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Objective: This study aimed to elucidate the prognostic significance of serum soluble thrombomodulin (sTM), lung ultrasound score (LUS), and lactate levels in patients with extrapulmonary acute respiratory distress syndrome (ARDS), with the goal of refining mortality risk prediction in this cohort. Methods: In a prospective cohort of 95 patients with extrapulmonary ARDS admitted to the intensive care unit, we investigated the primary endpoint of 28-day mortality. Utilizing Lasso-Cox regression analysis, we identified independent prognostic factors for mortality. A predictive nomogram was developed incorporating these factors, and its performance was validated through several statistical measures, including the consistency index, calibration plot, internal validation curve, decision curve analysis, interventions avoided analysis, receiver operating characteristic curve analysis, and Kaplan-Meier survival analysis. We further conducted a subgroup analysis to examine the impact of prone positioning on patient outcomes. Results: The study identified baseline serum sTM, LUS, and lactate levels as independent predictors of 28-day mortality in extrapulmonary ARDS patients. The predictive nomogram demonstrated superior prognostic accuracy compared to the use of sTM, LUS, or lactate levels alone, and outperformed traditional prognostic tools such as the Acute Physiology and Chronic Health Evaluation II score and the partial pressure of arterial oxygen to fractional inspired oxygen ratio. The subgroup analysis did not show a significant impact of prone positioning on the predictive value of the identified biomarkers. Conclusion: Our study results support the development and validation of a novel prognostic nomogram that integrates key clinical biomarkers and ultrasound imaging scores to predict mortality in patients with extrapulmonary ARDS. While our research is preliminary, further studies and validation are required. [ABSTRACT FROM AUTHOR]

Background/Objectives: Levels of circulating soluble thrombomodulin (sTM), an anticoagulant factor, are associated with the severity and progression of arteriosclerotic diseases. However, the role of elevated sTM levels remains to be clarified in patients on dialysis. As the calcification propensity time T50 is a novel marker of arterial calcification, we aimed to determine the association between sTM and T50 in patients on hemodialysis (HD). Methods: This cross-sectional study included 49 adult patients on maintenance HD. Correlation analysis was performed to test the association between T50 and patient characteristics. Linear regression was used to evaluate the association between T50 and sTM. Results: Partial correlation analysis showed a strong association between T50 and glycated albumin, phosphorous, and sTM levels (partial correlation coefficient: r [partial] = −0.359, p = 0.023; r [partial] = −0.579, p < 0.001; and r [partial] = 0.346, p = 0.029, respectively). Multivariate linear regression analysis revealed that only sTM level was significantly and positively associated with T50 (β = 0.288; t = 2.27; p = 0.029; 95% confidence interval, 0.082–1.403). Conclusions: sTM is independently and positively associated with the propensity time for calcification, suggesting that sTM could be a good marker of arterial calcification progression in patients on HD. [ABSTRACT FROM AUTHOR]

Background: Sepsis, a complex condition characterized by dysregulated immune response and organ dysfunction, is a leading cause of mortality in ICU patients. Current diagnostic and prognostic approaches primarily rely on non-specific biomarkers and illness severity scores, despite early endothelial activation being a key feature of sepsis. This study aimed to evaluate the levels of soluble thrombomodulin and soluble endoglin in seriously ill surgical septic patients and explore their association with organ dysfunction and disease severity. Methodology: A case control study was conducted from March 2022 to November 2022, involving seriously ill septic surgical patients. Baseline clinical and laboratory data were collected within 24 h of admission to the Surgical Intensive Care Unit. This included information such as age, sex, hemodynamic parameters, blood chemistry, SOFA score, qSOFA score, and APACHE-II score. A proforma was filled out to record these details. The outcome of each patient was noted at the time of discharge. Results: The study found significantly elevated levels of soluble thrombomodulin and soluble endoglin in seriously ill surgical septic patients. The RTqPCR analysis revealed a positive correlation between soluble thrombomodulin and soluble endoglin levels with the qSOFA score, as well as, there was a positive association between RTqPCR soluble thrombomodulin and the SOFA score. These findings indicate a correlation between these biomarkers and organ dysfunction and disease severity. Conclusion: The study concludes that elevated levels of soluble thrombomodulin and soluble endoglin can serve as endothelial biomarkers for early diagnosis and prognostication in seriously ill surgical septic patients. [ABSTRACT FROM AUTHOR]

Objective: to evaluate laboratory parameters of hemostasis, lipid metabolism and endothelial dysfunction and their relationship in men aged 18–50 years with atherothrombotic (ATS), lacunar (LS) and cardioembolic (CES) stroke. Material and methods. The study included 89 men with ATS (n=36), LS (n=34) and CES (n=19). Neuroimaging, ultrasound and laboratory blood serum analyses were performed in all patients. Results. The mean age of the patients was 42.6±5.3 years. The main risk factors for ATS, LS and CES included: arterial hypertension (75; 97.8 and 73.7% of cases, respectively), dyslipidemia (60; 41.3 and 42.1%), tobacco smoking (71.7; 67.4 and 52.6%), regular alcohol consumption (35; 19.6 and 36.8%), obesity (23.3; 8.7 and 15.8 %), diabetes mellitus (8.3; 6.5 and 10.5 %). Lower tissue plasminogen activator levels were found in patients with CES (2.66±1.77 ng/ml) compared to patients with LS (3.38±3.0 ng/ml) and ATS (3.48±2.45 ng/ml). Plasminogen activator inhibitor-1 levels were significantly increased in all stroke subtypes. The mean level of soluble thrombomodulin was highest in patients with LS (100.86±58.22 pg/ml) compared to patients with ATS (96.37±85.71 pg/ml) and CES (75.28±39.36 pg/ml). The level of asymmetric dimethylarginine was higher in patients with ATS (1.46±0.42 μmol/l) and in patients with LS (0.79±0.37 μmol/l), and in patients with CES (0.4±0.13 μmol/l) it was within the reference values. Conclusion. We noted differences in laboratory parameters of the hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different stroke subtypes (ATS, LS and CES), as well as clinical and laboratory correlations.

Aim: To evaluate coagulofibrinolytic abnormalities and the effects of ART-123 (recombinant human thrombomodulin alpha) in a porcine model of cardiac arrest and prolonged cardiopulmonary resuscitation (CA/CPR). Methods: Fifteen pigs (n = 5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR, while 2 pigs underwent sham arrest. CA/CPR animals were randomized to receive saline or 1 mg/kg ART-123 pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Arterial and venous blood samples were drawn at multiple time points for blood gas analysis and measurement of plasma and whole blood markers of coagulation and fibrinolysis. Results: In saline-treated CA/CPR, but not sham animals, robust and persistent activation of coagulation and fibrinolysis was observed throughout resuscitation. After 50 minutes of CPR, plasma tests and thromboelastography indicated a mix of hypercoagulability and consumptive coagulopathy. ART-123 had a robust anticoagulant effect, reducing both thrombin-antithrombin (TAT) complexes and d-dimer (p

Abstract Background To investigate the changes and clinical significance of vascular endothelial injury markers in type 2 diabetes mellitus (T2DM) complicated with pulmonary embolism (PE). Methods This prospective study enrolled patients with T2DM hospitalized in one hospital from January 2021 to June 2022. Soluble thrombomodulin (sTM) (ELISA), von Willebrand factor (vWF) (ELISA), and circulating endothelial cells (CECs) (flow cytometry) were measured. PE was diagnosed by computed tomography pulmonary angiography (CTPA). Results Thirty participants were enrolled in each group. The plasma levels of sTM (151.22 ± 120.57 vs. 532.93 ± 243.82 vs. 1016.51 ± 218.00 pg/mL, P 676.68 pg/mL for the diagnosis of T2DM + PE achieved an AUC of 0.973, while vWF > 13.75 ng/mL achieved an AUC of 0.954. The combination of sTM and vWF above their cutoff points achieved an AUC of 0.993, with 100% sensitivity and 96.7% specificity. Conclusions Patients with T2DM show endothelial injury and dysfunction, which were worse in patients with T2DM and PE. High sTM and vWF levels have certain clinical predictive values for screening T2DM accompanied by PE.

Background: To investigate the changes and clinical significance of vascular endothelial injury markers in type 2 diabetes mellitus (T2DM) complicated with pulmonary embolism (PE). Methods: This prospective study enrolled patients with T2DM hospitalized in one hospital from January 2021 to June 2022. Soluble thrombomodulin (sTM) (ELISA), von Willebrand factor (vWF) (ELISA), and circulating endothelial cells (CECs) (flow cytometry) were measured. PE was diagnosed by computed tomography pulmonary angiography (CTPA). Results: Thirty participants were enrolled in each group. The plasma levels of sTM (151.22 ± 120.57 vs. 532.93 ± 243.82 vs. 1016.51 ± 218.00 pg/mL, P < 0.001) and vWF (9.63 ± 2.73 vs. 11.50 ± 2.17 vs. 18.02 ± 3.40 ng/mL, P < 0.001) and the percentage of CECs (0.17 ± 0.46 vs. 0.30 ± 0.08 vs. 0.56 ± 0.18%, P < 0.001) gradually increased from the control group to the T2DM group to the T2DM + PE group. sTM (OR = 1.002, 95%CI: 1.002–1.025, P = 0.022) and vWF (OR = 1.168, 95%CI: 1.168–2.916, P = 0.009) were associated with T2DM + PE. sTM > 676.68 pg/mL for the diagnosis of T2DM + PE achieved an AUC of 0.973, while vWF > 13.75 ng/mL achieved an AUC of 0.954. The combination of sTM and vWF above their cutoff points achieved an AUC of 0.993, with 100% sensitivity and 96.7% specificity. Conclusions: Patients with T2DM show endothelial injury and dysfunction, which were worse in patients with T2DM and PE. High sTM and vWF levels have certain clinical predictive values for screening T2DM accompanied by PE. [ABSTRACT FROM AUTHOR]

Objective: To explore the expression of serum lactate (Lac), D-dimer (D-D), soluble thrombomodulin (s TM) and endothelium-specific molecule-1 (ESM-1) in patients with sepsis-associated acute respiratory distress syndrome (ARDS) and to investigate their clinical significance. Methods: 375 patients with sepsis related ARDS who were treated in the intensive medicine department of the Affiliated Hospital of Xuzhou Medical University from January 2020 to January 2022 were selected, they were divided into mild group (n=96), moderate group (n=152) and severe group (n=127) according to the difference of oxygenation index (OI) at admission. The levels of serum lac, D-D, s TM and ESM-1 in each group were compared. The correlation between serum lac, D-D, s TM and ESM-1 and OI was analyzed by Spearman correlation coefficient. According to the prognosis within 28 d, the patients were divided into death group (n=137) and survival group (n=238). The clinical data were collected. The prognostic factors of sepsis related ARDS patients were analyzed by multivariate logistic regression. The predictive value of serum lac, D-D, s TM and ESM-1 on the poor prognosis of patients with sepsis related ARDS was analyzed by receiver operating characteristic (ROC) curve. Results: The levels of serum lac, D-D, s TM and ESM-1 in mild group, moderate group and severe group increased successively (P＜0.05). Spearman correlation analysis showed that the levels of serum lac, D-D, s TM and ESM-1 in patients with sepsis related ARDS were negatively correlated with OI (P＜0.05). The age of death group was older than that of survival group, the proportion of septic shock, ICU stay time ≥10 d, mechanical ventilation time ≥3 d, SOFA score, serum lac, D-D, s TM and ESM-1 were higher than those of survival group, and OI was lower than that of survival group (P＜0.05). Multivariate logistic regression analysis showed that septic shock, SOFA score ≥13 and high levels of serum lac, D-D, STM and ESM-1 were the risk factors of poor prognosis in patients with sepsis related ARDS, while high OI was the protective factor of poor prognosis (P＜0.05). The results of ROC curve analysis showed that the AUC of the combined detection of serum lac, D-D, STM and ESM-1 in predicting the poor prognosis of patients with sepsis related ARDS was 0.907, which was significantly higher than that of 0.785, 0.747, 0.796 and 0.789. Conclusion: Serum Lac, D-D, s TM and ESM-1 levels are closely associated with the severity of disease and poor prognosis in SAARDS patients and can be used as predictors of poor prognosis in sepsis-associated ARDS patients. [ABSTRACT FROM AUTHOR]

Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. Conclusions: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Thrombomodulin (TM) is a type-I transmembrane protein that is mainly expressed on endothelial cells and plays important roles in many biological processes. Circulating TM of different forms are also present in biofluids, such as blood and urine. Soluble TM (sTM), comprised of several domains of TM, is the major circulating TM which is generated by either enzymatic or chemical cleavage of the intact protein under different conditions. Under normal conditions, sTM is present in low concentrations (

Background: Accurate diagnosis and classification of ovarian hyperstimulation syndrome (OHSS) is important for its management. We employed a new high-sensitivity chemiluminescence immunoassay to detect the thrombin-antithrombin complex (TAT), plasmin alpha2-plasmin inhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (TPAI-C), and evaluated their diagnostic and classification performance for OHSS.Methods: A total of 106 women were enrolled, including 51 patients with OHSS (25 mild or moderate OHSS, 26 severe OHSS), and 55 without OHSS (control group). TAT, PIC, sTM, and TPAI-C levels were measured using the Sysmex HISCL5000 automated analyzer.Results: Compared to the control group, TAT, PIC, and TPAI-C levels were significantly higher (P < 0.001, P < 0.001, P < 0.001, respectively), whereas the sTM level was significantly lower (P < 0.001) in the patients with OHSS. The receiver operating characteristic was used to evaluate the diagnostic efficiency. For the diagnosis of OHSS, the area under the curves (AUCs) for TAT, PIC, sTM, and TPAI-C were 0.991, 0.973, 0.809, and 0.722, respectively. In particular, the sensitivity, specificity, positive predictive value, and negative predictive value for TAT and PIC were all above 90%. For the differential diagnosis of mild–moderate and severe OHSS, the AUCs for TAT, PIC, and TPAI-C were 0.736, 0.735, and 0.818, respectively. The cutoff values of TAT, PIC, and TPAI-C for the differential diagnosis of mild–moderate and severe OHSS were 11.5 ng/mL, 2.4 μg/mL, and 5.8 ng/mL, respectively. Based on these cutoff values, eight cases of mild–moderate OHSS exceeded the cutoff values, two of which developed to severe OHSS in the following days. However, of the remaining 17 cases of mild–moderate OHSS patients with negative biomarkers, none subsequently developed severe OHSS.Conclusions: TAT, PIC, sTM, and TPAI-C can be used as sensitive biomarkers in the diagnosis of OHSS. Meanwhile, TAT, PIC, and TPAI-C also displayed remarkable potential in the classification of OHSS. In addition, the levels of TAT, PIC, and TPAI-C above the cutoff values in patients with mild–moderate OHSS might predict a high risk of developing severe OHSS.

BackgroundThe coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19.MethodsSARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions.ResultsEASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p

Background: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19. Methods: SARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions. Results: EASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha. Conclusion: EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance. [ABSTRACT FROM AUTHOR]

Abstract Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p 12 h from ICU admission (AKI>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p

Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. Conclusions: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention.

To study the expression and clinical significance of serum soluble thrombomodulin (STM), renal injury molecule-1 (KIM-1) and soluble CD134（sCD134）in patients with lupus nephritis (LN). 100 LN patients in our hospital from December 2016 to December 2018 were selected. According to the systemic lupus erythematosus disease activity index (SLEDAI), the patients were divided into active group (SLEDAI≥ 10 points) 56 cases, inactive group (SLEDAI<10 points) 44 cases. Another 50 healthy volunteers who received physical examination in our hospital in the same period were taken as the control group. The renal function indexes, serum levels of STM, KIM-1 and sCD134 were compared, and the correlation between serum levels of STM, KIM-1 and sCD134 and renal function indexes was analyzed. The energy efficiency of serum STM, KIM-1 and scd134 levels in LN diagnosis was analyzed by ROC curve. The levels of Blood urea nitrogen (BUN), creatinine (SCR) and erythrocyte sedimentation rate (ESR) in the active group were higher than those in the inactive group and the control group (P < 0.05). The serum levels of STM, KIM-1 and sCD134 in the active group were higher than those in the inactive group and the control group, and the serum levels of STM, KIM-1 and scd134 in the inactive group were higher than those in the control group (P < 0.05). The Pearson correlation analysis showed that the serum levels of STM, KIM-1 and sCD134 were positively correlated with the levels of BUN, SCR and ESR (P < 0.05). ROC curve analysis shows that the best critical value of STM was 24.46 ng/mL, the area under the curve was 0.823; the best critical value of KIM-1 was 8.27 滋g/L, the area under the curve was 0.823. The best critical value of sCD134 was 15.25 ng/mL, and the area under the curve was 0.823. The serum levels of STM, KIM-1 and sCD134 in LN patients are closely related to the disease activity, which has a good diagnostic effect on LN. The combined detection of serum levels of STM, KIM-1 and sCD134 may provide a reference for the diagnosis and disease activity of LN. [ABSTRACT FROM AUTHOR]

Background: Takotsubo cardiomyopathy (TTC) is a syndrome of acute non-coronary heart failure with similar symptoms and electrocardiograms to acute anterior ST-elevation myocardial infarction (STEMI). Little is known about the pathophysiology of TTC. We assessed admission plasma concentrations of biomarkers reflecting neuroendocrine response (copeptin, mid-regional-pro-adrenomedullin, pro-atrial-natriuretic-peptide, soluble thrombomodulin (sTM), syndecan-1) and inflammation (suppression-of-tumorigenicity 2 (ST2), high-sensitive C-reactive-protein) in TTC patients and compared to patients with acute anterior STEMI. Materials and methods: Twenty TTC patients were matched with 40 STEMI patients by age, gender and left ventricular ejection fraction. Blood was sampled upon hospital admission immediately before acute coronary angiography. Results: The groups had similar comorbidities. TTC patients had higher plasma concentrations of sTM: 7.94 (5.89;9.61) vs. 6.42 (5.50;7.82)ng/ml, p = 0.04 and ST2 (53 (32;157) vs. 45 (31;55)ng/ml, p = 0.008) and higher heart rate: 101 ( ± 33) vs. 76( ± 14)bpm, p = 0.0001, but lower concentrations of copeptin (10.4 (7.6;39) vs. 92.3 (13;197)pmol/l, p < 0.05) and troponin T (348 (98;759) vs. 1190 (261;4105)ng/l, p = 0.04). Conclusion: TTC patients had higher plasma concentrations of sTM and ST2, higher heart rate and lower copeptin and troponin T concentrations compared to acute anterior STEMI patients. This study contributes to the hypothesis that TTC patients have endothelial cell damage and are hemodynamically more stable than patients with acute anterior STEMI on admission. [ABSTRACT FROM AUTHOR]

Abstract Background Endothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomarkers of coagulation and inflammation and to determine a significant predictor of AKI in patients with sepsis. Methods We conducted a single-center, retrospective, observational study on patients with sepsis fulfilling the Third International Consensus Definitions for Sepsis and Septic Shock criteria admitted to an adult intensive care unit (ICU) at a university hospital from June 2011 to December 2016. Levels of 13 biomarkers were measured on ICU admission, including markers of endothelial injury (soluble thrombomodulin [sTM], E-selectin, protein C, and plasminogen activator inhibitor-1 [PAI-1]) and markers of coagulation derangement (platelet count, fibrin degradation product [FDP], prothrombin time [PT], fibrinogen, α2-plasminogen inhibitor [α2-PI], antithrombin III [AT III], plasminogen, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex). All patients with sepsis were reviewed, and the development of AKI was evaluated. Multivariate logistic regression analysis was performed to identify significant independent predictive factors for AKI. Results Of the 514 patients admitted with sepsis, 351 (68.3%) developed AKI. Compared with the non-AKI group, all the endothelial biomarkers were significantly different in the AKI group (sTM [23.6 vs. 15.6 U/ml, P

Introduction: It is known that atrial fibrillation can lead to a prothrombotic or hypercoagulable state with abnormal hemostasis, with the development of thromboembolic complications, fibrinolysis and endothelial dysfunction. Research in recent years has demonstrated increased interest in the development of new laboratory methods for assessing the risk of TEC. One of the biomarkers that exhibits important anti-inflammatory, anticoagulant and antifibrinolytic properties and is involved in maintaining vascular homeostasis is soluble thrombomodulin (sTM).Objective: to study the content of soluble thrombomodulin in the blood serum in patients with non-valvular atrial fibrillation receiving anticoagulant therapy and having a history of thrombotic complications and patients with atrial fibrillation without thrombotic complications.Materials and Methods: the study included 60 patients over 18 years of age with a diagnosis of atrial fibrillation, verified based on clinical recommendations, receiving anticoagulant therapy. Of these, 21 patients developed thrombotic complications during adequate anticoagulant therapy, and 22 healthy volunteers were included in the study. All patients gave their written informed consent for inclusion in the study. The study of soluble thrombomodulin (ng/ml) was carried out by enzyme immunoassay using the equipment of the Center for Collective Use "Medical Genomics" of the Tomsk National Research Medical Center.Results: All the examined patients were divided into 2 groups: a group of patients with atrial fibrillation without thrombotic complications and a group of patients with atrial fibrillation with thrombotic complications. The content of soluble thrombomodulin in the blood serum of patients with thrombotic complications was reduced compared with both the group of patients without thrombotic complications and the group of healthy volunteers. Analysis of the level of sTM in men and women in groups of patients and in healthy volunteers showed that the lowest values ​​of this biomarker in the blood serum were observed in women from the group of patients with atrial fibrillation with TO Me- 1.91 (1.80; 2.53) compared with women from the group of patients without thrombotic complications Me-2.65 (1.99;2.92) and with healthy women Me-2.60 (1.83;3.07), p ≤ 0.05. Also, there is a reduced content of soluble thrombomodulin in men with thrombosis compared to healthy men Me-2.15 (1.94; 2.50) and 3.03 (2.55; 3.31), respectively. A comparative analysis of the levels of soluble thrombomodulin in women and men in all groups of patients with atrial fibrillation and in healthy volunteers did not reveal statistically significant differences.Conclusion: in the studied group of patients with non-valvular atrial fibrillation receiving anticoagulant therapy, a decrease in soluble thrombomodulin was noted in the subgroup of patients with thrombotic complications.

The aim of this study was to investigate if thrombocytopenic haematology patients show signs of endothelial damage when transfused with platelets and if that damage correlates with platelet increment measured with corrected count increment (CCI). Endothelial damage secondary to radiation or chemotherapy may lead to consumption of transfused platelets but research in this field is scarce. Patients were divided into four groups: Group 1: Acute leukaemia; Group 2: Autologous stem cell transplantation (SCT); Group 3: Allogenic SCT; and Group 4: patients receiving platelets prior to interventions. Blood was sampled before (baseline) and immediately after (0 h) transfusion and then at 1, 4, 8, 16 and 24 h after transfusion. The biomarkers syndecan-1, soluble thrombomodulin (sTM) and vascular endothelial growth factor (VEGF) were analysed. The plasma concentration differences between baseline and later sampling times were referred to as delta (Δ). Fifty-four platelet transfusion events were studied. All biomarkers were within the normal ranges both before and after the transfusions. The Δsyndecan-1 increased at 0 h (p = .02), but there was no significant correlation between Δsyndecan-1 and CCI. There was no change in any of the other biomarkers after transfusion compared to before. There were no differences between the groups and no correlations were found between CCI and C-reactive protein, Δsyndecan-1, ΔsTM or ΔVEGF. There were no signs of endothelial damage before or after platelet transfusions. A transient significant change in syndecan-1 immediately after platelet transfusion did not influence platelet count or platelet CCI. [ABSTRACT FROM AUTHOR]

Protein C (PC) pathway homeostasis is implicated in heat stress (HS). This study determines whether cooling could improve the PC pathway in HS. Fifty‐six anesthetized rats were warmed to achieve HS (rectal temperature [Tr] 42°C). These rats were divided into seven groups: (a) control group:sacrifice immediately 15 min after HS; (b) HS+I:sacrifice immediately after 15 min ice‐water treatment or (c) 3 hr after HS; (d) HS+C:sacrifice immediately after 15‐min cold‐water treatment or (e) 3 hr after HS; (f) HS: sacrifice immediately 15 min after HS or (g) 3 hr after HS. Plasma PC, activated protein C (APC), and soluble thrombomodulin (sTM) levels were tested at both time points. After cooling, Tr in the HS+I and HS+C groups significantly decreased, when compared with the HS group, and Tr was significantly lower in the HS+I group than in the HS+C group (p < 0.05). Furthermore, sTM levels were highest in the HS group among the groups at both time points. Plasma PC and APC levels increased after HS. In the HS+I and HS+C groups, plasma APC levels and the APC/PC ratio significantly increased at both time points. The proportions were significantly higher in the HS+I group than in the HS+C group, and there was no significant increase in APC/PC ratio in the HS group. Cooling exerts an anticoagulant effect following HS by increasing APC levels. Ice‐water blanket therapy is more effective than cold‐water blanket therapy in increasing APC levels. [ABSTRACT FROM AUTHOR]

Interventions targeting the serum eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio could be useful for the prevention of coronary artery disease (CAD). Few data exist regarding the effects of administration of EPA on the serum levels of soluble thrombomodulin (sTM) as a marker of endothelial damage, or on the relationship between the sTM and EPA/AA ratio in patients with CAD receiving statin treatment. We assigned stable CAD patients already receiving statin therapy to an EPA group (1800 mg/day: n = 50) or control group (n = 50). A significant increase of the sTM level was observed in the EPA group as compared to that in the control group 0.40 (0.10/0.70) FU/mL vs. 0.20 (0/0.40) FU/mL, p = 0.004 at the 6-month follow-up examination. Multivariate regression analysis after adjustments for coronary risk factors and changes of the serum lipid levels identified an increased EPA/AA ratio as an independent predictor of increased serum sTM level (β = 0.244, p = 0.02). The results suggest that an increased sTM level caused by additional administration of EPA to statin might be associated with an increased EPA/AA ratio. The increase of the serum sTM after administration of EPA might reflect an increase of the TM expression on the endothelial surface rather than endothelial damage in CAD patients under statin treatment.Clinical Trial Registration Information UMIN (http://www.umin.ac.jp/), Study ID: UMIN000010452. [ABSTRACT FROM AUTHOR]

Abstract Background Accurate and early diagnosis is important in the management of disseminated intravascular coagulation (DIC). We employed new automation technology to detect plasma biomarkers, including thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC), and evaluated their diagnostic performance and prognostic value for DIC in Chinese population. Methods This prospective observational study included 444 patients with suspected DIC and 137 healthy people. The molecular markers were measured by qualitative chemiluminescence enzyme immunoassay performed on HISCL automated analyzers. All patients with suspected DIC were followed for 7 days to screen for the development of overt-DIC and 28 days for mortality. Results According to the International Society of Thrombosis and Haemostasis (ISTH) scoring system, 157 patients were diagnosed as overt-DIC and 36 were diagnosed as pre-DIC. All four biomarkers were significantly higher in DIC patients than in non-overt DIC patients; TAT, tPAIC, and sTM were significantly higher in pre-DIC patients than in non-overt DIC patients. Four molecular markers behaved differently among various underlying diseases. TAT, tPAIC, and sTM were also good predictors of 28-day mortality, high levels were associated with poor outcomes. Conclusions TAT, PIC, tPAIC, and sTM demonstrated good diagnostic performance and prognostic value in DIC patients with different underlying diseases. Besides, TAT, tPAIC and sTM have certain implications in pre-DIC stage. Combination of four makers was demonstrated better behavior than single one. Highlights • TAT, tPAIC and sTM have certain implication in pre-DIC stage. • TAT, PIC, tPAIC and sTM demonstrated good diagnostic performance and prognostic value in DIC. • Combination of four makers demonstrated better behavior than single one. [ABSTRACT FROM AUTHOR]

One common complication after joint arthroplasty is venous thromboembolism (VTE). Therefore, it is essential to measure the changes in coagulation and fibrinolysis in order to predict VTE among patients who underwent joint arthroplasty. This study aimed to identify potential useful biomarkers for prognosing to VTE. This was a prospective cohort study enrolling 83 patients who underwent joint arthroplasty. The levels of D-dimer, thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PIC), soluble thrombomodulin, and tissue plasminogen activator inhibitor complex were measured on day 0 (before surgery) and days 1, 3, and 6 after surgery. Ultrasound examination was used to diagnose VTE on preoperative day 0 and postoperative day 6. A total of 35 patients developed VTE after surgery. Patients with VTE exhibited significantly higher levels of D-dimer and TAT on postoperative days 3 and 6 (all P < .05). The area under curves (AUC) of receiver operating characteristic (ROC) were 0.65 and 0.68 and 0.68 and 0.74 for D-dimer and TAT levels on postoperative days 3 and 6, respectively. The level of TAT/PIC ratio on postoperative day 6 was significantly increased among patients with VTE compared to non-VTE patients (P < .0001). In addition, the AUC of ROC, cutoff level, sensitivity, specificity, positive-predictive value, and negative-predictive value of TAT/PIC ratio were 0.78, 4.03 ng/TU, 97.14%, 33.33%, 51.52%, and 94.12%, respectively. The high sensitivity and negative predictive value of TAT/PIC ratio make it a potential prognostic index for diagnosing VTE during the early phase of postoperative joint arthroplasty. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world and has a high risk of thromboembolism. The most effective approach, catheter ablation, requires evaluation by electrocardiography. The aim of our study was to investigate novel clinical markers that predict restoration of sinus rhythm (SR) after catheter ablation. Seventy-eight consecutive patients with AF underwent catheter ablation and were separated into 2 groups: restored SR and recurrent AF. The levels of 4 blood proteins (serum or plasma) and 3 mature microRNAs (miRNAs) and their primary miRNAs (pri-miRNAs) in serum were measured before and after ablation, and the associations between each parameter were analyzed statistically. Soluble thrombomodulin (s-TM) and plasminogen activator inhibitor-1 (PAI-1) levels increased above baseline after ablation in both the restored SR (s-TM 11.55 [2.92] vs 13.75 [3.38], P < .001; PAI-1 25.74 [15.25] vs 37.79 [19.56], P < .001) and recurrent AF (s-TM 10.28 [2.78] vs 11.67 [3.37], P < .001; PAI-1 26.16 [15.70] vs 40.74 [22.55], P < .001) groups. Levels of C-reactive protein and asymmetric dimethylarginine were not significantly changed. Pri-miR-126 levels significantly decreased after ablation in the recurrent AF group, but the other miRNAs and pri-miRNAs did not. The measurement of s-TM and pri-miR-126 in blood was a useful tool to reflect the condition of AF patients with catheter ablation. [ABSTRACT FROM AUTHOR]

Aim: To evaluate coagulofibrinolytic abnormalities and the effects of ART-123 (recombinant human thrombomodulin alpha) in a porcine model of cardiac arrest and prolonged cardiopulmonary resuscitation (CA/CPR)., Methods: Fifteen pigs ( n  = 5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR, while 2 pigs underwent sham arrest. CA/CPR animals were randomized to receive saline or 1 mg/kg ART-123 pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Arterial and venous blood samples were drawn at multiple time points for blood gas analysis and measurement of plasma and whole blood markers of coagulation and fibrinolysis., Results: In saline-treated CA/CPR, but not sham animals, robust and persistent activation of coagulation and fibrinolysis was observed throughout resuscitation. After 50 minutes of CPR, plasma tests and thromboelastography indicated a mix of hypercoagulability and consumptive coagulopathy. ART-123 had a robust anticoagulant effect, reducing both thrombin-antithrombin (TAT) complexes and d-dimer ( p  < 0.05 for each). The duration of anticoagulant effect varied depending on the timing of ART-123 administration. Similarly, ART-123 when given prior to cardiac arrest was found to have pro-fibrinolytic effects, increasing free tissue plasminogen activator (tPA, p  = 0.02) and decreasing free plasminogen activator inhibitor-1 (PAI-1, p  = 0.04)., Conclusion: A porcine model of prolonged CA/CPR reproduces many of the coagulofibrinolytic abnormalities observed in human cardiac arrest patients. ART-123 demonstrates a combination of anticoagulant and profibrinolytic effects, depending on the timing of its administration relative to cardiac arrest., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BZ and CFG received study drug (ART123) and research funding from Asahi Kasei Pharma (AKP) Corporation. AKP was not involved in experimental design, data analysis, or manuscript preparation. BMM, CCM, DL, NG, JAC, CHH, MHT, and RWN have no conflicts of interest to report., (© 2023 The Authors.)

This study explored the effects of probucol on atherosclerotic plaques and soluble thrombomodulin in patients with coronary heart disease (CHD). Five hundred and eighty-three patients with CHD who were admitted to Jining First People's Hospital from February 2013 to February 2014. A total of 300 of them received conventional treatment, and were assigned to the control group, while the remaining 283 patients were treated with probucol in addition to the conventional treatment, and were assigned to the observation group. A retrospective analysis was performed on the total cholesterol levels, atherosclerotic plaque sizes, and soluble thrombomodulin levels. Probucol was administered at a dose of 500 mg twice a day for a period of 16 weeks. The total cholesterol level decreased gradually over time during the treatment. After 8 weeks of treatment, the total cholesterol level in the observation group was lower than that in the control group (P<0.05). After 8 weeks of treatment, the atherosclerotic plaque area in the observation group decreased compared with that before treatment (P<0.05). After 8 and 16 weeks of treatment, the plaque area in the observation group was smaller than that in the control group (P<0.05). The soluble thrombomodulin level at any time-point after treatment was lower than that before treatment in both groups (P<0.05). At the same time-point, the level in the observation group was lower than that in the control group (P<0.05). The total cholesterol and soluble thrombomodulin levels were positively correlated with the atherosclerotic plaque area (r=0.841, P=0.001; r=0.725, P=0.008). When patients with CHD were treated with probucol in addition to the conventional treatment, a reduction of the atherosclerotic plaque area, as well as a decrease of both the total cholesterol and soluble thrombomodulin levels, was observed. Overall, patients with CHD experienced improved symptoms following treatment with probucol. [ABSTRACT FROM AUTHOR]

Background: Increased coagulation activity has been established in paroxysmal atrial fibrillation (PAF), but data on the anticoagulant system are scarce. Purpose: To examine the protein C anticoagulant pathway in the early hours of the disease. Materials and Methods: Fifty-one patients (26 men and 25 women; mean age 59.84 ± 1.60 years) and 52 controls (26 men and 26 women; mean age 59.50 ± 1.46 years) were selected for the study. Protein C antigen and its activity, total protein S, free protein S and its activity, soluble forms of endothelial protein C receptor (sEPCR), and thrombomodulin (sTM) were examined in the plasma. Results: The indicators were studied in patients between the 2nd and the 24th hour after the onset of arrhythmia. Levels of protein C were significantly elevated in patients compared to controls (111.40% ± 6.66% vs 94.83% ± 4.47%; P = .039). Protein C activity showed significant reduction in PAF (73.13% ± 5.80% vs 103.3% ± 3.80%; P < .001). Total protein S levels did not differ significantly (108.20% ± 4.07% vs 102.40% ± 3.65%; P = .30). Free protein S (76.81% ± 6.01% vs 122.10% ± 3.97%; P < .001) and its activity (71.39% ± 6.27% vs 119.50% ± 6.54%; P < .001) were reduced in patients. Higher levels of sEPCR (203.10 ± 10.33 vs 133.10 ± 7.37 ng/mL; P < .001) and sTM (6.50±0.40 vs 4.48±0.28 ng/mL; P < .001) were measured in PAF. Conclusion: Protein C activity is reduced still in the first hours (until the 24th hour) of PAF clinical manifestation, determining reduced activity of the anticoagulant pathway as a whole. The established low levels of free protein S and its activity as well as low sEPCR and sTM levels are a possible explanation of the changes in protein C activity. [ABSTRACT FROM AUTHOR]

Vascular endothelium is a target of cadmium (Cd) toxicity. Cd exposure has been reported to be associated with vascular disorders. In this study, we aimed to investigate the effects of Cd exposure on markers of endothelial function in human subjects chronically exposed to Cd. Based on blood Cd levels, seventy-five women were categorized into non-exposed, Cd-exposed and severely Cd-exposed groups. Nitrite, L-arginine, asymmetric dimethylarginine (ADMA), and soluble thrombomodulin levels in blood were measured. Nitrite levels were lower in Cd-exposed subjects than non-exposed subjects. Plasma L-arginine decreased while ADMA, an endogenous endothelial nitric oxide synthase (eNOS) inhibitor, increased in Cd-exposed subjects. Soluble thrombomodulin also increased in Cd-exposed subjects. In Cd-exposed subjects, plasma malondialdehyde and protein carbonyl groups increased while the erythrocytic glutathione decreased. Multiple linear regression analysis revealed a negative association between urinary Cd and nitrite levels in erythrocytes. Our research suggests that subjects with chronic Cd exposure have endothelial dysfunction. [ABSTRACT FROM AUTHOR]

This study aims to investigate the role of soluble thrombomodulin (sTM) in the evaluation of the severity and outcome of community-acquired pneumonia (CAP) in the emergency department (ED) and compare sTM with two biomarkers-procalcitonin (PCT) and C-reactive protein (CRP)-and two scoring systems-the Pneumonia Severity Index (PSI) and CURB65 score. Patients with CAP were consecutively enrolled in the ED of an urban university hospital. sTM, PCT, and CRP levels were measured on enrolment. In addition, the PSI and CURB65 scores were calculated. For all patients, a 30-day follow-up was performed. A total of 573 patients with CAP were enrolled in this study. sTM, PCT, and CRP levels increased with the aggravation of the disease severity as assessed by the PSI and CURB65 score (all P <0.01). The multivariate logistic regression analysis showed that sTM and the PSI were independent predictors of 30-day mortality, and the receiver operating characteristic curve analysis showed that the accuracy of sTM in the prediction of 30-day mortality was comparable with the PSI ( P >0.05) and better than PCT, CRP, and the CURB65 score ( P all <0.05). Furthermore, a combination of sTM and scoring systems can enhance the predictive accuracy of 30-day mortality. sTM is useful in the evaluation of the severity and outcome of CAP in the ED. A well-designed, multi-center study will be needed to further investigate the value of sTM in CAP. [ABSTRACT FROM AUTHOR]

Objective: This study aims to test the serum levels of soluble thrombomodulin (TM) in patients with chronic kidney disease (CKD)3-5 and to assess their connection with the different stages and severity of disease. Methods: Sixty-seven patients with CKD are included, disease severity was evaluated accordingly to CKD staging and clinical data is collected. Nineteen healthy volunteers served as healthy controls. Serum soluble TM is analyzed by ELISA. Results: The levels of soluble TM in all patients with CKD were significantly higher than those of healthy controls ( p < 0.001). CKD5 patients showed higher serum levels of soluble TM, in comparison to CKD4 patients ( p = 0.001), CKD3 patients ( p < 0.001), and healthy controls ( p < 0.001). The correlation analysis revealed significant correlation between serum soluble TM and disease severity ( r = 0.714, p < 0.001). Serum soluble TM was found to be correlated with eGFR ( r = −0.766; p < 0.001) and serum creatinine ( r = 0.778, p < 0.001). Conclusion: Soluble TM concentrations significantly increase in the CKD patients and are associated with the severity of the disease. Soluble TM may play critical roles in the development of CKD, as a biomarker of endothelial cells damage, anticoagulation and anti-inflammation. [ABSTRACT FROM AUTHOR]