Elevated endothelial dysfunction-related biomarker levels indicate the severity and predict sepsis incidence.

This study was conducted to investigate the relationship between serum endothelial dysfunction-related biomarker levels and organ dysfunction severity in septic patients and the predictive value of these levels during sepsis. In total, 105 patients admitted to the Department of Critical Care Medicine were enrolled between September 2020 and November 2021. Serum syndecan-1 and soluble thrombomodulin(sTM) levels were measured by enzyme-linked immunosorbent assay, and clinical and laboratory data were recorded. Enroll patients were divided into the infection (n = 28), septic nonshock (n = 31), and septic shock (n = 46) groups . Serum syndecan-1 (102.84 ± 16.53 vs. 55.38 ± 12.34 ng/ml), and sTM(6.60 ± 1.44 ng/ml vs. 5.23 ± 1.23 ng/ml, P < 0.01) levels were increased in the septic group compared with those in the infection group. Serum syndecan-1 levels were closely positively correlated with serum sTM (rs = 0.712, r2 = 0.507, P < 0.001). Additionally, serum syndecan-1(rs = 0.687, r2 = 0.472, P < 0.001) and sTM levels (rs = 0.6, r2 = 0.36, P < 0.01) levels were significantly positively correlated with the sequential organ failure assessment scores respectively. Syndecan-1 (AUC 0.95 ± 0.02, P < 0.0001) was more valuable for prediction sepsis than was sTM (AUC 0.87 ± 0.04, P < 0.0001). Compared with sTM (AUC 0.88 ± 0.03, P < 0.001), syndecan-1 (AUC 0.95 ± 0.02, P < 0.001) and SOFA score (AUC 0.95 ± 0.02, P < 0.001) were better predictors of septic shock. Serum syndecan-1 and sTM levels were associated with organ dysfunction severity in septic patients, and both were good predictors for early identification of sepsis, particularly in patients undergoing septic shock.

[Clinical value of pulse pressure/central venous pressure ratio in low cardiac output syndrome after cardiac surgery].

OBJECTIVE: To explore the relationship between the pulse pressure/central venous pressure (PP/CVP) ratio and the cardiac output (CO) of patients after cardiac surgery from the basic principles of hemodynamics, and to further evaluate the predictive value of PP/CVP ratio in patients with secondary low cardiac output syndrome (LCOS) after cardiac surgery. METHODS: A retrospective study was conducted, and patients who received pulse indicator continuous cardiac output (PiCCO) monitoring were enrolled at the department of critical care medicine of Peking Union Medical College Hospital from January 1, 2016, to September 1, 2021. Patients were divided into two groups: the LCOS group [cardiac index (CI) < 33.34 mL×s-1×m-2, 25 cases] and the non-LCOS group (CI ≥ 33.34 mL×s-1×m-2, 125 cases) according to the CI at 6 hours after surgery. The general clinical data and hemodynamic parameters were collected. Correlations between PP/CVP ratio and PiCCO monitoring indicators were performed with Pearson or Spearman correlation test. Receiver operator characteristic curve (ROC curve) analysis was carried out to evaluate the predictive value of the parameters in patients with LCOS after cardiac surgery. RESULTS: A total of 150 patients with PiCCO monitoring after cardiac surgery were included. There were no differences in baseline characteristics between the two groups, while PP in the LCOS group was lower than that in the non-LCOS group [mmHg (1 mmHg ≈ 0.133 kPa): 40 (37, 44) vs. 55 (46, 64)], CVP was higher than that in the non-LCOS group [mmHg: 12 (11, 14) vs. 10 (8, 12)], and PP/CVP ratio in the LCOS group was lower than that in the non-LCOS group [3.3 (2.9, 3.7) vs. 5.5 (4.6, 6.8)], with significant differences (all P < 0.05). Correlation analysis results showed that PP/CVP ratio was positively correlated with CI, CO, and stroke volume index (SVI), respectively (rs = 0.660, 0.592, 0.600, all P < 0.001). CI was negatively correlated with PP (rs = 0.509, P < 0.001) and positively correlated with CVP (rs = -0.297, P < 0.001). ROC curve analysis revealed that compared with PP, CVP, SVI and cardiac function index (CFI), PP/CVP ratio was the best predictor of LCOS after cardiac surgery [area under the ROC curve (AUC) was 0.94±0.02, P < 0.001], when the optimum cut-off value was 4.41, the sensitivity was 80.00%, and the specificity was 96.00%. CONCLUSIONS: PP/CVP ratio was moderately positively correlated with CO after cardiac surgery, and PP/CVP ratio could be used as a prognostic predictor for LCOS after cardiac surgery.

Metabolic reprogramming consequences of sepsis: adaptations and contradictions.

During sepsis, the importance of alterations in cell metabolism is underappreciated. The cellular metabolism, which has a variable metabolic profile in different cells and disease stages, is largely responsible for the immune imbalance and organ failure associated with sepsis. Metabolic reprogramming, in which glycolysis replaces OXPHOS as the main energy-producing pathway, is both a requirement for immune cell activation and a cause of immunosuppression. Meanwhile, the metabolites produced by OXPHOS and glycolysis can act as signaling molecules to control the immune response during sepsis. Sepsis-induced "energy shortage" leads to stagnated cell function and even organ dysfunction. Metabolic reprogramming can alleviate the energy crisis to some extent, enhance host tolerance to maintain cell survival functions, and ultimately increase the adaptation of cells during sepsis. However, a switch from glycolysis to OXPHOS is essential for restoring cell function. This review summarized the crosstalk between metabolic reprogramming and immune cell activity as well as organ function during sepsis, discussed the benefits and drawbacks of metabolic reprogramming to show the contradictions of metabolic reprogramming during sepsis, and assessed the feasibility of treating sepsis through targeted metabolism. Using metabolic reprogramming to achieve metabolic homeostasis could be a viable therapy option for sepsis.

Mitochondrial Sirt3 serves as a biomarker for sepsis diagnosis and mortality prediction.

The purpose of this study is to determine whether the levels of serum Sirt3 correlate with disease severity and perfusion indicators in septic patients, as well as to assess the clinical value of Sirt3 as a potential novel marker for sepsis diagnosis and mortality prediction. A total of 79 patients in the ICU were included in the study, of which 28 were postoperatively noninfectious and the remaining 51 patients were all diagnosed with sepsis during the study period. The levels of Sirt3 were detected and dynamically monitored by enzyme-linked adsorption method, Pearson or Spearman coefficient for correlation analysis between Sirt3 and clinical indicators, ROC curve for evaluation of diagnosis and mortality prediction, Kaplan-Meier method for the significance of Sirt3 in 28-day survival. The serum levels of Sirt3 were lower in the sepsis patients on day 1 (P < 0.0001), and the septic shock group had lower Sirt3 levels than the sepsis group (P = 0.013). Sirt3 had good negative correlations with SOFA scores both in sepsis and septic shock groups (Pearson: r2 = - 0.424, - 0.518; P = 0.011, 0.040), and Sirt3 correlated strongly with ScvO2 in the septic shock group (Pearson: r2 = - 0.679, P = 0.004) and with PCT in the sepsis group (Pearson: r2 = - 0.409, P = 0.015). Sirt3 not only performed well in identifying sepsis (AUC = 0.995, 95% CI 0.987-1, P < 0.0001) but also greatly enhanced lactate's specificity in detecting septic shock (from 91.43 to 94.29%). Patients in the low Sirt3 group had higher ScvO2, lactate, APACHE II score, SOFA score, longer ICU stays, and worse indicators of inflammation (TNF-α, IL-6) and infection (PCT) than those in the high Sirt3 group (P < 0.05). Additionally, Sirt3 can predict mortality of sepsis (AUC = 0.746, 95% CI 0.571-0.921, P = 0.022), patients with serum Sirt3 < 10.07 pg/ml have a lower 28-day survival (log-rank P = 0.008). Low serum levels of Sirt3 are significantly correlated with the disease severity. At the same time, Sirt3 increases the sensitivity of lactate to detect "cellular hypoxia" in septic shock. Sirt3 is a promising biomarker for the diagnosis of sepsis and predicting mortality risk in septic patients.

Variation of Left Ventricular Outflow Tract Velocity Time Integral at Different Positive End-Expiratory Pressure Levels Can Predict Fluid Responsiveness in Mechanically Ventilated Critically Ill Patients.

OBJECTIVES: To explore whether the variation of left ventricular outflow tract velocity time integral (LVOT VTI) between positive end-expiratory pressure (PEEP) 10 cmH2O and PEEP 0 cmH2O can predict fluid responsiveness in mechanically ventilated critically ill patients. DESIGN: An observational study. SETTING: A tertiary hospital intensive care unit. PARTICIPANTS: A total of 79 critically ill patients who were on controlled mechanical ventilation. INTERVENTIONS: Transthoracic echocardiography was performed at different PEEP levels and was also performed before and after passive leg raising (PLR). MEASUREMENTS AND MAIN RESULTS: The patients were classified as the fluid responders (n = 45) and the fluid nonresponders (n = 34) according to the LVOT VTI change after PLR (ΔVTIPLR). The difference of LVOT VTI between PEEP 10 cmH2O and PEEP 0 cmH2O (ΔVTIPEEP) was much higher in responders than in nonresponders (17.9% v 2.1%, p < 0.001). The ΔVTIPEEP and ΔVTIPLR were correlated among all patients (r = 0.582, p < 0.001). The receiver operating characteristic curve analysis revealed that the ΔVTIPEEP was a good predictor of fluid responsiveness, with an area under the curve of 0.935 (95% confidence interval: 0.885-0.986, p < 0.001), and the optimal cutoff value was 10.5%. CONCLUSIONS: Variation of LVOT VTI between PEEP 10 cmH2O and PEEP 0 cmH2O can be used to predict fluid responsiveness in critically ill patients on controlled mechanical ventilation.

Adverse Childhood Experiences and Psychological Well-Being in Chinese College Students: Moderated Mediation by Gender and Resilience.

Adverse childhood experiences (ACEs), including child abuse/neglect and household challenges, are a prevalent social issue that impacts individuals' well-being worldwide. Relatively few ACEs studies orient to the presence of psychological wellness, especially in ethnically Chinese populations. Furthermore, less is known about resilience as a mechanism between ACEs and psychological well-being, in addition to the moderating effect of gender. This study examined the relationship between ACEs and psychological well-being among Chinese college students and the potential mediating and moderating effects of resilience and gender, respectively. A total of 1,871 college students studying social science from 12 Chinese colleges completed an anonymous online survey between late September and early October 2020. Multiple-group path analyses were conducted to examine whether the relationships among ACEs, resilience, and psychological well-being differed as a function of gender. Results suggested that gender moderated the relationships studied. For female students, resilience mediated the association between abuse/neglect and psychological well-being, where abuse/neglect was negatively associated with resilience, which in turn had a negative relationship with psychological well-being. For male students, household challenges were negatively related to psychological well-being through reduced resilience. Based on the findings, various ACE-informed initiatives may be essential to prevent and protect individuals from ACEs. We also call for resilience-based interventions to enhance individuals' resilience and thus strengthen their psychological well-being.

Selective sphingosine-1-phosphate receptor 1 modulation ameliorates TBI-induced neurological deficit after CCI.

BACKGROUND AND PURPOSE: The inflammatory response after traumatic brain injury (TBI) can contribute to secondary brain injury. RP101075, a sphingosine-1-phosphate receptor modulator, can attenuate various inflammatory responses. Here, we hypothesized that consecutive administration of RP101075 over 3 days could broadly suppress the TBI-induced inflammatory response and ameliorate the outcomes of TBI. METHODS AND RESULTS: Young C57/BL6 mice were subjected to a controlled cortical impact (CCI) model. RP101075-treated mice exhibited significantly reduced scores on the modified neurological severity score (mNSS) test on days 3, 7, 14, and 21 after TBI, in comparison to TBI mice that received the vehicle. RP101075-treated mice had a remarkably decreased percentage of foot faults on the foot fault test on days 7, 14, and 21 after surgery, in comparison to TBI mice that received the vehicle. Using the wet brain weight/dry brain weight method, we found that RP101075 attenuated brain edema at 3 days post-TBI. According to the results of the Morris water maze (MWM), TBI mice treated with RP101075 exhibited reduced latency time and an increased percentage of target quadrant time from day 24 to day 25 after TBI, in comparison to TBI mice that received the vehicle. In addition, flow cytometry and immunohistochemistry showed that RP101075 markedly decreased the number of infiltrated T cells, B cells and NK cells at 3 days after TBI. Analysis of Western blot data showed that RP101075 lowered the expression of proinflammatory factors on day 3 after TBI. CONCLUSIONS: Our study demonstrated that consecutive administration of RP101075 over 3 days suppressed the TBI-induced inflammatory response and ameliorated neurological deficits after TBI. Thus, this procedure may be a potential treatment strategy for TBI in the clinical setting.

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock. METHODS: We genotyped two TREM-1 single nucleotide polymorphisms (SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis. RESULTS: TREM-1 rs2234246 A allele in the promoter region was significantly associated with the susceptibility of septic shock in recessive model (AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model (AG, OR=0.72, 95%CI 0.43-1.19, P=0.02; AA, OR=2.71, 95%CI 1.00-7.42; P=0.03). However, in three inherited models (dominant model, recessive model, and codominant model), none of the assayed loci was significantly associated with the prognosis of septic shock. The non-survivor group demonstrated higher plasma IL-6 levels (99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/mL, AG 85.4±43 pg/mL, and GG 65.3±30.7 pg/mL (P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were significantly higher than those in patients with GG genotypes (P<0.01). CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.

Association of myeloid cells of triggering receptor-1 with left ventricular systolic dysfunction in BALB/c mice with sepsis.

OBJECTIVE: To investigate the correlation between TREM-1 and LPS-induced left ventricular systolic dysfunction in BALB/c mice. METHODS: Male BALB/c mice were randomly divided into 3 groups: LPS, LPS/TREM-1, and control groups which were injected intraperitoneally with 25 mg/kg LPS, 5 µg TREM-1mAb 1 h after LPS challenge, and sterilized normal saline, respectively. Left ventricular systolic function was monitored by echocardiography at 6 h, 12 h, and 24 h. Meanwhile, TNF- α , IL-1 ß , and sTREM-1 in serum and myocardium were determined by ELISA or real-time PCR; at last left ventricles were taken for light microscopy examination. RESULTS: FS and EF in LPS/mAbTREM-1 group, significantly declined compared with LPS and control group at 12 h, were accompanied with a markedly increase in serum IL-1 ß (at 6 h) and sTREM-1 (at 12 h and 24 h) expression. Myocardium TNF- α (at 6 h and 24 h) and sTREM-1 (at 6 h) were significantly higher in LPS/mAbTrem-1-treated mice than in time-matched LPS-treated mice; meanwhile myocardium TNF- α mRNA were markedly increased in comparison with LPS-treated or saline-treated mice at 24 h. Besides, mAbTREM-1 aggravated LPS-induced myocardial damage was observed. CONCLUSIONS: Our results suggest that TREM-1 is significantly associated with LPS-induced left ventricular systolic dysfunction in BALB/c mice.