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      Procalcitonin for infections in the first week after pediatric liver transplantation

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          Abstract

          Background

          Procalcitonin (PCT) has become a commonly used serum inflammatory marker. Our aim was to describe the kinetics and usefulness of serial post-operative PCT measurements to detect bacterial infection in a cohort of children immediately after pediatric liver transplantation (pLT).

          Methods

          We performed a retrospective chart review of a cohort of pLT recipients with serial serum PCT measurements in the first week following pLT. The presence of infection was determined on clinical and biological parameters. Normal PCT was defined as < 0.5 (ng/ml).

          Results

          Thirty-nine patients underwent 41 pLT. PCT was measured daily during the first week post pLT. Values first increased following surgery and then decreased, nearing 0.5 ng/ml at day seven. Peak PCT reached a median of 5.61 ng/ml (IQR 3.83-10.8). Seventeen patients were considered to have an infection. There was no significant difference in daily PCT or peak PCT between infected and non infected patients during the first post-operative week. AUC of ROC curve for PCT during first week was never higher than 0.6.

          Conclusions

          We conclude that serial PCT measurements during the first week after pLT is not useful to identify patients with bacterial infections. Rather, we propose that serum PCT may be useful after the first week post pLT.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12879-017-2234-y) contains supplementary material, which is available to authorized users.

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          Most cited references26

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          High serum procalcitonin concentrations in patients with sepsis and infection.

          High concentrations of calcitonin-like immunoreactivity have been found in the blood of patients with various extrathyroid diseases. By means of a monoclonal immunoradiometric assay for calcitonin precursors, we have measured serum concentrations of procalcitonin in patients with various bacterial and viral infections. 79 children (newborn to age 12 years) in hospital with suspected infections were investigated prospectively. 19 patients with severe bacterial infections had very high serum concentrations of procalcitonin at diagnosis (range 6-53 ng/mL) in comparison with 21 children found to have no signs of infection (baseline concentrations < 0.1 ng/mL). Serum procalcitonin values decreased rapidly during antibiotic therapy. 11 patients with peripheral bacterial colonisation or local infections without invasive sepsis and 18 (86%) of 21 patients with viral infections had concentrations within or slightly above the normal range (0.1-1.5 ng/mL). Among 9 severely burned patients studied in an intensive care unit, the post-traumatic course of procalcitonin concentrations (range 0.1-120 ng/mL) was closely related to infectious complications and acute septic episodes. Concentrations of mature calcitonin were normal in all subjects, whatever procalcitonin concentrations were found. Concentrations of a substance immunologically identical to procalcitonin are raised during septic conditions. Serum concentrations seem to be correlated with the severity of microbial invasion.
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            Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes.

            To explore the roles of peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages in sepsis-related increased procalcitonin and calcitonin gene-related peptide (CGRP) I production. Prospective, in vitro primary human cell culture study and human tissue samples gene expression analysis. University hospital research laboratories. Cells from healthy donors and septic patients. PBMCs were obtained from healthy donors. Isolation of pure monocyte cultures was performed by magnetic depletion of nonmonocyte cells from PBMCs. Adipose tissue biopsies and circulating leukocytes were collected from septic patients. Expressions of calcitonin messenger RNA and CGRP I messenger RNA were analyzed using reverse transcriptase-polymerase chain reaction and quantitative real-time polymerase chain reaction. Supernatant procalcitonin and CGRP protein content were determined by ultrasensitive chemiluminometric and radioimmunoassays, respectively. PBMCs expressed and secreted procalcitonin and CGRP within 3-5 hrs after adherence to endothelial cells or plastic surfaces. This induction was transient, as it was not detectable after 18 hrs. No calcitonin or CGRP I messenger RNA was observed in leukocytes obtained from septic patients with markedly increased serum procalcitonin concentrations. Stimulation with cytokines, endotoxin, or Escherichia coli did not induce expression of calcitonin and CGRP I messenger RNA in PBMC-derived macrophages. However, inflammatory factors released from activated macrophages induced a marked expression of procalcitonin and CGRP in co-cultured human adipocytes. The adhesion-induced, transient expression and secretion of procalcitonin and CGRP in vitro may play an important role during monocyte adhesion and migration in vivo. PBMC-derived macrophages may contribute to the marked increase in circulating procalcitonin by recruiting parenchymal cells within the infected tissue, as exemplified with adipocytes.
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              Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro.

              Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear. Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT. Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation. Thus we demonstrate for the first time that PCT is expressed in PBMCs. This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.
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                Author and article information

                Contributors
                +41 22 372 5089 , vladimir.cousin@hcuge.ch
                Kalinka.lambert@hcuge.ch
                Shahar.trabelsi@hcuge.ch
                Annick.galetto@hcuge.ch
                Klara.posfaybarbe@hcuge.ch
                Barabara.wildhaber@hcuge.ch
                Valerie.mclin@hcuge.ch
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                15 February 2017
                15 February 2017
                2017
                : 17
                : 149
                Affiliations
                [1 ]ISNI 0000 0001 0721 9812, GRID grid.150338.c, Pediatric Gastroenterology Unit, , University Hospitals Geneva, ; Rue Willy-Donzé 6, 1211 Geneva, Switzerland
                [2 ]ISNI 0000 0001 2322 4988, GRID grid.8591.5, , Faculty of Medicine, ; Geneva, Switzerland
                [3 ]ISNI 0000 0001 0721 9812, GRID grid.150338.c, Pediatric Emergency Division, , University Hospitals Geneva, ; Geneva, Switzerland
                [4 ]ISNI 0000 0001 0721 9812, GRID grid.150338.c, Pediatric Infectious Disease Unit, Department of Pediatrics, , University Hospitals Geneva & University of Geneva, ; Geneva, Switzerland
                [5 ]ISNI 0000 0001 0721 9812, GRID grid.150338.c, University Center of Pediatric Surgery of Western Switzerland, Division of Pediatric Surgery, , University Hospitals of Geneva, ; Geneva, Switzerland
                Article
                2234
                10.1186/s12879-017-2234-y
                5311857
                28201980
                5ab718e6-3261-4bd7-a3a7-85f6f9deac3c
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 December 2016
                : 31 January 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Infectious disease & Microbiology
                pediatric,children,transplantation,liver,infection,procalcitonin
                Infectious disease & Microbiology
                pediatric, children, transplantation, liver, infection, procalcitonin

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