Procalcitonin and C-reactive protein as markers of systemic inflammatory response syndrome severity in critically ill children

OBJECTIVES: To analyse the clinical value of procalcitonin (PCT), C-reactive protein (CRP) and leucocyte count in the diagnosis of paediatric sepsis and in the stratification of patients according to severity. DESIGN: Prospective, observational study. SETTING: Paediatric intensive care unit (PICU). PATIENTS: Ninety-four children. MEASUREMENT AND RESULTS: Leucocyte count, PCT and CRP were measured when considered necessary during the PICU stay. Patients were classified, when PCT and CRP were measured, into one of six categories (negative, SIRS, localized infection, sepsis, severe sepsis, and septic shock) according to the definitions of the American College of Chest Physicians /Society of Critical Care Medicine. A total of 359 patient day episodes were obtained. Leucocyte count did not differ across the six diagnostic classes considered. Median plasma PCT concentrations were 0.17, 0.43, 0.79, 1.80, 15.40 and 19.13 ng/ml in negative, systemic inflammatory response syndrome (SIRS), localized infection, sepsis, severe sepsis, and septic shock groups, respectively, whereas median plasma CRP concentrations were 1.35, 3.80, 6.45, 5.70, 7.60 and 16.2 mg/dl, respectively. The area under the ROC curve for the diagnosis of septic patients was 0.532 for leucocyte count (95% CI, 0.462-0.602), 0.750 for CRP (95% CI, 0.699-0.802) and 0.912 for PCT (95% CI, 0.882-0.943). We obtained four groups using CRP values and five groups using PCT values that classified a significant percentage of patients according to the severity of the different SIRS groups. CONCLUSIONS: PCT is a better diagnostic marker of sepsis in critically ill children than CRP. The CRP, and especially PCT, may become a helpful clinical tool to stratify patients with SIRS according to disease severity.     

Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6

OBJECTIVE: To evaluate whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte elastase (elastase), and the C-reactive protein (CRP) determined directly after the clinical onset of sepsis or systemic inflammatory response syndrome (SIRS) discriminate between patients suffering from sepsis or SIRS and predict the outcome of these patients. DESIGN: Prospective study. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty-two patients with sepsis and 11 patients with SIRS. MEASUREMENTS AND MAIN RESULTS: The plasma concentrations of PCT, C3a, and IL-6 obtained < or =8 hrs after clinical onset of sepsis or SIRS but not those of elastase or CRP were significantly higher in septic patients (PCT: median, 16.8 ng/mL, range, 0.9-351.2 ng/mL, p = .003; C3a: median, 807 ng/mL, range, 422-4788 ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5-1004 pg/mL, p = .009, all Mann-Whitney rank sum test) compared with patients suffering from SIRS (PCT: median, 3.0 ng/mL, range, 0.7-29.5 ng/mL; C3a: median, 409 ng/mL, range, 279566 ng/mL; IL-6: median, 98 pg/mL, range, 23-586 pg/mL). The power of PCT, C3a, and IL-6 to discriminate between septic and SIRS patients was determined in a receiver operating characteristic analysis. C3a was the best variable to differentiate between both populations with a maximal sensitivity of 86% and a specificity of 80%. An even better discrimination (i.e., a maximal sensitivity of 91% and a specificity of 80%) was achieved when PCT and C3a were combined in a "sepsis score." C3a concentrations also helped to predict the outcome of patients. Based on the sepsis score, a logistic regression model was developed that allows a convenient and reliable determination of the probability of an individual patient to suffer from sepsis or SIRS. CONCLUSIONS: Our data show that the determination of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients than the variables CRP and elastase, routinely used at the intensive care unit. The determination of PCT and C3a plasma concentrations appears to be helpful for an early assessment of septic and SIRS patients in intensive care.     

Comparison of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS

OBJECTIVES: The relation of procalcitonin (PCT) plasma concentrations compared with C-reactive protein (CRP) was analyzed in patients with different severity of multiple organ dysfunction syndrome (MODS) and systemic inflammation. PATIENTS AND METHODS: PCT, CRP, the sepsis-related organ failure assessment (SOFA) score, the Acute Physiology, Age, Chronic Health Evaluation (APACHE) II score and survival were evaluated in 40 patients with systemic inflammation and consecutive MODS over a period of 15 days. RESULTS: Higher SOFA score levels were associated with significantly higher PCT plasma concentrations (SOFA 7-12: PCT 2.62 ng/ml, SOFA 19-24: PCT 15.22 ng/ml) (median), whereas CRP was elevated irrespective of the scores observed (SOFT 7-12: CRP 131 mg/l, SOFT 19-24: CRP 135 mg/l). PCT of non-surviving patients was initially not different from that of survivors but significantly increased after the fourth day following onset of the disease, whereas CRP was not different between both groups throughout the whole observation period. CONCLUSIONS: Measurement of PCT concentrations during multiple organ dysfunction syndrome provides more information about the severity and the course of the disease than that of CRP. Regarding the strong association of PCT and the respective score systems in future studies we recommend evaluation also of the severity of inflammation and MODS when PCT concentrations were compared between different types of disease.     

Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis

OBJECTIVE: To describe the course of plasma sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin (PCT), and C-reactive protein (CRP) concentrations during sepsis and their clinical informative value in predicting outcome. DESIGN: Prospective, noninterventional study. SETTING: Medical adult intensive care unit at a university hospital in France. PATIENTS: Sixty-three critically ill patients with sepsis, severe sepsis, or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Soluble TREM-1 concentrations were significantly lower at admission in nonsurvivors (n = 21) than in survivors (n = 42) (94 [30-258] vs. 154 [52-435] pg/mL, p = .02), whereas PCT levels were higher among nonsurvivors (19.2 [0.3-179] vs. 2.4 (0-254) pg/mL, p = .001). CRP levels did not differ between the two groups of patients. Plasma PCT and CRP decreased during the 14-day period of study in both survivors and nonsurvivors. Conversely, sTREM-1 plasma concentrations remained stable or even increased in nonsurviving patients and decreased in survivors. An elevated baseline sTREM-1 level was found to be an independent protective factor with an odds of dying of 0.1 (95% confidence interval, 0.1-0.8). CONCLUSION: A progressive decline of plasma sTREM-1 concentration indicates a favorable clinical evolution during the recovery phase of sepsis. In addition, baseline sTREM-1 level may prove useful in predicting outcome of septic patients.     

Soluble receptor for advanced glycation end products predicts 28-day mortality in critically ill patients with sepsis

Abstract

Objective. Multiple biomarkers are used to assess sepsis severity and prognosis. Increased levels of the soluble receptor for advanced glycation end products (sRAGE) were previously observed in sepsis but also in end-organ injury without sepsis. We evaluated associations between sRAGE and (i) 28-day mortality, (ii) sepsis severity, and (iii) individual organ failure. Traditional biomarkers procalcitonin (PCT), C-reactive protein (CRP) and lactate served as controls. Methods. sRAGE, PCT, CRP, and lactate levels were observed on days 1 (D1) and 3 (D3) in 54 septic patients. We also assessed the correlation between the biomarkers and acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute heart failure. Results. There were 38 survivors and 16 non-survivors. On D1, non-survivors had higher sRAGE levels than survivors (p = 0.027). On D3, sRAGE further increased only in non-survivors (p < 0.0001) but remained unchanged in survivors. Unadjusted odds ratio (OR) for 28-day mortality was 8.2 (95% CI: 1.02–60.64) for sRAGE, p = 0.048. Receiver operating characteristic analysis determined strong correlation with outcome on D3 (AUC = 0.906, p < 0.001), superior to other studied biomarkers. sRAGE correlated with sepsis severity (p < 0.00001). sRAGE showed a significant positive correlation with PCT and CRP on D3. In patients without ARDS, sRAGE was significantly higher in non-survivors (p < 0.0001) on D3. Conclusion. Increased sRAGE was associated with 28-day mortality in patients with sepsis, and was superior compared to PCT, CRP and lactate. sRAGE correlated with sepsis severity. sRAGE was increased in patients with individual organ failure. sRAGE could be used as an early biomarker in prognostication of outcome in septic patients.     

Procalcitonin: a valuable indicator of infection in a medical ICU?

OBJECTIVE: To assess the use of procalcitonin (PCT) for the diagnosis of infection in a medical ICU. DESIGN: Prospective, observational study. PATIENTS: Seventy-seven infected patients and 24 patients with systemic inflammatory response syndrome (SIRS) due to other causes. Seventy-five patients could be classified into sepsis (n = 24), severe sepsis (n = 27) and septic shock (n = 24), and 20 SIRS patients remained free from infection during the study. Plasma PCT and C-reactive protein (CRP) levels were evaluated within 48 h of admission (day 0), at day 2 and day 4. RESULTS: As compared with SIRS, PCT and CRP levels at day 0 were higher in infected patients, regardless of the severity of sepsis (25.2 +/- 54.2 ng/ml vs 4.8 +/- 8.7 ng/ml; 159 +/- 92 mg/l vs 71 +/- 58 mg/l, respectively). At cut-off values of 2 ng/ml (PCT) and 100 mg/l (CRP), sensitivity and specificity were 65% and 70% (PCT), 74% and 74% (CRP). PCT and CRP levels were significantly more elevated in septic shock (38.5 +/- 59.1 ng/ml and 173 +/- 98 mg/l) than in SIRS (3.8 +/- 6.9 ng/ml and 70 +/- 48 mg/l), sepsis (1.3 +/- 2.7 ng/ml and 98 +/- 76 mg/l) and severe sepsis (9.1 +/- 18. 2 ng/ml and 145 +/- 70 mg/l) (all p = 0.005). CRP, but not PCT, levels were more elevated in severe sepsis than in SIRS (p<0.0001). Higher PCT levels in the patients with four dysfunctional organs and higher PCT and CRP levels in nonsurvivors may only reflect the marked inflammatory response to septic shock. CONCLUSION: In this study, PCT and CRP had poor sensitivity and specificity for the diagnosis of infection. PCT did not clearly discriminate SIRS from sepsis or severe sepsis.     

Pancreatic stone protein as an early biomarker predicting mortality in a prospective cohort of patients with sepsis requiring ICU management

ABSTRACT: INTRODUCTION: Biomarkers, such as C-reactive protein [CRP] and procalcitonin [PCT], are insufficiently sensitive or specific to stratify patients with sepsis. We investigate the prognostic value of pancreatic stone protein/regenerating protein (PSP/reg) concentration in patients with severe infections. METHODS: PSP/reg, CRP, PCT, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1-β), IL-6 and IL-8 were prospectively measured in cohort of patients ≥ 18 years of age with severe sepsis or septic shock within 24 hours of admission in a medico-surgical intensive care unit (ICU) of a community and referral university hospital, and the ability to predict in-hospital mortality was determined. RESULTS: We evaluated 107 patients, 33 with severe sepsis and 74 with septic shock, with in-hospital mortality rates of 6% (2/33) and 25% (17/74), respectively. Plasma concentrations of PSP/reg (343.5 vs. 73.5 ng/ml, P < 0.001), PCT (39.3 vs. 12.0 ng/ml, P < 0.001), IL-8 (682 vs. 184 ng/ml, P < 0.001) and IL-6 (1955 vs. 544 pg/ml, P < 0.01) were significantly higher in patients with septic shock than with severe sepsis. Of note, median PSP/reg was 13.0 ng/ml (IQR: 4.8) in 20 severely burned patients without infection. The area under the ROC curve for PSP/reg (0.65 [95% CI: 0.51 to 0.80]) was higher than for CRP (0.44 [0.29 to 0.60]), PCT 0.46 [0.29 to 0.61]), IL-8 (0.61 [0.43 to 0.77]) or IL-6 (0.59 [0.44 to 0.75]) in predicting in-hospital mortality. In patients with septic shock, PSP/reg was the only biomarker associated with in-hospital mortality (P = 0.049). Risk of mortality increased continuously for each ascending quartile of PSP/reg. CONCLUSIONS: Measurement of PSP/reg concentration within 24 hours of ICU admission may predict in-hospital mortality in patients with septic shock, identifying patients who may benefit most from tailored ICU management.     

血浆PCT和CRP水平的动态变化对脓毒症严重程度的评估及其相关性研究

目的探讨动态监测血浆PCT和CRP水平在评估脓毒症患者严重程度的临床意义及其相关性研究。方法选择2009年9月至2011年9月我院ICU入住的脓毒症患者114例,在入科的第1,3,5,7天抽取外周血检测PCT、CRP水平,同时行血培养,根据血培养结果分为血培养阳性组和血培养阴性组,根据脓毒症严重程度分为脓毒症组、严重脓毒症组、脓毒性休克组,比较各组PCT、CRP水平有无差异及各指标之间的相关性。结果 （1）在脓毒症血培养阳性组第1、3、5、7天PCT水平及第1、3天的CRP水平明显高于血培养阴性组,ROC曲线图显示,在诊断是否存在血行性感染上,PCT具有较高的特异性和敏感性;（2）在脓毒症组、严重脓毒症组、脓毒性休克组,随着感染程度加重,PCT水平与CRP水平均呈上升趋势,以PCT和CRP来诊断严重脓毒症或脓毒性休克的ROC曲线图所示,PCT较CRP具有较高的敏感性和特异性。结论脓毒症患者血浆PCT水平较CRP水平与疾病严重程度有着更明显的相关性,动态监测PCT水平变化趋势有助于脓毒症严重程度的判断及指导治疗。     

Clinical laboratory differentiation of infectious versus non-infectious systemic inflammatory response syndrome

OBJECTIVE: To evaluate the accuracy of C-reactive protein (CRP), procalcitonin (PCT), neopterin, and endotoxin in the differential diagnosis of sepsis and non-infectious systemic inflammatory response syndrome (SIRS). METHODS: A Medline database and references from identified articles were used to perform a literature search relating to the differential diagnosis of sepsis versus non-infectious SIRS. RESULTS: CRP, PCT, and neopterin are released both in sepsis and in non-infectious inflammatory disease. CRP and PCT are equally effective, although not perfect, in differentiating between sepsis and non-infectious SIRS. However, CRP and PCT have different kinetics and profiles. The kinetics of CRP is slower than that of PCT, and CRP levels may not further increase during more severe stages of sepsis. On the contrary, PCT rises in proportion to the severity of sepsis and reaches its highest levels in septic shock. PCT tends to be higher in nonsurvivor than in survivor. Therefore, PCT demonstrated a closer correlation with the severity of sepsis and outcome than CRP. Unlike CRP and PCT, neopterin is increased in viral infection as well as bacterial infection, and neopterin is also a useful indicator of sepsis. Endotoxemia was detected in no more than half of patients with Gram-negative bacteremia, and Gram-negative bacteremia was detected in half of patients with endotoxemia. CONCLUSIONS: The diagnostic capacity of PCT is superior to that of CRP due to the close correlation between PCT levels and the severity of sepsis and outcome. Neopterin is very useful in the diagnosis of viral infection. The endotoxin assay in combination with CRP, PCT, or neopterin may help as a diagnostic marker for Gram-negative bacterial infection.     

Usefulness of procalcitonin for diagnosing complicating sepsis in patients with cardiogenic shock

Objective Patients in cardiogenic shock (CS) often present with signs of systemic inflammation that mimic infection, especially in the setting of multiple organ failure (MOF). To clarify the usefulness of procalcitonin (PCT) for diagnosing complicating sepsis in patients with CS, especially in the presence of MOF we compared PCT concentrations in patients with CS with and without MOF to those in patients with septic shock (SS).Design and setting Retrospective analysis in the cardiovascular ICU at a university hospital.Patients 40 patients with CS, 15 patients with SS, and 11 noncritically ill patients without infection.Measurements and results Infection was excluded by clinical and microbiological examination in all CS patients at the time of blood sampling. Nevertheless 35% exhibited CRP concentrations higher than 10 mg/dl and 25% PCT concentrations higher than 2 ng/ml. Median PCT concentrations were higher in CS patients than in controls but lower than in patients with SS. CS patients with MOF at the time of blood sampling exhibited higher PCT concentrations than patients without organ failure. In the pooled population of patients with CS and SS PCT had a higher area under the receiver operating characteristic curve (0.86 vs. 0.83) than CRP and a PCT concentration of 10 ng/ml or higher had greater specificity for sepsis than a PCT concentration of 2 ng/ml or higher but lower negative predictive value.Conclusions PCT concentrations above 2 ng/ml are frequently found in CS patients with MOF and do not necessarily indicate infection. PCT was slightly better than CRP for diagnosing sepsis in our study, but a PCT concentration of 10 ng/ml or higher seems to be more appropriate for diagnosing this complication in CS patients than 2 ng/ml.     

Umbilical cord blood serum procalcitonin by Time-Resolved Amplified Cryptate Emission (TRACE) technology: reference values of a potential marker of vertically transmitted neonatal sepsis.

BACKGROUND: Neonatal infection remains a major diagnostic problem because of non-specific clinical signs and symptoms, as well as low sensitivity and specificity of routine laboratory tests. C-reactive protein (CRP), white blood cell count, absolute neutrophil count and immature/total neutrophil ratio are the most widely used tests in the diagnosis of sepsis and provide useful information, but none of these has demonstrated to be reliable in detecting all septic infants. Procalcitonin (PCT) has been suggested as a potentially useful laboratory test performed in umbilical cord blood when perinatal bacterial sepsis is under investigation. METHODS: In this study, the reference interval for umbilical cord blood serum PCT was established for the first time by Time-Resolved Amplified Cryptate Emission (TRACE) technology. RESULTS: The reference interval for PCT in umbilical cord blood serum ranged from 0.04 to 0.43 microg/L in 168 non-infected newborn infants (95% CI 0.02-0.06 and 0.35-0.60 microg/L, respectively). Cord blood serum PCT correctly classified one infected patient out of 90 newborn infants at risk of vertically transmitted sepsis and identified another neonate as a potentially infected patient despite having negative blood cultures. However, cord blood CRP misclassified 21 out of the 90 patients as infected neonates. CONCLUSIONS: Cord blood PCT measured by TRACE is a potentially more useful early marker of neonatal sepsis than cord blood CRP.     

Procalcitonin as a marker for the early diagnosis of severe infection after thermal injury.

High serum concentrations of procalcitonin (PCT), the 116 amino acid precursor protein of the hormone calcitonin, have been found in patients with various bacterial infections, particularly in those with sepsis. Because recent reports have shown that serum PCT constitutes a useful parameter for the diagnosis of sepsis in patients with several clinical conditions, a temporal analysis of the PCT concentrations in the plasma of 19 patients with severe burns (median body surface area burned, 32%) was conducted retrospectively. Nine patients were classified as septic on the basis of standardized clinical and laboratory parameters. Compared with the nonseptic group, these patients showed higher plasma PCT throughout the study period (median concentrations of septic vs nonseptic patient groups: 0.4 vs. 0.2 microg/L on postburn day 2; 1.0 vs. 0.3 microg/L on postburn day 4; 5.5 vs. 0.3 microg/L on postburn day 7; 10.8 vs. 0.5 microg/L on postburn day 9; 4.2 vs. 0.4 microg/L on postburn day 12; and 1.7 vs. 0.5 microg/L on postburn day 14), with differences considered to be significant (P<.05) from day 7 on. In contrast, differences in the plasma C-reactive protein concentrations were less pronounced and never reached statistical significance. PCT concentrations exceeding 15 microg/L were only observed in the 3 patients who died of sepsis-induced multiple organ failure. In addition to absolute PCT, individual time courses were also of diagnostic value. PCT is a highly efficient laboratory parameter for the diagnosis of severe infectious complications after a burn injury.     

血浆miR-223-3p，PCT，IL-6和CRP水平联合检测对脓毒症实验诊断及预后的价值研究

目的　探讨微小核糖核酸-223-3p（miR223-3p）联合降钙素原（PCT）、白细胞介素-6（IL-6）及C反应蛋白（CRP）对脓毒症诊断及预后预测的意义。方法　选取2018年1月～2020年10月三亚市中医院和三亚中心医院收治的脓毒症患者146例,根据患者28天的生存情况,将其分为存活组（n=101）和死亡组（n=45）。选取同期60例体检健康者作为对照组。检测各组血浆miR-223-3p,PCT,IL-6及CRP水平。应用受试者工作特征（ROC）曲线分析miR-223-3p联合PCT,IL-6及CRP对脓毒症诊断及预后预测的价值。结果　脓毒症组血浆miR-223-3p（2.15±0.92 vs 0.37±0.08）,PCT（13.50±6.48 ng/ml vs 0.02±0.01ng/ml）,IL-6（74.12±15.70 pg/ml vs 5.37±1.45pg/ml）及CRP（37.26±10.15 mg/L vs 3.82±1.46mg/L）水平均明显高于对照组,差异均有统计学意义（t=8.783~14.620,P<0.001）。死亡组血浆miR-223-3p（3.04±1.16 vs 1.31±0.50）,PCT（21.28±10.28 ng/ml vs 6.72±3.15ng/ml）,IL-6（102.83±21.75 pg/ml vs 56.17±10.20pg/ml）及CRP（56.40±15.30mg/L vs 25.75±8.24mg/L）水平均明显高于存活组,差异均有统计学意义（t=7.415~16.317,均P<0.001）。ROC曲线分析显示,miR-223-3p联合PCT,IL-6及CRP诊断脓毒症的曲线下面积最大（0.905,95%CI :0.847~0.968）,其敏感度和特异度分别为92.0%和83.4%;miR-223-3p联合PCT,IL-6及CRP预测脓毒症患者死亡的曲线下面积最大（0.933,95%CI :0.875～0.990）,其敏感度和特异度为分别95.3%和87.5%。相关性分析显示,脓毒症患者血浆miR-223-3p表达水平与PCT,IL-6及CRP均呈正相关性（r=0.825,0.792,0.753,均P<0.001）。结论　脓毒症患者血浆miR-223-3p表达水平明显升高,联合PCT,IL-6及CRP检测对脓毒症的诊断及预后预测具有良好的价值。     

Discriminative value of inflammatory biomarkers for suspected sepsis

Background

Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.

Study Objectives

To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.

Methods

PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care.

Results

Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care.

Conclusions

In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.     

Is C-reactive protein a good prognostic marker in septic patients?

Rationale  Several studies have shown that C-reactive protein (CRP) is a marker of infection. The aim of this study was to evaluate CRP as marker of prognosis outcome in septic patients and to assess the correlation of CRP with severity of sepsis. Methods  During a 14-month period, we prospectively included all patients with sepsis admitted to an intensive care unit (ICU). Patients were categorized into sepsis, severe sepsis and septic shock. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, CRP, body temperature and white cell count (WCC) of the day of sepsis diagnosis were collected. Results  One hundred and fifty-eight consecutive septic patients (mean age 59 years, 98 men, ICU mortality 34%) were studied. The area under the receiver operating characteristics curves of APACHE II, SAPS II, SOFA, CRP, body temperature and WCC as prognostic markers of sepsis were 0.75 [95% confidence interval (CI) 0.67–0.83], 0.82 (95% CI 0.75–0.89), 0.8 (95% CI 0.72–0.88), 0.55 (95% CI 0.45–0.65), 0.48 (95% CI 0.38–0.58) and 0.46 (95% CI 0.35–0.56), respectively. In the subgroup of patients with documented sepsis we obtained similar results. The ICU mortality rate of septic patients with CRP < 10, 10–20, 20–30, 30–40 and >40 mg/dL was 20, 34, 30.8, 42.3 and 39.1%, respectively (P = 0.7). No correlation was found between CRP concentrations and severity of sepsis. Conclusions  In septic patients, CRP of the day of sepsis diagnosis is not a good marker of prognosis.     

Plasma endothelin-1 levels in septic patients

Dysfunction of the vascular endothelium (ET) causes an increase in serum ET-1 concentration, as observed in septic patients. It was assumed that in this patient population the ET-1 level correlates with the degree of sepsis severity, including the level of organ dysfunction and, in particular, the level of circulatory dysfunction. The aim of the present study was to assess the relationship between levels of ET-1 and levels of N-terminal brain natriuretic propeptide (NT-proBNP), procalcitonin (PCT), and C-reactive protein (CRP), as well as the Sepsis-related Organ Failure Assessment (SOFA) score in septic patients. PCT and CRP were used to estimate the level of sepsis severity; the SOFA score was used to estimate multiorgan dysfunction; and NT-proBNP was used as a marker of cardiac dysfunction. Twenty patients with sepsis and severe sepsis were included in the study. Blood serum ET-1, NT-proBNP, PCT, and CRP concentrations were determined at specific time intervals, and the SOFA score was calculated. Mean ET-1, NT-proBNP, PCT, and CRP concentrations were 8.39 pg/ml +/- 6.39 pg/mL, 140.80 pg/mL +/- 84.65 pg/mL, 22.32 ng/mL +/- 97.41 ng/mL, and 128.51 mg/L +/- 79.05 mg/L, respectively. Correlation between ET-1 levels and levels of NT-proBNP, PCT, and CRP was .3879 (P < .001), .358 (P < .001), and .225 (P = .011), respectively. Mean SOFA score was 6.31 pts +/- 3.75 pts. Correlation between the ET-1 levels and SOFA score was .470 (P < .001). Six patients (30%) died during the observation period of 28 days. ET-1 levels correlate with levels of NT-proBNP, PCT, and CRP, as well as the SOFA score in septic patients.     

脓毒症患儿血浆miR-455-5p和miR-483-5p检测的临床应用

目的 分析脓毒症（Sepsis）患儿血浆微小核糖核酸（micro RNA,miR）-455-5p和miR-483-5p检测及其临床价值。方法 选择2019年1月～2020年12月三亚市人民医院收治的108例脓毒症患儿,根据其病情严重程度分为脓毒症非休克组（n=65）和脓毒症休克组（n=43）;根据脓毒症患儿28天的生存情况,将其分为存活组（n=74）和死亡组（n=34）,另选取50例健康儿童作为对照组,检测各组血浆miR-455-5p和miR-483-5p表达水平。应用受试者工作特征曲线（ROC）分析血浆miR-455-5p,miR-483-5p及降钙素原（procalcitonin,PCT）水平对脓毒症诊断及预后评估的价值。结果 脓毒症休克组血浆miR-455-5p(4.06±1.35),miR-483-5p(3.40±1.13)及PCT(19.97±9.12μg/L)水平均明显高于脓毒症非休克组（1.95±0.81,1.38±0.57,5.73±2.36μg/L）和对照组（0.78±0.24,0.35±0.10,0.02±0.01μg/L）,差异均有统计学意义（t=12.985～2...     

Procalcitonin in patients with acute and chronic renal insufficiency

BACKGROUND: Bacterial infections are associated with a high morbidity and mortality rate in patients with acute and chronic renal failure. Because C-reactive-protein (CRP) is elevated in many patients with renal failure, even in the absence of infection, procalcitonin (PCT) might be useful for the detection of systemic bacterial infections. This cross-sectional observation study measured PCT and CRP in several groups of patients with various types, degrees and treatments of kidney diseases, including patients with sepsis treated with renal replacement therapy. PATIENTS AND METHODS: We determined PCT and CRP in 85 renal patients with different stages and treatments of renal insufficiency: chronic renal failure (CRF) n=23, patients undergoing continuous ambulatory peritoneal dialysis (CAPD) n=20, patients undergoing hemodialysis therapy (HD) n=42 and in a group of 40 patients with septic conditions, including 20 patients with acute renal failure (ARF). The infectious status of the patients was monitored. RESULTS: PCT in serum (reference value in healthy controls < 1 microg/l) was within the normal range in patients with CRF and in patients on both short-term HD (< 1 year) and long-term HD (> 1 year) (median of 0.25 microg/l and 0.61 microg/l). However, PCT was elevated in patients on CAPD (median of 1.18 microg/l). In patients with sepsis, PCT was massively elevated in both the presence and absence of ARF. In contrast, CRP (reference value < 5 mg/l) was markedly increased in patients undergoing short- and long-term HD (medians of 14.5 and 51.1 mg/l) but not in patients on CAPD. In patients with CRF and systemic bacterial infections, both PCT and CRP were markedly elevated (median PCT 63 microg/l, CRP 130 mg/l) but, in contrast to PCT, CRP values overlapped in infected and non-infected patients. There was no relevant decrease in plasma concentrations of PCT by hemofiltration or hemodialysis in patients with sepsis. CONCLUSION: With the exception of CAPD patients, PCT levels were not significantly affected by renal diseases or treatments but were markedly elevated in the presence of infections. Thus PCT is a valuable marker for early diagnosis of systemic bacterial infections in patients with CRF or patients undergoing HD. In contrast, CRP is elevated in several groups with renal diseases and has low specificity for the diagnosis of bacterial infections.     

Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock

BACKGROUND: Procalcitonin (PCT), a marker of bacterial sepsis, may also act as a mediator of the inflammatory response to infection, and thus influence outcome. OBJECTIVE: To investigate the relationship between PCT, interleukin (IL)-10, tumor necrosis factor (TNF), organ failure, and mortality in pediatric septic shock. DESIGN: Prospective observational study. SETTING: A 16-bed pediatric intensive care unit of a university hospital. PATIENTS: A total of 75 children with septic shock having a median age of 43.1 months (range, 0.1-192 months). Children who had received antibiotics for >24 hrs were excluded. A total of 37 patients (49%) had meningococcal disease, and 72 patients (96%) required mechanical ventilation. INTERVENTIONS: The pediatric risk of mortality (PRISM) score, multiple organ system failure (MOSF) score, duration of ventilation, length of ICU stay, and outcome were recorded. PCT, IL-10, and TNF were measured at admission to the intensive care unit. Sequential PCT levels were available at 0 hrs and 24 hrs in 39 patients (52%). RESULTS: Observed mortality was 21/75 (28%). Data are median (range). The admission PCT (p = .0002) and TNF levels (p = .0001) were higher in children with higher MOSF scores. In survivors and nonsurvivors, the admission PCT was 82 ng/mL vs. 273 ng/mL (p = .03), IL-10 was 62 pg/mL vs. 534 pg/mL (p = .03), and TNF was 76 pg/mL vs. 480 pg/mL (p = .001), respectively. Area under the mortality receiver operating characteristic curve was 0.73 for PCT, 0.67 for IL-10, and 0.76 for TNF, compared with 0.83 for the PRISM score. Of 39 children, 16 (41%) with sequential PCT measurements showed no fall in PCT after 24 hrs treatment. These children had higher admission levels of IL-10 (p = .03), and TNF (p = .03) compared with children who demonstrated a subsequent fall in PCT. Although the former did not have a higher median PRISM (p = .28) or MOSF score (p = .19), observed mortality was 44% (7 of 16) compared with 9% (2 of 23) (p = .02). CONCLUSION: The admission PCT, like TNF and IL-10, is related to the severity of organ failure and mortality in children with septic shock. A fall in PCT after 24 hrs of treatment may have favorable prognostic significance.     

血清降钙素原和常用炎症指标结合SOFA评分对脓毒症早期诊断和预后价值的评价

目的 结合感染相关器官功能衰竭评分(SOFA)评价血清降钙素原(PCT)和临床常用炎症指标对脓毒症的早期诊断和预后价值.方法 采用前瞻性、临床病例观察及诊断试验研究.根据美国胸科医师协会/危重病医学会(ACCP/SCCM)共识会议,严格将入选病例分为全身炎症反应综合征(SIRS)组、脓毒症组、严重脓毒症组、脓毒性休克组、非SIRS对照组.测定24 h内的炎症指标、SOFA评分及PCT浓度并进行相关分析.结果 208例患者入选,其中对照组59例,SIRS组57例,脓毒症组52例,严重脓毒症组28例,脓毒性休克组12例.血清PCT浓度与脓毒症严重程度呈正相关,Spearman相关系数为0.909(P=0.000).根据受试者工作特征曲线(ROC曲线)分析,PCT的ROC曲线下面积(AUC)为0.936±0.020,SOFA评分的AUC为0.973±0.011(P均=0.000).判断最佳诊断界值PCT为＞0.375 μg/L,SOFA评分为＞3.5分,其约登(Youden)指数分别为0.808和0.801.二分类Logistic回归分析显示,在排除了年龄、CRP混杂因素后PCT和SOFA评分与脓毒症发病明显相关,相对危险度(OR值)分别为84.794和10.761(P均=0.000),并且可以预测脓毒症的发病概率.SOFA评分是脓毒症疾病预后的最显著因子,OR值为2.084(P=0.000 2).结论 传统炎症指标和C-反应蛋白(CRP)是鉴别SIRS和非SIRS的有用指标,但不是早期诊断脓毒症的可靠指标.PCT是早期诊断脓毒症并能与SIRS鉴别的特异性较高的炎症指标;结合SOFA评分和PCT可以预测脓度症的发病概率;根据PCT值的变化,再结合SOFA评分可以客观判断脓毒症病情的严重性.SOFA评分与脓毒症预后明显相关.