Protocol for isolating high-purity natural killer cells from peripheral blood of septic patients using magnetic cell separation.

In human sepsis, myelocytosis and concomitant lymphopenia complicate the study of peripheral blood natural killer (NK) cells. Here, we present a protocol for isolating NK cells from peripheral blood of septic patients using magnetic cell separation. We describe steps for the depletion of non-NK cells and NK cell enrichment.

Mortality Prediction by Kinetic Parameters of Lactate and S-Adenosylhomocysteine in a Cohort of Critically Ill Patients.

Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death.

Downregulation of Hypoxia Inducible Factor-1α in Primary Human Natural Killer Cells Using Small Interfering RNA Delivery with ExPERT ATx by MaxCyte.

Natural killer (NK) cells are innate cytokine-producing and cytolytic effector lymphocytes. Their function is responsive to environmental factors, e.g.

Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator.

Background: Pneumonia develops frequently after major surgery and polytrauma and thus in the presence of systemic inflammatory response syndrome (SIRS) and organ dysfunction. Immune checkpoints balance self-tolerance and immune activation. Altered checkpoint blood levels were reported for sepsis.

S-Adenosylhomocysteine Is a Useful Metabolic Factor in the Early Prediction of Septic Disease Progression and Death in Critically Ill Patients: A Prospective Cohort Study.

A common final pathway of pathogenetic mechanisms in septic organ dysfunction and death is a lack or non-utilization of oxygen. Plasma concentrations of lactate serve as surrogates for the oxygen-deficiency-induced imbalance between energy supply and demand. As S-adenosylhomocysteine (SAH) was shown to reflect tissue hypoxia, we compared the ability of SAH versus lactate to predict the progression of inflammatory and septic disease to septic organ dysfunction and death.

Key Signature Genes of Early Terminal Granulocytic Differentiation Distinguish Sepsis From Systemic Inflammatory Response Syndrome on Intensive Care Unit Admission.

Infection can induce granulopoiesis. This process potentially contributes to blood gene classifiers of sepsis in systemic inflammatory response syndrome (SIRS) patients. This study aimed to identify signature genes of blood granulocytes from patients with sepsis and SIRS on intensive care unit (ICU) admission.

Differential Network Testing Reveals Diverging Dynamics of Organ System Interactions for Survivors and Non-survivors in Intensive Care Medicine.

Statistical network analyses have become popular in many scientific disciplines, where an important task is to test for differences between two networks. We describe an overall framework for differential network testing procedures that vary regarding (1) the network estimation method, typically based on specific concepts of association, and (2) the network characteristic employed to measure the difference. Using permutation-based tests, our approach is general and applicable to various overall, node-specific or edge-specific network difference characteristics.

Ground truth labels challenge the validity of sepsis consensus definitions in critical illness.

Background: Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity.

STAT3 governs the HIF-1α response in IL-15 primed human NK cells.

Natural killer (NK) cells mediate innate host defense against microbial infection and cancer. Hypoxia and low glucose are characteristic for these tissue lesions but do not affect early interferon (IFN) γ and CC chemokine release by interleukin 15 (IL-15) primed human NK cells in vitro. Hypoxia inducible factor 1α (HIF-1α) mediates cellular adaption to hypoxia.

Lung Protection vs. Infection Resolution: Interleukin 10 Suspected of Double-Dealing in COVID-19.

The pathological processes by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that make the virus a major threat to global health are insufficiently understood. Inefficient viral clearance at any stage is a hallmark of coronavirus disease 2019 (COVID-19). Disease severity is associated with increases in peripheral blood cytokines among which interleukin 10 (IL-10) increases particularly early and independent of patient age, which is not seen in active SARS-CoV infection.

Impact of different consensus definition criteria on sepsis diagnosis in a cohort of critically ill patients-Insights from a new mathematical probabilistic approach to mortality-based validation of sepsis criteria.

Background: Sepsis-3 definition uses SOFA score to discriminate sepsis from uncomplicated infection, replacing SIRS criteria that were criticized for being inaccurate. Eligibility of sepsis-3 criteria for sepsis diagnosis and the applied validation methodology using mortality as endpoint are topic of ongoing debate. We assessed the impact of different criteria on sepsis diagnosis in our ICU and devised a mathematical approach for mortality-based validation of sepsis criteria.

Innate Cytokine Induced Early Release of IFNγ and CC Chemokines from Hypoxic Human NK Cells Is Independent of Glucose.

Natural killer (NK) cells are among the first innate immune cells to arrive at sites of tissue inflammation and regulate the immune response to infection and tumors by the release of cytokines including interferon (IFN)γ. In vitro exposure to the innate cytokines interleukin 15 (IL-15) and IL-12/IL-18 enhances NK cell IFNγ production which, beyond 16 h of culture, was shown to depend on metabolic switching to glycolysis. NK effector responses are, however, rapid by comparison.

Interleukin-15 Signaling in HIF-1α Regulation in Natural Killer Cells, Insights Through Mathematical Models.

Natural killer (NK) cells belong to the first line of host defense against infection and cancer. Cytokines, including interleukin-15 (IL-15), critically regulate NK cell activity, resulting in recognition and direct killing of transformed and infected target cells. NK cells have to adapt and respond in inflamed and often hypoxic areas.

Leveraging implicit expert knowledge for non-circular machine learning in sepsis prediction.

Sepsis is the leading cause of death in non-coronary intensive care units. Moreover, a delay of antibiotic treatment of patients with severe sepsis by only few hours is associated with increased mortality. This insight makes accurate models for early prediction of sepsis a key task in machine learning for healthcare.

: A Potential New Reference Gene in Human Natural Killer Cells and Granulocytes in Sepsis.

Timely and reliable distinction of sepsis from non-infectious systemic inflammatory response syndrome (SIRS) supports adequate antimicrobial therapy and saves lives but is clinically challenging. Blood transcriptional profiling promises to deliver insights into the pathomechanisms of SIRS and sepsis and to accelerate the discovery of urgently sought sepsis biomarkers. However, suitable reference genes for normalizing gene expression in these disease conditions are lacking.

Sequential transmigration of polymorphonuclear cells and naive CD3 T lymphocytes across the blood-cerebrospinal-fluid barrier in vitro following infection with Echovirus 30.

Viral meningitis by non-polio enteroviruses (NPEV) is a major public health burden causing fatal outcomes especially in the younger population. Strong evidence exists that the blood-cerebrospinal-fluid (CSF) barrier (BCSFB) serves as an entry point for enterovirus and leucocytes into the central nervous system (CNS). Moreover, analysis of clinical CSF specimens of patients with a NPEV infection revealed a predominance of polymorphonuclear granulocytes (PMN) in the early phase and mononuclear cells in the later course of meningitis.

Correction: Monoclonal Antibody RYSK173 Recognizes the Dinuclear Zn Center of Serum Carnosinase 1 (CN-1): Possible Consequences of Zn Binding for CN-1 Recognition by RYSK173.

[This corrects the article DOI: 10.1371/journal.pone.

An Algorithm for Systemic Inflammatory Response Syndrome Criteria-Based Prediction of Sepsis in a Polytrauma Cohort.

Objectives: Lifesaving early distinction of infectious systemic inflammatory response syndrome, known as "sepsis," from noninfectious systemic inflammatory response syndrome is challenging in the ICU because of high systemic inflammatory response syndrome prevalence and lack of specific biomarkers. The purpose of this study was to use an automatic algorithm to detect systemic inflammatory response syndrome criteria (tachycardia, tachypnea, leukocytosis, and fever) in surgical ICU patients for ICU-wide systemic inflammatory response syndrome prevalence determination and evaluation of algorithm-derived systemic inflammatory response syndrome descriptors for sepsis prediction and diagnosis in a polytrauma cohort.

Design: Cross-sectional descriptive study and retrospective cohort study.

Short Term Hypoxia Synergizes with Interleukin 15 Priming in Driving Glycolytic Gene Transcription and Supports Human Natural Killer Cell Activities.

Natural killer (NK) cells induce apoptosis in infected and transformed cells and are important producers of immunoregulatory cytokines. Therefore, they operate under low oxygen conditions (hypoxia) in inflammatory and tumor environments. In vitro studies of NK cells are, however, commonly performed in ambient air (normoxia).