Accuracy of Pancreatic Stone Protein for diagnosis of sepsis in children admitted to pediatric intensive care or high-dependency care: a pilot study

doi:10.21203/rs.3.rs-3111225/v1

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Research Article

Accuracy of Pancreatic Stone Protein for diagnosis of sepsis in children admitted to pediatric intensive care or high-dependency care: a pilot study

https://doi.org/10.21203/rs.3.rs-3111225/v1

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Journal Publication

published 07 Oct, 2023

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Background

Pancreatic Stone Protein (PSP) is one of the most promising diagnostic and prognostic marker. The aim of the study was to assess the accuracy of PSP, compared to C-Reactive Protein (CRP), and Procalcitonin (PCT) for diagnosis of sepsis in pediatric patients. Furthermore, we explored the correlation of PSP levels with sepsis severity and organ failure measured with PELOD-2 score.

Methods

40 pediatric patients were enrolled following admission to pediatric intensive care, high dependency care or pediatric ward. Blood levels of PSP were measured in Emergency Department (nanofluidic point-of-care immunoassay; abioSCOPE, Abionic SA, Switzerland) on day 1, 2, 3, 5 and 7 from the onset of the clinical signs and symptoms of sepsis or SIRS. Inclusion criteria were: 1) patient age (1 month to 18 years old), 2) signs and symptoms of SIRS, irrespective of association with organ dysfunction. Exclusion criteria were: 1) hemato-oncological diseases and/or immunodeficiencies, 2) pancreatic diseases.

Results

Septic patients showed higher PSP levels than patients with systemic inflammation of no infectious etiology. The optimal cut off in diagnosis of sepsis for PSP at day 1 was 167 ng/ml resulted in a sensitivity 59% (95% IC 36% − 79%) and a specificity 83% (95% IC 58%-96%) with an AUC of 0.636 for PSP in comparison AUC of 0.722 for PCT and 0.503 for C-RP. ROC analysis for outcome (survival versus no survival) has showed AUC 0.814 for PSP; AUC 0.814 for PCT; AUC of 0.657 for C-RP.

Conclusions

PSP could distinguish sepsis cases versus systemic inflammation of no infective etiology; however, our results need to be confirmed in larger pediatric population.

Biomarker

Pediatric Sepsis

Pediatric Septic shock

Procalcitonin

C-Reactive protein

Sepsis represents one of the major causes of morbidity and mortality in children, with 1.2 million cases per year (1) and a mortality rate between 4 to 50% (2), with most of deaths occurring during the first 48–72 hours from sepsis onset (3). Diagnostic biomarkers serve to establish the presence or absence of a clinical condition: this is the most common class of biomarkers when considering sepsis, wherein there is substantial interest in developing biomarkers that can distinguish between infection and noninfectious systemic inflammation. Traditional microbiological cultures obtained from blood or other body fluids remain the gold standard. While specific, they can lack sensitivity and there is typically a significant delay between obtaining cultures and generating actionable data. Furthermore, biomarkers that provide a reliable, early estimate of the likelihood of bacterial infection before culture results are available would obviate the risk of treatment of unnecessary antibiotics (4)

Currently only procalcitonin (PCT) has Food and Drug Administration approval for diagnosis of sepsis (3)(5) However, when comparing the diagnostic accuracy of PCT and CRP there is a trade-off between sensitivity and specificity and authors reported different diagnostic performance depending on the clinical context (5).

Among emerging biomarkers, Pancreatic Stone Protein (PSP) is one of the most promising diagnostic and prognostic marker of sepsis. It belongs to the family of lectin-binding proteins secreted by acinar pancreatic cells, beta-insular cells, intestinal Paneth cells and fundic gastric cells. In animal models a rise of serum PSP occurred in all stressed conditions irrespective of pancreatic damage (6). A review published in 2018 reported that the sensitivity of PSP was comparable to that of CRP and PCT, and that its specificity was better than that of PCT in discriminating between “infected” and “inflamed” patients, underlining the possibility of a bed-side dosage (7)

Aim of our study was firstly to assess accuracy of PSP in diagnosis of sepsis in pediatric patients admitted to pediatric intensive care, high dependency care or general pediatric ward; secondly, we explored the ability of PSP to indicate severity of illness and to predict the risk of mortality.

Study population

Prospective longitudinal pilot study. The study was approved by Ethical Committee of Children Hospital Bambino Gesù (n°1103). Parents or child’s next of kin signed the consent form to participate to the study.

Between July 2021 and November 2021, we enrolled pediatric patients admitted to the Children Hospital Bambino Gesù in two departments (emergency department − 6 PICU beds, 12 emergency room beds and the 26 general pediatric ward beds - and infectious disease department − 21 beds).

Inclusion criteria were: 1) children aged between > 1 month and < 18 years; 2) signs and symptoms of Systemic Inflammation Response Syndrome (SIRS) associated or not to organ dysfunction defined according the International Pediatric Sepsis Consensus Conference criteria (9). Exclusion criteria were: 1) pediatric patients affected by hemato-oncological diseases, and/or immunodeficiencies; 2) pediatric patients affected by pancreatic diseases; 3) refused consent by parents. All data were anonymized.

Diagnosis of sepsis was based on SIRS plus proven infection. A proven infection was defined by: 1) a positive culture from a sterile body fluid and/or 2) a rapid molecular identification of microorganisms from sterile body fluids by use of FilmArray or T2 Bacteria Panel; and/or imaging suggestive for an infection). Categorization in sepsis, severe sepsis or septic shock was made on the International Pediatric Sepsis Consensus Conference criteria (8).

To measure the severity of the organ dysfunction in children admitted to the Pediatric Intensive care Unit PELOD-2 score was adopted (9). A follow-up of 40 days starting from recruitment was performed to monitor incidence of mortality, length of PICU stay and length of hospital stay.

External adjudication committee

An independent external adjunction committee composed by two infectiologist members of the study team (MDL and LR) retrospectively and independently reviewed case report forms for each patient and determined whether a septic event had occurred during the patients’ stay. The committee members had access to all case report forms including results of all microbiological investigations but were blinded to PSP levels.

Blood sampling and measurement of plasma biomarkers

We measured blood levels of PSP on days 1, 2, 3, 5 and 7 from the onset of clinical signs and symptoms indicating systemic inflammation in pediatric patients for the first time admitted in PICU, emergency room or pediatric ward depending on the severity of the clinical picture. PSP levels were determined from 50 uL of K2-EDTA anticoagulated venous whole blood samples with the CE-marked IVD PSP CAPSULE on the point-of-care abioSCOPE® device (Abionic SA, Epalinges, Switzerland). The abioSCOPE® is a portable tabletop system that reads capsules containing nanofluidic biosensors to quantify PSP in 7.5 minutes. The system is comprised of a compact optical measurement unit, a mechatronic system for capsule handling and positioning, an embedded software including data management, connectivity, an interface for human-machine interaction and to display the results.

At the same time points of PSP measurements, we measured blood levels of White Blood Cells, C reactive Protein, Procalcitonin and Ferritin and PELOD-2 score. Procalcitonin was determined with electrochemiluminescence immunoassay “ECLIA” (Elecsys BRAHMS PCT, COBAS e801, ROCHE). C-reactive protein was measured by immunoturbidimetric assay (Tina-quant C Reactive Protein IV, COBAS c 702, ROCHE). Ferritin was measured with electrochemiluminescence immunoassay “ECLIA”: (Elecsys Ferritin, COBAS e801, ROCHE). White Blood Cells were determined with ADVIA 2120 Hematology System (Siemens Healthineers).

Study outcome

The primary outcome of the study was to measure accuracy of PSP in diagnosis of sepsis, severe sepsis and septic shock in pediatric patients admitted to PICU or high dependency pediatric units. Secondary outcomes included: a) to measure accuracy of PSP in diagnosis of sepsis in comparison to C-RP and procalcitonin. b) to measure accuracy of PSP in diagnosis of outcome (survival versus no survival) in comparison to procalcitonin and CRP; c) to measure a correlation between PSP and PELOD-2 score in children admitted to PICU.

Statistical analysis

Data are expressed as mean and standard deviation, median and Interquartile range (IQR) for continuous variables and counts and frequencies and for categorical ones. Comparison between groups was performed by chi square test or Mann Whitney test, as appropriate.

The diagnostic performance of PSP, PCR, PCT were assessed by the area under the curve (AUC) plotting receiver operating characteristic (ROC) curves that were designed to differentiate between the patients with sepsis and the patients without sepsis, we consider also the outcome measured with a follow-up till 40 days (survived/not survived). Optimal cut-off values were chosen to maximize the sum of sensitivity and specificity.

We calculated diagnostic accuracy measure, sensitivity, specificity, predictive values, likelihood ratios with the 95% Confidence interval (Wilson method).

All tests were two-tailed, and a value of P < .05 was considered as statistically significant. Analyses were performed using R version 4.0.1 (The R Project for Statistical Computing).

Baseline characteristics and PSP levels

During the study period 40 pediatric patients were enrolled: in Table 1 are reported the main characteristics (age, sex, site of infection, etiology, diagnosis and outcome) of the cohort. 45% of the patients had a non-infection etiology of the systemic inflammation (Table 2) and 55% had a diagnosis of sepsis with different severity according to the pediatric sepsis definition (8). The great majority of septic patients had a focus of infection in the respiratory tract (8/22 pulmonary 36.4%) and in 7/22 (31.8%) we have observed a combined etiology. Outcome measured with a follow-up till 40 days evidenced: 34 patients survived and 6 deceased, a median length of PICU stay days 9 [IQR 3–14,25] and a median length of hospital stay days 9.5 [IQR 3,75 − 16,5]. Table 3 reports relationship between etiology of infection and severity of clinical picture in patients with sepsis. The median PELOD-2 score for those patients admitted to PICU was 3 (0–5).

Table 1

shows demographic, infective and prognostic characteristics of the pediatric population observed.
Parameter	Survival (n = 34)	Non Survival (n = 6)	All (n = 40)
Age
• Infants	13 (38%)	1 (17%)	14 (35%)
• Pre-scholar	8 (24%)	1 (17%)	9 (22,5%)
• Scholar	4 (12%)	2 (33%)	6 (15%)
• Adolescents	0	2 (33%)	11 (27,5%)
Sex
• Female	18 (53%)	5 (83%)	23 (57,5%)
• Male	16 (47%)	1 (17%)	17 (42,5%)
Site of infection
• Blood Stream	1 (3%)	2 (33%)	3 (7,5%)
• Respiratory tract	8 (24%)	0 (0%)	8 (20%)
• Abdomen	1 (3%)	0 (0%)	1 (2,5%)
• Other	3 (9%)	0 (0%)	3 (7,5%)
• Combined	5 (15%)	2 (33%)	7 (17,5%)
• None	16 (47%)	2 (33%)	18 (45%)
Etiology
• Bacterial	5 (15%)	1 (17%)	6 (15%)
• Viral	4 (12%)	1 (17%)	5 (12,5%)
• Combined	9 (26%)	2 (33%)	11 (27,5%)
• None	16 (47%)	2 (33%)	18 (45%)
Diagnosis
• SIRS	9 (26%)	0 (0%)	9 (22,5%)
• SIRS and Organ Dysfunction	7 (21%)	2 (33%)	9 (22,5%)
• Sepsis	6 (18%)	0 (0%)	6 (15%)
• Severe sepsis	9 (26%)	1 (17%)	10 (25%)
• Septic shock	3 (9%)	3 (50%)	6 (15%)
Lenght of PICU stay median [Q1-Q3]	7,5 [2,25–13]	14,5 [11–18,75]	9 [3–14,25]
Lenght of Hospital stay median [Q1-Q3]	12 [6,25 − 18,25]	0,5 [0–1]	9,5 [3,75 − 16,5]
PELOD − 2 median [Q1-Q3]	3 [0–4,8]	6 [2,8–8,5]	3 [0–5]

Table 2

In Table 2 are reported causes of systemic inflammation of no infectious etiology.
Etiology of SIRS	n° of patients
trauma/politrauma	4 (23)
cerebral hemorrhage	2 (23)
solid tumor	1 (23)
inflammatory/reumatologic disease	2 (23)
respiratory failure in central hypoventilation	1 (23)
chemical/inflammatory pneumonia	3 (23)
fever of unknow origin	10 (23)

Table 3

In Table 3 are showed the relationship between microbiological and sepsis characteristics of the sepsis patients.
Variable	Sepsis N = 6	Severe sepsis N = 10	Septic shock N = 6	Total N = 22
Etiology
Bacterial	4	1	1	6
Polymicrobial	0	6	5	11
Viral	2	3	0	5
Focus
Blood stream	1	0	2	3
Pulmonary	2	6	0	8
Abdominal	1	0	0	1
Combined	1	2	4	7
Other	1	2	0	3

The median concentrations of PSP at different time points were 88,00 ng/mL (day 1) [range 19–601; IQR range 58,50-318.8]; 104,00 ng/mL (day 2) [range 19–601; IQR range 51.7–268.2]; 119,00 ng/mL (day 3) [range 19–601; IQR range 54.0-261.0]; 135,00 ng/mL (day 5) [range 19–601; IQR range 66.0-311.0]; 171,50 ng/mL (day 7) [range 19–601; IQR range 47.5-278.5] ng/ml. Median concentrations of PSP in relation to the diagnosis of SIRS of infectious etiology (sepsis) versus SIRS without a no infectious etiology and to the severity of illness were 140.0 ng/mL (sepsis) [IQR range 58.0- 200.2]; 92,5 ng/mL (severe sepsis) [IQR range 55.2- 156.7]; 454 ng/mL (septic shock) [IQR range 428.8–483.0]; 62.5 ng/mL (SIRS) [IQR range 27.0–68.0]; 129 ng/mL (SIRS plus organ dysfunction) [IQR range 111.0- 452.0].

Relationship between Biomarkers levels and diagnosis of sepsis

PSP concentration was correlated with PCT (Rho = 0.648; p < 0.001); with Ferritin (Rho = 0.350; p = 0.184); with White Blood Cells (Rho = 0.139; p = 0.491). In Fig. 1 are showed box plots of PSP, CRP and PCT median value at different time points and in relation to the diagnosis of SIRS versus sepsis. The median values at day 1 showed with receiving operating curve (ROC) analysis an Area Under the Curve (AUC) of 0.636 for PSP; AUC of 0.722 for PCT; AUC of 0.503 for C-RP (Fig. 2a). Based on ROC analyses the optimal cut-off in diagnosis of sepsis for PSP at day1 was of 167 ng/ml resulted in in a sensitivity 59% (95% IC 36% − 79%) and a specificity 83% (95% IC 58%-96%)

For the three biomarkers (PSP, PCT, and C-RP) ROC analysis was performed based on the median of the measures at different time points. The area under the curve (AUC) was 0.739 for PSP; AUC for PCT was 0.754; AUC for C-RP was 0.468 (Fig. 2b). The corresponding optimal cut-off for PSP in the diagnosis of sepsis was 166 ng/ml, resulting in a sensitivity of 54% (95%CI: 32% − 76%) and a specificity of 83% (95%CI: 59% − 96%).

Table 4 reports diagnostic performance of biomarkers (day 1 and median times) in distinguishing sepsis fromnon-sepsis in the analyzed population.

Table 4

shows diagnostic performance of biomarkers including median time of five timepoints (T1 = day 1, T2 = day 2, T3 = day 3, T4 = day 5, T5 = day 7) and the median of timepoint 1 (T1 = day 1) in distinguishing sepsis patients from non sepsis patients. PSP = Pancreatic Stone Protein; C-RP = C reactive protein; PCT = procalcitonin. AUC = Area Under the Curve; CI = confince interval; PPV = positive predictive value; NPV = negative predictive value;LR + = positive likelihood ratio.
Marker	AUC 95%CI	Cut-off	Sensitivity 95%CI	Specificity 95%CI	PPV 95%CI	NPV 95%CI	LR+ 95%CI
PSP Median value	0.636 (0.457–0.815)	166.0	0.54 (0.32, 0.75)	0.83 (0.58, 0.96)	0.80 (0.51, 0.95)	0.60 (0.38, 0.78)	3.7 (1.2, 11.2)
C-RP Median value	0.503 (0.316–0.689)	7.08	0.45 (0.24, 0.67)	0.72 (0.46, 0.90)	0.66 (0.38, 0.88)	0.52 (0.31, 0.72)	2.0 (0.83, 4.8)
PCT Median value	0.722 (0,556-0.888)	1.6	0.63 (0.40, 0.82)	0.83 (0.58, 0.96)	0.82 (0.56, 0.96)	0.65 (0.42, 0.83)	4.67 (1.58, 13.77)
PSP T1	0.739 (0.578–0.899)	167.0	0.59 (0.36, 0.79)	0.83 (0.58, 0.96)	0.81 (0.54, 0.96)	0.62 (0.40 0.81)	2.80 (1.24, 6.30)
C-RP T1	0.468 (0.284–0.653)	6.2	0.54 (0.32, 0.75)	0.55 (0.30, 0.78)	0.60 (0.36, 0.80)	0.50 (0.27, 0.72)	1.50 (0.79, 2.86)
PCT T1	0.754 (0.583–0.924)	1.1	0.71 (0.47, 0.88)	0.76 (0.50, 0.93)	0.78 (0.54, 0.93)	0.68 (0.43, 0.87)	3.20 (1.47, 6.96)

Relationship between Biomarkers levels and outcome (survival versus no survival)

PSP concentration was correlated with PELOD-2 score (Rho = 0.404; p = 0.056). Figure 3 shows box plots of distribution of PSP, CRP and PCT median values at different time points and in relation to the outcome survival versus no survival. ROC analysis for outcome has showed: AUC 0.814 for PSP; AUC 0.814 for PCT; AUC of 0.657 for C-RP (Fig. 4). Based on ROC analyses of all median values at different time-points the optimal cut-off to predict outcome for PSP was 421.0 resulted in a sensitivity 83% and a specificity 85%.

Table 5 reports diagnostic performance of biomarkers (median time) in distinguishing survival from no survival in population analyzed.

Table 5

shows diagnostic performance of biomarkers including median of five timepoints (T1 = day 1, T2 = day 2, T3 = day 3, T4 = day 5, T5 = day 7) in distinguishing survival from no survival in paediatric patients observed. PSP = Pancreatic Stone Protein; C-RP = C reactive protein; PCT = procalcitonin. AUC = Area Under the Curve; CI = confidence interval; PPV = positive predictive value; NPV = negative predictive value; LR + = positive likelihood ratio.
Marker	AUC 95%CI	Cut-off	Sensitivity 95%CI	Specificity 95%CI	PPV 95%CI	NPV 95%CI	LR+ 95%CI
PSP Median value	0.814 (0.584-1.000)	421	0.833 (0.359, 0.996)	0.853 (0.689, 0.950)	0.500 (0.187, 0.813)	0.967 (0.828, 0.999)	5.667 (2.339, 13.731)
PCR Median value	0.657 (0.355–0.958)	15.1	0.500 (0.118, 0.882)	0.882 (0.725, 0.967)	0.429 (0.099, 0.816)	0.909 (0.757, 0.981)	4.250 (1.255, 14.391)
PCT Median value	0.814 (0.633–0.994)	14.4	0.667 (0.223, 0.957)	0.853 (0.689, 0.950)	0.444 (0.137, 0.788)	0.935 (0.786, 0.992)	4.533 (1.688, 12.171)

In this pilot study we have explored accuracy of PSP in diagnosis of sepsis in children and we have shown as also in pediatric setting PSP could be a promising bedside biomarker that can help clinicians with a point of care technology to rapidly evaluate an infective etiology of systemic inflammatory response syndrome.

Schlapbach et al. have described normal values of PSP in different age groups in healthy children, including neonates, showing an age-dependent increase of PSP from birth to childhood ranging from 1.0 to 16.1 ng/ml (10). The authors in this latter study used an ELISA methodology to measure PSP (10), instead we used point of care test with nanofluidic technology: based on the method comparison there is a 4.6 fold between two methods (11).

PSP has been also investigated in neonatal sepsis showing a performance comparable or superior to other biomarkers (PCT, CRP) (12). Furthermore, PSP has been evaluated alone or in combination with other inflammatory biomarker in critically ill children to predict outcome, showing a correlation with the illness severity and 28-day mortality (13) (14).

Many publications have shown in adult population high accuracy of PSP in diagnosis of sepsis and to predict mortality. Currently, from the analysis of the available literature regarding PSP, it is not possible, however, to identify a cut-off value for the early diagnosis of sepsis. A unique feature of PSP is that it can begin to increase above the normal range of levels before the development of clinical signs and symptoms of sepsis. In a pivotal study, serial measurements of PSP in multiple trauma patients identified patients who were developing sepsis prior to the ascent of other biomarkers and prior to clinical diagnosis, in most cases (15). In a population of patients with sepsis-related complications, PSP levels have demonstrated high diagnostic accuracy for discriminating peritonitis severity and predicting ICU mortality (16). In another study, PSP levels reflected organ dysfunction and predicted death in ventilator-associated pneumonia (VAP), which allowed for stratification of patients with good and poor outcome (17). The value of PSP to predict in-hospital mortality in patients with severe sepsis and septic shock who require intensive care management was further demonstrated by Que et al., who also highlighted in another research that a model combining severity scores with PCT and PSP improves the prediction of mortality in these patients (18).

We have founded an optimal Youden cut off for PSP of 167 ng/ml for diagnostic accuracy of sepsis at timepoint 1 (day 1) resulting in a in sensitivity 59% but with a specificity 83% equal to PCT. For each patient, the values of the three biomarkers were highly fluctuating among different time points potentially related also to the impact of antimicrobials therapies. Therefore to have more robust data we have summarized the five measures by the median value and it is interesting to observe that we have found almost the same cut off (167 ng/ml versus 166 ng/ml) for timepoint 1 (day 1) and the median of the five timepoints during the study time.

Previous studies have not found significant difference in PSP values in pediatric patient with SIRS of infectious etiology (sepsis) versus SIRS without a no infectious etiology when a clinical condition of severe organ dysfunction was present (13). We have founded instead a higher AUC in diagnosis of sepsis versus no-sepsis in the median of all timepoint of observation, thus also in those children who showed clinical evolution with multiple organ dysfunction from the admission to timepoint 7. ROC analysis for outcome (survival versus no survival) has evidenced also a performance of PSP equal to PCT. We have found an optimal cut-off of 421 ng/ml to predict mortality in our pediatric population with a sensitivity 83% and a specificity 85%. Jiri et al observed a cut off value of 858 to best discriminate pediatric patients with PELOD < 12 and 12 and higher (13), but in our population PELOD-2 score median values were lower (median values 6), thus we were not able to show strong relationship between PSP values and high values of PELOD-2 score.

We have observed higher PSP values in median of patients with sepsis and septic shock in comparison to those pediatric patients with SIRS and SIRS associated to organ dysfunction. Severe sepsis median values of PSP resulted inferior to sepsis, we conjecture that this result could be related the etiology of the infection (viral infections versus bacterial infections), but further studies on larger population are required to confirm this hypothesis. Furthermore, we have to consider that definition of severe sepsis was recently abolished in adult population with new SEPSIS-3 criteria, thus a low clinical feasibility of this categorization should be considered.

Strengths of our study are that for the first time we have explored accuracy of PSP in diagnosis of sepsis versus no sepsis pediatric patients admitted to the hospital with signs and symptoms of systemic inflammation associated or not to organ failure. We have also evaluated patients with multiple time points during a period of observation of 7 days which is an appropriate time in evaluating the incidence and evolution of a sepsis clinical picture. We have also showed as PSP could be used as a Point Of Care Technology which could be a major advantage for clinicians at bedside.

Our study has also some limits, firstly it is a preliminary pilot study with a need of a confirmative study in larger pediatric population, furthermore future studies on more patients will allow to better explore the role of PSP also in pediatric population in diagnosis of localized infections versus sepsis or in relation to the microbiological etiology of the infection.

To the best of our knowledge this is the first study on a pediatric population about the accuracy of PSP in diagnosis of sepsis. From our preliminary results PSP could distinguish sepsis cases versus systemic inflammation of no infective etiology, but in our small population shows a relatively low sensitivity. Studies on a larger population are warranted to confirm our initial results.

PSP

Pancreatic Stone Protein

CRP

C-Reactive Protein

PCT

Procalcitonin

PICU

Pediatric Intensive Care Unit

SIRS

Systemic Inflammation Response Syndrome

ROC

Receiver Operating Characteristic

AUC

Area Under the Curve (AUC)

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Availability of data and materials

All data analyzed and discussed in the framework of this study are included in this published article. The corresponding author may provide specified analyses or fully de‐identified parts of the dataset upon reasonable request.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

No funds to declare.

Authors' contributions

All the authors gave a substantial contribution to the conception of the work, the acquisition, analysis and interpretation of the data. GB drafted the work with EP, MDL and LR. MC, MP, AG, LG, GZ and CG followed data collection in emergency department, pediatric ward and pediatric intensive care. ARV, DAF and MCDA performed statistical analysis. CC, LL, OP interpreted the data. AOM, AV and MR, revised it critically. All the authors approved the version to be published. All the authors have approved the submitted version of the manuscript and have agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

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Accuracy of Pancreatic Stone Protein for diagnosis of sepsis in children admitted to pediatric intensive care or high-dependency care: a pilot study

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Journal Publication

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Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Study population

External adjudication committee

Blood sampling and measurement of plasma biomarkers

Study outcome

Statistical analysis

Results

Baseline characteristics and PSP levels

Relationship between Biomarkers levels and diagnosis of sepsis

Relationship between Biomarkers levels and outcome (survival versus no survival)

Discussion

Conclusions

Abbreviations

Declarations

References

Status:

Journal Publication

Version 1