Accuracy of Presepsin in Sepsis Diagnosis: A Systematic Review and Meta-Analysis.
ABSTRACT: It's difficult to differentiate sepsis from non-sepsis, especially non-infectious SIRS, because no good standard exists for proof of infection. Soluble CD14 subtype (sCD14-ST), recently re-named presepsin, was identified as a new marker for the diagnosis of sepsis in several reports. However, the findings were based on the results of individual clinical trials, rather than a comprehensive and overall estimation. Thus, we conducted this systematic review and meta-analysis to estimate the pooled accuracy of presepsin in patients with sepsis suspect.A comprehensive electronic search was performed via internet retrieval system up to 15 December 2014. Methodological quality assessment was applied by using the QUADAS2 tool. The diagnostic value of presepsin in sepsis was evaluated by using the pooled estimate of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio, as well as summary receiver operating characteristics curve.Nine studies with 10 trials and 2159 cases were included in the study. Only two trials had low concerns regarding applicability, whereas all trials were deemed to be at high risk of bias. Heterogeneity existed in the non-threshold effect, but not in the threshold effect. The pooled sensitivity of presepsin for sepsis was 0.78 (0.76-0.80), pooled specificity was 0.83 (0.80-0.85), pooled positive likelihood ratio was 4.63 (3.27-6.55), pooled negative likelihood ratio was 0.22 (0.16-0.30), and pooled diagnostic odds ratio was 21.73 (12.81-36.86). The area under curve of summary receiver operating characteristics curve was 0.89 (95%CI: 0.84 to 0.94) and Q* index was 0.82 (95%CI: 0.77 to 0.87).This meta-analysis demonstrates that presepsin had some superiority in the management of patients, and may be a helpful and valuable biomarker in early diagnosis of sepsis. However, presepsin showed a moderate diagnostic accuracy in differentiating sepsis from non-sepsis which prevented it from being recommended as a definitive test for diagnosing sepsis in isolation, but the results should be interpreted cautiously.
Project description:BACKGROUND:Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential. METHOD:Our aim was to compare the diagnostic accuracy of procalcitonin (PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT?+?CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses. RESULTS:A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT?+?CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT?+?CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT?+?CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5-2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value >?10 mg/L for CRP had high sensitivity and specificity. CONCLUSIONS:The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings.
Project description:Background:Early and accurate diagnosis of sepsis is challenging. Although procalcitonin and presepsin have been identified as potential biomarkers to differentiate between sepsis and other non-infectious causes of systemic inflammation, the diagnostic accuracy of these biomarkers remains controversial. Herein, we performed a comprehensive meta-analysis to assess the overall diagnostic value of procalcitonin and presepsin for the diagnosis of sepsis. Methods:We searched three electronic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials) for relevant studies. Two authors independently screened articles on the basis of inclusion and exclusion criteria. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated. The quality of evidence for diagnostic accuracy in absolute effects, i.e., the number of true or false positives and true or false negatives, gave a particular pre-test probability. Results:We included 19 studies (19 observational studies and no randomized controlled trials) that had enrolled 3012 patients. Analyses of summary receiver operating characteristic curves revealed areas under the receiver operating characteristic curves of 0.84 for procalcitonin and 0.87 for presepsin. The pooled sensitivities and specificities were 0.80 (95% confidence interval 0.75 to 0.84) and 0.75 (95% confidence interval 0.67 to 0.81) for procalcitonin. For presepsin, these values were 0.84 (95% confidence interval 0.80 to 0.88) and 0.73 (95% confidence interval 0.61 to 0.82), respectively. There were no statistically significant differences in both pooled sensitivities (p = 0.48) and specificities (p = 0.57) between procalcitonin and presepsin. Conclusion:Our meta-analysis provided evidence that the diagnostic accuracy of procalcitonin and presepsin in detecting infection was similar and that both are useful for early diagnosis of sepsis and subsequent reduction of mortality in critically ill adult patients. Systematic review registration:The study was registered in PROSPERO under the registration number CRD42016035784.
Project description:BACKGROUND:Early diagnosis of sepsis in pediatric patients is vital but remains a major challenge. Previous studies showed that presepsin is potentially a reliable diagnostic biomarker for sepsis in adult and neonates. However, there is no pooled analysis of its efficacy as a diagnostic biomarker for sepsis in children. The aims of the present meta-analysis were to assess the overall diagnostic accuracy of presepsin in pediatric sepsis and compare it to those for C-reactive protein (CRP) and procalcitonin (PCT). METHODS:A systematic literature search was performed in Medline/Pubmed, Embase, the Cochrane Library, and ISI Web of Science to identify relevant studies reporting the diagnostic accuracy of presepsin in patients with pediatric sepsis. Sensitivities and specificities were pooled by bivariate meta-analysis. Heterogeneity was evaluated by χ2 test. RESULTS:We identified 129 studies in total. Most were disqualified on the basis of their titles/abstracts and duplication. Four studies were included in the final analysis. They comprised 308 patients aged between 1 mo and 18 y. The pooled diagnostic sensitivity and specificity of presepsin were 0.94 (95% confidence interval [CI]: 0.74-0.99) and 0.71 (95% CI: 0.35-0.92), respectively. The pooled diagnostic odds ratio, positive likelihood ratio (LR), and negative LR of presepsin were 32.87 (95% CI: 2.12-510.09), 3.24 (95% CI, 1.14-12.38), and 0.08 (95% CI, 0.01-0.74), respectively. Heterogeneity was found in both sensitivity (χ2 = 11.17; P = 0.011) and specificity (χ2 = 65.78; P < 0.001). No threshold effect was identified among the studies (r = - 0.938). The pooled sensitivity of presepsin (0.94) was higher than that of CRP (0.51) and PCT (0.76), whereas the overall specificity of presepsin (0.71) was lower than that of CRP (0.81) and PCT (0.76). The AUC of presepsin (0.925) was higher than that of CRP (0.715) and PCT (0.820). CONCLUSION:Currently available evidence indicates that presepsin has higher sensitivity and diagnostic accuracy, but lower specificity, than PCT or CRP in detecting sepsis in children. However, these results must be carefully interpreted as the number of studies included was small and the studies were statistically heterogeneous.
Project description:Presepsin is a novel biomarker to diagnose sepsis but its prognostic value has not been comprehensively reviewed. We conducted this meta-analysis to evaluate the mortality prediction value of presepsin in sepsis.We searched comprehensive electronic databases from PubMed, EMBASE, and Cochrane Library through September 2017 using the key words of ('presepsin' or 'sCD14-ST' or 'soluble CD14 subtype') and ('sepsis' or 'septic shock') and ('prognosis' or 'prognostic value' or 'prognostic biomarker' or 'mortality'). We extracted the presepsin levels in survivors and non-survivors from each individual study and evaluated the standardized mean difference (SMD) using a web-based meta-analysis with the R statistical analysis program.A total of 10 studies and 1617 patients were included. Presepsin levels in the first sampling (within 24 hours) were significantly lower among survivors as compared with non-survivors: the pooled SMD between survivors and non-survivors was 0.92 (95% CI: 0.62-1.22) in the random effects model (I2 = 79%, P< 0.01). In subgroups, divided by the sepsis severity or study site, pooled SMD was consistently noting higher presepsin levels in non-survivals (P< 0.05).This meta-analysis demonstrates some mortality prediction value in presepsin in patients with sepsis. Further studies are needed to define the optimal cut-off point to predict mortality in sepsis.
Project description:Background:Neonatal septicemia is a critical medical situation; current conventional laboratory methods still have many limitations and diagnostic obstacles. For this purpose, last decades have witnessed a challenge between the battery of sepsis biomarkers including many leukocyte surface antigens, not only for early diagnostic purposes but also for better follow-up and good management of sepsis patients. Aim:To evaluate the diagnostic, prognostic, and monitoring performance of both neutrophil CD64 (nCD64) and presepsin as sepsis biomarkers compared to each other and to the conventional laboratory sepsis parameters aiming to decide which is the best fitting for routine daily use in neonatal intensive care units (NICUs). Methods:235 neonates were enrolled from three Egyptian neonatal ICUs, during the period from November 2015 till March 2018; they were classified into two main groups: the control group (n?=?102) and the sepsis group (n?=?133). Laboratory sepsis evaluation included highly sensitive CRP (hs-CRP), CBC, in addition to nCD64 (flow cytometry technique), and presepsin measurement (CLEIA technique combined with Magtration® technology); the diagnosis was confirmed thereafter by positive blood culture results (BacT/Alert system). Sixty-two of the enrolled sepsis neonates were subjected to follow-up assessment; they were reclassified according to their clinical improvement at the second time assessment into (group 1: sepsis group without improvement) (n?=?20) and (group 2: improved sepsis group) (n?=?42). Results:Significant increase in nCD64 and presepsin values was found in sepsis groups compared to the controls. At cutoff 41.6%, nCD64% could discriminate the presence of septicemia with sensitivity 94.7%, specificity 93.6 %, and AUC 0.925, while presepsin at cutoff 686?pg/ml achieves sensitivity 82.7%, specificity 95.5%, and AUC 0.887, respectively. Significant increase in nCD64 (P < 0.001) and hs-CRP (P=0.018) values was observed in severe sepsis/septic shock patients compared to nonsevere sepsis patients. Delta change percentage (dC%) between initial and follow-up evaluations for both improved and nonimproved sepsis patients was dC Z value -5.904 for nCD64% followed by dC Z value -4.494 for presepsin. Conclusion:nCD64 and presepsin are valuable early diagnostic and monitoring sepsis biomarkers; the highest sensitivity could be achieved by a univariant sepsis marker in this study was recorded by the nCD64% biomarker, while the highest specificity was documented by presepsin. Combined measurement of both achieves the highest diagnostic performance in sepsis neonates. Either of CD64 or presepsin combined with hs-CRP associated with better performance than any of them alone. nCD64 carries an additional promising role in reflecting sepsis prognosis.
Project description: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.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.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.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.ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.
Project description:Presepsin is highlighted as a diagnostic and prognostic marker of sepsis. Little information is available regarding the accurate association between presepsin levels and the degree of kidney function. We analyzed presepsin levels in patients with a glomerular filtration rate (GFR) in the categories G1 to G5, evaluated via inulin renal clearance test, and receiving hemodialysis (HD).Patients who were not receiving HD were included if they had undergone inulin renal clearance measurements for the accurate measurement of GFR (measured GFR), and patients who were receiving hemodialysis (HD) were included if they had anuria. Exclusion criteria were infection, cancer, liver disease, autoimmune disorders, or steroid or immunosuppressant use. GFR category was defined as follows; G1: GFR ? 90 ml/min/1.73 m2, G2: GFR = 60 to 90 ml/min/1.73 m2, G3: GFR = 30 to 60 ml/min/1.73 m2, G4: GFR = 15 to 30 ml/min/1.73 m2, G5: GFR ? 15 ml/min/1.73 m2.Seventy-one patients were included. The median (IQR) presepsin values of patients in each GFR category were as follows: G1 + G2: 69.8 (60.8-85.9) pg/ml; G3: 107.0 (68.7-150.0) pg/ml; G4: 171.0 (117.0-200.0) pg/ml; G5: 251.0 (213.0-297.5) pg/ml; and HD: 1160.0 (1070.0-1400.0) pg/ml. The log-transformed presepsin values, excluding patients receiving HD, inversely correlated with the measured GFR (Pearson's correlation coefficient = -0.687, P < 0.001). The multivariate analysis revealed that measured GFR and hemoglobin levels significantly correlated with elevated presepsin levels.Presepsin levels were markedly high in patients receiving HD, similar to values seen in patients with severe sepsis or septic shock. In patients who were not receiving HD, presepsin levels increased as GFR decreased. Thus, the evaluation of presepsin levels in patients with chronic kidney disease requires further consideration, and a different cutoff value is needed for diagnosing sepsis in such patients.
Project description:Presepsin (soluble CD14 subtype) has been shown to be beneficial as a sepsis marker in adults. Nevertheless, very few data are available in neonates. The aim of the present study was to determine reference ranges of presepsin in term and preterm neonates.Healthy term neonates and preterm neonates without clinical signs of infection admitted to the Neonatal Unit were consecutively enrolled. Presepsin concentrations in whole blood were measured using a point-of-care assay system located in the Unit. Demographic data, antenatal and perinatal variables commonly affecting C-reactive protein and procalcitonin values were considered.Of the 684 neonates enrolled in the study, 484 (70.8%) were born at term and 200 (29.2%) were preterm (24-36 weeks' gestation). In term infants, presepsin median value was 603.5 pg/mL (interquartile range: 466.5-791 pg/mL; 5th and 95th centiles: 315 and 1178 pg/mL respectively). In preterm infants, presepsin median value was slightly higher, equal to 620 pg/mL (interquartile range: 503-864 pg/mL; 5th and 95th centiles: 352 and 1370 pg/mL respectively). The reference ranges of presepsin we determined were much higher than those seen in healthy adults. No correlation between presepsin levels and postnatal age was observed, as well as no significant difference was demonstrated in preterm neonates at different gestational ages. None of the variables analyzed affected presepsin levels at a clinical significant extent.For the first time, this study provides reference ranges of presepsin in term and preterm neonates. Having reliable reference values is crucial for obtaining an adequate diagnostic accuracy. Based on our results, most variables commonly affecting C-reactive protein and procalcitonin values do not affect presepsin levels, which suggests that presepsin could be an effective sepsis marker. Further investigations in large groups of neonates with sepsis are needed to determine the diagnostic and prognostic value of this biomarker.
Project description:BACKGROUND:Diagnosis is the most strenuous step in the evaluation of neonatal sepsis. No gold standard diagnostic method is available except for blood culture. We aimed to investigate the role of positive and negative acute phase reactants, namely presepsin and fetuin-A, in the diagnosis of culture-proven late-onset sepsis. METHODS:A prospective, case-control study with the infants ?32?weeks of age with a diagnosis of culture-proven late-onset sepsis was designed. Twenty-nine preterm infants with similar gestational and postnatal ages without sepsis constituted the control group. Serum values of presepsin, fetuin-A, C-reactive protein and interleukin-6 were evaluated at the enrollment, third and seventh days of the diagnosis in the infants with positive blood culture results. RESULTS:First-day presepsin values were significantly higher in the culture-positive infants than the control group [1583?ng/L (1023-1731) vs. 426?ng/L (287-589), p?=?<?0.0001]. Presepsin was found to have an 88.9% sensitivity and 88.9% specificity with a cut-off value of 823?ng/ml for culture-proven LOS in our study, and area under the receiver-operating curve was 0.939. Fetuin-A levels were similar between the study and control groups (p?>?0.05). CONCLUSION:Presepsin may be an accurate marker for both diagnosis and monitoring of treatment response for culture-proven late-onset sepsis in preterm infants. However, fetuin-A does not seem to be a useful tool for the diagnosis of sepsis.
Project description:Sepsis-related acute respiratory distress syndrome (ARDS) has worse clinical outcomes than non-sepsis-related ARDS. Presepsin is known to be elevated in sepsis, but little is known about its discriminatory ability and prognostic evaluation in patients with sepsis-related ARDS. This study was a multicenter prospective cohort study of 225 consecutive ARDS patients. Patients with sepsis-related ARDS had higher presepsin levels than patients with non-sepsis-related ARDS (P?<?0.001). The area under the receiver operating characteristic (ROC) curve of presepsin (0.81) was significantly greater than that of PCT (0.62) in diagnosing sepsis-related ARDS (P?=?0.001). Among patients with sepsis-related ARDS, presepsin levels were significantly higher in non-survivors than in survivors (P?<?0.001). Presepsin was found to be an independent predictor of in-hospital mortality in sepsis-related ARDS. Based on ROC analysis, the addition of presepsin improved discrimination based on SOFA or APACHE II scores from 0.77 to 0.87 or 0.73 to 0.85 (all P?<?0.05), respectively. The levels of plasma presepsin were positively correlated with disease severity, as determined by the SOFA score in the sepsis-related ARDS group (P?<?0.001). Presepsin is a valuable biomarker for early stratification of sepsis-related ARDS. Higher plasma presepsin levels are associated with increased mortality in sepsis-related ARDS.