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Triggering receptors expressed on myeloid cells-1 (TREM-1) are transmembrane molecules expressed in cells of the immune system. Activation of TREM-1 leads to the release of pro-inflammatory mediators, which act as amplifiers of inflammation and thereby contribute to the pathogenesis of various diseases, whether inflammatory or not. This study explored the role of TREM-1 in the etiopathogenic context of fibromyalgia syndrome (FMS) and its association with disease activity. This randomized controlled and observational study included 45 patients diagnosed with FMS according to the 2016 American College of Rheumatology criteria. Serum TREM-1 levels were assessed using ELISA, and disease activity was measured using various scales such as the fibromyalgia impact questionnaire (FIQ). Patients were divided into 2 groups according to disease severity based on the FIQ score. Compared to a control group of 46 healthy individuals, patients with FMS exhibited significantly elevated concentrations of TREM-1 (mean ± SD = 216.97 pg/mL ± 16.04), P < .05. The FIQ, Pittsburgh sleep quality index, hospital anxiety and depression scale, fatigue severity scale, and visual analog scale, which confirm symptoms such as pain, disease severity, sleep disturbance, depression, anxiety, and fatigue seen in FMS was significantly correlated with TREM-1 level (P < .001). The optimal threshold value for TREM-1 to disease activity was determined to be 182.250, showing (area under the curve) (CI (95%)): [0.940] (0.887-0.993), a sensitivity of 97% and a specificity of 89% according to the receiver operating characteristic analysis. The positive correlation of TREM-1 with various symptom severity scales and hematological inflammatory indices may be a suitable biomarker for the diagnosis of FMS and a potential therapeutic target., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

In 2022, stroke emerged as the most significant cerebrovascular disorder globally, causing 6.55 million deaths. Microglia, crucial for CNS preservation, can exacerbate brain damage in ischemic stroke by triggering neuroinflammation. This process is mediated by receptors on microglia, triggering receptors expressed on myeloid cells (TREM-1 and TREM-2), which have contrasting roles in neuroinflammation. In this study, we recruited 38 patients within 4.5 h from the onset of ischemic stroke. The degree of severity was evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) at admission (T0) and after one week of ischemic events (TW) and the Modified Rankin Scale (mRS) at three months. The plasma concentration of TREMs (sTREM) was analyzed by next-generation ELISA at T0 and TW. The sTREM-1 concentrations at T0 were associated with mRS, while the sTREM-2 concentrations at T0 were associated with both the NIHSS at T0 and the mRS. A strong correlation between sTREM-1 and sTREM-2 was observed, suggesting a dependent modulation of the levels. This study provides insights into the potential pathway of TREM-1 and TREM-2 as a future biomarker for stratifying high-risk patients with ischemic stroke.

Objective: Early diagnosis of Severity Mycoplasma Pneumoniae Pneumonia (SMPP) has been a worldwide concern in clinical practice. Two cytokines, soluble Triggering Receptor Expressed on Myeloid cells (sTREM-1) and Interferon-Inducible Protein-10 (IP-10), were proved to be implicated in bacterial infection diseases. However, the diagnostic value of sTREM-1 and IP-10 in MPP was poorly known. This study aimed to investigate the diagnostic value of sTREM-1 and IP-10 for SMPP., Methods: In this prospective study, the authors enrolled 44 children with MPP, along with their clinical information. Blood samples were collected, and cytokine levels of sTREM-1 and IP-10 were detected with ELISA assay., Results: Serum levels of sTREM-1 and IP-10 were positively correlated with the severity of MPP. In addition, sTREM-1 and IP-10 have significant potential in the diagnosis of SMPP with an Area Under Curve (AUC) of 0.8564 (p-value = 0.0001, 95% CI 0.7461 to 0.9668) and 0.8086 (p-value = 0.0002, 95% CI 0.6918 to 0.9254) respectively. Notably, the combined diagnostic value of sTREM-1 and IP-10 is up to 0.911 in children with SMPP (p-value < 0.001, 95% CI 0.830 to 0.993)., Conclusions: Serum cytokine levels of sTREM-1 and IP-10 have a great potential diagnostic value in children with SMPP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Aims: This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-tumour necrosis factor [anti-TNF] therapy in patients with ulcerative colitis [UC] or Crohn's disease [CD]., Methods: TREM-1 whole blood gene expression was analysed by RNA sequencing in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD]., Results: TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p = 0.48], endoscopic remission [p = 0.53], clinical response [p = 0.58], or clinical remission [p = 0.79] at Week 8, or clinical response [p = 0.60] at Week 52. However, an association was observed with endoscopic response [p = 0.01], endoscopic remission [p = 0.048], and clinical remission [p = 0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p = 0.56], endoscopic remission [p = 0.33], clinical response [p = 0.07], or clinical remission [p = 0.65] at Week 12, or endoscopic response [p = 0.61], endoscopic remission [p = 0.51], clinical response [p = 0.62], or clinical remission [p = 0.97] at Week 56., Conclusions: Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with inflammatory bowel disease., Clinicaltrials.gov Identifiers: NCT02065622; NCT02065570., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Aim: Identifying and intervening with high-risk postoperative pulmonary infections patients pose challenges in clinical practice. This study aims to conduct a comprehensively analysis of the risk factors and predictive factors associated with post-gastrointestinal surgery pulmonary infections and to develop a predictive model that can predict occurrence of pulmonary infection., Methods: A retrospective analysis was conducted on 96 patients who underwent gastrointestinal surgery at our hospital from May 2021 to October 2023. The occurrence rate of postoperative pulmonary infections was calculated, and patients were categorized into two groups: those with pulmonary infections (the occurrence group) and those without pulmonary infections (the non-occurrence group). Logistic regression analysis was utilized to identify the risk factors for post-gastrointestinal surgery pulmonary infections and to evaluate the predictive value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and T cell immunoglobulin and mucin domain-4 (TIM-4) using nomograms, calibration curves, and Receiver Operating Characteristic (ROC) curves., Results: Out of 96 patients, 20 (20.83%) developed postoperative pulmonary infections. Significant differences were noted between occurrence and non-occurrence groups in terms of smoking (65.00% vs. 34.21%, p = 0.013), surgical duration (70.00% vs. 31.58%, p = 0.002), Preoperative hemoglobin level (35.00% vs. 65.79%, p = 0.013), sTREM-1 levels (23.57 ± 3.16 pg/mL vs. 15.62 ± 2.48 pg/mL, p < 0.001), and TIM-4 levels (61.48 ± 6.35 pg/mL vs. 44.73 ± 5.22 pg/mL, p < 0.001). Logistic regression analysis leads to the development of a risk prediction model for post-gastrointestinal surgery pulmonary infections. The high predictive values of sTREM-1 (Area Under Curve (AUC) = 0.962, 95% confidence interval (CI) 0.917~0.999) and TIM-4 (AUC = 0.970, 95% CI 0.925~1.000) were highlighted by the AUC values, underscoring their clinical importance., Conclusions: A predictive model utilizing sTREM-1 and TIM-4 for pulmonary infection following gastrointestinal surgery was developed. Additionally, other risk factors such as smoking, surgical duration, and preoperative hemoglobin level were evaluated. This finding can be applied in clinical practice to identify potentially susceptible patients and facilitate early intervention measures.

Objectives: Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers., Methods: Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers., Results: Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index., Conclusions: Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Aims: Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS., Methods and Results: This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96-120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724-2128) vs. 621 (525-1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96-120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48-6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008)., Conclusion: In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background and Objectives: The aim of this study is to investigate the effect of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in idiopathic granulomatous mastitis (IGM)., Methods: This case-control study was conducted in Saglik Bilimleri and Necmettin Erbakan Universities. Sixty patients with IGM diagnosis (Group P) and 25 healthy females as control group (Group C) were included. Group P was divided into two subgroups according to the activity of disease: patients with active lesion (Group P A ), and patients without any symptoms, in remission (Group P R ). The ELISA method was used to measure sTREM-1 level., Results: Group P's sTREM-1 were higher than Group C ( p < .0001). The difference between sTREM-1 levels of Groups P A , P R and C was significant statistically ( p < .0001). Group P A 's sTREM-1 levels were higher than Group C ( p < .0001). Also, sTREM-1 levels of Group P R were higher than Group C ( p = .006). When sTREM-1 levels of patients receiving steroid therapy and did not in Group P R were analyzed, the sTREM-1 levels of the patients not receiving steroid treatment were found to be statistically higher than Group C ( p = .002). Although the sTREM-1 levels of the patients who did not receive steroid therapy were higher than those who received steroid therapy, the difference was not statistically significant ( p > .05)., Conclusion: We concluded that the detected high sTREM-1 levels contributed to inflammation in IGM. In particular, blockade of TREM may be a promising treatment option in resistant or multiple recurrent patients.

Background: Innate immune dysregulation may contribute to age-related differences in outcomes among critically ill adults. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an important innate immune marker with prognostic value in sepsis, but age-related differences have not been studied., Methods: This was a prospective cohort from a large tertiary care hospital enrolling adults from both medical and trauma-surgical intensive care units (ICUs). Plasma sTREM-1 was measured in participants within 24 h of ICU admission. We analyzed associations between age (≤50 and >50 years) and sTREM-1 using linear regression. We then examined associations between sTREM-1 and both 28-day mortality and persistent organ dysfunction (defined as need for dialysis, vasopressors, or invasive mechanical ventilation) 7 days following admission using relative risk regression., Results: Of 231 critically ill adults, older patients (n = 122) had higher prevalence of chronic disease and sepsis on enrollment than younger patients, but acute illness severity was similar. Age over 50 was associated with 27% higher sTREM-1 concentrations (95% CI 6%-53%), adjusted for sex and Charlson comorbidity index (CCI). Two-fold higher sTREM-1 was associated with 2.42-fold higher risk for mortality (95% CI 1.57, 3.73) and 1.86-fold higher risk for persistent organ dysfunction (95% CI 1.45, 2.39), adjusted for sex, CCI, and age., Conclusions: sTREM-1 was elevated among critically ill older adults, and strongly associated with both death and persistent organ dysfunction. Immune responses associated with sTREM-1 may contribute to age-related differences in ICU outcomes, warranting further study as a potential therapeutic target in older adults., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients ( n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

Triggering receptor expressed on myeloid cells-1 (TREM-1) exists in two forms: a transmembrane form and a soluble form (sTREM-1). The levels of sTREM-1 are elevated in supernatants of activated HSCs. However, the role of sTREM-1 in HSC activation and liver fibrosis remains undefined. Previous studies have primarily focused on the transmembrane form of TREM-1; we innovatively observed the function of sTREM-1 as a ligand in liver fibrosis and screened its receptor. Here, recombinant sTREM-1 was used as a stimulator which induced HSC activation and further aggravated liver fibrosis. Then, screening for sTREM-1 interacting membrane receptors was performed using pull-down assay followed by mass spectrometry, and the membrane receptor roundabout guidance receptor 2 (Robo2) was identified as a candidate receptor for sTREM-1. The interaction between sTREM-1 and Robo2 was verified by pull-down and immunofluorescence. The role of Robo2 on sTREM-1-induced HSC activation and its downstream signal pathways was assessed by knockdown of Robo2 in LX-2 cells. Furthermore, HSC-specific knockdown of Robo2 was achieved in a mouse model of liver fibrosis by using a recombinant adeno-associated virus (AAV) vector to confirm the role of the receptor, and we proved that Robo2 knockdown inhibited the activation of HSC and liver fibrosis, which also led to the inactivation of Smad2/3 and PI3K/Akt pathways in sTREM-1-induced HSC activation and liver fibrosis. In conclusion, sTREM-1 acts as a new ligand of Robo2; the binding of sTREM-1 to Robo2 initiates the activation of the downstream Smad2/3 and PI3K/Akt signalling pathways, thereby promoting HSC activation and liver fibrosis., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Triggering receptor expressed on myeloid cells-1 (TREM-1) participates in neuroinflammation. We intended to ascertain whether serum soluble TREM-1 (sTREM-1) could be utilized as a biomarker of inflammation, severity, early neurologic deterioration (END) and outcome after primary intracerebral hemorrhage (ICH)., Methods: Serum sTREM-1 levels were gauged in 104 ICH patients and 104 healthy controls. END was diagnosed when the National Institutes of Health Stroke Scale (NIHSS) score increased ≥ 4 points or death between admission and 24 h after admission. Patients with a modified Rankin scale score of > 2 at 3 months were considered to have poor outcome., Results: As compared to controls, patients exhibited significantly elevated serum sTREM-1 levels (median: 309.0 vs 67.9 pg/ml). Serum sTREM-1 concentrations were intimately correlated with NIHSS score (r = 0.574), hematoma volume (r = 0.554), blood leukocyte count (r = 0.529) and serum C-reactive protein concentrations (r = 0.509). Serum sTREM-1 concentrations > 309.0 pg/ml independently predicted END and poor outcome with odds ratio values of 4.054 and 4.721 respectively. Serum sTREM-1 concentrations distinguished END and poor outcome with areas under receiver operating characteristic curve of 0.789 and 0.813 respectively., Conclusion: Serum sTREM-1 may represent a promising inflammatory biomarker for assessment of severity and prediction of END and poor outcome after ICH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Triggering receptor expressing on myeloid cells (TREM)-1 is involved in the pathophysiology of ischemic heart disease. Plasma soluble TREM-1 levels (sTREM-1) has been associated with increased risk of major adverse cardiovascular events (MACE) in acute myocardial infarction (AMI) patients. However, the causative link between TREM-1 and MACE remains unknown and requires further investigation before developing potential therapeutic approaches., Methods and Results: Using the serum and DNA data bank from the prospective, nationwide French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI 2010, N = 1293), we studied the association of plasma levels of sTREM-1 with 9 common genetic variants at the TREM1 locus and their relationship with recurrent MACE over a 3-year follow up. Plasma levels of sTREM-1 were associated with an increased risk of MACEs (death, recurrent MI or stroke) (adjusted HR = 1.86, 95%CI = 1.06-3.26 and HR = 1.11, 95%CI = 0.61-2.02 respectively for tertiles 3 and 2 versus tertile 1, P < 0.001). The study of common variants identified two major genetic determinants of sTREM-1 (rs4714449: beta = -0.11, P add  = 7.85 × 10 -5 and rs3804276: beta = 0.18, P add  = 2.65 × 10 -11 ) with a potential role on maintenance and/or differentiation of hematopoietic stem cells. However, associated variants only explained 4% of sTREM-1 variance (P = 2.74 × 10 -14 ). Moreover, the rs4714449 variant, individually and in haplotype, was not significantly associated with MACE (HR = 0.61, 95%CI: 0.35-1.05, P = 0.07)., Conclusions: Despite its relationship with increased risk of death, recurrent MI and stroke, genetic determinants of plasma levels of sTREM-1 were not found to be causal prognostic factors in patients with acute myocardial infarction., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Triggering receptors expressed on myeloid cells 1 and 2 (TREM-1 and TREM-2) are cell surface receptors important for modulation of microglia immune response. In this study, we evaluate serum levels of TREM-1 and TREM-2 as potential biomarkers in acute ischemic stroke (AIS)., Material and Methods: Prospective cohort study of 50 patients with AIS admitted at our hospital. Serum TREM-1 and TREM-2 was evaluated within 24 h of the acute event and on the third and fifth days after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times and at the time of hospital discharge., Results: TREM-1 and TREM-2 levels were elevated in stroke. TREM-1, but not TREM-2, exhibited correlations with NIHSS and mRS within 24 h (NIHSS and TREM-1: r S  = 0.31, p = 0.029; mRS and TREM-1: r S  = 0.32, p = 0.023). The serum level of TREM-1 within 24 h correlated with the neurological outcomes at hospital discharge (NIHSS and TREM-1: p = 0.021; mRS and TREM-1: p = 0.049). The serum concentrations of TREM-1 protein within 24 h after stroke was significantly higher in patients with poor outcome (mRS > 2) at hospital discharge (p = 0.021). After Exact Logistic Regression, large segmental stroke (O.R. = 4.14; 95CI = 1.07-16.09; p = 0.040) and initial sTREM levels (O.R. = 1.02; 95CI 1.00-1.04; p = 0.045) remained independent prognostic factors for AIS poor outcome (mRS > 2)., Conclusion: In our study, TREM-1 and TREM-2 were significantly increased in AIS. Early elevation of TREM-1 correlated with stroke severity and it was an independent prognostic factor for stroke outcome., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to explore the relationship between the severity and prognosis of elderly patients with ventilator-associated pneumonia (VAP) and the expression of serum interleukin-18 mRNA (IL-18 mRNA), Clara cell secretory protein 16 (CC16) and the soluble triggering receptor expressed on myeloid cells 1 (sTREM-1)., Methods: The patients were divided into a VAP group (n=75) and a non-VAP group (n=110). According to the Acute Physiology and Chronic Health Evaluation II (APACHEII) score, the patients with VAP were divided into a low-risk group, an intermediate-risk group and a high-risk group. According to the 28-day outcome, the patients were divided into a survival group and a death group. Serum levels of IL-18, CC16 and sTREM-1 were detected, and their value in the prediction and prognosis of VAP was analyzed using a receiver operating characteristic (ROC) curve., Results: Serum levels of IL-18 and sTREM-1 in the VAP group were higher than those in the non-VAP group, while CC16 levels were lower in the VAP group than those in the non-VAP group (P<0.05). Serum levels of IL-18 and sTREM-1 decreased in order from the high-risk group to the intermediate-risk group to the low-risk group, while CC16 levels increased in order (P<0.05). ROC curve analysis showed that the Youden index and AUC of combined diagnosis of VAP with serum IL-18 mRNA, CC16 and sTREM-1 were 0.710 and 0.930, which were higher than those of single diagnosis (P<0.05). Serum levels of IL-18 mRNA and sTREM-1 in the survival group were lower than those in the death group, and the CC16 level was higher than that in the death group (P<0.05). ROC curve analysis showed that the Youden index and AUC of combined diagnosis with serum IL-18 mRNA, CC16 and sTREM-1 were 0.506 and 0.731, which were higher than those of single diagnosis (P<0.05)., Conclusions: The combination of these 3 factors is of high value in predicting the severity and prognosis of VAP and can provide reference for clinical treatment.

Background: Quercetin (QUE) is a flavonol reported with anti-inflammatory and antioxidant activities, and previous results from the group of this study have demonstrated its neuroprotective effect against lipopolysaccharide-induced neuropsychiatric injuries. However, little is known about its potential effect on neuropsychiatric injuries induced or accompanied by metabolic dysfunction of glucose and lipids., Methods: A nonalcoholic fatty liver disease (NAFLD) rat model was induced via a high-fat diet (HFD), and glucolipid parameters and liver function were measured. Behavioral performance was observed via the open field test (OFT) and the Morris water maze (MWM). The plasma levels of triggering receptor expressed on myeloid cells-1 (TREM1) and TREM2 were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of Synapsin-1 (Syn-1), Synaptatogmin-1 (Syt-1), TREM1 and TREM2 in the hippocampus were detected using western blotting. Morphological changes in the liver and hippocampus were detected by HE and Oil red or silver staining., Results: Compared with the control rats, HFD-induced NAFLD model rats presented significant metabolic dysfunction, hepatocyte steatosis, and impaired learning and memory ability, as indicated by the increased plasma concentrations of total cholesterol (TC) and triglyceride (TG), the impaired glucose tolerance, the accumulated fat droplets and balloon-like changes in the liver, and the increased escaping latency but decreased duration in the target quadrant in the Morris water maze. All these changes were reversed in QUE-treated rats. Moreover, apart from improving the morphological injuries in the hippocampus, treatment with QUE could increase the decreased plasma concentration and hippocampal protein expression of TREM1 in NAFLD rats and increase the decreased expression of Syn-1 and Syt-1 in the hippocampus., Conclusions: These results suggested the therapeutic potential of QUE against NAFLD-associated impairment of learning and memory, and the mechanism might involve regulating the metabolic dysfunction of glucose and lipids and balancing the protein expression of synaptic plasticity markers and TREM1/2 in the hippocampus., (© 2021. The Author(s).)

Neuroinflammation is a key process in the pathogenesis of subarachnoid hemorrhage (SAH) and contributes to poor outcome in patients. The purpose of this study is to explore the effect of triggering receptor expressed on myeloid cells 1 (TREM1) in the SAH, as well as its potential mechanism. In our study, plasma levels of soluble TREM1 was increased significantly after SAH and correlated to SAH severity and serum C-reactiveprotein. TREM1 inhibitory peptide LP17 alleviated the neurological deficits, attenuated brain water content, and reduced neuronal damage after SAH. Meanwhile, TREM1 inhibitory peptide decreased neuroinflammation (evidenced by the decreased levels of markers including IL-6, IL-1β, TNF-α) by attenuating proinflammatory subtype transition of microglia (evidenced by the decreased levels of markers including CD68, CD16, CD86) and decreasing the formation of neutrophil extracellular traps (evidenced by the decreased levels of markers including CitH3, MPO, and NE). Further mechanistic study identified that TREM1 can activate downstream proinflammatory pathways through interacting with spleen tyrosine kinase (SYK). In conclusion, inhibition of TREM1 alleviates neuroinflammation by attenuating proinflammatory subtype transition of microglia and decreasing the formation of neutrophil extracellular traps through interacting with SYK after SAH. TREM1 may be a a promising therapeutic target for SAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Zeng, Xu, Chen, Fan, Zhou, Yu, Fu, Peng, Yan, Yu and Chen.)

Background and Aims: Patients with cirrhosis are susceptible to bacterial infections (BIs) that are major causes of specific complications and mortality. However, the diagnosis of BIs can often be difficult in advanced disease stage since their symptoms may overlap with the ones of acute decompensation (AD). Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from monocytes/macrophages and neutrophils during activation and has been reported to correlate with activity of various inflammatory processes. We investigated its diagnostic and prognostic performance in patients with cirrhosis and BI., Methods: Sera of 269 patients were assayed for sTREM-1 by ELISA (172 outpatients and 97 patients with AD of whom 56 had BI). We investigated capacity of sTREM-1 to identify patients with BI and conducted a 90-day follow-up observational study to assess its possible association with short-term mortality., Results: sTREM-1 levels were significantly higher in patients with more severe liver disease, BI, and acute-on-chronic liver failure than in patients without these conditions. sTREM-1 had similar accuracy to CRP identifying BI [sTREM-1: AUROC (95%CI) 0.804 (0.711-0.897), p < 0.0001; CRP: 0.791 (0.702-0.881), p < 0.0001)] among AD patients. The combination of these two molecules and the presence of ascites into a composite score significantly increased their discriminative power (AUROC: 0.878, 95%CI: 0.812-0.944, p < 0.0001). High sTREM-1 level (>660 pg/mL) was an independent predictor of 90-day mortality in patients with BI [HR: 2.941, (95%CI: 1.009-8.573), p = 0.048] in our multivariate model., Conclusions: Use of sTREM-1 could increase the recognition of BIs in cirrhosis and help clinicians in mortality risk assessment of these patients., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Patients with sepsis display increased concentrations of sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells 1), and a phase II clinical trial focusing on TREM-1 modulation is ongoing. We investigated whether sTREM-1 circulating concentrations are associated with the outcome of patients with coronavirus disease 2019 (COVID-19) to assess the role of this pathway in COVID-19. This observational study was performed in two independent cohorts of patients with COVID-19. Plasma concentrations of sTREM-1 were assessed after ICU admission (pilot cohort) or after COVID-19 diagnosis (validation cohort). Routine laboratory and clinical parameters were collected from electronic patient files. Results showed sTREM-1 plasma concentrations were significantly elevated in patients with COVID-19 (161 [129-196] pg/ml) compared to healthy controls (104 [75-124] pg/ml; P<0.001). Patients with severe COVID-19 needing ICU admission displayed even higher sTREM-1 concentrations compared to less severely ill COVID-19 patients receiving clinical ward-based care (235 [176-319] pg/ml and 195 [139-283] pg/ml, respectively, P = 0.017). In addition, higher sTREM-1 plasma concentrations were observed in patients who did not survive the infection (326 [207-445] pg/ml) compared to survivors (199 [142-278] pg/ml, P<0.001). Survival analyses indicated that patients with higher sTREM-1 concentrations are at higher risk for death (hazard ratio = 3.3, 95%CI: 1.4-7.8). In conclusion, plasma sTREM-1 concentrations are elevated in patients with COVID-19, relate to disease severity, and discriminate between survivors and non-survivors. This suggests that the TREM-1 pathway is involved in the inflammatory reaction and the disease course of COVID-19, and therefore may be considered as a therapeutic target in severely ill patients with COVID-19., (© 2021 The Author(s).)

Background and Aims: Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome., Methods: Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30., Results: Fifty-nine patients (48.7%) were diagnosed with ACS and 62 (51.3%) with nonspecific chest pain (NSCP). Median plasma sTREM-1 level at admission was significantly higher in the ACS group than the NSCP group and the control group (539.4 ± 330.3 pg/ml vs. 432.5 ± 196.4 pg/ml vs. 230.1 ± 85.5 pg/ml, respectively; P < 0.001) and positively correlated with the number of stenosed/occluded coronary arteries on angiography ( P < 0.001). On logistic regression analysis, higher sTREM-1 levels predicted definite ACS vs. NSCP determined on day 30 (OR 1.29, 95% CI 1.07-1.54, P = 0.01) as well as with recurrent ACS ( P = 0.04) and stroke ( P = 0.02) at 6 months., Conclusions: Plasma sTREM-1 levels are significantly elevated in patients with ACS and might serve as a biomarker differentiating ACS from NSCP in the ED as well as an inflammatory biomarker for coronary artery disease severity and outcome., Competing Interests: All authors declare they have no conflicts of interest., (Copyright © 2021 Shachaf Shiber et al.)

The triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are involved in the propagation of inflammatory responses. This study investigated whether serum levels of TREM-1 and PGLYRP1 correlate with periodontitis in rheumatoid arthritis (RA) patients. A total of 154 non-smoking participants with RA (n = 55, F/M: 41/14), Behçet´s disease (BD, n = 41, F/M: 30/11) and healthy controls (HC, n = 58, F/M: 40/18) were recruited. Serum and saliva were collected, the 28-joint disease activity score (DAS-28) was calculated and dental/periodontal measurements were recorded. Serum TREM-1 and PGLYRP1 levels were measured by ELISA and salivary bacterial DNA counts by quantitative polymerase chain reaction. TREM-1 and PGLYRP1 levels were higher in RA (166.3 ± 94.3; 155.5 ± 226.9 pg/ml) than BD (102.3 ± 42.8; 52.5 ± 26.3 pg/ml) and HCs (89.8 ± 55.7; 67.4 ± 37.3 pg/ml) (p < 0.05). In RA, periodontitis was associated with increased TREM-1 and PGLYRP1 levels (p < 0.05), yet in patients under methotrexate TREM-1 levels were lower. TREM-1 correlated with C-reactive protein (CRP) levels, DAS-28 and erythrocyte sedimentation rate, whereas PGLYRP1 positively correlated with CRP. RA patients displayed 3.5-fold higher salivary bacterial DNA counts than HCs. Increased serum TREM-1 levels correlated with PGLYRP1, CRP and DAS-28-ESR in RA patients with periodontitis.

Objectives : Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a monocyte and neutrophil receptor functioning in innate immunity. TREM-1 activity has been studied in various autoimmune diseases such as RA and SLE but there is no data in autoinflammatory pathologies. We studied soluble TREM-1 (sTREM-1) activity in Familial Mediterranean Fever (FMF) cases to evaluate the clinical role of TREM-1 in amyloidosis. Methods : The study includes 62 patients with FMF (42 with amyloidosis) who are regular attendees of a tertiary center for autoinflammatory diseases. For control purposes, 5 patients with AA amyloidosis secondary to other inflammatory diseases, and 20 healthy individuals were also included. Soluble TREM-1 levels were measured using enzyme-linked immunosorbent assay (ELISA). All FMF patients were in an attack-free period during the collection of the blood samples. Results : Soluble TREM-1 levels were found to be significantly higher in the FMF amyloidosis group compared to FMF without amyloidosis group and healthy controls ( p = .001 and 0.002). Nevertheless, this difference between sTREM-1 levels was not found among FMF amyloidosis and other AA amyloidosis groups ( p = .447) as well as between only FMF patients and healthy controls ( p = .532). Soluble TREM-1 levels were found in correlation with creatinine and CRP in the FMF patient group regardless of their amyloidosis diagnosis (r = 0.314, p = .013; r = 0.846, p < .001). Conclusion : TREM-1 seems to be related to renal function rather than disease activity in FMF. Its role as an early diagnostic marker of amyloidosis in FMF complicated with AA amyloidosis should be tested in larger patient groups.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to surges of patients presenting to emergency departments (EDs) and potentially overwhelming health systems., Objective: We sought to assess the predictive accuracy of host biomarkers at clinical presentation to the ED for adverse outcome., Methods: Prospective observational study of PCR-confirmed COVID-19 patients in the ED of a Swiss hospital. Concentrations of inflammatory and endothelial dysfunction biomarkers were determined at clinical presentation. We evaluated the accuracy of clinical signs and these biomarkers in predicting 30-day intubation/mortality, and oxygen requirement by calculating the area under the receiver-operating characteristic curve and by classification and regression tree analysis., Results: Of 76 included patients with COVID-19, 24 were outpatients or hospitalized without oxygen requirement, 35 hospitalized with oxygen requirement, and 17 intubated/died. We found that soluble triggering receptor expressed on myeloid cells had the best prognostic accuracy for 30-day intubation/mortality (area under the receiver-operating characteristic curve, 0.86; 95% CI, 0.77-0.95) and IL-6 measured at presentation to the ED had the best accuracy for 30-day oxygen requirement (area under the receiver-operating characteristic curve, 0.84; 95% CI, 0.74-0.94). An algorithm based on respiratory rate and sTREM-1 predicted 30-day intubation/mortality with 94% sensitivity and 0.1 negative likelihood ratio. An IL-6-based algorithm had 98% sensitivity and 0.04 negative likelihood ratio for 30-day oxygen requirement., Conclusions: sTREM-1 and IL-6 concentrations in COVID-19 in the ED have good predictive accuracy for intubation/mortality and oxygen requirement. sTREM-1- and IL-6-based algorithms are highly sensitive to identify patients with adverse outcome and could serve as early triage tools., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of inflammatory signals. Recently, a soluble form of TREM-1 (sTREM-1) was described. This study aimed to investigate the role of serum sTREM-1 in patients with adult-onset Still's disease (AOSD)., Methods: Serum sTREM-1 levels were detected in 108 AOSD patients, 88 RA patients and 112 healthy controls (HC). The correlations of sTREM-1 with disease activity, clinical characteristics and laboratory parameters in AOSD patients were analysed by the Spearman correlation test. Risk factors for the chronic course of AOSD were evaluated by multivariate logistic regression analysis., Results: AOSD patients had significantly higher serum sTREM-1 levels than RA patients and HC, and serum sTREM-1 levels were correlated with the systemic score, ferritin, leucocyte count, CRP, IL-1β and IL-6. The elevation in the initial sTREM-1 level by itself could discriminate patients developing the chronic course from patients developing the nonchronic course. Moreover, an elevated sTREM-1 level (> 526.4475 pg/ml) was an independent risk factor for the chronic course in active AOSD patients. Furthermore, interfering with TREM-1 engagement led to reductions in the secretion of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, in neutrophils and monocytes from active AOSD patients., Conclusion: Serum sTREM-1 levels are correlated with disease activity, and an elevation in the initial serum sTREM-1 level is a potential predictor of the chronic course in AOSD patients, which currently provides the best predictive model for identifying patients prone to developing the chronic course of AOSD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To study the value of serum procalcitonin (PCT) combined with soluble triggering receptor expressed on myeloid cells-1 (STREM-1) in the differential diagnosis of bacterial diarrhea and viral diarrhea in children., Methods: A retrospective analysis was performed on the medical data of 73 children with bacterial infectious diarrhea (bacteria group) and 68 children with viral infectious diarrhea (virus group) who were treated from February 2018 to May 2019. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum PCT and STREM-1 for bacterial infectious diarrhea and viral infectious diarrhea., Results: Compared with the virus group, the bacteria group had significantly higher detection rates of fecal red blood cells (79% vs 43%, P<0.05) and pus (51% vs 19%, P<0.05), as well as significantly higher serum levels of PCT and STREM-1 (P<0.05). The ROC curve analysis showed that in the differential diagnosis of bacterial infectious diarrhea and viral infectious diarrhea, serum PCT had a cut-off value of 0.97 ng/mL and an area under the ROC curve (AUC) of 0.792, and STREM-1 had a cut-off value of 15.66 ng/mL and an AUC of 0.889. Serum PCT combined with STREM-1 had an AUC of 0.955, which was significantly higher than that of each index alone (P<0.05)., Conclusions: Children with bacterial diarrhea have increased serum levels of PCT and STREM-1 than those with viral diarrhea. Both serum PCT and STREM-1 can be used as the indices for the differential diagnosis of bacterial diarrhea and viral diarrhea in children, and the combined measurement of PCT and STREM-1 can improve the efficiency of differential diagnosis.

Background: To evaluate whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) can be used as an early predictor of ventilator-associated pneumonia (VAP)., Methods: Ventilated neonatal patients admitted into the neonatology department between January 2017 and January 2018 were divided into VAP (n = 30) and non-VAP (n = 30) groups. Serum sTREM, procalcitonin (PCT), C-reactive protein and interleukin-6 levels were measured at 0, 24, 72, and 120 h after initiation of mechanical ventilation (MV). Correlations between blood biomarker concentrations and VAP occurrence were analyzed. Predictive factors for VAP were identified by logistic regression analysis and Hosmer-Lemeshow test, and the predictive value of sTREM-1 and biomarker combinations for VAP was determined by receiver operating characteristic curve analysis., Results: The serum sTREM-1 concentration was significantly higher in the VAP group than in the non-VAP group after 72 and 120 h of MV (72 h: 289.5 (179.6-427.0) vs 202.9 (154.8-279.6) pg/ml, P < 0.001; 120 h: 183.9 (119.8-232.1) vs 141.3 (99.8-179.1) pg/ml, P = 0.042). The area under the curve (AUC) for sTREM-1 at 72 h was 0.902 with a sensitivity of 90% and specificity of 77% for the optimal cut-off value of 165.05 pg/ml. Addition of PCT to sTERM-1 at 72 h further improved the predictive value, with this combination having an AUC of 0.971 (95% confidence interval: 0.938-1.000), sensitivity of 0.96, specificity of 0.88, and Youden index of 0.84., Conclusion: sTREM-1 is a reliable predictor of VAP in neonates, and combined measurement of serum levels of sTREM-1 and PCT after 72 h of MV provided the most accurate prediction of VAP in neonatal patients.

Purpose: The aim of this study was to evaluate the diagnostic and prognostic value of IL-6 and sTREM-1 in the course of SIRS and sepsis in children with reference to routinely used CRP and PCT., Methods: A prospective study included 180 patients at the ages from 2 months to 18 years hospitalized due to fever from November 2015 to January 2017. Forty-nine children without fever hospitalized due to noninfectious causes formed the control group. IL-6 and sTREM-1 serum concentrations were assessed with the enzyme-linked immunosorbent assay method., Results: The mean serum concentrations of all the analyzed biomarkers were statistically significantly higher in the study group compared to the control group. Mean IL-6, sTREM-1, and PCT serum concentrations were statistically significantly higher in the group of patients with SIRS/sepsis compared to the group of feverish patients without diagnosed SIRS (N-SIRS). Based on the ROC curve analysis, it was shown that of all the biomarkers tested, only two-IL-6 and procalcitonin-had potential usefulness in the diagnosis of SIRS/sepsis in children with fever., Conclusion: Elevated levels of IL-6 and PCT are important risk factors for the development of SIRS/sepsis in children with fever. It seems that elevated IL-6 baseline serum level may predict a more severe course of febrile illness in children, because based on the ROC curve analysis, it was found that IL-6 is a statistically significant prognostic marker of prolonged fever ≥ 3 days and prolonged hospitalization > 10 days. The assessment of the usefulness of sTREM-1 in the diagnosis of SIRS/sepsis in feverish children requires further research., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Beata Smok et al.)

Background: Sepsis is a common complication of acute cholangitis (AC), which is associated with a high mortality rate. Our study is aimed at exploring the significance of white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), and temperature (T) alone or combined together in early identification and curative effect monitoring of AC with or without sepsis., Methods: 65 consecutive cases with AC and 76 control cases were enrolled. They were divided into three groups: Group A (AC with sepsis), Group B (AC without sepsis), and Group C (inpatients without AC or other infections). The levels of WBC, CRP, PCT, sTREM-1, and temperature were measured dynamically. The study was carried out and reported according to STARD 2015 reporting guidelines., Results: CRP had the highest AUC to identify AC from individuals without AC or other infections (AUC 1.000, sensitivity 100.0%, specificity 100.0%, positive predictive value 100.0%, and negative predictive value 100.0%). Among various single indexes, PCT performed best (AUC 0.785, sensitivity 75.8%, specificity 72.2%, positive predictive value 68.7%, and negative predictive value 78.8%) to distinguish sepsis with AC, while different combinations of indexes did not perform better. From day 1 to day 5 of hospitalization, the levels of sTREM-1 in Group A were the highest, followed by Groups B and C ( P < 0.05); on day 8, sTREM-1 levels in Groups A and B declined back to normal. However, other index levels among three groups still had a significant difference on day 10. Both in Groups A and B, sTREM-1 levels declined fast between day 1 and day 2 ( P < 0.05)., Conclusions: CRP is the best biomarker to suggest infection here. PCT alone is sufficient enough to diagnose sepsis with AC. sTREM-1 is the best biomarker to monitor patients' response to antimicrobial therapy and biliary drainage., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Jiahui Jiang et al.)

Background: Sepsis is a condition prevalent among hospitalized patients which carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, and then effective treatment can be initiated rapidly. Traditionally, diagnosis was based on the presence of two or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exists, and clinicians still rely on a number of traditional and novel biomarkers to discriminate between patients with and without infection, as the cause of deterioration. The present study aims to observe the changes of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and presepsin (sCD14-ST) 1evels in plasma of sepsis patients and explore the diagnosis and prognosis of sepsis., Methods: Sixty patients with sepsis admitted to the Department of Critical Care medicine in Hainan General Hospital from October 2013 to March 2019 were selected as the experimental group. Also chosen in the same period were 60 cases of hospitalized non-sepsis patients as a control group. Plasma levels of sTREM-1 and presepsin were determined by enzyme-linked immunosorbent assay (ELISA) in the 60 patients with sepsis and the 60 non-sepsis patients. Changes of sTREM-1 and presepsin plasma 1evels were observed in the survival subgroup and non-survival subgroup of the patients with sepsis on days 1, 4, 7, and the day of discharge or death., Results: Plasma levels of sTREM-1 and presepsin in the patients with sepsis were higher than those in the control group on the day of admission (p < 0.01). The levels of sTREM-1 and presepsin in the septic shock group were significantly higher than those in the sepsis group (p < 0.01). Plasma levels of sTREM-1 and presepsin showed a decreasing trend in the survival subgroup of the patients with sepsis, while maintaining high 1evels or increased in the subgroup of non-survivors. At different time points, the plasma levels of sTREM-1 and presepsin of the subgroup of non-survivors were all significantly higher than the subgroup of survivors. There was a significant positive correlation between plasma 1evels of sTREM-1 and presepsin (r = 0.596, p < 0.01). According to the plasma sTREM-1, presepsin, CRP, and PCT levels on the first day of enrollment in patients with sepsis, ROC curve analysis was performed and AUC was calculated. The results showed that the AUC values of sTREM-1 and presepsin were relatively high, which was 0.925 and 0.910, respectively. The AUC of PCT and CRP were slightly lower, which was 0.861 and 0.816, respectively (p < 0.01)., Conclusions: ROC curve was used to study the value of sTREM-1 and presepsin in the diagnosis of sepsis, which suggested that sTREM-1 and presepsin should be significantly superior to CRP and PCT levels. The sTREM-1 combined with presepsin had the highest AUC. sTREM-1 has been shown to have an optimal threshold of 125.00 pg/mL for the diagnosis of sepsis, the specificity was 86.0% and the sensitivity was 87.0%. Presepsin has been shown to have an optimal threshold of 1,025.00 pg/mL for the diagnosis of sepsis, the specificity was 83.0% and the sensitivity was 85.0%. The sTREM-1 and presepsin plasma levels have great reference value for the diagnosis of sepsis, and the sTREM-1 and presepsin plasma levels are relative to the severity of sepsis. It is helpful to evaluate treatment effect and prognosis of sepsis by dynamically monitoring the plasma 1evels of sTREM-1 and presepsin.

Background: We aim to synthesize the up-to-date studies to investigate the diagnostic value of serum soluble triggering expressed receptor on myeloid cells 1 (sTREM-1) in suspected sepsis., Results: A total of 19 studies with 2418 patients were finally enrolled in the meta-analysis. The pooled sensitivity was 0.82 (95% CI 0.73 to 0.89), specificity 0.81 (95% CI 0.75 to 0.86), positive likelihood ratio 4.3 (95% CI 3.02 to 6.12), negative likelihood ratio 0.22 (95% CI 0.24 to 0.35), diagnostic odds ratio 20 (95% CI 9 to 41) and AuROC 0.88 (95% CI 0.85 to 0.91). The meta-regression analysis revealed that the sample size, reference standard description, prevalence of sepsis in the trials and consecution of patient recruitment might be the source of heterogeneity., Conclusions: The serum sTREM-1 had a moderate ability in diagnosis in suspected sepsis based on the current studies. However, more large-scale studies were needed to further evaluate the diagnostic accuracy of sTREM-1.

The diagnosis of sepsis, and especially its differentiation from sterile inflammation, may be challenging. The triggering receptor expressed on myeloid cells-1 is an amplifier of the innate immune response. Its soluble form is detectable in various biological fluids and can be used as a surrogate marker of triggering receptor expressed on myeloid cells-1 activation. In this article, we review the abundant literature evaluating the usefulness of soluble triggering receptor expressed on myeloid cells-1 for the diagnosis and the prognosis evaluation of sepsis or localized infections., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Early onset bacterial sepsis in neonates (EOS) is recognized as an important health condition. Early diagnosis is crucial. However, blood culture results are released in 48-72 hours. Many biomarkers have been investigated but none have been accepted as the gold standard. This study aimed to investigate the diagnostic value of the molecules: soluble form of triggering receptor expressed on myeloid cells-1 (sTREM-1), pentraxin-3 (PTX-3) and pro adrenomedullin (pro-ADM) in EOS and compare with currently used biomarkers., Methods: In this multicenter prospective study, patients were enrolled from different NICUs around the Turkey. Patient data were collected via web-based registry system from attending centers. Neonates, hospitalized with a suspicion of EOS were enrolled. Blood culture and routine blood tests were collected and a serum sample was obtained and kept in - 80°C for studying the molecules. According to laboratory results, patients were divided into three groups as; proven sepsis, clinical sepsis and control group. Groups were compared in terms of demographic, clinical and laboratory findings. The primary outcome of the study was to assess any difference between groups in terms of the diagnostic value of the markers aforementioned., Results: A total of 130 patients were enrolled; proven sepsis (n = 36), clinical sepsis (n = 53) and control (n = 41) groups. Groups were similar in terms of demographic findings; mean WBC (P = 0.445), procalcitonin (PCT) (P = 0.083) and IL-6 (P = 0.814) levels. Mean C-reactive protein (CRP) level was significantly higher in clinical sepsis and proven sepsis groups compared to control group (P < 0.001). Mean PTX-3 (P = 0.547), pro-ADM (P = 0.766) and sTREM-1 (P = 0.838) levels were similar between groups., Conclusion: These promising molecules failed to help in early diagnosis of EOS. Their relation to correlation with disease progression may make more sense as they seem to be expressed in higher amounts with the progression of the disease in previous studies. CRP was the most frequently used biomarker for detecting the sepsis in our study population.

Background: There is a need for rapid and accurate diagnostic biomarker for diagnosis of Salmonella fever., Aims: The aim of the present study was to assess the importance of procalcitonin (PCT), Soluble Triggering Receptors expressed on Myeloid Cells 1 (sTREM1) and C- reactive protein (CRP) in the diagnosis of enteric fever with positive blood culture for S.typhi., Methods: Blood samples were withdrawn from 200 patients with suspected enteric fever and subjected for the determination of CRP, PCT and sTREM-1., Results: The sensitivity and specificity for PCT cut off were 97.7% & 82.5%, for CRP the sensitivity and specificity were 95.3% and 77% and for s-TREM-1 the sensitivity and specificity were 95.3% & 77%., Conclusion: S-TREM-1 may be considered as a novel biomarker for the diagnosis of enteric fever with good sensitivity and specificity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Stroke is a major cause of death and disability worldwide. Among its complications, post-stroke depression (PSD) leads to a significant burden. The diagnosis of PSD is complex, and there are no biomarkers that can assist in its early identification and adequate management., Objective: The aim of the present study is to investigate peripheral biomarkers in the acute phase of stroke and their potential association with depressive symptoms., Methods: We evaluated 60 patients in the acute phase of stroke by using standardized instruments of psychiatric and neurological assessment (Mini International Neuropsychiatric Interview-Plus- MINI-Plus, Hospital Anxiety and Depression Scale-HADS, and National Institutes of Health Stroke Scale-NIHSS) and measured peripheral biomarkers., Results: In multivariate analysis, low peripheral levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and higher NIHSS scores were associated with PSD. The severity of depressive symptoms was inversely correlated with sTREM-1 and glial cell-derived neurotrophic factor (GDNF) levels., Conclusion: This is the first study indicating an association between sTREM-1 and PSD. Our results may point to the involvement of glial mechanisms in the manifestation of depressive symptoms after stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Triggering receptor expressed on myeloid cells 1 (TREM-1) is secreted by phagocytes in adipose tissue and it also upregulates the expression of genes involved in the inflammatory response and atherosclerotic conditions. This study was aimed to investigate the serum TREM-1 levels in overweight patients., Methods: Twenty-eight subjects in the overweight group (OG) and 20 age-matched healthy subjects in the control group (CG) (BMI 27.6±1.2 vs 23.1±2.17 kg/m2, respectively, p<0.001) were included in the study. The serum sTREM-1 level was measured by ELISA. The homeostasis model assessment score (HOMA-IR) was also calculated., Results: The mean TREM-1 levels were significantly higher in OG than in CG (407.3±323.7 vs 150.3±152.7 pg/mL, respectively, p<0.001). The HOMA-IR score was also significantly higher in OG than in CG (3.42±3.63 vs 2.77±1.61, respectively). A positive correlation was detected between TREM-1 and BMI (r=0.318, p=0.028)., Conclusions: This study mainly demonstrated that a high serum TREM-1 level might be an early inflammatory marker in overweight patients. We found that TREM-1 might be associated with BMI in overweight patients regardless of insulin resistance (Tab. 1, Ref. 21). Text in PDF www.elis.sk.

Background/aims: Recently, we showed that triggering receptor expressed on myeloid cells 1 (TREM1) was involved in the pathogenesis of Alzheimer's disease (AD) since it modulated microglial phagocytic functions and thus affected amyloid-β clearance in the brain. Interestingly, a soluble form of TREM1 (sTREM1) can be detected in the plasma of human. To date, whether sTREM1 concentrations were altered in the plasma under AD context remained unclear., Methods: In this study, we compared the plasma concentrations of sTREM1 between 110 AD patients and 128 age- and gender-matched controls. Meanwhile, the relationship of sTREM1 concentrations with total tau levels in the plasma of AD patients was also assessed., Results: We revealed that the concentrations of sTREM1 were significantly increased in AD patients. Meanwhile, the sTREM1 concentrations were gradually increased during disease progression. More importantly, we showed that the sTREM1 concentrations were positively correlated with the levels of total tau in the plasma of AD patients (r = 0.61, P < 0.001). The subsequent subgroup analysis indicated that this correlation was more pronounced in patients with severe dementia (Mini-Mental State Exam score < 10, r = 0.81, P < 0.01)., Conclusion: These findings indicate a potential association between sTREM1 and tau pathology, and further confirm an involvement of this immune receptor in AD pathogenesis.

Objective: Increased inflammation is considered as a risk factor and a promoter of preterm birth (PTB). Monocytes and neutrophils are the main sources of cytokines in the early inflammatory phase. So far, very few studies have indicated CD14/TLR4 and TREM-1 on the monocytes and neutrophils as important targets in PTB. Materials and methods: TLR4 and TREM-1 on CD14 + maternal and cord blood monocytes and neutrophils were detected using flow cytometry in 48 normal term women, 48 PTB with chorioamnionitis (CCA) women, and 40 PTB without CCA women. In the fetal membranes, mRNA and protein levels of the CD14/TLR4-TREM-1 signaling pathway, CD14, TLR4, NF-κBp65, and TREM-1 were analyzed by qRT-PCR and western blot. ELISA was further used to detect TLR4 and TREM-1 levels in maternal and cord serums. Results: Compared with the normal term and PTB without CCA women, we found that (1) TLR4 and TREM-1 levels on CD14 + maternal and cord blood monocytes and neutrophils in the PTB with CCA group were elevated ( p  < .001); (2) the protein and mRNA expressions of CA14, TLR4, NF-κBp65, and TREM-1 of the PTB with CCA group were upregulated ( p  < .001); (3) Maternal and cord serum concentrations of TLR4 and TREM-1 in the PTB with CCA group were greater ( p  < .001). Conclusions: The high levels of TLR4 and TREM-1 surface expression were observed on CD14 + maternal and cord blood monocyte and neutrophils, confirming their proinflammatory profiles in PTB with CCA. TLR4 and TREM-1 on monocyte and neutrophils might have a role in infection-related PTB.

Sepsis is a major cause of death in hospitalised patients accounting for mortality rates as high as 60% and, hence, is called 'a hidden public health disaster'. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is not a disease but is a clinical syndrome, where the initial features are nonspecific resulting in delayed diagnosis. Lack of specific laboratory tests to diagnose the syndrome adds to the diagnostic confusion. Failure to identify sepsis in the early stages itself delays effective treatment resulting in high morbidity and mortality. Various biomarkers and newer laboratory tests help to address these issues. However, to date there is no ideal test to diagnose sepsis. The most commonly used markers are C-reactive protein (CRP) and procalcitonin (PCT). There are around 180 biomarkers reported to be useful in sepsis. In addition to CRP and PCT, various emerging laboratory markers, such as like serum amyloid A, soluble triggering receptor expressed on myeloid cell-1, mannan and antimannan antibodies, and interferon γ inducible protein-10 etc., have been reviewed and their clinical usefulness discussed in this paper., Competing Interests: No conflict of interests declared

Background: Candida albicans is an opportunistic pathogen, but since it also belongs to the normal fungal flora, positive sputum culture as the solely basis for the diagnosis of invasive Candida albicans pneumonia can easily lead to excessive antifungal therapy. Therefore, identification of a pneumonia biomarker might improve diagnostic accuracy., Methods: A rabbit model was established by inoculating 5 × 10 7  cfu/mL C. albicans into the trachea of 20 rabbits with 20 rabbits as control group. Infection was monitored by chest thin-layer computed tomography (CT). 2 mL blood samples were collected daily during each infection and serum levels of potential biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Seven-day post-inoculation the rabbits were sacrificed by CO 2 asphyxiation and lung tissue was histopathologically examined and blood was brought to culture. Data were statistically analyzed., Results: Infection became evident as early as day 3 post-inoculation. The levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble hemoglobin-haptoglobin scavenger receptor (sCD163), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) were elevated in the experimental group compared to the control (P < 0.01), whereas the levels of C-reactive protein (CRP), interleukin-6 (IL-6), IL-8 and IL-10 showed no significant differences (P > 0.05). The dynamic curves of the levels of CRP, IL-6, IL-8, IL-10, SCD163 and TNF-α in both groups demonstrated a similar trend during infection but differences between the groups was observed only in the sTREM-1 levels. Receiver-operating characteristics (ROC) curve analysis showed that the sensitivity and specificity were 85 and 80% for sTREM-1 (cut-off value: 45.88 pg/mL) and 80 and 75% for SCD163 (cut-off value: 16.44 U/mL), respectively. The values of the area under the ROC curve (AUC ROC ) of sTREM-1 and SCD163 were 0.882 (95% CI: 0.922-0.976) and 0.814 (95% CI: 0.678-0.950), respectively. Other markers did not exhibit significant differences., Conclusion: sTREM-1 and SCD163 might be suitable biomarkers for pneumonia.

Aim: Peripheral artery disease (PAD) is a manifestation of atherosclerosis with poor prognosis. It is generally complicated by vascular calcification, which is located either in the intima as patchy infiltrates; or circumferentially in the media, also known as medial arterial calcification (MAC). Obstructive PAD is reflected by low anklebrachial index (ABI ≤ 0.9), whereas MAC is revealed by high ABI (ABI ＞1.4). Considering the increase in cardiovascular mortality at both ends of the ABI spectrum, this study aimed to explore the underlying pathology through cytokines with established prognostic significance; namely pentraxin-3(PTX3), high sensitivity C-reactive protein (hsCRP), copeptin, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), NT-proBNP, and neopterin., Methods: We categorized 180 patients with previous multivessel coronary artery bypass grafting surgery into three groups based on their ABI measurements; 60 patients with ABI ≤ 0.9, 60 patients with ABI within 0.91 and 1.4 (normal ABI), and 60 patients with ABI ＞1.4 constituted the "PAD," "normal," "MAC" groups, respectively. The circulating levels of the biochemical markers were determined., Results: In the PAD group, the cytokine levels with predominantly proatherogenic actions such as PTX3, hsCRP, copeptin, and sTREM-1 were increased and these cytokine levels declined as the ABI increased. In the MAC group, the cytokine concentrations with pleiotropic actions such as NT-proBNP and neopterin increased and; NT-proBNP and neopterin concentrations decreased as ABI decreased. The linear regression analysis revealed that neopterin (β=0.72), PTX3 (β=－0.32), and copeptin (β=－0.48) were independent predictors of ABI., Conclusions: These findings suggest that different inflammatory pathways influence the pathology at the opposing ends of the ABI spectrum. Consequently, we suggest that PTX3, copeptin, and neopterin are promising biomarkers for future research.

Bacterial and opportunistic infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis owing to treatment with immunosuppressants. Commonly used laboratory tests are unreliable in differentiating infection from active disease patients. Fc receptor (FcγR1 or CD64) expression on neutrophils and soluble TREM-1 (triggering receptor expressed on monocytes) are potential biomarkers of bacterial infections. Our aim was to measure the clinical usefulness of quantitative CD64 measurement on neutrophils and soluble TREM-1 measurements in differentiating bacterial infection from active disease in patients with SLE and ANCA vasculitis. Patients with bacterial infection (n = 25), active disease (n = 51), and healthy controls (n = 20) were included. Neutrophil CD64 expression using flow cytometry and sTREM-1 and procalcitonin levels by ELISA were studied. The percentage of neutrophils with CD64 expression and their mean fluorescence intensity in patients with infection (68.8 (56.9-86.5)%, 1037 (229-1828)) were significantly (p < 0.05) higher as compared to those without infection (7.7 (2.6-13.1)%, 456 (20-968)) and controls (7.05 (1.4-9.5)%, 99.5 (54.7-140.7)). The sensitivity and specificity of CD64 expression on neutrophils to diagnose bacterial infection (using a cutoff value of 30%) was 85% and 84%, respectively, whereas the sensitivity and specificity of procalcitonin was 75% and 85%, respectively. There was no significant difference in soluble TREM-1 levels between the two groups. Quantitative measurement of CD64 on neutrophils can distinguish between systemic infection and the flare of autoimmune diseases.

Background: With the changed therapeutic armamentarium for Crohn's disease (CD) and ulcerative colitis (UC), biomarkers predicting treatment response are urgently needed. We studied whole blood and mucosal expression of genes previously reported to predict outcome to anti-TNF therapy, and investigated if the signature was specific for anti-TNF agents., Methods: We prospectively included 54 active IBD patients (24CD, 30UC) initiating anti-TNF therapy, as well as 22 CD patients initiating ustekinumab and 51 patients initiating vedolizumab (25CD, 26UC). Whole blood expression of OSM, TREM1, TNF and TNFR2 was measured prior to start of therapy using qPCR, and mucosal gene expression in inflamed biopsies using RNA-sequencing. Response was defined as endoscopic remission (SES-CD ≤ 2 at week 24 for CD and Mayo endoscopic sub-score ≤ 1 at week 10 for UC)., Findings: Baseline whole blood TREM1 was downregulated in future anti-TNF responders, both in UC (FC = 0.53, p = .001) and CD (FC = 0.66, p = .007), as well as in the complete cohort (FC = 0.67, p < .001). Receiver operator characteristic statistics showed an area under the curve (AUC) of 0.78 (p = .001). A similar accuracy could be achieved with mucosal TREM1 (AUC 0.77, p = .003), which outperformed the accuracy of serum TREM1 (AUC 0.58, p = .31). Although differentially expressed in tissue, OSM, TNF and TNFR2 were not differentially expressed in whole blood. The TREM1 predictive signal was anti-TNF specific, as no changes were seen in ustekinumab and vedolizumab treated patients., Interpretation: We identified low TREM-1 as a specific biomarker for anti-TNF induced endoscopic remission. These results can aid in the selection of therapy in biologic-naïve patients., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an innate-immune receptor found in blood. Its presence reflects innate immune cell activation. We sought to investigate plasma sTREM-1 levels in patients with primary antiphospholipid syndrome (PAPS)., Methods: A cross-sectional, case-control design was used. Plasma sTREM-1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in consecutive patients diagnosed with PAPS or asymptomatic antiphospholipid antibody (APLA) carriers and controls., Results: The study cohort included 33 patients with PAPS, 10 asymptomatic APLA carriers, and 73 controls. Mean plasma sTREM-1 levels were significantly higher in patients with PAPS (299.2 ± 146.7 pg/ml) and thrombotic PAPS-ever (current and past thrombotic event) (327.2 ± 151.3 pg/ml) compared with controls (230.2 ± 85.5 pg/ml; p = 0.006 and p = 0.003, respectively), patients with thrombotic PAPS compared with patients with past obstetric APS (195.12 ± 58.52 pg/ml, p = 0.01) and APLA carriers (215.8 ± 51.6 pg/ml, p = 0.02), patients with current thrombotic PAPS (429.5 ± 227.5 pg/ml) compared with patients with past thrombotic PAPS (289.5 ± 94.65 pg/ml, p = 0.01), and patients with PAPS who had ever had a stroke or venous thromboembolic event compared with patients who had not (p = 0.007 and p = 0.02, respectively). On receiver operator characteristic curve analysis, plasma sTREM-1 levels differentiated patients with current thrombotic PAPS from asymptomatic APLA carriers and controls, with an area under the curve of 0.7292 (p = 0.0014) and 0.88 (p < 0.0001), respectively. Multivariate regression analysis to identify sTREM-1 predictors (thrombotic PAPS-ever, age, and sex) yielded an independent association of sTREM-1 levels with thrombotic PAPS (p < 0.0001)., Conclusions: Plasma sTREM-1 levels are significantly elevated in patients with thrombotic PAPS. Levels of sTREM-1 might serve as a biomarker for thrombosis in patients with PAPS.

Aims: To comparatively analyze the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) and Clinical Pulmonary Infection Score (CPIS) for assessing the severity and prognosis of community-acquired pneumonia (CAP) in the elderly., Methods: A total of 214 elderly patients with CAP and 106 healthy persons were enrolled in this prospective study. On the admission day, serum inflammatory markers, including CRP, PCT, sTREM-1, and CPIS were analyzed. By severity, the CAP patients were subdivided into non-severe CAP group and severe CAP group. By outcome, the patients were classified into survival group and death group. The efficiency of three inflammatory markers and CPIS on predicting prognosis of pneumonia patients was then analyzed., Results: The serum inflammatory markers and CPIS were significantly higher in CAP patients than in healthy controls. These biomarkers and CPIS were significantly higher in patients with severe CAP than in patients with non-severe CAP. Compared with patients who would survive, these markers and CPIS were significantly higher in patients who would die. Receiver operating characteristic curve analysis showed that the area under the curve and sensitivity were higher for serum sTREM-1 than for other indicators, while the specificity of serum PCT was the highest., Conclusions: Serum CRP, PCT, and sTREM-1 and CPIS determined on the admission day are effective indicators to evaluate the severity and prognosis of CAP in the elderly. The prognostic value of PCT and sTREM-1 is better than that of CRP and CPIS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Özdemir ZC, Düzenli-Kar Y, Canik A, Küskü-Kiraz Z, Özen H, Bör Ö. The predictive value of procalcitonin, C-reactive protein, presepsin, and soluble-triggering receptor expressed on myeloid cell levels in bloodstream infections in pediatric patients with febrile neutropenia. Turk J Pediatr 2019; 61: 359-367. The present study investigates the predictive value of procalcitonin (PCT), C-reactive protein (CRP), presepsin (PRE-SEP) and soluble-triggering receptor, as expressed on myeloid cells (sTREM-1) levels in bloodstream infections in pediatric patients with febrile neutropenia. A total of 47 episodes of febrile neutropenia that developed in 30 children with malignancy were analyzed in this study, while the control group comprised 27 children who had undergone chemotherapy for malignancy (completed ≥2 years ago) without neutropenia, fever or drug use. Median PCT, CRP, PRE-SEP and sTREM-1 levels on admission were found to be significantly higher in the patient group than in the control group, while in the blood cultures, the microbiological agent was isolated in 13 (27.7%) of the 47 episodes. Median PCT and CRP levels on days 1, 2 and 7 were higher in the blood culture-positive episodes than in the blood culture-negative episodes. There was no significant difference in the PRE-SEP and sTREM-1 levels on days 1, 2 and 7 between the blood culture-positive and blood culture-negative episodes. The results of the study suggest that PRESEP and sTREM-1 are at measurable levels upon admission in children with febrile neutropenia, but that these markers may not be appropriate for the predicting of bloodstream infections, although CRP and PCT levels within the first 24 hours may serve as a guide for clinicians.

Herein, we found that serum content of the triggering receptor expressed on myeloid cells-1 (TREM1) was increased, and positively correlated with Mycoplasma pneumoniae (MP)-DNA in children with MP infection. In this study, A549 cells, known as human lung epithelial cells, were co-cultured with 10 7 CCU/ml of MP to established in vitro model of MP infection. We studied the roles of TREM1 in inflammatory response of A549 cell by regulating the secretions of cytokine interleukin (IL)-8 and tumor necrosis factor (TNF)-α in cell culture supernatants. Moreover, transcriptional activity of nuclear factor kappa B (NF-кB) was assessed by measuring protein levels of NF-кB in the cytoplasm and nuclear. Our data suggested that sanguinarine chloride significantly decreased TREM1 expression, and alleviated inflammatory response of MP-infected A549 cells via preventing NF-кB nuclear translocation. To study the roles of TREM1 in inflammatory regulation in MP-infected A549 cells and the underlying mechanisms, we established TREM1 overexpression transfected A549 cells. PDTC was used for inhibiting NF-кB nuclear translocation. We found that TREM1 overexpression induced server inflammatory response of A549 cells. Besides, TREM1 overexpression attenuated anti-inflammatory effects of sanguinarine chloride in MP-infected cells. More importantly, pro-inflammatory effects of TREM1 overexpression was significantly reversed with additional PDTC treatment in MP-infected cells treated with sanguinarine chloride, suggesting that TREM1 was a pro-inflammatory factor via regulating NF-кB nuclear translocation in MP-infected A549 cells., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: There is no specific marker that shows the disease activity in Behçet's disease., Aim: In this study, we aimed to investigate VEGF-B and VEGF gene expressions and sTREM-1 levels in association with the activation of Behçet's disease., Study Design: Case-control study., Methods: Clinical features of patients who applied in the rheumatology clinic and were diagnosed with BD according to the international working group's criteria were investigated. 30 healthy volunteers and 30 patients in the active period according to the EBDCAF scoring were studied. VEGF-B and VEGF gene expressions and sTREM-1 levels were studied in the serum samples of the patients and the control subjects., Results: The VEGF-B expressions and sTREM-1 levels were higher in the BD than those in the healthy group, but this difference did not reach statistical significance. VEGF gene expression was statistically significant ( p = 0.008). Behçet's disease patients with oral aphthae, genital ulcer, eye, joint, vascular, skin, and neurological involvement were analyzed separately as subgroups. We find that VEGF gene expression level of Behçet's disease patients with joint involvement (arthritis/arthralgia) and also VEGF-B and VEGF gene expression of Behçet's disease with vascular involvement (DVT/thrombophlebitis) were significantly higher ( p = 0.035, p = 0.021). Each subgroup was analyzed with the control group. We determined that VEGF gene expression in all subgroups was significantly higher than that in the control group. At the same time, VEGF-B levels of patients with genital ulcer and vascular involvement (DVT/thrombophlebitis) were significantly higher than those in the control group., Conclusion: VEGF-B and VEGF gene expressions can be activity indicators for BD. In addition, this study shows that new treatment options should be explored for Behçet's disease patients with joint and vascular involvement. In the following years, new treatment methods are needed to investigate for revealing the role of the etiopathogenesis of BD and the activation and prognosis of VEGF by examining this study and providing much more participation. In our study group, the sTREM-1 levels were high but the results did not reach statistical significance. More studies are needed with larger groups in order the highlight the exact role of STREM-1 in Behçet's disease.

Early prognostic prediction of sepsis is essential in adjusting therapeutic protocols to prevent deterioration and reduce mortality. We compared the predictive value of the serum concentration of the soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) for 28-day mortality and for the development of severe sepsis or septic shock on the third day with the levels of interleukin (IL)-6, C-reactive protein (CRP) and procalcitonin (PCT). The study was conducted on 85 patients with sepsis. sTREM-1, CRP, PCT and IL-6 concentrations were measured upon study inclusion (day 0) and on days 1, 2, 3 and 5. APACHE II, SAPS II and SOFA scores were analyzed. The sTREM-1 levels (pg/ml) were higher in non-survivors than in survivors at admission (773 vs. 391, p < 0.001) and on days 1, 2, 3 and 5. In predicting the development of severe sepsis, the highest AUCs were found for PCT (0.744, 95% CI 0.638-0.85) and sTREM-1 (0.664, 95% CI 0.55-0.778); and in septic shock prediction, for PCT (0.766, 95% CI 0.665-0.867) and IL-6 (0.707, 95% CI 0.595-0.819). sTREM-1 positively correlated with APACHE II, SAPS II and SOFA scores. At inclusion, significant AUC for predicting 28-day mortality was 0.772 for the sTREM-1 (95% CI 0.672-0.871), 0.858 for APACHE II (95% CI 0.768-0.948), 0.847 for SAPS II (95% CI 0.733-0.96), 0.806 for SOFA score (95% CI 0.698-0.915). sTREM-1 can early predict the 28-day sepsis mortality, although its effectiveness is lower in comparison with clinical severity scores.