Diagnostic accuracy of pancreatic stone protein in patients with sepsis: a systematic review and meta-analysis.

BACKGROUND: Sepsis is a common syndrome of multiorgan system dysfunction secondary to the dysregulated inflammatory response to infection. The role of pancreatic stone protein (PSP) in diagnosing sepsis has been investigated in previous studies. The meta-analysis aimed to comprehensively investigate the diagnostic value of PSP in identifying sepsis. METHODS: PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), were systematically searched. Studies investigating the diagnostic performance of PSP were included. Pooled sensitivity, specificity, positive Likelihood Ratio (+ LR) and negative Likelihood Ratio (-LR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (SROC) were calculated. RESULTS: The sensitivity of PSP was 0.88 (95% CI: 0.77-0.94), and the pooled specificity was 0.78 (95% CI: 0.65-0.87). Pooled + LR, -LR, and DOR were 4.1 (2.3, 7.3), 0.16 (0.07, 0.34), and 26 (7, 98). The AUC value for the SROC of PSP was 0.90 (0.87, 0.92). The pooled sensitivity, specificity, + LR and - LR, and DOR for PSP among neonates were 0.91 (95% CI: 0.84, 0.96), 0.66 (95% CI: 0.58, 0.74), 3.97 (95% CI: 0.53, 29.58), 0.13 (95% CI: 0.02, 1.00), and 31.27 (95% CI: 0.97, 1004.60). CONCLUSIONS: This study indicates that PSP demonstrated favorable diagnostic accuracy in detecting sepsis. Well-designed studies are warranted to ascertain the value of PSP measurement to guide early empirical antibiotic treatment, particularly in neonates.

Diagnostic and Prognostic Ability of Pancreatic Stone Protein: A Scoping Review.

Pancreatic stone protein (PSP) is an acute-phase reactant mainly produced in response to stress. Its diagnostic and prognostic accuracy for several types of infection has been studied in several clinical settings. The aim of the current review was to assess all studies examining a possible connection of pancreatic stone protein levels with the severity and possible complications of patients diagnosed with infection. We performed a systematic search in PubMed, Scopus, the Cochrane Library and Clinicaltrials.gov to identify original clinical studies assessing the role of pancreatic stone protein in the diagnosis and prognosis of infectious diseases. We identified 22 eligible studies. Ten of them provided diagnostic aspects, ten studies provided prognostic aspects, and another two studies provided both diagnostic and prognostic information. The majority of the studies were performed in an intensive care unit (ICU) setting, five studies were on patients who visited the emergency department (ED), and three studies were on burn-injury patients. According to the literature, pancreatic stone protein has been utilized in patients with different sites of infection, including pneumonia, soft tissue infections, intra-abdominal infections, urinary tract infections, and sepsis. In conclusion, PSP appears to be a useful point-of-care biomarker for the ED and ICU due to its ability to recognize bacterial infections and sepsis early. Further studies are required to examine PSP's kinetics and utility in specific populations and conditions.

Prognostic and diagnostic utility of pancreatic stone protein in pediatric sepsis and mortality.

Background/aim: Early detection and prognosis of sepsis in critically ill children is crucial. The aim of this research was to investigate the prognostic ability of pancreatic stone protein (PSP) in validating sepsis and predicting mortality in a prospective observational study. Materials and methods: In a single-center study, pediatric intensive care unit patients were divided into cohorts of confirmed and suspected sepsis, as well as survivors and nonsurvivors. Patients with positive blood culture growth were considered to have confirmed sepsis, while their negative counterparts were considered to have suspected sepsis. Comparisons were made between complete blood counts, laboratory parameters, mortality indices, and C-reactive protein (CRP), procalcitonin (PCT), and PSP levels. The correlations between PSP and alternative inflammatory markers and mortality indices were then analyzed. The diagnostic and prognostic applicability of PSP for sepsis confirmation and mortality prediction was assessed using receiver operating characteristic curve analysis. Results: PSP levels were significantly elevated in patients with confirmed sepsis and within the nonsurvivor segment. In confirming sepsis and predicting mortality, PSP outperformed CRP and PCT in terms of sensitivity. It had sensitivity of 95% in diagnosing sepsis at a cut-off level of 50 ng/L, with an area under the curve (AUC) of 0.67 (95% CI: 0.52-0.81), and sensitivity of 92% in predicting mortality, with an AUC of 0.71 (95% CI: 0.56-0.83). In addition, PSP showed significant correlations with CRP, PCT, and mortality scores. Conclusion: PSP is emerging as a highly sensitive marker for confirming sepsis and predicting mortality in critically ill pediatric patients. Incorporating the PSP biomarker into routine clinical practice could potentially improve the management of pediatric sepsis.

Measurement of Pancreatic Stone Protein Compared with C-Reactive Protein and Procalcitonin in the Diagnosis of Sepsis in an Intensive Care Unit: A Systematic Review.

Sepsis remains a significant challenge in the intensive care unit (ICU), with prompt diagnosis and management being critical to improving patient outcomes. Biomarkers have emerged as valuable tools for identifying and predicting sepsis outcomes, with pancreatic stone protein (PSP), procalcitonin (PCT) and C-reactive protein (CRP) as three promising candidates. This systematic review aimed to analyse and compare the diagnostic accuracy of PSP, PCT and CRP regarding sepsis in the ICU. A review of the literature on the diagnostic performance of the three biomarkers was performed using PubMed Central, PubMed, ScienceDirect, Oxford Academic, SpringerLink and Cochrane Library. Data regarding the diagnostic accuracy of the three biomarkers were extracted, compared, and represented as the area under the curve (AUC) receiver operating characteristics (ROC). Three studies examining PSP, PCT and CRP biomarkers in 858 adult patients admitted to the ICU were included in this review. Compared with PCT and CRP, the PSP biomarker, with its unique applications and properties that may potentially benefit patients, doctors and hospitals, performed well and proved reliable in diagnosing sepsis in adult patients. PSP demonstrated reliability in sepsis diagnosis. Further analysis should be conducted to establish a formal, appropriate indication, as well as to determine a suspected sepsis patient's condition when testing each biomarker.

Discriminative performance of pancreatic stone protein in predicting ICU mortality and infection severity in adult patients with infection: a systematic review and individual patient level meta-analysis.

BACKGROUND: Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection. METHODS: A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using 'pancreatic stone protein', 'PSP', 'regenerative protein', 'lithostatin' combined with 'infection' and 'sepsis' found 46 records. The search was restricted to the five trials that measured PSP using the enzyme-linked immunosorbent assay technique (ELISA). We used Bayesian hierarchical regression models for pooled estimates and to predict mortality or disease severity using PSP, C-Reactive Protein (CRP) and procalcitonin (PCT) as main predictor. We used statistical discriminative measures, such as the area under the receiver operating characteristic curve (AUC) and classification plots. RESULTS: Among the 678 patients included, the pooled ICU mortality was 17.8% (95% prediction interval 4.1% to 54.6%) with a between-study heterogeneity (I-squared 87%). PSP was strongly associated with ICU mortality (OR = 2.7, 95% credible interval (CrI) [1.3-6.0] per one standard deviation increase; age, gender and sepsis severity adjusted OR = 1.5, 95% CrI [0.98-2.8]). The AUC was 0.69 for PSP 95% confidence interval (CI) [0.64-0.74], 0.61 [0.56-0.66] for PCT and 0.52 [0.47-0.57] for CRP. The sensitivity was 0.96, 0.52, 0.30 for risk thresholds 0.1, 0.2 and 0.3; respective false positive rate values were 0.84, 0.25, 0.10. CONCLUSIONS: We found that PSP showed a very good discriminative ability for both investigated study endpoints ICU mortality and infection severity; better in comparison to CRP, similar to PCT. Combinations of biomarkers did not improve their predictive ability.

Point-of-care pancreatic stone protein measurement in critically ill COVID-19 patients.

INTRODUCTION: Pancreatic stone protein (PSP) is a novel biomarker that is reported to be increased in pneumonia and acute conditions. The primary aim of this study was to prospectively study plasma levels of PSP in a COVID-19 intensive care unit (ICU) population to determine how well PSP performed as a marker of mortality in comparison to other plasma biomarkers, such as C reactive protein (CRP) and procalcitonin (PCT). METHODS: We collected clinical data and blood samples from COVID-19 ICU patients at the time of admission (T0), 72 h later (T1), five days later (T2), and finally, seven days later. The PSP plasma level was measured with a point-of-care system; PCT and CRP levels were measured simultaneously with laboratory tests. The inclusion criteria were being a critical COVID-19 ICU patient requiring ventilatory mechanical assistance. RESULTS: We enrolled 21 patients and evaluated 80 blood samples; we found an increase in PSP plasma levels according to mixed model analysis over time (p < 0.001), with higher levels found in the nonsurvivor population (p < 0.001). Plasma PSP levels achieved a statistically significant result in terms of the AUROC, with a value higher than 0.7 at T0, T1, T2, and T3. The overall AUROC of PSP was 0.8271 (CI (0.73-0.93), p < 0.001). These results were not observed for CRP and PCT. CONCLUSION: These first results suggest the potential advantages of monitoring PSP plasma levels through point-of-care technology, which could be useful in the absence of a specific COVID-19 biomarker. Additional data are needed to confirm these results.

Role of Pancreatic Stone Protein as an Early Biomarker for Risk Stratification of Acute Pancreatitis.

BACKGROUND: Early risk stratification of acute pancreatitis is crucial to improve clinical outcomes. The objective of this study was to evaluate the ability of pancreatic stone protein (PSP) to predict acute pancreatitis severity and to compare it with the biomarkers and severity scores currently used for that purpose. PATIENTS AND METHODS: Prospective single-center observational study enrolling 268 adult patients with acute pancreatitis. Biomarkers including PSP were measured upon admission to the Emergency Department and severity scores as SOFA, PANC-3, and BISAP were computed. Patients were classified into mild-moderate (non-severe) and severe acute pancreatitis according to the Determinant-Based Classification Criteria. Area under the curve (AUC) and regression analysis were used to analyze the discrimination abilities and the association of biomarkers and scores with severity. RESULTS: Two hundred and thirty-five patients (87.7%) were classified as non-severe and 33 (12.3%) as severe acute pancreatitis. Median [IQR] PSP was increased in patients with severe acute pancreatitis (890 µg/L [559-1142] vs. 279 µg/L [141-496]; p < 0.001) and it was the best predictor (ROC AUC: 0.827). In multivariate analysis, PSP and urea were the only independent predictors for severe acute pancreatitis and a model combining them both ("biomarker model") showed an AUC of 0.841 for prediction of severe acute pancreatitis, higher than the other severity scores. CONCLUSIONS: PSP is a promising biomarker for predicting the severity of acute pancreatitis upon admission. A model combining PSP and urea might further constitute a potential tool for early risk stratification of this disease.

Accuracy of pancreatic stone protein for the diagnosis of infection in hospitalized adults: a systematic review and individual patient level meta-analysis.

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.

Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study.

BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .

Pancreatic stone protein - sepsis and the riddles of the exocrine pancreas.

Pancreatic stone protein (PSP), discovered in the 1970ies, was first associated with stone formation during chronic pancreatitis. Later, the same protein was independently detected in islet preparations and named regenerating protein 1 (REG1). Additional isoforms of PSP, including pancreatitis-associated protein (PAP), belong to the same protein family. Although the names indicate a potential function in stone formation or islet regeneration, involvements in cellular processes were only suggestive and never unequivocally proven. We established an association between PSP levels in patient blood samples and the development of sepsis. In this review, written in connection with receiving the Lifetime Achievement Award of the European Pancreatic Club, the evolution of the sepsis aspect of PSP is described. We conclude that the true functional properties of this fascinating pancreatic protein still remain an enigma.

Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia.

Background Early diagnosis of infection is essential for the initial management of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this study, we have evaluated two emerging infection biomarkers, pancreatic stone protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of differentiation 25 (sCD25), for the detection of an infectious cause in FN, in comparison with other commonly used infection biomarkers, such as procalcitonin (PCT). Methods A total of 105 cancer patients presenting to the emergency department were prospectively enrolled. We observed 114 episodes of chemotherapy-associated FN. At presentation, a blood sample was collected for the measurement of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these markers for the diagnosis of infection, the area under the curve (AUC) of the receiver operating characteristic curves was calculated. Results Infection was documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher in infected patients. PCT was the biomarker with the highest diagnostic accuracy for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance, with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and sCD25 were shown to be independently associated with infection. Conclusions Two novel biomarkers, PSP and sCD25, correlated with infection in cancer patients with chemotherapy-associated FN, but neither PSP nor sCD25 improved the performance of PCT. Based on the results obtained, the introduction of these novel biomarkers as a tool for the diagnosis of infection in this patient group is not recommended.

Pancreatic stone protein and soluble CD25 for infection and sepsis in an emergency department.

BACKGROUND: Infection is a common problem in emergency departments (EDs) and is associated with high mortality, morbidity and costs. Identifying infection in ED patients can be challenging. Biomarkers can facilitate its diagnosis, enabling an early management and improving outcomes. In the critical care setting, two emerging biomarkers, pancreatic stone protein (PSP) and soluble CD25 (sCD25), have demonstrated to be useful for diagnosis of sepsis. We aimed to assess the diagnostic value of these biomarkers, in comparison with procalcitonin (PCT), for infection and sepsis in an ED population with suspected infection. MATERIALS AND METHODS: Through a prospective, observational study, we investigated the utility of serum PCT, PSP and sCD25 levels, measured on admission, for diagnosis of infection and sepsis, defined according to the recently updated for sepsis (Sepsis-3), in patients presenting to the ED for suspected infection. Diagnostic accuracy was evaluated by using receiver operating characteristic curves (ROC) analysis. RESULTS: Of the 152 patients enrolled in this study, 129 had a final diagnosis of infection, including 82 with noncomplicated infection and 47 with sepsis. Median PCT, PSP and sCD25 levels were significantly higher in patients with infection and sepsis. The ROC curve analysis revealed a similar diagnostic accuracy for infection (ROC area under the curve (AUC) PCT: 0·904; sCD25: 0·869 and PSP: 0·839) and for sepsis (ROC AUC: PCT: 0·820; sCD25: 0·835 and PSP: 0·872). CONCLUSIONS: Pancreatic stone protein and sCD25 perform well as infection and sepsis biomarkers, with a similar performance than PCT, in ED patients with suspected infection. Further larger studies investigating use of PSP and sCD25 are needed.

[Value of Procalcitonin, High Sensitivity C-reactive Protein and Pancreatic Stone Protein in Predicting Prognosis of Children with Sepsis].

OBJECTIVES: To determine the value of procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP) and pancreatic stone protein(PSP) in predicting the prognosis of children with sepsis. METHODS: A total of 106 hospitalized children [(4.4±1.6) year-old] with sepsis were enrolled in this study. The expressions of PTC, hs-CRP and PSP in the serum samples of the children were detected on the first day of admission to hospital. Pearson correlation analyses were performed to test the correlations between pediatric critical illness score (PCIS) and PTC, hs-CRP and PSP. Logistic regression models were established to determine factors predicting death of children. The value of PTC, hs-CRP and PSP in predicting the prognosis of children with sepsis was determined using ROC curves. RESULTS: About 32% children (34 cases) died. Higher expressions of PTC, hs-CRP and PSP were found in those who died (P<0.001). Serum PTC, hs-CRP and PSP were negatively correlated with PCIS (P<0.001). The multivariate logistic regression showed that PTC, hs-CRP and PSP were independent predictors of death in patients with sepsis (P<0.001). PTC, hs-CRP and PSP had an area under the curve (AUC) value of 0.86[ (95% confidence interval (CI), 0.78-0.92], 0.70 (95%CI, 0.61-0.79) and 0.69 (95%CI, 0.60-0.78) , respectively.The AUC value increased (P<0.001) to 0.92 (95%CI, 0.85-0.96) when the three indicators were combined (0.481×PCT+0.392×hs-CRP +0.314*PSP), with a value of less than 122.3 indicating good prognosis in 28 d. CONCLUSIONS: Serum PTC, hs-CRP and PSP can predict prognosis of children with sepsis.

Pancreatic stone protein - a possible biomarker of multiorgan failure and mortality in children sepsis.

Pancreatic stone protein (PSP)/regenerating protein 1-alpha (reg) is associated with inflammation, infection, and other disease-related stimuli. The prognostic value of PSP/reg among critically ill pediatric patients is unknown. The aim of this pilot study was to evaluate PSP/reg in children with systemic inflammatory response syndrome or sepsis. Prospective observational study, a five day evaluation period in children 0-19years old with systemic inflammatory response syndrome or septic state. Blood tests to determine levels of PSP/reg were obtained as long as the patient met the criteria for systemic inflammatory response syndrome or sepsis. PSP/reg levels did not differ between patients with systemic inflammatory response syndrome and septic condition until organ dysfunction signs were present. PSP/reg levels were significantly higher in patients with a PELOD score of 12 or higher or in those with MODS. Patients who died tended to have higher PSP/reg levels.

The Possible Pathophysiological Role of Pancreatic Stone Protein in Sepsis and Its Potential Therapeutic Implication.

According to the current understanding of the pathophysiology of sepsis, key host dysregulated responses leading to organ failure are mediated by innate immunity, through interactions between pathogen-associated molecular patterns (PAMPs) and damaged-associated molecular patterns (DAMPs) binding to four types of pattern recognition receptors (PRRs). PRRs activation triggers the protein kinase cascade, initiating the cellular response seen during sepsis. Pancreatic stone protein (PSP), a C-type lectin protein, is a well-defined biomarker of sepsis. Studies have shown that stressed and immune-activated pancreatic ß-cells secrete PSP. Animal studies have shown that PSP injection aggravates sepsis, and that the disease severity score and mortality were directly correlated with the doses of PSP injected. In humans, studies have shown that PSP activates polymorphonuclear neutrophils (PMNs) and aggravates multiple organ dysfunction syndrome. Clinical studies have shown that PSP levels are correlated with disease severity, vasopressor support, progression to organ failure, mechanical ventilation, renal replacement therapy, length of stay, and mortality. As PSP is a C-type lectin protein, it may have a role in activating innate immunity through the C-type lectin receptors (CLRs), which is one of the four PRRs. Herein, we review the literature on PSP and its possible role in the pathophysiology of sepsis, and we discuss its potential therapeutic role.

Diagnostic and Prognostic Utilities of Pancreatic Stone Protein in Patients with Suspected Sepsis.

Background/Objectives: Pancreatic stone protein (PSP) is an emerging biomarker of sepsis that is secreted from pancreas sensing remote organ damages. We explored the diagnostic and prognostic utilities of PSP in patients with suspected sepsis. Methods: In a total of 285 patients (suspected sepsis, n = 148; sepsis, n = 137), we compared PSP with procalcitonin (PCT) and sequential organ failure assessment (SOFA) score. Sepsis diagnoses were explored using receiver operating characteristic curve analyses with area under the curves (AUCs). Clinical outcomes (in-hospital mortality, 30-day mortality, and kidney replacement therapy [KRT]) were explored using the Kaplan-Meier method and a multivariate analysis with hazard ratio (HR). Results: PCT and PSP were comparable for sepsis diagnosis (AUC = 0.71-0.72, p < 0.001). The sepsis proportion was significantly higher when both biomarkers increased than when either one or both biomarkers did not increase (89.0% vs. 21.3-47.7%, p < 0.001). Each biomarker quartile (Q1-Q4) differed significantly according to their SOFA score (all p < 0.001). Compared with Q1, the Q2-Q4 groups showed worse clinical outcomes (p = 0.002-0.041). Both biomarkers added to the SOFA score showed higher HRs than the SOFA score alone (3.3-9.6 vs. 2.8-4.2, p < 0.001-0.011), with nearly 2.5-fold higher HR (9.6 vs. 4.2) for predicting KRT. Conclusions: Although PCT and PSP did not independently predict clinical outcomes in the multivariate analysis, PSP demonstrated diagnostic and prognostic utilities in patients with suspected sepsis, especially for predicting kidney dysfunction. PSP, alone or in combination with PCT, would be a valuable tool that can be added to clinical assessments.

Examining pancreatic stone protein response in ICU-acquired bloodstream infections: a matched event analysis.

BACKGROUND: Pancreatic stone protein (PSP) exhibits potential as a plasma biomarker for infection diagnosis and risk stratification in critically ill patients, but its significance in nosocomial infection and intensive care unit (ICU)-acquired bloodstream infection (BSI) remains unclear. This study explores the temporal responses of PSP in ICU-acquired BSI caused by different pathogens. METHODS: From a large cohort of ICU patients, we selected episodes of ICU-acquired BSI caused by Gram-negative rods (GNRs), enterococci, or Candida species. Events were matched on length of ICU stay at infection onset, Severe Organ Failure Assessment (SOFA) score, presence of immune deficiency, and use of renal replacement therapy. PSP concentrations were measured at infection onset (T0) and at 24, 48 and 72 h prior to infection onset as defined by the first occurrence of a positive blood culture. Absolute and trend differences in PSP levels between pathogen groups were analysed using one-way analysis of variance. Sensitivity analyses were performed in events with a new or worsening systematic inflammatory response based on C-reactive protein, white cell count and fever. RESULTS: We analysed 30 BSI cases per pathogen group. Median (IQR) BSI onset was on day 9 (6-12). Overall, PSP levels were high (381 (237-539) ng/ml), with 18% of values exceeding the assay's measurement range. Across all 90 BSI cases, there was no clear trend over time (median change 34 (- 75-189) ng/ml from T-72 to T0). PSP concentrations at infection onset were 406 (229-497), 350 (223-608), and 480 (327-965) ng/ml, for GNR, enterococci, and Candida species, respectively (p = 0.32). At every time point, absolute PSP levels and trends did not differ significantly between pathogens. PSP values at T0 correlated with SOFA scores. Eighteen (20%) of 90 BSI events did not exhibit a systemic inflammatory response, primarily in Candida species. No clear change in PSP concentration before BSI onset or between-group differences were found in sensitivity analyses of 72 cases. CONCLUSIONS: Against a background of overall (very) high plasma PSP levels in critically ill patients, we did not find clear temporal patterns or any pathogen-specific differences in PSP response in the days preceding onset of ICU-acquired BSI.

Evaluation of the Kinetics of Pancreatic Stone Protein as a Predictor of Ventilator-Associated Pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe condition. Early and adequate antibiotic treatment is the most important strategy for improving prognosis. Pancreatic Stone Protein (PSP) has been described as a biomarker that increases values 3-4 days before the clinical diagnosis of nosocomial sepsis in different clinical settings. We hypothesized that serial measures of PSP and its kinetics allow for an early diagnosis of VAP. METHODS: The BioVAP study was a prospective observational study designed to evaluate the role of biomarker dynamics in the diagnosis of VAP. To determine the association between repeatedly measured PSP and the risk of VAP, we used joint models for longitudinal and time-to-event data. RESULTS: Of 209 patients, 43 (20.6%) patients developed VAP, with a median time of 4 days. Multivariate joint models with PSP, CRP, and PCT did not show an association between biomarkers and VAP for the daily absolute value, with a hazard ratio (HR) for PSP of 1.01 (95% credible interval: 0.97 to 1.05), for CRP of 1.00 (0.83 to 1.22), and for PCT of 0.95 (0.82 to 1.08). The daily change of biomarkers provided similar results, with an HR for PSP of 1.15 (0.94 to 1.41), for CRP of 0.76 (0.35 to 1.58), and for PCT of 0.77 (0.40 to 1.45). CONCLUSION: Neither absolute PSP values nor PSP kinetics alone nor in combination with other biomarkers were useful in improving the prediction diagnosis accuracy in patients with VAP. CLINICAL TRIAL REGISTRATION: Registered retrospectively on August 3rd, 2012. NCT02078999.

Serum Pancreatic Stone Protein Reference Values in Healthy Pregnant Women: A Prospective Cohort Study.

BACKGROUND: In non-pregnant populations, pancreatic stone protein (PSP) has been reported to have a higher diagnostic performance for identifying severe inflammatory and infectious disease than other established biomarkers. OBJECTIVE: To generate reference values for serum PSP in pregnancy and compare them to the values of the general healthy population. DESIGN: A prospective cohort study. SETTING: A single center. POPULATION: Healthy women with singleton and multiple pregnancies. METHODS: This is a prospective single-center cohort study. Between 2013 and 2021, samples of 5 mL peripheral blood were drawn from 440 healthy pregnant women. Therein, 393 cases were singletons and 47 were multiple pregnancies. Serum PSP levels were measured by specific enzyme-linked immunosorbent assay. The main outcome measures were serum PSP level (ng/mL) reference values in healthy pregnant women. RESULTS: The mean PSP reference values in women with singleton pregnancies were 7.9 ± 2.6 ng/mL (95% CI; 2.69-13.03 ng/mL). The PSP values in women with multiple pregnancies (9.17 ± 3.06 ng/mL (95% CI; 3.05-15.28 ng/mL)) were significantly higher (p = 0.001). The PSP values in the first trimester (6.94 ± 2.53 ng/mL) were lower compared to the second (7.42 ± 2.21 ng/mL) and third trimesters (8.33 ± 2.68 ng/mL, p = 0.0001). Subgroup analyses in singletons revealed no correlations between PSP values, maternal characteristics, and pre-existing medical conditions. CONCLUSION: The PSP values in healthy pregnant women (4-12 ng/mL) were in the range of the reference values of the general healthy population (8-16 ng/mL). This insight blazes a trail for further clinical studies on the use of PSP as a potential novel biomarker for the early detection of pregnancy-related diseases such as chorioamnionitis.

The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure.

Introduction: Multiple organ dysfunction syndrome (MODS) is common in patients with sepsistic admitted to an intensive care unit (ICU) and greatly increases mortality. Pancreatic stone protein/regenerating protein (PSP/Reg) is a type of C-type lectin protein that is overexpressed during sepsis. This study aimed to evaluate the potential involvement of PSP/Reg in MODS development in patients with sepsis. Materials and methods: The relationship between circulating PSP/Reg levels, patient prognosis, and progression to MODS was analyzed in patients with sepsis admitted to the ICU of a general tertiary hospital. Furthermore, to examine the potential involvement of PSP/Reg in sepsis-induced MODS, a septic mouse model was established per the cecal ligation and puncture procedure, randomized into three groups, and subjected to a caudal vein injection of recombinant PSP/Reg at two different doses and phosphate-buffered saline. Survival analyses and disease severity scoring were performed to evaluate the survival status of the mice; enzyme-linked immunosorbent assays were performed to detect the levels of inflammatory factors and organ-damage markers in murine peripheral blood; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to measure apoptosis levels in lung, heart, liver, and kidney tissue sections and to visualize the degree of organ damage in the mouse model; myeloperoxidase activity assay, immunofluorescence staining, and flow cytometry were performed to detect neutrophil infiltration levels in vital murine organs and the activation indexes of neutrophils. Results and discussion: Our findings indicated that Circulating PSP/Reg levels were correlated with patient prognosis and sequential organ failure assessment scores. Furthermore, PSP/Reg administration increased disease severity scores, shortened survival time, increased the TUNEL-positive staining rate, and increased the levels of inflammatory factors, organ-damage markers, and neutrophil infiltration in the organs. Neutrophils can be activated by PSP/Reg to an inflammatory state, both in vivo and in vitro, which is characterized by the increased levels of intercellular adhesion molecule 1 and CD29. Conclusion: Patient prognosis and progression to MODS can be visualized by monitoring PSP/Reg levels upon ICU admission. Additionally, PSP/Reg administration in animal models exacerbates the inflammatory response and severity of multiorgan damage, which may be accomplished by promoting the inflammatory state of neutrophils.