Pancreatic stone protein as a novel marker for neonatal sepsis

Purpose

Early-onset sepsis (EOS) is one of the main causes for the admission of newborns to the neonatal intensive care unit. However, traditional infection markers are poor diagnostic markers of EOS. Pancreatic stone protein (PSP) is a promising sepsis marker in adults. The aim of this study was to investigate whether determining PSP improves the diagnosis of EOS in comparison with other infection markers.

Methods

This was a prospective multicentre study involving 137 infants with a gestational age of >34 weeks who were admitted with suspected EOS. PSP, procalcitonin (PCT), soluble human triggering receptor expressed on myeloid cells-1 (sTREM-1), macrophage migration inhibitory factor (MIF) and C-reactive protein (CRP) were measured at admission. Receiver-operating characteristic (ROC) curve analysis was performed.

Results

The level of PSP in infected infants was significantly higher than that in uninfected ones (median 11.3 vs. 7.5 ng/ml, respectively; p = 0.001). The ROC area under the curve was 0.69 [95 % confidence interval (CI) 0.59–0.80; p < 0.001] for PSP, 0.77 (95 % CI 0.66–0.87; p < 0.001) for PCT, 0.66 (95 % CI 0.55–0.77; p = 0.006) for CRP, 0.62 (0.51–0.73; p = 0.055) for sTREM-1 and 0.54 (0.41–0.67; p = 0.54) for MIF. PSP independently of PCT predicted EOS (p < 0.001), and the use of both markers concomitantly significantly increased the ability to diagnose EOS. A bioscore combining PSP (>9 ng/ml) and PCT (>2 ng/ml) was the best predictor of EOS (0.83; 95 % CI 0.74–0.93; p < 0.001) and resulted in a negative predictive value of 100 % and a positive predictive value of 71 %.

Conclusions

In this prospective study, the diagnostic performance of PSP and PCT was superior to that of traditional markers and a combination bioscore improved the diagnosis of sepsis. Our findings suggest that PSP is a valuable biomarker in combination with PCT in EOS.     

Cardiovascular oscillations at the bedside: early diagnosis of neonatal sepsis using heart rate characteristics monitoring

We have applied principles of statistical signal processing and nonlinear dynamics to analyze heart rate time series from premature newborn infants in order to assist in the early diagnosis of sepsis, a common and potentially deadly bacterial infection of the bloodstream. We began with the observation of reduced variability and transient decelerations in heart rate interval time series for hours up to days prior to clinical signs of illness. We find that measurements of standard deviation, sample asymmetry and sample entropy are highly related to imminent clinical illness. We developed multivariable statistical predictive models, and an interface to display the real-time results to clinicians. Using this approach, we have observed numerous cases in which incipient neonatal sepsis was diagnosed and treated without any clinical illness at all. This review focuses on the mathematical and statistical time series approaches used to detect these abnormal heart rate characteristics and present predictive monitoring information to the clinician.     

Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis

Purpose  

To assess the value of serum procalcitonin (PCT) for the differentiation between patients with and without neonatal sepsis.     

Clinical assessment of neutrophil gelatinase-associated lipocalin as a potential diagnostic marker for neonatal sepsis: a prospective cohort study

Sepsis is a life-threatening condition associated with high morbidity and mortality rates among neonates. Clinical diagnosis is limited due to the neonates’ unspecific signs and symptoms as well as the long time required to obtain the blood culture results. Consequently, there is an urgent need for new biomarkers to early diagnose neonatal sepsis. We aimed to evaluate Neutrophil Gelatinase-Associated Lipocalin (NGAL) diagnostic performance to detect neonatal sepsis. We enrolled 30 neonates with sepsis admitted to the neonatal intensive care units and 30 age- and sex-matched healthy neonates recruited from the neonatal outpatient clinic during their routine follow-up visits. We measured NGAL levels by sandwich enzyme-linked immunosorbent assay, the C-reactive protein (CRP) with nephelometry technique using BN II nephelometer, and the complete blood count by Mindray BC-6800 analysers. NGAL, CRP, TLC, haemoglobin, and platelet levels showed significant differences between cases and control (all p < .001). Of the 30 neonates with sepsis, 17 neonates (56.7%) survived. At 0 h, the NGAL level showed no statistically significant difference between the non-survivors and survivors’ groups; however, after 96 h, NGAL was significantly higher in the non-survivors group (p ˂ .001). Our diagnostic analysis showed that NGAL levels have strong discrimination power to early differentiate neonates with sepsis; at the 475.00 pg/ml cut-off value, NGAL showed both sensitivity and specificity of 100% with an area under curve of 100%. Conclusion: Our study suggests that NGAL could be a promising biomarker for neonatal sepsis detection. Further studies with larger sample sizes and survival analysis are warranted to confirm this finding and to clarify the efficacy of NGAL in survival prediction.

Key findings

• NGAL level was high in neonates with sepsis
• NGAL level was high in non-survived neonates
• NGAL could be a promising diagnostic marker for sepsis

     

Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis

The diagnosis and prognosis of sepsis after antimicrobial therapy among systemic inflammatory response syndrome (SIRS) patients were evaluated with the biomarkers procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell counts.     

Interleukin-6 as diagnostic marker for neonatal sepsis: determination of Access IL-6 cutoff for newborns

Neonatal infections are by far the most common cause of childhood morbidity and mortality. To accelerate the diagnosis of a bacterial infection, IL-6 is increasingly used in neonatal diagnostics. The advantage is the level of IL-6 rises at the onset of infection while CRP reaches the maximum concentration with a noticeable delay. This analytical study was conducted to determine the Access IL-6 immunoassay normal range in neonates on postnatal day 1. A total of 124 serum samples from newborns were collected for IL-6 determination. Only those values were accepted for normal range calculation when the children's leukocyte count and CRP were not elevated and the newborns did not receive any antibiotic medication. The median was determined as 19.5 (SD = 14.7). The minimal and maximal IL-6 value was measured as 0.10 and 113 pg/mL, respectively. The upper value of the 95% reference interval was calculated as 44.4 pg/mL with a 90% confidence interval from 30.3 to 66.4 pg/mL. The cutoff determined can now be used to measure IL-6 as a prematurely pro-inflammatory marker in neonates.     

Parametric spectral analysis of umbilical artery doppler signals for fetal heart rate variability evaluation

Objective: To improve the measurement resolution of the fetal heart rate (FHR) beat-to-beat variation, which is an important prognostic indicator of fetal well-being. Method: The goal was reached using an autoregressive (AR) approach, instead of conventional algorithms based on the Fast Fourier Transform (FFT), for the analysis of the umbilical artery Doppler signals. Results: The resolution improvement obtainable with the proposed technique in the FHR beat-to-beat variation was proved both with simulation and with experimental results. The method was implemented in a personal computer (PC) based equipment which works in a quasi-real time mode. Conclusions: The proposed technique can be usefully applied to the FHR beat-to-beat variation measurements; the developed prototype is at present used for clinical practice at the ^cClinica Ostetrica e Ginecologica' of the University of Firenze.     

Complement anaphylatoxin C3a as a novel independent prognostic marker in heart failure

Objectives

The purpose of this study was to evaluate complement activation in a heart failure cohort. Based on their powerful biological activity, we hypothesized that the levels of anaphylatoxin C3a are related to pathological signs and outcomes in heart failure.

Design, setting and patients

Complement activation products C3a and SC5b9 were determined in 182 consecutive CHF patients (single centre, prospective cohort study), with a left ventricular ejection fraction <45%. Mortality and re-hospitalisation due to the progression of CHF were assessed after a median follow-up of 14?months.

Interventions

None.

Results

In the univariate analysis, high level of anaphylatoxin C3a was significantly associated with clinical events (p?p?=?0.094). In multivariable Cox analysis, adjusted for age, NT-proBNP, diastolic blood pressure, body mass index (BMI), haemoglobin and creatinine levels, C3a was a significant predictor of HF-related re-hospitalization or death (HR 1.189 per 1-SD increase, 95% CI 1.023–1.383), and of cardiovascular events or death (HR 1.302, CI 1.083–1.566). C3a was strongly associated with the presence of peripheral oedema, inflammatory markers (CRP, prealbumin, IL-6, sTNFRI, sTNFRII), heat-shock protein 70 levels and endothelial activation markers (von-Willebrand factor and endothelin-1).

Conclusions

Results of the present study showed that complement activation is strongly linked to unfavourable outcomes in heart failure. High levels of anaphylatoxin C3a predicted re-hospitalization, cardiovascular events and mortality in adjusted survival model. Increased C3a levels were associated with biomarkers of acute-phase reaction, inflammation, cellular stress response, endothelial-cell activation and oedematous complications independently from disease severity.     

Development and characterization of a novel porcine model of neonatal sepsis

Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality. To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity. The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h. Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 +/- 3 mmHg in sepsis vs. 64 +/- 3 mmHg in control at 3 h, 38 +/- 7 mmHg in sepsis vs. 59 +/- 4 mmHg in control at 6 h, mean +/- SEM). They also showed an increase of serum levels of endotoxin (5.6 x 10 +/- 4.5 x 10 pg/mL in sepsis vs. 6.0 x 10 +/- 3.8 x 10 pg/mL in control at 6 h). Serum levels of TNF-alpha in the animals with sepsis became significantly higher than the control animals at 0 h (96 +/- 31 pg/mL in sepsis vs. 12 +/- 1 pg/mL in control) and remained significantly higher than all through the experiment. Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 +/- 231 pg/mL in sepsis in its peak at 6 h vs. 24 +/- 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups. Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms. These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.     

Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study

Introduction  

Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores.     

Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis

IntroductionNeutrophil CD64 (nCD64) expression appears to be a promising marker of bacterial infections. The aim of this meta-analysis was to assess the accuracy of nCD64 expression for the diagnosis of sepsis in critically ill adult patients.MethodsWe systematically searched PubMed, Embase, ISI Web of Knowledge, and the Cochrane Library for literature published between database inception and 19 May 2014, as well as reference lists of identified primary studies. Studies were included if they included assessment of the accuracy of nCD64 expression for sepsis diagnosis in adult patients and provided sufficient information to construct a 2×2 contingency table.ResultsA total of 8 studies comprising 1986 patients fulfilled the inclusion criteria for the final analysis. The pooled sensitivity and specificity were 0.76 (95 % confidence interval [CI], 0.73–0.78) and 0.85 (95 % CI, 0.82–0.87), respectively. The positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 8.15 (95 % CI, 3.82–17.36), 0.16 (95 % CI, 0.09–0.30), and 60.41 (95 % CI, 15.87–229.90), respectively. The area under the summary receiver operating characteristic curve of nCD64 expression with Q* value were 0.95 (Q* =0.89).ConclusionsOn the basis of our meta-analysis, nCD64 expression is a helpful marker for early diagnosis of sepsis in critically ill patients. The results of the test should not be used alone to diagnose sepsis, but instead should be interpreted in combination with medical history, physical examination, and other test results.     

Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis

CD14, a high-affinity receptor for lipopolysaccharide (LPS), is a glycoprotein expressed on the surface membranes of monocytes/macrophages. We have identified a previously unknown form of soluble CD14, named soluble CD14 subtype (sCD14-ST), that is increased in patients with sepsis. To measure sCD14-ST concentrations in plasma, we prepared anti-sCD14-ST antibodies and developed an enzyme immunoassay (EIA) for this soluble form of CD14. With this assay, quantitative measurements are available within 4 h, and we compared the levels of sCD14-ST in plasma from normal subjects (healthy controls), patients with systemic inflammatory response syndrome (SIRS), and sepsis patients. The level of sCD14-ST in subjects with sepsis was much higher than the levels in subjects with SIRS and the healthy controls. Additionally, when a subject's sCD14-ST level was used as a diagnostic marker for sepsis, the area under the receiver operating characteristic (ROC) curve was 0.817, thereby demonstrating that elevated sCD14-ST levels were a better marker for sepsis than the other molecular markers we tested. sCD14-ST levels also correlated with procalcitonin (PCT) levels and with sequential organ failure assessment (SOFA) scores. Finally, changes in sCD14-ST concentration correlated with the severity of sepsis. Taken together, these results indicate that sCD14-ST is a useful marker for the rapid diagnosis of sepsis and for monitoring the severity of the disease.     

Blood gas analysis as a surrogate for microhemodynamic monitoring in sepsis

BACKGROUND:Emergency patients with sepsis or septic shock are at high risk of death.Despite increasing attention to microhemodynamics,the clinical use of advanced microcirculatory assessment is limited due to its shortcomings.Since blood gas analysis is a widely used technique reflecting global oxygen supply and consumption,it may serve as a surrogate for microcirculation monitoring in septic treatment.METHODS:We performed a search using PubMed,Web of Science,and Google scholar.The studies and r...     

Identification of a novel marker associated with risk for delayed chemotherapy-induced vomiting

Purpose

Besides chemotherapy drugs, a number of patient-related factors (i.e., gender, age, history of alcohol consumption, and/or motion sickness) may be used to calculate the risk for chemotherapy-induced vomiting. We evaluated data with the intent of identifying a unique variable associated with delayed vomiting in patients receiving moderately emetogenic chemotherapy (MEC).

Methods

From an ongoing research study, the serotonin metabolite, 5-hydroxyindole acetic acid (5-HIAA), creatinine, and substance P were measured over a 72-h period in 25 patients receiving MEC. All patients were treated with a 5-hydroxytryptamine-3 receptor antagonist plus dexamethasone according to published guidelines; none received aprepitant prophylactically. Urine 5-HIAA/creatinine and serum substance P values were grouped according to the development (+) or absence (?) of delayed emesis. Baseline mean values associated with the two neurotransmitters were analyzed by analysis of variance.

Results

Eleven patients developed moderate to severe delayed vomiting; the other 14 were symptom-free. The pretreatment log (mean 5-HIAA/creatinine) was 1.22 and 1.81 in the (+) and (?) emesis groups, respectively, p?=?0.0049; the pretreatment log (mean substance P) for the same respective groups was 5.33 and 4.09?pg/mL, p?>?0.05. The log (mean ratio of substance P to 5-HIAA/creatinine) between-group difference in those with and without emesis was 4.53 and 2.52, respectively, p?=?0.0002. The 5-HIAA/creatinine and ratio of substance P to 5-HIAA/creatinine data were also used to determine cutoff points which resulted in the optimal predictive accuracy.

Conclusions

These preliminary findings suggest that an elevated pretreatment ratio of substance P to 5-HIAA/creatinine >70 is associated with the development of delayed vomiting induced by MEC.