[Usefulness of Presepsin Measurement: A New Biomarker for Sepsis].

Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, and it is one of the major causes of mortality of critical care patients. Since it has been reported that early, optimal treatment of patients is important to reduce mortality from sepsis, a sepsis marker with a high sensitivity and specificity is required. Presepsin (P-SEP) was discovered as a new marker whose levels elevated specifically in the blood of patients with sepsis in Japan in 2002. Presepsin is a 13-kDa glycoprotein that is a truncated N-terminal fragment of CD14. Since one of the production mechanisms of presepsin is related to the phagocytosis of bacteria, the biological characteristics of presepsin are different from those of other inflammatory markers. Presepsin has three features in comparison with procalcitonin(PCT), C-reactive protein(CRP), and interleukin-6 (IL-6): 1) Presepsin can be detected earlier after the onset of infection; 2) Presepsin is not affected by severe trauma, severe burn, or invasive surgical procedures, which lead to SIRS, more than PCT, CRP, or IL-6; 3) Presepsin levels reflect the clinical condition of septic patients. Although clinical evidence is not sufficient at present, presepsin may be a strong tool for the development of novel treatment strategies for sepsis.

Presepsin as a powerful monitoring tool for the prognosis and treatment of sepsis: a multicenter prospective study.

Presepsin is a protein whose levels increase specifically in the blood of patients with sepsis. It is proposed as a diagnostic and prognostic marker for assessing the degree of sepsis severity. The present multicenter prospective study compared the clinical utility of presepsin with other conventional sepsis biomarkers including procalcitonin, interleukin-6, and C-reactive protein for evaluating the severity of sepsis during follow-up. Patients with sepsis (n = 103) admitted to the emergency room or intensive care unit were enrolled in this study and classified into 3 diagnostic groups: sepsis, severe sepsis, and septic shock. Blood samples were obtained from each patient on admission and after 1, 3, 5, and 7 days. The patients were further divided into the favorable and unfavorable prognosis groups on the basis of several indicators of sepsis severity (i.e., Sequential Organ Failure Assessment score, and Acute Physiology and Chronic Health Evaluation II score). The patients in the favorable prognosis group exhibited significant decreases in all biomarker levels on days 3 and 7 after admission. In the unfavorable prognosis group, only presepsin levels did not decrease significantly during follow-up. The period of antibiotics treatment in the unfavorable prognosis group was significantly longer than those in the favorable prognosis group (P < 0.05). The unfavorable prognosis group had significantly higher 28-day mortality than the favorable prognosis group (P < 0.05). Therefore, the results suggest that presepsin levels correlated with the severity of sepsis during follow-up in comparison with other conventional sepsis biomarkers.

Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study.

The clinical usefulness of presepsin for discriminating between bacterial and nonbacterial infections (including systemic inflammatory response syndrome) was studied and compared with procalcitonin (PCT) and interleukin-6 (IL-6) in a multicenter prospective study. Suspected sepsis patients (n = 207) were enrolled into the study. Presepsin levels in patients with systemic bacterial infection and localized bacterial infection were significantly higher than in those with nonbacterial infections. In addition, presepsin, PCT, and IL-6 levels in patients with bacterial infectious disease were significantly higher than in those with nonbacterial infectious disease (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under the receiver operating characteristic curve was 0.908 for presepsin, 0.905 for PCT, and 0.825 for IL-6 in patients with bacterial infectious disease and those with nonbacterial infectious disease. The cutoff value of presepsin for discrimination of bacterial and nonbacterial infectious diseases was determined to be 600 pg/ml, of which the clinical sensitivity and specificity were 87.8 % and 81.4 %, respectively. Presepsin levels did not differ significantly between patients with gram-positive and gram-negative bacterial infections. The sensitivity of blood culture was 35.4 %; that for presepsin was 91.9 %. Also there were no significant differences in presepsin levels between the blood culture-positive and -negative groups. Consequently, presepsin is useful for the diagnosis of sepsis, and it is superior to conventional markers and blood culture.

Performance evaluation of the new rapid fertility assays in whole blood and plasma on PATHFAST.

BACKGROUND: The purpose of this study was to evaluate the validity of the PATHFAST fertility marker assays for the rapid measurement of female hormones including: LH, FSH, Estradiol (E2), Progesterone (P4), Prolactin (PRL), and HCG. As for the PATHFAST fertility marker assays, female hormones can be measured by whole blood, plasma, and serum. METHODS: The correlation of the heparin whole blood and the plasma samples in the PATHFAST was examined. The method comparison study of PATHFAST fertility marker assays was performed with the Elecsys 2010, AIA-360, IMMULITE 2000, miniVIDAS, and ARCHITECT i2000. Determination of the reference range values of the PATHFAST fertility marker assays was performed with serum samples which were obtained during the follicular phase, mid-cycle, luteal phase, and postmenopausal phase. RESULTS: The results of plasma samples of female hormones measured by the PATHFAST correlated highly with those of whole blood samples (r > 0.9). The results of LH, FSH, E2, P4, PRL, and HCG as measured by the PATHFAST correlated well with other commercial fertility assays (r > 0.9). Reference values of PATHFAST fertility marker assays were equivalent to those of other commercial methods. CONCLUSIONS: The PATHFAST system is an accurate diagnostic tool for the rapid assay of female hormones. The PATHFAST fertility marker assays can be useful in a physician's office laboratory (POL) as well as various clinical sites during infertility treatment.

Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome.

CD14 is present in macrophage, monocyte, and granulocyte cells and their cell membranes, and it is said to be responsible for intracellular transduction of endotoxin signals. Its soluble fraction is present in blood and is thought to be produced in association with infections. It is called the soluble CD14-subtype (sCD14-ST), and in the following text it is referred to by its generic name, presepsin. We have previously reported that presepsin is produced in association with infection and that it is specifically expressed in sepsis. In the present study we developed a new rapid diagnostic method by using a chemiluminescent enzyme immunoassay that allowed making automated measurements in a shorter time. The results of using this method to measure presepsin values in different pathological conditions were normal, 294.2 ± 121.4 pg/ml; local infection, 721.0 ± 611.3 pg/ml; systemic inflammatory response syndrome, 333.5 ± 130.6 pg/ml; sepsis, 817.9 ± 572.7 pg/ml; and severe sepsis, 1,992.9 ± 1509.2 pg/ml; the presepsin values were significantly higher in patients with local infection, sepsis, and severe sepsis than in patients who did not have infection as a complication. In a comparative study with other diagnostic markers of sepsis based on ROC curves, the area under the curve (AUC) of presepsin was 0.845, and greater than the AUC of procalcitonin (PCT, 0.652), C-reactive protein (CRP, 0.815), or interleukin 6 (IL-6, 0.672). In addition, a significant correlation was found between the APACHE II scores, an index of disease severity, and the presepsin values, suggesting that presepsin values can serve as a parameter that closely reflects the pathology.

Two modes of microsatellite instability in human cancer: differential connection of defective DNA mismatch repair to dinucleotide repeat instability.

Microsatellite instability (MSI) is associated with defective DNA mismatch repair in various human malignancies. Using a unique fluorescent technique, we have observed two distinct modes of dinucleotide microsatellite alterations in human colorectal cancer. Type A alterations are defined as length changes of < or =6 bp. Type B changes are more drastic and involve modifications of > or =8 bp. We show here that defective mismatch repair is necessary and sufficient for Type A changes. These changes were observed in cell lines and in tumours from mismatch repair gene-knockout mice. No Type B instability was seen in these cells or tumours. In a panel of human colorectal tumours, both Type A MSI and Type B instability were observed. Both types of MSI were associated with hMSH2 or hMLH1 mismatch repair gene alterations. Intriguingly, p53 mutations, which are generally regarded as uncommon in human tumours of the MSI+ phenotype, were frequently associated with Type A instability, whereas none was found in tumours with Type B instability, reflecting the prevailing viewpoint. Inspection of published data reveals that the microsatellite instability that has been observed in various malignancies, including those associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is predominantly Type B. Our findings indicate that Type B instability is not a simple reflection of a repair defect. We suggest that there are at least two qualitatively distinct modes of dinucleotide MSI in human colorectal cancer, and that different molecular mechanisms may underlie these modes of MSI. The relationship between MSI and defective mismatch repair may be more complex than hitherto suspected.

Diagnostic accuracy of procalcitonin and presepsin for infectious disease in patients with acute kidney injury.

Procalcitonin (PCT) and presepsin (PSEP) are sepsis markers, but their diagnostic accuracy may be compromised in acute kidney injury (AKI). We evaluated their diagnostic accuracy in patients with/without AKI. This retrospective study comprised 91 patients with at least one criterion of systematic inflammatory response syndrome. AKI markers plasma neutrophil gelatinase-associated lipocalin (NGAL), plasma cystatin C (CysC), and estimated glomerular filtration rate (eGFR) were measured upon hospital admission and on days 1, 3, 5, and 7. Patients were divided into non-AKI and AKI groups. APACHE II severity scores were determined. PCT and PSEP levels were increased significantly in non-AKI and AKI patients with infection. NGAL, CysC, and eGFR in patients with infection were associated with PCT, PSEP, and APACHE II score, and levels of PCT and PSEP were correlated significantly with disease severity. PCT and PSEP are useful markers of bacterial infections in AKI but different thresholds should be applied.

Development of a point-of-care assay system for measurement of presepsin (sCD14-ST).

BACKGROUND: The soluble CD14 subtype (sCD14-ST: renamed as presepsin) is a novel soluble CD14 molecule that is useful for diagnosing sepsis because sCD14-ST levels increase specifically in sepsis patients. METHODS: A fully automated PATHFAST® Presepsin assay system based on a chemiluminescent enzyme immunoassay was developed for detecting presepsin in human whole blood. RESULTS: The limit of blank, limit of detection, and limit of quantification were 2.33, 13.4, and 47.6 pg/ml, respectively. The assay linearity was achieved up to 20,000 pg/ml. Intra-assay imprecision was 3.4-4.8% for plasma and 2.7-7.1% for whole blood. Within-run imprecision and total imprecision for plasma were 3.6-4.4% and 5.2-6.5%, respectively. No interference was observed with bilirubin, hemoglobin, lipids, triglyceride, or rheumatoid factors. The reference intervals (95% percentile, n=127) were 333 pg/ml for plasma and 314 pg/ml for whole blood. The PATHFAST® Presepsin assay correlated well with a previously reported two-step presepsin ELISA (r=0.984, n=40). Furthermore, the concentration of presepsin was significantly higher in the sepsis group than in the healthy group. CONCLUSION: The PATHFAST® Presepsin assay performed well and can be used for point-of-care.

Evaluation of cardiac assays on a benchtop chemiluminescent enzyme immunoassay analyzer, PATHFAST.

Devices for cardiac immunoassay are widely available at point of care settings. The lateral flow method is the most popular solution for ease of use. But its major shortcomings, poor assay precision, and low analytical sensitivity may lead to false negative results. Therefore, confirmatory testing by a routine lab analyzer sometimes is necessary. In the current study, we evaluated the cardiac assays troponin I, MB isoenzyme of creatine kinase, myoglobin, and N-terminal pro brain natriuretic peptide on a chemiluminescent enzyme immunoassay analyzer, PATHFAST. All of the assays demonstrated correlation coefficients higher than 0.97 against the predicate devices along with good total precision (coefficients of variation <10%), and the troponin I assay showed analytical sensitivity in conformance with the guidelines of European Society of Cardiology/American College of Cardiology and National Academy of Clinical Biochemistry. We concluded that the system was rapid and easy to use without compromising analytical performance.