sTREM-1 Levels Research Articles

Soluble triggering receptor expressed on myeloid cells-1 as a serum biomarker of early neurologic deterioration and prognosis in acute supratentorial intracerebral hemorrhage

BackgroundTriggering 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). MethodsSerum 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. ResultsAs 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. ConclusionSerum sTREM-1 may represent a promising inflammatory biomarker for assessment of severity and prediction of END and poor outcome after ICH.

Utility of P-SEP, sTREM-1 and suPAR as Novel Sepsis Biomarkers in SARS-CoV-2 Infection.

The coronavirus disease 2019 is a highly contagious viral infection caused by SARS-CoV-2 virus, member of coronaviridae family. It causes life threatening complications due to complexity and rapid onset course of the disease. Early identification of high-risk patients who require close monitoring and aggressive treatment remains challengeable till date. Novel biomarkers which help to identify high risk patients at the early stage is high priority. Objective of this review to find utility of P-SEP, sTREM-1 and suPAR for diagnosis, risk stratification and prognosis of SARS-CoV-2 infected cases. Soluble receptors like, P-SEP, sTREM-1 and suPAR have been involved in immune regulation in SARS-CoV-2 infection and elevate more in severe cases. A comprehensive research of databases like PubMed, EMBASE, CNKI and Web of Science was performed for relevant studies. A total of nine out of fifteen research literature in initial screening were included for this review. Interestingly all studies have reported high levels of P-SEP, sTREM-1 and suPAR in SARS-CoV-2 infected cases and the biomarkers positively correlated with severity of infection. This implies that P-SEP, sTREM-1 and suPAR can be implemented as surrogate marker in blood profile for early diagnosis, risk stratification and prognosis in SARS-CoV-2 for better management in Indian population at the current situation.

Plasma and genetic determinants of soluble TREM-1 and major adverse cardiovascular events in a prospective cohort of acute myocardial infarction patients. Results from the FAST-MI 2010 study

IntroductionTriggering 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 resultsUsing 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, Padd = 7.85 × 10−5 and rs3804276: beta = 0.18, Padd = 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). ConclusionsDespite 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.

Дифференцированный подход к диагностике раннего неонатального сепсиса у преждевременно рожденных детей

Актуальность. Ранний неонатальный сепсис остается ведущей причиной заболеваемости и смертности недоношенных детей. Проблема своевременной диагностики обусловливает необходимость внедрения новых эффективных мониторинговых биомаркеров сепсиса новорожденных. Цель: совершенствование диагностики раннего неонатального сепсиса у преждевременно рожденных детей на основании определения диагностической значимости сывороточного уровня sTREM-1, разработка комплексного алгоритма и оценка эффективности подхода. Материалы и методы. Был проведен анализ клинико-лабораторных наблюдений 70 недоношенных детей с ранним неонатальным сепсисом (n = 22) и внутриутробной пневмонией (n = 48) с определением содержания sTREM-1 сыворотки крови. Результаты. У новорожденных с ранним неонатальным сепсисом выявлено достоверное снижение уровня sTREM-1 по сравнению с новорожденными с внутриутробной пневмонией (97,1 ± 4,5 пг/мл против 134,00 ± 7,73 пг/мл). При использовании неоднородной последовательной процедуры Вальда — Генкина установлены ранговые структуры диагностических показателей и разработана эффективная мультимаркерная диагностическая модель. Выводы. Определено, что содержание sTREM-1 в сыворотке крови детей из группы риска реализации внутриутробной инфекции &lt; 148 пг/мл в первые сутки жизни достоверно ассоциируется с неонатальным сепсисом. Использование разработанного мультимаркерного алгоритма способствует совершенствованию диагностики раннего неонатального сепсиса.

Role of soluble triggering receptor expressed in myeloid cells-1 in distinguishing SIRS, sepsis, and septic shock in the pediatric intensive care unit

BackgroundResearch into new markers has been intensified for early diagnosis, prognosis, and differentiation of SIRS, sepsis, and septic shock in recent years. This study aimed to investigate the role of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) and interleukin (IL)-6 in distinguishing between systemic inflammatory response syndrome (SIRS), sepsis, and septic shock in pediatric intensive care unit (PICU) patients. MethodsBetween June 2014 and July 2015, 90 consecutive patients who were treated in the PICU were included in this prospective observational study. Patients were divided into four groups: control (n = 23), SIRS (n = 22), sepsis (n = 23), and septic shock (n = 22). All patients were evaluated for white blood cell (WBC), serum C-reactive protein (CRP), procalcitonin (PCT), IL-6, and sTREM-1 levels at 0, 24, and 72 h of admission. The prognostic evaluations were made using the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores. Patients were evaluated in terms of age, gender, prognosis, pathogen growth in culture, PRISM III and PELOD score, WBC, CRP, PCT, IL-6, and sTREM-1 levels and a comparison was made between groups. ResultsThere was no significant difference between all groups in terms of the 0-, 24-, and 72-h sTREM-1 values (p = 0.761, p = 0.360, and p = 0.822, respectively). CRP and PCT values did not differ between the septic shock, sepsis, and SIRS groups at 0, 24, and 72 h. In the septic shock group, the 0-h IL-6 value was significantly higher than that of the SIRS group (p = 0.025). The 24-h IL-6 value in the septic shock group was significantly higher than the values of the sepsis and SIRS groups (p = 0.048 and p = 0.043, respectively). No significant difference was detected between the septic shock, sepsis, and SIRS groups in terms of IL-6 values at 72 h. ConclusionsTREM-1 is not useful for the diagnosis of infection and for distinguishing between sepsis, septic shock, and SIRS since it does not offer a clear diagnostic value for PICU patients, unlike other reliable markers such as WBC, CRP, and PCT. Elevated IL-6 levels may indicate septic shock in PICU patients. More research on sTREM-1 is needed in this setting.

Specific Features of the Coagulopathy Signature in Severe COVID-19 Pneumonia.

Rationale: COVID-19 displays distinct characteristics that suggest a unique pathogenesis. The objective of this study was to compare biomarkers of coagulopathy and outcomes in COVID-19 and non-COVID-19 patients with severe pneumonia.Methods: Thirty-six non-COVID-19 and 27 COVID-19 non-immunocompromised patients with severe pneumonia were prospectively enrolled, most requiring intensive care. Clinical and biological characteristics (including plasma biomarkers of coagulopathy) were compared.Results: At similar baseline severity, COVID-19 patients required mechanical ventilation (MV) for significantly longer than non-COVID-19 patients (p = 0.0049) and more frequently developed venous thrombotic complications (p = 0.031). COVID-19 patients had significantly higher plasma concentrations of soluble VCAM1 (sVCAM1) (5,739 ± 3,293 vs. 3,700 ± 2,124 ng/ml; p = 0.009), but lower levels of D-dimers, vWF-A2, sICAM1, sTREM1, VEGF, and P-selectin, compared to non-COVID-19 patients. Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariable regression analysis confirmed that sVCAM1 rising levels were independently associated with a longer duration of MV. Finally, we identified close correlations between sVCAM1 and some features of COVID-19 immune dysregulation (ie. CXCL10, GM-CSF, and IL-10).Conclusion: We identified specific features of the coagulopathy signature in severe COVID-19 patients, with higher plasma sVCAM1 levels, that were independently associated with the longer duration of mechanical ventilation.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03505281.

Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient.

PurposeNesfatin-1 plays a crucial role in glucose metabolism and cognitive function. This study aimed to investigate the correlation between plasma nesfatin-1 levels and clinical indicators and cognitive function in patients with type 2 diabetes mellitus (T2DM).MethodsDemographic and medical history data, physical examination, and biochemical test results of 132 T2DM patients were collected. The plasma concentrations of nesfatin-1, C-reactive protein (CRP), interleukin-6 (IL-6), soluble triggering receptors expressed on myeloid cells 1 (sTREM1), and sTREM2 in T2DM patients were measured. Cognitive function was evaluated using the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). The patients were divided into two groups: a low-nesfatin-1 group (n = 75) and a high-nesfatin-1 group (n = 57) based on a plasma nesfatin-1 concentration less than or above the 50th percentile value of all the samples.ResultsThe results showed that plasma HbA1c levels were positively correlated with CRP, IL-6, sTREM1, and sTREM2 levels in patients with T2DM (P < 0.05). Plasma nesfatin-1 concentrations were positively associated with diabetes-related biochemical indicators including glycated haemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and inflammation-related indicators including CRP, IL-6, sTREM1, and sTREM2 among patients with T2DM (P < 0.05). Moreover, T2DM patients with high nesfatin-1 levels showed higher HbA1c and fasting plasma glucose (FPG) levels (P < 0.05). Furthermore, T2DM patients with high nesfatin-1 levels also showed higher BRIEF-A scores (P = 0.01). Additionally, T2DM patients with high total scores of BRIEF-A (scores > 50th percentile) could be identified with a sensitivity of 59.1% and a specificity of 72.7% by nesfatin-1.ConclusionThese findings indicate that plasma nesfatin-1 might be involved in the T2DM-associated comorbidities and the development of cognitive dysfunction, and the mechanism underlying this involvement is related to the imbalance in the expression of CRP, IL-6, sTREM1, and sTREM2 levels.

Soluble Triggering Receptors Expressed on Myeloid Cells-1 as a Neonatal Ventilator-Associated Pneumonia Biomarker

BackgroundNeonatal ventilator-associated pneumonia (NVAP) is one of the main infections acquired in hospitals, and soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) are a TREM-1 subtype that can be released into the blood or bodily fluids during an infection.MethodsThe patients included in the present study were divided into three groups: the NVAP group, the first control group, and the second control group (n = 20, each). Children requiring respiratory treatment were assigned to the NVAP group, newborns who received mechanical ventilation and had neonatal respiratory distress syndrome were assigned to the first control group, and newborns with normal X-ray and electrocardiogram results but no non-pulmonary infection was assigned to the second control group. The blood and bronchoalveolar lavage fluid (BALF) sTREM-1 levels in all newborns were analyzed.ResultsThe acute-phase blood and BALF sTREM-1 levels were significantly higher in the NVAP group than in the first control group, and the blood sTREM-1 expression level was lower in the second control group than in the NVAP group.ConclusionThe present results suggest that sTREM-1 might be a useful biomarker for NVAP prediction in the Department of Pediatrics.

Evaluation of sTREM1 and suPAR Biomarkers as Diagnostic and Prognostic Predictors in Sepsis Patients.

BackgroundThe purpose of this study was to explore the diagnostic role of sTREM1 in the diagnosis of sepsis and in differentiating between sepsis and systemic inflammatory response syndrome (SIRS). We also aimed to assess the prognostic value of suPAR in comparison to sequential organ-failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II scores, and 28-day mortality.MethodsThis was a cross-sectional study conducted in the Medical Microbiology and Immunology Department and Central Research Laboratory, Faculty of Medicine, Sohag University from June 2019 to January 2021. The study population was classified into two groups: SIRS (no evidence of infection) and sepsis (with SIRS and evidence of infection). Patients were rated on the SOFA and APACHE II scoring systems at admission and after 7 days. Serum levels of sTREM1 and suPAR were measured by ELISA at the same time points.ResultsCRP and sTREM1 values were significantly higher in the sepsis group than the SIRS group on both days (P<0.0001). The area under the curve (AUC) for CRP was 0.87 on the first day and 0.97 on the seventh, while the AUC for sTREM1 was 1.00 and 0.93 on the first and seventh days, respectively. The sensitivity of sTREM1 was 100% and specificity 84% at a cutoff of 49 pg/mL. There was a significantly positive correlation between CRP and sTREM1 values (P<0.0001). On the seventh day, nonsurvivors had significantly higher serum levels of suPAR (median 4.9 ng/mL) than survivors (median 2.9 ng/mL; P<0.0001). Nonsurvivors also had significantly higher SOFA and APACHE II scores than survivors (P<0.0001 and P<0.0001, respectively).ConclusionsTREM1 can be used as a good indicator for diagnosing sepsis in intensive care–unit patients. suPAR can also be used as a predictor of bad prognosis and poor survival at 7 days following admission.

THE RELATIONSHIP BETWEEN sTREM-1 AND ACTIVATION OF INFLAMMATORY BOWEL DISEASES

Objective: In inflammatory bowel disease (IBD), there is no reliable biomarker, yet. We aimed to determine whether Serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) could be useful as a marker for the diagnosis and/or the determination of disease activity in patients with IBD. Material and Method: A total of 47 patients with ulcerative colitis (UC) and 25 patients with Crohn’s disease (CD) were prospectively enrolled. Clinical disease activity was analyzed using the Crohn’s Disease Activity Index (CDAI) for CD and the Truelove-Witts index for UC. Results: sTREM-1 levels were significantly lower in patients with IBD compared to healthy controls (p=0.001). In comparison of the levels of sTREM-1 between the different groups (CD, UC, and healthy controls) the difference was statistically significant. No considerable differences in sTREM-1 levels were determined in patients with active versus quiescent disease. The sTREM-1 levels negatively correlated with C-reactive protein, blood neutrophil-lymphocyte ratio, and positively with haemoglobin levels. Conclusion: sTREM-1 levels are decreased in IBD patients compared with the healthy individuals. It may, therefore, be useful for the diagnosis of IBD. However, it does not seem to be a precise marker of disease activity in IBD and cannot be suggested for assessing disease activity in these patients.

Relationship between levels of serum gastric inhibitory polypeptide (GIP), soluble interleukin-2 receptor (sIL-2R), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and disease condition and prognosis of patients with severe acute pancreatitis.

To explore the relationship between levels of serum gastric inhibitory polypeptide (GIP), soluble interleukin-2 receptor (sIL-2R), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and the disease condition and prognosis in patients with severe acute pancreatitis (SAP). A total of 52 patients with SAP (SAP group) and 50 patients with mild acute pancreatitis (MAP group) admitted to Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China between April 2017 and December 2019 were included in the present study. A further 50 people who had received a healthy physical examination during the same period constituted the healthy control group. The levels of serum GIP, sIL-2R, and sTREM-1 were measured. The levels of serum GIP, sIL-2R, and sTREM-1 were compared among the SAP, MAP and healthy control groups, and the severity of disease (Ranson scoring system) was compared between the SAP and MAP groups. Pearson correlation analysis was used to analyze the correlation between the levels of serum GIP, sIL-2R, and sTREM-1 with the Ranson scores in the SAP group. A receiver operating characteristic (ROC) curve was drawn to evaluate the predictive efficacy of serum GIP, sIL-2R, and sTREM-1 on prognosis. The levels of serum GIP, sIL-2R, and sTREM-1 in the SAP and MAP groups were higher than those in the healthy control group, and the levels in the SAP group were higher than those in the MAP group. The Pearson correlation analysis showed that the levels of serum GIP, sIL-2R, and sTREM-1 in the SAP group were positively correlated with Ranson scores. The levels of serum GIP, sIL-2R, and sTREM-1 in the survival group were lower than those in the deceased group. The ROC curve showed that the best cut-off values of serum GIP, sIL-2R, and sTREM-1 in predicting prognostic survival were 167.040 pg/mL, 70.840 pg/mL, and 128.325 ng/mL, respectively. The levels of serum GIP, sIL-2R, and sTREM-1 are closely related to the severity of illness in patients with SAP and can be used as reference indicators for assessing the onset of SAP and predicting prognosis.

TREM1 Blockade Ameliorates Lipopolysaccharide-Induced Acute Intestinal Dysfunction through Inhibiting Intestinal Apoptosis and Inflammation Response.

Objective The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. Methods Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1β were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. Results LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1β levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. Conclusion LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.

Increased sTREM-1 levels identify cirrhotic patients with bacterial infection and predict their 90-day mortality

Background and aimsPatients 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. MethodsSera 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. ResultssTREM-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. ConclusionsUse of sTREM-1 could increase the recognition of BIs in cirrhosis and help clinicians in mortality risk assessment of these patients.

STREM-1 as a diagnostic biomarker for acute appendicitis in children

BackgroundThe typical history of acute appendicitis is observed in less than 60% of cases. Therefore, searching for a surrogate marker is mandatory. Our goal was to determine whether the soluble triggering receptor expressed on myeloid cells (sTREM-1) is an efficient biomarker for acute appendicitis. MethodssTREM-1 serum levels were measured in addition to carrying out routine diagnostic tests (urine dipstick, complete blood count and CRP) in children admitted to the Emergency Department with suspected appendicitis. Statistical analysis was performed in order to examine whether sTREM-1 was a significant predictor of appendicitis. ResultsFifty three of 134 children enrolled in the study were diagnosed with appendicitis. There was no significant difference in serum sTREM-1 levels (p = 0.111) between children with or without appendicitis (n = 81). Leukocytes, neutrophils and CRP were significantly elevated in the appendicitis group (p < 0.001). The appendix diameter was significantly larger and the Alvarado score significantly higher in the appendicitis group (p < 0.001). Conclusionserum sTREM-1 is not a good marker for acute appendicitis. Customary tests in addition to a proper patient history and physical examination are still the most effective methods to diagnose acute appendicitis.

Lipopolysaccharide Levels in Ex Vivo Lung Perfusion are Associated with Lung Function and Suitability for Transplantation

Purpose Ex vivo lung perfusion (EVLP) has emerged as an important platform to assess marginal donor lungs prior to transplantation. Derived from the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS) can stimulate strong immune responses. Studies have shown that donor lungs infected with bacteria may have worse outcomes, suggesting bacteria-induced donor lung injury. However, no large-scale studies have looked at the relationship between LPS levels and donor lung performance on EVLP. Methods LPS levels were measured after one and four hours of perfusion in n=100 clinical EVLP cases. To assess the effects of LPS on lung inflammation, IL-6, 8, 10, and 1β, sTNF-R1, sTREM-1 and ET-1 levels were measured with an ELISA-based platform. Biochemical and physiological assessments were compared to LPS levels. Finally, LPS levels and recipient intensive care unit length of stay after transplantation were investigated. Results There was a significant increase from 0.14 [0.09-0.21] to 0.23 [0.13-0.38] EU/mL (p Conclusion This study demonstrates the trends and importance of circulating LPS levels during EVLP assessment of human donor lung injury. We show that high LPS levels and increasing levels over time were associated with poor donor lung performance in EVLP. These results support the need for therapeutic strategies to target LPS during EVLP, which may improve lung function and rescue more donor lungs for transplantation.

Elevated Plasma Soluble Triggering Receptor Expressed on Myeloid Cells-1 Level in Patients with Acute Coronary Syndrome (ACS): A Biomarker of Disease Severity and Outcome

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.

Role of TREM-1 in the development of early brain injury after subarachnoid hemorrhage

Triggering receptor expressed on myeloid cells-1 (TREM-1) was found to be induced in the context of subarachnoid hemorrhage (SAH) before. This study further investigates its role in the development of SAH-induced early brain injury (EBI). Firstly, rats were randomly divided into Sham and SAH groups for analysis of temporal patterns and cellular localization of TREM-1. Secondly, TREM-1 intervention was administrated to produce Sham, vehicle, antagonist and agonist groups, for analyzing TREM-1, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and NF-κB expressions at 24 h post-modeling, and EBI assessment at 24 h and 72 h. Thirdly, TLR4 inhibitor (TAK-242) was exploited to produce Sham, Sham+TAK-242, SAH, and SAH + TAK-242 groups to analyze the effects of TLR4 inhibition on TREM-1 induction and EBI evaluation at 72 h. Fourthly, the relationship of soluble TREM-1 (sTREM-1) levels in cerebrospinal fluid of SAH patients with Hunt-Hess grades were explored. The results showed that TREM-1 increased in the brain after experimental SAH (eSAH) early at 6 h and peaked at 48 h, which was found to be located in microglia and endothelial cells. TREM-1 inhibition attenuated EBI associated with TLR4/MyD88/NF-κB suppression, while enhancement had the opposite effects. Contrarily, TLR4 inhibition prevented TREM-1 induction and ameliorated EBI. In addition, sTREM-1 levels in SAH patients positively correlated with Hunt-Hess grades. Overall, the present study provides new evidence that TREM-1 increases dynamically in the brain after eSAH and it is located in microglia and endothelial cells, which may aggravate EBI by interacting with TLR4 pathway. And sTREM-1 in patients might act as a monitoring biomarker of EBI, providing new insights for future studies.

Soluble Triggering Receptor on Myeloid Cell-1 and its Predictive Factors in Patients With End-Stage Kidney Disease on Hemodialysis.

Triggering receptor expressed on myeloid cells (TREM)-1 is a potent and early amplifier of the inflammatory response expressed on neutrophils and monocytes/macrophages. TREM-1, and its soluble form (sTREM-1), are increased in sepsis and other noninfectious inflammatory conditions. However, virtually no data are available in kidney disease. To determine serum sTREM-1 and its associated variables in patients on hemodialysis (HD), cross-sectional study including 264 HD patients and 148 controls. sTREM-1 was measured by quantitative sandwich enzyme immunoassay; soluble tumor necrosis factor receptor-1 (sTNF-R1), interleukin-6 (IL-6), and C-reactive protein (CRP) were also measured. All inflammation markers were significantly higher in HD patients than controls. Median (IQR) sTREM-1 was 1,006 (613-1,650) pg/mL but undetectable in controls. Considering only HD patients, sTREM-1 was positively correlated with IL-6 (r = 0.19, p = 0.008), and its levels were significantly higher in patients with arteriovenous fistula than in those with temporary catheter (1,226 vs. 743 pg/mL), in patients with 3 HD sessions/week than in those with 2 sessions/week (1,150 vs. 646 pg/mL), and in patients with >1 year on HD than in those with ≤1 year (1,100 vs. 948 pg/mL), whereas they were not different regarding age or presence of infection. Serum sTREM-1, sTNF-R1, IL-6, and CRP were higher in HD patients compared to controls. In HD patients, sTREM-1 displayed higher levels in individuals with arteriovenous fistula, 3 sessions/week and longer vintage, but not in those with infection or older age; in multivariate analysis, only the first two variables significantly predicted higher sTREM-1 levels.

Severe Periodontitis and Biomarkers of Bacterial Burden. Results From a Case-Control and Intervention Clinical Trial.

Background and aims: Periodontitis is an inflammatory-infectious disease. Identifying markers of systemic exposure of periodontitis might be of interest to study its interaction with other conditions. Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is upregulated during bacterial infections. Our aim was therefore to investigate whether periodontitis and its treatment are associated with bacterial endotoxin and sTREM-1.Methods: Fifty patients with severe periodontitis and 50 age-matched controls were included in a case-control study (all never smokers). A secondary analysis of a previously published intervention study was performed, in which included 69 patients with severe periodontitis were randomized to receive either intensive (IPT) or control periodontal therapy (CPT) and monitored over 6 months. Serum levels of bacterial endotoxin and sTREM-1 were determined at one time point (case-control study) and at baseline, 1 day, 1 and 6 months after periodontal treatment (intervention study).Results: Severe periodontitis was associated with elevated circulating endotoxin levels when cases (22.9 ± 2.2 EU/ml) were compared to controls (3.6 ± 0.5 EU/ml, p < 0.001) and with sTREM-1 levels (1302.6 ± 47.8 vs. 870.6 ± 62.0 pg/ml, p < 0.001). A positive correlation was observed between sTREM-1 and endotoxin levels (r = 0.4, p < 0.001). At 6 months after treatment, IPT significantly decreased serum levels of sTREM-1 compared to CPT (adjusted mean difference of 500.2 pg/ml, 95% CI: 18.9–981.4; p = 0.042). No substantial differences were noted in endotoxin levels at any time point after treatment between groups.Conclusions: Severe periodontitis is linked to increased circulating endotoxin and sTREM-1 levels and following IPT a reduction in sTREM-1 levels is observed.

Diagnostic Value of Plasma Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Children with Urinary Tract Infections

Abstract Objective The aim of the present study was to evaluate the diagnostic value of soluble triggering receptor on myeloid cells-1 as a novel marker for diagnosis of childhood urinary tract infections (UTI). Methods This study enrolled 30 pediatric patients diagnosed with acute febrile UTIs; 30 healthy children were included as the control group. The blood samples from the patients and healthy controls were collected for a soluble triggering receptor on myeloid cells-1 (sTREM-1) test. Results The study group was composed of 9 males and 21 females, and the mean age of the study population was 6.6 ± 3.2 (range = 1–14) years. sTREM-1 levels were significantly higher in UTI patients than in the controls (592 ± 323 vs. 490 ± 299 pg/mL, p = 0.04). The receiver operating curve analysis revealed a cut-off value of soluble triggering receptor expressed on myeloid cells-1 of 514 ng/mL (area under the curve = 0.562). When the cut-off value was taken 514 pg/mL, soluble triggering receptor expressed on myeloid cells-1 had a sensitivity of 57% and a specificity of 50% for the diagnosis of UTI. Conclusion The present study revealed that plasma sTREM-1 level may be elevated in UTI and may therefore serve as a useful predictive tool for the diagnosis of UTI.