by Josef Prazak, Irina Irincheeva, Martin J. Llewelyn,
Daiana Stolz, Luis García de Guadiana Romualdo, Rolf Graf, Theresia Reding,
Holger J. Klein, Philippe Eggimann and Yok-Ai Que
Critical Care volume 25,
Article number: 182 (2021)
Background
Accurate biomarkers to diagnose infection are lacking.
Studies reported good performance of pancreatic stone protein (PSP) to detect
infection. The objective of the study was to determine the performance of PSP
in diagnosing infection across hospitalized patients and calculate a threshold
value for that purpose.
Methods
A systematic search across Cochrane Central Register of
Controlled Trials and MEDLINE databases (1966–March 2019) for studies on PSP
published in English using ‘pancreatic stone protein’, ‘PSP’, ‘regenerative
protein’, ‘lithostatin’ combined with ‘infection’ and ‘sepsis’ found 44
records. The search was restricted to the five trials that evaluated PSP for
the initial detection of infection in hospitalized adults. Individual patient
data were obtained from the investigators of all eligible trials. Data quality
and validity was assessed according to PRISMA guidelines. We choose a
fixed-effect model to calculate the PSP cut-off value that best discriminates
infected from non-infected patients.
Results
Infection was confirmed in 371 of 631 patients. The median
(IQR) PSP value of infected versus uninfected patients was 81.5 (30.0–237.5)
versus 19.2 (12.6–33.57) ng/ml, compared to 150 (82.70–229.55) versus 58.25
(15.85–120) mg/l for C-reactive protein (CRP) and 0.9 (0.29–4.4) versus 0.15
(0.08–0.5) ng/ml for procalcitonin (PCT). Using a PSP cut-off of
44.18 ng/ml, the ROC AUC to detect infection was 0.81 (0.78–0.85) with a
sensitivity of 0.66 (0.61–0.71), specificity of 0.83 (0.78–0.88), PPV of 0.85 (0.81–0.89)
and NPV of 0.63 (0.58–0.68). When a model combining PSP and CRP was used, the
ROC AUC improved to 0.90 (0.87–0.92) with higher sensitivity 0.81 (0.77–0.85)
and specificity 0.84 (0.79–0.90) for discriminating infection from
non-infection. Adding PCT did not improve the performance further.
Conclusions
PSP is a promising biomarker to diagnose infections in
hospitalized patients. Using a cut-off value of 44.18 ng/ml, PSP performs
better than CRP or PCT across the considered studies. The combination of PSP
with CRP further enhances its accuracy.
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