Circulating Immature Granulocytes With T-Cell Killing Functions Predict Sepsis Deterioration* (original) (raw)
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Shock, 2012
Exocytosis of granules containing the cytolytic effector (CE) molecules granzyme A (GzmA), granzyme B (GzmB), and perforin is one major pathway of lymphocyte-mediated cytotoxicity. Studies in murine models and the finding of elevated granzyme levels in the plasma of septic patients have implicated cytotoxic lymphocytes in the pathogenesis of sepsis. We sought to evaluate the role of cytotoxic cells and CE in sepsis and determine if intracellular levels of CE in cytotoxic cells correlate with disease severity. We conducted a prospective cohort study of 40 patients enrolled into one of three groups: controls (C), acutely ill nonseptic illnesses, or patients with severe sepsis (SS) (lactate, 94 mmol/L; systolic blood pressure, G90 mmHg after 2 L normal saline). Peripheral blood mononuclear cells were isolated and stained for extracellular markers for defined subpopulations and for intracellular expression of GzmA and GzmB and perforin. Levels of CE were quantified by geometric mean fluorescent intensity (GMFI) via flow cytometry. Cytotoxic T lymphocyte (CTL) expression was higher in SS (P = 0.04). The GMFI of GzmB was significantly higher in CTLs of SS patients versus acutely ill nonseptic illnesses or C. The GMFI of each GzmA and GzmB in CTLs were associated with the Acute Physiology and Chronic Health Evaluation II score (P = 0.01). A significant increase in the number of granulocytes in the peripheral blood mononuclear cells of SS patients consisted primarily of low-density neutrophils, which expressed increased levels of GzmA (P G 0.01). The results suggest that CTLs are activated in SS and express significantly higher intracellular levels of GzmB and that GzmA and B levels correlate with disease severity.
BMC Immunology, 2013
Background: Sepsis is a serious disease condition and a major cause of intensive care unit (ICU) admission. Its diagnosis in critically ill patients is complicated. To diagnose an infection rapidly, and to accurately differentiate systemic inflammatory response syndrome (SIRS) from sepsis, is challenging yet early diagnosis is vital for early induction of an appropriate therapy. The aim of this study was to evaluate whether the immature granulocyte (IG) count is a useful early diagnostic marker of sepsis compared to other markers. Therefore, a total of 70 consecutive surgical intensive care patients were assessed. IGs were measured from whole blood samples using an automated analyzer. C-reactive protein (CRP), lipopolysaccharide binding protein (LBP) and interleukin-6 (IL-6) concentrations were also determined. The observation period was a maximum of 21 days and ended with the patients' discharge from ICU or death. Receiver operating characteristic (ROC) analyses were conducted and area under the curve (AUC) was calculated to determine sensitivities and specificities for the parameters. Results: We found that the IG count significantly discriminates between infected and non-infected patients (P < 0.0001) with a sensitivity of 89.2% and a specificity of 76.4%, particularly within the first 48 hours after SIRS onset. Regarding the discriminative power for infection, the IG count was more indicative than other clinical parameters such as CRP, LBP and IL-6, which had a sensitivity of less than 68%. Additionally, the highest diagnostic odds ratio (DOR) with 26.7 was calculated for the IG count within the first 48 hours. During the course of the disease ROC curve analyses showed a superior positive predictive value of the IG count compared to the other measured parameters during the first five days following the fulfillment of SIRS criteria. However, the number of IGs was not correlated with ICU mortality. Conclusions: The total number of IG in peripheral blood from ICU patients is a good marker to discriminate infected and non-infected patients very early during SIRS. However, the IG count is not suitable as a prognostic marker for mortality. Routine and serial measurement of IGs may provide new possibilities for rapid screening of SIRS patients on ICU with suspected infections.
American journal of respiratory and critical care medicine, 2017
Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression but their clinical impact remains poorly defined. To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in septic patients. Peripheral blood transcriptomic analysis was performed on 29 septic patients and 15 healthy donors. A second cohort of 94 consecutive septic patients, 11 severity-matched intensive care patients and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments. Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8 and ARG1, were upregulated in the peripheral blood of septic patients. CD14(pos)HLA-DR(low/neg) monocytic (M)-MDSCs were expanded in intensive care septic and non-septic patients and CD14(neg)CD15(pos) low-density granulocytes/ granul...
Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis
Indian Journal of Critical Care Medicine, 2022
Background: Diagnosing sepsis early is important for its successful management. Various biomarkers are being used currently, but mostly they are either expensive or not readily available. This study aims to evaluate usefulness of automated immature granulocyte count (IG#) and immature granulocyte percentage (IG%) as early diagnostic markers of sepsis and compares it to other established predictive markers. Patients and methods: In this prospective observational study, 137 eligible, critically ill, nonseptic intensive care unit patients were analyzed for automated IG#, IG%, serum procalcitonin (PCT), and blood lactate (Lac), daily for 7 days after recruitment. Patients were followed for the development of sepsis, defined by the new Sepsis-3 criteria. The study was divided into four time periods of 24 hours each with respect to the day of developing organ dysfunction. Using area under receiver operator characteristic and diagnostic odds ratio (DOR) methods, the best biomarker for the prediction of sepsis in each time period was calculated. Results: IG# and IG% were the earliest biomarkers to have a significant discriminating value with area under the curve of 0.81 and 0.82, respectively, as early as 24 hours before clinical sepsis is diagnosed by Sepsis-3 criteria. Both IG# and IG% have a high DOR of 34.91 and 18.11, respectively, when compared to others like PCT and Lac having a DOR of 27.06 and 4.78, respectively. Conclusion: IG# and IG% are easily available, rapid, and inexpensive tools to differentiate between septic and nonseptic patients with high specificity and sensitivity. It is the earliest biomarker to show a significant rise in patients developing sepsis.
Myeloid-derived suppressor cells in secondary sepsis: Is there association with lethal outcome?
Vojnosanitetski pregled
Background/Aim. Role of myeloid-derived suppressor cells (MDSCs) in human host response to sepsis still needs to be clarified. The aim of our study was to determine whether frequency and/or absolute numbers of the MDSCs were associated with outcome in critically ill patients with secondary sepsis and/or septic shock. Methods. Total of 40 critically ill patients with secondary sepsis were enrolled in a prospective study. We detected and enumerated both main subsets of MDSCs: granulocytic (G)-MDSCs and monocytic (M)- MDSCs on the Day 1 (the day of hospital admission) and the Day 5 after the. The primary end-point was hospital mortality. Results. Increased frequencies and absolute numbers of subpopulations corresponding to MDSCs were associated with poor outcome. As far as relative kinetics was concerned, in both survivors and non-survivors, sepsis duration from 1th to 5th day was accompanied by an increase in MDSCs values of both investigated subpopulations. In contrast to findings of...
Epidemiology and Prognostic Utility of Cellular Components of Hematological System in Sepsis
Indian Journal of Critical Care Medicine, 2021
Background: Data are lacking on the role of cellular components of hematological system as biomarkers for prognosis of sepsis. We planned to identify if these parameters measured at admission to ICU and at 72 hours can be useful as prognostic marker in septic critically ill patients. Materials and methods: In this prospective observational study, 130 adult patients with sepsis were recruited. Various hematological study parameters (total, differential, and absolute leukocyte count, platelet count, platelet distribution width, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio) were noted at day 1 and day 3 of admission. Primary outcome was 28-day mortality, and secondary outcomes were duration of mechanical ventilation, vasopressor requirement, ICU length of stay, and requirement of renal replacement therapy. The variables were compared between two groups and using binary regression model and were evaluated as prognostic markers for 28-day mortality. Results: Data from n = 129 were analyzed. At day-28, n = 58 (44.96%) patients survived. Baseline and demographic parameters were comparable between survivors and nonsurvivors. Admission Sequential Organ Failure Assessment score was more in nonsurvivors than survivors [8 (6-8) vs 6 (4-8); p = 0.002]. In nonsurvivors, monocyte, lymphocyte, basophil, eosinophil, and platelet count were significantly less at day 1 and lymphocyte, eosinophil, basophil and platelet count were significantly less at day 3. NLR and PLR at day 3 were significantly more in nonsurvivors. On logistic regression analysis, age, thrombocytopenia on day 1, and low eosinophil count on day 3 predicted 28-day mortality (p = 0.006, p = 0.02, and p = 0.04, respectively). Conclusion: Thrombocytopenia on day 1 and eosinopenia on day 3 may predict 28-day mortality in sepsis.
Ficoll-separated mononuclear cells from sepsis patients are contaminated with granulocytes
Intensive Care Medicine, 2008
Objective: To determine the cell content and purity of Ficoll-separated peripheral blood mononuclear cells and granulocyte isolates in sepsis patients compared to healthy controls. Design and setting: Prospective study in the adult and pediatric intensive care departments of the Erasmus University Medical Center in the Netherlands. Patients: Three sepsis patients (two adults, one child) and four healthy controls. Measurements and results: Blood leukocytes were separated by Ficoll into an interface and a bottom fraction. The cell content and purity was analyzed by cytospin and flow-cytometric used for studying granulocytes with high purity. The mononuclear cell fraction is highly contaminated with granulocytes. Additional separation techniques are necessary to obtain a pure cell fraction.