Systemic levels of cytokines are altered during infection and sepsis. This prospective observational study aimed to investigate whether plasma levels of multiple inflammatory mediators differed between sepsis patients with and those without bacteremia during the initial phase of hospitalization. A total of 80 sepsis patients with proven bacterial infection and no immunosuppression were included in the study. Plasma samples were collected within 24 h of hospitalization, and Luminex^® analysis was performed on 35 mediators: 16 cytokines, six growth factors, four adhesion molecules, and nine matrix metalloproteases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs). Forty-two patients (52.5%) and 38 (47.5%) patients showed positive and negative blood cultures, respectively. There were significant differences in plasma levels of six soluble mediators between the two “bacteremia” and “non-bacteremia” groups, using Mann–Whitney U test (p < 0.0014): tumor necrosis factor alpha (TNFα), CCL4, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and TIMP-1. Ten soluble mediators also significantly differed in plasma levels between the two groups, with p-values ranging between 0.05 and 0.0014: interleukin (IL)-1ra, IL-10, CCL2, CCL5, CXCL8, CXCL11, hepatocyte growth factor, MMP-8, TIMP-2, and TIMP-4. VCAM-1 showed the most robust results using univariate and multivariate logistic regression. Using unsupervised hierarchical clustering, we found that TNFα, CCL4, E-selectin, VCAM-1, ICAM-1, and TIMP-1 could be used to discriminate between patients with and those without bacteremia. Patients with bacteremia were mainly clustered in two separate groups (two upper clusters, 41/42, 98%), with higher levels of the mediators. One (2%) patient with bacteremia was clustered in the lower cluster, which compromised most of the patients without bacteremia (23/38, 61%) (χ² test, p < 0.0001). Our study showed that analysis of the plasma inflammatory mediator profile could represent a potential strategy for early identification of patients with bacteremia.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Common causes include gram-negative and gram-positive bacteria as well as fungi. Neutrophils are among the first cells to arrive at an infection site where they function as important effector cells of the innate immune system and as regulators of the host immune response. The regulation of neutrophil migration is therefore important both for the infection-directed host response and for the development of organ dysfunctions in sepsis. Downregulation of CXCR4/CXCL12 stimulates neutrophil migration from the bone marrow. This is followed by transmigration/extravasation across the endothelial cell barrier at the infection site; this process is directed by adhesion molecules and various chemotactic gradients created by chemotactic cytokines, lipid mediators, bacterial peptides, and peptides from damaged cells. These mechanisms of neutrophil migration are modulated by sepsis, leading to reduced neutrophil migration and even reversed migration that contributes to distant organ failure. The sepsis-induced modulation seems to differ between neutrophil subsets. Furthermore, sepsis patients should be regarded as heterogeneous because neutrophil migration will possibly be further modulated by the infecting microorganisms, antimicrobial treatment, patient age/frailty/sex, other diseases (e.g., hematological malignancies and stem cell transplantation), and the metabolic status. The present review describes molecular mechanisms involved in the regulation of neutrophil migration; how these mechanisms are altered during sepsis; and how bacteria/fungi, antimicrobial treatment, and aging/frailty/comorbidity influence the regulation of neutrophil migration.

Sepsis is a dysregulated host response to infection that causes potentially life-threatening organ dysfunction. We investigated the serum metabolomic profile at hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria whereas the remaining 25 patients only fulfilled the previous Sepsis-2 criteria and could therefore be classified as having systemic inflammatory response syndrome (SIRS). A total of 1011 identified metabolites were detected in our serum samples. Ninety-seven metabolites differed significantly when comparing Sepsis-3 and Sepsis-2/SIRS patients; 40 of these metabolites constituted a heterogeneous group of amino acid metabolites/peptides. When comparing patients with and without bacteremia, we identified 51 metabolites that differed significantly, including 16 lipid metabolites and 11 amino acid metabolites. Furthermore, 42 metabolites showed a highly significant association with the maximal total Sequential Organ Failure Assessment (SOFA )score during the course of the disease (i.e., Pearson’s correlation test, p-value < 0.005, and correlation factor > 0.6); these top-ranked metabolites included 23 amino acid metabolites and a subset of pregnenolone/progestin metabolites. Unsupervised hierarchical clustering analyses based on all 42 top-ranked SOFA correlated metabolites or the subset of 23 top-ranked amino acid metabolites showed that most Sepsis-3 patients differed from Sepsis-2/SIRS patients in their systemic metabolic profile at the time of hospital admission. However, a minority of Sepsis-3 patients showed similarities with the Sepsis-2/SIRS metabolic profile even though several of them showed a high total SOFA score. To conclude, Sepsis-3 patients are heterogeneous with regard to their metabolic profile at the time of hospitalization.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In the present study, we investigated the systemic/serum lipidomic profile at the time of hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria (referred to as Sepsis-3) whereas the remaining 25 patients had sepsis only according to the previous Sepsis-2 definition and could be classified as having Systemic Inflammatory Response Syndrome (SIRS). A total of 966 lipid metabolites were identified. Patients fulfilling the Sepsis-3 criteria differed from the Sepsis-2 patients with regard to only 15 lipid metabolites, and especially sphingolipids metabolism differed between these patient subsets. A total of only 43 metabolites differed between patients with and without bacteremia, including 12 lysophosphatidylcholines and 18 triacylglycerols (15 C18/C20 fatty acid metabolites decreased and three C14 myristate acid metabolites that were increased in bacteremia). Unsupervised hierarchical clustering analyses based on the identified sphingolipids, phosphatidylcholine and triacylglycerols showed that (i) the majority of Sepsis-3 patients differed from SIRS patients especially with regard to lysophosphatidylcholine levels; (ii) the minority of Sepsis-3 patients that clustered together with the majority of SIRS patients showed lower Sequential Organ Failure Assessment (SOFA) scores than the other Sepsis-3 patients; and (iii) the variation between the patients in the identified/altered sphingolipid and triacylglycerol metabolites further increased the heterogeneity of Sepsis-3 patients with regard to their systemic lipidomic profile at the time of diagnosis. To conclude, patients fulfilling the Sepsis-3 criteria differ with regard to their metabolic profile, and this variation depends on disease severity.

30.01.2023: Originalartikkel - Skåringsverktøyet NEWS2 er egnet til å oppdage sepsis hos pasienter innlagt på sengepost.

08.05.2018: Leder - Intermediate care units in hospitals are important for the treatment and care of seriously ill patients who do not need full intensive-care monitoring, but who are too ill to be cared for in an ordinary ward.