Surgery, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Miklosh Bala
- Trauma and Acute Care Surgery Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Oussama Baraket
- Department of general surgery Bizerte hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Suman Baral
- Department of Surgery, Lumbini Medical College and Teaching Hospital Ltd., Palpa, Tansen, Nepal
| | - Walter L. Biffl
- Division of Trauma/Acute Care Surgery, Scripps Clinic Medical Group, La Jolla, CA USA
| | - Marja A. Boermeester
- Department of Surgery, Amsterdam University Medical Centers, location AMC, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, The Netherlands
| | - Marco Ceresoli
- Emergency and General Surgery Department, University of Milan-Bicocca, Milan, Italy
| | - Elisabetta Cerutti
- Anesthesia and Transplant Surgical Intensive Care Unit, Ospedali Riuniti, Ancona, Italy
| | - Osvaldo Chiara
- Emergency Department, Niguarda Ca’Granda Hospital, Milan, Italy
| | - Enrico Cicuttin
- Department of General, Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy
| | - Massimo Chiarugi
- Department of General, Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy
| | - Raul Coimbra
- Riverside University Health System, CECORC Research Center, Loma Linda University, Loma Linda, USA
| | - Elif Colak
- Department of General Surgery, Health Sciences University, Samsun Training and Research Hospital, Samsun, Turkey
| | - Daniela Corsi
- General Direction, Area Vasta 3, ASUR Marche, Macerata, Italy
| | | | - Yunfeng Cui
- Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China
| | | | - Nicola de’ Angelis
- Minimally Invasive and Robotic Digestive Surgery Unit, Regional General Hospital F. Miulli, Bari, Italy
- Université Paris Est, UPEC, Creteil, France
| | - Samir Delibegovic
- Department of Surgery, University Clinical Center of Tuzla, Tuzla, Bosnia and Herzegovina
| | - Zaza Demetrashvili
- Department General Surgery, Kipshidze Central University Hospital, Tbilisi, Georgia
| | - Belinda De Simone
- Department of general, Digestive and Metabolic Minimally Invasive Surgery, Centre Hospitalier Intercommunal De Poissy/St Germain en Laye, Poissy, France
| | - Stijn W. de Jonge
- Division of Trauma/Acute Care Surgery, Scripps Clinic Medical Group, La Jolla, CA USA
| | - Sameer Dhingra
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar India
| | - Stefano Di Bella
- Clinical Department of Medical, Surgical and Health sciences, Trieste University, Trieste, Italy
| | | | - Salomone Di Saverio
- Department of General Surgery, University of Insubria, University Hospital of Varese, ASST Sette Laghi, Regione Lombardia, Varese, Italy
| | - Agron Dogjani
- Department of Surgery, University Hospital of Trauma, Tirana, Albania
| | - Therese M. Duane
- Department of Surgery, Texas Health Resources, Fort Worth, TX USA
| | - Mushira Abdulaziz Enani
- Department of Medicine, Infectious Disease Division, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Paola Fugazzola
- Department of Surgery, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Joseph M. Galante
- Division of Trauma and Acute Care Surgery, Department of Surgery, University of California Davis, Sacramento, CA USA
| | - Mahir Gachabayov
- Department of Abdominal Surgery, Vladimir City Clinical Hospital of Emergency Medicine, Vladimir, Russia
| | - Wagih Ghnnam
- Department of General Surgery, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - George Gkiokas
- Second Department of Surgery, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Carlos Augusto Gomes
- Department of Surgery, Hospital Universitário Terezinha de Jesus, Faculdade de Ciências Médicas e da Saúde de Juiz de Fora, Juiz de Fora, Brazil
| | - Ewen A. Griffiths
- Department of Upper GI Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Timothy C. Hardcastle
- Trauma Service, Inkosi Albert Luthuli Central Hospital and Department of Surgery, Nelson R Mandela School of Clinical Medicine, Durban, South Africa
| | - Andreas Hecker
- Department of General and Thoracic Surgery, University Hospital Giessen, Giessen, Germany
| | - Torsten Herzog
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Syed Mohammad Umar Kabir
- Donegal Clinical Research Academy Emergency Surgery Outcome Project, Letterkenny University Hospital, Donegal, Ireland
| | - Aleksandar Karamarkovic
- Surgical Clinic “Nikola Spasic”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Khokha
- Department of Emergency Surgery, City Hospital, Mozyr, Belarus
| | - Peter K. Kim
- Department of Surgery, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Jae Il Kim
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Andrew W. Kirkpatrick
- General, Acute Care, Abdominal Wall Reconstruction, and Trauma Surgery, Foothills Medical Centre, Calgary, AB Canada
| | - Victor Kong
- Department of Surgery, Edendale Hospital, Pietermaritzburg, South Africa
| | - Renol M. Koshy
- Department of General Surgery, University Hospital of Coventry & Warwickshire, Coventry, UK
| | | | - Kenji Inaba
- Division of Trauma and Surgical Critical Care, Department of Surgery, University of Southern California, Los Angeles, CA USA
| | - Arda Isik
- Department of General Surgery, School of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Katia Iskandar
- Department of Pharmacy, Lebanese International University, Beirut, Lebanon
| | - Rao Ivatury
- Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA USA
| | | | - Yeong Yeh Lee
- School of Medical Sciences, Universitiy Sains Malaysia, Kota Bharu, Kelantan Malaysia
| | - Ari Leppäniemi
- Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Andrey Litvin
- Department of Surgical Disciplines, Immanuel Kant Baltic Federal University, Regional Clinical Hospital, Kaliningrad, Russia
| | - Davide Luppi
- Department of General and Emergency Surgery, ASMN, Reggio Emilia, Italy
| | - Gustavo M. Machain
- Department of Surgery, Universidad Nacional de Asuncion, Asuncion, Paraguay
| | - Ronald V. Maier
- Department of Surgery, University of Washington, Seattle, WA USA
| | | | - Cristina Marmorale
- Department of Surgery, Università Politecnica delle Marche, Ancona, Italy
| | - Sanjay Marwah
- Department of Surgery, Post-Graduate Institute of Medical Sciences, Rohtak, India
| | - Cristian Mesina
- Second Surgical Clinic, Emergency Hospital of Craiova, Craiova, Romania
| | - Ernest E. Moore
- Ernest E Moore Shock Trauma Center at Denver Health, Denver, USA
| | - Frederick A. Moore
- Department of Surgery, Division of Acute Care Surgery, and Center for Sepsis and Critical Illness Research, University of Florida College of Medicine, Gainesville, FL USA
| | - Ionut Negoi
- Department of Surgery, Emergency Hospital of Bucharest, Bucharest, Romania
| | - Iyiade Olaoye
- Department of Surgery, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - Carlos A. Ordoñez
- Division of Trauma and Acute Care Surgery, Fundacion Valle del Lili, Cali, Colombia
- Department of Surgery, Universidad del Valle, Cali, Colombia
| | - Mouaqit Ouadii
- Department of Surgery, Hassan II University Hospital, Medical School of Fez, Sidi Mohamed Benabdellah University, Fez, Morocco
| | - Andrew B. Peitzman
- Department of Surgery, University of Pittsburgh School of Medicine, UPMC-Presbyterian, Pittsburgh, USA
| | - Gennaro Perrone
- Department of Emergency Surgery, Parma Maggiore Hospital, Parma, Italy
| | - Manos Pikoulis
- 3rd Department of Surgery, Attiko Hospital, MSc “Global Health-Disaster Medicine”, National and Kapodistrian University of Athens (NKUA), Athens, Greece
| | - Tadeja Pintar
- Department of Surgery, UMC Ljubljana, Ljubljana, Slovenia
| | - Giuseppe Pipitone
- National Institute for Infectious Diseases - INMI - Lazzaro Spallanzani IRCCS, Rome, Italy
| | - Mauro Podda
- Department of General and Emergency Surgery, Cagliari University Hospital, Cagliari, Italy
| | - Kemal Raşa
- Department of Surgery, Anadolu Medical Center, Kocaeli, Turkey
| | | | - Gabriel Rodrigues
- Department of General Surgery, Kasturba Medical College & Hospital, Manipal Academy of Higher Education, Manipal, India
| | - Ines Rubio-Perez
- General Surgery Department, Colorectal Surgery Unit, La Paz University Hospital, Madrid, Spain
| | - Ibrahima Sall
- General Surgery Department, Military Teaching Hospital, Dakar, Senegal
| | - Norio Sato
- Department of Aeromedical Services for Emergency and Trauma Care, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Robert G. Sawyer
- Department of Surgery, Western Michigan University School of Medicine, Kalamazoo, MI USA
| | | | - Gabriele Sganga
- Department of Medical and Surgical Sciences, Emergency Surgery & Trauma, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Vishal G. Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Ian Stephens
- Donegal Clinical Research Academy Emergency Surgery Outcome Project, Letterkenny University Hospital, Donegal, Ireland
| | - Michael Sugrue
- Donegal Clinical Research Academy Emergency Surgery Outcome Project, Letterkenny University Hospital, Donegal, Ireland
| | - Antonio Tarasconi
- Department of Emergency Surgery, Parma Maggiore Hospital, Parma, Italy
| | - Joel Noutakdie Tochie
- Department of Emergency medicine, Anesthesiology and critical care, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Matti Tolonen
- Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Gia Tomadze
- Surgery Department, Tbilisi State Medical University, Tbilisi, Georgia
| | - Jan Ulrych
- First Department of Surgery, Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Andras Vereczkei
- Department of Surgery, Clinical Center University of Pecs, Pecs, Hungary
| | - Bruno Viaggi
- Department of Anesthesiology, Neuro Intensive Care Unit, Florence Careggi University Hospital, Florence, Italy
| | - Chiara Gurioli
- Department of Surgery, Camerino Hospital, Macerata, Italy
| | - Claudio Casella
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Leonardo Pagani
- Department of Infectious Diseases, Bolzano Hospital, Bolzano, Italy
| | - Gian Luca Baiocchi
- Department of Surgery, AAST Cremona, Cremona, Italy
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Fausto Catena
- Department of Emergency Surgery, Parma Maggiore Hospital, Parma, Italy
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21
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Darden DB, Dong X, Brusko MA, Kelly L, Fenner B, Rincon JC, Dirain ML, Ungaro R, Nacionales DC, Gauthier M, Kladde M, Brusko TM, Bihorac A, Moore FA, Loftus T, Bacher R, Moldawer LL, Mohr AM, Efron PA. A Novel Single Cell RNA-seq Analysis of Non-Myeloid Circulating Cells in Late Sepsis. Front Immunol 2021; 12:696536. [PMID: 34484194 PMCID: PMC8415415 DOI: 10.3389/fimmu.2021.696536] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/30/2021] [Indexed: 12/11/2022] Open
Abstract
Background With the successful implementation of the Surviving Sepsis Campaign guidelines, post-sepsis in-hospital mortality to sepsis continues to decrease. Those who acutely survive surgical sepsis will either rapidly recover or develop a chronic critical illness (CCI). CCI is associated with adverse long-term outcomes and 1-year mortality. Although the pathobiology of CCI remains undefined, emerging evidence suggests a post-sepsis state of pathologic myeloid activation, inducing suboptimal lymphopoiesis and erythropoiesis, as well as downstream leukocyte dysfunction. Our goal was to use single-cell RNA sequencing (scRNA-seq) to perform a detailed transcriptomic analysis of lymphoid-derived leukocytes to better understand the pathology of late sepsis. Methods A mixture of whole blood myeloid-enriched and Ficoll-enriched peripheral blood mononuclear cells from four late septic patients (post-sepsis day 14-21) and five healthy subjects underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq). Results We identified unique transcriptomic patterns for multiple circulating immune cell subtypes, including B- and CD4+, CD8+, activated CD4+ and activated CD8+ T-lymphocytes, as well as natural killer (NK), NKT, and plasmacytoid dendritic cells in late sepsis patients. Analysis demonstrated that the circulating lymphoid cells maintained a transcriptome reflecting immunosuppression and low-grade inflammation. We also identified transcriptomic differences between patients with bacterial versus fungal sepsis, such as greater expression of cytotoxic genes among CD8+ T-lymphocytes in late bacterial sepsis. Conclusion Circulating non-myeloid cells display a unique transcriptomic pattern late after sepsis. Non-myeloid leukocytes in particular reveal a host endotype of inflammation, immunosuppression, and dysfunction, suggesting a role for precision medicine-guided immunomodulatory therapy.
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Affiliation(s)
- Dijoia B Darden
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Xiaoru Dong
- Department of Biomedical Engineering, University of Florida College of Medicine, Gainesville, FL, United States
| | - Maigan A Brusko
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States
| | - Lauren Kelly
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Brittany Fenner
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Jaimar C Rincon
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Marvin L Dirain
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Ricardo Ungaro
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Dina C Nacionales
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Marie Gauthier
- Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, United States
| | - Michael Kladde
- Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, United States
| | - Todd M Brusko
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States
| | - Azra Bihorac
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL, United States
| | - Frederick A Moore
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Tyler Loftus
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Rhonda Bacher
- Department of Biostatistics, University of Florida, Gainesville, FL, United States
| | - Lyle L Moldawer
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Alicia M Mohr
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
| | - Philip A Efron
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
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22
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Brakenridge SC, Wilfret DA, Maislin G, Andrade KE, Walker V, May AK, Dankner WM, Bulger EM. Resolution of organ dysfunction as a predictor of long-term survival in necrotizing soft tissue infections: Analysis of the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections trial and a retrospective claims database-linked chart study. J Trauma Acute Care Surg 2021; 91:384-392. [PMID: 33797490 DOI: 10.1097/ta.0000000000003183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction. METHODS We performed a combined analysis of NSTI patients from the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections randomized-controlled interventional trial (ATB-202) and comprehensive administrative database (ATB-204) to determine the association of persistent organ dysfunction on inpatient and long-term outcomes. Persistent organ dysfunction was defined as a modified Sequential Organ Failure Assessment (mSOFA) score of 2 or greater at Day 14 (D14) after NSTI diagnosis, and resolution of organ dysfunction defined as mSOFA score of 1 or less. RESULTS The analysis included 506 hospitalized NSTI patients requiring surgical debridement, including 247 from ATB-202, and 259 from ATB-204. In both study cohorts, age and comorbidity burden were higher in the D14 mSOFA ≥2 group. Patients with D14 mSOFA score of 1 or less had significantly lower 90-day mortality than those with mSOFA score of 2 or higher in both ATB-202 (2.4% vs. 21.5%; p < 0.001) and ATB-204 (6% vs. 16%: p = 0.008) studies. In addition, in an adjusted covariate analysis of the combined study data sets D14 mSOFA score of 1 or lesss was an independent predictor of lower 90-day mortality (odds ratio, 0.26; 95% confidence interval, 0.13-0.53; p = 0.001). In both studies, D14 mSOFA score of 1 or less was associated with more favorable discharge status and decreased resource utilization. CONCLUSION For patients with NSTI undergoing surgical management, persistent organ dysfunction at 14 days, strongly predicts higher resource utilization, poor discharge disposition, and higher long-term mortality. Promoting the resolution of acute organ dysfunction after NSTI should be considered as a target for investigational therapies to improve long-term outcomes after NSTI. LEVEL OF EVIDENCE Prognostic/epidemiology study, level III.
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Affiliation(s)
- Scott C Brakenridge
- From the Department of Surgery (S.C.B.), University of Florida College of Medicine, Gainesville, Florida; Atox Bio, Ltd (D.A.W., W.M.D.), Durham, North Carolina; Biomedical Statistical Consulting (G.M.), Wynnewood, Pennsylvania; Health Economics and Outcomes Research, Optum (K.E.A., V.W.), Eden Prairie, Minnesota; Division of Acute Care Surgery (A.K.M.), Atrium Health, Charlotte, North Carolina; Department of Surgery (E.M.B.) University of Washington, Harborview Medical Center, Seattle, Washington
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23
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Pravda J. Sepsis: Evidence-based pathogenesis and treatment. World J Crit Care Med 2021; 10:66-80. [PMID: 34316443 PMCID: PMC8291008 DOI: 10.5492/wjccm.v10.i4.66] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/13/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common factor underlying sepsis is the characteristic hypermetabolic response as the body ramps up every physiological system in its fight against the underlying critical illness. A hypermetabolic response requires supraphysiological amounts of energy, which is mostly supplied via oxidative phosphorylation generated ATP. A by-product of oxidative phosphorylation is hydrogen peroxide (H2O2), a toxic, membrane-permeable oxidizing agent that is produced in far greater amounts during a hypermetabolic state. Continued production of mitochondrial H2O2 can overwhelm cellular reductive (antioxidant) capacity leading to a build-up within cells and eventual diffusion into the bloodstream. H2O2 is a metabolic poison that can inhibit enzyme systems leading to organ failure, microangiopathic dysfunction, and irreversible septic shock. The toxic effects of H2O2 mirror the clinical and laboratory abnormalities observed in sepsis, and toxic levels of blood H2O2 have been reported in patients with septic shock. This review provides evidence to support a causal role for H2O2 in the pathogenesis of sepsis, and an evidence-based therapeutic intervention to reduce H2O2 levels in the body and restore redox homeostasis, which is necessary for normal organ function and vascular responsiveness.
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Affiliation(s)
- Jay Pravda
- Inflammatory Disease Research Centre, Therashock LLC, Palm Beach Gardens, FL 33410, United States
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24
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Darden DB, Kelly LS, Fenner BP, Moldawer LL, Mohr AM, Efron PA. Dysregulated Immunity and Immunotherapy after Sepsis. J Clin Med 2021; 10:jcm10081742. [PMID: 33920518 PMCID: PMC8073536 DOI: 10.3390/jcm10081742] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/08/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many patients will not rapidly recover, but instead will go on to develop chronic critical illness (CCI) and experience dismal long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets for immunomodulatory therapy.
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25
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Efron PA, Darden DB, Wang Z, Nacionales DC, Lopez MC, Hawkins RB, Cox MC, Rincon JC, Ungaro R, Dirain ML, Ghita GL, Chen T, Billiar TR, Delano MJ, Leeuwenburgh C, Bihorac A, Brakenridge SC, Moore FA, Mohr AM, Tompkins RG, Brumback BA, Baker HV, Upchurch GR, Moldawer LL. Transcriptomic responses from improved murine sepsis models can better mimic human surgical sepsis. FASEB J 2020; 35:e21156. [PMID: 33140449 DOI: 10.1096/fj.202002150r] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/16/2020] [Accepted: 10/19/2020] [Indexed: 12/24/2022]
Abstract
Historically, murine models of inflammation in biomedical research have been shown to minimally correlate with genomic expression patterns from blood leukocytes in humans. In 2019, our laboratory reported an improved surgical sepsis model of cecal ligation and puncture (CLP) that provides additional daily chronic stress (DCS), as well as adhering to the Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) guidelines. This model phenotypically recapitulates the persistent inflammation, immunosuppression, and catabolism syndrome observed in adult human surgical sepsis survivors. Whether these phenotypic similarities between septic humans and mice are replicated at the circulating blood leukocyte transcriptome has not been demonstrated. Our analysis, in contrast with previous findings, demonstrated that genome-wide expression in our new murine model more closely approximated human surgical sepsis patients, particularly in the more chronic phases of sepsis. Importantly, our new model of murine surgical sepsis with chronic stress did not reflect well gene expression patterns from humans with community-acquired sepsis. Our work indicates that improved preclinical murine sepsis modeling can better replicate both the phenotypic and transcriptomic responses to surgical sepsis, but cannot be extrapolated to other sepsis etiologies. Importantly, these improved models can be a useful adjunct to human-focused and artificial intelligence-based forms of research in order to improve septic patients' morbidity and mortality.
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Affiliation(s)
- Philip A Efron
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Dijoia B Darden
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Zhongkai Wang
- Department of Biostatistics, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Dina C Nacionales
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Maria-Cecilia Lopez
- Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Russell B Hawkins
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Michael C Cox
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Jaimar C Rincon
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Ricardo Ungaro
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Marvin L Dirain
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Gabriela L Ghita
- Department of Biostatistics, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Tianmeng Chen
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Timothy R Billiar
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Matthew J Delano
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Christiaan Leeuwenburgh
- Department of Aging and Geriatric Research, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Azra Bihorac
- Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Scott C Brakenridge
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Frederick A Moore
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Alicia M Mohr
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Ronald G Tompkins
- Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
| | - Babette A Brumback
- Department of Biostatistics, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Henry V Baker
- Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Gilbert R Upchurch
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Lyle L Moldawer
- Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA
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