Table 1 Clinical studies investigating the association of glycocalyx levels with clinical outcomes
From: The glycocalyx: a novel diagnostic and therapeutic target in sepsis
| Â | Year | Authors | Design | Patients population | Patient classification | N | Outcome | Brief result |
|---|---|---|---|---|---|---|---|---|
Syndecan-1 | 2008 | Nelson et al. [34] | Obsevational | Intensive care unit | Cont vs Septic shock | 18 vs 18 | septic shock | Septic shock significantly higher median syndecan-1 vs healthy controls (246 [IQR 180-496] vs 26 ng/ml, [23 - 31], p<0.01) |
Septic shock | 18 | Mortality | No significant association of syndecan-1 with mortality | |||||
Septic shock | 18 | Severity | Septic shock significantly higher median syndecan-1 vs healthy controls (246 ng/mL, [180-496] vs 26 ng/ml, [23 - 31], p<0.01) | |||||
2011 | Steppan et al. [35] | Obsevational | (not specifically referred ) | Cont vs Abdominal surgery vs Severe sepsis or septic shock | 18 vs 28 vs 104 | Severe sepsis or septic shock | Septic patients significantly higher mean syndecan-1 than healthy control (160±109 vs 20.5± 5.1 ng/mL, p<0.001) and than surgery patients (50.5±46.9 ng/mL, p=0.001) | |
Severe sepsis or septic shock | 104 | Level of IL-6 | Syndecan-1 significantly correlated with IL-6 (p=0.004) | |||||
2012 | Sallisalmi et al. [36] | Obsevational | Intensive care unit | Cont vs Septic shock | 20 vs 20 | septic shock | Septic shock higher median syndecan-1 vs controls (p<0.0001) | |
Septic shock | 20 | Severity | syndecan-1 corelates with SOFA score (r=0.654, p<0.002) | |||||
Septic shock | 20 | Level of VAP-1 | syndecan-1 correlated with VAP-1 level (r=0.729, p<0.0001) | |||||
2013 | Ostrowski et al. [73] | Obsevational | Intensive care unit | Experimental endotoxemia vs Severe sepsis or septic shock | 9 vs 20 | Presence of Severe sepsis or septic shock | Septic patients had higher syndecan-1 vs experimental endotoxemia patients (172 ± 102 VS 51 ± 12 ng/mL, p <0.05) | |
Severe sepsis or septic shock | 20 | Severity | No significant correlations of syndecan-1 level with SOFA score (r=0.42, p=NS) and SAPS2(r=0.04, p=NS) | |||||
Severe sepsis or septic shock | 20 | Level of biomarkers | Syndecan-1 correalted with noradrenaline (r=0.45, p=0.045), adrenaline(r=0.62, p=0.004), lactate(r=0.77, p<0.001), APTT(r=0.63, p=0.005), INR(r=0.57, p=0.013) | |||||
2014 | Donati et al. [74] | RCT | Intensive care unit | Non-leukodepleted RBC transfusion vs leukodepleted RBC transfusion | 10 vs 10 | Level of syndecan-1 | In non-leukodepleted RBC transfusion group, the median level of syndecan-1 was significantly increased. No significant association between syndecan-1 and leukodepleted RBC transfusion | |
2014 | Johansson et al. [75] | Obsevational | Intensive care unit | Severe sepsis or septic shock | 67 | Treatment with noradrenalin infusion at the time of blood sampling | No significant association between syndecan and noradrenaline infusion. (p=0.902, data not shown) | |
Severe sepsis or septic shock not treated with noradrenaline infusion at blood sampling | 53 | Level of biomarkers | Significant correlations of syndecan-1 level with noradrenaline (r=0.29, p=0.034), sTM(r=0.35, p=0.01), hcDNA(r=0.29, p=0.038), protein C(r=-0.56, p<0.0001), tPA(r=0.44, p=0.001), sVEGFR1(r=0.56, p<0.0001), Ang-1(r=-0.51, p<0.001), Ang-2(r=- 0.40, p=0.003), TFPI(r=0.44, p=0.001), platelet count(r=-0.45, p=0.001), creatinine(r=0.34, p=0.012), bilirubin(r=0.45, p=0.001) | |||||
Severe sepsis or septic shock not treated with noradrenaline infusion at blood sampling | 53 | Presence of septic shock | Significant correlation of syndecan-1 level with shock. (r=0.40, p=0.003) | |||||
Severe sepsis or septic shock not treated with noradrenaline infusion at blood sampling | 53 | Severity | There were significant correlations of syndecan-1 level with SOFA score (r=0.33, p=0.027) and SAPS2 (r=0.33, p=0.015) | |||||
2015 | Straat et al. [67] | Obsevational | Intensive care unit | non-bleeding critically ill patients | 33 | Level of syndecan-1 | The median level of syndecan-1 after fresh frozen plasma transfusion was significantly lower than the level before the transfusion (565 [IQR 127–1176] ng/mL vs 675 [IQR 132–1690] ng/mL, p=0.01) | |
2015 | Ostrowski et al. [76] | Obsevational | Intensive care unit | Severe sepsis or septic shock | 184 | Coagulopathy | There were siginificant associations of syndecan-1 with TEG R-time (β: 0.64 ± 0.25, p=0.013), TEG MA (β: -1.78 ± 0.87, p=0.042) and FF MA (β: -0.84 ± 0.42, p=0.045) | |
2015 | Ostrowski et al. [37] | Obsevational | Department of internal medicine | No infection vs Local infection vs Sepsis vs Severe sepsis vs Septic shock | 50 vs 63 vs 95 vs 100 vs 13 | Presence of severe sepsis or septic shock | Septic shock (61 ng/mL, [IQR 39 - 119], p<0.05), severe sepsis (61 ng/mL, [IQR 35 - 95], p<0.05) had a significantly higher median level of syndecan than sepsis (31 ng/mL, [IQR 22 - 50]) | |
No infection or Local infection or Sepsis or Severe sepsis or Septic shock | 321 | 28 days mortality | There was a significant association of the median syndecan-1 level with comulative survival over 28days. (p=0.029) | |||||
2016 | Anand et al. [77] | Obsevational | Intensive care unit | Cont vs Sepsis vs Severe sepsis vs Septic shock | 50 vs 15 vs 45 vs 90 | Presence of sepsis | Septic shock (653.5 ng/mL, [IQR 338.93 - 1430.23], p<0.001), severe sepsis(342.1 ng/mL, [IQR 130 - 568.1], p<0.001) and sepsis patitents(85.78 ng/mL, [IQR 40.16 - 141.2], p<0.001) had a significantly higher median level of syndecan than healthy control(28.15 ng/mL, [IQR 7.47 - 45.7]) | |
Sepsis or Severe sepsis or Septic shock | 150 | 90 days mortality | Non-survivor had a significantly higher median level of syndecan-1 than survivor (782 ng/mL, [IQR 235.5 - 1514.31 vs 412.3 ng/mL, [IQR 135.25 - 855.34]; p=0.007). AUC of syndecan-1 level for mortality was 0.644 [95%CI 0.54-0.74]. There was a significant association of the cut off level of syndecan-1:625 ng/ml on DAY 1 ICU admission with comulative survival on Kaplan-Meier plot (p=0.003) | |||||
Sepsis or Severe sepsis or Septic shock | 150 | Severity | There were significant correlations between syndecan-1 levels level with SOFA score (r=0.437, p<0.001) and APACHE2 score (r=0.294, p<0.001). | |||||
2016 | Puskarich et al. [38] | Obsevational | Emergency department | Severe sepsis or septic shock | 175 | Intubation | Intubated patients had syndecan-1 similar to non-intubated patients (181 ng/mL [61 - 568] vs 141 ng/mL [46 - 275], p=0.06) | |
Severe sepsis or septic shock | 175 | Mortality | Non-survivor had a significantly higher level of syndecan-1 than survivor ( 223 ng/mL [67 - 464] vs 142 ng/mL [38 - 294], p=0.04) | |||||
Severe sepsis or septic shock | 175 | Development of AKI | Patients with AKI developlment had a significantly higher level of syndecan-1 than those without AKI development (193 ng/mL [IQR, 63 - 441] vs 93 ng/mL [IQR 23 - 187], p<0 .001) | |||||
Heparan sulfate | 2011 | Steppan et al. [35] | Obsevational | not shown | Cont vs Abdominal surgery vs Severe sepsis or septic shock | 18 vs 28 vs 104 | Severe sepsis or septic shock | Septic patients had a significantly higher mean level of heparan sulfate than healthy control (3.23 ± 2.43 μg/ml vs 1.96 ± 1.21 μg/ml, p = 0.03). Septic patients had a significantly lower mean level of heparan sulfate than surgery patients (3.23 ± 2.43 μg/ml vs 7.96 ± 3.26 μg/ml, p <0.001) |
2014 | Nelson et al. [39] | Obsevational | Intensive care unit | Cont vs Septic shock | 24 vs 24 | septic shock | Septic shock patients had a significantly higher mean level of heparan sulfate than control (p<0.001, data not shown) | |
Septic shock | 24 | Severity | There was a significant correlation between heparan sulfate level with SOFA score (r=0.47, p=0.02) | |||||
Septic shock | 24 | Mortality | Non-survivor had a significantly higher mean level of heparan sulfate than survivor (p=0.02, data not shown) | |||||
Septic shock | 24 | Level of biomarkers | There were no significant correlations of heparan sulfate level with the levels of IL-6 (r=0.40, p=0.06), IL-10 (r=0.34, p=0.10), CRP (r=-0.19, p>0.3), and MPO (r=0.21, p>0.3) | |||||
2016 | Schmidt et al. [41] | Obsevational | Intensive care unit | Severe trauma vs Septic shock | 25 vs 30 | Septic shock | Septic shock patients had a significantly highe mean level of heparan sulfate than sever trauma patitents (p<0.05, data not shown) | |
No AKI development vs AKI development in Septic shock | 16 vs 14 | Development of AKI | Patient who developed AKI had a significantly higher mean level of heparan sulfate than those who do not (p<0.05, data not shown) Non adjusted AUC for the development of AKI was 0.7634 (p=0.014). Aadjusted AUC was not significant (data not shown) | |||||
Septic shock | 30 | Mortality | Non-survivor had a significantly higher mean level of heparan sulfate than survivor (p<0.05, data not shown) | |||||
Non adjusted AUC for the mortality was 0.86 (p=0.0009) Adjusted AUC was 0.91 (p=0.0003) | ||||||||
Hyaluronan | 2012 | Yagmur et al. [42] | Obsevational | Intensive care unit | No SIRS vs SIRS vs Sepsis(sepsis, severe sepsis or septic shock) without cirrhosis | 20 vs 33 vs 97 | Sepsis | Septic patients(344 μg/ml [IQR 0 – 2641]) had a significantly higher median level of hyaluronan than No SIRS (115.5 μg/L [IQR 10 – 2457], p=0.014) and SIRS patients (168 μg/L [IQR 0 – 2117], p=0.015) |
Severity | Hyaluronan correalted with SOFA score (r=0.278, p=0.001) | |||||||
Level of biomarkers | Hyaluronan correlated with Procalcitonin(r=0.46, p<0.001), CRP (r=0.34, p<0.001), IL-6 (r=0.34, p=0.004) and IL-10 (r=0.38, p=0.001) | |||||||
2014 | Nelson et al. [39] | Obsevational | Intensive care unit | Cont vs Septic shock | 24 vs 24 | Septic shock | Septic had a significantly higherdisaccharides from hyaluronan than control (p<0.001) | |
Septic shock | 24 | Severity | Hyaluronan correlated with SOFA score (r=0.47, p=0.02) | |||||
Septic shock | 24 | Mortality | Non survivor had a significantly higher disaccharides from hyaluronan than survivor (p=0.006, data not shown) | |||||
2016 | Schmidt et al. [41] | Obsevational | Intensive care unit | Sever trauma vs Septic shock | 25 vs 30 | Septic shock | Septic shock patients had a significantly higher level of hyaluronan than sever trauma patitents (p<0.05, data not shown) | |
No AKI development vs AKI development in Septic shock patients | 16 vs 14 | Development of AKI | Patient who developed AKI had a significantly higher level of hyaluronan than not (p<0.05, data not shown) | |||||
Septic shock | 30 | Mortality | Non adjusted AUC for the development of AKI was 0.75 (p=0.018) | |||||
Adjusted AUC was 0.77 (p=0.01) | ||||||||
Non survivor had a significantly higher level of hyaluronan than survivor (p<0.05, data not shown) | ||||||||
Non adjusted AUC for the mortality was 0.86 (p=0.0009). Adjusted AUC was not significant (data not shown) |