Pentraxin-3 Predicts Short- and Mid-term Mortality in Patients with Sepsis and Septic Shock During Intensive Care Treatment.

BACKGROUND: The prognostic value of the acute phase protein Pentraxin 3 (PTX-3) is not well evaluated in patients with septic shock, which reveal an unacceptably high short- and long-term mortality. New Sepsis-3 definitions are not yet implemented in most biomarker studies. Therefore, this study assesses the prognostic value of PTX-3 for short- and mid-term mortality in patients with sepsis or septic shock, as defined by the latest definitions, treated at a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3, and 8. All-cause mortality was followed up to 30 days and at 6 months. RESULTS: On all three days, PTX-3 levels were able to discriminate non-survivors from survivors at 30 days and 6 months (AUC range: 0.59 - 0.70; 95% CI: 0.52 - 0.79; p ≤ 0.02). Highest PTX-3 levels within the fourth quartiles during the first week of ICU treatment were associated with an increased mortality rate at 30 days (OR = 7; 95% CI: 2.0 - 23.5; p ≤ 0.002) and at 6 months (OR = 5; 95% CI: 2.1 - 11.4; p ≤ 0.006). Additionally, the prognostic value of PTX-3 was proven for all patients as well as in subcohorts of patients with sepsis and septic shock, according to Sepsis-3 criteria, both in univariate and multivariate analyses for 30-day and 6-months all-cause mortality, especially predicting all-cause mortality in septic shock (HRs range: 1.0 - 2.9; 95% CI: 0.3 - 5.1; p ≤ 0.03). CONCLUSIONS: PTX-3 offers prognostic value for the prediction of short- and mid-term all-cause mortality in patients suffering from sepsis and septic shock according to the latest Sepsis-3 criteria.

Revisiting the prognostic value of monocyte chemotactic protein 1 and interleukin-6 in the sepsis-3 era.

BACKGROUND: Monocyte Chemotactic Protein 1 (MCP1) and latest sepsis-3 criteria are poorly represented within studies evaluating biomarkers in sepsis. Therefore, this study evaluates the prognostic value of MCP-1 compared to interleukin-6 (IL-6) in patients with sepsis and septic shock according to sepsis-3 criteria. METHODS: 136 patients with sepsis or septic shock were included within 24h of intensive care unit (ICU) admission. MCP-1, IL-6, procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC) were measured on days 1, 3 and 8. All-cause mortality was followed up at 30days and 6months. RESULTS: Both MCP-1 and IL-6 levels revealed valuable prognostic discrimination of 30-day and 6-months all-cause mortality on day 1 and 3 (MCP-1: range of AUCs 0.62-0.65, p<0.039; IL-6: range of AUCs 0.65-0.70, p<0.021) compared to PCT, CRP, SOFA and APACHE II score. MCP-1 levels within the 4th quartile revealed the highest mortality at 30days and 6months compared to patients with lower levels (range of hazard ratio (HR)=2.1-3.3, p<0.041). The prognostic value of MCP-1 sustained in multivariate regression models and was comparable to that of IL-6. CONCLUSION: Both MCP-1 and IL-6 revealed prognostic value for short- and mid-term all-cause mortality in patients with sepsis and septic shock according to latest sepsis-3 definitions.

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

BACKGROUND: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. RESULTS: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). CONCLUSION: PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. TRIAL REGISTRATION: NCT01535534 . Registered 14.02.2012.

Endothelial cell-specific molecule-1/endocan: Diagnostic and prognostic value in patients suffering from severe sepsis and septic shock.

PURPOSE: This study aims to assess the diagnostic and prognostic value of endocan in patients with severe sepsis or septic shock on a medical intensive care unit (ICU). METHODS: 150 patients suspected for at least severe sepsis were enrolled on a medical ICU. On days 1, 3, and 8, plasma levels of endocan, procalcitonin (PCT), and interleukin (IL)-6 were measured. Follow-up on all-cause mortality was performed after 30 days and 6 months. RESULTS: Endocan correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score II (SAPS II) (P < .006). Endocan was higher in patients with at least severe sepsis compared with systemic inflammatory response syndrome (SIRS) or sepsis patients (P = .0006) on days 1, 3, and 8. With a minimum sensitivity of 70%, uniform cutoff levels were set for ≥ sepsis at 1.8 ng/mL, for ≥ severe sepsis at 2.6 ng/mL, for ≥ septic shock at 2.9 ng/mL. On day 1, endocan levels of the fourth quartile were significantly associated with 30-days and 6-months mortality compared to lower levels. After adjustment in Cox regressions, endocan still revealed prognostic value. CONCLUSIONS: Endocan showed diagnostic capacity to diagnose patients with severe sepsis and septic shock and revealed prognostic information for 30-days and 6-months all-cause mortality.

C-terminal agrin fragment (CAF) reflects renal function in patients suffering from severe sepsis or septic shock.

BACKGROUND: One of the main causes of acute kidney injury (AKI) in patients treated on an intensive care unit (ICU) is sepsis. The identification of new biomarkers indicating the early development and future course of AKI are of utmost medical interest. The C-terminal agrin fragment (CAF) is measurable in blood serum and might reflect kidney function. Therefore, this study evaluates CAF in patients presenting to an internal ICU with severe sepsis or septic shock. Serum levels of CAF are correlated with biomarkers of kidney function, markers of systemic inflammation, and the presence of AKI and renal replacement therapy (RRT). METHODS: 61 patients suffering from severe sepsis or septic shock were included during the first 24 hours of ICU treatment and blood samples for biomarker measurements, i.e., CAF, creatinine, cystatin C, procalcitonin (PCT), interleukin 6, C reactive protein (CRP), and white blood cells (WBC) were collected on the first day of intensive care treatment. The number of RRT days and the incidence of AKI were documented. RESULTS: 13% of the patients (8/61) suffered from SIRS/sepsis, 20% (12/61) from severe sepsis, and 67% (41/61) from septic shock. Serum levels of CAF significantly correlated with creatinine (r = 0.623, p < 0.001) and cystatin C (r = 0.578, p < 0.001). Multiple linear regression analyses adjusting CAF for inflammatory parameters (i.e., WBC, CRP, interleukin 6, PCT), age, and gender showed a strong correlation between CAF and creatinine (r = 0.643, p < 0.001). Serum levels of CAF were significantly associated with the need of RRT (area under the curve (AUC) = 0.772, 95% CI: 0.641-0.903, p = 0.002) and the incidence of AKI (AUC = 0.721, 95% CI: 591-0.850, p = 0.004) as indicated by ROC analysis. CONCLUSIONS: In patients suffering from severe sepsis and septic shock, serum levels of CAF were significantly associated with kidney function and RRT and were not influenced by severe septic conditions.

Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment.

INTRODUCTION: The aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment. METHODS: In total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models. RESULTS: Presepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC. CONCLUSIONS: In patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment. TRIAL REGISTRATION: ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.