The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib.

Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.

The relevance of Short-Term Variation (STV) value measured within 1 hour before delivery in predicting adverse neonatal outcome.

OBJECTIVES: Computer CTG analysis (cCTG) included short-term variation (STV) is one of the methods of monitoring fetal condition during delivery. The aim of our study was to define appropriability of STV measured within 1 hour before delivery in prediction of neonatal outcomes. MATERIAL AND METHODS: The retrospective study included 1014 pregnant women, who gave birth in the Department of Obstetrics and Perinatology. Participants were divided into two groups: group 1 - term pregnancies (37-41 weeks) and group 2 - preterm pregnancies (lower than 37 weeks). In each of them, two subgroups have been separated: control (STV ≥ 3 ms) and study group (STV < 3 ms). RESULTS: In both groups 1 and 2, there were no statistically significant differences related to Apgar scores in 1st, 3rd and 5th minute between group with STV < 3 ms and group with STV > 3 ms Moreover, for 37-41 weeks the sensitivity, specificity, positive predictive value and negative predictive value were: 22.7%, 83.9%, 3.3% and 97.8% and for lower than 37: 45.7%, 65.4%, 47.1%, 64.2% in 1st minute after delivery. In group 1 the area under curve (AUC) measurements were 0.45 (95% CI: 0.32-0.58) for 1st minute and 0.55 (95% CI: 0.35-0.74) for 5th minute and in group 2: 0.58 (95% CI: 0.45-0.71) for 1st minute and 0.57 (95% CI: 0.42-0.72) for 5th minute. CONCLUSIONS: High specificity and negative predictive value of STV indicates a good Apgar score of newborns in term pregnancies. Analysis of STV in preterm pregnancy is not clear. Fetal well-being in preterm pregnancy should include STV and other non-invasive and invasive tools.

Comparison of eleven commonly used formulae for sonographic estimation of fetal weight in prediction of actual birth weight.

OBJECTIVES: The aim of the study is to compare the accuracy of 11 formulas in predicting fetal weight. MATERIAL AND METHODS: The study includes 1072 pregnant women of gestational age from 28 to 42 weeks, who gave birth between January and June 2017. Pregnant women were divided into five groups; group 1, where actual birth weight (ABW) was less than 2500 g, group 2, where ABW was between 2500-4000 g, group 3, where ABW was above 4000 g. Group 4 - newborns with birth weight under 10 percentile and group 5 - newborns with birth weight above 90 percentile. The accuracy of the estimated fetal weight (EFW) was assessed by calculating absolute percentage error (APE) and 'limits-of-agreement'. R Spearman correlation was utilized between EFW and ABW. RESULTS: The most accurate formula for group 1 is Hadlock3 (MAPE = 7.04%), the narrowest limits of agreement has Combs - [mean (SD): 99.41 g (269.57 g)]. For group 2, the lowest MAPE (5.43%) has Ott, the narrowest limits of agreement belongs to Combs - [mean (SD): -101.36 g (275.88 g)] . For group 3 is Hadlock3 (MAPE = 5.79%), the narrowest limits of agreement has Hadlock5 [mean (SD): -637.32 g (209.59 g)]. For group 4 is Combs (MAPE = 7.72%), the narrowest limits of agreement has Combs [mean (SD): 195.77 g (264.97 g)]. For gr oup 5 is Warsof2 (MAPE = 7.06%), the narrowest limits of agreement has Campbell [mean (SD): 227.81 g (299.26 g)]. CONCLUSIONS: Median of absolute percentage error is the most useful parameter to predict birth weight. Each group of fetuses needs different formula to predict the most accurate weight.

Evaluation of Pregnancy Outcomes at Advanced Maternal Age.

AIM: The study aimed to investigate the association between advanced maternal age (AMA) and the risk of adverse maternal, perinatal and neonatal outcomes about parity in singleton pregnancies. METHODS: We retrospectively analysed 950 women who gave birth in the Department of Obstetrics and Perinatology of the University Hospital in Kraków for six months (between 1st January and 30th June 2018). The patients were divided into 3 groups according to their age (30-34 years old, 35-39 years old and over 40 years old). Each of these groups was subsequently subdivided into 2 groups depending on parity (primiparae and multiparae). Maternal, perinatal and neonatal outcomes were compared between the groups and the subgroups. RESULTS: Comparison of the three age groups revealed that advanced maternal age might constitute a predisposing factor for preterm birth, caesarean section and large for gestational age (LGA). From these parameters, statistical significance was reached in case of greater risk of LGA (OR = 2.17), caesarean section (OR = 2.03) and elective C-section (OR = 1.84) in women over 40 years old when compared to the patients aged 30-34. Furthermore, AMA increases the risk of postpartum haemorrhage (OR = 6.43). Additionally, there is a negative correlation between maternal age and gestational age at delivery (R = -0.106, p < 0.05). CONCLUSIONS: Advanced maternal age can undoubtedly be associated with several adverse perinatal outcomes. At the same time, the risk of perinatal complications begins to increase after the age of 35 but becomes significant in women aged ≥ 40.

Labor induction at full-term and post-term pregnancies.

INTRODUCTION: Induction of labor is an intervention in the obstetrics, which aim is to achieve cervical ripening and stimulate contractions of uterus before beginning of labor. The purpose of our study was to evaluate efficacy of combinations of vaginal misoprostol, intracervical dinoprostone and Foley catheter at term with regard to mode of delivery and rate of emergency C-sections due to birth asphyxia. MATERIAL AND METHODS: 403 singleton pregnant women, who underwent pharmacological labor induction at term, were reviewed. Patients were divided into 2 main cohorts due to beginning of induction algorithm: vaginal misoprostol (66) or intracervical dinoprostone (337) consisting of 3 subgroups - PGE2 alone (184), PGE2+Foley catheter (125), PGE2+Foley catheter+PGE1 (28). RESULTS: Comparison of maternal age, presence of cervical dilation and parity revealed no major differences between cohorts. Effectiveness of labor induction with misoprostol, dinoprostone and dinoprostone followed by Foley catheter were respectively 90.9%, 51.3%, and 82.8%. Addition of PGE1 was effective in 83% of patients with negative response to PGE2 followed by Foley catheter. ere was no statistically significant difference in rate of C-sections between dinoprostone and misoprostol cohorts, C-section due to birth asphyxia were insignificantly more frequent in PGE1 than in PGE2 cohort. Efficacy in the subgroup administered only dinoprostone was significantly higher in 40th than in 41th (p = 0.016). CONCLUSIONS: Intracervical dinoprostone seems to be safer, but less effective in labor induction than vaginal misoprostol. Following PGE2 by other methods increased efficacy of induction in this cohort.