Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin,matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study

Introduction

The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED).

Methods

In total, 480 consecutive adult patients were enrolled in this study. They fulfilled the systemic inflammatory response syndrome (SIRS) criteria and were admitted to the ED of Beijing Chaoyang Hospital from February 2013 to August 2013. A total of 40 healthy controls comprised the control group. The patients were classified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Serum NGAL, MMP-9, TIMP-1 and PCT were measured, and MEDS score was calculated at enrollment. The prognostic values of NGAL, MMP-9 and TIMP-1 were compared with PCT and MEDS score. A 28-day follow-up was performed for all patients.

Results

The median levels of serum NGAL and TIMP-1 increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of NGAL or TIMP-1 were greater than those of PCT and MEDS score in diagnosing and predicting 28-day mortality, and the AUC of a combination of NGAL and MEDS score or TIMP-1 and MEDS score was more significant. Serum NGAL, MMP-9 and TIMP-1 levels were significantly higher in non-survivors than survivors at 28 days’ follow-up. In addition, the level of NGAL was much higher in septic patients with acute kidney injury (AKI) than those without AKI. NGAL, TIMP-1, MMP-9 and MEDS score were found to be independent predictors of 28-day mortality in septic patients. The levels of serum NGAL and TIMP-1 were positively correlated with PCT and MEDS score in every septic group.

Conclusions

NGAL and TIMP-1 are valuable for the risk stratification, early diagnosis and prognostication of sepsis in the ED. NGAL is also a valuable biomarker for prognosis of septic patients with AKI in the ED.     

Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study

Introduction

Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock.

Methods

This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records.

Results

Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival.

Conclusions

In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock.     

Risk stratification and prognostic performance of the predisposition,infection, response,and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study

Introduction

The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores.

Methods

Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems.

Results

Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD.

Conclusions

The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.     

Risk stratification of severe sepsis patients in the emergency department

Objective

To determine the efficacy of the Mortality in Emergency Department Sepsis (MEDS) score in the stratification of patients who presented to the emergency department (ED) with severe sepsis.

Methods

Adults who presented to the ED with severe sepsis were retrospectively recruited and divided into group A (MEDS score <12) and group B (MEDS score ⩾12). Their outcomes were evaluated with 28 day hospital mortality rate, length of hospital stay, Kaplan‐Meier survival analysis, and receiver operating characteristic (ROC) analysis. Discriminatory power of the MEDS score in mortality prediction was further compared with the Acute Physiology and Chronic Health Evaluation (APACHE) II model.

Results

In total, 276 patients (44.6% men and 55.4% women) were analysed, with 143 patients placed in group A and 133 patients in group B. Patients with MEDS score ⩾12 had a significantly higher mortality rate (48.9% v 17.5%, p<0.01) and higher median APACHE II score (25 v 20 points, p<0.01). Significant difference in mortality risk was also demonstrated with Kaplan‐Meier survival analysis (log rank test, p<0.01). No difference in the length of hospital stay was found between the groups. ROC analysis indicated a better performance in mortality prediction by the MEDS score compared with the APACHE II score (ROC 0.75 v 0.62, p<0.01).

Conclusion

Our results showed that mortality risk stratification of severe sepsis patients in the ED with MEDS score is effective. The MEDS score also discriminated better than the APACHE II model in mortality prediction.     

Comparison of Predisposition, Insult/Infection, Response, and Organ dysfunction, Acute Physiology And Chronic Health Evaluation II, and Mortality in Emergency Department Sepsis in patients meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle

Purpose

The aim of the study was to examine the performance of the Predisposition, Insult/Infection, Response, and Organ dysfunction (PIRO) model compared with the Acute Physiology and Chronic Health Evaluation (APACHE) II and Mortality in Emergency Department Sepsis (MEDS) scoring systems in predicting in-hospital mortality for patients presenting to the emergency department (ED) with severe sepsis or septic shock.

Materials and Methods

This study was an analysis of a prospectively maintained registry including adult patients with severe sepsis or septic shock meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle over a 6-year period. The registry contains data on patient demographics, sepsis category, vital signs, laboratory values, ED length of stay, hospital length of stay, physiologic scores, and outcome status. The discrimination and calibration characteristics of PIRO, APACHE II, and MEDS were analyzed.

Results

Five-hundred forty-one patients with age 63.5 ± 18.5 years were enrolled, 61.9% in septic shock, 46.9% blood-culture positive, and 31.8% in-hospital mortality. Median (25th and 75th percentile) PIRO, APACHE II, and MEDS scores were 6 (5 and 8), 28 (22 and 34), and 12 (9 and 15), with predicted mortalities of 48.5% (40.1 and 63.9), 66.0% (42.0 and 83.0), and 16.0% (9.0 and 39.0), respectively. The area under the receiver operating characteristic curves for PIRO was 0.71 (95% confidence interval, 0.66-0.75); APACHE II, 0.71 (0.66-0.76); and MEDS, 0.63 (0.60-0.70). The standardized mortality ratio was 0.70 (0.08-1.41), 0.70 (−0.46 to 1.80), and 4.00 (−8.53 to 16.62), respectively. Actual mortality significantly increased with increasing PIRO score in patients with APACHE II 25 or more (P < .01).

Conclusions

The PIRO, APACHE II, and MEDS have variable abilities to early discriminate and estimate in-hospital mortality of patients presenting to the ED meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle. The PIRO may provide additional risk stratification in patients with APACHE II 25 or more. More studies are required to evaluate the clinical applicability of PIRO in high-risk patients with severe sepsis and septic shock.     

Evaluation of the Mortality in Emergency Department Sepsis score combined with procalcitonin in septic patients

Objective

To determine an effective method for predicting severity of sepsis and 28-day mortality of emergency department (ED) patients, we compared the Mortality in Emergency Department Sepsis (MEDS) score with procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) and evaluated the MEDS score combined with relevant biomarkers.

Methods

A total of 501 adult ED patients with sepsis were selected for this prospective clinical study. The optimal combination was assessed by logistic regression. All cases were divided into the sepsis group (319 cases) and the severe sepsis and septic shock group (182 cases) according to the severity of sepsis, as well as the survivor group (367 cases) and nonsurvivor group (134 cases) according to the 28-day outcomes.

Results

The area under the curve of the MEDS score, PCT, IL-6, and CRP was 0.793, 0.712, 0.695, and 0.681 for severity of sepsis and 0.776, 0.681, 0.692, and 0.661 for 28-day mortality, respectively. Only PCT was an independent predictor when combined with the MEDS score. The new combination of the MEDS score with PCT improved the area under the curve for severity (0.852) and mortality (0.813). This new combination for evaluation of severity had better sensitivity (63.2%), specificity (92.2%), and positive predictive (82.1%) and negative predictive (81.4%) values.

Conclusions

The predictive ability of the MEDS score for severity and 28-day mortality of septic ED patients is better than PCT, IL-6, and CRP levels. The MEDS score combined with PCT enhances the ability of risk stratification and prognostic evaluation.     

Prognostic value of adrenomedullin in septic patients in the ED

Objective

The aims of the present study were to evaluate the prognostic value of adrenomedullin (AM) in septic patients in the emergency department (ED) and to compare it with procalcitonin (PCT) and Mortality in Emergency Department Sepsis (MEDS) score.

Methods

We enrolled 837 consecutive patients who fulfilled the systemic inflammatory response syndrome criteria and were admitted to the ED of Beijing Chaoyang Hospital and 100 age-matched healthy controls. Serum AM and PCT were determined, and MEDS score was calculated at enrollment. The prognostic value of AM was compared with PCT and MEDS score. Primary outcome was in-hospital mortality.

Results

On admission, mean levels of AM were 28.66 ± 6.05 ng/L in 100 healthy controls, 31.65 ± 6.47 ng/L in 153 systemic inflammatory response syndrome patients, 33.24 ± 8.59 ng/L in 376 sepsis patients, 34.81 ± 8.33 ng/L in 210 severe sepsis patients, and 45.15 ± 9.87 ng/L in 98 septic shock patients. The differences between the 2 groups were significant. Adrenomedullin level was higher in nonsurvivors than in survivors in every group. The area under receiver operating characteristic curve of AM for predicting in-hospital mortality in septic patients was 0.773, which was better than PCT (0.701) and MEDS score (0.721). Combination of AM and MEDS score improved the accuracy of AM and MEDS score in predicting the risk of in-hospital mortality (area under receiver operating characteristic curve, 0.817). In logistic regression analysis, AM and MEDS score were independent predictors of in-hospital mortality.

Conclusions

Adrenomedullin is valuable for prognosis in septic patients in the ED.     

Arterial lactate improves the prognostic performance of severity score systems in septic patients in the ED

Objective

To evaluate the prognostic performance of lactate in septic patients in the emergency department (ED) and investigate how to add lactate to the traditional score systems.

Methods

This was a single-centered, prospective, observational cohort study conducted in ED of Beijing Chao-Yang Hospital. The study enrolled adult septic patients admitted to the ED. Arterial lactate was measured in every patient. Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), and Mortality in Emergency Department Sepsis (MEDS) scores were calculated on ED arrival. The primary outcome was 28-day mortality.

Results

The average levels of lactate, MEDS, APACHE II, and SOFA were much higher in nonsurvivors than in survivors (P < .001), and they were the independent predictors of 28-day mortality. Area under receiver operating characteristic (AUC) curves of MEDS, APACHE II, SOFA, and lactate were 0.74, 0.74, 0.75, and 0.79, respectively. The AUCs of combination lactate and MEDS, APACHE II, and SOFA were 0.81, 0.81, and 0.82, respectively and were much higher than that of score systems alone (P < .05). The AUCs of modified MEDS, APACHE II, and SOFA were 0.80, 0.80, and 0.81, respectively. The prognostic value of the modified score systems was superior to the original score systems and similar to the combination of the lactate and original score systems.

Conclusions

Lactate is a prognostic predictor in septic patients in the ED, and it may improve the performance of APACHE II, SOFA, and MEDS scores in predicting mortality.     

The risk stratification and prognostic evaluation of soluble programmed death-1 on patients with sepsis in emergency department

Objective

To evaluate the efficacy of soluble programmed death-1 (sPD-1) for risk stratification and prediction of 28-day mortality in patients with sepsis, we compared serum sPD-1 with procalcitonin (PCT), C-reactive protein (CRP), and the Mortality in Emergency Department Sepsis (MEDS) score.

The prognostic and risk-stratified value of heart-type fatty acid–binding protein in septic patients in the emergency department

Purpose

To evaluate the prognostic and risk-stratified ability of heart-type fatty acid–binding protein (H-FABP) in septic patients in the emergency department (ED).

Materials and Methods

From August to November 2012, 295 consecutive septic patients were enrolled. Circulating H-FABP was measured. The predictive value of H-FABP for 28-day mortality, organ dysfunction on ED arrival, and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was assessed by the receiver operating characteristic curve and logistic regression and was compared with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Mortality in Emergency Department Sepsis (MEDS) score, and Sequential Organ Failure Assessment score.

Results

The 28-day mortality, APACHE II, MEDS, and Sequential Organ Failure Assessment scores were much higher in H-FABP–positive patients. The incidence of organ dysfunction at ED arrival and requirement for mechanical ventilation or a vasopressor within 6 hours after ED arrival was higher in H-FABP–positive patients. Heart-type fatty acid–binding protein was an independent predictor of 28-day mortality and organ dysfunction. The area under the receiver operating characteristic curve for H-FABP predicting 28-day mortality and organ dysfunction was 0.784 and 0.755, respectively. Combination of H-FABP and MEDS improved the performance of MEDS in predicting organ dysfunction, and the difference of AUC was statistically significant (P < .05). The combinations of H-FABP and MEDS or H-FABP and APACHE II also improved the prognostic value of MEDS and APACHE II, but the areas under the curve were not statistically different.

Conclusions

Heart-type fatty acid–binding protein was helpful for prognosis and risk stratification of septic patients in the ED.     

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 4^th 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, precipices 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 {"type":"clinical-trial","attrs":{"text":"NCT01535534","term_id":"NCT01535534"}}NCT01535534. Registered 14 February 2012.     

急诊脓毒症死亡风险评分、降钙素原对脓毒血症预后评估的价值

目的:探讨急诊脓毒症死亡风险(MEDS)评分、血清降钙素原(PCT)对脓毒血症预后评估的临床意义。方法:102例脓毒血症患者按预后分为存活组和死亡组,比较治疗早期MEDS评分、PCT及急性生理与慢性健康状况(APACHEⅡ)评分,并建立ROC曲线观察三者对预后评估的临床价值。结果:两组MEDS评分、PCT和APACHEⅡ评分均有明显差异,且MEDS评分、PCT与APACHEⅡ评分存在明显相关;MEDS评分和PCT预测死亡的ROC曲线下面积分别为0.85和0.78,MEDS的敏感性和特异性分别为80.6%和86.7%,PCT的敏感性和特异性分别为82.3%和78.4%,MEDS评分对脓毒血症预后的评估特异性优于PCT、敏感性逊于PCT;两种联合应用敏感性及特异性更高(86.3%、89.9%)。结论:MEDS评分和PCT对脓毒血症患者预后有较好的预测作用,联合使用可提高敏感性及特异性。     

Presepsin在脓毒症早期诊断和预后评估中应用价值

目的探讨血浆Presepsin水平对脓毒症的诊断和预后评估的临床意义。方法 90例脓毒症患者根据是否休克分为脓毒症组和脓毒症休克组各45例,体检健康者45例为对照组,检测并比较3组血浆Presepsin、降钙素原(procalcitonin, PCT)、高敏C反应蛋白(high-sensitivity C-reactive protein, hs-CRP)水平;比较脓毒症休克组与脓毒症组小儿危重症评分、SOFA评分、白细胞计数、血小板计数、乳酸、B型钠尿肽原水平,比较脓毒症患者中死亡者(死亡组)与存活者(存活组)血浆Presepsin、PCT和hs-CRP水平、小儿危重症评分和SOFA评分,采用Spearman相关分析Presepsin与PCT、hs-CRP、小儿危重症评分、SOFA评分的相关性;采用ROC曲线评估Presepsin、PCT、hs-CRP对脓毒症的诊断效能。结果脓毒症休克组患者血浆Presepsin[(1 581.74±1 142.54)ng/L]、PCT[(3 242.61±1 693.47)ng/L]和hs-CRP[(159.47±85.78)mg/L]水平明显高于脓毒症组[(279.78±123.57)ng/L、(2 158.96±1 529.77)ng/L、(116.74±71.85)mg/L]和对照组[(67.71±33.15)ng/L、(7.79±5.52)ng/L、(2.51±1.47)mg/L](P<0.05),脓毒症组高于对照组(P<0.05);脓毒症休克组患者SOFA评分及乳酸、B型钠尿肽原水平高于脓毒症组(P<0.05),小儿危重症评分、血小板计数、白细胞计数低于脓毒症组(P<0.05);死亡组血浆Presepsin、PCT、hs-CRP水平及小儿危重症评分、SOFA评分均明显高于存活组(P<0.05);血浆Presepsin水平与血浆PCT、hs-CRP水平、SOFA评分均呈正相关(r=0.714,P<0.001;r=0.756,P<0.001;r=0.838,P<0.001),与小儿危重症评分呈负相关(r=-2.787,P<0.001);血浆Presepsin水平诊断脓毒症的AUC(0.924)、灵敏度(72.0%)和特异度(90.0%)均高于PCT(0.684、60.0%、80.0%)和hs-CRP(0.617、50.0%、70.0%)(P<0.05)。结论检测血浆Presepsin水平有助于脓毒症的早期诊断、病情程度判断和预后评估。     

降钙素原联合血小板检测对脓毒症诊断及判断预后的临床意义

目的探讨降钙素原(PCT)联合血小板(PLT)对脓毒症的诊断及判断预后的意义。方法收集160例ICU危重全身炎症反应综合征(SIRS)患者,按脓毒症诊断标准分为脓毒症组与对照组,按是否发生脓毒性休克,将脓毒症组分为非脓毒性休克组与脓毒性休克组。所有患者急性生理学及慢性健康状况评分系统(APACHEⅡ)评分大于10分。收集入院24hAPACHEⅡ评分、序贯器官衰竭估计(SOFA)评分、白细胞(WBC)、C反应蛋白(CRP)、降钙素原(PCT)、血小板计数(PLT)情况。采用SPSS21.0统计软件进行统计分析,比较非脓毒性休克组、脓毒性休克组和对照组间的PLT、CRP、PCT差异,脓毒症组PCT、PLT与SOFA、APACHEⅡ评分的相关性采用Pearson相关分析,绘制受试者工作特征(ROC)曲线确定PCT、PLT的诊断价值。结果脓毒症组PLT明显低于对照组,脓毒性休克组PLT明显低于非脓毒性休克组,脓毒症组CRP、PCT明显高于对照组,脓毒性休克组CRP、PCT明显高于非脓毒性休克组,差异均有统计学意义(P0.05)。Pearson相关分析显示,脓毒症组PCT与SOFA、APACHEⅡ评分呈显著正相关,PLT与二者呈显著负相关。ROC曲线确定PLT≤100×10~9/L,PCT≥2.0μg/L为最佳截点值,ROC曲线下面积(AUC)分别为0.839、0.857,灵敏度分别为89.4%、87.4%,特异度分别为74.2%、69.8%。结论 PCT联合PLT对脓毒症诊断具有较高的临床意义。     

Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial

Introduction

Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT).

Methods

This is a retrospective, case–control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment.

Results

Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65).

Conclusions

In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.     

降钙素原对脓毒症患者病情及预后的临床价值

目的：探讨降钙素原（procalcitonin,PCT）对脓毒症患者病情及预后的临床价值,及其与急性生理学与慢性健康状况Ⅱ评分（APACHEⅡ评分）的相关性。方法回顾性分析2013年1月1日至2014年12月31日收住本院急诊科（包括普通病房及急诊重症监护室 EICU）、感染科的109例脓毒症患者的临床资料（包括入院24 h 内 PCT 值、白细胞计数 WBC 及中性粒细胞百分比Neut％、APACHEⅡ评分等）。据患者病情严重程度（脓毒血症组、严重脓毒症组和脓毒性休克组）、临床结局（存活组和死亡组）及多器官功能障碍综合征 MODS （MODS 组和非 MODS 组）不同进行分组,比较各组中各指标差异,分析 PCT 与 APACHEⅡ评分两者之间的相关性,评价 PCT、APACHEⅡ评分和 APACHEⅡ评分＋PCT 在评估患者预后及多器官功能障碍综合征中的价值,及分析 PCT 对脓毒症患者预后的独立效应及脓毒症患者预后的影响因素。结果脓毒血症组中 PCT 值、APACHEⅡ评分均低于严重脓毒症组和脓毒性休克组,严重脓毒症组均低于脓毒性休克组,三组之间差异均有统计学意义（P ＜0.05）。脓毒血症组中 WBC 明显低于脓毒性休克组（P ＜0.05）。死亡组较存活组中的 APACHEⅡ评分显著升高,差异有统计学意义（P ＜0.01）,而 PCT 值、WBC、Neut％在两组间则差异无统计学意义。非 MODS 组中 APACHEⅡ评分、WBC、Neut％、PCT 值均显著低于 MODS 组（均 P ＜0.05）。PCT 与 APACHEⅡ评分之间呈显著正相关关系（rs ＝0.403,P ＜0.01）。通过绘制 PCT、APACHEⅡ评分、APACHEⅡ评分＋PCT 三者的受试者工作曲线（ROC）来评估脓毒症患者预后情况,得出三者的 ROC 曲线下面积（AUC）分别为0.617、0.899、0.917,而APACHEⅡ评分、APACHE Ⅱ评分＋PCT 的预后评估价值均较 PCT 高（均 P ＜0.01）,且 PCT、APACHEⅡ评分的截断值（cut-off）、灵敏度、特异度分别为（3.40 ng／mL、88.24％、38.04％）和（20分、94.12％、81.52％）。同样 PCT、APACHEⅡ评分、APACHEⅡ评分＋PCT 三者评估脓毒症患者多器官功能障碍综合征的 AUC 分别为0.824、0.796、0.871,PCT 分别与 APACHEⅡ评分、APACHEⅡ评分＋PCT 间差异无统计学意义,且 PCT、APACHEⅡ评分的截断值、灵敏度、特异度分别为（7.26 ng／mL、88.24％、63.79％）和（17分、64.71％、87.93％）。PCT 对脓毒症患者预后的 COR、AOR 分别为1.008、1.014,性别与 APACHEⅡ评分是影响脓毒症患者预后的独立危险因素。结论 PCT 值、APACHEⅡ评分能评估脓毒症患者病情,三者间均呈正相关关系。APACHEⅡ评分、APACHEⅡ评分＋PCT 较 PCT 能更好评估患者预后,且 PCT 不能作为预后评估的独立指标;而 PCT、APACHEⅡ评分、APACHEⅡ评分＋PCT 对脓毒症患者多器官功能障碍综合征的评估效能均较好。PCT 研究需考虑混杂因素,性别与 APACHEⅡ评分是脓毒症患者预后的两个独立危险因素。     

Procalcitonin as a diagnostic marker for sepsis/septic shock in the emergency department; a study based on Sepsis-3 definition

Introduction

The recent definition of sepsis was modified based on a scoring system focused on organ failure (Sepsis-3). It would be a time-consuming process to detect the sepsis patient using Sepsis-3. Procalcitonin (PCT) is a well-known biomarker for diagnosing sepsis/septic shock and monitoring the efficacy of treatment. We conducted a study to verify the predictability of PCT for diagnosing sepsis based on Sepsis-3 definition.

Prognostic significance of hypothalamic–pituitary–adrenal axis hormones in early sepsis: a study performed in the emergency department

Purpose

The response of the hypothalamic–pituitary–adrenal (HPA) axis to the sustained stress of sepsis has been the focus of study in recent years because the early phase of sepsis is known to be dominated by major alterations in the HPA axis. This prospective observational study aimed at assessing the predictive values of copeptin and HPA hormones in determining sepsis progression and mortality in the emergency department (ED).

Methods

Serum arginine vasopressin (AVP) and copeptin concentrations were measured upon ED admission. Baseline levels of total and free cortisol and adrenocorticotrophic hormone (ACTH) were measured within 24 h of ED admission. Mortality in Emergency Department Sepsis (MEDS) score was calculated at enrollment.

Results

Our findings demonstrated that serum copeptin, baseline total cortisol, baseline free cortisol and baseline ACTH concentrations gradually increased, based upon the increasing severity of the disease (p < 0.001). Multivariate logistic regression analysis showed that copeptin and total cortisol baseline concentrations were independent predictors of septic shock (odds ratio = 1.034 and 1.355, respectively) and 28-day mortality (odds ratio = 1.039 and 1.499, respectively). The areas under the receiver operating characteristic curve (AUC) for copeptin level in prediction of septic shock was 0.856 and 28-day mortality was 0.826. Importantly, AUC analysis of the combination of copeptin, total cortisol baseline, MEDS score, and procalcitonin level resulted in a more significant prognostic ability than analysis of each parameter alone (p < 0.001).

Conclusions

Increased copeptin and HPA hormones baseline levels may provide crucial information for risk stratification in a variety of septic states in the ED. Furthermore, measurements of copeptin level and serum baseline cortisol concentration are promising independent prognostic markers for mortality in patients with severe sepsis or septic shock.     

Prognostic and diagnostic value of eosinopenia,C-reactive protein,procalcitonin, and circulating cell-free DNA in critically ill patients admitted with suspicion of sepsis

Introduction

The aims of this study were to assess the reliability of circulating cell-free DNA (cf-DNA) concentrations, compared with C-reactive protein (CRP), procalcitonin (PCT) and eosinophil count, in the diagnosis of infections in patients with systemic inflammatory response syndrome (SIRS) and their prognostic values in a cohort of critically ill patients.

Methods

We conducted a prospective cohort study in a medical-surgical intensive care unit of a university hospital. Eosinophil count and concentrations of cf-DNA, CRP, and PCT were measured in patients who fulfilled SIRS criteria at admission to the intensive care unit (ICU) and a second determination 24 hours later. DNA levels were determined by a PCR method using primers for the human beta-haemoglobin gene.

Results

One hundred and sixty consecutive patients were included: 43 SIRS without sepsis and 117 with sepsis. Levels of CRP and PCT, but not cf-DNA or eosinophil count, were significantly higher in patients with sepsis than in SIRS-no sepsis group on days 1 and 2. PCT on day 1 achieves the best area under the curve (AUC) for sepsis diagnosis (0.87; 95% confidence interval = 0.81-0.94). Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for mortality prediction was lower than that shown by APACHE II score. PCT decreases significantly from day 1 to day 2 in survivors in the entire cohort and in patients with sepsis without significant changes in the other biomarkers.

Conclusions

Our data do not support the clinical utility of cf-DNA measurement in critical care patients with SIRS. PCT is of value especially for infection identification in patients with SIRS at admission to the ICU.     

Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis

OBJECTIVE: To evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein, leukocyte count, D-dimer, and antithrombin III at onset of septic episode and 24 h later in prediction of hospital mortality in critically ill patients with suspected sepsis. DESIGN AND SETTING: Prospective, cohort study in two university hospital intensive care units. PATIENTS: 61 critically ill patients with suspected sepsis. MEASUREMENTS AND RESULTS: The outcome measure was hospital mortality. Hospital survivors ( n=41) and nonsurvivors ( n=20) differed statistically significantly on day 1 (admission) in PCT, IL-6, SOFA score, and APACHE II score, and 24 h later in PCT, IL-6, and D-dimer values. AT III, CRP, and leukocyte count did not differ. The areas under receiver operating curves showed reasonable discriminative power (>0.75) in predicting hospital mortality only for day 2 IL-6 (0.799) and day 2 PCT (0.777) values which were comparable to that of APACHE II (0.786), and which remained the only independent predictor of mortality. CONCLUSIONS: Admission and day 2 IL-6, and day 2 PCT, and day 2 D-dimer values differed significantly between hospital survivors and nonsurvivors among critically ill patients with suspected sepsis. However, in prediction of hospital mortality, only the discriminative power of day 2 PCT and IL-6 values, and APACHE II was reasonable as judged by AUC analysis (>0.75).