PlGF Levels Research Articles

A phase two trial evaluating FOLFIRI plus aflibercept after failure of FOLFOXIRI plus bevacizumab in patients with unresectable metastatic colorectal cancer.

FOLFOXIRI plus bevacizumab (BEV) is an option for first-line treatment of metastatic colorectal cancer (mCRC). However, there is no consensus on the optimal treatment strategy when disease progresses. The EFFORT open-label, multicenter, single-arm phase II study investigated whether FOLFIRI plus aflibercept retains activity after progression of FOLFOXIRI plus BEV treatment. The patients with unresectable mCRC who failed first-line FOLFOXIRI plus BEV received FOLFIRI plus aflibercept. The primary endpoint was progression-free survival (PFS) in the full analysis set (FAS). Angiogenic biomarkers were measured before treatment initiation. From April 2019 to May 2021, 35 patients were enrolled and 34 were analysed in the FAS population (men, 18; median age, 63years [range: 32-78]). The primary tumor was left-sided in most cases (23/34), 23 patients were RAS mutant, 3 patients had BRAF V600E mutation and 27 patients had liver metastases. The primary end-point was met with a median PFS of 4.3months [80% confidence interval [CI] 3.7-5.1]. Median overall survival was 15.2months [95% CI 8.9-22.7]. Per RECIST, there were 1 complete response, 4 partial responses, 21 stable diseases and 8 disease progressions. Overall response rate was 14.7% [95% CI 5.0-31.1], and disease control rate was 76.5% [95% CI 58.8-89.3]. Responses were more common in patients with high VEGF-C, low VEGF-D and low PlGF levels before treatment. FOLFIRI plus aflibercept, administered after failure of FOLFOXIRI plus BEV, is effective and has a manageable safety profile. This regimen may be a useful second-line treatment option for these patients.

Cumulative effects of extreme ambient temperatures on placental perfusion and function markers in early pregnancy: analysis from a birth cohort study.

Exposure to suboptimal temperatures during pregnancy has been associated with adverse pregnancy and birth outcomes related to placental development disorders. No prior studies have examined the potential impacts of temperature on placental markers. We conducted an investigation into the cumulative impact of daily ambient temperature on critical clinical placental perfusion and function markers during the placentation period, utilizing data from a prospective birth cohort in Nanjing, China. We collected UtA-PI data and blood samples during the first follow-up (11-13.5 weeks of gestation) and measured PlGF and PAPP-A concentrations in plasma. We estimated individual daily temperature exposure over the 30 days preceding the follow-up and applied a Distributed Lag Nonlinear Model to evaluate its associations with UtA-PI, PlGF, and PAPP-A levels. We included 3403, 3407, and 3427 women in the UtA-PI, PlGF, and PAPP-A analyses, respectively. Cold exposure was associated with higher UtA-PI measurements, with the strongest estimated percent change being 14.80% (95% CI: 3.32, 27.55). Both cold and heat exposures were associated with decreased PlGF concentrations, with the strongest estimated percent changes being -44.23% (95% CI: -63.28, -15.30) and -48.27% (95% CI: -64.33, -24.98), respectively. Temperature effects on UtA-PI were immediate, whereas changes in PlGF concentrations manifested after a cumulative lag of 24 days. Both cold and heat exposures were associated with changes in placental markers, providing new insights into the potential mechanisms connecting ambient temperature to adverse pregnancy and birth outcomes through disorders of placental development.

Treatment of polypoidal choroidal vasculopathy in the real world and its underlying mechanisms

Aims/Purpose: To evaluate the efficacy of combined therapy (verteporfin PDT plus anti‐VEGF) vs. anti‐VEGF monotherapy in symptomatic macular polypoidal choroidal vasculopathy (PCV) and its underlying therapeutic mechanisms.Methods: In this retrospective indocyanine green angiography (ICG)–proved PCV study, 21 Chinese (mean age: 67.50 ± 2.22 years; 17 males; 4 females; 11 left eyes) were treated randomized to mainly verteporfin PDT (standard fluence) + anti‐VEGF, or anti‐VEGF monotherapy. Patients were followed monthly by 3D OCT and re‐treated if signs/symptoms (e.g. cystoid macular edema/deteriorated best corrected vision, BCVA) recurred or persisted. Patients were evaluated with ICG to observe the regression of polyps. Change in BCVA/central retinal thickness, CRT, and safety were also included.Results: The mean follow‐up period (37.04 ± 7.74 months) showed that verteporfin PDT combined with antibodies (bevacizumab, ranibizumab or aflibercept) was compared to anti‐VEGF monotherapy in reducing the CRT (151.75 ± 40.37μm vs. 151.00 ± 58.83); BCVA changes (LogMAR) were ‐0.01 ± 0.21 (verteporfin PDT+antibodies) vs. 0.08 ± 0.09 (anti‐VEGF monotherapy). The mean injection numbers are 1.1# PDT+2# anti‐VEGF agents for combined therapy; 4.6 ± 1.2 anti‐VEGF agents for monotherapy. Three patients of PCV (30%) were recurrent and averaged 18.50 ± 9.26 months. Incomplete remission of polyps/BVN were observed in all eyes. There were no new safety issues with defined therapies. The PCV/nvAMD (control) levels of PLGF, VEGF, HIF1α and Wnt were 3.60 ± 1.48 (n = 8)/32.45 ± 10.53 (n = 28), 105.52 ± 16.15 (n = 8)/235.38 ± 42.13 (n = 27), 2.78 ± 1.40 (n = 3)/2.27 ± 0.43 (n = 63) and 2.13 ± 1.22 (n = 5)/2.40 ± 0.34 (n = 20). As compared to nvAMD, those concentrations of PLGF and VEGF in PCV were much lower.Conclusions: Verteporfin PDT plus antibodies was compared to anti‐VEGF monotherapy in achieving less number of visits/injections in this study in symptomatic macular PCV. However, BCVA was only stable (‐0.01 ± 0.21) but not improved, which was not correlating to the anatomic improvement. All treatments were well tolerated over the around 2‐year follow‐up period. As shown by various biomarkers, PCV should be a variant of nvAMD. It might therefore explain dissimilarity in response to anti‐VEGF and/or PDT treatment.

Clinical, Analytical, and Echocardiographic Associations of Impaired Cardiorespiratory Fitness After Anthracycline Chemotherapy in Breast Cancer: EPIC Fitness Study.

This study explores the effects of anthracycline chemotherapy (AC) on breast cancer patients, focusing on changes in body composition, advanced echocardiographic parameters at rest and during exercise, and biomarkers; and subsequently assesses whether these parameters are associated with impaired cardiorespiratory fitness (CRF). In this prospective study, we evaluated women with early-stage breast cancer undergoing AC at three visits: before AC, 1 month after, and 6 months post-AC. The study included 32 women with breast cancer, with functional disability increasing from 9.0% pre-AC to 43.8% at 1 month and 53.1% at 6 months post-AC. At 1 month, patients with functional disability exhibited higher rates of cancer therapy-related cardiac dysfunction (CTRCD) (85.7%vs. 55.5%) and, during exercise, showed lowerleft ventricular ejection fraction (LVEF), reduced contractile reserve and stroke volume (SV); along with elevated IL-6, PlGF, and MPO levels. By 6 months, these patients maintained higher CTRCD rates (35.3%vs. 0%), lower SV and cardiac output (CO), reduced global longitudinal strain (GLS), and decreased global work index (GWI). During exercise, they had lower SV; additionally, they exhibited higher MPO levels and increased body and visceral fat. In our multivariable model: age, body fat, resting GWI, exercise LVEF, and CO were independently associated with VO2peak. Significant and persistent CRF reductions are common in breast cancer patients post-AC. While resting LVEF and GLS were not linked to VO2peak, resting MWI and exercise LVEF and CO were, potentially identifying patients at increased long-term heart failure risk who would benefit from cardioprotective strategies like cardio-oncology rehabilitation. It is important to recognize that impaired CRF is multifactorial, as demonstrated by age and body fat being independently associated with VO2peak, and the impact of non-cardiac factors should be better studied. Our findings highlight the need for further research on CTRCD definition, suggesting that CPET and advanced exercise echocardiography could enhance risk stratification.

Angiogenic Markers in Gestational Diabetes and their Association with Placental Dimensions.

GDM is an increasing global concern, with its etiology not fully understood, though altered placental function is likely to play a role. Placental angiogenesis, essential for sufficient blood flow and nutrient exchange between mother and fetus, may be affected by GDM. However, the role of angiogenic markers in GDM remains unclear. This study aims to investigate angiogenic markers from early pregnancy till delivery and their relationship with placental dimensions. This study is a part of a longitudinal study, where a total of 1154 women were recruited, out of which 167 women developed GDM (15.2%). The current study includes a total of 130 women randomly selected (65 GDM and 65 Non-GDM women). Plasma and placental levels of angiogenic markers such as VEGF, PLGF and sFlt-1/Flt-1 were estimated. Placental dimensions and birth outcomes were recorded, and associations between angiogenic markers and these parameters were examined. sFlt-1 (p < 0.05) levels were higher at V1 (11-14weeks) in GDM women as compared to Non-GDM women. Placental PLGF (p < 0.01) and Flt-1 (p < 0.05) levels were lower in the GDM group. PLGF and Flt-1 were negatively associated with placental dimensions such as major axis, minor axis and breadth of the placenta. This study reveals altered expression of placental angiogenic markers in women with GDM, potentially affecting placental development and function. Negative correlations between these markers and placental dimensions suggest their influence on pregnancy outcomes in GDM.

Effect of Phenol and Saponin on Apis Dorsata Forest Honey and docking molecule on preeclamptic markers

Molecular docking is an important computational method for drug design. It can be used to predict receptor binding interactions with ligans. In addition, phenol-derived compounds and Saponins are also reported to have various activities such as anti-hypertensive, anti-inflammatory and anti-apoptosis agents. The purpose of this study is to predict whether the Phenol and Saponin compounds are active as anti-inflammatory agents and also to ensure that the binding interactions are stable before and after the docking calculations. The protocol is carried out in accordance with the standards set by the LPPT-UGM Testing Laboratory. The tools, programs, and applications used in this study were Lenovo IdeaPad Flex 5 Processor, AMD Ryzen 5000 Series 5, AutoDock Tools (v1.5.6), Biovia Discovery Studio, AutodockVina, Swiss ADME, VegaZZ, Pubchem, and the and the pkCSM web server (http://biosig.unimelb.edu.au/pkcsm/). Trans-ADFH three-dimensional structure, as a test compound, and Prednisolone, as a standard compound, were downloaded from https://pubchem.ncbi.nlm.nih.gov/. The phytochemical analysis of ADFH includes phenol and saponin. Structure of PlGF 3D (IRV6) and VEGF (4KZN). Identification of ligands and proteins prepared using Pubchem results of molecular docking between preeclampsia through examination of PlGF and VEGF with phenols and saponins Identification of protein ligands using Pubchem, i.e., PlGF (IRV6) with phenol produced 2 interactions and 2 amino acid residues, while saponins produced 2 interactions and 6 residues. pharmacokinetics and toxicity using Swiss ADME, i.e., phenol and saponins are non-mutagenic to bacteria; the maximum safe dose for humans is 0.54 log mg/kg/day; it does not cause toxicity to the heart; the estimated dose for animals is 2.471 mol/kg; it does not cause allergies; it does not cause liver damage; a dose of 0.288 logμ/L can inhibit the growth of 50% of the protozoa T. Pyformis. The content of phenols and saponins in Apis Dorsata forest honey has a high docking score from the original ligand. Molecular docking on phenols and saponins identified PlGF with scores of -2.85, -2.85, and -2.85 kcal/mol, while saponins have +2.84, +2.29, and +2.29 kcal/mol values, which are stated to be better results than the original ligands. This means that phenol has a role as a standard drug that can have an effect on lowering PlGF levels for people with preeclampsia. Molecular docking on VEGF identified phenol with scores of -2.88, -2.88, and -2.88 kcal/mol, and saponins have +1.36, +3.46, and +1.36 kcal/mol values, which are stated to have better results than the original ligands. This means that saponins have a role as a standard drug that can have an effect on increasing VEGF levels for people with preeclampsia.

Isolated HELLP syndrome without hypertension or proteinuria exhibiting increases in serum levels of both PlGF and sFlt-1

Isolated HELLP syndrome without hypertension or proteinuria exhibiting increases in serum levels of both PlGF and sFlt-1

Repeat Placental Growth Factor-Based Testing in Women With Suspected Preterm Preeclampsia (PARROT-2): A Multicenter, Parallel-Group, Superiority, Randomized Controlled Trial

(Lancet. 2024;403: 619–631. https://doi.org/10.1016/S0140-6736(23)02357-7) Hypertensive disorders affect 10% of pregnant women, including chronic hypertension, gestational hypertension, and preeclampsia, which impacts 2.8% of pregnancies. Preeclampsia, especially when preterm, increases maternal and perinatal complications. Suspected preeclampsia complicates about 10% of pregnancies but lacks an ICD-10 code, complicating accurate identification. Better early detection and risk stratification methods are needed to reduce complications and optimize resources. Abnormal levels of PlGF and sFlt-1 were linked to preeclampsia 25 years ago. Studies show PlGF is lower and sFlt-1 higher in preeclampsia cases. The PARROT-1 trial found that PlGF testing improved diagnosis time and reduced severe maternal outcomes. NICE and ISSHP recommend PlGF testing. Further evaluation is needed to determine the benefits of repeat PlGF testing.

Growth factor dysregulation and placental dysfunction

The article is devoted to the study of angiogenic and antiangiogenic vascular growth factors in placental dysfunction, which is of great importance in obstetrics and perinatology. The study of growth factors as predictors of the development of placental dysfunction makes it possible to determine in advance the development of many obstetric pathologies, including preeclampsia and fetal growth retardation, which is of great practical importance. The authors conducted an immunological study of pregnant women with placental dysfunction and pregnant women with a physiological pregnancy. Purpose of the study: to study serum growth factors in women with placental dysfunction. We examined 47 pregnant women with a gestation period of 26-40 weeks, with a diagnosis of placental dysfunction, who were under observation in the obstetric department of the city maternity complex No. 3 of the city of Tashkent. The control group consisted of 35 women with a physiological pregnancy. All women underwent an immunological blood test: cellular and humoral immunity, as well as cytokines (VEGF-A, PlGF, sFlt-1, sFlt-1/PlGF) were studied. Based on the results obtained, the authors suggest that an increased level of soluble sFlt-1 and a simultaneous decrease in the levels of VEGF-A and PlGF in pregnant women at 26-40 weeks of gestation may portend the development of pregnancy complications, including preeclampsia and fetal growth restriction, and increase the risk of premature birth. Ddelivery due to impaired placental blood flow and oxygen deficiency for the fetus, lead to deterioration of microcirculation, and insufficient levels of VEGF-A and PlGF can contribute to vascular endothelial dysfunction, which can also contribute to the development of preeclampsia. The studied angiogenic and antiangiogenic vascular growth factors are important indicators and can serve as markers for predicting pregnancy complications for active medical intervention in maintaining the health of both mother and child.

CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity

Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of anNK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151brightCD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis.

The influence of trophectoderm biopsy for preimplantation genetic testing in the serum level of first trimester biomarkers: PAPP-a, βhCG and PIGF

Research questionDoes trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A) affect maternal serum first trimester pregnancy biomarkers (PAPP- A, free β-hCG, PlGF)? DesignRetrospective cohort study, including all singleton pregnancies (n=9794) following either spontaneous conceived (SC) (n=8005) in vitro fertilization and fresh embryo transfers (IVF) (n=478) or frozen embryo transfer of non PGT-A (FET)(n=963) or PGT-A tested embryos (FET+PGT-A) (n=348). In all women with a viable pregnancy at 8-13.6 weeks of pregnancy, we measured serum levels of free β-hCG and PAPP-A . PlGF was measured in 3784 patients. These biomarkers were converted to a multiple of the expected normal median (MoM) for a pregnancy of the same gestational day. We calculated the medians for the multiple of the median and compared them. ResultsFree β-hCG did not differ according to the mode of conception. PAPP-A concentrations were significantly lower in in vitro fertilization and fresh embryo transfers (-0,1 Log10 MoM raw PAPP-A) when comparing to FET+PGT-A (-0,04 Log 10 MoM raw PAPP-A) and SC (-0,0187 Log 10 MoM raw PAPP-A) (p<0,05). PlGF levels were significantly lower in the FET+PGTA group (p<0.05). The difference in means adjusted by CRL was 4.6 pg/ml 95%CI [2.7-6.6] for SC, 3.5 pg/ml 95%CI [0.34-6.6] for IVF and 2.2 pg/ml 95%CI [0.06-4.4] for FET. ConclusionThis study demonstrates that trophectoderm biopsy for PGT-A has a significant impact on first trimester maternal serum PAPP-A and PIGF. This needs to be further validated since it may mislead the estimation of the first trimester risk of aneuploidies and preeclampsia.

Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care (PoC) test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (DiabetOmics Inc.). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 μg/mL and 510 μg/mL). Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 μg/mL and > 510 μg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 μg/mL and > 510 μg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 μg/mL and > 510 μg/mL. The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 μg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Maternal angiogenic factor disruptions prior to clinical diagnosis of preeclampsia: insights from the REVAMP study.

Preeclampsia is characterized by impaired angiogenesis and assessment of angiogenic factors can play a crucial role in the early diagnosis of preeclampsia. The current study reports the levels of angiogenic factors longitudinally from early pregnancy in women with preeclampsia and in the subtypes of preeclampsia, to identify their role in early prediction of preeclampsia. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from 2 hospitals. Blood samples were collected, plasma samples were separated and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery. The current study includes a total of 108 women developed preeclampsia (PE), and 216 matched controls. Angiogenic factors were estimated using commercially available ELISA kits. Receiver operating characteristic (ROC) curves were used to evaluate the potential diagnostic value in the prediction of PE. Lower levels of VEGF, PlGF, and higher levels of sEng and sEng/PlGF ratio (p < 0.05 for all) predate clinical diagnosis in women with preeclampsia. sEng levels and sEng/PlGF ratio showed significant correlation with odds of preeclampsia at all the timepoints. This study identifies a cut off of 33.5 for sFlt-1/PlGF and 25.9 for sEng/PlGF for prediction of early onset preeclampsia. This study reports various angiogenic factors serially across gestation in a general population to identify women at risk of developing preeclampsia and its subtypes. The study also reports a potential biomarker and a pragmatic window for estimation of angiogenic markers to identify women at risk.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Abstract Tu003: The angiotensinogen/vasorin ratio in peripheral blood, a biomarker for preeclampsia

Background: Preeclampsia (PE) significantly impacts maternal and perinatal health worldwide. Despite limited treatment options, predictive tests could help in early diagnosis and personalized treatment/prevention strategies. Current biomarker, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PIGF) offer reasonable negative predictive values, but their use as positive predictive markers is limited. Using unbiased discovery proteomics on urine extracellular vesicles (EV), followed by verification by ELISA and western blotting we identified a novel biomarker candidate for PE, vasorin (VASN), which is significantly decreased in PE, along with a known mediator of PE, angiotensinogen (AGT), that was significantly increased in PE as biomarker candidates. Hypothesis: Levels of AGT, VASN and their ratios in peripheral blood can be utilized as biomarkers for PE. Goals/Aims: 1) To determine gestational age (GA)-dependence of AGT, VASN and AGT/VASN plasma levels in human and murine pregnancy. 2) To assess disease association of AGT, VASN and AGT/VASN in a cohort of pregnant women with PE with severe features (sPE) and gestational age-matched normotensive pregnant women (NTP) and in a murine model of PE. Methods: Plasma was collected from GA-matched NTP and sPE. Timed pregnant mice were injected with adenoviral vector (AD) encoding sFLT-1 on embryonic day 10.5 (mouse PE), or with AD encoding enhanced green fluorescent protein injection (mouse control). AGT and VASN were measured by ELISA in human samples and were quantified by western blotting in murine samples. Results: AGT and AGT/VASN showed negative correlations with GA, while VASN levels showed positive correlation with GA in NTP and in mouse controls. PlGF and sFLT-1 levels had weak/no correlations with GA. AGT and AGT/VASN were significantly higher in sPE and mouse PE, while VASN was significantly decreased in sPE and mouse PE as compared to NTP and mouse controls, respectively. To differentiate between sPE vs NTP with receiver operating characteristic curve (ROC) for AGT/VASN: AUC (0.90), Sensitivity =92%, Specificity = 85% at AGT/VASN&gt;81.6. Conclusion: AGT and AGT/VASN ratio increase, and VASN decrease can serve as biomarkers for PE.

Placental biophysical model for prediction of early onset fetal growth restriction in first and second trimester of pregnancy: A prospective cohort study

IntroductionTo assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR). MethodsIn this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11–14, 20–24 and 28–32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls. ResultsOut of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR. ConclusionThe PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR.

Estimating level of serum PLGF and sFLT-1 in Egyptian pregnant women with and without preeclampsia

Estimating level of serum PLGF and sFLT-1 in Egyptian pregnant women with and without preeclampsia

Comparison of the cytokines levels in aqueous humor in vitrectomized eyes versus non-vitrectomized eyes with diabetic macular edema.

This study was conducted to compare concentrations of VEGF family growth factors, inflammation-related factors, and adhesion molecules in the aqueous humor of eyes with diabetic macular edema (DME), with and without prior vitrectomy. A total of 31 eyes were included, 11 with DME that had undergone vitrectomy, 9 with DME but without vitrectomy, and 11 from age-related cataract patients as controls. The concentrations of cytokines including TNF-α, IL-6, IL-8, IP-10, MCP-1, IFN-γ, MIP-1 α, MIP-1 β, PECAM-1, MIF, VCAM-1, ICAM-1, PIGF were quantified using Luminex Human Discovery Assay. Central macular thickness (CMT) values of all eyes were measured using optical coherence tomography (OCT). (1) Vitrectomized DME eyes exhibited significantly higher levels of IL-6 and IL-8 compared to non-vitrectomized eyes (P < 0.05). (2) In vitrectomized group, after Benjamini-Hochberg correction, there was a significant positive correlation between the levels of VEGF and PlGF (rs = 0.855, P < 0.05), as well as the levels of TNF-α and IFN-γ (rs = 0.858, P < 0.05). In non-vitrectomized group, significant positive correlations were found between VEGF and PlGF levels after correcting for multiple comparisons (rs = 0.9, P < 0.05). (3) In non-vitrectomized group, the concentrations of VEGF and PlGF in aqueous humor were significantly positively correlated with CMT values (rs = 0.95, P < 0.05; rs = 0.9, P < 0.05, respectively). The concentrations of IL-6 and IL-8 in the aqueous humor were significantly higher in vitrectomized DME eyes compared to nonvitrectomized DME eyes and the levels of VEGF were similar in the two groups, suggesting that inflammation after vitrectomy may be a key factor in the occurrence and development of DME.

PlGF Levels and Blood Pressure in Pregnant Women with Hypertension

Hypertension in pregnancy is one of the causes of morbidity and mortality in mothers and babies. PlGF has been shown to be associated with the diagnosis of hypertensive disorders in pregnancy. Pregnant women with hypertension are characterized by reduced circulating PlGF levels, even before clinical signs and symptoms. A decrease in the amount of PlGF is positively correlated with the severity of disease progression This study aimed to analyze the relationship between PlGF levels and blood pressure in pregnant women with hypertension. Observational analytic with cross sectional study design. Sampling was total sampling. The number of subject were 34 peoples. The results showed that there was no significant correlation between PlGF levels and blood pressure in pregnant women with hypertension. PlGF levels have no relationship with blood pressure.

CCN1-Mediated Signaling in Placental Villous Tissues after SARS-CoV-2 Infection in Term Pregnant Women: Implications for Dysregulated Angiogenesis.

The global spread of SARS-CoV-2 has increased infections among pregnant women. This study aimed to explore placental pathology alterations and angiogenic factor levels in term pregnant women after SARS-CoV-2 infection in a retrospective single-center study. Additionally, we investigated the role and underlying mechanism of the vascular inflammation-promoting, cysteine-rich protein 61 (CYR61/CCN1) in this context. All analyses were performed in term pregnant women infected with or without SARS-CoV-2. The sFlt-1, PlGF, and sEng serum levels were quantified using ELISA. Placental protein expressions were examined by immunoblot and immunostaining. Additionally, the effect of CCN1 protein on SGHPL-5 trophoblast cells was examined. We found that SARS-CoV-2 activated the inflammatory response in pregnant women, leading to pronounced vascular alterations in placental villous tissues. Elevated serum anti-angiogenic factors (sFlt-1, sEng) upon SARS-CoV-2 infection may directly contribute to these pathological changes. Upregulated CCN1 and pNF-κB in placental villous tissues of infected patients are identified as crucial factors in placental alterations. As a conclusion, CCN1 was significantly elevated in the placentas of term pregnant women infected with SARS-CoV-2. By activating a cascade of inflammatory responses, CCN1 induced the production of the anti-angiogenic factors sFlt-1 and sEng, which may lead to abnormal placental vascular architecture.