Marker For Diagnosis Of Sepsis Research Articles

Sepsis Biomarkers: CRP, Procalcitonin, and Presepsin—Diagnostic and Prognostic Significance in Sepsis

Abstract Background: Sepsis is undeniably a serious worldwide health threat, causing millions of deaths each year and a real diagnostic challenge to the clinicians. The conventional standard culture methods are often negative and time-consuming; therefore, alternatively specific and easily measurable biomarkers could help in predicting the diagnosis and prognosis of sepsis, as well as monitor the response to the treatments. This study will compare the role of the three markers procalcitonin (PCT), C-reactive protein (CRP), and presepsin in the diagnosis of sepsis in suspected patients admitted to a tertiary care hospital in eastern India. Materials and Methods: A hospital-based cross-sectional study was conducted from April 2021 to March 2022. Blood samples were collected from the patients admitted in various intensive care units with evidence of sepsis and the biomarkers were estimated. Results: Presepsin was found to be the best among the three biomarkers with sensitivity 89.1% and specificity 88.9%, followed by PCT with sensitivity 82.7% and specificity 80%, and then CRP with sensitivity 74.5% and specificity 75.6%. The diagnostic accuracy of presepsin was also found to be maximum as its area under the receiver-operating characteristic (ROC) curve was highest (0.858) followed by PCT whose area under the ROC curve was 0.793, and then CRP with area under the ROC curve 0.741. Conclusion: Based on the result of the present study, biomarkers were found to be quick, easy and effective test for diagnosing sepsis, and presepsin proved to be the most promising marker for diagnosis of sepsis as compared to PCT or CRP.

A-151 Evaluation of Monocyte Distribution Width as an Early Marker for Diagnosis of Sepsis

Abstract Background Since sepsis has a high mortality rate, early diagnosis and treatment can increase the survival rate and improve prognosis. However, it is difficult to diagnose sepsis accurately in actual clinical practice. Determination of Procalcitonin or C-reactive protein (CRP) levels, which are conventionally used for diagnosing sepsis, are time-consuming. Recent studies have shown that monocyte distribution width (MDW), which is observed simultaneously during the complete blood count (CBC)/diff test in Beckman Coulter DxH900, is a potential marker for the early detection of patients with or developing sepsis. This study evaluated MDW for early detection of sepsis in patients visiting the emergency department. Methods This study enrolled a total of 1167 patients (>18 and ≤80 years of age) who visited the emergency department of a single institution from August 4, 2020 to March 31, 2021, whose initial evaluation included CBC with differential tests and other blood tests (CRP and Procalcitonin). Samples for CBC and MDW were collected in K3-EDTA tubes and analyzed in a UniCel DxH 900 analyzer (Beckman Coulter, Inc., USA). Sepsis was diagnosed according to the sepsis-3 definition through a medical record review. All patients were grouped into no sepsis, sepsis, and septic shock. The diagnostic performance of MDW and other biomarkers for the detection of sepsis was evaluated through statistical analysis. The subgroup analysis for diagnostic performance was performed in subjects with malignancy or without malignancy. All statistical analyses were carried out using Analyze-it, and P < 0.05 was considered statistically significant. Results Of the 1167 patients enrolled, 156 patients (13.4%) were diagnosed with sepsis (135 (11.6%) sepsis and 21 (1.8%) septic shock). Among sepsis patients, those with positive culture results were 46.8%, and the rest either had negative culture results (43.6%) or did not proceed with culture testing (9.6%). The MDWs of the no sepsis group, sepsis group, and septic shock group were 19.70, 27.20, and 31.10, respectively, CRPs were 1.82 mg/dL, 8.84 mg/dL, and 20.44 mg/dL, and Procalcitonins were 0.19 ng/mL, 1.72 ng/mL, and 18.20 ng/mL (median, P < 0.0001). All biomarkers showed a higher value in the sepsis group compared to the no sepsis group. Median MDW showed an increasing trend in patients with malignancy and without malignancy. The AUC of MDW, WBC, CRP, and Procalcitonin for the prediction of sepsis were 0.869, 0.604, 0.773, and 0.868, respectively (P < 0.0001), thus MDW and Procalcitonin showed similar diagnostic performance. At the cutoff of MDW (21.5), the sensitivity was 91.0% and the negative predictive value (NPV) was 98%. The diagnostic performance of MDW showed similar results in cancer patients and cancer-negative patients (AUC 0.873 vs 0.869). Conclusions MDW, which is automatically measured in Beckman Coulter DxH900 hematology analyzer without the requirement of additional reagents during CBC/diff test, has high accuracy in detecting patients with sepsis and could be a reliable tool for early detection of patients with sepsis in the emergency department compared to results of culture or other biomarkers which take longer time to get the result. Furthermore, high NPV may help clinicians rule out sepsis.

Absolute Neutrophil Count in Diagnosis of Neonatal Sepsis : A Hospital Based Cross Sectional Study

Background : Sepsis is the leading cause of neonatal death in developing countries. Delay in initiating treatment can considerably increase the morbidity and mortality. So early diagnosis is important.Traditional methods such as blood culture do not provide a rapid diagnosis. Absolute neutrophil count is one of the important hematological markers for diagnosis of sepsis. The purpose of the study to see the absolute neutrophil count in diognosis of neonatal sepsis.
 Materials and methods: This is a hospital based cross sectional study conducted from January to June 2014. A total of 100 sick neonates admitted in the Neonatal ward of Chattagram Maa Shishu O General Hospital (CMSOGH) with suspected neonatal sepsis (Based on history and physical examination) constituted the study population. Investigation sent for Absolute neutrophil count, C-reactive Protein (CRP) and blood culture. The collected data was analyzed by statistical software packages SPSS method version 15.
 Results: A total of 100 sick neonates of both sexes with suspected sepsis were enrolled in this study, out of which most of the patient showed neutropenia (66%), C-reactive protein positive 65% and blood culture positive 33%. Within the Creactive protein positive patients 78.8% patient had neutropenia (c2 =17.711, p= .001). From blood culture positive patients 85% showed neutropenia (c2 =8.510, p= 0.014).
 Conclusion: Neutropenia is a common hematological finding in neonatal sepsis along with other screening test and neutropenia is more significant than neutrophilia.
 Chatt Maa Shi Hosp Med Coll J; Vol.22 (1); January 2023; Page 66-70

Development of a newly immunoassay specific for mouse presepsin (sCD14-ST)

Presepsin (sCD14-ST) is used as a marker for sepsis diagnosis. The production mechanism of presepsin is unique in that it is produced through phagocytosis of microorganisms. However, some studies have demonstrated that non-infected patients had increased presepsin levels and that presepsin is related to the risk or severity of diseases. This study was designed to describe a sensitive sandwich enzyme-linked immunosorbent assay for mouse presepsin developed to investigate the association of presepsin with diseases. Polyclonal antibodies were generated from peptide-immunized rabbit antiserum. Mouse presepsin standard was prepared using the recombinant method as an Fc-fusion protein. The linear detection range of the method was 4.7–300 pg/mL with a detection limit of 1.4 pg/mL. The assay detected mouse presepsin where mouse soluble CD14 (sCD14) was digested by cathepsin D proteinase and the cross-reactivity of sCD14 was not observed. The normal levels of mouse presepsin and sCD14 were compared; 65.9 ± 21.4 pg/mL and 43.2 ± 7.2 ng/mL were determined, respectively. Moreover, the levels of presepsin and sCD14 were compared with a lipopolysaccharide (LPS)-injected sepsis mouse model. The newly developed analytical method had high specificity to presepsin and is an efficient tool for studying the association between presepsin and diseases.

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.

Could presepsin be an alternative marker in the early diagnosis of sepsis in COVID-19?

In critical patients with Coronavirus Disease (COVID-19), we investigated the diagnostic value of presepsin in the early diagnosis of superinfection with sepsis, and the effect of antibiotic treatment (AT) in the levels of presepsin and procalcitonin and C-reactive protein. A total of 68 critical patients with sepsis and septic shock in the intensive care unit and 20 outpatients (control group) with COVID-19 were taken. ICU patients (n = 68) were further divided into three groups. C(−)AT(−) had negative blood or tracheal aspirate cultures (C) and not AT on admission to ICU (n = 18), C(−)AT(+) had negative C and AT on admission to intensive care unit (n = 31) and C(+) had positive C (n = 19). Presepsin, procalcitonin, C-reactive protein results were compared between the groups. There were no significant relationships between presepsin levels with sepsis, septic shock, mortality, or length of stay in ICU in patients with COVID-19. For procalcitonin and C-reactive protein levels in C(−)AT(+) and C(+) groups were significantly higher than in control and C(−)AT(−) groups (p < .001). C-reactive protein levels in C(−)AT(−) group were significantly higher than in the control group (p < .001). PCT and CRP, there was no difference between C(−)AT(+) and C(+) groups, and procalcitonin there was no difference between control and C(−)AT(−) groups. Presepsin was not found as a useful biomarker for the prediction of sepsis in COVID-19 patients. These study findings indicate that procalcitonin and C-reactive protein may be an indicator of an early diagnostic marker for superinfection in critical COVID-19 patients.

Eosinopenia as a Marker of Sepsis in Intensive Care Unit Patients

Sepsis is one of the most common cases of mortality and morbidity in the intensive care unit (ICU). This study was done to evaluate eonsinopenia as a marker of sepsis in intensive care unit patients. This cross sectional study was carried out in the Department of Clinical Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka from March 2012 to February 2013. Absolute Eosinophil Count (AEC) was done by automated cell counter and rechecked manually microscopically. In this study 74 suspected case of sepsis were enrolled from intensive care unit, BSMMU, Dhaka. Out of these patients 34 were included in the infection group and 40 in the non-infection group depending on blood culture report. The area under ROCcurve was 0.765 in current study. At the cutoff valve of AEC&lt; 40 cell/cumm, the sensitivity and specificity of AEC for diagnosis of sepsis was 72.5% and 61.8% respectively. This present data revealed that decreased absolute eosinophil count was significantly associated with sepsis. So eosinopenia may be a reliable marker for early diagnosis of sepsis.

Evaluation of Biomarkers in Sepsis: High Dimethylarginine (ADMA and SDMA) Concentrations Are Associated with Mortality.

As modulators of nitric oxide generation, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) may play important roles in sepsis. Current data on dimethylarginines are conflicting, and direct comparison data with other biomarkers are limited. Fifty-five patients were included in the final analysis and were divided into 4 groups: infection without sepsis, sepsis, severe sepsis, and septic shock. The first available samples on hospital admission were analyzed for ADMA, SDMA, procalcitonin (PCT), C-reactive protein, heparin binding protein (HBP), zonulin, soluble CD25 (sCD25), and soluble CD163 (sCD163). White blood cell (WBC) counts and lactate results were obtained from the medical record. There were no statistically significant differences in ADMA and SDMA concentrations among the 4 groups; however, PCT, WBC, HBP, and sCD25 showed statistically significant differences. Lactate only trended toward statistical significance, likely because of limited availability in the medical record. Differences between survivors of sepsis and nonsurvivors at 30 days were highly statistically significant for ADMA and SDMA. Areas under the curve (AUCs) for ROC analysis were 0.88 and 0.95, respectively. There was also a statistically significant difference between survivors of sepsis and nonsurvivors for HBP, lactate, sCD25, and sCD163; however, AUCs for ROC curves were not statistically significantly different from 0.5. Analysis of biomarkers other than dimethylarginines were in general agreement with expectations from the literature. ADMA and SDMA may not be specific markers for diagnosis of sepsis; however, they may be useful in short-term mortality risk assessment.

Acute Inflammation Induces Lactate Release By Bone Marrow Neutrophils That Promotes Their Mobilization Via Endothelial GPR81 Signaling

Innate immune neutrophils provide the first line of host defense against bacterial infections. Neutrophils under steady state rely almost entirely on glycolysis and exhibit very low levels of oxidative phosphorylation. The metabolite lactate has long been considered a "waste byproduct" of cell metabolism which accumulates during inflammation and sepsis. Increased plasma lactate levels in human patients is used as a marker for sepsis diagnosis. However, the direct effector actions of lactate, particularly in regulating neutrophil mobilization and function during inflammation has remained obscure. To better understand the metabolic consequences of BM neutrophil activation during the onset of inflammation, we tested how bacterial lipopolysaccharides (mimicking gram negative bacterial inflammation) introduced intraperitoneally (i.p.) affect neutrophil metabolism and mobilization. RNAseq of sorted BM neutrophils revealed that LPS-activated neutrophils upregulate enzymes catalyzing the first part of glycolysis (hexokinase and PFKL) and downregulate the expression of TCA cycle enzymatic genes. In addition, LPS enhanced neutrophil lactate production and release as indicated by higher levels of BM lactate and higher expression of LDHA and MCT4. In addition, LPS increased NADPH oxidase (NOX)-mediated reactive oxygen species and HIF-1α levels in BM neutrophils, which are up-stream of glycolytic enzymes and lactate production and release. Recently, we reported that i.p. lactate administration rapidly activated and mobilized neutrophils from BM to the circulation (ASH, 2017). To test if lactate acts preferentially on neutrophils, we also examined other types of hematopoietic cells. Interestingly, we found that lactate specifically and rapidly (i.e., within 4 hrs) mobilized neutrophils to the circulation whereas the levels of peripheral blood (PB) monocytes, lymphocytes, granulocyte monocyte progenitors (GMPs) and hematopoietic progenitor stem cells (LSK) were reduced following lactate administration. LPS treatment failed to mobilize activated ROShigh neutrophils to the PB in NOX-/- mice, while lactate administration partially rescued this defect following LPS treatment. Our data also reveal that the NOX/ROS axis operates upstream of lactate production in BM neutrophils since abnormal metabolic rates were found in NOX-/- neutrophils during the onset of the acute inflammatory responses. Moreover, we found that BM endothelial cells (BMEC) abundantly express the highly selective lactate receptor GPR81, and that neutrophil-released lactate increased BM vascular permeability via BMEC GPR81 signaling (ASH, 2017). Consistent with a role of the lactate/GPR81 axis in enhanced vascular permeability, we find that i.p. injected LPS reduced VE-Cadherin expression on highly permeable sBMECs in GPR81 dependent manner. Notably, neutralizing VE-Cadherin in GPR81-/- mice can rescue and elevate PB neutrophil levels, similarly to wild-type (WT) mice, suggesting that VE-Cadherin is downstream of GPR81 signaling and plays a role in neutrophil mobilization. Finally, to examine the potential clinical relevance of our findings, we infected WT, NOX-/- and GPR81-/- mice with Salmonella Typhimurium and found out that this pathogen drove high generation of ROS, elevated HIF-1αlevels, and triggered lactate production and release in WT BM neutrophils. In contrast, BM neutrophils of infected NOX-/- mice exhibited significantly lower HIF-1αand impaired lactate production and release. Consequently, WT mice infected with Salmonella had a higher levels of neutrophils in the blood, as compared to their NOX-/- or GPR81-/- mice counterparts. Altogether, our data reveal that the same regulatory mechanisms by which neutrophils respond to LPS challenges are used during bacterial infection with Salmonella. Our study highlights lactate released by BM neutrophils as a key pro-inflammatory stimulus of a novel immune-metabolic crosstalk which is triggered by infection and locally opens the BM vascular barrier to facilitate neutrophil mobilization and recruitment to sites of inflammation. Targeting this immune-metabolic crosstalk between lactate-producing neutrophils and the BM endothelium could be useful for the control of pathological neutrophil activation and mobilization during bacterial infections and help treatments of neutrophil related immune disorders. Disclosures No relevant conflicts of interest to declare.

Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis

Background The soluble cluster of differentiation 14 (or presepsin) is a free fragment of glycoprotein expressed on monocytes and macrophages. Although many studies have been conducted recently, the diagnostic performance of presepsin for sepsis remains debated. We performed a systematic review and meta-analysis of the available literature to assess the accuracy of presepsin for the diagnosis of sepsis in adult patients and compared the performance between presepsin, C-reactive protein (CRP), and procalcitonin (PCT).MethodsA comprehensive systemic search was conducted in PubMed, EMBASE, and Google Scholar for studies that evaluated the diagnostic accuracy of presepsin for sepsis until January 2017. The hierarchical summary receiver operating characteristic method was used to pool individual sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the receiver operating characteristic curve (AUC).ResultsEighteen studies, comprising 3470 patients, met our inclusion criteria. The pooled diagnosis sensitivity and specificity of presepsin for sepsis were 0.84 (95% CI 0.80–0.87) and 0.76 (95% CI 0.67–0.82), respectively. Furthermore, the pooled DOR, PLR, NLR, and AUC were 16 (95% CI 10–25), 3.4 (95% CI 2.5–4.6), 0.22 (95% CI 0.17–0.27), and 0.88 (95% CI 0.85–0.90), respectively. Significant heterogeneity was found in both sensitivities (Cochrane Q = 137.43, p < 0.001, I2 = 87.63%) and specificities (Cochrane Q = 180.76, p < 0.001, I2 = 90.60%). Additionally, we found no significant difference between presepsin and PCT (AUC 0.87 vs. 0.86) or CRP (AUC 0.85 vs. 0.85). However, for studies conducted in ICU, the pooled sensitivity of presepsin was found to be higher than PCT (0.88, 95% CI 0.82–0.92 vs. 0.75, 95% CI 0.68–0.81), while the pooled specificity of presepsin was lower than PCT (0.58, 95% CI 0.42–0.73 vs. 0.75, 95% CI 0.65–0.83).ConclusionBased on the results of our meta-analysis, presepsin is a promising marker for diagnosis of sepsis as PCT or CRP, but its results should be interpreted more carefully and cautiously since too few studies were included and those studies had high heterogeneity between them. In addition, continuing re-evaluation during the course of sepsis is advisable.

Cord blood interleukin-6 as a predictor of early-onset sepsis in preterm babies

Background Despite extensive investigation, no single test meets the criteria that could make it an ideal marker for early diagnosis of sepsis in the newborn. Generally, screening includes a complete blood count with differential white blood cell count and may be accompanied by other adjuvant tests such as evaluation of C-reactive protein. Objective The aim of the study was to evaluate the role of cord blood interleukin-6 (IL-6) as an early predictor of early-onset neonatal sepsis in preterm babies. Patients and methods We studied 75 preterm babies with risk factors of early-onset sepsis in Benha University Hospitals and measured IL-6 in cord blood samples to correlate them with C-reactive protein, hemoglobin percentage, white blood cells count with immature/total (I/T) ratio, and platelet count. Patients were classified into three groups according to gestational age and subdivided according to sepsis state into proven sepsis group (12 cases), probable sepsis group (48 cases) and noninfected group (15 cases). Samples were taken from the patients early just after birth in the resuscitation room. Statistical analysis The collected data were coded, tabulated and statistically analysed using SPSS (Statistical Package for Social Sciences), version 18.0. Results were considered significant if P value is less than 0.05 and highly significant if P value is less than 0.01. Results In our study, cord blood IL-6 was significantly higher in the septic group (probable and proven) with median 371.92 and 124.85 pg/ml, respectively, than in the noninfected group, with median 8.53 pg/ml ( P < 0.0001). The best cutoff level for IL-6 to diagnose neonatal sepsis is 47.5 pg/ml, with sensitivity 98.3% and specificity 93.3%. Conclusion Cord blood IL-6 can be used as a predictor of early-onset neonatal sepsis in preterm babies.

Clinical study of Pentraxin 3 in diagnosing the severity and cardiovascular function of the children with sepsis

To study the value of Pentraxin 3 (PTX3) in diagnosing the severity and cardiovascular function of the critically ill children. Method A total of 178 patients who were older than 28 days, with acute infection of respiratory or neurological system, excluding chronic or special disease, and admitted to the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 1, 2013 to April 30, 2014 were enrolled, including 102 male cases and 76 female cases. The ages ranged from 1 month to 13 years and 1 month, 78 of them were less than 1 year old ; 58 cases were between 1 to 3 years old; 42 cases were above 3 years old; 101 cases were diagnosed as respiratory system diseases, 77 cases had nervous system diseases. PTX3 was detected with enzyme-linked immunosorbent assay (ELISA) within 1 d after enrollment, at 3 days and 7 days, meanwhile, troponin, myocardial enzyme, brain-type natriuretic peptide (BNP), C-reactive protein (CRP), plasma calcitonin (PCT) and WBC etc. Were measured. According to the plasma PTX3 value which were measured within 24 h after enrollment the patients were divided into three groups: mildly elevated group (< 44 µg/L) 41 cases; moderately elevated group (44 - < 132 µg/L) in 66 cases; severely elevated group 71 cases (132 µg/L or higher). Those 178 patients were divided into 3 groups according to the degree of infection: non-sepsis group (78 cases), sepsis group (70 cases), severe sepsis group (30 cases), and in each group, those with heart failure were respectively 19 cases, 28 cases, 17 cases. Analysis of the plasma PTX3 expression changes in different clinical manifestations, different condition, different degrees of organ damages and prognosis for the patient. The continuous variables were analyzed with t-test, F-test, H-test, the categorical variables were analyzed with Chi-square test, and the correlation analysis was performed to calculate Pearson coefficients. The PTX3 value measured within 24 h after enrollment increased with the degree of infection (50. 4(35. 2,70. 4) µg/L; 175. 8 (99. 6, 309. 9) µg/L;419. 9 (168. 3, 468. 6) µg/L; H = 88. 345, P = 0. 000). PTX3 level gradually declined, while in severe sepsis group decreased slowly (P <0. 05); the area under the ROC curve of Plasma PTX3 was larger than that of other inflammatory markers such as CRP and PCT, white blood cells and neutrophils in the diagnosis of sepsis; while the former three are PTX3, PCT and CRP (the sensitivity and specificity respectively were 0. 77, 0. 68; 0. 66, 0. 6; 0. 47, 0. 55); the PTX3 value of the severely elevated group was significantly higher than those of the mildly and moderately elevated groups (P <0. 05). The proportion of having 3 or more organs failure increased as the PTX3 rising among the groups of mildly elevated group, moderately elevated group and severely elevated group (1(2. 4%), 4(6. 1%), 14(19. 7%) χ2 =16. 16,P = 0. 000); and in each group, the proportion of having good and poor prognosis for these three groups were different (33 (80.5%) and 8 (19. 5%), 35 (53%) and 31 (47%), 28 (39.4%) and 43 (60.6%), χ = 17. 663, P = 0. 000). The K-M curve for these three groups had statistically significant difference (χ2 = 7. 086, P = 0. 029). Those with heart failure had higher PTX3 value than those in non-heart failure at the same degree of infection. PTX3 value increased with myocardial enzyme (troponin, creatine kinase isoenzyme, BNP) levels. In the diagnosis of heart failure, the area under the ROC curve were respectively PTX3 0. 824; BNP 0. 772; CM-KB 0. 643; CNTIO. 671, the sensitivity and specificity were PTX3 0. 8, 0. 58; CK-MB 0. 56,0. 79; CTNI 0. 60,0. 69; BNP 0. 73, 0. 58. In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472). The PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage.

Role of procalcitonin in diagnosis of bacterial infection in trans-arterial chemoembolisation treated hepatocellular carcinoma patients

Background and study aimTrans-arterial chemoembolisation (TACE) became the treatment of choice for multinodular hepatocellular carcinoma. The use of prophylactic antibiotics following intervention is controversial. This study aimed to assess the role of serum procalcitonin level in early diagnosis of bacterial infection following TACE to optimise antibiotic intake in those patients. Patients and methodsThis study was carried on HCC patients diagnosed according to AASLD who underwent TACE and developed post interventional fever within 48h. Laboratory investigations including CBC, neutrophil count, C-reactive protein and ESR (pre and after intervention) were done. Cultures were done according to the suspected site of infection. Serum procalcitonin was done for all the included patients before and after TACE. ResultsForty two TACE treated patients were included with post interventional fever within 48h. Their ages ranged between 45 and 65 (mean 53.83±5.23). All patients received antibiotic prophylaxis started 24h pre intervention and for 5days after according to the local protocol. Five patients (11.9%) had positive blood cultures post intervention. The analysis of laboratory results showed statistical significant correlation between procalcitonin levels and positive cultures, post interventional CRP and TLC and pre interventional INR and bilirubin, while there was statistical significant correlation between CRP and post interventional temperature, total leucocytic count and site of focal lesion. ConclusionProcalcitonin seems to be a promising marker for diagnosis of sepsis in TACE treated HCC patients to optimise the unnecessary use of antibiotics.

Levels of Presepsin and Midregion-Proadrenomedullin in Septic Patients with End-Stage Renal Disease after Cardiovascular Surgery: 1-Year Follow Up Study

Background: Procalcitonin (PCT) is a marker for sepsis diagnosis, identification of bacterial infection and monitoring of antibiotic therapy. It has been shown that PCT is not a good choice in patients with hemodialysis. Therefore, we have explored two biomarkers: a) presepsin, and, b) midregion-proadrenomedullin (MR-proADM) in patients having End-Stage Renal Disease (ESRD). Patients and Methods: We prospectively enlisted 20 patients, who underwent cardiovascular surgery and had been on dialysis. The diagnosis of sepsis has been established clinically and confirmed by PCT. Blood samples were taken before and after dialysis. Additionally, plasma and sera of 10 healthy blood donors without any complications were used as controls. Results: Presepsin plasma concentrations (4368 ± 3088 vs. 694.1 ± 239.1 pg/mL) were significantly higher in patients with sepsis compared with controls (p 0.05) with no significance between alive and deceased (p=0.53) patients. Adjustments have shown that the difference for MR-proADM level is due to the random sampling variability (p=0.989), whereas difference for presepsin remained highly significant (p<0.001). Conclusions: Our results indicate that the accuracy of new biomarkers is equal to that of PCT in patients with ESRD. Presepsin might be as good marker in repeated measurements, before and after dialysis, as it is PCT.

The diagnostic value and prognostic significance of plasma soluble triggering receptor-1 on myeloid cells-1 in patients with sepsis

Objective To investigate the diagnostic value and prognostic significance of plasma soluble triggering receptor-1 on myeloid cells ( sTREM-1 ) in patients with sepsis in the early stage.Methods A total of 56 patients with systemic inflammatory response syndrome (SIRS) were enrolled for prospective and control study from May 2009 through July 2010. According to the criteria of sepsis set by SCCN/ESICM/ACCP/ATS/SIS in 2001, patients were divided into sepsis group ( n = 32), SIRS group (n = 24) . Meanwhile, 25 non-SIRS patients were enrolled in the control group. The sepsis group was further divided into two subgroups, namely survival subgroup and non-survival subgroup according to 28-day outcomes. The sTREM-1, procalcitonin (PCT), C-reactive protein (CRP), white blood cell count and neutrophil percentage count (NPC) were measured and APACHE Ⅱ scores were determined within 24 hours after admission. The correlation between sTREM-1 and APACHE Ⅱ score was analyzed. Quantitative data were analyzed by using F-test or Kruskal-Wallis test. Results The plasma level of sTREM-1 in patients of sepsis group was significantly higher than that in SIRS group and control group [215. 1 (157.9 ～397.3) ng/L vs 103.6 (89.4 ～ 176.2) ng/L vs 33.6 (26.2 ～ 43.0) ng/L, P＜0. 05]. The plasma level of sTREM-1 in non-survival group was significantly higher than that in survival group[360.5 (262.2～434.5) ng/L vs 204. 1 (175.0～269.6) ng/L, P=0.002]. In sepsis group, the plasma level of sTREM-1 was positively correlated with APACHE Ⅱ score ( r, = 0. 426, P = 0. 032 ) The area under the ROC curve of sTREM-1 was 0. 935, larger than that of PCT and CRP. Conclusions Plasma sTREM-1 is a useful marker in diagnosis of sepsis at early stage. The increase in the level of sTREM-1 during the first 24 hours might be correlated with poor outcome of patients with sepsis. Key words: Sepsis; sTREM-1; Diagnosis; Prognosis; Acute physiology and chronic health evaluation Ⅱ score; Enzyme-Linked Immunosorbent Assay; Procalcitonin; C-reactive protein

The new sepsis marker, sCD14-ST, induction mechanism in the rabbit sepsis models

Soluble CD14 subtype (sCD14-ST) is a fragment of CD14 and is markedly increased in sepsis patients. We developed a new immunoassay to detect sCD14-ST and evaluated the efficacy of this marker for diagnosis of sepsis. For developing the strategies of sCD14-ST as a sepsis diagnostic marker, the induction mechanism must be known.

C-Reactive Protein in Neonatal Sepsis

SEPSIS IS ONE OF THE MOST COMMON diagnostic challenges in the NICU. Currently a definitive diagnosis can be made only with the gold-standard blood culture, which is generally not available for 48 hours.1,2 Difficulty obtaining a large enough sample to detect a positive blood culture, as well as increased use of antenatal antibiotics, has complicated the ability to make a definitive diagnosis of sepsis.3 If left untreated, sepsis can increase morbidity and mortality. Therefore, many infants are treated empirically with broad-spectrum antibiotics.4,5 Two kinds of tests would be most helpful in the diagnosis of neonatal sepsis: one that quickly confirms the diagnosis and one that conclusively rules it out. In fact, a diagnostic sepsis marker with a high negative predictive value (the value representing patients without sepsis who are correctly diagnosed) might reduce the short- and long-term adverse effects of antibiotics, health care costs, and length of hospital stay.6 Despite extensive investigation no single test meets the criteria that would make it an ideal marker for the early diagnosis of sepsis in the newborn.5,7,8 Generally, screening includes a complete blood count with differential and may be accompanied by other adjunctive tests such as a C-reactive protein (CRP).9–11 This column examines CRP, an acute phase reactant (APR), as a diagnostic marker for neonatal sepsis.

DIAGNOSTIC MARKERS OF SEPSIS IN THE EMERGENCY DEPARTMENT

Sepsis is defined as the systemic inflammatory response to infection. However, changes in body temperature, heart and respiratory rate and white cell count (the “SIRS” criteria) are not specific enough to identify infected patients in the emergency department. Among many biological parameters, measurement of lactate, central venous oxygen saturation (ScvO2), C-reactive protein (CRP) and procalcitonin (PCT) are of particular interest.Early (within 6h) and goal-directed (ScvO2 > 70%) resuscitation increases survival in severe sepsis and septic shock, particularly in patients with high lactate clearances. CRP and PCT are both useful markers of sepsis but PCT increases earlier, better differentiates infective from non-infective causes of inflammation, more closely correlates with sepsis severity in terms of shock and organ dysfunction and better predicts outcome when followed in time. However, PCT measurement is more costly, time-consuming, and not widespread available. New markers for rapid diagnosis of sepsis (e.g. TREM-1) are under investigation.