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Eleni Karakike, Maria-Evangelia Adami, Malvina Lada, Theologia Gkavogianni, Ioannis M Koutelidakis, Michael Bauer, Evangelos J Giamarellos-Bourboulis, Iraklis Tsangaris
High mobility group box 1 (HMGB1) is released from macrophages as a late biomarker of sepsis. Conditions associated with pre-existing macrophage activation may modify HMGB1 expression. This study aimed to assess the impact of HMGB1 kinetics on 28-day mortality. In a sub-study of a previous randomized clinical trial among patients with SIRS and Gram-negative infections, patients were classified in early and late HMGB1 peak groups. Serial measurements of HMGB1, ferritin and interferon-gamma (IFNγ) were performed in all available sera...
September 19, 2018: Shock
Jean-Marc Cavaillon, Evangelos J Giamarellos-Bourboulis
Immunosuppression is the most commonly used concept to qualify the immune status of patients with either sterile systemic inflammatory response syndrome (SIRS) or sepsis. In this review we attempt to demonstrate that the concept of immunosuppression is an oversimplification of the complex anti-inflammatory response that occurs in patients dealing with a severe sterile or infectious insult. Particularly, the immune status of leukocytes varies greatly depending on the compartment from where they are derived from...
September 19, 2018: Shock
Bonpei Takase, Yuko Higashimura, Kenichi Hashimoto, Haruka Asahina, Masayuki Ishihara, Hiromi Sakai
INTRODUCTION: Prolonged low blood pressure < 40 mmHg in hemorrhagic shock (HS) causes irreversible heart dysfunction, "Shock Heart Syndrome" (SHS), which is associated with lethal arrhythmias (VT/VF) leading to a poor prognosis. METHODS: To investigate whether the liposome-encapsulated human hemoglobin oxygen carrier (HbV) is comparable in effectiveness to autologous washed red blood cells (wRBCs) for improving arrhythmogenic properties in SHS, optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examinations were performed in Sprague-Dawley rat hearts obtained from rats subjected to acute HS by withdrawing 30% of total blood volume...
September 19, 2018: Shock
Andrew Murton, Fredrick J Bohanon, John O Ogunbileje, Karel D Capek, Ellen A Tran, Tony Chao, Labros S Sidossis, Craig Porter, David N Herndon
Sepsis is a common and often fatal consequence of severe burn injury, but its exact effects on whole body and muscle metabolism in the burn patient is unclear. To address this, 13 septic and 11 nonseptic patients (age: 36.9 ± 13.0 years) with burns encompassing >30% of their total body surface area underwent muscle protein kinetic studies under postabsorptive conditions using bolus injections of ring-C6 and N phenylalanine isotopes. In parallel, whole-body lipid and carbohydrate kinetics were assessed using constant infusions of [U-C6]palmitate, [6,6-H2]glucose, and [H5]glycerol, and during a 2-h hyperinsulinemic euglycemic clamp...
September 19, 2018: Shock
Zishuo Wang, Zhenlu Li, Dongcheng Feng, Guo Zu, Yang Li, Yan Zhao, Guangzhi Wang, Shili Ning, Jie Zhu, Feng Zhang, Jihong Yao, Xiaofeng Tian
Intestinal ischemia/reperfusion (I/R)-induced systemic inflammation leads to multiple organ dysfunction syndrome (MODS). Previous studies have indicated that the NLRP3 inflammasome modulates intestinal inflammation; however, the pathophysiological mechanisms remain unclear. Autophagy is a critical metabolic mechanism that promotes cellular survival following ischemic injury. Recently, basal autophagy has been implicated in the alleviation of extensive inflammation. However, the role of autophagy in NLRP3 inflammasome activation in intestinal I/R-induced inflammatory injury remains undefined...
September 13, 2018: Shock
Zhiyuan Wu, Yafeng Liang, Zhihao Li, Guangjian Liu, Jianbin Zheng, Yunlong Zuo, Lijuan Li, Xiaojun Cao, Jianhui Zhang, Huiying Liang
OBJECTIVES: Sepsis-3 consensus suggests "the need to develop similar updated definitions for pediatric populations". Sequential organ failure assessment (SOFA) and systemic inflammatory response syndrome (SIRS) criteria are two systems widely used to define the status of infection. However, It is still unclear whether SOFA is more accurate than SIRS in predicting children mortality in low- and middle-income countries. Thus, we validated the accuracy of age-adapted SOFA and SIRS in predicating the poor prognosis of infected children in China's pediatric intensive care unit (PICU)...
September 11, 2018: Shock
Simon Skibsted, Manoj K Bhasin, Daniel J Henning, Shou Ching Jaminet, Jeffrey Lewandowski, Hans Kirkegaard, William C Aird, Nathan I Shapiro
BACKGROUND: The complex host response to sepsis is incompletely understood. The aim of this investigation is to use leukocyte RNA sequencing to characterize biological functions, cellular pathways, and key regulatory molecules driving sepsis pathophysiology. METHODS: This was a prospective, observational study of Emergency Department patients with sepsis, at an urban, academic, tertiary care center. In the derivation cohort, we collected blood at enrollment and 90 days after hospital discharge allowing each patient to serve as an internal control...
September 11, 2018: Shock
Xibing Ding, Shuqing Jin, Zhenzhen Shao, Li Xu, Zhuang Yu, Yao Tong, Zhixia Chen, Heth Turnquist, Bruce R Pitt, Timothy R Billiar, Li-Ming Zhang, Quan Li
Mechanical ventilation (MV) is frequently employed to manage respiratory failure in sepsis patients and is required for the surgical management of intra-abdominal sepsis. The impact of MV varies dramatically depending on tidal volume, with even moderate tidal volume (MTV) ventilation leading to ventilator-induced lung injury, whereas low tidal volume (LTV) ventilation protects against sepsis-induced ARDS. IL-33 is known to contribute to lung injury in sepsis and its release can be induced by mechanical stress...
September 5, 2018: Shock
Hui Jin, Monowar Aziz, Yasumasa Ode, Ping Wang
Extracellular cold-inducible RNA-binding protein (CIRP) exaggerates inflammation in sepsis. Neutrophil reverse transendothelial migration (rTEM) allows neutrophils to migrate from tissues into the circulation. The phenotype of neutrophils following reverse migration is CD54CXCR1. We hypothesize that CIRP induces neutrophil rTEM in sepsis. Sepsis was induced in male C57BL/6 mice by cecal ligation and puncture (CLP), and at 5, 10, or 20 h after CLP, the frequencies of reversely migrated (RM) neutrophils were assessed in the blood by flow cytometry...
August 24, 2018: Shock
Hongpeng Jia, Chhinder P Sodhi, Yukihiro Yamaguchi, Peng Lu, Mitchell R Ladd, Adam Werts, William B Fulton, Sanxia Wang, Thomas Prindle, David J Hackam
Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants, and is associated with the development of severe lung inflammation. The pathogenesis of NEC-induced lung injury remains unknown, yet infiltrating immune cells may play a role. In support of this possibility, we now show that NEC in mice and humans was associated with the development of profound lung injury that was characterized by an influx of Th17 cells and a reduction in Tregs. Importantly, the adoptive transfer of CD4 T cells isolated from lungs of mice with NEC into the lungs of immune incompetent mice (Rag1 mice) induced profound inflammation in the lung, while the depletion of Tregs exacerbated NEC induced lung injury, demonstrating that imbalance of Th17/Treg in the lung is required for the induction of injury...
August 24, 2018: Shock
Youn-Jung Kim, Jihoon Kang, Seung Mok Ryoo, Shin Ahn, Jin Won Huh, Won Young Kim
INTRODUCTION: Chemotherapy-induced febrile neutropenia (FN) causes life-threatening complications, but little is known in septic shock patients with FN. The aim of this study was to investigate the prognostic value of inflammatory markers, including C-reactive protein level, immature granulocyte count, white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR), in septic shock patients with FN at admission and after granulocyte colony-stimulating factor (G-CSF) administration...
August 24, 2018: Shock
Ting Hu, Hang Sun, Wan-Yan Deng, Wen-Qi Huang, Qi Liu
Most cases of acute liver failure are caused by acetaminophen (APAP) overdose. Oxidative stress is a key factor in APAP toxicity. While augmenter of liver regeneration (ALR) has both anti-oxidative and anti-apoptotic effects, its therapeutic potential in APAP hepatotoxicity remains unknown. The current study assessed the protective effects and associated mechanisms of ALR against APAP-induced acute liver injury in female BALB/c mice. We found that serum ALT and AST levels, intrahepatic hemorrhage and necrosis were increased at 3, 6, 12, 24, 48 and 72 h after 600 mg/kg APAP intraperitoneal injection...
August 22, 2018: Shock
Jinghong Xu, Li Tong, Jiyou Yao, Zilu Guo, Ka Yin Lui, XiaoGuang Hu, Lu Cao, Yanping Zhu, Fa Huang, Xiangdong Guan, Changjie Cai
INTRODUCTION: The objective of our study was to explore the association between sex and clinical outcome in sepsis patients in a large, diverse population. MATERIALS AND METHODS: We analysed 6134 adult patients with sepsis from the critical care units of Beth Israel Deaconess Medical Center between 2001 and 2012. Study data were retrospectively extracted from MIMIC-III, a multiparameter intensive care database. RESULTS: There were 2677 (43...
August 22, 2018: Shock
Christoph Arens, Timo Kramm, Sebastian Decker, Jens Spannenberger, Thorsten Brenner, Daniel Christoph Richter, Markus Alexander Weigand, Florian Uhle, Christoph Lichtenstern
BACKGROUND: In non-neutropenic intensive care unit (ICU) patients, current risk stratification scores lack specificity to reliably predict the risk of a prospective invasive candidiasis (IC). We aimed to explore possible associations of distinct immunological markers with different degrees of Candida affection in patients with abdominal sepsis. METHODS: The presented explorative, non-interventional diagnosis study, recruited patients admitted to the surgical ICU at Heidelberg University Hospital with abdominal sepsis...
August 22, 2018: Shock
Jia Yu, Lan Ni, Xiaoyi Zhang, Jing Zhang, Osama Abdel-Razek, Guirong Wang
Severe acute pancreatitis (SAP) often causes acute lung injury (ALI) by systemic inflammatory response. Surfactant protein D (SP-D) plays critical roles in host defense and inflammation regulation. NLRP3 inflammasomes and NF-κB signaling are key regulators in innate immunity and inflammation. We hypothesized that SP-D attenuates ALI by suppressing NLRP3 inflammasome and NF-κB activation. METHODS: Wild-type C57BL/6 (WT), SP-D knockout (KO), and humanized transgenic SP-D (hTG) mice were used in this study...
August 17, 2018: Shock
Yessica Alina Rodriguez-Rosales, Matthijs Kox, Esther van Rijssen, Bram van Cranenbroek, Marina van Welie, Peter Pickkers, Irma Joosten, Hans Koenen
Sepsis is the cause of more than 5.3 million deaths per year, and novel immunotherapeutic strategies are highly warranted. Human models that mirror sepsis immunology are instrumental to this aim. The response to endotoxin in humans during the first 24 hours captures many hallmarks of the inflammatory response observed in sepsis. However, the long-term immunologic effects of human experimental endotoxemia have been sparsely studied and could be determinant for the use of this model in sepsis therapy research...
August 17, 2018: Shock
Marlies Ballegeer, Jolien Vandewalle, Melanie Eggermont, Gert Van Isterdael, Lien Dejager, Liesbet De Bus, Johan Decruyenaere, Roosmarijn E Vandenbroucke, Claude Libert
Sepsis in humans and experimental animals is characterized by an acute inflammatory response. Glucocorticoids (GCs) are widely used for the treatment of many inflammatory disorders, yet their effectiveness in sepsis is debatable. One of the major anti-inflammatory proteins induced by GCs is GILZ (Glucocorticoid-Induced Leucine Zipper, coded by the TSC22D3 gene). We found that TSC22D3 mRNA expression is downregulated in white blood cells of human sepsis patients. Interestingly, transgenic Gilz overexpressing mice (Gilz-tg) showed better survival rates in the cecal ligation and puncture (CLP) model of mouse sepsis...
August 17, 2018: Shock
Sander Rozemeijer, Jelle L G Haitsma Mulier, Jantine G Röttgering, Paul W G Elbers, Angélique M E Spoelstra-de Man, Pieter Roel Tuinman, Monique C de Waard, Heleen M Oudemans-van Straaten
INTRODUCTION: Shock is characterised by micro- and macrovascular flow impairment contributing to acute kidney injury (AKI). Routine monitoring of the circulation regards the macrocirculation but not the renal circulation which can be assessed with Doppler ultrasound as renal resistive index (RRI). RRI reflects resistance to flow. High RRI predicts persistent AKI. Study aims were to determine whether RRI is elevated in shock and to identify determinants of RRI. MATERIALS AND METHODS: This prospective observational cohort study included two cohorts of patients, with and without shock <24-h after intensive care admission...
August 14, 2018: Shock
Stefan Rasche, Alexander Trumpp, Martin Schmidt, Katrin Plötze, Frederik Gätjen, Hagen Malberg, Klaus Matschke, Matthias Rudolf, Fabian Baum, Sebastian Zaunseder
PURPOSE: Camera-based photoplethysmography (cbPPG) remotely detects the volume pulse of cardiac ejection in the peripheral circulation. The cbPPG signal is sourced from the cutaneous microcirculation, yields a two-dimensional intensity map and is therefore an interesting monitoring technique. In this study we investigated, whether cbPPG is in general sufficiently sensitive to discern hemodynamic conditions. METHODS: cbPPG recordings of seventy patients recovering from cardiac surgery were analyzed...
August 14, 2018: Shock
Basilia Zingarelli, Craig M Coopersmith, Susanne Drechsler, Philip Efron, John C Marshall, Lyle Moldawer, W Joost Wiersinga, Xianzhong Xiao, Marcin F Osuchowski, Christoph Thiemermann
Pre-clinical animal studies are mandatory before new treatments can be tested in clinical trials. However, their use in developing new therapies for sepsis has been controversial because of limitations of the models and inconsistencies with the clinical conditions. In consideration of the revised definition for clinical sepsis and septic shock (Sepsis-3), a Wiggers-Bernard Conference was held in Vienna in May 2017 to propose standardized guidelines on pre-clinical sepsis modeling. The participants conducted a literature review of 260 most highly cited scientific articles on sepsis models published between 2003 and 2012...
August 14, 2018: Shock
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