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PIVKA-II: A biomarker for diagnosing and monitoring patients with pancreatic adenocarcinoma.
Tartaglione, S, Mancini, P, Viggiani, V, Chirletti, P, Angeloni, A, Anastasi, E
PloS one. 2021;(5):e0251656
Abstract
BACKGROUND Pancreatic adenocarcinoma (PDAC) is an incurable cancer without adequate tumor markers. Our previous study has showed a better diagnostic performance of Protein Induced by Vitamin K Absence II (PIVKA-II) compared to currently used PDAC biomarkers. To corroborate our previous data with a larger sample size and to assess a possible role of PIVKA-II in predicting surgical success. Additionally, to further evaluate the hypothesis of a direct PIVKA-II production by PDAC cells, we examined PIVKA-II tissue expression in a case of PDAC using immunofluorescence. METHODS We enrolled 76 newly diagnosed PDAC patients and selected 11 patients to determine PIVKA-II levels also after surgical resection. An immunofluorescence (IF) study of PIVKA-II tissue expression was carried out in one of them. PIVKA-II serum values were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Belgium). RESULTS PIVKA-II serum levels were above the cut-off at baseline in 71 patients (94%) with a median value of 464 mAU/Ml (range 27-40783 mAU/mL); the sensitivity and specificity were 78.67% and 90.67% respectively. Patients with pre-operative PIVKA-II positivity showed a significant decrease (P < 0.015) of median PIVKA-II serum concentrations after surgery: 820 (91-40783) mAU/mL at diagnosis vs 123 (31-4666) mAU/mL post-operatively. IF assay on PDAC sections demonstrated PIVKA-II expression in cancer cells. CONCLUSION These data are the first showing a decreased PIVKA-II serum levels after surgery in PDAC patients and reporting PIVKA-II expression in PDAC tissue. Further studies are needed to confirm these findings and to determine PIVKA-II usefulness in diagnosing and monitoring PDAC patients.
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Proenkephalin for the early detection of acute kidney injury in hospitalized patients with chronic kidney disease.
Breidthardt, T, Jaeger, C, Christ, A, Klima, T, Mosimann, T, Twerenbold, R, Boeddinghaus, J, Nestelberger, T, Badertscher, P, Struck, J, et al
European journal of clinical investigation. 2018;(10):e12999
Abstract
BACKGROUND The early detection of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is an unmet clinical need. Proenkephalin (PENK) might improve the early detection of AKI. METHODS One hundred and eleven hospitalized CKD patients undergoing radiographic contrast procedures were enrolled. PENK was measured in a blinded fashion at baseline (before contrast media administration) and on day 1 (after contrast media administration). The potential of PENK levels to predict contrast-induced AKI was the primary endpoint. RESULTS Baseline creatinine and baseline PENK were similar in AKI and no-AKI patients. In AKI patients, day 1 PENK (198 pmol/L vs 121 pmol/L, P < 0.01) was significantly higher compared to no-AKI patients. The area under the curve (AUC) for the prediction of AKI by day 1 PENK was 0.79, 95% CI: 0.70-0.87, similar to serum creatinine: 0.78, 95% CI: 0.61-0.95. Delta PENK was significantly higher in AKI compared to no-AKI patients (53 pmol/L vs 1 pmol/L, P < 0.01). The AUC for the prediction of AKI by delta PENK was high (0.92, 95%CI 0.82-1.00) and remained high for creatinine-blind AKI (0.94, 95% CI: 0.87-0.97). CONCLUSION Delta PENK levels improve the early detection of contrast-induced AKI in CKD patients over serial creatinine sampling. Delta PENK accelerates the detection of creatinine-blind AKI by 24 hours.
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Procalcitonin as a marker of serious bacterial infections in febrile children younger than 3 years old.
Mahajan, P, Grzybowski, M, Chen, X, Kannikeswaran, N, Stanley, R, Singal, B, Hoyle, J, Borgialli, D, Duffy, E, Kuppermann, N
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2014;(2):171-9
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Abstract
OBJECTIVES There is no perfectly sensitive or specific test for identifying young, febrile infants and children with occult serious bacterial infections (SBIs). Studies of procalcitonin (PCT), a 116-amino-acid precursor of the hormone calcitonin, have demonstrated its potential as an acute-phase biomarker for SBI. The objective of this study was to compare performance of serum PCT with traditional screening tests for detecting SBIs in young febrile infants and children. METHODS This was a prospective, multicenter study on a convenience sample from May 2004 to December 2005. The study was conducted in four emergency departments (EDs): one pediatric ED and three EDs with pediatric units, all with academic faculty on staff. A total of 226 febrile children 36 months old or younger who presented to the four participating EDs and were evaluated for SBI by blood, urine, and/or cerebral spinal fluid (CSF) cultures were included. RESULTS The test characteristics (with 95% confidence intervals [CIs]) of the white blood cell (WBC) counts including neutrophil and band counts were compared with PCT for identifying SBI. Thirty children had SBIs (13.3%, 95% CI = 8.85 to 17.70). Four (13.3%) had bacteremia (including one with meningitis), 18 (60.0%) had urinary tract infections (UTIs), and eight (26.6%) had pneumonia. Children with SBIs had higher WBC counts (18.6 × 10(9) ± 8.6 × 10(9) cells/L vs. 11.5 × 10(9) ± 5.3 × 10(9) cells/L, p < 0.001), higher absolute neutrophil counts (ANCs; 10.6 × 10(9) ± 6.7 × 10(9) cells/L vs. 5.6 × 10(9) ± 3.8 × 10(9) cells/L, p = 0.009), higher absolute band counts (0.90 × 10(9) ± 1.1 × 10(9) cells/L vs. 0.35 × 10(9) ± 0.6 × 10(9) cells/L, p = 0.009), and higher PCT levels (2.9 ± 5.6 ng/mL vs. 0.4 ± 0.8 ng/mL, p = 0.021) than those without SBIs. In a multivariable logistic regression analysis, the absolute band count and PCT were the two screening tests independently associated with SBI, although the area under the receiver operating characteristic (ROC) curve for PCT was the largest (0.80, 95% CI = 0.71 to 0.89). CONCLUSIONS Procalcitonin is a more accurate biomarker than traditional screening tests for identifying young febrile infants and children with serious SBIs. Further study on a larger cohort of young febrile children is required to definitively determine the benefit of PCT over traditional laboratory screening tests for SBIs.
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Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial.
Müller, F, Christ-Crain, M, Bregenzer, T, Krause, M, Zimmerli, W, Mueller, B, Schuetz, P, ,
Chest. 2010;(1):121-9
Abstract
BACKGROUND Guidelines recommend blood culture sampling from hospitalized patients with suspected community-acquired pneumonia (CAP). However, the yield of true-positive results is low. We investigated the benefit of procalcitonin (PCT) on hospital admission to predict blood culture positivity in CAP. METHODS This was a prospective cohort study with a derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission. RESULTS A total of 73 (7.9%) patients had true bacteremia (43 of 463 in the derivation cohort, 30 of 462 in the validation cohort). The area under the receiver operating characteristics curve of PCT in the derivation and validation cohorts was similar (derivation cohort, 0.83; 95% CI, 0.78-0.89; validation cohort, 0.79; 95% CI, 0.72-0.88). Overall, PCT was a significantly better predictor for blood culture positivity than WBC count, C-reactive protein, and other clinical parameters. In multivariate regression analysis, only antibiotic pretreatment (adjusted odds ratio, 0.25; P < .05) and PCT serum levels (adjusted odds ratio, 3.72; P < .001) were independent predictors. Overall, a PCT cutoff of 0.1 microg/L would enable reduction of the total number of blood cultures by 12.6% and still identify 99% of the positive blood cultures. Similarly, 0.25 microg/L and 0.5 microg/L cutoffs would enable reduction of blood cultures by 37% and 52%, respectively, and still identify 96% and 88%, respectively, of positive blood cultures. CONCLUSIONS Initial PCT level accurately predicted blood culture positivity in patients with CAP. PCT measurement has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care resources.
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Mutagenesis and computer modelling approach to study determinants for recognition of signal peptides by the mitochondrial processing peptidase.
Zhang, XP, Sjöling, S, Tanudji, M, Somogyi, L, Andreu, D, Eriksson, LE, Gräslund, A, Whelan, J, Glaser, E
The Plant journal : for cell and molecular biology. 2001;(5):427-38
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Abstract
Determinants for the recognition of a mitochondrial presequence by the mitochondrial processing peptidase (MPP) have been investigated using mutagenesis and bioinformatics approaches. All plant mitochondrial presequences with a cleavage site that was confirmed by experimental studies can be grouped into three classes. Two major classes contain an arginine residue at position -2 or -3, and the third class does not have any conserved arginines. Sequence logos revealed loosely conserved cleavage motifs for the first two classes but no significant amino acid conservation for the third class. Investigation of processing determinants for a class III precursor, Nicotiana plumbaginifolia F1beta precursor of ATP synthase (pF1beta), was performed using a series of pF1beta presequence mutants and mutant presequence peptides derived from the C-terminal portion of the presequence. Replacement of -2 Gln by Arg inhibited processing, whereas replacement of either the most proximally located -5 Arg or -15 Arg by Leu had only a low inhibitory effect. The C-terminal portion of the pF1beta presequence forms a helix-turn-helix structure. Mutations disturbing or prolonging the helical element upstream of the cleavage site inhibited processing significantly. Structural models of potato MPP and the C-terminal pF1beta presequence peptide were built by homology modelling and empirical conformational energy search methods, respectively. Molecular docking of the pF1beta presequence peptide to the MPP model suggested binding of the peptide to the negatively charged binding cleft formed by the alpha-MPP and beta-MPP subunits in close proximity to the H111XXE114H115X(116-190)E191 proteolytic active site on beta-MPP. Our results show for the first time that the amino acid at the -2 position, even if not an arginine, as well as structural properties of the C-terminal portion of the presequence are important determinants for the processing of a class III precursor by MPP.