No abstract

Thymidine kinase (TK1) is an enzyme involved in DNA synthesis that leaks into the blood as a result of high cell turnover, particularly in the case of cancer. Serum TK1 activity has been used for prognosis and monitoring of leukemia and lymphoma patients for many years. Here, we describe the first clinical results with the newly developed TK 210 ELISA from AroCell AB. Sera from 124 breast cancer patients with known TNM classification along with sera from 53 healthy females were analyzed by TK 210 ELISA for TK1 protein and TK1 activity levels by the 3[H]-deoxythymidine (dThd) phosphorylation assay. The limit of detection for the TK 210 ELISA was 0.17 ng/ml, and 60 % of the sera from female blood donors were below this value. The median TK1 levels found in sera from breast cancer patients with T1 to T4 stage disease were 0.31, 0.46, 0.47, and 0.55 ng/ml, and these levels significantly differed from healthy controls. The median values of the biomarker CA 15-3 were also increased in patient sera from T1 to T4 patients (16, 34, 36, 40 U/ml, respectively). TK 210 ELISA showed significantly higher sensitivity for the T1 and T2 breast cancer patients compared to the TK activity assay. The combination of the TK1 ELISA and CA 15-3 biomarkers demonstrated a significant increase in sensitivity up to 15 % compared to each marker alone. This evaluation of the TK 210 ELISA strongly suggests that it can provide independent and complementary information for patients with breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-016-5024-z) contains supplementary material, which is available to authorized users.

<b><i>Objective:</i></b> The aim of this work was to define a differential marker profile for pregnancy complications near delivery. <b><i>Methods:</i></b> We enrolled pregnant women who were referred to the outpatient pregnancy clinic of the University Medical Center, Ljubljana, Slovenia, due to symptoms of pregnancy complications and women with a history of pregnancy complications attending the high-risk hospital clinic for close surveillance. They were evaluated for prior risk and were tested for biophysical and biochemical markers at the time of enrolment. Biochemical markers included the pro- and anti-angiogenic markers, along with additional previously reported markers of potential value, all tested by various formats of immuno-diagnostics. Biophysical markers included blood pressure, sonographic markers, and EndoPAT. Statistical differences were determined with Kruskal-Wallis and Mann-Whitney tests for continuous parameters, and Pearson χ² for categorical values. <i>p</i> &#x3c; 0.05 was considered significant. <b><i>Results:</i></b> The cohort included 125 pregnant patients, 31 developed preeclampsia (PE) alone (13 were &#x3c;34 weeks’ gestation), 16 had intrauterine growth restriction (IUGR) alone (12 were &#x3c;34 weeks), 42 had both IUGR and PE (22 were &#x3c;34 weeks), and 15 had an iatrogenic preterm delivery (PTD; 6 were &#x3c;34 weeks). Twenty-one were unaffected and delivered a healthy baby at term. Mean arterial blood pressure and proteinuria were significantly higher in PE and PE+IUGR but not in pure IUGR or PTD. In PE, IUGR, and PE+IUGR, the levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) were significantly higher, while placental growth factor (PlGF) was very low compared to unaffected controls and PTD. PE, IUGR, and PE+IUGR also had a high anti-angiogenic ratio (sFlt-1/PlGF) and a low proangiogenic ratio of PlGF/(sFlt-1+Eng). Levels of inhibin A were significantly higher in pure PE across subgroups but had many extreme values, which made it a poor differentiator. Higher uterine artery Doppler pulsatility indexes were detected in PE, IUGR, and PE+IUGR, with similar resistance indexes and peaks of systolic velocity. A significantly different marker level between PE and IUGR was found using arterial stiffness that was 10 times higher in PE; concurrently with an increase of the reactive hyperemia index, both were accompanied by a slight increase in placental protein 13. Higher tumor necrosis factor alpha (TNFα) differentially identified iatrogenic very early PTD (&#x3c;34 weeks). <b><i>Conclusion:</i></b> Arterial stiffness can serve as a major marker to differentiate PE (with/without IUGR) from pure IUGR near delivery. TNFα can differentiate iatrogenic early PTD from other complications of pregnancy and term IUGR.

P lacement of external ventricular drainage (EVD) and draining of the cerebrospinal fluid (CSF) when intracranial pressure (ICP) is elevated are frequently used for treating intracranial hypertension caused by a variety of neurological conditions. However, such an invasive procedure allows free entrance for bacteria and presents an increased risk of infection that can lead to meningitis, ventriculitis, or even death. The incidence of EVD-related ventriculitis ranges from 10% to 27% according to the literature (1-5). The most significant group of microorganisms causing ventriculitis is Staphylococcus spp., especially coagulase-negative staphylococci, followed by Staphylococcus aureus. Other Grampositive organisms, such as Streptococcus spp., Enterococcus spp., Corynebacterium spp., and Propionibacterium spp., may be involved. Most ventricular infections are a result of contamination during the insertion of the EVD (6, 7). In order to prevent this complication or to detect initiating steps of the disease, early diagnosis and treatment are crucial, yet little has been reported in the literature about its management. The CSF total cell count, differential count, and concentration of proteins and glucose are parameters providing early information pertaining to the diagnosis of bacterial CSF infection. However, cell counts are often unreliable because of blood contamination of the CSF caused by primary or secondary ventricular hemorrhage or by chemical reactions to the drain material. Blood laboratory markers are also frequently elevated because of concomitant bacterial infection (8). C-reactive protein (CRP) and procalcitonin (PCT) were tested for their use to predict infection, but the results were contradictory (8, 9). Bacteriological culture methods such as CSF cultures may take several days until bacterial growth can safely be excluded (9). Furthermore, many patients with EVD are on antibiotic therapy and isolation of bacteria from CSF is often difficult. Thus, there is a need for new markers with higher specificity for early detection of meningitis and ventriculitis. Brain macrophages play a pivotal role during inflammatory reactions of the central nervous system (CNS) parenchyma, ventricles, and meninges, and are involved in the release of soluble CD14 (sCD14) (10). In a study of 91 patients, serum sCD14 levels were measured, and the levels increased during acute bacterial meningitis. Increased CSF and serum sCD14 concentrations were also observed in meningitis caused by viral infection. Repeated measurement of sCD14 in CSF revealed a normalization of sCD14 levels during clinical recovery (10). Determination of presepsin (sCD14-ST) in CSF could overcome problems with time-consuming procedures while measuring sCD14. CD14 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein