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.

Radial incision and cutting combined with balloon dilation for refractory pancreaticojejunostomy anastomotic strictures

Background and study aims Endoscopic balloon dilation (BD) and temporary stent placement for pancreaticojejunostomy anastomotic stricture (PJAS) achieves good short-term outcomes; however, stricture recurrences remain frequent. We examined the feasibility of performing radial incision and cutting (RIC) combined with BD for refractory PJAS. Patients and methods Five consecutive patients with refractory PJAS who underwent RIC with BD between 2015 and 2018 were retrospectively investigated. We evaluated the technical and clinical success, adverse event (AE), and recurrence rates associated with RIC with BD. Results In all five patients, technical and clinical success were achieved. Pancreatic stone removal was simultaneously performed in one patient. The mean procedure time was 18 minutes (range 12–23 minutes). There were no procedure-related AEs. All patients were followed for over 2 years, with a mean follow-up period of 33 months (range 24–40 months). During the follow-up period, none of the patients developed stricture recurrence and all anastomoses remained patent. Conclusions This is the first report of RIC with BD for the treatment of refractory PJAS, showing favorable results. This combined procedure might be a useful option for treating refractory PJAS.

Serial Measurement of Pancreatic Stone Protein for the Early Detection of Sepsis in Intensive Care Unit Patients: A Prospective Multicentric Study

BackgroundThe 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).MethodsThis 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 associations 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.ResultsOf the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3–8 days). The association of clinical sepsis diagnosis with an increase in a biomarker value in the 3 days preceding this diagnosis was stronger for PSP (p = 0.003) than for PCT (p = 0.025) and CRP (p = 0.009). 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).ConclusionsWhile the diagnostic accuracy for sepsis of PSP, CRP and PCT were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary for a clinical diagnosis the 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 registrationThe 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