Diagnostic potential of soluble ST2 and D-dimer for Stanford Type B aortic dissection and intramural aortic hematoma.

OBJECTIVE: Type B aortic dissection (TBAD) and intramural aortic hematoma (IMH) are common manifestations of Acute Aortic Syndrome (AAS), exhibiting overlapping clinical features. The timely and accurate diagnosis and differentiation between TBAD and IMH are critical for appropriate management. Tumorigenicity 2 (sST2) and D-dimer have been shown to elevate levels in both TBAD and IMH, making them valuable as "rule-out" markers. Hence, we aimed to assess the diagnostic utility of sST2 and D-dimer in distinguishing TBAD from IMH. METHODS: In this retrospective study, we analyzed serum levels of sST2 and D-dimer in 182 AAS patients, comprising 90 TBAD cases, 92 IMH cases, and 90 non-AAS cases. Serial measurements were taken at 1 h, 6 h, 12 h, 24 h, and 72 h post-admission. Comparative analyses were conducted between TBAD and non-AAS cases, IMH and non-AAS cases, and TBAD and IMH cases. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of sST2 and D-dimer in identifying TBAD or IMH cases. RESULTS: Both TBAD and IMH patients displayed elevated levels of sST2 and D-dimer compared to non-AAS cases. Notably, sST2 levels were significantly higher in TBAD patients than in IMH patients, whereas D-dimer levels exhibited moderate differences. TBAD patients tended to exhibit elevated levels of either sST2 or D-dimer, with a modest correlation between the two (Pearson correlation coefficient = 0.3614). In contrast, IMH patients showed elevations in both markers, with a positive correlation between them (Pearson correlation coefficient = 0.6814). The ROC analysis revealed that both sST2 (AUC, 0.657; 95 % CI, 0.552-0.753; cutoff value, 27.54 ng/ml) and D-dimer (AUC, 0.695; 95 % CI, 0.591-0.787, cutoff value, 1.215 ng/ml) demonstrated favorable diagnostic performance for TBAD. sST2 exhibited a sensitivity of 80.92 % and a specificity of 75.00 %, while D-dimer showed a sensitivity of 80.92 % and a specificity of 75.00 %. For the diagnosis of IMH, the combined assessment of sST2 and D-dimer (AUC, 0.674; 95 % CI, 0.599-0.768; sensitivity, 69.20 %; specificity, 80.00 %) proved effective. CONCLUSIONS: Our results indicate that both sST2 and D-dimer show diagnostic potential for TBAD. Elevated levels of either serve as an indicator of TBAD onset. However, concurrent elevation of both markers seems to be indicative of IMH. The combination of increased sST2 and D-dimer levels demonstrates strong diagnostic performance in identifying IMH cases.

Serum interleukin-33 and soluble suppression of tumorigenicity 2 in pediatric leukemia with febrile neutropenia.

The purpose of this study was to evaluate the association between interleukin-33 (IL-33) and its receptor Soluble Suppression of Tumorigenicity-2 (sST2) levels and bacterial infections during febrile neutropenia (FN) in pediatric patients with acute lymphoblastic leukemia (ALL). In this prospective, case-control study, participants were divided into 3 groups: ALL patients with FN (Group A), ALL patients without neutropenia and fever (Group B), and healthy children without infection and chronic disease (Group C). There were 30 cases in each group. Blood samples for IL-33 and sST2 have been drawn from patients in Group A before the initiation of treatment and on days 1 and 5 of treatment, and from patients in Groups B and C at initiation. At admission, mean IL-33 level (39.02 ± 26.40 ng/L) in Group B and mean sST2 level (185.3 ± 371.49 ng/ml) in Group A were significantly higher than the other groups (p = 0.038, p < 0.001, respectively). No difference was observed in the mean IL-33 and sST2 levels in the 5-day follow-up of patients in Group A (p = 0.82, p = 0.86, respectively). IL-33 and sST2 levels were not associated with fever duration, neutropenia duration or length of hospitalization. While C-reactive protein (CRP) was significantly higher in patients with positive blood culture (p = 0.021), IL-33 (p = 0.49) and sST2 (p = 0.21) levels were not associated with culture positivity.  Conclusion: IL-33 and sST2 levels were not found valuable as diagnostic and prognostic markers to predict bacterial sepsis in patients with FN. What is Known: • Neutropenic patients are at high risk of serious bacterial and viral infections, but the admission symptom is often only fever. • Febrile neutropenia has a high mortality rate if not treated effectively. What is New: • Febrile neutropenia is not only caused by bacterial infections. Therefore, new biomarkers should be identified to prevent overuse of antibiotics. • Specific biomarkers are needed to diagnose bacterial sepsis in the early phase of febrile neutropenia.

Performance Evaluation of AFIAS ST2 and Ichroma ST2 Assays in Comparison with Presage ST2 Assay.

Background: Elevated soluble suppression of tumorigenicity 2 (sST2) levels may predict mortality in heart failure (HF) patients. The AFIAS ST2 assay (AFIAS ST2, Boditech Med Inc., Chuncheon, Korea) and ichroma ST2 assay (ichroma ST2, Boditech Med Inc.) are newly developed point-of-care (POC) assays for measuring sST2 level. We evaluated the performance of these assays, in terms of cut-off validation and prognosis, and compared them with that of the Presage ST2 assay (Presage ST2, Critical Diagnostics, San Diego, CA, USA). Methods: We validated the US FDA-claimed sST2 clinical cut-off of 35 ng/mL using 420 serum samples (298 samples from the universal sample bank of the American Association for Clinical Chemistry and 122 samples from reference individuals from Konkuk University Medical Center). We compared AFIAS ST2 and ichroma ST2 with Presage ST2, using 206 samples from patients with HF. We assessed prognosis using the three assays in 252 samples from the Barcelona ambulatory HF cohort subsets. Results: The upper reference limits of AFIAS ST2 and ichroma ST2 were within the clinical cut-off of Presage ST2. The results of AFIAS ST2 and ichroma ST2 were highly correlated with those of Presage ST2 (r = 0.82 and 0.81, respectively). Based on this cut-off, all three assays predicted cardiovascular death. Conclusions: The new POC assays, AFIAS ST2 and ichroma ST2, would be useful in clinical practice for managing HF patients, with performances equivalent to that of Presage ST2.

Circulating Gal-3 and sST2 are associated with acute exercise-induced sustained endothelial activation: Possible relevance for fibrosis development?

Long-term, intense endurance exercise training can occasionally induce endothelial micro-damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well-trained male participants (10 runners and 10 cyclists) performed a strenuous high-intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal-3 and sST2 concentrations were investigated by enzyme-linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal-3 and sST2 concentrations and ECs were elevated after exercise (P < 0.001), without interaction between exercise modalities. Circulating Gal-3 and sST2 concentrations both showed a positive relationship with ECs (rrm  = 0.68, P = 0.001 and rrm  = 0.57, P = 0.010, respectively, both n = 18). The EC association with Gal-3 was significant only in cyclists, but equally strong for both modalities. Gal-3 was also related to exercise-induced CTi (rrm  = 0.57, P = 0.011, n = 18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise-released Gal-3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise-induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long-term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. NEW FINDINGS: What is the central question of this study? Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear. What is the main finding and its importance? We show that galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal-3 is an enhanced cardiac contractility. Acute exercise-released Gal-3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations.

sST2 Levels Show No Association with Helicobacter pylori Infection in Asymptomatic Patients: Implications for Biomarker Research.

INTRODUCTION: Helicobacter pylori (H. pylori) is a prevalent stomach bacterium that can cause a range of clinical outcomes, including gastric cancer. In recent years, soluble suppression of tumorigenicity-2 (sST2) has gained attention as a biomarker associated with various diseases, such as gastric cancer. The purpose of this study was to explore the possible connection between H. pylori infection and sST2 levels in patients who do not exhibit symptoms. METHODS: A total of 694 patients from the Salzburg Colon Cancer Prevention Initiative (Sakkopi) were included in the study. The prevalence of H. pylori infection was determined by histology, and sST2 levels were measured in serum samples. Clinical and laboratory parameters, such as age, sex, BMI, smoking status, hypertension, and metabolic syndrome, were also collected. RESULTS: The median sST2 concentration was similar between patients with (9.62; 7.18-13.44 ng/mL; p = 0.66) and without (9.67; 7.08-13.06 ng/mL) H. pylori. Logistic regression analysis did not show any association (OR 1.00; 95%CI 0.97-1.04; p = 0.93) between sST2 levels and H. pylori infection, which remained so (aOR 0.99; 95%CI 0.95-1.03; p = 0.60) after adjustment for age, sex, educational status, and metabolic syndrome. In addition, sensitivity analyses stratified by age, sex, BMI, smoking status, educational status, and the concomitant diagnosis of metabolic syndrome could not show any association between sST2 levels and H. pylori infection. CONCLUSION: The results indicate that sST2 may not serve as a valuable biomarker in the diagnosis and treatment of H. pylori infection. Our findings are of relevance for further research investigating sST2, as we could not find an influence of asymptomatic H. pylori infection on sST2 concentration. WHAT IS ALREADY KNOWN?: Soluble suppression of tumorigenicity-2 (sST2) has gained attention as a biomarker associated with various diseases, such as gastric cancer. WHAT IS NEW IN THIS STUDY?: The median sST2 concentration was similar between patients with (9.62; 7.18-13.44 ng/mL; p = 0.66) and without (9.67; 7.08-13.06 ng/mL) H. pylori. WHAT ARE THE FUTURE CLINICAL AND RESEARCH IMPLICATIONS OF THE STUDY FINDINGS?: The results indicate that sST2 may not serve as a valuable biomarker in the diagnosis and treatment of H. pylori infection.

Role of Soluble ST2 Biomarker in Predicting Recurrence of Atrial Fibrillation after Electrical Cardioversion or Pulmonary Vein Isolation.

This study aims to determine the predictive value of the soluble suppression of tumorigenicity 2 (sST2) biomarker in atrial fibrillation (AF) recurrence. This prospective, observational study included patients with AF referred for electrical cardioversion (ECV) or pulmonary vein isolation (PVI) procedures. Baseline characteristics were collected, and sST2 was determined at baseline and at 3 and 6 months of follow-up. sST2 was determined at baseline in a matched control group. Left atrial voltage mapping was performed in patients undergoing PVI. The sST2 maximal predictive capacity of AF recurrence was at the 3-month FU in the cohort of patients undergoing ECV with respect to 6-month AF recurrence with an AUC of 0.669, a cut-off point of 15,511 pg/mL, a sensitivity of 60.97%, and a specificity of 69.81%. The ROC curve of the sST2 biomarker at baseline and 3 months in the cohort of patients undergoing PVI showed AUCs of 0.539 and 0.490, respectively. The logistic regression model identified the rhythm (AF) and the sST2 biomarker at 3 months as independent factors for recurrence at 6 months in the ECV cohort. In the logistic regression model, sST2 was not an independent factor for recurrence at 6 months of follow-up in the PVI cohort. In patients who underwent ECV, sST2 values at 3 months may provide utility to predict AF recurrence at 6 months of follow-up. In patients who underwent PVI, sST2 had no value in predicting AF recurrence at 6 months of follow-up.

The prognostic value of sST2 in connective tissue disease patients with pulmonary hypertension.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a severe complication of CTD, being one of the leading causes of mortality for patients with this condition. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker associated with adverse clinical outcomes in cardiovascular patients. In this study, we investigated the role of sST2 as a predictor of poor clinical outcome in patients with CTD associated with pulmonary hypertension (CTD-PH). METHODS: This retrospective cohort study enrolled 71 CTD-PH patients diagnosed by echocardiography. Twenty-one CTD patients without PH were selected for a control group. A receiver operating characteristic (ROC) curve assessed the predictive value of sST2 in assessing 3-year clinical worsening. Hazard ratios associated with potential predictors of clinical worsening were estimated using Cox proportional hazard models. The primary end point was clinical worsening. RESULTS: The level of sST2 was significantly elevated in CTD-PH patients compared with the control group. After a mean follow-up of 25.29 (1.88) months, end point events occurred in 26 patients. sST2 was an independent predictor of clinical worsening and all-cause death in patients with CTD-PH. sST2 ≥ 39.99 ng/ml discriminated 3-year clinical worsening with a sensitivity and specificity of 100% and 84.9%, respectively. The patients with both higher levels of sST2 (≥39.99 ng/ml) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (≥300 ng/l) had the worst prognosis. CONCLUSION: sST2 ≥ 39.99 ng/ml predicts higher incidence of clinical worsening events in CTD-PH patients. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP.

Association of Soluble Suppression of Tumorigenicity 2 with New-Onset Atrial Fibrillation in Acute Myocardial Infarction.

BACKGROUND: The combination of acute myocardial infarction (AMI) and atrial fibrillation (AF) is still a thorny problem in the clinic. At present, there are few reports on the role of soluble suppression of tumorigenicity 2 (sST2) in AF after AMI. This study was to explore the predictive value of sST2 in patients with AMI for new-onset AF. METHODS: This is a single-center retrospective clinical observation study. We continuously included AMI patients from September 2019 to November 2021. The concentration of sST2 in blood samples was determined. During admission, a suspicious heart rhythm was recorded by electrocardiogram (ECG) monitoring, and new-onset AF was confirmed by immediate body surface ECG. RESULTS: After multiple factors were included, age, right coronary artery, high-sensitivity C-reactive protein, left ventricular ejection fraction, and sST2 were still risk factors for new-onset AF. The area under curve value of age and sST2 was more than 0.7, which showed good diagnostic value. For reevaluation, the sST2 was added to the clinical new-onset AF prediction model. It was found that the integrated discrimination improvement and net reclassification index in the model were improved significantly. CONCLUSION: sST2 is an independent predictor of new-onset AF in patients with AMI and can improve the accuracy of the AF risk model.

Serum Cardiac Biomarkers in Asymptomatic Hemodialysis Patients: Role of Soluble Suppression of Tumorigenicity-2.

INTRODUCTION: Cardiovascular events (CVE) remain the leading cause of mortality in hemodialysis (HD) patients. The ability to assess the risk of short-term CVE is of great importance. Soluble suppression of tumorogenicity-2 (sST2) is a novel biomarker that better stratifies risk of CVE than troponins in patients with heart failure. Few studies have investigated the role of sST2 in the HD population. The aim of this single-center study was to assess the predictive ability of sST2 on CVE in comparison to high-sensitive cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) in HD patients. METHODS: This study used a prospective, observational cohort design. We enrolled 40 chronic HD patients asymptomatic for chest pain and without recent history of acute coronary syndrome. We tested sST2 pre-/post-HD, hs-cTnI, and BNP. Demographic/dialytic/echocardiographic data were evaluated. We recorded the number of CVE for 12 months. The patients were classified into 2 groups: those who developed CVE and those who did not. RESULTS: Ten of the 40 patients (25%) developed CVE during a 12-month follow-up. Increased sST2 levels (p < 0.0001) as well as hs-cTnI and BNP are predictive of CVE. When analyzing biomarkers as binary variables for values above or below the normal range, the correlation remained significant only for sST2 (p = 0.001). A small variation in sST2 levels before and after HD sessions was found (-2.1 ng/mL). sST2 was correlated with left ventricular (LV) echocardiographic data: LV mass index (p = 0.0001), LV ejection fraction (p = 0.01), and diastolic bulging of septum (p = 0.015). BNP and sST2 combination increased the prediction of CVE in a statistical model. CONCLUSION: Our study confirms that sST2 is useful for stratifying CV risk in the HD population. sST2 can be evaluated simply as a dichotomous value higher or lower than the normal range, making it easily interpretable. Dialysis and residual diuresis did not affect significantly sST2. A multimarker approach that incorporates sST2 and BNP may improve the prediction of CVE.

Diagnostic efficacy of serum ST2 in patients with ASC.

BACKGROUND: Soluble suppression of tumorigenicity 2 (ST2) is closely related to the development of cardiovascular disease, but the level of acute coronary syndrome (ACS) and the relationship between ST2 and ACS are unclear. PATIENTS AND METHODS: Patients with the acute coronary syndrome were divided into the unstable angina pectoris (USAP) group (n = 65) and non-ST-segment elevation myocardial infarction (NSTEMI) group (n = 58), and the healthy population, without chest pain and with normal coronary CT, was included as a control group (n = 55). Laboratory index levels were collected from each participant. The baseline information was reviewed and analyzed. The binary logistic regression was used to explore the relation of ST2 levels with the occurrence of ACS and NSTEMI, and the diagnostic performance of ST2 for diagnosing ACS or NSTEMI was evaluated using a receiver-operating characteristic (ROC) curve. RESULTS: The level of ST2 was found significantly higher in NSTEMI than in USAP and was higher in USAP than in control (p < 0.01). ST2 levels were positively correlated with ALT, AST, and BNP in the control group, were negatively correlated with HGB and TG in the USAP group, and were positively correlated with WBC, GLU, BNP, and Gensini scores in the NSTEMI group. Multivariate analysis revealed that the occurrence of ACS was associated with ST2, BNP, GLU, TC, BUN, WBC, and PLT, and the occurrence of NSTEMI was associated with AST, WBC, LDL-C, and ST2. Meanwhile, ST2 levels achieved good performance for ACS and NSTEMI diagnostician. CONCLUSION: ST2 could be used as an auxiliary diagnostic indicator for the occurrence of ACS and NSTEMI.

Synergistic Effects of Weighted Genetic Risk Scores and Resistin and sST2 Levels on the Prognostication of Long-Term Outcomes in Patients with Coronary Artery Disease.

Resistin and soluble suppression of tumorigenicity 2 (sST2) are useful predictors in patients with coronary artery disease (CAD). Their serum levels are significantly attributed to variations in RETN and IL1RL1 loci. We investigated candidate variants in the RETN locus for resistin levels and those in the IL1RL1 locus for sST2 levels and evaluated the prognostication of these two biomarkers and the corresponding variants for long-term outcomes in the patients with CAD. We included 4652, 557, and 512 Chinese participants from the Taiwan Biobank (TWB), cardiovascular health examination (CH), and CAD cohorts, respectively. Candidate variants in RETN and IL1RL1 were investigated using whole-genome sequence (WGS) and genome-wide association study (GWAS) data in the TWB cohort. The weighted genetic risk scores (WGRS) of RETN and IL1RL1 with resistin and sST2 levels were calculated. Kaplan-Meier curves were used to analyze the prognostication of resistin and sST2 levels, WGRS of RETN and IL1RL1, and their combinations. Three RETN variants (rs3219175, rs370006313, and rs3745368) and two IL1RL1 variants (rs10183388 and rs4142132) were independently associated with resistin and sST2 levels as per the WGS and GWAS data in the TWB cohort and were further validated in the CH and CAD cohorts. In combination, these variants explained 53.7% and 28.0% of the variation in resistin and sST2 levels, respectively. In the CAD cohort, higher resistin and sST2 levels predicted higher rates of all-cause mortality and major adverse cardiac events (MACEs) during long-term follow-up, but WGRS of RETN and IL1RL1 variants had no impact on these outcomes. A synergistic effect of certain combinations of biomarkers with RETN and IL1RL1 variants was found on the prognostication of long-term outcomes: Patients with high resistin levels/low RETN WGRS and those with high sST2 levels/low IL1RL1 WGRS had significantly higher all-cause mortality and MACEs rates, and those with both these combinations had the poorest outcomes. Both higher resistin and sST2 levels, but not RETN and IL1RL1 variants, predict poor long-term outcomes in patients with CAD. Furthermore, combining resistin and sST2 levels with the WGRS of RETN and IL1RL1 genotyping exerts a synergistic effect on the prognostication of CAD outcomes. Future studies including a large sample size of participants with different ethnic populations are needed to verify this finding.

Plasma soluble suppression of tumorigenicity 2 and depression after acute ischemic stroke.

BACKGROUND AND PURPOSE: Soluble suppression of tumorigenicity 2 (sST2) might be related to stroke and depression, but the association of sST2 with poststroke depression (PSD) is unclear. The study aimed to prospectively assess the association between plasma sST2 levels and PSD. METHODS: A total of 635 acute ischemic stroke patients with sST2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Rating Scale for Depression to assess depression at 3 months, and PSD was defined as a score of ≥8. Logistic regression analysis was performed to estimate the risk of PSD associated with sST2, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sST2. RESULTS: Two hundred fifty (39.4%) patients developed depression at 3 months after ischemic stroke. Patients with PSD had higher sST2 levels than patients without PSD (172.7 vs. 153.8 pg/ml; p = 0.003). After adjustment for age, sex, education, National Institutes of Health Stroke Scale score, and other covariates, the odds ratio for the highest quartile of sST2 compared with the lowest quartile was 1.84 (95% confidence interval, 1.10-3.08) for PSD. Adding sST2 to a conventional model notably improved risk prediction for PSD (category-free NRI = 19.34%, 95% confidence interval = 4.39%-34.28%, p = 0.017; IDI = 1.20%, 95% confidence interval = 0.25%-2.15%, p = 0.014). CONCLUSIONS: Increased plasma sST2 levels in the acute phase of ischemic stroke were significantly associated with the increased risk of PSD, independently of conventional risk factors.

Long-Term and Short-Term Prognostic Value of Circulating Soluble Suppression of Tumorigenicity-2 Concentration in Chronic Heart Failure: A Systematic Review and Meta-Analysis.

INTRODUCTION: Soluble suppression of tumorigenicity-2 (sST2) has been considered as a prognostic factor of cardiovascular disease. However, the prognostic value of sST2 concentration in chronic heart failure remains to be summarized. METHODS: We searched PubMed, Embase, and Web of Science for eligible studies up to January 1, 2020. Data extracted from articles and provided by authors were used in agreement with the PRISMA statement. The endpoints were all-cause mortality (ACM), cardiovascular mortality (CVM)/heart failure-related hospitalization (HFH), and all-cause mortality (ACM)/heart failure-related readmission (HFR). RESULTS: A total of 11 studies with 5,121 participants were included in this analysis. Higher concentration of sST2 predicted the incidence of long-term ACM (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02-1.04), long-term ACM/HFR (HR: 1.42, CI: 1.27-1.59), and long-term CVM/HFH (HR: 2.25, CI: 1.82-2.79), regardless of short-term ACM/HFR (HR: 2.31, CI: 0.71-7.49). CONCLUSION: Higher sST2 concentration at baseline is associated with increasing risk of long-term ACM, ACM/HFR, and CVM/HFH and can be a tool for the prognosis of chronic heart failure.

Increased ratio of sST2/LVMI predicted cardiovascular mortality and heart failure rehospitalization in heart failure with reduced ejection fraction patients: a prospective cohort study.

BACKGROUND: Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction. METHODS: This was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model. RESULTS: Forty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan-Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (< 0.24) (log-rank, P = 0.022). The fully adjusted multivariable Cox regression analysis showed that the sST2/LVMI ratio was positively associated with the composite outcome in patients with heart failure with reduced ejection fraction after adjusting for confounders (hazard ratio 1.64, 95% confidence interval 1.06 to 2.54). By subgroup analysis, a stronger association was found with age between 40 and 55 years, systolic blood pressure < 115 or ≥ 129 mmHg, diastolic blood pressure < 74 mmHg, hematocrit < 44.5%, and interventricular septum thickness ≥ 8.5 mm. CONCLUSION: In patients with heart failure with reduced ejection fraction, the relationship between the sST2/LVMI ratio and the composite outcome was linear. A higher baseline ratio of sST2/LVMI was associated with an increased risk of cardiovascular mortality and heart failure rehospitalization in the short-term follow-up.

[Clinical significance of combined sST2 and NT-proBNP detection for the short-term prognosis of acute organophosphorus pesticide poisoning].

Objective: To explore the value of soluble growth stimulation expression gene 2 protein (soluble suppression of tumorigenicity 2; sST2) and N terminal B type brain natriuretic peptide (N-terminal probrainnatriuretic peptide, NT-proBNP) in evaluating the short-term prognosis of acute organophosphorus pesticide poisoning. Methods: select 228 patients with acute organophosphorus pesticide poisoning in our hospital from October 2017 to March 2020. According to the grade of poisoning degree, it was divided into 82 cases in mild and moderate group and 146 cases in severe group. hs-cTnI、CK-MB、sST2、NT-proBNP、APACHE Ⅱ score and cholinesterase activity were detected 4 h、12 h、24 h after admission. ROC curve was used to evaluate sST2 and NT-proBNP to predict the prognosis of AOPP. Results: 4 hours after admission, there was no significant difference in the scores of hs-cTnI, APACHE Ⅱ, cholinesterase and CK-MB between the Severe Group and the mild and moderate Group (P<0.05) . At 12 and 24 hours after admission, the scores of hs-cTnI, CK-MB and APACHE Ⅱ in severe group were higher than those in mild and moderate group, and the changes of Cholinesterase were more significant than those in 12 hours after Admission (P<0.05) . 4 hours after admission, SST2 and NT-proBNP levels were significantly higher in severe group than those in mild and moderate Group (P<0.05) . The level of SST2 and NT-proBNP in the severe group was significantly higher than that in the mild and moderate group 12 and 24 hours after Admission (P<0.01) , and the level of SST2 and NT-proBNP was significantly higher than that in the mild group 12 hours after Admission (P<0.05) . Correlation analysis showed that 24 hours after admission, sST2, NT-proBNP were positively correlated with APACHE-Ⅱ scores (R=0.634, 0.723, P<0.01) . The area under sST2 combined with NT-proBNP was 0.891, higher than that under sST2 and NT-proBNP at 12 h after admission. The 24 h APACHE Ⅱ score after admission area under the curve was 0.838. Conclusion: sST2 and NT-proBNP combined detection can early predict the occurrence of recent complications in AOPP patients.

IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection.

BACKGROUND: Mechanisms influencing severity of acute lower respiratory infection (ALRI) in children are not established. We aimed to assess the role of inflammatory markers and respiratory viruses in ALRI severity. METHODS: Concentrations of interleukin(IL)-33, soluble suppression of tumorigenicity (sST)2, IL-1ß, tumor necrosis factor α, IL-4, IL-6 and IL- 8 and types of respiratory viruses were evaluated in children at the first and fifth days after hospital admission. Disease severity was defined as need for mechanical ventilation. RESULTS: Seventy-nine children <5 years-old were included; 33(41.8%) received mechanical ventilation. No associations between virus type, viral load or co-detections and severity of disease were observed. Detection of IL-33 and sST2 in nasopharyngeal aspirates (NPA) on admission were associated with higher risk for mechanical ventilation (RR = 2.89 and RR = 4.57, respectively). IL-6 and IL-8 concentrations were higher on Day 5 in mechanically ventilated children. IL-6 NPA concentrations decreased from Day 1 to Day 5 in children who did not receive mechanical ventilation. Increase in sST2 NPA concentrations from Day 1 to Day 5 was associated with longer hospital length of stay (p < 0.01). CONCLUSIONS: An exacerbated local activation of the IL-33/ST2 axis and persistently high sST2 concentrations over time were associated with severity of viral ALRI in children.

Superior prognostic value of soluble suppression of tumorigenicity 2 for the short-term mortality of maintenance hemodialysis patients compared with NT-proBNP: a prospective cohort study.

Background: Both soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are promising biomarkers associated with the adverse clinical outcomes of dialysis patients. Our research aims at exploring and comparing the roles of sST2 and NT-proBNP in predicting the short-term and long-term mortality of maintenance hemodialysis (MHD) patients.Methods: A prospective cohort study was performed. Patients undergoing hemodialysis in July 2014 were enrolled from the Blood Purification Center of Ruijin Hospital. MHD patients were followed up for 3 years. The primary outcome was all-cause mortality at the 1-year and 3-year follow-up, while the secondary outcome was cardiovascular mortality. Serum sST2 level was detected by quantified ELISA kits. Clinical data were analyzed by SPSS 23.0 version.Results: 205 patients were recruited. The median sST2 level was 15.99 (11.60, 20.49) ng/ml. After 3 years of follow-up, both all-cause and cardiovascular mortality in 1 year and all-cause and cardiovascular mortality in 3 years increased significantly with serum sST2. For short-term mortality, no significant difference was observed in patients with increasing NT-proBNP levels. Cox regression analysis indicated that only sST2 was independent in predicting the risk of short-term outcomes. For long-term mortality, both sST2 and NT-proBNP were independent risk factors, while a higher hazard ratio was observed for NT-proBNP.Conclusions: Serum sST2 is a novel biomarker associated with adverse clinical outcomes in MHD patients. It was significant for both all-cause and cardiovascular mortality in MHD patients and may provide better prognostic value in short-term prognosis than the classic biomarker NT-proBNP.

[Predictive value of early detection of hs-cTnI and sST2 for secondary cardiac damage in severe acute organophosphorus pesticide poisoning].

Objective: To investigate the value of high-sensitivity cardiac troponin I (hs-cTnI) and soluble suppression of tumorigenicity 2 (sST2) in predicting cardiac complications of severe acute organophosphorus pesticide poisoning (SAOPP) . Methods: All 274 SAOPP patients from September 2014 to February 2019 were selected. According to the results of hs-cTnI detection, the patients were divided into non-elevated troponin group (78 cases) and troponin elevation group (196 cases) at 1 hour after admission. 3 days after admission, there were 109 cases of complication and 165 cases of non-complication according to the presence or absence of cardiac complications. The changes of hs-cTnI, sST2, N-terminal B-type brain natriuretic peptide (NT proBNP) , acute physiology and chronic health (APACHE-Ⅱ) , cholinesterase activity, left ventricular ejection fraction (LVEF) , short axis shortening rate (FS) were observed and analyzed. The predictive value of hs-cTnI and sST2 were evaluated by receiver operating characteristic curve (ROC) analysis. Results: The sST2 level in patients with troponin elevation group was significantly higher than that in non-elevated troponin group (P<0.05) . Compared with the non-complication and non-elevated troponin group, the patients with non-complication and troponin elevation group had elevated hs-cTnI, sST2 and decreased cholinesterase (P<0.05) . Compared with other groups, the hs-cTnI, sST2, NT-proBNP, and APACHE-Ⅱ scores in the complication and troponin elevation group were significantly increased, and cholinesterase was significantly reduced (P<0.05) . In the non-complication group, LVEF and FS were in the normal range, and there was no significant difference between the groups (P>0.05) . Compared with other groups, the LVEF and FS of patients with elevated troponin in the complications group were significantly decreased (P<0.05) . Correlation analysis showed that hs-cTnI and sST2 were positively correlated in patients with SAOPP complications (r=0.725, P<0.01) . hs-cTnI, sST2 and APACHE-Ⅱ scores were positively correlated in the complications group (r=0.846, 0.885, P<0.01) . ROC results showed that the areas under the curve for predicting SAOPP secondary heart damage of hs-cTnI (1 hour after admission) and sST2 (3 days after admission) were 0.945 and 0.833, respectively. Conclusion: hs-cTnI and sST2 may have important clinical value in the early diagnosis and prognosis evaluation of patients with SAOPP secondary cardiac damage.

Diagnosis of chronic heart failure by the soluble suppression of tumorigenicity 2 and N-terminal pro-brain natriuretic peptide.

OBJECTIVE: Our study was to explore the roles between serum soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) while evaluating ventricular function to properly diagnose chronic heart failure (CHF). METHODS: In total, 197 CHF patients were recruited and classified into ventricular function's II, III, and IV groups, and 106 healthy people into normal control group. To detect concentrations of Sst2 and NT-proBNP, ELISA and electro-chemiluminescence immuno assay were implemented. An automatic biochemical analyzer was used to determine the levels of the following: blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and uric acid (UA). A receiver operating characteristic (ROC) curve was adopted to detect the diagnostic value sST2 and NT-ProBNP in CHF and the logistic regression analysis involving the risk factors of CHF. RESULTS: Serum sST2 and NT-proBNP concentrations were increased significantly in the ventricular function's II, III, and IV groups in a manner dependent on concentration as opposed to the manner the normal control group occupied. The area under the curve (AUC) of sST2, found NT-proBNP and sST2+NT-proBNP to be 0.942 (95% CI: 0.917-0.966), 0.920 (95% CI: 0.891-0.948), and 0.968 (95% CI: 0.953-0.984), respectively. sST2, NT-proBNP, UA, and Cr were verified as important risk factors of CHF. CONCLUSION: Serum sST2 and NT-ProBNP could act as diagnostic indicators for CHF.

Metabolic Complications Precede Alloreactivity and Are Characterized by Changes in Suppression of Tumorigenicity 2 Signaling.

New-onset post-transplantation diabetes mellitus (PTDM) occurs commonly after allogeneic hematopoietic cell transplantation (HCT) and is associated with inferior survival. We hypothesize that PTDM and nonrelapse mortality (NRM) are related to IL-33/suppression of tumorigenicity 2 (ST2) signaling and that soluble ST2 (sST2) levels will predict PTDM diagnosis. sST2 was measured at engraftment and day +30 in 36 euglycemic HCT recipients followed prospectively for PTDM (cohort 1). Results were confirmed in a validation cohort of 26 patients without pre-existing diabetes analyzed retrospectively for PTDM (cohort 2). Twelve patients with established diabetes before HCT were analyzed in cohort 3. When compared with recipients without PTDM, patients developing PTDM (n = 24) from cohort 1 had elevated sST2 levels at engraftment (P = .02) and at day +30 (P < .01). Cohort 2 confirmed this finding at engraftment (P = .01). Cohort 3 patients with pretransplantation diabetes had higher sST2 at engraftment than patients maintaining euglycemia after HCT from cohort 2 (P = .03). Multivariate analysis of cohorts 1 and 2 showed high engraftment sST2 predicted increased PTDM and NRM risk, independent of conditioning and grades 3 to 4 acute graft-versus-host-disease. sST2 was elevated in PTDM, indicating a relationship between glucose homeostasis and the IL-33/ST2 axis after transplantation. Correction of metabolic complications may decrease sST2 and improve NRM.