scholarly journals Granulocytic myeloid-derived suppressor cells inversely correlate with plasma arginine and overall survival in critically ill patients

2015 ◽  
Vol 180 (2) ◽  
pp. 280-288 ◽  
Author(s):  
A. Gey ◽  
J.-M. Tadie ◽  
A. Caumont-Prim ◽  
C. Hauw-Berlemont ◽  
L. Cynober ◽  
...  
2020 ◽  
Vol 77 (8) ◽  
pp. 773-783
Author(s):  
Ivo Udovicic ◽  
Maja Surbatovic ◽  
Goran Rondovic ◽  
Ivan Stanojevic ◽  
Snjezana Zeba ◽  
...  

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 stepwise multivariate logistic regression analysis of the variables on the Day 1, on the Day 5 it was determined that the Sequential Organ Failure Assessment (SOFA) score (OR 2.350; p < 0.05) and G-MDSCs frequencies (OR 3.575; p < 0.05) were independent predictors of lethal outcome. Conclusion. These findings suggest harmful role of MDSCs in secondary sepsis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clémence Marais ◽  
Caroline Claude ◽  
Nada Semaan ◽  
Ramy Charbel ◽  
Simon Barreault ◽  
...  

Abstract Background De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit. Methods Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression. Results Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression. Conclusions Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.


Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 990
Author(s):  
Theresa H. Wirtz ◽  
Lukas Buendgens ◽  
Ralf Weiskirchen ◽  
Sven H. Loosen ◽  
Nina Haehnsen ◽  
...  

Background: Calprotectin is present in the cytosol of neutrophil granulocytes and released upon activation. Fecal calprotectin is applied in the clinical management of inflammatory bowel disease whereas serum calprotectin has been discussed as a biomarker in inflammatory disorders. However, its long-term prognostic relevance in critical illness remains unclear. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients. Methods: Serum calprotectin concentrations were analyzed in 165 critically ill patients (108 with sepsis, 57 without sepsis) included in our observational study. Patients were enrolled upon admission to the medical intensive care unit (ICU) of the RWTH Aachen University Hospital. Calprotectin concentrations were compared to 24 healthy controls and correlated with clinical parameters, therapeutic interventions, and survival. Results: Serum calprotectin concentrations were significantly increased in ICU patients as well as in septic patients compared to respective controls (p < 0.001 for ICU patients and p = 0.001 for septic patients). Lower calprotectin concentrations were measured in patients with comorbidities i.e., coronary artery disease. Calprotectin concentrations strongly correlated with the C-reactive protein (p < 0.001) and were closely associated to parameters of mechanical ventilation (i.a. inspiratory oxygen fraction, FiO2; p < 0.001). The overall survival was significantly impaired in septic patients with high baseline calprotectin concentrations (p = 0.036). However, patients with increasing calprotectin serum concentrations within the first week of ICU admission showed an improved overall survival (p = 0.009). Conclusions: In summary, serum calprotectin concentrations are significantly increased in critically ill patients with sepsis. High calprotectin concentrations at ICU admission predict long-term mortality risk, whereas increasing calprotectin concentrations are associated with a favorable long-term outcome.


2020 ◽  
Vol 77 (9) ◽  
pp. 923-933
Author(s):  
Ivo Udovicic ◽  
Maja Surbatovic ◽  
Goran Rondovic ◽  
Ivan Stanojevic ◽  
Snjezana Zeba ◽  
...  

Background/Aim. Gram-positive and Gram-negative bacteria may induce different inflammatory patterns. The aim of this study was to examine the association of the myeloid-derived suppressor cells (MDSCs) with the type of infecting microorganisms (Gram positive, Gram negative, polymicrobial) and underlying cause of secondary sepsis (peritonitis, pancreatitis, trauma). Methods. Totally, 40 critically ill patients with secondary sepsis were enrolled in the prospective study. Two patients without documented positive blood culture were excluded. We detected and enumerated both main subsets of MDSCs: granulocytic (G)-MDSCs and monocytic (M)-MDSCs on the Days 1 and 5. Blood was simultaneously drawn for a blood culture. The patients with different underlying causes of sepsis (peritonitis, pancreatitis, trauma) were perceived as separated groups and the frequencies and absolute numbers of their G-MDSCs and M-MDSCs were compared. Results. Both main MDSC subpopulations were accumulated significantly in Grampositive sepsis. Univariate logistic regression analyses of investigated variables regarding Gram-positive sepsis on the Day 5 revealed that G-MDSCs absolute number along with both MMDSCs frequency and absolute number had statistically significant power for predicting Gram-positive sepsis. Stepwise multivariate logistic regression analyses of the variables on the Day 5 determined that M-MDSCs absolute number was independent predictor of Gram-positive sepsis [odds ratio (OR) 1.012; p < 0.05]. Clinical accuracy of neutrophil (Ne)/GMDSCs (Ne/G-MDSCs) and monocyte (Mo)/M-MDSCs (Mo/M-MDSCs) ratios in predicting nature of bacteremia and outcome were investigated. Discriminative power of both Ne/G-MDSCs and Mo/M-MDSCs ratios in predicting Grampositive blood culture was statistically significant both on the Day 1 and Day 5 [areas under curve (AUCs): 0.684 and 0.692, and 0.707 and 0.793, respectively). Ne/G-MDSCs both on the Day 1 and Day 5 were statistically significant predictors of lethal outcome (AUCs: 0.694 and 0.678, respectively). There were no statistically significant differences in G-MDSCs and M-MDSCs among different three groups of patients regarding peritonitis, pancreatitis and trauma as causes of sepsis neither on the Day 1 nor on the Day 5. Conclusion. Gram-positive infectious agents were powerful inducers of MDSCs generation in sepsis. Also, underlying causes of secondary sepsis might not seem to influence the MDSCs accumulation.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 6017-6017
Author(s):  
Carolina Oliver ◽  
Adriana Peixoto ◽  
Cecilia Guillermo ◽  
Juan Zunino ◽  
Mariana Stevenazzi ◽  
...  

Abstract Introduction: patients with hematologic malignancies (HM) admitted in intensive care units (ICU) have been traditionally seen as patients with very poor prognostic. Recently reports have informed that mortality has dropped and nowadays is in the order of 40-60 %, this is still high but closer to mortality in non-malignant patients admitted in an ICU. In an attempt to change this view we perform a study in order to evaluate the results and prognostic factors that contribute to mortality in HM patients who need critical care assistance. Methods: a retrospective study in 62 patients with HM who were admitted in ICU in the University Hospital, Hospital de Clinicas from Uruguay from 2003 to 2012. These 62 patients had 82 admissions, which are the population of our trial. Statistical analysis: Values are expressed as mean +/- standard deviation (SD), median and percentages. Comparison variable most used: discharge of ICU: dead or alive. Both groups were compared using Student's t test and Chi square. Multivariate logistic regression analysis was performed. Overall survival with Kaplan Meier. Significance p<0.05. Results: 50% of the episodes were in men. The median age was 56 years old (17-80). The distribution according to HM was: Non-Hodgkin Lymphoma 40.2%, Acute Myeloid Leukemia 23.2%, Multiple Myeloma 13.4%, Chronic Lymphocytic Leukemia 7.3%, Acute Lymphoblastic Leukemia 4.9%, Hodgkin Lymphoma 3.7%, other 3.7%, Myeloproliferative Neoplasm 2.4% and aplasia 1.2%. The mortality during ICU’s treatment was 47.6%. The causes of death in ICU were: septic shock: 74.4%; disease progression: 10.3%; Other: 7.7%; refractory respiratory failure: 5,1%; severe hemorrhage: 2.6%. Median days of overall survival in ICU were 11 days (CI 1.9 to 20.06). In table 1 we show the univariate analysis of prognostic factors. The parameters that showed a significant difference were; underlying diagnosis of ALL, presence of central catheter line prior to entering ICU; need for mechanical ventilation, diagnosis of septic shock, use and hours of vasopressors and the value of APACHE II. Of the 47 patients who required mechanical ventilation 33 died (70.2%), this is a risk factor for death, with an OR of 1.83 (CI: 1.1 to 3.02). The diagnosis on admission to ICU septic shock is a significant risk factor for death with an OR of 0.449 (CI: 0.351 to 0.574). In the multivariable analysis, admission to ICU for mechanical ventilation, use of mechanical ventilation at some point and use of vasopressors were statistically significant. TABLE 1. Univariate analysis of prognostic factors: Alive Death P value Diagnostic ALL Yes: 0 No: 43 Yes: 4 No: 35 0,03 Type of Chemotherapy Standard: 19High dose: 11Allogeneic SCT: 1Purine analogs: 1No Chemotherapy: 11 Standard: 19High dose: 11Allogeneic SCT: 0Purine analogs: 1No Chemotherapy: 8 0,920,430,340,940,58 Neutropenic No data: 8 Yes: 14 No: 29 Yes: 17 No: 14 0,304 Catheter No data: 2 Yes: 16 No: 26 Yes: 24 No: 14 0,025 Cretinine, mean (SD) 1,53 ±(1,55) 1,75 ±(1,17) 0,66 Urea, mean (SD) 68,2 ±(53,41) 89,27 ±(61,24) 0,09 Prothrombin time, mean (SD) 68,36 ±(21,37) 59,65 ±(20,67) 0,87 PAFI, mean (SD) 301,63 ±(110,41) 290,24 ±(123,25) 0,22 Bilirubin, mean (SD) 1,2 ±(1,78) 1,5 ±(2,49) 0,701 Use of mechanical Ventilatory Yes: 14 No: 29 Yes: 33 No: 6 <0,001 Septic Shock at admission Yes: 0 No: 43 Yes: 4 No: 35 0,032 Use of vasopressor Yes: 7 No: 36 Yes: 31 No: 8 < 0,001 Hours of vasopressors 46,29 86,63 0,023 Renal replacement Therapy Yes: 3 No: 40 Yes: 8 No: 31 0,074 APACHE II 17,05 ± (8,24) 20,66 ± (6,00) 0,042 SOFA at admission 4,99 ± (3,84) 7,32 ± (3,24) 0,35 SOFA at 48 hours 3,89 ± (3,83) 9,20 ± (4,43) 0,13 Conclusions: this is the first report on the impact of prognostic factors in the outcome of HM patients admitted to ICU in Hospital de Clinicas. HM patient’s acute complications are strong factors that contribute to prognostic in critically ill patients and not only the hematologic disease per se or presence of neutropenia or type of chemotherapy. The mortality rate in this series is similar to international reports and also in patients without HM admitted in ICU. Therefore, we support the idea that survival in critically ill HM patient is related with the intercurrent complication in a significant part, and we have to make more efforts to improve results in this area by working together with intensive care medicine physicians. Disclosures No relevant conflicts of interest to declare.


2004 ◽  
Vol 58 (4) ◽  
pp. 587-593 ◽  
Author(s):  
R J Nijveldt ◽  
M P C Siroen ◽  
B van der Hoven ◽  
T Teerlink ◽  
H A Prins ◽  
...  

2021 ◽  
Vol 9 (6) ◽  
pp. e002323
Author(s):  
Carlos Jiménez-Cortegana ◽  
Natalia Palazón-Carrión ◽  
Alejandro Martin Garcia-Sancho ◽  
Esteban Nogales-Fernandez ◽  
Fernando Carnicero-González ◽  
...  

BackgroundThe search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator.MethodsBlood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations.ResultsIn this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival.ConclusionsIn conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.


2021 ◽  
Author(s):  
Yue Zheng ◽  
Nana Xu ◽  
Jiaojiao Pang ◽  
Hui Han ◽  
Hongna Yang ◽  
...  

Abstract BackgroundAcinetobacter baumannii is one of the most frequently isolated opportunistic pathogens in intensive care units (ICUs). Extensively drug-resistant A. baumannii (XDR-AB) strains lack susceptibility to almost all antibiotics and pose a heavy burden on healthcare institutions. In this study, we evaluated the impact of XDR-AB colonization on both the short-term and long-term survival of critically ill patients.MethodsWe prospectively enrolled patients from two adult ICUs in Qilu Hospital of Shandong University from March 2018 through December 2018. Using nasopharyngeal and perirectal swabs, we evaluated the presence of XDR-AB colonization. Participants were followed up for 6 months. The primary endpoints were 28-day and 6-month mortality after ICU admission. The overall survival rate was estimated by the Kaplan-Meier method. We identified risk factors associated with 28-day and 6-month mortality using the logistic regression model and a time-dependent Cox regression model, respectively. ResultsOut of 431 patients, 77 were colonized with XDR-AB. Based on the Kaplan-Meier curve results, the overall survival before 28 days did not differ by colonization status; however, a significantly lower overall survival rate was obtained at 6 months in colonized patients. Univariate and multivariate analysis results confirmed that XDR-AB colonization was not associated with 28-day mortality, but was an independent risk factor of lower overall survival at 6 months (HR = 1.749, 95% CI = 1.174–2.608).ConclusionsXDR-AB colonization has no effect on short-term overall survival, but is associated with lower long-term overall survival in critically ill patients.


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