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.

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.

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.

Predictive Factors Correlated with Successful Early Endoscopic Removal of Pancreaticolithiasis in Chronic Pancreatitis after Extracorporeal Shock Wave Lithotripsy.

BACKGROUND: The treatment of chronic pancreatitis (CP) and symptomatic pancreatic duct (PD) calculi often involves techniques like endoscopic retrograde cholangiopancreatography (ERCP), extracorporeal shock wave lithotripsy (ESWL), or a combination of both. However, identifying predictive factors for the successful removal of these calculi remains variable. This study aimed to determine the factors predicting successful ESWL and endoscopic removal in CP and PD calculi patients. METHODS: We examined data from CP patients who underwent complete PD calculi removal via ESWL combined with ERCP between July 2012 and 2022, and assessed baseline characteristics, imaging findings, and treatment details. Patients were categorized into early- and late-endoscopic complete removal groups (EER and LER groups, respectively). RESULTS: Of the 27 patients analyzed, 74.1% were male with an average age of 44 ± 9.6 years. EER was achieved in 74% of the patients. Patients in the EER group exhibited smaller PD calculi diameter (8.5 vs. 19 mm, p = 0.012) and lower calculus density (964.6 vs. 1313.3 HU, p = 0.041) compared to the LER group. Notably, PD stricture and the rate of PD stent insertion were not different between the groups. A calculus density threshold of 1300 HU on non-contrast CT demonstrated 71% sensitivity and 80% specificity in predicting EER. CONCLUSIONS: Smaller and low-density PD calculi may serve as predictors for successful EER, potentially aiding in the management of CP patients with PD calculi.

Kinetics and Role of Pancreatic Stone Protein and Midregional Proadrenomedullin as Predictors of Sepsis and Bacteremia in Children with Hematological Malignancies.

Background: To investigate the kinetics and prognostic value of pancreatic stone protein (PSP) and mid-regional proadrenomedullin (MR-proADM) during episodes of febrile neutropenia (FN) in children with hematological malignancies. Material and methods: We evaluated prospectively a total of 70 FN episodes in 70 children with acute leukemias and lymphomas. CRP, PSP, and MR-proADM levels were measured at the onset of the febrile episode (day 1), day 3, and day 7. The outcome and survival of children were evaluated during the study period until day 28. The performance of each marker in identifying sepsis or severe sepsis was assessed as an area under a receiver operating characteristic (ROC) curve. ROC curves were used for each biomarker to derive cut-offs for sensitivity and specificity in distinguishing sepsis from non-sepsis. Results: During the 2-year study period, 70 febrile neutropenia episodes in 70 children with hematological malignancies were enrolled. Of 70 episodes of febrile neutropenia, in 17 (24%), a bacterial/fungal infection was documented. Criteria for sepsis were fulfilled for 31 (44%) and 7 (10%) patients were admitted to PICU. The median values of all biomarkers on day 1 differed significantly between patients with and without sepsis. PSP, MR-proADM, and CRP specificity were 0.82, 0.70, and 0.57, respectively. The sensitivity of PSP, MR-proADM, and CRP were 0.84, 0.74, and 0.88, respectively. Conclusions: PSP and MR-proADM are promising biomarkers for early diagnosis of sepsis during FN episodes in children with hematological malignancies. However, PSP has a higher sensitivity and specificity.

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.

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.

The Role of Pancreatic Stone Protein (PSP) as a Biomarker of Pregnancy-Related Diseases.

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions.

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.

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.

Development and application of a novel aldehyde nanoparticle-based amplified luminescent proximity homogeneous assay for rapid quantitation of pancreatic stone protein.

BACKGROUND: Timely diagnosis of bacterial infections is important to prevent sepsis. Classical infection biomarkers have some flaws, and common detection methods are time-consuming. Thus, we aimed to establish an efficient detection method that precisely detects pancreatic stone protein (PSP) in human plasma for the timely diagnosis of bacterial infections. METHODS: Based on the novel amplified luminescent proximity homogeneous assay (AlphaLISA) method, donor and acceptor beads modified with aldehyde groups were directly coupled to the anti-PSP antibodies. PSP was quickly detected by a double-antibody sandwich method. Plasma samples from healthy individuals, bacterially infected patients, and acute-phase response patients were tested. RESULTS: The detection time of the developed method is only 5 min. The results of PSP-AlphaLISA and time-resolved fluorescence were consistent (ρ = 0.9722). The plasma PSP levels of patients with bacterial infection were significantly higher than those of acute-phase response patients and healthy individuals (P < 0.05). PSP levels in patients with bacterial infection with sepsis were significantly higher than those in patients with bacterial infection without sepsis (P < 0.05). CONCLUSIONS: The PSP-AlphaLISA exhibited excellent performance and may be applied to the differential diagnosis between bacterial infection and sepsis in patients without interference from patients with acute-phase response.

Comparison of three culture media in assessing the sensitivity of antibiotics to common foodborne microorganisms.

This study aimed to determine the antibiotic susceptibility of seven antibiotics, (Amoxicillin (AX), Ampicillin (AM), Chloramphenicol (C), Ciprofloxacin (CIP), Doxycycline (DO), Gentamicin (CN) and Neomycin (N)) on some common microorganisms that cause food poisoning. Furthermore, we aimed to compare three types of culture media in assessing antibiotics susceptibility. A sensitivity test was carried out using six bacterial isolates: Micrococcus spp., Staphylococcus aureus, Escherichia coli, Salmonella spp., Proteus mirabilis, Pseudomonas aeruginosa. These bacterial isolates were identified at the Food Microbiology Division, Public Health Laboratory using three culture media: Mueller Hinton Agar (MHA), Antibiotic Assay Medium A (AAM), and nutrient agar (NA). The results showed that all of these media are suitable to test antibiotic sensitivity. Bacterial sensitivity and resistance between these media (P≤0.01) were recorded, with significant differences found at the tested probability level.

Pancreatic stone protein point-of-care testing can reduce healthcare expenditure in sepsis.

BACKGROUND: Sepsis is a life-threatening organ dysfunction in response to infection. Early recognition and rapid treatment are critical to patient outcomes and cost savings, but sepsis is difficult to diagnose because of its non-specific symptoms. Biomarkers such as pancreatic stone protein (PSP) offer rapid results with greater sensitivity and specificity than standard laboratory tests. METHODS: This study developed a decision tree model to compare a rapid PSP test to standard of care in the emergency department (ED) and intensive care unit (ICU) to diagnose patients with suspected sepsis. Key model parameters included length of hospital and ICU stay, readmission due to infection, cost of sepsis testing, length of antibiotic treatment, antibiotic resistance, and clostridium difficile infections. Model inputs were determined by review of sepsis literature. RESULTS: The rapid PSP test was found to reduce costs by $1688 per patient in the ED and $3315 per patient in the ICU compared to standard of care. Cost reductions were primarily driven by the specificity of PSP in the ED and the sensitivity of PSP in the ICU. CONCLUSIONS: The results of the model indicate that PSP testing is cost saving compared to standard of care in diagnosis of sepsis. The abundance of sepsis cases in the ED and ICU make these findings important in the clinical field and further support the potential of sensitive and specific markers of sepsis to not only improve patient outcomes but also reduce healthcare expenditures.

Pancreatic Stone Protein as a Biomarker for Sepsis at the Emergency Department of a Large Tertiary Hospital.

Early recognition of sepsis is essential for improving outcomes and preventing complications such as organ failure, depression, and neurocognitive impairment. The emergency department (ED) plays a key role in the early identification of sepsis, but clinicians lack diagnostic tools. Potentially, biomarkers could be helpful in assisting clinicians in the ED, but no marker has yet been successfully implemented in daily practice with good clinical performance. Pancreatic stone protein (PSP) is a promising biomarker in the context of sepsis, but little is known about the diagnostic performance of PSP in the ED. We prospectively investigated the diagnostic value of PSP in such a population for patients suspected of infection. PSP was compared with currently used biomarkers, including white blood cell count (WBC) and C-reactive protein (CRP). Of the 156 patients included in this study, 74 (47.4%) were diagnosed with uncomplicated infection and 26 (16.7%) patients with sepsis, while 56 (35.9%) eventually had no infection. PSP was significantly higher for sepsis patients compared to patients with no sepsis. In multivariate regression, PSP was a significant predictor for sepsis, with an area under the curve (AUC) of 0.69. Positive and negative predictive values for this model were 100% and 84.4%, respectively. Altogether, these findings show that PSP, measured at the ED of a tertiary hospital, is associated with sepsis but lacks the diagnostic performance to be used as single marker.

Pancreatic extracorporeal shock wave lithotripsy for a patient concurrent with autosomal dominant polycystic kidney disease: a case report.

Whether pancreatic extracorporeal shock wave lithotripsy (ESWL) is safe for patients with autosomal dominant polycystic kidney disease (ADPKD) is unclear. A woman in her early 30s was admitted to our hospital because of intermittent upper abdominal pain and recurrent pancreatitis. The imaging results confirmed the diagnosis of pancreatic stones and ADPKD. We performed pancreatic ESWL using a third-generation lithotripter to pulverize the pancreatic stones. A maximum of 5000 shock waves was delivered per therapeutic session. A second session of ESWL was performed the next day. The patient developed no adverse events or complications related to pancreatic ESWL. Three years after treatment, the patient had developed no relapse of pancreatitis or abdominal pain. Shock waves do not lead to complications such as hematuria, cyst rupture, or deterioration of the inner bleeding of renal cysts. Multiple kidney cysts are not a contraindication for pancreatic ESWL.

Pancreatic Stone Protein: Review of a New Biomarker in Sepsis.

Sepsis is a life-threatening syndrome characterized by a dysregulated host response to an infection that may evolve rapidly into septic shock and multiple organ failure. Management of sepsis relies on the early recognition and diagnosis of infection and the providing of adequate and prompt antibiotic therapy and organ support. A novel protein biomarker, the pancreatic stone protein (PSP), has recently been studied as a biomarker of sepsis and the available evidence suggests that it has a higher diagnostic performance for the identification of infection than the most used available biomarkers and adds prognostic value. This review summarizes the clinical evidence available for PSP in the diagnosis and prognosis of sepsis.

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 .