Scientific Papers

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

Study population

This was a prospective longitudinal pilot study, 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 [8]. 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.

The diagnosis of sepsis was based on SIRS plus proven infection. The 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 Film Array 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 the incidence of mortality, the length of stay (LOS) in PICU and in hospital.

External adjudication committee

An independent external adjunction committee composed of 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 the PSP blood levels on days 1, 2, 3, 5 and 7 from the onset of clinical signs and symptoms indicating systemic inflammation in pediatric patients at their first admission in PICU, emergency room or pediatric ward depending on the severity of the clinical picture. PSP levels were determined on 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 min. 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 the blood levels of White Blood Cells, C reactive Protein, Procalcitonin and Ferritin and PELOD-2 score. Procalcitonin was determined by 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 the accuracy of PSP in the 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 the accuracy of PSP in diagnosis of sepsis in comparison to C-RP and procalcitonin ones. b) to measure the predictive accuracy of PSP for patients’ survival in comparison to procalcitonin and C-RP; c) to measure the correlation between PSP and PELOD-2 score in children admitted to PICU.

Statistical analysis

Continuous variables data are expressed as mean and standard deviation, median and Interquartile range (IQR), while counts and frequencies are used for the categorical ones. Comparisons between groups were performed by chi-square test or Mann Whitney test, as appropriate.

The diagnostic performances of PSP, PCR, PCT were assessed by the area under the curve (AUC) plotting receiver operating characteristic (ROC) curves designed to differentiate between the patients with sepsis and the patients without which we also considered the survival time observed with a 40 days follow-up. Optimal cut-off values were selected as the values that maximize the sum of sensitivity and specificity.

We determined the diagnostic accuracy, the sensitivity, the specificity and the predictive values, using the Wilson method to obtain the likelihood ratios with the 95% Confidence interval.

All tests were two-tailed. All p-values < 0.05 were considered statistically significant. Analyses were performed using R version 4.0.1 (The R Project for Statistical Computing).

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