Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).

BACKGROUND: Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors. METHODS: Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole. RESULTS: Mean maternal age was 30 years, and median gestational age was 30+3 weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%, P=0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio's 0.43-0.59), while only esomeprazole inhibited placental sFlt-1 release. CONCLUSIONS: Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.

Evaluation of inter- and intra-operator reliability of manual segmentation of femoral metastatic lesions.

PURPOSE: Accurate identification of metastatic lesions is important for improvement in biomechanical models that calculate the fracture risk of metastatic bones. The aim of this study was therefore to assess the inter- and intra-operator reliability of manual segmentation of femoral metastatic lesions. METHODS: CT scans of 54 metastatic femurs (19 osteolytic, 17 osteoblastic, and 18 mixed) were segmented two times by two operators. Dice coefficients (DCs) were calculated adopting the quantification that a DC˃0.7 indicates good reliability. RESULTS: Generally, rather poor inter- and intra-operator reliability of lesion segmentation were found. Inter-operator DCs were 0.54 (± 0.28) and 0.50 (± 0.32) for the first and second segmentations, respectively, whereas intra-operator DCs were 0.56 (± 0.28) for operator I and 0.71 (± 0.23) for operator II. Larger lesions scored significantly higher DCs in comparison with smaller lesions. Of the femurs with larger mean segmentation volumes, 83% and 93% were segmented with good inter- and intra-operator DCs (> 0.7), respectively. There was no difference between the mean DCs of osteolytic, osteoblastic, and mixed lesions. CONCLUSION: Manual segmentation of femoral bone metastases is very challenging and resulted in unsatisfactory mean reliability values. There is a need for development of a segmentation protocol to reduce the inter- and intra-operator segmentation variation as the first step and use of computer-assisted segmentation tools as a second step as this study shows that manual segmentation of femoral metastatic lesions is highly challenging.