Efficacy and safety of infliximab and adalimumab in inflammatory bowel disease patients.

INTRODUCTION: Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn's Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD. AIM: This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD. METHOD: This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn's Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period. RESULTS: In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002). CONCLUSION: Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients. CLINICAL TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).

sTREM-1 as a Predictive Biomarker for Disease Severity and Prognosis in COVID-19 Patients.

Background: Research on biomarkers associated with the severity and adverse prognosis of COVID-19 can be beneficial for improving patient outcomes. However, there is limited research on the role of soluble TREM-1 (sTREM-1) in predicting the severity and prognosis of COVID-19 patients. Methods: A total of 115 COVID-19 patients admitted to the emergency department of Beijing Youan Hospital from February to May 2023 were included in the study. Demographic information, laboratory measurements, and blood samples for sTREM-1 levels were collected upon admission. Results: Our study found that sTREM-1 levels in the plasma of COVID-19 patients increased with the severity of the disease (moderate vs mild, p=0.0013; severe vs moderate, p=0.0195). sTREM-1 had good predictive value for disease severity and 28-day mortality (area under the ROC curve was 0.762 and 0.805, respectively). sTREM-1 also exhibited significant correlations with age, body temperature, respiratory rate, PaO2/FiO2, PCT, CRP, and CAR. Ultimately, through multivariate logistic regression analysis, we determined that sTREM-1 (OR 1.008, 95% CI: 1.002-1.013, p=0.005), HGB (OR 0.966, 95% CI: 0.935-0.998, p=0.036), D-dimer (OR 1.001, 95% CI: 1.000-1.001, p=0.009), and CAR (OR 1.761, 95% CI: 1.154-2.688, p=0.009) were independent predictors of 28-day mortality in COVID-19 patients. The combination of these four markers yielded a strong predictive value for 28-day mortality in COVID-19 cases with an AUC of 0.919 (95% CI: 0.857 -0.981). Conclusion: sTREM-1 demonstrated good predictive value for disease severity and 28-day mortality, serving as an independent prognostic factor for adverse patient outcomes. In the future, we anticipate conducting large-scale multicenter studies to validate our research findings.

Diagnostic values of soluble triggering receptor expressed on myeloid cells (sTREM-1) and interferon-inducible protein-10 (IP-10) for severe mycoplasma pneumoniae pneumonia in children.

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.

sTREM-1: A Biomarker of Mortality in Severe Malaria Impacted by Acute Kidney Injury.

BACKGROUND: Malaria is an important cause of mortality in African children. Identification of biomarkers to identify children at risk of mortality has the potential to improve outcomes. METHODS: We evaluated 11 biomarkers of host response in 592 children with severe malaria. The primary outcome was biomarker performance for predicting mortality. Biomarkers were evaluated using receiver operating characteristic (ROC) curve analysis comparing the area under the ROC curve (AUROC). RESULTS: Mortality was 7.3% among children in the study with 72% of deaths occurring within 24 hours of admission. Among the candidate biomarkers, soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) had the highest AUROC (0.78 [95% confidence interval, .70-.86]), outperforming several other biomarkers including C-reactive protein and procalcitonin. sTREM-1 was the top-performing biomarker across prespecified subgroups (malaria definition, site, sex, nutritional status, age). Using established cutoffs, we evaluated mortality across sTREM-1 risk zones. Among children with acute kidney injury, 39.9% of children with a critical-risk sTREM-1 result had an indication for dialysis. When evaluated relative to a disease severity score, sTREM-1 improved mortality prediction (difference in AUROC, P = .016). CONCLUSIONS: sTREM-1 is a promising biomarker to guide rational allocation of clinical resources and should be integrated into clinical decision support algorithms, particularly when acute kidney injury is suspected.

Association of sTREM-1 and Neutrophil-to-Lymphocyte Ratio as Prognostic Markers in COVID-19 Short- and Long-Term Mortality.

Aim: Current problem related to COVID-19 is various complications after disease, especially long-term mortality after COVID-19. Routine blood tests presented their effectiveness in the diagnosis, prognosis and mortality of COVID-19. The neutrophil-to-lymphocyte ratio (NLR) is an important marker of systemic inflammation. Soluble Trigger receptor expressed on myeloid cells-1 (sTREM-1) is considered an intrinsic enhancer of inflammatory signals. This study examined the predictive value of these markers in COVID-19 mortality. Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The neutrophil-to-lymphocyte ratio (NLR) was calculated as the absolute number of neutrophils divided by the absolute number of lymphocytes. The level of sTREM-1 in the blood serum was evaluated by ELISA. Results: Plasma sTREM-1 concentration greater than 59.08 pg/mL and an NLR greater than 2.29 had an increased risk of early mortality (hazard ratio = 8.07; 95% CI: 1.03-62.17 and 9.24; 95% CI: 1.202-71.08, respectively); for long-term mortality of sTREM-1 greater than 47.34 pg/mL (hazard ratio = 7.96; 95% CI: 1.072-59.18) and NLR greater than 2.10 (hazard ratio = 11.52; 95% CI: 1.551-85.52). Conclusion: This study suggests that early levels of sTREM-1 and NLR are associated with the risk of 6-month mortality after experiencing COVID-19.

Soluble triggering receptor expressed on myeloid cell-1 reflects the cross-sectional activity of microscopic polyangiitis and granulomatosis with polyangiitis.

Objectives: We investigated whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflects cross-sectional activity of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods: Forty-seven MPA and 32 GPA patients with well-documented clinical records and stored sera were enrolled. sTREM-1 levels were evaluated using Magnetic Luminex® assay, and disease activity was assessed using Birmingham vasculitis activity score (BVAS). Patients were divided into two groups according to the upper and lower halves of BVAS. Receiver operator characteristic (ROC) curve analysis was used to identify cut-off for determining upper half of BVAS. Linear and binary logistic regression was performed to evaluate the association between sTREM-1 and disease activity and status. Results: The median age of patients was 67.0 years, and 58.2 % were women. The median BVAS and sTREM-1 were 12.0 and 467.1 pg/mL. sTREM-1 was significantly correlated with BVAS along with five-factor score, Short-Form 36-Item Health Surveys, and C-reactive protein. In multivariable linear regression analysis, erythrocyte sedimentation rate (standardised ß 0.241), and sTREM-1 (standardised ß 0.288) were correlated with BVAS. ROC analysis revealed that the cut-off of sTREM-1 for the upper half of BVAS was 474.1 pg/mL. MPA and GPA patients with sTREM-1 ≥474.1 pg/mL exhibited a significantly higher risk for the upper half of BVAS than those without (relative risk 5.932). Multivariable logistic regression analysis demonstrated sTREM-1 ≥474.1 pg/mL (odds ratio 5.662) was associated with the upper half of BVAS. Conclusion: sTREM-1 reflects the activity of MPA and GPA, suggesting its role as a potential biomarker for assessing disease severity.

Validation of sTREM-1 and IL-6 based algorithms for outcome prediction of COVID-19.

BACKGROUND: A prospective observational cohort study of COVID-19 patients in a single Emergency Department (ED) showed that sTREM-1- and IL-6-based algorithms were highly predictive of adverse outcome (Van Singer et al. J Allergy Clin Immunol 2021). We aim to validate the performance of these algorithms at ED presentation. METHODS: This multicentric prospective observational study of PCR-confirmed COVID-19 adult patients was conducted in the ED of three Swiss hospitals. Data of the three centers were retrospectively completed and merged. We determined the predictive accuracy of the sTREM-1-based algorithm for 30-day intubation/mortality. We also determined the performance of the IL-6-based algorithm using data from one center for 30-day oxygen requirement. RESULTS: 373 patients were included in the validation cohort, 139 (37%) in Lausanne, 93 (25%) in St.Gallen and 141 (38%) in EOC. Overall, 18% (93/373) patients died or were intubated by day 30. In Lausanne, 66% (92/139) patients required oxygen by day 30. The predictive accuracy of sTREM-1 and IL-6 were similar compared to the derivation cohort. The sTREM-1-based algorithm confirmed excellent sensitivity (90% versus 100% in the derivation cohort) and negative predictive value (94% versus 100%) for 30-day intubation/mortality. The IL-6-based algorithm performance was acceptable with a sensitivity of 85% versus 98% in the derivation cohort and a negative predictive value of 60% versus 92%. CONCLUSION: The sTREM-1 algorithm demonstrated good reproducibility. A prospective randomized controlled trial, comparing outcomes with and without the algorithm, is necessary to assess its safety and impact on hospital and ICU admission rates. The IL-6 algorithm showed acceptable validity in a single center and need additional validation before widespread implementation.

IL-1R2-based biomarker models predict melioidosis mortality independent of clinical data.

Introduction: Melioidosis is an often-fatal tropical infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, but few studies have identified promising biomarker candidates to predict outcome. Methods: In 78 prospectively enrolled patients hospitalized with melioidosis, six candidate protein biomarkers, identified from the literature, were measured in plasma at enrollment. A multi-biomarker model was developed using least absolute shrinkage and selection operator (LASSO) regression, and mortality discrimination was compared to a clinical variable model by receiver operating characteristic curve analysis. Mortality prediction was confirmed in an external validation set of 191 prospectively enrolled patients hospitalized with melioidosis. Results: LASSO regression selected IL-1R2 and soluble triggering receptor on myeloid cells 1 (sTREM-1) for inclusion in the candidate biomarker model. The areas under the receiver operating characteristic curve (AUC) for mortality discrimination for the IL-1R2 + sTREM-1 model (AUC 0.81, 95% CI 0.72-0.91) as well as for an IL-1R2-only model (AUC 0.78, 95% CI 0.68-0.88) were higher than for a model based on a modified Sequential Organ Failure Assessment (SOFA) score (AUC 0.69, 95% CI 0.56-0.81, p < 0.01, p = 0.03, respectively). In the external validation set, the IL-1R2 + sTREM-1 model (AUC 0.86, 95% CI 0.81-0.92) had superior 28-day mortality discrimination compared to a modified SOFA model (AUC 0.80, 95% CI 0.74-0.86, p < 0.01) and was similar to a model containing IL-1R2 alone (AUC 0.82, 95% CI 0.76-0.88, p = 0.33). Conclusion: Biomarker models containing IL-1R2 had improved 28-day mortality prediction compared to clinical variable models in melioidosis and may be targets for future, rapid test development.

TREM-1 as a Marker of Multiple Organ Failure in Cardiac Surgery.

Systemic inflammatory response syndrome (SIRS) frequently accompanies early postoperative period after cardiac surgery and in some cases is complicated by multiple organ failure (MOF). Inherited variation in the innate immune response genes (e.g., TREM1) is among the major factors determining the development of SIRS and the risk of MOF. This research was aimed to study whether the polymorphisms within the TREM1 gene are associated with MOF after the coronary artery bypass graft (CABG) surgery. Here we enrolled 592 patients who underwent CABG surgery in the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russia) and documented 28 cases of MOF. Genotyping was performed by allele-specific PCR using TaqMan probes. In addition, we measured serum soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) using enzyme-linked immunosorbent assay. Five polymorphisms (rs1817537, rs2234246, rs3804277, rs7768162 andrs4711668) within the TREM1 gene were significantly associated with MOF. Patients with MOF had higher serum sTREM-1 as compared with those without MOF at both pre- and post-intervention stages. Serum sTREM-1 was associated with the rs1817537,rs2234246 and rs3804277 polymorphisms within the TREM1 gene. Minor alleles within the TREM1 gene define the level of serum sTREM-1 and are associated with MOF after CABG surgery.

Dengue Virus Increases the Expression of TREM-1 and CD10 on Human Neutrophils.

Every year, dengue is responsible for 400 million infections worldwide. Inflammation is related to the development of severe forms of dengue. Neutrophils are a heterogeneous cell population with a key role in the immune response. During viral infection, neutrophils are mainly recruited to the infection site; however, their excessive activation is linked to deleterious results. During dengue infection, neutrophils are involved in the pathogenesis through neutrophils extracellular traps production, tumor necrosis factor-alpha, and interleukin-8 secretion. However, other molecules regulate the neutrophil role during viral infection. TREM-1 is expressed on neutrophils and its activation is related to increased production of inflammatory mediators. CD10 is expressed on mature neutrophils and has been associated with the regulation of neutrophil migration and immunosuppression. However, the role of both molecules during viral infection is limited, particularly during dengue infection. Here, we report for the first time that DENV-2 can significantly increase TREM-1 and CD10 expression as well as sTREM-1 production in cultured human neutrophils. Furthermore, we observed that treatment with granulocyte-macrophage colony stimulating factor, a molecule mostly produced in severe cases of dengue, is capable of inducing the overexpression of TREM-1 and CD10 on human neutrophils. These results suggest the participation of neutrophil CD10 and TREM-1 in the pathogenesis of dengue infection.

Circulating sTREM-1 as a predictive biomarker of pediatric multisystemic inflammatory syndrome (MIS-C).

The exacerbation of the inflammatory response caused by SARS-CoV-2 in adults promotes the production of soluble mediators that could act as diagnostic and prognostic biomarkers for COVID-19. Among the potential biomarkers, the soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been described as a predictor of inflammation severity. The aim was to evaluate sTREM-1 and cytokine serum concentrations in pediatric patients during the acute and convalescent phases of COVID-19. This was a prospective study that included 53 children/adolescents with acute COVID-19 (Acute-CoV group); 54 who recovered from COVID-19 (Post-CoV group) and 54 controls (Control group). Preexisting chronic conditions were present in the three groups, which were defined as follows: immunological diseases, neurological disorders, and renal and hepatic failures. The three groups were matched by age, sex, and similar preexisting chronic conditions. No differences in sTREM-1 levels were detected among the groups or when the groups were separately analyzed by preexisting chronic conditions. However, sTREM-1 analysis in the seven multisystemic inflammatory syndrome children (MIS-C) within the Acute-Cov group showed that sTREM-1 concentrations were higher in MIS-C vs non-MIS-C acute patients. Then, the receiver operating curve analysis (ROC) performed with MIS-C acute patients revealed a significant AUC of 0.870, and the sTREM-1 cutoff value of > 5781 pg/mL yielded a sensitivity of 71.4 % and a specificity of 91.3 % for disease severity, and patients with sTREM-1 levels above this cutoff presented an elevated risk for MIS-C development in 22.85-fold (OR = 22.85 [95 % CI 1.64-317.5], p = 0.02). The cytokine analyses in the acute phase revealed that IL-6, IL-8, and IL-10 concentrations were elevated regardless of whether the patient developed MIS-C, and those levels decreased in the convalescent phase, even when compared with controls. Spearman correlation analysis generated positive indexes between sTREM-1 and IL-12 and TNF-α concentrations, only within the Acute-CoV group. Our findings revealed that sTREM-1 in pediatric patients has good predictive accuracy as an early screening tool for surveillance of MIS-C cases, even in patients with chronic underlying conditions.

Role of biomarkers in the diagnosis of invasive aspergillosis in immunocompromised patients.

BACKGROUND: Invasive aspergillosis is one of the important causes of infection in immunocompromised patients. This study aimed to evaluate the roles of biomarkers in the diagnosis of invasive aspergillosis and their relationship with antifungal stewardship programs. METHODS: 190 sera from 52 immunocompromised patients and volunteer individuals were included in this study. 18 immunocompromised volunteers without IA and 34 patients with probable and proven aspergillosis according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group consensus definitions were entered in this study. The respective sera were evaluated for procalcitonin, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels; white blood cells count (WBC) count, C reactive protein (CRP), lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) values. Demographic data and clinical characteristics of patients were extracted from their files. RESULTS: The male-to-female ratio and mean age of patients were 22/12 and 38.9 years, respectively. The hematologic disorder was the most predisposing factor (29/34, 85.3%). Sensitivity of biomarkers for diagnosis of invasive aspergillosis was 70.6% (cut off value > 190 pg/mL for sTREM-1, 71% (cut off value > 260 pg/mL) for PCT, 85.3% (cut off value > 193 U/L) for LDH, 94.1% (cut off value > 8 mg/l) for CRP, 64.7% (cut off value < 5200 cells/ml) for WBC, and 85.3% (cut off value > 23 mm/h) for ESR. Twelve patients died, with significantly increased sTREM-1 levels and decreased WBC count in them. CONCLUSION: According to our data, evaluation of the biomarkers can help in the diagnosis, management, and prediction of the severity of Aspergillus infection, and the rational use of antifungal agents in immunocompromised patients.

Clinical value of serum sTREM-1 and HBP levels in combination with traditional inflammatory markers in diagnosing hospital-acquired pneumonia in elderly.

BACKGROUND: The clinical presentation of hospital-acquired pneumonia (HAP) in older patients is often complex and non-specific, posing a diagnostic challenge. This study evaluates the value of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and heparin-binding protein (HBP) in combination with traditional inflammatory markers procalcitonin (PCT) and C-reactive protein (CRP) in diagnosing HAP in older patients. METHODS: Thirty-eight elderly male patients with HAP (≥ 80 years old) and 46 age-matched controls, who were hospitalized for other reasons than HAP, were enrolled. The serum sTREM-1, HBP, PCT and CRP levels were measured by ELISA on the first day after enrollment. In addition, routine blood test, blood gas, sputum analysis, clinical pulmonary infection score (CPIS) assessment, and chest X-ray were performed, and the correlations with HAP were analyzed. RESULTS: The serum sTREM-1 (n = 38, 170.75 ± 158.33 pg/ml), HBP (2.08 ± 0.50), PCT (9.44 ± 17.73) and CRP (79.63 ± 71.37) were all significantly higher in the HAP group, when compared to the control group (P < 0.05). Furthermore, the values were positively correlated with the CPIS. The ROC curve analysis revealed that the AUC for sTREM-1 (0.667) and HBP (0.711) were lower, when compared to that for PCT (AUC = 0.839) and CRP (AUC = 0.840). The combination of PCT and CRP with sTREM-1 (AUC = 0.927) or HBP (AUC = 0.930) had the highest AUC values. CONCLUSION: Serum sTREM-1, HBP, PCT and CRP can all be used as diagnostic markers for HAP in the elderly. The combination of traditional inflammatory markers PCT and CRP with novel inflammatory marker sTREM-1 or HBP further improves the diagnostic performance.

The associations between plasma soluble Trem1 and neurological diseases: a Mendelian randomization study.

BACKGROUND: Triggering receptor expressed on myeloid cell 1 (Trem1) is an important regulator of cellular inflammatory responses. Neuroinflammation is a common thread across various neurological diseases. Soluble Trem1 (sTrem1) in plasma is associated with the development of central nervous system disorders. However, the extent of any causative effects of plasma sTrem1 on the risk of these disorders is still unclear. METHOD: Genetic variants for plasma sTrem1 levels were selected as instrumental variables. Summary-level statistics of neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), epilepsy, cerebrovascular diseases, and migraine were collected from genome-wide association studies (GWASs). Whether plasma sTrem1 was causally associated with neurological disorders was assessed using a two-sample Mendelian randomization (MR) analysis, with false discovery rate (FDR)-adjusted methods applied. RESULTS: We inferred suggestive association of higher plasma sTrem1 with the risk of AD (odds ratio [OR] per one standard deviation [SD] increase = 1.064, 95% CI 1.012-1.119, P = 0.014, PFDR = 0.056). Moreover, there was significant association between plasma sTrem1 level and the risk of epilepsy (OR per one SD increase = 1.044, 95% CI 1.016-1.072, P = 0.002, PFDR = 0.032), with a modest statistical power of 41%. Null associations were found for plasma sTrem1 with other neurological diseases and their subtypes. CONCLUSIONS: Taken together, this study indicates suggestive association between plasma sTrem1 and AD. Moreover, higher plasma sTrem1 was associated with the increased risk of epilepsy. The findings support the hypothesis that sTrem1 may be a vital element on the causal pathway to AD and epilepsy.

Diagnostic and prognostic predictive values of triggering receptor expressed on myeloid cell-1 expression in neonatal sepsis: A meta-analysis and systematic review.

Objective: The purpose of this systematic review was to explore the value of the expression level of the triggering receptor expressed on myeloid cell-1 (TREM-1) in the diagnosis and prognosis of neonatal sepsis. Methods: A comprehensive search was performed to identify the diagnostic and prognostic predictive values of the TREM-1 expression level in neonatal sepsis. Based on the retrieval strategy, Cochrane Library, Embase, Ovid, ProQuest, PubMed, Scopus, and Web of Science databases were searched from inception to February 2022. Studies were included if they assessed the accuracy of TREM-1 expression in the diagnosis of neonatal sepsis and distinguished survival and death in neonatal sepsis. Two authors independently evaluated the study and extracted the data, including the first author of the literature, country, total study population, basic population characteristics of the study group and the control group, study design (observational studies), type of sample, sepsis onset, type of biomarker, assay method, cut-off, sensitivity, specificity, true positives (TP), false positives (FP), false negatives (FN), and true negatives (TN). A third party will be consulted if disputed. The accuracy of TREM-1 expression in the diagnosis and prognostic prediction of neonatal sepsis was evaluated by a bivariate mixed-effects model. The source of heterogeneity was explored through meta-regression analysis. Results: Thirteen articles that met the research criteria were included in qualitative analysis, and 11 of them were included in quantitative analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operator characteristic (SROC) curve of soluble TREM-1 (sTREM-1) were 0.94 (95% CI: 0.82, 0.98), 0.87 (95% CI: 0.70, 0.95), 7.36 (95% CI: 2.75, 19.74), 0.07 (95% CI: 0.02, 0.24), 111.71 (95% CI: 13.24, 942.92), and 0.96 (95% CI: 0.94, 0.98), respectively. Meta-regression and subgroup analysis were used to investigate the heterogeneity, owing to non-threshold effects caused by types of test sample and research design. sTREM-1 as a biomarker for distinguishing survival and death in neonates with sepsis had pooled sensitivity, specificity, area under the SROC curve, PLR, NLR, and DOR of 0.95 (95% CI: 0.83, 0.99), 0.98 (95% CI: 0.68, 1.00), 0.99 (95% CI: 0.97, 0.99), 39.28 (95% CI: 2.13, 723.99), 0.05 (95% CI: 0.01, 0.19), and 789.61 (95% CI: 17.53, 35,560.72), respectively. Conclusion: The study showed that TREM-1 was a potential biomarker for the diagnosis and prognosis of neonatal sepsis. The biggest advantage of this study is that it is the first to comprehensively explore the role of TREM-1 expression in the diagnosis and prognosis of neonatal sepsis. However, there are some limitations in this study, such as the reduced number of clinical studies on TREM-1 expression as a biomarker of neonatal sepsis, regional bias, and differences in detection methods. Hence, more large-scale and high-quality studies are needed to improve diagnostic accuracy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022338041.

Significance of biomarkers in stewardship program in pediatric patients infected with Aspergillus species.

BACKGROUND: The potential use of biomarkers in the diagnosis of fungal infections is a challenge. The aim of this study was to evaluate the role of a biomarker-guided antifungal stewardship program for hospitalized pediatrics suffering from invasive aspergillosis (IA). METHODS: Pediatric patients with suspected probable or proven IA were enrolled in this study. Demographic data were collected from their records. Clinical samples were examined by wet mount KOH smear, culture, galactomannan Ag test, and real-time PCR. Patients' sera were evaluated for procalcitonin (PCT) and soluble-triggering receptor expressed on myeloid cells -1 (sTREM-1) levels by ELISA Kits. RESULTS: A total of 73 children were entered in this study with a mean age of 5 years and the male to female ratio 39/34. The most predisposing factors were hematologic disorders (71.2%). The area under the curves (95% confidence interval) for each biomarker were 0.9 (0.85% to 97%) for lactate de hydrogenase (LDH), 0.9 (0.85% to 0.94%) for C-reactive protein, 0.8 (0.75% to 0.84%) for PCT, 0.8 (0.73% to 0.85%) for erythrocyte sedimentation rate, 0.7 (0.6% to 0.8%) for sTREM-1, and 0.5 (0.45% to 0.58%) for white blood cell count. During the study period, 27.4% patients died. The LDH and sTREM-1 levels were significant increase in died patient (p < 0.05). CONCLUSIONS: According to our data, evaluation of biomarkers along with radiologic and clinical signs and symptoms of pediatric patients can lead to proper antifungal therapy and decreased side effects, antifungal resistance, and cost. The combined measurements could be better than a single marker in the prediction of IA.

Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress.

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.

Role of soluble triggering receptors expressed on myeloid cells-1 and 25-hydroxy vitamin D as early diagnostic markers of neonatal Ventilator-associated pneumonia: A prospective cohort study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common causes of nosocomial pneumonia in ventilated neonates. Nevertheless, its diagnosis is challenging due to the nonspecific clinical parameters and the lack of sensitive biomarkers. The main objective of this study was to compare soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) and 25-hydroxy vitamin D as early predictors of neonatal VAP. METHODS: This prospective cohort study included 85 ventilated neonates divided into the VAP group (n = 33) and the non-VAP group (n = 52). sTREM-1 levels in the endotracheal aspirate (ETA) and serum 25-hydroxy vitamin D levels were measured on the third and seventh days following mechanical ventilation. The Ethical and Research Committee approved the study at Tanta University Hospitals, Egypt (with the Approval code: 32751/12/18). RESULTS: The sTREM-1 cutoff value of >0.46 and >0.44 ng/ml at 3 and 7 days had a sensitivity of 93.94% and 96.97%, a specificity of 92.31% and 100%, and an area under the receiver operating characteristic curve (AUC) of 0.963 and 0.993, respectively, to predict the development of neonatal VAP. A serum 25-hydroxy vitamin D cutoff value of ≤17.5 ng/ml at 3 and 7 days had a sensitivity of 90.91% and 81.82%, a specificity of 75% and 78.85%, and area under the curve of 0.877 and 0.939, respectively. CONCLUSION: Both sTREM-1 in ETA and serum 25-hydroxy vitamin D could be used as early predictors of neonatal VAP, but sTREM-1 appears more useful.