PlGF
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INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- MeSH
- dospělí MeSH
- lidé MeSH
- placentární oběh fyziologie MeSH
- placentární růstový faktor * krev MeSH
- plocha pod křivkou MeSH
- prediktivní hodnota testů MeSH
- preeklampsie * krev diagnostické zobrazování MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- reologie * metody statistika a číselné údaje MeSH
- reprodukovatelnost výsledků MeSH
- rychlost toku krve fyziologie MeSH
- těhotenství MeSH
- třetí trimestr těhotenství * krev fyziologie MeSH
- ultrasonografie dopplerovská metody statistika a číselné údaje MeSH
- ultrasonografie prenatální * metody statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- MeSH
- biologické markery MeSH
- lidé MeSH
- novorozenec MeSH
- placentární růstový faktor MeSH
- předčasná porodní činnost * MeSH
- prediktivní hodnota testů MeSH
- preeklampsie * MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
INTRODUCTION: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively. METHODS: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays. RESULTS: Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p < 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p < 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL. CONCLUSION: Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.
- MeSH
- biologické markery krev MeSH
- chorioamnionitida krev diagnóza MeSH
- dospělí MeSH
- fetální krev metabolismus MeSH
- interleukin-6 * krev MeSH
- lidé MeSH
- placenta metabolismus MeSH
- placentární růstový faktor * krev MeSH
- plodová voda metabolismus MeSH
- předčasná porodní činnost * krev MeSH
- prediktivní hodnota testů * MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra-amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations. MATERIAL AND METHODS: This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra-amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra-amniotic inflammation (by amniotic fluid interleukin-6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt-1 and PlGF were assessed using the Elecsys® sFlt-1 and Elecsys® PlGF immunoassays and converted into multiples of medians. RESULTS: Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt-1 and sFlt-1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt-1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt-1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt-1 and sFlt-1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion. CONCLUSIONS: Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra-amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.
- MeSH
- amniocentéza MeSH
- biologické markery krev MeSH
- chorioamnionitida krev MeSH
- dospělí MeSH
- gestační stáří MeSH
- lidé MeSH
- placentární růstový faktor * krev MeSH
- plodová voda * mikrobiologie metabolismus MeSH
- předčasný odtok plodové vody * krev MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.
- MeSH
- biologické markery MeSH
- císařský řez MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- novorozenec MeSH
- placentární růstový faktor MeSH
- prediktivní hodnota testů MeSH
- preeklampsie * diagnóza prevence a kontrola epidemiologie MeSH
- randomizované kontrolované studie jako téma MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- dospělí MeSH
- lidé MeSH
- placentární růstový faktor * krev MeSH
- předčasný odtok plodové vody * MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
PURPOSE: The aim of this study was to investigate whether there is any association between the levels of the angiogenic growth factors and the vascular oxygen saturation in eyes with diabetic retinopathy. METHODS: The study was designed as a prospective trial. The cohort consisted of 29 diabetic patients with scheduled vitreous procedures (intravitreal injection or pars plana vitrectomy). The control group included 30 patients scheduled for macular surgery (macular hole or epiretinal membrane). Nine patients (four from the diabetic maculopathy [DM] group and five from the control group) were excluded from the study because of unsuccessful vitreous samples. Retinal oximetry was performed several hours before the vitreous procedure was performed, and vitreous samples were obtained during the procedure. The concentrations of VEGF, Serpin F1/pigment epithelium-derived factor (PEDF), and placental growth factor (PlGF) were measured by ELISA. RESULTS: A negative correlation between level of VEGF and arteriovenous (AV) saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.607; two-tailed test, P = 0.002). Also a negative correlation between level of PlGF and AV saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.521; two-tailed test, P = 0.011) A positive correlation between PlGF level and the vein saturation was not statistically significant (Pearson correlation coefficient r = 0.325; two-tailed test, P = 0.130). We did not find any correlation between vitreous level of PEDF and vascular saturation within the DM group. CONCLUSIONS: Our findings in diabetic patients suggests a correlation between the intravitreal level of proangiogenic factors and the AV difference measured by retinal oximetry.
- MeSH
- diabetes mellitus * MeSH
- diabetická retinopatie * MeSH
- lidé MeSH
- placentární růstový faktor MeSH
- prospektivní studie MeSH
- retina MeSH
- retinální cévy MeSH
- saturace kyslíkem MeSH
- vaskulární endoteliální růstový faktor A MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To assess the performance and impact of first-trimester preterm pre-eclampsia screening in a single center. METHODS: This was a single-center study of women with a singleton pregnancy who were screened prospectively for preterm pre-eclampsia (i.e. delivery before 37 weeks' gestation) using maternal characteristics, mean arterial pressure (MAP), uterine artery Doppler pulsatility index, maternal serum pregnancy-associated plasma protein-A and placental growth factor. The individual risk for preterm pre-eclampsia was estimated from a published model, and those with a risk above 1 in 200 were recommended to take 150 mg soluble aspirin per day until 34 weeks. Information on the incidence of pre-eclampsia was obtained from the hospital register of adverse pregnancy outcomes. Screening performance indicators, including detection and false-positive rates, were estimated from the distribution of risks. Screening impact was estimated by dividing the observed prevalence by the expected prevalence, which was derived from the distribution of risks. RESULTS: The distributions of MAP, uterine artery Doppler pulsatility index and serum markers were consistent with the risk model parameters. The estimated detection and false-positive rates were 79.7% and 16.2%, respectively. There were six cases of preterm pre-eclampsia, four of which occurred in women with a positive screening result. The prevalence was 62% of that expected, but the 95% CI of 23-140% indicated that the study was underpowered to assess the impact. CONCLUSIONS: This study demonstrates that the performance of preterm pre-eclampsia screening can be estimated in a single center with fewer than 2000 women screened. However, in order to assess the impact of screening on the prevalence of the condition, a much larger cohort is needed. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
- MeSH
- arteria uterina diagnostické zobrazování MeSH
- biologické markery MeSH
- hodnocení rizik MeSH
- lidé MeSH
- novorozenec MeSH
- placentární růstový faktor MeSH
- preeklampsie * diagnóza epidemiologie MeSH
- první trimestr těhotenství MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIM: Placental Growth Factor (PlGF) plays a crucial role in angiogenesis and was identified as a potential prognostic biomarker in various types of cancer. Therefore, we evaluated the diagnostic accuracy and prognostic value of PlGF serum concentration in patients with clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: A total of 49 patients subjected to partial or radical nephrectomy for ccRCC [localized without relapse (lccRCC; n=31), localized with later relapse (rccRCC; n=8), primary metastatic cancer (mccRCC; n=10); median of follow-up 4.4 years] were enrolled in a prospective study to assess the significance of PlGF serum concentration. PlGF was measured prior to surgery and 3 months postoperatively. Our control group consisted of 38 healthy subjects. RESULTS: PlGF serum concentration was significantly higher in ccRCC compared to controls (P=0.002). The cut-off value of PlGF concentration for the risk of ccRCC was determined at 12.71 pg/mL (AUC=0.729; P=0.0001). Prior to surgery, among ccRCC subgroups, significantly higher PlGF concentration was detected in mccRCC compared to lccRCC (P=0.002). Postoperatively, we observed a tendency to higher PlGF serum concentration in rccRCC compared to lccRCC subgroup, however without significance (P=0.17). The cut-off value for the risk of relapse was 11.41 pg/mL (AUC=0.792; P=0.0003). In subjects with localized ccRCC with PlGF concentration below 11.41 pg/mL 3-years cancer specific survival was 93% compared to 61% in subject with concentration above the cut-off value (P=0.018). CONCLUSION: Based on our findings, PlGF serum concentration seems to be a useful biomarker in diagnostics and prediction of prognosis in ccRCC.