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Sontam T, Deutz NEP, Cruthirds CL, Mbilinyi R, Ruebush LE, Ten Have GA, Thaden JJ, Engelen MPKJ. Prolonged disturbances in citrulline metabolism following resistance exercise in COPD. Clin Nutr 2025; 49:21-32. [PMID: 40233541 DOI: 10.1016/j.clnu.2025.03.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/21/2025] [Accepted: 03/28/2025] [Indexed: 04/17/2025]
Abstract
BACKGROUND & AIMS Disturbances in arginine (ARG) and protein metabolism, as well as in gut function have been observed in response to an endurance exercise session in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied whether resistance exercise also affects the acute response in arginine (role in nitric oxide synthesis), citrulline (CIT, marker of gut health), and (muscle) protein metabolism differently in COPD as compared to healthy older adults. METHODS Patients with stable moderate to severe COPD (n = 24) and healthy controls (n = 25) completed a high-intensity resistance exercise session in the postabsorptive state. We administered a pulse of multiple stable isotopes of amino acids before, and 1 h and 24 h post-resistance exercise to assess the whole body production (WBP) and intracellular productions by compartmental analysis of ARG and CIT, and of tau-methylhistidine (TauMETHIS), phenylalanine (PHE), tyrosine (TYR), and PHE > TYR conversion as markers of muscle (myofibrillar) protein breakdown and whole body (net) protein breakdown, respectively. Muscle fatigue was determined by assessing the decay in peak leg extension torque post-resistance exercise. RESULTS COPD patients overall exhibited lower WBP ARG (p < 0.0001), CIT (p < 0.0001), PHE (p = 0.0001), TYR (p < 0.0001), and tau-METHIS (p = 0.0004) compared to controls. Resistance exercise did not change WBP of PHE, tau-METHIS, or PHE > TYR conversion, despite prolonged muscle fatigue in COPD. WBP CIT was increased at 1- and 24-h post-exercise in both groups (p < 0.003). Plasma CIT concentrations were reduced in both groups (p < 0.006) and remained lower at 24 h post-exercise in COPD only (p < 0.05) despite a third less work performed. CONCLUSIONS Both COPD and healthy participants exhibited upregulated whole-body citrulline production following resistance exercise. However, in COPD, this increase was insufficient to counteract the sustained reduction in plasma citrulline concentration, despite performing significantly less work during the exercise session. This prolonged disturbance in citrulline metabolism in COPD points to a potential exercise-induced enterocyte dysfunction, highlighting a novel area for understanding the impact of resistance exercise on gut health in this population. CLINICAL TRIAL REGISTRY Trial registration ClinicalTrials.gov: NCT02780219.
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Affiliation(s)
- Tarun Sontam
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA; Department of Medical Education, Texas A&M School of Medicine, College Station, TX, USA
| | - Nicolaas E P Deutz
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA; Department of Primary Care & Rural Medicine, Texas A&M School of Medicine, College Station, TX, USA
| | - Clayton L Cruthirds
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA
| | - Robert Mbilinyi
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA; Department of Medical Education, Texas A&M School of Medicine, College Station, TX, USA
| | - Laura E Ruebush
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA
| | - Gabriella Am Ten Have
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA
| | - John J Thaden
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA
| | - Mariёlle P K J Engelen
- Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA; Department of Primary Care & Rural Medicine, Texas A&M School of Medicine, College Station, TX, USA.
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Kanda T, Kawachi Y, Kitami C, Funaoka H, Iwafuchi Y. Longitudinal analysis of serum intestinal fatty acid-binding protein in a patient with non-occlusive mesenteric ischemia following brachial plexus block-induced hypotension: a case study. Clin J Gastroenterol 2025; 18:282-287. [PMID: 39673026 DOI: 10.1007/s12328-024-02081-z] [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: 10/04/2024] [Accepted: 12/02/2024] [Indexed: 12/15/2024]
Abstract
Intestinal fatty acid-binding protein (I-FABP) is a promising biomarker for small-bowel ischemia including non-occlusive mesenteric ischemia (NOMI). A 75-year-old woman with diabetic nephropathy sustained a distal radius fracture. Two days later, she underwent a brachial plexus block to facilitate orthopedic surgery, which resulted in hypotension. Despite prompt fluid resuscitation and ephedrine administration, the patient developed abdominal pain. Contrast-enhanced computed tomography revealed hepatic portal venous gas, but no direct evidence of small-bowel ischemia. The gastrointestinal surgery team opted for cautious in-hospital observation overnight. Unfortunately, the patient's condition significantly worsened the following day, prompting an urgent laparotomy. Surgery confirmed ileal segment necrosis, macroscopically characterized by a distinctive geographic pattern. Retrospective analysis of stored serum samples using a human enzyme-linked immunosorbent assay demonstrated that I-FABP levels were moderately elevated (7.2 ng/mL) at the initial outpatient visit for the fracture, peaked (17.9 ng/mL) at the clinical onset of NOMI, and returned to normal (0.7 ng/mL) by postoperative day 2. Serum I-FABP levels correlated with the progression of NOMI, showing potential as an early detection marker. However, the longitudinal analysis of serum I-FABP also highlighted significant challenges of this biomarker, including the influence of renal function and the importance of sampling timing.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology, Southern TOHOKU General Hospital, 7-115 Yatsuyamada, Koriyama, Fukushima, 963-8563, Japan.
| | - Yasuyuki Kawachi
- Department of Surgery, Nagaoka Chuo General Hospital, Nagaoka, Niigata, 940-8653, Japan
| | - Chie Kitami
- Department of Surgery, Nagaoka Chuo General Hospital, Nagaoka, Niigata, 940-8653, Japan
| | | | - Yoichi Iwafuchi
- Department of Nephrology, Saiseikai Niigata Kenoh Kikan Hospital, Sanjo, Niigata, 955-0091, Japan
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Soranno DE, Coopersmith CM, Brinkworth JF, Factora FNF, Muntean JH, Mythen MG, Raphael J, Shaw AD, Vachharajani V, Messer JS. A review of gut failure as a cause and consequence of critical illness. Crit Care 2025; 29:91. [PMID: 40011975 PMCID: PMC11866815 DOI: 10.1186/s13054-025-05309-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 02/05/2025] [Indexed: 02/28/2025] Open
Abstract
In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of gastrointestinal dysfunction drive and then perpetuate multi-organ dysfunction syndrome. Despite the clear importance of maintaining gut homeostasis, there are very few reliable measures of gut function in critical illness. Further, while multiple therapeutic strategies have been proposed, most have not been shown to conclusively demonstrate benefit, and care is still largely supportive. The key role of the gut in critical illness was the subject of the tenth Perioperative Quality Initiative meeting, a conference to summarize the current state of the literature and identify key knowledge gaps for future study. This review is the product of that conference.
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Affiliation(s)
- Danielle E Soranno
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Craig M Coopersmith
- Department of Surgery and Emory Critical Care Center, Emory University, Atlanta, GA, USA
| | - Jessica F Brinkworth
- Department of Anthropology, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - Faith N F Factora
- Intensive Care and Resuscitation, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Julia H Muntean
- Intensive Care and Resuscitation, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Monty G Mythen
- Perioperative Medicine, University College London, London, England
| | - Jacob Raphael
- Anesthesiology and Perioperative Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Andrew D Shaw
- Intensive Care and Resuscitation, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Vidula Vachharajani
- Department of Pulmonary and Critical Care, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Jeannette S Messer
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
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Galusko V, Wenzl FA, Vandenbriele C, Panoulas V, Lüscher TF, Gorog DA. Current and novel biomarkers in cardiogenic shock. Eur J Heart Fail 2025. [PMID: 39822053 DOI: 10.1002/ejhf.3531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 10/11/2024] [Accepted: 10/29/2024] [Indexed: 01/19/2025] Open
Abstract
Cardiogenic shock (CS) carries a 30-50% in-hospital mortality rate, with little improvement in outcomes in the last decade. Challenges in improving outcomes are closely linked to the frequent late presentation or diagnosis of CS where the 'point of no return' has often passed, leading to haemodynamic dysregulation, progressive myocardial depression, hypotension, and a downward spiral of hypoperfusion, organ dysfunction and decreasing myocardial function, driven by inflammation and metabolic derangements. Novel therapeutic interventions may have varying efficacy depending on the type and stage of shock in which they are applied. Biomarkers that aid prediction and early detection of CS, provide early signs of organ dysfunction and define prognosis could help optimize management. Temporal change in such biomarkers, particularly in response to pharmacological interventions and/or mechanical circulatory support, can guide management and predict outcome. Several novel biomarkers enhance the prediction of mortality in CS, compared to conventional parameters such as lactate, with some, such as adrenomedullin and circulating dipeptidyl peptidase 3, also able to predict the development of CS. Some biomarkers reflect systemic inflammation (e.g. interleukin-6, angiopoietin 2, fibroblast growth factor 23 and suppressor of tumorigenicity 2) and are not specific to CS, yet inform on the activation of important pathways involved in the downward shock spiral. Other biomarkers signal end-organ hypoperfusion and could guide targeted interventions, while some may serve as novel therapeutic targets. We critically review current and novel biomarkers that guide prediction, detection, and prognostication in CS. Future use of biomarkers may help improve management in these high-risk patients.
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Affiliation(s)
- Victor Galusko
- Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK
| | - Florian A Wenzl
- Centre for Molecular Cardiology, University of Zurich, Schlieren, Switzerland
- National Disease Registration and Analysis Service, NHS, London, UK
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden
| | - Christophe Vandenbriele
- Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK
- Heart Center, OLV Hospital, Aalst, Belgium
| | - Vasileios Panoulas
- Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK
- Faculty of Medicine, National Heart and Lung Institute, Imperial College, London, UK
| | - Thomas F Lüscher
- Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK
- Centre for Molecular Cardiology, University of Zurich, Schlieren, Switzerland
- Faculty of Medicine, National Heart and Lung Institute, Imperial College, London, UK
- School of Cardiovascular Medicine and Sciences, Kings College London, London, UK
| | - Diana A Gorog
- Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK
- School of Cardiovascular Medicine and Sciences, Kings College London, London, UK
- School of Life and Medical Sciences, Postgraduate Medical School, University of Hertfordshire, Hertfordshire, UK
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Sun YH, Song YY, Sha S, Sun Q, Huang DC, Gao L, Li H, Shi QD. Diagnostic value of digital continuous bowel sounds in critically ill patients with acute gastrointestinal injury: A prospective observational study. World J Gastrointest Surg 2024; 16:3818-3834. [PMID: 39734468 PMCID: PMC11650232 DOI: 10.4240/wjgs.v16.i12.3818] [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: 04/12/2024] [Revised: 09/05/2024] [Accepted: 10/22/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND Acute gastrointestinal injury (AGI) is common in intensive care unit (ICU) and worsens the prognosis of critically ill patients. The four-point grading system proposed by the European Society of Intensive Care Medicine is subjective and lacks specificity. Therefore, a more objective method is required to evaluate and determine the grade of gastrointestinal dysfunction in this patient population. Digital continuous monitoring of bowel sounds and some biomarkers can change in gastrointestinal injuries. We aimed to develop a model of AGI using continuous monitoring of bowel sounds and biomarkers. AIM To develop a model to discriminate AGI by monitoring bowel sounds and biomarker indicators. METHODS We conducted a prospective observational study with 75 patients in an ICU of a tertiary-care hospital to create a diagnostic model for AGI. We recorded their bowel sounds, assessed AGI grading, collected clinical data, and measured biomarkers. We evaluated the model using misjudgment probability and leave-one-out cross-validation. RESULTS Mean bowel sound rate and citrulline level are independent risk factors for AGI. Gastrin was identified as a risk factor for the severity of AGI. Other factors that correlated with AGI include mean bowel sound rate, amplitude, interval time, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, platelet count, total protein level, blood gas potential of hydrogen (pH), and bicarbonate (HCO3 -) level. Two discriminant models were constructed with a misclassification probability of < 0.1. Leave-one-out cross-validation correctly classified 69.8% of the cases. CONCLUSION Our AGI diagnostic model represents a potentially effective approach for clinical AGI grading and holds promise as an objective diagnostic standard for AGI.
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Affiliation(s)
- Yuan-Hui Sun
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
- Shaanxi Province Key Laboratory of Sepsis in Critical Care Medical, Xi'an 710061, Shaanxi Province, China
| | - Yun-Yun Song
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Sha Sha
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Qi Sun
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Deng-Chao Huang
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Lan Gao
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
- Shaanxi Province Key Laboratory of Sepsis in Critical Care Medical, Xi'an 710061, Shaanxi Province, China
| | - Hao Li
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
- Shaanxi Province Key Laboratory of Sepsis in Critical Care Medical, Xi'an 710061, Shaanxi Province, China
| | - Qin-Dong Shi
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
- Shaanxi Province Key Laboratory of Sepsis in Critical Care Medical, Xi'an 710061, Shaanxi Province, China
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Wang Y, Li Y, Zhang Y, Wang H, Li Y, Zhang L, Zhang C, Gao M, Li H, Zhang D. Development and validation of a nomogram for predicting 28-day mortality in critically ill patients with acute gastrointestinal injury: prospective observational study. Front Nutr 2024; 11:1469870. [PMID: 39449820 PMCID: PMC11499162 DOI: 10.3389/fnut.2024.1469870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 09/30/2024] [Indexed: 10/26/2024] Open
Abstract
Objective Developing and validating a clinical prediction nomogram of 28-day mortality in critically ill patients with acute gastrointestinal injury (AGI). Methods Firstly, the construction of a clinical prediction model was developed using data obtained from a prospective observational study from May 2023 to April 2024. Then, data from a prospective multicenter observational study conducted in the intensive care units of 12 teaching hospitals in 2014 were utilized to independently and externally validate the clinical prediction model developed in the first part. We first screened the covariates of the development cohort by univariate cox regression, and then carried out cox regression analysis on the development cohort by backward stepwise regression to determine the optimal fitting model. Subsequently, a nomogram was derived from this model. Results A total of 1102 and 379 patients, 28-day mortality occurred in 20.3% and 15.8% of patients respectively, were included in the development and validation cohort, respectively. We developed a nomogram in critically ill patients with AGI and the AGI grade, APACHE II score, Mechanical ventilation (MV), Feeding intolerance (FI) and daily calorie intake (DCI) in 72 h, were independent predictors of 28-day mortality, with the OR of the AGI grade was 1.910 (95% CI, 1.588-2.298; P < 0.001), the OR of APACHE II score was 1.099 (95% CI, 1.069-1.130; P < 0.001), the OR of MV was 1.880 (95% CI, 1.215-2.911; P = 0.005), the OR of FI was 3.453 (95% CI, 2.414-4.939; P < 0.001) and the DCI > 0.7 or < 0.5 of calorie target is associated with increased 28-day mortality, with OR of 1.566 (95% CI, 1.024-2.395; P = 0.039) and 1.769 (95% CI, 1.170-2.674; P = 0.007), respectively. Independent external validation of the prediction model was performed. This model has good discrimination and calibration. The DCA and CIC also validated the good clinical utility of the nomogram. Conclusion The prediction of 28-day mortality can be conveniently facilitated by the nomogram that integrates AGI grade, APACHE II score, MV, FI and DCI in 72 h in critically ill patients with AGI.
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Affiliation(s)
- Youquan Wang
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Yanhua Li
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Yuhan Zhang
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Huimei Wang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Yuting Li
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Liying Zhang
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Chaoyang Zhang
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Meng Gao
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Hongxiang Li
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Dong Zhang
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
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Ziaka M, Exadaktylos A. Gut-derived immune cells and the gut-lung axis in ARDS. Crit Care 2024; 28:220. [PMID: 38965622 PMCID: PMC11225303 DOI: 10.1186/s13054-024-05006-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 06/26/2024] [Indexed: 07/06/2024] Open
Abstract
The gut serves as a vital immunological organ orchestrating immune responses and influencing distant mucosal sites, notably the respiratory mucosa. It is increasingly recognized as a central driver of critical illnesses, with intestinal hyperpermeability facilitating bacterial translocation, systemic inflammation, and organ damage. The "gut-lung" axis emerges as a pivotal pathway, where gut-derived injurious factors trigger acute lung injury (ALI) through the systemic circulation. Direct and indirect effects of gut microbiota significantly impact immune responses. Dysbiosis, particularly intestinal dysbiosis, termed as an imbalance of microbial species and a reduction in microbial diversity within certain bodily microbiomes, influences adaptive immune responses, including differentiating T regulatory cells (Tregs) and T helper 17 (Th17) cells, which are critical in various lung inflammatory conditions. Additionally, gut and bone marrow immune cells impact pulmonary immune activity, underscoring the complex gut-lung interplay. Moreover, lung microbiota alterations are implicated in diverse gut pathologies, affecting local and systemic immune landscapes. Notably, lung dysbiosis can reciprocally influence gut microbiota composition, indicating bidirectional gut-lung communication. In this review, we investigate the pathophysiology of ALI/acute respiratory distress syndrome (ARDS), elucidating the role of immune cells in the gut-lung axis based on recent experimental and clinical research. This exploration aims to enhance understanding of ALI/ARDS pathogenesis and to underscore the significance of gut-lung interactions in respiratory diseases.
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Affiliation(s)
- Mairi Ziaka
- Clinic of Geriatric Medicine, Center of Geriatric Medicine and Rehabilitation, Kantonsspital Baselland, Bruderholz, Switzerland.
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
| | - Aristomenis Exadaktylos
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
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Hof S, Untiedt H, Hübner A, Marcus C, Kuebart A, Herminghaus A, Vollmer C, Bauer I, Picker O, Truse R. Effects of remote ischemic preconditioning on early markers of intestinal injury in experimental hemorrhage in rats. Sci Rep 2024; 14:12960. [PMID: 38839819 PMCID: PMC11153647 DOI: 10.1038/s41598-024-63293-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 05/27/2024] [Indexed: 06/07/2024] Open
Abstract
The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging. Since microcirculation and mitochondrial respiration are main components of the terminal stretch of tissue oxygenation, the evaluation of microcirculatory and mitochondrial variables could identify tissues at risk during hypoxic challenges, indicate an increase of intestinal injury, and improve our understanding of regional pathophysiology during acute hemorrhage. Furthermore, improving intestinal microcirculation or mitochondrial respiration, e.g. by remote ischemic preconditioning (RIPC) that was reported to exert a sufficient tissue protection in various tissues and was linked to mediators with vasoactive properties could maintain intestinal integrity. In this study, postcapillary oxygen saturation (µHbO2), microvascular flow index (MFI) and plasmatic D-lactate concentration revealed to be early markers of intestinal injury in a rodent model of experimental hemorrhagic shock. Mitochondrial function was not impaired in this experimental model of acute hemorrhage. Remote ischemic preconditioning (RIPC) failed to improve intestinal microcirculation and intestinal damage during hemorrhagic shock.
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Affiliation(s)
- Stefan Hof
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany.
| | - Hendrik Untiedt
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Anne Hübner
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Carsten Marcus
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Anne Kuebart
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Anna Herminghaus
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Christian Vollmer
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Inge Bauer
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Olaf Picker
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Richard Truse
- Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany
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Ajeje ET, Gandolfi JV, Cavallari V, Silva-Jr JM, de Freitas Chaves RC, Berger-Estilita J, Lobo SM. Measurements of I-FABP and citrulline in the postoperative period of non-cardiac surgeries with gastrointestinal complications: A prospective cohort observational study. J Crit Care 2024; 81:154530. [PMID: 38335862 DOI: 10.1016/j.jcrc.2024.154530] [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: 11/28/2023] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024]
Abstract
BACKGROUND Acute Gastrointestinal Injury (AGI) is associated with adverse clinical outcomes, including increased mortality. We aimed to investigate the potential of citrulline and intestinal fatty acid binding protein (I-FABP) as biomarkers for early AGI diagnosis and predicting outcomes in surgical patients. METHODS Prospective cohort study involving patients who underwent non-cardiac surgeries and were admitted to Intensive Care Units. AGI diagnosis was based on specific criteria, and severity was categorised following established guidelines. Statistical analyses were performed to assess the diagnostic accuracy of the biomarkers and their association with outcomes, P significant when <0.05. RESULTS AGI was identified in 40.3% of patients with varying severity. Mortality rates were significantly higher in the AGI group in the ICU (19.4% vs. 0%, p = 0.001) and hospital (22.6% vs. 2.17%, p = 0.003). Urinary I-FABP levels on days 3 and 7 showed reasonable and good accuracy for AGI diagnosis (AUC 0.732 and 0.813, respectively). Urinary I-FABP levels on days 2 and 3 accurately predict sepsis. Urinary citrulline levels on day one predicted mortality (AUC 0.87) furthermore urinary I-FABP levels on day 2 showed reasonable accuracy (sensitivity 83.3%, specificity 92.4%). CONCLUSION Urinary I-FABP and citrulline levels are promising diagnostic and prognostic markers in ICU patients following non-cardiac surgeries.
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Affiliation(s)
- Eduarda Tebet Ajeje
- Intensive Care Division. Hospital de Base, Faculdade de Medicina de São José do Rio Preto - São José do Rio Preto (SP), Brazil
| | - Joelma Villafanha Gandolfi
- Intensive Care Division. Hospital de Base, Faculdade de Medicina de São José do Rio Preto - São José do Rio Preto (SP), Brazil
| | - Vinicius Cavallari
- Intensive Care Division. Hospital de Base, Faculdade de Medicina de São José do Rio Preto - São José do Rio Preto (SP), Brazil
| | - João Manoel Silva-Jr
- Hospital Israelita Albert Einstein- São Paulo (SP), Brazil; Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - São Paulo (SP), Brazil
| | - Renato Carneiro de Freitas Chaves
- Hospital Israelita Albert Einstein- São Paulo (SP), Brazil; MIT Critical Data, Laboratory for Computational Physiology, Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Joana Berger-Estilita
- Institute of Anaesthesiology and Intensive Care, Salemspital, Hirslanden Medical Group, Schänzlistrasse 39, 3013 Bern, Switzerland; Institute for Medical Education, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland; CINTESIS, Centre for Health Technology and Services Research, Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, s/n, 4200-450 Porto, Portugal
| | - Suzana Margareth Lobo
- Intensive Care Division. Hospital de Base, Faculdade de Medicina de São José do Rio Preto - São José do Rio Preto (SP), Brazil.
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10
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Robayo-Amortegui H, Quintero-Altare A, Florez-Navas C, Serna-Palacios I, Súarez-Saavedra A, Buitrago-Bernal R, Casallas-Barrera JO. Fluid dynamics of life: exploring the physiology and importance of water in the critical illness. Front Med (Lausanne) 2024; 11:1368502. [PMID: 38745736 PMCID: PMC11092983 DOI: 10.3389/fmed.2024.1368502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 04/12/2024] [Indexed: 05/16/2024] Open
Abstract
Water acknowledged as a vital component for life and the universal solvent, is crucial for diverse physiological processes in the human body. While essential for survival, the human body lacks the capacity to produce water, emphasizing the need for regular ingestion to maintain a homeostatic environment. The human body, predominantly composed of water, exhibits remarkable biochemical properties, playing a pivotal role in processes such as protein transport, thermoregulation, the cell cycle, and acid–base balance. This review delves into comprehending the molecular characteristics of water and its interactions within the human body. The article offers valuable insights into the intricate relationship between water and critical illness. Through a comprehensive exploration, it seeks to enhance our understanding of water’s pivotal role in sustaining overall human health.
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Affiliation(s)
- Henry Robayo-Amortegui
- Department of Critical Care Medicine, Fundación Clínica Shaio, Bogotá, DC, Colombia
- Department of Medicine, Critical Care Resident, Universidad de La Sabana, Chía Cundinamarca, Colombia
| | - Alejandro Quintero-Altare
- Department of Critical Care Medicine, Fundación Clínica Shaio, Bogotá, DC, Colombia
- Department of Medicine, Critical Care Resident, Universidad de La Sabana, Chía Cundinamarca, Colombia
| | - Catalina Florez-Navas
- Department of Critical Care Medicine, Fundación Clínica Shaio, Bogotá, DC, Colombia
- Department of Medicine, Critical Care Resident, Universidad de La Sabana, Chía Cundinamarca, Colombia
| | - Isacio Serna-Palacios
- Department of Medicine, Critical Care Resident, Universidad de La Sabana, Chía Cundinamarca, Colombia
| | | | - Ricardo Buitrago-Bernal
- Department of Critical Care Medicine, Fundación Clínica Shaio, Bogotá, DC, Colombia
- Exploratorium group, Fundación Clínica Shaio, Bogotá, DC, Colombia
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11
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Kasotakis G, Whitmore C. Fat malabsorption in critical illness. Nutr Clin Pract 2024; 39 Suppl 1:S29-S34. [PMID: 38429961 DOI: 10.1002/ncp.11121] [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: 09/07/2023] [Revised: 11/21/2023] [Accepted: 12/28/2023] [Indexed: 03/03/2024] Open
Abstract
Malnutrition in critical illness is common and is associated with significant increases in adverse outcomes. A hypermetabolic state and underfeeding both contribute to the incidence of malnutrition. Malabsorption caused by critical illness is also an important contributor to the development of malnutrition. The early provision of enteral nutrition is associated with improved outcomes. Strategies for nutrition therapy must be informed by the alterations in absorption of macronutrients present in these patients. The following review examines alterations in fat metabolism during critical illness, and its consequences to overall nutrition status. Critical illness, as well as the sequalae of common medical interventions, may lead to alterations in the mechanical and chemical processes by which fat is digested and absorbed. Mechanical alterations include delayed gastric emptying and changes to the normal gut transit time. Pharmacologic interventions aimed at reducing these impacts may themselves, negatively affect efficient fat absorption. Exocrine pancreatic insufficiency can also occur in critical illness and may be underappreciated as a cause of fat malabsorption. Dysfunction of the gut lymphatics has been proposed as a contributing factor to fat malabsorption, and additional work is needed to better describe and quantify those effects. Achieving optimal outcomes for nutrition therapy requires recognition of these alterations in fat digestion.
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Affiliation(s)
- George Kasotakis
- Division of Trauma and Acute Care Surgery, Department of Surgery, Inova Healthcare System, University of Virginia, Falls Church, Virginia, USA
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12
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Dai N, Gu J, Luo Y, Tao Y, Chou Y, He Y, Qin H, Chen T, Fu X, Chen M, Xing Z. Impact of hyperoxia on the gut during critical illnesses. Crit Care 2024; 28:66. [PMID: 38429791 PMCID: PMC10905909 DOI: 10.1186/s13054-024-04848-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 02/22/2024] [Indexed: 03/03/2024] Open
Abstract
Molecular oxygen is typically delivered to patients via oxygen inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal oxygen inhalation or localized hyperoxia in the lower body from peripheral venoarterial (VA) ECMO. Consequently, this exposes the gastrointestinal tract to excessive oxygen levels. Hyperoxia can trigger organ damage due to the overproduction of reactive oxygen species and is associated with increased mortality. The gut and gut microbiome play pivotal roles in critical illnesses and even small variations in oxygen levels can have a dramatic influence on the physiology and ecology of gut microbes. Here, we reviewed the emerging preclinical evidence which highlights how excessive inhaled oxygen can provoke diffuse villous damage, barrier dysfunction in the gut, and gut dysbiosis. The hallmark of this dysbiosis includes the expansion of oxygen-tolerant pathogens (e.g., Enterobacteriaceae) and the depletion of beneficial oxygen-intolerant microbes (e.g., Muribaculaceae). Furthermore, we discussed potential impact of oxygen on the gut in various underlying critical illnesses involving inspiratory oxygen and peripheral VA-ECMO. Currently, the available findings in this area are somewhat controversial, and a consensus has not yet to be reached. It appears that targeting near-physiological oxygenation levels may offer a means to avoid hyperoxia-induced gut injury and hypoxia-induced mesenteric ischemia. However, the optimal oxygenation target may vary depending on special clinical conditions, including acute hypoxia in adults and neonates, as well as particular patients undergoing gastrointestinal surgery or VA-ECMO support. Last, we outlined the current challenges and the need for future studies in this area. Insights into this vital ongoing research can assist clinicians in optimizing oxygenation for critically ill patients.
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Affiliation(s)
- Ninan Dai
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Juan Gu
- Department of Pharmacy, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28, Malmö, Sweden
| | - Yanhong Luo
- First Clinical College, Zunyi Medical University, Zunyi, China
| | - Yuanfa Tao
- Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuehting Chou
- Department of Cardiopulmonary Bypass, Wuhan Asian Heart Hospital, Wuhan, China
| | - Ying He
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Han Qin
- Department of Respiratory and Critical Care Medicine, Kweichow Moutai Hospital, Guizhou Province, Zunyi, China
| | - Tao Chen
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xiaoyun Fu
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
| | - Miao Chen
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
| | - Zhouxiong Xing
- Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
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13
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Chaignat C, Lagrost L, Moretto K, de Barros JPP, Winiszewski H, Grober J, Saas P, Piton G. Plasma citrulline concentration and plasma LPS detection among critically ill patients a prospective observational study. J Crit Care 2024; 79:154438. [PMID: 37797404 DOI: 10.1016/j.jcrc.2023.154438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 09/13/2023] [Accepted: 09/25/2023] [Indexed: 10/07/2023]
Abstract
PURPOSE Gut can be a source of sepsis but sepsis itself can induce gut dysfunction. We aimed to study whether plasma citrulline, a marker of enterocyte mass, was correlated with plasma lipopolysaccharide, a potential marker of bacterial translocation among critically ill patients. MATERIALS AND METHODS Critically ill patients admitted to the ICU. Plasma citrulline and plasma LPS concentration and activity were measured at ICU admission. Patients were compared according to the presence of sepsis at ICU admission. RESULTS 109 critically ill patients, with SOFA score 8 [6-12], were prospectively included. Sixty six patients (61%) had sepsis at ICU admission. There was no correlation between plasma citrulline concentration and plasma LPS concentration or activity. However, sepsis at ICU admission was associated with a lower plasma citrulline concentration (13.4 μmol.L-1 vs 21.3 μmol.L-1, p = 0.02). Plasma LPS activity was significantly higher among patients with abdominal sepsis compared to patients with extra-abdominal sepsis (1.04 EU/mL vs 0.63, p = 0.01). CONCLUSIONS Plasma citrulline is not associated with the level of plasma LPS but is strongly decreased among septic patients. Detection of LPS is ubiquitous among critically ill patients but abdominal sepsis is associated with increased plasma LPS activity compared to extra-abdominal sepsis.
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Affiliation(s)
- Claire Chaignat
- Medical Intensive Care Unit, Besançon University Hospital, Besançon, France
| | | | - Karena Moretto
- Biochemistry Unit, Besançon University Hospital, Besançon, France
| | - Jean-Paul Pais de Barros
- INSERM, LNC UMR1231, LabEx LipSTIC, Dijon, France; Plateforme de Lipidomique, Université de Bourgogne, Dijon, France
| | - Hadrien Winiszewski
- Medical Intensive Care Unit, Besançon University Hospital, Besançon, France; Equipe d'Accueil 3920, Université de Franche Comté, Besançon, France
| | - Jacques Grober
- INSERM, LNC UMR1231, LabEx LipSTIC, Dijon, France; Institut Agro Dijon, Boulevard Petit Jean, Dijon, France
| | - Philippe Saas
- Etablissement Français du Sang Bourgogne-Franche Comté, Plateforme de BioMonitoring, Besançon, France; Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, LabEx LipSTIC, Besançon, France
| | - Gaël Piton
- Medical Intensive Care Unit, Besançon University Hospital, Besançon, France; Equipe d'Accueil 3920, Université de Franche Comté, Besançon, France.
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14
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Martinez J, Rodriguez Hovnanian KM, Martinez EE. Biomarkers and Functional Assays of Epithelial Barrier Disruption and Gastrointestinal Dysmotility in Critical Illness-A Narrative Review. Nutrients 2023; 15:4052. [PMID: 37764835 PMCID: PMC10535972 DOI: 10.3390/nu15184052] [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: 08/15/2023] [Revised: 09/14/2023] [Accepted: 09/15/2023] [Indexed: 09/29/2023] Open
Abstract
Enteral nutrition in critically ill children has been associated with improved clinical outcomes. Gastrointestinal dysfunction often impedes the timely initiation and advancement of enteral nutrition and can contribute to immune dysregulation and systemic inflammation. Therefore, assessing gastrointestinal function, at a cellular and functional level, is important to provide optimal enteral nutrition therapy and reduce the gastrointestinal tract's contribution to the inflammatory cascade of critical illness. In this narrative review, we present an overview of biomarker and functional assays for gastrointestinal dysfunction, including epithelial barrier disruption and gastrointestinal dysmotility, that have been considered for critically ill patients.
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Affiliation(s)
- Julianna Martinez
- Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA;
| | - K. Marco Rodriguez Hovnanian
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, USA;
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
| | - Enid E. Martinez
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, USA;
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
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15
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Liu X, Wang Q, Yang D, Fu M, Yang M, Bi Y, Wang C, Song X. Association between Gastrointestinal Dysfunction Score (GIDS) and disease severity and prognosis in critically ill patients: A prospective, observational study. Clin Nutr 2023; 42:700-705. [PMID: 36958226 DOI: 10.1016/j.clnu.2023.03.004] [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: 12/01/2022] [Revised: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 03/09/2023]
Abstract
OBJECTIVES Recently, the Gastrointestinal Dysfunction Score (GIDS) was developed for use with critically ill patients. This study evaluated the association of GIDS with disease severity and clinical outcomes to assess the technical feasibility of using GIDS to reflect the severity and short-term prognosis of critically ill patients. METHODS Association between Gastrointestinal Dysfunction Score (GIDS) and disease severity and prognosis in critically ill patients: A prospective, observational study. This was a prospective observational study involving adult patients in two Intensive Care Units (ICUs). During the first seven days of ICU admission, GIDS, acute gastrointestinal injury (AGI), Acute Physiology and Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores were assessed daily. RESULTS A total of 276 patients from two centers were enrolled in this study. Patients were divided into GIDS 0-1 (121, 43.8%) and GIDS 2-4 (155, 56.2%). The ICU length of stay and 28-day mortality in the GIDS 2-4 group were significantly higher than the GIDS 0-1 group (P = 0.032, P = 0.001, respectively). The APACHE II and SOFA scores in the GIDS 2-4 group were also significantly higher (P < 0.001). The ROC curves of GIDS, AGI, APACHE II, and SOFA scores on the first day of ICU admission for the prediction of 28-day mortality showed that the AUC of GIDS was 0.702 (95%CI 0.628, 0.775; P < 0.001). The AUC for GIDS + SOFA was 0.719 (95%CI 0.648, 0.790; P < 0.001), compared with SOFA alone (AUC = 0.703), showing improved predictive power for 28-day mortality. CONCLUSIONS GIDS represents a step toward a reliable clinical tool for GI dysfunction to assess disease severity and short-term prognosis in critically ill patients. In addition, combining GIDS with SOFA score may better predict mortality risk compared to SOFA score alone.
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Affiliation(s)
- Xinyan Liu
- ICU, Dong E Hospital, Liaocheng, Shandong, China
| | - Qizhi Wang
- ICU, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China
| | - Daqiang Yang
- ICU, Dong E Hospital, Liaocheng, Shandong, China
| | - Maoliang Fu
- ICU, Dong E Hospital, Liaocheng, Shandong, China
| | - Maopeng Yang
- ICU, Dong E Hospital, Liaocheng, Shandong, China
| | - Yang Bi
- Intensive Care Medicine, Shandong First Medical University, Jinan, Shandong, China
| | - Chunting Wang
- ICU, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China
| | - Xuan Song
- ICU, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China; Shandong Institute of Endocrine & Metabolic Diseases Affiliated to Shandong First Medical University, Jinan, Shandong, China.
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16
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Tyszko M, Lemańska-Perek A, Śmiechowicz J, Tomaszewska P, Biecek P, Gozdzik W, Adamik B. Citrulline, Intestinal Fatty Acid-Binding Protein and the Acute Gastrointestinal Injury Score as Predictors of Gastrointestinal Failure in Patients with Sepsis and Septic Shock. Nutrients 2023; 15:2100. [PMID: 37432225 DOI: 10.3390/nu15092100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/23/2023] [Accepted: 04/25/2023] [Indexed: 07/12/2023] Open
Abstract
Gastrointestinal (GI) failure can be both a cause of sepsis and a consequence of the systemic pro-inflammatory response in sepsis. Changes in biomarkers of enterocyte damage, citrulline and I-FABP (intestinal fatty acid binding protein), may indicate altered intestinal permeability and damage. The study group consisted of patients with sepsis (N = 28) and septic shock (N = 30); the control group included patients without infection (N = 10). Blood samples were collected for citrulline and I-FABP and a 4-point AGI score (acute GI injury score) was calculated to monitor GI function on days 1, 3, 5, 7, and 10. Citrulline concentrations in the study group were lower than in the control. Lower values were also noted in septic patients with shock when compared to the non-shock group throughout the study period. I-FABP was higher in the septic shock group than in the sepsis group only on days 1 and 3. Citrulline was lower in patients with GI failure (AGI III) when compared to AGI I/II, reaching significance on days 7 (p = 0.034) and 10 (p = 0.015); moreover, a higher AGI score was associated with an increased 28 day mortality (p = 0.038). The results indicate that citrulline measurements, along with the AGI assessment, have clinical potential in monitoring GI function and integrity in sepsis.
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Affiliation(s)
- Maciej Tyszko
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Anna Lemańska-Perek
- Department of Chemistry and Immunochemistry, Wroclaw Medical University, M. Sklodowskiej-Curie 48/50, 50-369 Wroclaw, Poland
| | - Jakub Śmiechowicz
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Paulina Tomaszewska
- Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland
| | - Przemyslaw Biecek
- Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland
- Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland
| | - Waldemar Gozdzik
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Barbara Adamik
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
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17
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Nguyen M, Gautier T, Masson D, Bouhemad B, Guinot PG. Endotoxemia in Acute Heart Failure and Cardiogenic Shock: Evidence, Mechanisms and Therapeutic Options. J Clin Med 2023; 12:jcm12072579. [PMID: 37048662 PMCID: PMC10094881 DOI: 10.3390/jcm12072579] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 03/22/2023] [Accepted: 03/25/2023] [Indexed: 03/31/2023] Open
Abstract
Acute heart failure and cardiogenic shock are frequently occurring and deadly conditions. In patients with those conditions, endotoxemia related to gut injury and gut barrier dysfunction is usually described as a driver of organ dysfunction. Because endotoxemia might reciprocally alter cardiac function, this phenomenon has been suggested as a potent vicious cycle that worsens organ perfusion and leading to adverse outcomes. Yet, evidence beyond this phenomenon might be overlooked, and mechanisms are not fully understood. Subsequently, even though therapeutics available to reduce endotoxin load, there are no indications to treat endotoxemia during acute heart failure and cardiogenic shock. In this review, we first explore the evidence regarding endotoxemia in acute heart failure and cardiogenic shock. Then, we describe the main treatments for endotoxemia in the acute setting, and we present the challenges that remain before personalized treatments against endotoxemia can be used in patients with acute heart failure and cardiogenic shock.
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18
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Onuk S, Ozer NT, Ozel M, Sipahioglu H, Kahriman G, Baskol G, Temel S, Gundogan K, Akin A. Gastric ultrasound, citrulline, and intestinal fatty acid-binding protein as markers of gastrointestinal dysfunction in critically ill patients: A pilot prospective cohort study. JPEN J Parenter Enteral Nutr 2023; 47:429-436. [PMID: 36609803 DOI: 10.1002/jpen.2473] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 12/23/2022] [Accepted: 12/31/2022] [Indexed: 01/09/2023]
Abstract
BACKGROUND Gastrointestinal (GI) dysfunction is common in the intensive care unit (ICU), although there is no consensus on biomarkers of GI dysfunction. We aimed to evaluate ultrasound-based gastric antrum measurements and serum intestinal fatty acid-binding protein (IFABP) and citrulline levels in relation to GI dysfunction in critically ill patients. METHODS Adult critically ill patients receiving enteral nutrition and stayed for in the ICU for ≥48 h was included. GI dysfunction was described using Gastrointestinal Dysfunction Score (GIDS). Gastric antrum measurements, including craniocaudal (CC) diameter, anteroposterior diameter, and antral-cross sectional area (CSA), as well as serum levels for IFABP and citrulline, were prospectively recorded at baseline and on day 3 and day 5 of enteral nutrition. The receiver operating characteristic (ROC) analysis was performed to evaluate gastric ultrasound parameters, serum IFABP, and citrulline concentrations in predicting GI dysfunction. RESULTS Thirty-nine participants with a median age of 60 years were recruited and 46.2% of participants had GI dysfunction. ROC analysis revealed that the cutoff value of CSA score to predict GI dysfunction was 4.48 cm2 , which provided 72.7% sensitivity and 77.2% specificity (area under the curve = 0.768, 95% CI: 0.555-0.980). At baseline, gastric residual volume was highly correlated with CC diameter and CSA (r = 0.764, P < 0.001 and r = 0.675, P < 0.001, respectively). Serum IFABP and citrulline levels had no correlation with GI dysfunction or gastric ultrasound parameters (P > 0.05). CONCLUSION CSA was associated with GI dysfunction in critically ill patients. Serum IFABP and citrulline concentrations were poor in predicting GI dysfunction.
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Affiliation(s)
- Sevda Onuk
- Division of Intensive Care Unit, Kayseri City Training and Research Hospital, Kayseri, Turkey
| | - Nurhayat Tugra Ozer
- Department of Clinical Nutrition, Health Science Institute, Erciyes University, Kayseri, Turkey
| | - Merve Ozel
- Department of Clinical Biochemistry, Erciyes University, Kayseri, Turkey
| | - Hilal Sipahioglu
- Division of Intensive Care Unit, Kayseri City Training and Research Hospital, Kayseri, Turkey
| | - Güven Kahriman
- Department of Radiology, School of Medicine, Erciyes University, Kayseri, Turkey
| | - Gulden Baskol
- Department of Clinical Biochemistry, Erciyes University, Kayseri, Turkey
| | - Sahin Temel
- Division of Intensive Care, School of Medicine, Erciyes University, Kayseri, Turkey
| | - Kursat Gundogan
- Division of Intensive Care, School of Medicine, Erciyes University, Kayseri, Turkey
| | - Aynur Akin
- Division of Anestesiology and Reanimation Intensive Care, School of Medicine, Erciyes University, Kayseri, Turkey
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19
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Hoftun Farbu B, Langeland H, Ueland T, Michelsen AE, Jørstad Krüger A, Klepstad P, Nordseth T. Intestinal injury in cardiac arrest is associated with multiple organ dysfunction: A prospective cohort study. Resuscitation 2023; 185:109748. [PMID: 36842675 DOI: 10.1016/j.resuscitation.2023.109748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 02/20/2023] [Indexed: 02/28/2023]
Abstract
BACKGROUND The impact of intestinal injury in cardiac arrest is not established. The first aim of this study was to assess associations between clinical characteristics in out-of-hospital cardiac arrest (OHCA) and a biomarker for intestinal injury, Intestinal Fatty Acid Binding Protein (IFABP). The second aim was to assess associations between IFABP and multiple organ dysfunction and 30-day mortality. METHODS We measured plasma IFABP in 50 patients at admission to intensive care unit (ICU) after OHCA. Demographic and clinical variables were analysed by stratifying patients on median IFABP, and by linear regression. We compared Sequential Organ Failure Assessment (SOFA) score, haemodynamic variables, and clinical-chemistry tests at day two between the "high" and "low" IFABP groups. Logistic regression was applied to assess factors associated with 30-day mortality. RESULTS Several markers of whole body ischaemia correlated with intestinal injury. Duration of arrest and lactate serum concentrations contributed to elevated IFABP in a multivariable model (p < 0.01 and p = 0.04, respectively). At day two, all seven patients who had died were in the "high" IFABP group, and all six patients who had been transferred to ward were in the "low" group. Of patients still treated in the ICU, the "high" group had higher total, renal and respiratory SOFA score (p < 0.01) and included all patients receiving inotropic drugs. IFABP predicted mortality (OR 16.9 per standard deviation increase, p = 0.04). CONCLUSION Cardiac arrest duration and lactate serum concentrations were risk factors for intestinal injury. High levels of IFABP at admission were associated with multiple organ dysfunction and mortality. TRIAL REGISTRATION ClinicalTrials.gov: NCT02648061.
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Affiliation(s)
- Bjørn Hoftun Farbu
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Norwegian Air Ambulance Foundation, Department of Research and Development, Oslo, Norway.
| | - Halvor Langeland
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Thor Ueland
- K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital (Rikshospitalet), Oslo, Norway
| | - Annika E Michelsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital (Rikshospitalet), Oslo, Norway
| | - Andreas Jørstad Krüger
- Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Norwegian Air Ambulance Foundation, Department of Research and Development, Oslo, Norway; Department of Emergency Medicine and Pre-Hospital Services, St. Olav's University Hospital, Trondheim, Norway
| | - Pål Klepstad
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Trond Nordseth
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital, Trondheim, Norway; Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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20
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Chen Z, Liu X, Shou C, Yang W, Yu J. Advances in the diagnosis of non-occlusive mesenteric ischemia and challenges in intra-abdominal sepsis patients: a narrative review. PeerJ 2023; 11:e15307. [PMID: 37128207 PMCID: PMC10148637 DOI: 10.7717/peerj.15307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 04/06/2023] [Indexed: 05/03/2023] Open
Abstract
Non-occlusive mesenteric ischemia (NOMI) is a type of acute mesenteric ischemia (AMI) with a high mortality rate mainly because of a delayed or misdiagnosis. Intra-abdominal sepsis is one of the risk factors for developing NOMI, and its presence makes early diagnosis much more difficult. An increase in routine abdominal surgeries carries a corresponding risk of abdominal infection, which is a complication that should not be overlooked. It is critical that physicians are aware of the possibility for intestinal necrosis in abdominal sepsis patients due to the poor survival rate of NOMI. This review aims to summarize advances in the diagnosis of NOMI, and focuses on the diagnostic challenges of mesenteric ischemia in patients with intra-abdominal sepsis.
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21
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Bourcier S, Ulmann G, Jamme M, Savary G, Paul M, Benghanem S, Lavillegrand JR, Schmidt M, Luyt CE, Maury E, Combes A, Pène F, Neveux N, Cariou A. A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study. Ann Intensive Care 2022; 12:113. [PMID: 36527517 PMCID: PMC9759607 DOI: 10.1186/s13613-022-01092-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis. METHODS We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria. RESULTS Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70-0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50-86], specificity of 85% [55-98], a negative predictive value of 58% [36-93] and a positive predictive value 90% [67-96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12-0.75], p = 0.01). CONCLUSION In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.
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Affiliation(s)
- Simon Bourcier
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France ,grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France
| | - Guillaume Ulmann
- grid.5842.b0000 0001 2171 2558Clinical Chemistry Department, AP-HP Centre, Hôpital Cochin, Université de Paris, Paris, France ,grid.5842.b0000 0001 2171 2558EA 4466 PRETRAM, Faculty of Pharmacy, Université de Paris, Paris, France
| | - Matthieu Jamme
- grid.418433.90000 0000 8804 2678Réanimation Polyvalente, Hôpital Privé de l’Ouest Parisien, Ramsay Générale de Santé, Trappes, France ,grid.12832.3a0000 0001 2323 0229INSERM U1018, Centre de Recherche en Epidémiologie et Santé des Populations, Team 5 (EpReC, Renal and Cardiovascular Epidemiology), Université Versailles Saint-Quentin, Villejuif, France
| | - Guillaume Savary
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Marine Paul
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Sarah Benghanem
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Jean-Rémi Lavillegrand
- grid.50550.350000 0001 2175 4109AP-HP, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Médecine Intensive Réanimation, Paris, France
| | - Matthieu Schmidt
- grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France ,grid.462844.80000 0001 2308 1657INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France
| | - Charles-Edouard Luyt
- grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France ,grid.462844.80000 0001 2308 1657INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France
| | - Eric Maury
- grid.50550.350000 0001 2175 4109AP-HP, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Médecine Intensive Réanimation, Paris, France
| | - Alain Combes
- grid.411439.a0000 0001 2150 9058Assistance Publique-Hôpitaux de Paris, AP-HP, Médecine Intensive Réanimation, Pitié-Salpêtrière Hospital, Paris, France ,grid.462844.80000 0001 2308 1657INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France
| | - Frédéric Pène
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Nathalie Neveux
- grid.5842.b0000 0001 2171 2558Clinical Chemistry Department, AP-HP Centre, Hôpital Cochin, Université de Paris, Paris, France ,grid.5842.b0000 0001 2171 2558EA 4466 PRETRAM, Faculty of Pharmacy, Université de Paris, Paris, France
| | - Alain Cariou
- grid.411784.f0000 0001 0274 3893Medical Intensive Care Unit, AP-HP, Institut Cochin, Cochin Hospital, Centre & Université de Paris, INSERM U1016, CNRS UMR8104, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France
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22
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Intestinal Fatty Acid Binding Protein (I-FABP) as a Prognostic Marker in Critically Ill COVID-19 Patients. Pathogens 2022; 11:pathogens11121526. [PMID: 36558860 PMCID: PMC9784725 DOI: 10.3390/pathogens11121526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/07/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Gastrointestinal symptoms are common in critically ill COVID-19 patients. There is currently no generally recognized method of assessing gastrointestinal injury in unconscious or sedated intensive care unit (ICU) patients. I-FABP (intestinal fatty acid binding protein) and citrulline have previously been studied as potential biomarkers of enterocyte damage in various gastrointestinal tract diseases, and changes in the levels of these markers may reflect intestinal wall damage in COVID-19. Patients with critical COVID-19, with diagnosed sepsis, or septic shock requiring ICU treatment were included in the study. Blood samples for citrulline and I-FABP were taken daily from day 1 to 5. I-FABP levels were significantly higher in patients who eventually died from COVID-19 than in survivors, and the optimal I-FABP cut-off point for predicting 28-day mortality was 668.57 pg/mL (sensitivity 0.739, specificity 0.765). Plasma levels of I-FABP, but not citrulline, were associated with significantly higher mortality and appeared to be a predictor of poor outcome in multivariate logistic regression analysis. In conclusion, I-FABP seems to be an effective prognostic marker in critically ill COVID-19 patients. Assessing mortality risk based on intestinal markers may be helpful in making clinical decisions regarding the management of intestinal injury, imaging diagnostics, and potential surgical interventions.
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23
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Robayo-Amortegui H, Forero-Delgadillo A, Pérez-Garzón M, Poveda-Henao C, Muñoz-Claros C, Bayona-Solano A, Orozco C, Buitrago-Bernal R. Severe gastrointestinal injury associated with SARS-CoV-2 infection: Thrombosis or Inflammation?: A retrospective case series study. Medicine (Baltimore) 2022; 101:e31188. [PMID: 36281196 PMCID: PMC9592134 DOI: 10.1097/md.0000000000031188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
OBJECTIVES Acute gastrointestinal injury (AGI) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a low incidence of complications in patients admitted to the intensive care unit (ICU). Pathophysiological knowledge related to AGI is limited, as few studies have been published on this topic. Therefore, this study was carried out to identify the clinical and histopathological features of patients with SARS-CoV-2 infection and grade IV AGI. METHODS This is a retrospective case study of fifteen patients with SARS-CoV-2 infection and grade IV AGI who underwent emergency surgery. RESULTS This study revealed a mortality rate of 62.5%. The most frequent gastrointestinal symptoms were abdominal distension (100%) and increased gastric residual volume (93.3%). Distended bowel loops on plain abdominal radiography (90%) and intestinal pneumatosis on computed tomography (50%) were the most frequent imaging findings. Surgical exploration revealed intestinal ischemia (66.6%) and necrosis (46.6%), and histopathology showed ischemic and liquefactive necrosis with mixed inflammatory involvement and absence of thrombosis as the cause of AGI. CONCLUSIONS AGI associated with severe SARS-CoV-2 infection has a high mortality rate and poses a diagnostic challenge in the ICU. The complex pathophysiology and histopathological findings indicate an associated inflammatory phenomenon as the main alteration in the absence of thrombosis, as per the intestinal biopsies of the cases studied. Further clinical studies are required to gain a better understanding of this pathology.
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Affiliation(s)
| | | | | | - Claudia Poveda-Henao
- Intensive Care, Fundación Clínica Shaio, Bogotá, Colombia
- * Correspondence: Claudia Poveda Henao, Intensive Care, Fundación Clínica Shaio, Bogotá 111166, Colombia (e-mail: )
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24
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Winiszewski H, Guinot PG, Schmidt M, Besch G, Piton G, Perrotti A, Lorusso R, Kimmoun A, Capellier G. Optimizing PO 2 during peripheral veno-arterial ECMO: a narrative review. Crit Care 2022; 26:226. [PMID: 35883117 PMCID: PMC9316319 DOI: 10.1186/s13054-022-04102-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 07/13/2022] [Indexed: 01/01/2023] Open
Abstract
During refractory cardiogenic shock and cardiac arrest, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used to restore a circulatory output. However, it also impacts significantly arterial oxygenation. Recent guidelines of the Extracorporeal Life Support Organization (ELSO) recommend targeting postoxygenator partial pressure of oxygen (PPOSTO2) around 150 mmHg. In this narrative review, we intend to summarize the rationale and evidence for this PPOSTO2 target recommendation. Because this is the most used configuration, we focus on peripheral VA-ECMO. To date, clinicians do not know how to set the sweep gas oxygen fraction (FSO2). Because of the oxygenator's performance, arterial hyperoxemia is common during VA-ECMO support. Interpretation of oxygenation is complex in this setting because of the dual circulation phenomenon, depending on both the native cardiac output and the VA-ECMO blood flow. Such dual circulation results in dual oxygenation, with heterogeneous oxygen partial pressure (PO2) along the aorta, and heterogeneous oxygenation between organs, depending on the mixing zone location. Data regarding oxygenation during VA-ECMO are scarce, but several observational studies have reported an association between hyperoxemia and mortality, especially after refractory cardiac arrest. While hyperoxemia should be avoided, there are also more and more studies in non-ECMO patients suggesting the harm of a too restrictive oxygenation strategy. Finally, setting FSO2 to target strict normoxemia is challenging because continuous monitoring of postoxygenator oxygen saturation is not widely available. The threshold of PPOSTO2 around 150 mmHg is supported by limited evidence but aims at respecting a safe margin, avoiding both hypoxemia and severe hyperoxemia.
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Affiliation(s)
- Hadrien Winiszewski
- Service de Réanimation Médicale, centre hospitalier universitaire de Besançon, Besançon, France. .,Research Unit EA 3920 and SFR FED 4234, University of Franche Comté, Besancon, France.
| | - Pierre-Grégoire Guinot
- Service d'Anesthésie-Réanimation Chirurgicale, centre hospitalier universitaire de Dijon, Dijon, France
| | - Matthieu Schmidt
- Service de Médecine Intensive Réanimation, Institut de Cardiologie, APHP Sorbonne Université Hôpital Pitié-Salpêtrière, Paris, France
| | - Guillaume Besch
- Service d'Anesthésie-Réanimation Chirurgicale, centre hospitalier universitaire de Besançon, Besançon, France.,Research Unit EA 3920 and SFR FED 4234, University of Franche Comté, Besancon, France
| | - Gael Piton
- Service de Réanimation Médicale, centre hospitalier universitaire de Besançon, Besançon, France.,Research Unit EA 3920 and SFR FED 4234, University of Franche Comté, Besancon, France
| | - Andrea Perrotti
- Service de Chirurgie Cardiaque, centre hospitalier universitaire de Besançon, Besançon, France.,Research Unit EA 3920 and SFR FED 4234, University of Franche Comté, Besancon, France
| | - Roberto Lorusso
- Cardio-Thoracic Surgery Department, Maastricht University Medical Centre (MUMC), Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
| | - Antoine Kimmoun
- Service de Médecine Intensive Réanimation, centre hospitalier universitaire de Nancy Brabois, Vandœuvre-lès-Nancy, France
| | - Gilles Capellier
- Service de Réanimation Médicale, centre hospitalier universitaire de Besançon, Besançon, France.,Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Clayton, Australia.,Research Unit EA 3920 and SFR FED 4234, University of Franche Comté, Besancon, France
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25
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Flordelís Lasierra JL, Montejo González JC, López Delgado JC, Zárate Chug P, Martínez Lozano-Aranaga F, Lorencio Cárdenas C, Bordejé Laguna ML, Maichle S, Terceros Almanza LJ, Trasmonte Martínez MV, Mateu Campos L, Servià Goixart L, Vaquerizo Alonso C, Vila García B. Enteral Nutrition in Critically Ill Patients Under Vasoactive Drug Therapy. The NUTRIVAD Study. JPEN J Parenter Enteral Nutr 2022; 46:1420-1430. [PMID: 35274345 DOI: 10.1002/jpen.2371] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/18/2022] [Accepted: 03/08/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND Enteral nutrition (EN) in critically ill patients requiring vasoactive drug (VAD) support is controversial. This study assesses the tolerability and safety of EN in such patients. METHODS This prospective observational study was conducted in 23 ICUs over 30 months. Inclusion criteria were a need for VAD and/or mechanic circulatory support (MCS) over a minimum of 48 h, a need for at least 48 h of mechanical ventilation, an estimated life expectancy longer than 72 h, and at least 72 h of ICU stay. Patients with refractory shock were excluded. EN was performed according to established protocols during which descriptive, daily hemodynamic and efficacy and safety data were collected. An independent research group conducted the statistical analysis. RESULTS Of 200 patients included, 30 (15%) required MCS and 145 (73%) met early multiorgan dysfunction criteria. Mortality was 24%. Patients needed a mean dose of norepinephrine in the first 48 h of 0.71 μg/kg/min (95%CI: 0.63-0.8) targeting a mean arterial pressure of 68 mmHg (95%CI: 67-70) during the first 48 h. EN was started 34 h (95%CI: 31-37) after ICU admission. Mean energy and protein delivered by EN/patient/day were 1159 Kcal (95%CI: 1098-1220) and 55.6 g (52.4-58.7) respectively. Daily energy balance during EN/patient/day was -432 (95%CI: -496 to -368). 154 (77%) patients experienced EN-related complications. However, severe complications such as mesenteric ischemia were recorded in only 1 patient (0.5%). CONCLUSIONS EN in these patients seems feasible, safe and unrelated to serious complications. Reaching the energy target only through EN is difficult. CLINICAL RELEVANCY STATEMENT Enteral nutrition (EN) in critically ill patients requiring vasoactive drugs (VAD) is currently a subject of controversy. Factors such as when to start EN, dosing, monitoring, or whether to avoid EN altogether are a real challenge because of its link to a risk of bowel ischemia. We describe our experience with EN in 200 critically ill patients on mechanical ventilation and requiring VAD. Under adequate supervision, EN proved feasible and safe. Our findings require confirmation in clinical intervention trials. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- José Luis Flordelís Lasierra
- Intensive Care Medicine Service. Research Institute Hospital 12 de Octubre (i+12), Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Juan Carlos Montejo González
- Intensive Care Medicine Service. Research Institute Hospital 12 de Octubre (i+12), Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Juan Carlos López Delgado
- Intensive Care Medicine Department. L'Hospitalet de Llobregat, Hospital Universitari de Bellvitge, (Barcelona), Spain
| | - Paola Zárate Chug
- Intensive Care Medicine Service, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | | | | | - María Luisa Bordejé Laguna
- Intensive Care Medicine Service, Hospital Universitario Germans Trias i Pujol, Barcelona, Cataluña, Spain
| | - Silmary Maichle
- Intensive Care Medicine Service, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | | | | | - Lidón Mateu Campos
- Hospital General Universitario de Castellón, Comunidad Valenciana, Spain
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Liu T, Wang C, Wang YY, Wang LL, Ojo O, Feng QQ, Jiang XS, Wang XH. The effect of dietary fiber on gut barrier function, gut microbiota, short-chain fatty acids, inflammation and clinical outcomes in critically ill patients: A systematic review and meta-analysis. JPEN J Parenter Enteral Nutr 2021; 46:997-1010. [PMID: 34951702 DOI: 10.1002/jpen.2319] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/18/2021] [Accepted: 12/21/2021] [Indexed: 01/30/2023]
Abstract
BACKGROUND Although some studies have explored the relationships between dietary fiber (DF) supplement and gut barrier function, changes of gut microbiota and other clinical outcomes in critically ill patients, the results from different studies were not consistent. OBJECTIVE The purpose of this study was to explore the effect of dietary fiber on gut barrier function, gut microbiota, short-chain fatty acids (SCFAs), inflammation and clinical outcomes in critically ill patients. METHODS A search was performed through PubMed, Embase, the Cochrane Central Register of Clinical Trials, Web of Science and EBSCO-host that includes Health Sciences Research from inception to July 12, 2021. Data were pooled using fixed effects model for low heterogeneity and random effects model for high heterogeneity. Data were expressed as mean difference (MD) or odds ratio (OR) with confidence interval. RESULTS A total of 21 studies involving 2084 critically ill patients were included. The results showed that there was a significant reduction in intestinal permeability demonstrated by lactulose/rhamnose ratio (MD:-0.04; 95%CI:-0.08, -0.00; P = 0.03) on day 8 in DF supplement group. Three studies reported the relative abundance (RA) of gut microbiota and the results showed the RA of some SCFAs producers increased higher in DF supplement group. There was a significant decrease in C-reactive protein on day 14 (MD:-36.66; 95%CI:-44.40, -28.93; P<0.001) and the duration of hospital stay (MD:-3.16; 95%CI:-5.82, -0.49; P<0.05) after DF supplement. There were no significant differences on SCFAs levels, the duration of mechanical ventilation and mortality between the two groups. However, in subgroup analysis, the results indicated there was a significant reduction on the duration of mechanical ventilation in fiber combined probiotic group (MD:-13; 95%CI:-19.69, -6.31; P<0.001). Besides, significant decreases in the duration of hospital stay and risk of mortality were seen in the subgroups with fiber supplementary dose ≥20 g/d (MD:-5.62; 95%CI: -8.04, -3.21; P<0.0001; OR: 0.18, 95%CI: 0.06, 0.57, P = 0.004), as well as in medical ICU (MD:-4.77; 95%CI: -7.48, -2.07; P<0.01; OR: 0.13; 95%CI: 0.03, 0.65; P<0.05). CONCLUSIONS Dietary fiber may improve the gut barrier function, modulate the intestinal microbiota, decrease systemic inflammatory response and may advance the clinical outcomes in critically ill patients. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Ting Liu
- Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Can Wang
- Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Yu-Yu Wang
- Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Li-Li Wang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Omorogieva Ojo
- Department of Adult Nursing and Paramedic Science, University of Greenwich, London, United Kingdom
| | - Qian-Qian Feng
- School of Nursing, Medical College of Soochow University, Suzhou, 215006, China
| | - Xiao-Song Jiang
- Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Xiao-Hua Wang
- Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
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Yokoyama H, Sekino M, Funaoka H, Sato S, Araki H, Egashira T, Yano R, Matsumoto S, Ichinomiya T, Higashijima U, Hara T. Association between enterocyte injury and fluid balance in patients with septic shock: a post hoc exploratory analysis of a prospective observational study. BMC Anesthesiol 2021; 21:293. [PMID: 34814831 PMCID: PMC8609797 DOI: 10.1186/s12871-021-01515-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 11/15/2021] [Indexed: 12/29/2022] Open
Abstract
Background The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock. Methods This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed. Results Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson’s r = 0.490 [95% confidence interval: 0.263–0.666]; P < 0.001 and r = 0.479 [95% confidence interval: 0.240–0.664]; P < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1–24.7]; P = 0.007 and estimate, 26.9 [95% confidence interval: 11.0–42.7]; P = 0.001, respectively) adjusting for severity score and renal function. Conclusions Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admission.
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Affiliation(s)
- Haruka Yokoyama
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Motohiro Sekino
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Hiroyuki Funaoka
- Department of Research and Development, SB Bioscience Co. Ltd., 3-47 Higashi-Tsukaguchi-cho, 2-chome, Amagasaki, Hyogo, 661-0011, Japan
| | - Shuntaro Sato
- Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Hiroshi Araki
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Takashi Egashira
- Department of Intensive Care, Nagasaki Harbor Medical Center, 6-39 Shinchi-machi, Nagasaki, 850-8555, Japan
| | - Rintaro Yano
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Sojiro Matsumoto
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Taiga Ichinomiya
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Ushio Higashijima
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Tetsuya Hara
- Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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Padar M, Starkopf J, Starkopf L, Forbes A, Hiesmayr M, Jakob SM, Rooijackers O, Wernerman J, Ojavee SE, Reintam Blaser A. Enteral nutrition and dynamics of citrulline and intestinal fatty acid-binding protein in adult ICU patients. Clin Nutr ESPEN 2021; 45:322-332. [PMID: 34620335 DOI: 10.1016/j.clnesp.2021.07.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 07/26/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND AND AIMS Plasma citrulline and intestinal fatty acid binding protein (I-FABP) are biomarkers reflecting enterocyte function and intestinal mucosal injury. The aim was to describe daily dynamics of citrulline and I-FABP concentrations in association with enteral nutrition (EN) in adult ICU patients. We hypothesized that success or failure of EN is reflected by differences in citrulline and I-FABP levels at admission, as well as in daily dynamics over the first week. METHODS The present study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000). With delayed informed consent we included adult (18 years or older) patients admitted for unlimited care to 5 ICUs in Europe. Citrulline and I-FABP were assessed and nutritional data recorded daily during the first week of the patients' ICU stay. RESULTS The study included 224 patients with 693 plasma samples analyzed for citrulline and 695 for I-FABP. The median ICU stay was 2 (IQR 1-4) days and 35 patients (15.6 %) stayed in the ICU for ≥ 7 days. The majority of patients (184/224; 82.1 %) received EN or oral nutrition (ON) during their ICU stay, in 164 patients (73.2 %) nutrition was started within 48 h of admission (early enteral or oral nutrition, EEN/ON). Median biomarker concentrations on admission were: citrulline 24.5 (IQR 18.1-31.7) μmol/L and I-FABP 2763 (1326-4805) pg/mL. Reference range for citrulline was 17-46 μmol/L and for I-FABP 377-2049 pg/mL. Patients with EEN/ON demonstrated an increase in citrulline concentrations over the first week in ICU unlike those not receiving EEN/ON (P = 0.049 for the mean log-citrulline values over time between groups) as well as higher average citrulline concentrations. Success of EEN/ON (80 % of caloric target achieved by day 4) was associated with citrulline values increasing from day 4, whereas a slight decrease was observed with unsuccessful EEN/ON. However, these dynamics over time were not statistically significantly different (P = 0.654). Patients with EEN/ON unexpectedly had I-FABP values higher than those without (average values for all days P = 0.004). Median I-FABP values on day 3 were higher with successful EEN/ON (646 (IQR 313-1116) vs 278 (IQR 190-701) pg/mL, P = 0.022). CONCLUSIONS EEN/ON was associated with higher values and different dynamics of citrulline over the first week in ICU. No clear difference of measured biomarkers was seen when patients were compared according to success of EEN/ON. Our study does not allow suggesting certain thresholds of citrulline nor I-FABP that could be used for bedside decision-making with regard to EN. This study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000).
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Affiliation(s)
- Martin Padar
- Department of Anaesthesiology and Intensive Care, Tartu University Hospital, L. Puusepa 8, 51014 Tartu, Estonia; Department of Anaesthesiology and Intensive Care, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia.
| | - Joel Starkopf
- Department of Anaesthesiology and Intensive Care, Tartu University Hospital, L. Puusepa 8, 51014 Tartu, Estonia; Department of Anaesthesiology and Intensive Care, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia
| | - Liis Starkopf
- Section of Biostatistics, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, DK-1014 Copenhagen, Denmark
| | - Alastair Forbes
- Norwich Medical School, University of East Anglia, Bob Champion Building, James Watson Road, Norwich, NR4 7UQ, United Kingdom
| | - Michael Hiesmayr
- Division of Cardio-Thoracic-Vascular Surgical Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria. Spitalgasse 23, Wien, 1090, Austria
| | - Stephan M Jakob
- Department of Intensive Care Medicine, University Hospital, University of Bern, Bern, Switzerland
| | - Olav Rooijackers
- Department of Clinical Science, Intervention and Technology, Division of Anaesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jan Wernerman
- Department of Clinical Science, Intervention and Technology, Division of Anaesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Sven Erik Ojavee
- Department of Computational Biology, University of Lausanne, 1015 Lausanne, Switzerland
| | - Annika Reintam Blaser
- Department of Anaesthesiology and Intensive Care, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia; Department of Intensive Care Medicine, Lucerne Cantonal Hospital, 6000 Lucerne, Switzerland
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Abstract
PURPOSE OF REVIEW Progress has been made in our understanding of gut dysfunction in critical illness. This review will outline new findings and give perspectives based on previous knowledge and concurrent advances in nutrition. RECENT FINDINGS The relationship between gut dysfunction and poor outcomes in critical illness has received considerable interest. It remains uncertain whether gut dysfunction is merely a marker of illness severity or if it is directly responsible for prolonged critical illness and increased mortality. This relationship is difficult to ascertain given there is no agreed method for identification and quantification; biomarkers such as intestinal fatty acid binding protein and citrulline show promise but require further study. Recent studies have investigated strategies to deliver enteral nutrition targets with impacts on gut function, including high calorie or protein formulae, intermittent regimes and novel prokinetics. SUMMARY Gut dysfunction is associated with poor outcomes, but it remains uncertain whether strategies to improve gut function will influence survival and recovery.
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Shen L, Zhou Y, Wu X, Sun Y, Xiao T, Gao Y, Wang J. TREM1 Blockade Ameliorates Lipopolysaccharide-Induced Acute Intestinal Dysfunction through Inhibiting Intestinal Apoptosis and Inflammation Response. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6635452. [PMID: 33954188 PMCID: PMC8068534 DOI: 10.1155/2021/6635452] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/26/2021] [Accepted: 03/11/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. METHODS Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1β were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. RESULTS LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1β levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. CONCLUSION LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.
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Affiliation(s)
- Lijuan Shen
- Wuxi Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Affiliated Wuxi Hospital, Wuxi, 214071 Jiangsu, China
| | - Yonghua Zhou
- Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Jiangsu Provincial Key Subject on Parasitic Diseases, Wuxi 214064, China
| | - Xiping Wu
- Wuxi Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Affiliated Wuxi Hospital, Wuxi, 214071 Jiangsu, China
| | - Yuewen Sun
- Wuxi Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Affiliated Wuxi Hospital, Wuxi, 214071 Jiangsu, China
| | - Tao Xiao
- Wuxi Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Affiliated Wuxi Hospital, Wuxi, 214071 Jiangsu, China
| | - Yin Gao
- Wuxi Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Affiliated Wuxi Hospital, Wuxi, 214071 Jiangsu, China
| | - Jingui Wang
- Wuxi Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Affiliated Wuxi Hospital, Wuxi, 214071 Jiangsu, China
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Blesl A, Stadlbauer V. The Gut-Liver Axis in Cholestatic Liver Diseases. Nutrients 2021; 13:nu13031018. [PMID: 33801133 PMCID: PMC8004151 DOI: 10.3390/nu13031018] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/12/2021] [Accepted: 03/18/2021] [Indexed: 12/12/2022] Open
Abstract
The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.
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Affiliation(s)
- Andreas Blesl
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria;
- Correspondence:
| | - Vanessa Stadlbauer
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria;
- Center for Biomarker Research in Medicine (CBmed), 8010 Graz, Austria
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Chen X, Wu M, Li J. Electroacupuncture therapy for acute gastrointestinal injury: review and perspectives. Acupunct Med 2021; 39:567-568. [PMID: 33715448 DOI: 10.1177/0964528421989714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Xiaotong Chen
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengdie Wu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jing Li
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Associations between urinary 3-indoxyl sulfate, a gut microbiome-derived biomarker, and patient outcomes after intensive care unit admission. J Crit Care 2021; 63:15-21. [PMID: 33549909 DOI: 10.1016/j.jcrc.2021.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 12/26/2020] [Accepted: 01/15/2021] [Indexed: 11/22/2022]
Abstract
PURPOSE 3-indoxyl sulfate (3-IS) is an indole metabolism byproduct produced by commensal gut bacteria and excreted in the urine; low urinary 3-IS has been associated with increased mortality in bone marrow transplant recipients. This study investigated urinary 3-IS and patient outcomes in the ICU. MATERIALS AND METHODS Prospective study that collected urine samples, rectal swabs, and clinical data on 78 adult ICU patients at admission and again 72 h later. Urine was analyzed for 3-IS by mass spectrometry. RESULTS Median urinary 3-IS levels were 17.1 μmol/mmol creatinine (IQR 9.5 to 26.2) at admission and 15.6 (IQR 4.2 to 30.7) 72 h later. 22% of patients had low 3-IS (≤6.9 μmol/mmol) on ICU admission and 28% after 72 h. Low 3-IS at 72 h was associated with fewer ICU-free days (22.5 low versus 26 high, p = 0.03) and with death during one year of follow-up (36% low versus 9% high 3-IS, p < 0.01); there was no detectable difference in 30-day mortality (18% low versus 5% high, p = 0.07). CONCLUSIONS Low urinary 3-IS level 72 h after ICU admission was associated with fewer ICU-free days and with increased one-year but not 30-day mortality. Further studies should investigate urinary 3-IS as an ICU biomarker.
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Sekino M, Okada K, Funaoka H, Sato S, Ichinomiya T, Higashijima U, Matsumoto S, Yoshitomi O, Eishi K, Hara T. Association between Enterocyte Injury and Mortality in Patients on Hemodialysis Who Underwent Cardiac Surgery: An Exploratory Study. J Surg Res 2020; 255:420-427. [DOI: 10.1016/j.jss.2020.05.091] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 05/12/2020] [Accepted: 05/25/2020] [Indexed: 12/26/2022]
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Martinez EE, Zurakowski D, Pereira L, Freire R, Emans JB, Nurko S, Duggan CP, Fasano A, Mehta NM. Interleukin-10 and Zonulin Are Associated With Postoperative Delayed Gastric Emptying in Critically Ill Surgical Pediatric Patients: A Prospective Pilot Study. JPEN J Parenter Enteral Nutr 2020; 44:1407-1416. [PMID: 32386238 PMCID: PMC7754495 DOI: 10.1002/jpen.1874] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 04/27/2020] [Accepted: 05/04/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND Impaired gastric emptying (GE) is associated with morbidity in surgical critically ill children. The relationship between inflammation, gut barrier integrity (lipopolysaccharide binding protein [LBP]; zonulin), and GE has not been described in this cohort. METHODS Children ≥2 years of age and requiring critical care after surgery were enrolled. Preoperative and postoperative levels of serum cytokines, LBP, and zonulin, and GE by the acetaminophen absorption test, were measured, allowing patients to serve as their own controls. Postoperative delayed GE was defined as a decrease in GE by ≥20% compared with preoperative GE. The following were examined : comparison between postoperative andpreoperative values, correlations between fold change (postoperative/preoperative) in study variables, and fold change in study variables between patients with and without postoperative delayed GE. RESULTS Twenty patients, median age 14 years (12.25, 18), 12 female, were included. Eight of 20 patients had postoperative delayed GE. Postoperative interleukin-6 (IL-6), IL-8, IL-10, and LBP were increased, and zonulin was decreased (P-values < .05). Fold change in IL-10 and zonulin were inversely correlated (ρ -0.618, P = .004). Patients with postoperative delayed GE had greater fold increase in IL-10 (P = .0159) and fold decrease in zonulin (P = .0160). Five of 7 (71%) patients with both fold increase in IL-10 and decrease in zonulin had delayed GE. CONCLUSION Postoperative changes in IL-10 and zonulin were associated with delayed GE in surgical critically ill children, which might suggest a mechanism to for delayed GE in postoperative inflammation and gut barrier dysregulation after surgery.
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Affiliation(s)
- Enid E. Martinez
- Department of Anesthesiology, Critical Care and Pain MedicineBoston Children's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - David Zurakowski
- Department of Anesthesiology, Critical Care and Pain MedicineBoston Children's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Luis Pereira
- Department of Anesthesiology, Critical Care and Pain MedicineBoston Children's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Rachel Freire
- Division of Pediatric Gastroenterology and NutritionDepartment of PediatricsMassachusetts General Hospital for ChildrenBostonMassachusettsUSA
| | - John B. Emans
- Harvard Medical SchoolBostonMassachusettsUSA
- Orthopedic CenterBoston Children's HospitalBostonMassachusettsUSA
| | - Samuel Nurko
- Harvard Medical SchoolBostonMassachusettsUSA
- Division of Gastroenterology, Hepatology and NutritionBoston Children's HospitalBostonMassachusettsUSA
| | - Christopher P. Duggan
- Harvard Medical SchoolBostonMassachusettsUSA
- Division of Gastroenterology, Hepatology and NutritionBoston Children's HospitalBostonMassachusettsUSA
- Center for NutritionBoston Children's HospitalBostonMassachusettsUSA
| | - Alessio Fasano
- Harvard Medical SchoolBostonMassachusettsUSA
- Division of Pediatric Gastroenterology and NutritionDepartment of PediatricsMassachusetts General Hospital for ChildrenBostonMassachusettsUSA
| | - Nilesh M. Mehta
- Department of Anesthesiology, Critical Care and Pain MedicineBoston Children's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
- Center for NutritionBoston Children's HospitalBostonMassachusettsUSA
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Jung CY, Bae JM. Pathophysiology and protective approaches of gut injury in critical illness. Yeungnam Univ J Med 2020; 38:27-33. [PMID: 33022904 PMCID: PMC7787898 DOI: 10.12701/yujm.2020.00703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 08/31/2020] [Indexed: 12/14/2022] Open
Abstract
The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.
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Affiliation(s)
- Chang Yeon Jung
- Department of Surgery, Yeungnam University Hospital, Daegu, Korea
| | - Jung Min Bae
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
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Blesl A, Jüngst C, Lammert F, Fauler G, Rainer F, Leber B, Feldbacher N, Stromberger S, Wildburger R, Spindelböck W, Fickert P, Horvath A, Stadlbauer V. Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut-Liver Axis: A Case Control Study. Nutrients 2020; 12:E2728. [PMID: 32906634 PMCID: PMC7551864 DOI: 10.3390/nu12092728] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 09/02/2020] [Accepted: 09/03/2020] [Indexed: 12/12/2022] Open
Abstract
Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut-liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut-liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment.
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Affiliation(s)
- Andreas Blesl
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Christoph Jüngst
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Zürich, 8032 Zürich, Switzerland;
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany;
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany;
| | - Günter Fauler
- Institute for Medical and Chemical Laboratory Diagnosis, Medical University of Graz, 8036 Graz, Austria;
| | - Florian Rainer
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Bettina Leber
- Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, 8036 Graz, Austria;
| | - Nicole Feldbacher
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Silvia Stromberger
- AUVA Rehabilitation Clinic Tobelbad, 8144 Tobelbad, Austria; (S.S.); (R.W.)
| | - Renate Wildburger
- AUVA Rehabilitation Clinic Tobelbad, 8144 Tobelbad, Austria; (S.S.); (R.W.)
| | - Walter Spindelböck
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Peter Fickert
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Angela Horvath
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Vanessa Stadlbauer
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
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Jiang M, Li CL, Pan CQ, Lv WZ, Ren YF, Cui XW, Dietrich CF. Nomogram for predicting transmural bowel infarction in patients with acute superior mesenteric venous thrombosis. World J Gastroenterol 2020; 26:3800-3813. [PMID: 32774059 PMCID: PMC7383843 DOI: 10.3748/wjg.v26.i26.3800] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 05/23/2020] [Accepted: 06/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prognosis of acute mesenteric ischemia (AMI) caused by superior mesenteric venous thrombosis (SMVT) remains undetermined and early detection of transmural bowel infarction (TBI) is crucial. The predisposition to develop TBI is of clinical concern, which can lead to fatal sepsis with hemodynamic instability and multi-organ failure. Early resection of necrotic bowel could improve the prognosis of AMI, however, accurate prediction of TBI remains a challenge for clinicians. When determining the eligibility for explorative laparotomy, the underlying risk factors for bowel infarction should be fully evaluated. AIM To develop and externally validate a nomogram for prediction of TBI in patients with acute SMVT. METHODS Consecutive data from 207 acute SMVT patients at the Wuhan Tongji Hospital and 89 patients at the Guangzhou Nanfang Hospital between July 2005 and December 2018 were included in this study. They were grouped as training and external validation cohort. The 207 cases (training cohort) from Tongji Hospital were divided into TBI and reversible intestinal ischemia groups based on the final therapeutic outcomes. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for TBI using the training data, and a nomogram was subsequently developed. The performance of the nomogram was evaluated with respect to discrimination, calibration, and clinical usefulness in the training and external validation cohort. RESULTS Univariate and multivariate logistic regression analyses identified the following independent prognostic factors associated with TBI in the training cohort: The decreased bowel wall enhancement (OR = 6.37, P < 0.001), rebound tenderness (OR = 7.14, P < 0.001), serum lactate levels > 2 mmol/L (OR = 3.14, P = 0.009) and previous history of deep venous thrombosis (OR = 6.37, P < 0.001). Incorporating these four factors, the nomogram achieved good calibration in the training set [area under the receiver operator characteristic curve (AUC) 0.860; 95%CI: 0.771-0.925] and the external validation set (AUC 0.851; 95%CI: 0.796-0.897). The positive and negative predictive values (95%CIs) of the nomogram were calculated, resulting in positive predictive values of 54.55% (40.07%-68.29%) and 53.85% (43.66%-63.72%) and negative predictive values of 93.33% (82.14%-97.71%) and 92.24% (85.91%-95.86%) for the training and validation cohorts, respectively. Based on the nomogram, patients who had a Nomo-score of more than 90 were considered to have high risk for TBI. Decision curve analysis indicated that the nomogram was clinically useful. CONCLUSION The nomogram achieved an optimal prediction of TBI in patients with AMI. Using the model, the risk for an individual patient inclined to TBI can be assessed, thus providing a rational therapeutic choice.
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Affiliation(s)
- Meng Jiang
- Sino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Chang-Li Li
- Department of Geratology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan 430015, Hubei Province, China
| | - Chun-Qiu Pan
- Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Wen-Zhi Lv
- Department of Artificial Intelligence, Julei Technology Company, Wuhan 430030, Hubei Province, China
| | - Yu-Fei Ren
- Department of Computer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xin-Wu Cui
- Sino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Sabino KM, Fuller J, May S, Wakefield D. Safety and Tolerance of Enteral Nutrition in the Medical and Surgical Intensive Care Unit Patient Receiving Vasopressors. Nutr Clin Pract 2020; 36:192-200. [PMID: 32643840 DOI: 10.1002/ncp.10548] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 05/05/2020] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Multiple societal guidelines recommend enteral nutrition (EN) be initiated within 24 to 48 hours of admission to the intensive care unit (ICU) once a patient is hemodynamically stable. Gastrointestinal intolerance and occurrence of bowel ischemia have been a concern for patients receiving vasopressors while concurrently receiving luminal nutrients. The study objective was to determine whether patients receiving vasopressors while concomitantly receiving enteral nutrients had more incidences of bowel ischemia and intolerance than those receiving EN without vasopressor agents. METHODS This retrospective study included 319 medical and surgical ICU patients from a level 1 trauma center. The patients were either receiving vasopressors simultaneously with EN (n = 178) or EN alone (n = 141). Data regarding gastric residual volume (GRV), new abdominal pain, emesis, and bowel ischemia were collected. RESULTS There were more patients who had elevated GRV in the group that received vasopressors than patients who did not (20% vs 7%; P-value < .01). There were no differences between rates of bowel ischemia, emesis, or new abdominal pain between the 2 groups. CONCLUSION Based on our findings, EN is generally well tolerated and safe for those patients simultaneously receiving vasopressors.
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Affiliation(s)
- Kim M Sabino
- Trinity Health Of New England, Saint Francis Hospital and Medical Center, Hartford, Connecticut, 06105, USA
| | - Julie Fuller
- Trinity Health Of New England, Saint Francis Hospital and Medical Center, Hartford, Connecticut, 06105, USA
| | - Scott May
- Trinity Health Of New England, Saint Francis Hospital and Medical Center, Hartford, Connecticut, 06105, USA
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40
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Kale SD, Mehrkens BN, Stegman MM, Kastelberg B, Carnes H, McNeill RJ, Rizzo A, Karyala SV, Coutermarsh-Ott S, Fretz JA, Sun Y, Koff JL, Rajagopalan G. "Small" Intestinal Immunopathology Plays a "Big" Role in Lethal Cytokine Release Syndrome, and Its Modulation by Interferon-γ, IL-17A, and a Janus Kinase Inhibitor. Front Immunol 2020; 11:1311. [PMID: 32676080 PMCID: PMC7333770 DOI: 10.3389/fimmu.2020.01311] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 05/22/2020] [Indexed: 12/11/2022] Open
Abstract
Chimeric antigen receptor T cell (CART) therapy, administration of certain T cell-agonistic antibodies, immune check point inhibitors, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) and Toxic shock syndrome (TSS) caused by streptococcal as well as staphylococcal superantigens share one common complication, that is T cell-driven cytokine release syndrome (CRS) accompanied by multiple organ dysfunction (MOD). It is not understood whether the failure of a particular organ contributes more significantly to the severity of CRS. Also not known is whether a specific cytokine or signaling pathway plays a more pathogenic role in precipitating MOD compared to others. As a result, there is no specific treatment available to date for CRS, and it is managed only symptomatically to support the deteriorating organ functions and maintain the blood pressure. Therefore, we used the superantigen-induced CRS model in HLA-DR3 transgenic mice, that closely mimics human CRS, to delineate the immunopathogenesis of CRS as well as to validate a novel treatment for CRS. Using this model, we demonstrate that (i) CRS is characterized by a rapid rise in systemic levels of several Th1/Th2/Th17/Th22 type cytokines within a few hours, followed by a quick decline. (ii) Even though multiple organs are affected, small intestinal immunopathology is the major contributor to mortality in CRS. (iii) IFN-γ deficiency significantly protected from lethal CRS by attenuating small bowel pathology, whereas IL-17A deficiency significantly increased mortality by augmenting small bowel pathology. (iv) RNA sequencing of small intestinal tissues indicated that IFN-γ-STAT1-driven inflammatory pathways combined with enhanced expression of pro-apoptotic molecules as well as extracellular matrix degradation contributed to small bowel pathology in CRS. These pathways were further enhanced by IL-17A deficiency and significantly down-regulated in mice lacking IFN-γ. (v) Ruxolitinib, a selective JAK-1/2 inhibitor, attenuated SAg-induced T cell activation, cytokine production, and small bowel pathology, thereby completely protecting from lethal CRS in both WT and IL-17A deficient HLA-DR3 mice. Overall, IFN-γ-JAK-STAT-driven pathways contribute to lethal small intestinal immunopathology in T cell-driven CRS.
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Affiliation(s)
- Shiv D Kale
- Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA, United States
| | - Brittney N Mehrkens
- The Discipline of Microbiology and Immunology, Edward via College of Osteopathic Medicine, Blacksburg, VA, United States
| | - Molly M Stegman
- College of Sciences, Virginia Tech, Blacksburg, VA, United States
| | - Bridget Kastelberg
- Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA, United States
| | - Henry Carnes
- The Discipline of Microbiology and Immunology, Edward via College of Osteopathic Medicine, Blacksburg, VA, United States
| | - Rachel J McNeill
- Research and Graduate Studies, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Amy Rizzo
- Office of the University Veterinarian, Virginia Tech, Blacksburg, VA, United States
| | - Saikumar V Karyala
- Genomics Sequencing Center, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA, United States
| | - Sheryl Coutermarsh-Ott
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Jackie A Fretz
- Histology and Histomorphometry Laboratory, Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT, United States
| | - Ying Sun
- Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT, United States
| | - Jonathan L Koff
- Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT, United States
| | - Govindarajan Rajagopalan
- The Discipline of Microbiology and Immunology, Edward via College of Osteopathic Medicine, Blacksburg, VA, United States.,Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.,Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT, United States
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Zhao J, He Y, Xu P, Liu J, Ye S, Cao Y. Serum ammonia levels on admission for predicting sepsis patient mortality at D28 in the emergency department: A 2-center retrospective study. Medicine (Baltimore) 2020; 99:e19477. [PMID: 32176079 PMCID: PMC7220506 DOI: 10.1097/md.0000000000019477] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 12/11/2019] [Accepted: 02/10/2020] [Indexed: 02/05/2023] Open
Abstract
We assessed the predictive value of serum ammonia level on admission for the 28-day mortality of patients with sepsis.We retrospectively included septic patients admitted to the emergency department of West China Hospital, Sichuan University and The Fourth People's Hospital of Zigong city from June 2017 to May 2018. Patients were divided into 2 groups according to 28-day survival. Comparisons of serum ammonia level and sequential organ failure assessment (SOFA) score were made between 2 groups. Multivariate logistic regression models were employed to determine independent risk factors affecting 28-day mortality rate, and receiver operating characteristic (ROC) curve was also used to evaluate the efficacy of risk factors.Total of 316 patients were included into the study, 221 survived to 28 days and 95 were died before 28 days. The 28-day mortality rate was 30.06%. Multivariate logistic regression analyses revealed that the ammonia level, C reactive protein, SOFA score, and the leukocyte were independent risk factors for the 28-day mortality rate. In predicting the 28-day mortality rate, the SOFA score presented an area under the ROC curve (AUC) of 0.815, and the ammonia levels presented the AUC of 0.813.The ammonia level, C reactive protein, SOFA score, and the leukocyte are independent risk factors for 28-day mortality rate in septic patients. Moreover, the serum ammonia and SOFA score have similar predictive values. The serum ammonia level is also a suitable early indicator for prognostic evaluation of patients with sepsis as well.
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Affiliation(s)
- Jie Zhao
- Emergency Department, West China Hospital, Sichuan University, Chengdu
| | - Yarong He
- Emergency Department, West China Hospital, Sichuan University, Chengdu
| | - Ping Xu
- Emergency Department, The Fourth People's Hospital of Zigong City, Zigong
| | - Junzhao Liu
- Emergency Department, West China Hospital, Sichuan University, Chengdu
| | - Sheng Ye
- Emergency Department, West China Hospital, Sichuan University, Chengdu
| | - Yu Cao
- Emergency Department, West China Hospital, Sichuan University, Chengdu
- Disaster Medicine Center, Sichuan University, Chengdu, China
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Postresuscitation Care after Out-of-hospital Cardiac Arrest: Clinical Update and Focus on Targeted Temperature Management. Anesthesiology 2020; 131:186-208. [PMID: 31021845 DOI: 10.1097/aln.0000000000002700] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Out-of-hospital cardiac arrest is a major cause of mortality and morbidity worldwide. With the introduction of targeted temperature management more than a decade ago, postresuscitation care has attracted increased attention. In the present review, we discuss best practice hospital management of unconscious out-of-hospital cardiac arrest patients with a special focus on targeted temperature management. What is termed post-cardiac arrest syndrome strikes all organs and mandates access to specialized intensive care. All patients need a secured airway, and most patients need hemodynamic support with fluids and/or vasopressors. Furthermore, immediate coronary angiography and percutaneous coronary intervention, when indicated, has become an essential part of the postresuscitation treatment. Targeted temperature management with controlled sedation and mechanical ventilation is the most important neuroprotective strategy to take. Targeted temperature management should be initiated as quickly as possible, and according to international guidelines, it should be maintained at 32° to 36°C for at least 24 h, whereas rewarming should not increase more than 0.5°C per hour. However, uncertainty remains regarding targeted temperature management components, warranting further research into the optimal cooling rate, target temperature, duration of cooling, and the rewarming rate. Moreover, targeted temperature management is linked to some adverse effects. The risk of infection and bleeding is moderately increased, as is the risk of hypokalemia and magnesemia. Circulation needs to be monitored invasively and any deviances corrected in a timely fashion. Outcome prediction in the individual patient is challenging, and a self-fulfilling prophecy poses a real threat to early prognostication based on clinical assessment alone. Therefore, delayed and multimodal prognostication is now considered a key element of postresuscitation care. Finally, modern postresuscitation care can produce good outcomes in the majority of patients but requires major diagnostic and therapeutic resources and specific training. Hence, recent international guidelines strongly recommend the implementation of regional prehospital resuscitation systems with integrated and specialized cardiac arrest centers.
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Ilaiwy A, Ten Have GAM, Bain JR, Muehlbauer MJ, O'Neal SK, Berthiaume JM, Parry TL, Deutz NE, Willis MS. Identification of Metabolic Changes in Ileum, Jejunum, Skeletal Muscle, Liver, and Lung in a Continuous I.V. Pseudomonas aeruginosa Model of Sepsis Using Nontargeted Metabolomics Analysis. THE AMERICAN JOURNAL OF PATHOLOGY 2019; 189:1797-1813. [PMID: 31439155 PMCID: PMC6723233 DOI: 10.1016/j.ajpath.2019.05.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Revised: 04/26/2019] [Accepted: 05/23/2019] [Indexed: 02/06/2023]
Abstract
Sepsis is a multiorgan disease affecting the ileum and jejunum (small intestine), liver, skeletal muscle, and lung clinically. The specific metabolic changes in the ileum, jejunum, liver, skeletal muscle, and lung have not previously been investigated. Live Pseudomonas aeruginosa, isolated from a patient, was given via i.v. catheter to pigs to induce severe sepsis. Eighteen hours later, ileum, jejunum, medial gastrocnemius skeletal muscle, liver, and lung were analyzed by nontargeted metabolomics analysis using gas chromatography/mass spectrometry. The ileum and the liver demonstrated significant changes in metabolites involved in linoleic acid metabolism: the ileum and lung had significant changes in the metabolism of valine/leucine/isoleucine; the jejunum, skeletal muscle, and liver had significant changes in arginine/proline metabolism; and the skeletal muscle and lung had significant changes in aminoacyl-tRNA biosynthesis, as analyzed by pathway analysis. Pathway analysis also identified changes in metabolic pathways unique for different tissues, including changes in the citric acid cycle (jejunum), β-alanine metabolism (skeletal muscle), and purine metabolism (liver). These findings demonstrate both overlapping metabolic pathways affected in different tissues and those that are unique to others and provide insight into the metabolic changes in sepsis leading to organ dysfunction. This may allow therapeutic interventions that focus on multiple tissues or single tissues once the relationship of the altered metabolites/metabolism to the underlying pathogenesis of sepsis is determined.
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Affiliation(s)
- Amro Ilaiwy
- Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina; Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Gabriella A M Ten Have
- Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, Texas
| | - James R Bain
- Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina; Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Durham, North Carolina
| | - Michael J Muehlbauer
- Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina
| | - Sara K O'Neal
- Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina
| | - Jessica M Berthiaume
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Traci L Parry
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Nicolaas E Deutz
- Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, Texas
| | - Monte S Willis
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana.
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44
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Biomarqueurs entérocytaires et nutrition artificielle en réanimation. NUTR CLIN METAB 2019. [DOI: 10.1016/j.nupar.2019.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Abstract
Sepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Knowledge of the pathophysiology of organ failure in sepsis is crucial for optimizing the management and treatment of patients and for the development of potential new therapies. In clinical practice, six major organ systems - the cardiovascular (including the microcirculation), respiratory, renal, neurological, haematological and hepatic systems - can be assessed and monitored, whereas others, such as the gut, are less accessible. Over the past 2 decades, considerable amounts of new data have helped improve our understanding of sepsis pathophysiology, including the regulation of inflammatory pathways and the role played by immune suppression during sepsis. The effects of impaired cellular function, including mitochondrial dysfunction and altered cell death mechanisms, on the development of organ dysfunction are also being unravelled. Insights have been gained into interactions between key organs (such as the kidneys and the gut) and organ-organ crosstalk during sepsis. The important role of the microcirculation in sepsis is increasingly apparent, and new techniques have been developed that make it possible to visualize the microcirculation at the bedside, although these techniques are only research tools at present.
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Affiliation(s)
- Christophe Lelubre
- Laboratoire de Médecine Expérimentale (ULB 222 Unit), Université Libre de Bruxelles, CHU de Charleroi, A. Vésale Hospital, Montigny-Le-Tilleul, Belgium.,Department of Internal Medicine, CHU Charleroi - Hôpital Civil Marie Curie, Lodelinsart, Belgium
| | - Jean-Louis Vincent
- Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium.
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Elke G, Hartl WH, Kreymann KG, Adolph M, Felbinger TW, Graf T, de Heer G, Heller AR, Kampa U, Mayer K, Muhl E, Niemann B, Rümelin A, Steiner S, Stoppe C, Weimann A, Bischoff SC. Clinical Nutrition in Critical Care Medicine - Guideline of the German Society for Nutritional Medicine (DGEM). Clin Nutr ESPEN 2019; 33:220-275. [PMID: 31451265 DOI: 10.1016/j.clnesp.2019.05.002] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 05/03/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. METHODS The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. RESULTS In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. CONCLUSION The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).
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Affiliation(s)
- Gunnar Elke
- Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus 12, 24105, Kiel, Germany.
| | - Wolfgang H Hartl
- Department of Surgery, University School of Medicine, Grosshadern Campus, Ludwig-Maximilian University, Marchioninistr. 15, 81377 Munich, Germany.
| | | | - Michael Adolph
- University Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany.
| | - Thomas W Felbinger
- Department of Anesthesiology, Critical Care and Pain Medicine, Neuperlach and Harlaching Medical Center, The Munich Municipal Hospitals Ltd, Oskar-Maria-Graf-Ring 51, 81737, Munich, Germany.
| | - Tobias Graf
- Medical Clinic II, University Heart Center Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
| | - Geraldine de Heer
- Center for Anesthesiology and Intensive Care Medicine, Clinic for Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Axel R Heller
- Clinic for Anesthesiology and Surgical Intensive Care Medicine, University of Augsburg, Stenglinstrasse 2, 86156, Augsburg, Germany.
| | - Ulrich Kampa
- Clinic for Anesthesiology, Lutheran Hospital Hattingen, Bredenscheider Strasse 54, 45525, Hattingen, Germany.
| | - Konstantin Mayer
- Department of Internal Medicine, Justus-Liebig University Giessen, University of Giessen and Marburg Lung Center, Klinikstr. 36, 35392, Gießen, Germany.
| | - Elke Muhl
- Eichhörnchenweg 7, 23627, Gross Grönau, Germany.
| | - Bernd Niemann
- Department of Adult and Pediatric Cardiovascular Surgery, Giessen University Hospital, Rudolf-Buchheim-Str. 7, 35392, Gießen, Germany.
| | - Andreas Rümelin
- Clinic for Anesthesia and Surgical Intensive Care Medicine, HELIOS St. Elisabeth Hospital Bad Kissingen, Kissinger Straße 150, 97688, Bad Kissingen, Germany.
| | - Stephan Steiner
- Department of Cardiology, Pneumology and Intensive Care Medicine, St Vincenz Hospital Limburg, Auf dem Schafsberg, 65549, Limburg, Germany.
| | - Christian Stoppe
- Department of Intensive Care Medicine and Intermediate Care, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, Klinikum St. Georg, Delitzscher Straße 141, 04129, Leipzig, Germany.
| | - Stephan C Bischoff
- Department for Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599, Stuttgart, Germany.
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Piton G, Le Gouge A, Brulé N, Cypriani B, Lacherade JC, Nseir S, Mira JP, Mercier E, Sirodot M, Rigaud JP, Malaquin S, Soum E, Djibre M, Gaudry S, Thévenin D, Reignier J. Impact of the route of nutrition on gut mucosa in ventilated adults with shock: an ancillary of the NUTRIREA-2 trial. Intensive Care Med 2019; 45:948-956. [PMID: 31143999 DOI: 10.1007/s00134-019-05649-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 05/15/2019] [Indexed: 12/18/2022]
Abstract
PURPOSE The effects of the route of nutrition on the gut mucosa of patients with shock are unclear. Plasma citrulline concentration is a marker of enterocyte mass, and plasma intestinal fatty acid binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to study the effect of the route of nutrition on plasma citrulline concentration measured at day 3 of nutrition. MATERIALS AND METHODS Ancillary study of the NUTRIREA-2 trial. Ventilated adults with shock were randomly assigned to receive enteral or parenteral nutrition. Enterocyte biomarkers were measured at baseline, day 3, and day 8 of nutrition. RESULT A total of 165 patients from 13 French ICUs were included in the study: 85 patients in the enteral group and 80 patients in the parenteral group. At baseline, plasma citrulline was low without difference between groups (12.2 µmol L-1 vs 13.3 µmol L-1). At day 3, plasma citrulline concentration was higher in the enteral group than in the parenteral group (18.7 µmol L-1 vs 15.3 µmol L-1, p = 0.01). Plasma I-FABP concentration was increased at baseline, without difference between groups (245 pg mL-1 vs 244 pg mL-1). Plasma I-FABP concentration was higher in the enteral group than in the parenteral group at day 3 and day 8 (158 pg mL-1 vs 50 pg mL-1, p = 0.005 and 225 pg mL-1 vs 50 pg mL-1, p = 0.03). CONCLUSION Plasma citrulline concentration was higher after 3 days of enteral nutrition than after 3 days of parenteral nutrition. This result raises the question of the possibility that enteral nutrition is associated with a more rapid restoration of enterocyte mass than parenteral nutrition.
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Affiliation(s)
- Gaël Piton
- Medical Intensive Care Unit, CHRU Besançon, Besançon, France. .,EA3920, Université de Franche Comté, Besançon, France. .,Service de Réanimation Médicale, CHRU de Besançon, Boulevard Fleming, 25030, Besançon, France.
| | - Amélie Le Gouge
- Inserm CIC 1415, Tours, France.,Université de Tours, Tours, France.,CHU Tours, Tours, France
| | - Noelle Brulé
- Médecine Intensive Réanimation, CHU de Nantes, Nantes, France
| | - Benoit Cypriani
- Biochemistry Unit, Besançon University Hospital, Besançon, France
| | - Jean-Claude Lacherade
- Médecine Intensive Réanimation, Centre Hospitalier Départemental de la Vendée, La Roche sur Yon, France
| | - Saad Nseir
- Medical Intensive Care Unit, CHU Lille, Lille, France.,Medicine School, Université Lille, Lille, France
| | - Jean-Paul Mira
- Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Emmanuelle Mercier
- Médecine Intensive Réanimation, Hôpital Bretonneau, CHU Tours, Tours, France
| | - Michel Sirodot
- Medical-Surgical Intensive Care Unit, Centre Hospitalier Annecy-Genevois, Metz-Tessy, Pringy, France
| | | | | | - Edouard Soum
- Medical Intensive Care Unit, Hôpital Gabriel Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France
| | - Michel Djibre
- Medical-Surgical Intensive Care Unit, Tenon University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Stéphane Gaudry
- Medical-Surgical Intensive Care Unit, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris (AP-HP), Colombes, France.,Université Paris Diderot, ECEVE, UMR 1123, Sorbonne Paris Cité, Paris, France
| | - Didier Thévenin
- Medical-Surgical Intensive Care Unit, Centre Hospitalier Docteur Schaffner, Lens, France
| | - Jean Reignier
- Médecine Intensive Réanimation, CHU de Nantes, Nantes, France.,Université de Nantes, Nantes, France
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48
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Intestinal Fatty Acid Binding Protein is Associated With Mortality in Patients With Acute Heart Failure or Cardiogenic Shock. Shock 2019; 51:410-415. [DOI: 10.1097/shk.0000000000001195] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Gut rest strategy and trophic feeding in the acute phase of critical illness with acute gastrointestinal injury. Nutr Res Rev 2019; 32:176-182. [PMID: 30919797 DOI: 10.1017/s0954422419000027] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Critically ill patients frequently suffer from gastrointestinal dysfunction as the intestine is a vulnerable organ. In critically ill patients who require nutritional support, the current guidelines recommend the use of enteral nutrition within 24-48 h and advancing towards optimal nutritional goals over the next 48-72 h; however, this may be contraindicated in patients with acute gastrointestinal injury because overuse of the gut in the acute phase of critical illness may have an adverse effect on the prognosis. We propose that trophic feeding after 72 h, as a partial gut rest strategy, should be provided to critically ill patients during the acute phase of illness as an organ-protective strategy, especially for those with acute gastrointestinal injury.
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Hu Q, Ren H, Li G, Wang D, Zhou Q, Wu J, Zheng J, Huang J, Slade DA, Wu X, Ren J. STING-mediated intestinal barrier dysfunction contributes to lethal sepsis. EBioMedicine 2019; 41:497-508. [PMID: 30878597 PMCID: PMC6443583 DOI: 10.1016/j.ebiom.2019.02.055] [Citation(s) in RCA: 141] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 02/18/2019] [Accepted: 02/26/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Gut integrity is compromised in abdominal sepsis with increased cellular apoptosis and altered barrier permeability. Intestinal epithelial cells (IEC) form a physiochemical barrier that separates the intestinal lumen from the host's internal milieu and is strongly involved in the mucosal inflammatory response and immune response. Recent research indicates the involvement of the stimulator of interferons genes (STING) pathway in uncontrolled inflammation and gut mucosal immune response. METHODS We investigated the role of STING signaling in sepsis and intestinal barrier function using intestinal biopsies from human patients with abdominal sepsis and with an established model of abdominal sepsis in mice. FINDINGS In human abdominal sepsis, STING expression was elevated in peripheral blood mononuclear cells and intestinal biopsies compared with healthy controls, and the degree of STING expression in the human intestinal lamina propria correlated with the intestinal inflammation in septic patients. Moreover, elevated STING expression was associated with high levels of serum intestinal fatty acid binding protein that served as a marker of enterocyte damage. In mice, the intestinal STING signaling pathway was markedly activated following the induction of sepsis induced by cecal ligation perforation (CLP). STING knockout mice showed an alleviated inflammatory response, attenuated gut permeability, and decreased bacterial translocation. Whereas mice treated with a STING agonist (DMXAA) following CLP developed greater intestinal apoptosis and a more severe systemic inflammatory response. We demonstrated that mitochondrial DNA (mtDNA) was released during sepsis, inducing the intestinal inflammatory response through activating the STING pathway. We finally investigated DNase I administration at 5 hours post CLP surgery, showing that it reduced systemic mtDNA and inflammatory cytokines levels, organ damage, and bacterial translocation, suggesting that inhibition of mtDNA-STING signaling pathway protects against CLP-induced intestinal barrier dysfunction. INTERPRETATION Our results indicate that the STING signaling pathway can contribute to lethal sepsis by promoting IEC apoptosis and through disrupting the intestinal barrier. Our findings suggest that regulation of the mtDNA-STING pathway may be a promising therapeutic strategy to promote mucosal healing and protect the intestinal barrier in septic patients. FUND: National Natural Science Foundation of China.
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Affiliation(s)
- Qiongyuan Hu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; Medical School of Nanjing University, Nanjing, China
| | - Huajian Ren
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guanwei Li
- Department of colorectal and anal surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Dingyu Wang
- Medical School of Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Collaborative Innovation Center of Genetics and Development, Model Animal Research Center, Nanjing, China
| | - Quan Zhou
- Medical School of Nanjing University, Nanjing, China
| | - Jie Wu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; Medical School of Nanjing University, Nanjing, China
| | - Jiashuo Zheng
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; Medical School of Nanjing University, Nanjing, China
| | - Jinjian Huang
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Dominic A Slade
- Medical School of Nanjing University, Nanjing, China; Department of Surgery, Salford Royal NHS Foundation Trust, Stott Lane, Salford, United Kingdom.
| | - Xiuwen Wu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
| | - Jianan Ren
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
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