Are Twin Pregnancies Complicated by Weight Discordance or Fetal Growth Restriction at Higher Risk of Preeclampsia?

Studies have reported controversial findings on the association between fetal growth restriction (FGR) or intertwin weight discordance and the risk of hypertensive disorders of pregnancy (HDP) in twin pregnancies. The aim of this study was to investigate the association between twin growth disorders and HDP. Twin pregnancies resulting in two live births at St George's Hospital between 2000 and 2019 were included. FGR or small-for-gestational-age (SGA) at birth was assessed using singleton and twin reference charts. Intertwin discordance [(large birthweight - small birthweight)/(large birthweight) × 100%)] was calculated. Logistic regression models were performed. SGA (aOR 2.34, 95% CI 1.60-3.44, p < 0.001), intertwin discordance ≥25% (aOR 2.10, 95% CI 1.26-3.49, p = 0.004) and their co-existence (aOR 2.03, 95% CI 1.16-3.54, p = 0.013) were significantly associated with HDP. After adjusting for the known maternal risk factors of HDP and the intertwin discordance, SGA (using the twin charts) was the strongest independent risk factor associated with HDP (aOR 2.12, 95% CI 1.40-3.22, p < 0.001) and preeclampsia (aOR 2.34, 95% CI 1.45-3.76, p < 0.001). This study highlights that the presence of at least one SGA twin is significantly associated with HDP during pregnancy. Therefore, maternal blood pressure should be closely monitored in twin pregnancies complicated by SGA with or without intertwin discordance

Peripartum echocardiographic changes in women with hypertensive disorders of pregnancy

Women with hypertensive disorders of pregnancy (HDP) present with evidence of significant myocardial dysfunction on echocardiographic assessment at the time of diagnosis. Birth not only cures the syndrome of HDP, but is also associated with a reduction in cardiovascular (CV) volume and resistance load in the mother due to the delivery of the fetoplacental unit. The impact of this physiological change on maternal myocardial function in women with HDP has not been systematically evaluated. The aim of this study is to compare echocardiographic findings immediately before and after childbirth in women with HDP. In this prospective longitudinal study, 30 women with a diagnosis of HDP underwent two consecutive transthoracic echocardiography (TTE) examinations: the first prepartum and the second in the early postpartum period. Paired comparisons of these assessments were performed. Left ventricular (LV) concentric remodelling or hypertrophy were found in 21 (70%) patients and there were no significant differences in cardiac morphology indices: LV mass index (78.9±16.3 g/m vs 77.9 ±15.4 g/m , p=0.611) and relative wall thickness (0.45±0.1 vs 0.44±0.1, p=0.453). LV diastolic function did not demonstrate any peripartum variation: left atrial volume (52.40±15.3 vs 50.97±15.6, p=0.433); lateral E' (0.12±0.03 vs 0.12±0.03, p=0.307) and E/E' ratio (7.88±2.19 vs 7.91±1.74, p=0.934). Systolic function indices such as LV ejection fraction (57.5±4.4% vs 56.4±2.1%, p=0.295) and global longitudinal strain (-15.3±2.6% vs -15.1±3.1%, p=0.715) also remained unchanged. Maternal hemodynamic changes associated with birth did not significantly influence peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy CV load changes or pre-existing maternal CV impairment. Severity and persistence of myocardial dysfunction into the postpartum period may be related to the long-term maternal CV disease legacy of HDP. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.

Perinatal Outcomes of Small for Gestational Age in Twin Pregnancies: Twin vs. Singleton Charts.

Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts (p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally

Current hepatocellular carcinoma systemic pharmacological treatment options

Liver cancer is the sixth common cancer and the second leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) accounts for ~90% of cases of liver cancer and is the fourth most common cause of cancer-related death in the world. Up to now, 4 oral multityrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 5 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, tremelimumab in combination with durvalumab, nivolumab and pembrolizumab in monotherapy) have been commercialized for advanced HCC patients’ treatment. The aim of this editorial is to provide an insight in current hepatocellular carcinoma systemic pharmacological treatment options

Single extracellular vesicle analysis in human amniotic fluid shows evidence of phenotype alterations in preeclampsia.

Amniotic fluid surrounding the developing fetus is a complex biological fluid rich in metabolically active bio-factors. The presence of extracellular vesicles (EVs) in amniotic fluid has been mainly related to foetal urine. We here characterized EVs from term amniotic fluid in terms of surface marker expression using different orthogonal techniques. EVs appeared to be a heterogeneous population expressing markers of renal, placental, epithelial and stem cells. Moreover, we compared amniotic fluid EVs from normal pregnancies with those of preeclampsia, a hypertensive disorder affecting up to 8% of pregnancies worldwide. An increase of CD105 (endoglin) expressing EVs was observed in preeclamptic amniotic fluid by bead-based cytofluorimetric analysis, and further confirmed using a chip-based analysis. HLA-G, a typical placental marker, was not co-expressed by the majority of CD105+ EVs, in analogy with amniotic fluid stromal cell derived-EVs. At a functional level, preeclampsia-derived EVs, but not normal pregnancy EVs, showed an antiangiogenic effect, possibly due to the decoy effect of endoglin. Our results provide a characterization of term amniotic fluid-EVs, supporting their origin from foetal and placental cells. In preeclampsia, the observed antiangiogenic characteristics of amniotic fluid-EVs may reflect the hypoxic and antiangiogenic microenvironment and could possibly impact on the developing fetus or on the surrounding foetal membranes

Transthoracic Echocardiographic Assessment of the Heart in Pregnancy-a position statement on behalf of the British Society of Echocardiography and the United Kingdom Maternal Cardiology Society.

Pregnancy is a dynamic process associated with profound hormonally mediated haemodynamic changes which result in structural and functional adaptations in the cardiovascular system. An understanding of the myocardial adaptations is important for echocardiographers and clinicians undertaking or interpreting echocardiograms on pregnant and post-partum women. This guideline, on behalf of the British Society of Echocardiography and United Kingdom Maternal Cardiology Society, reviews the expected echocardiographic findings in normal pregnancy and in different cardiac disease states, as well as echocardiographic signs of decompensation. It aims to lay out a structure for echocardiographic scanning and surveillance during and after pregnancy as well as suggesting practical advice on scanning pregnant women

Membrane Recruitment of Scaffold Proteins Drives Specific Signaling

Cells must give the right response to each stimulus they receive. Scaffolding, a signaling process mediated by scaffold proteins, participates in the decoding of the cues by specifically directing signal transduction. The aim of this paper is to describe the molecular mechanisms of scaffolding, i.e. the principles by which scaffold proteins drive a specific response of the cell. Since similar scaffold proteins are found in many species, they evolved according to the purpose of each organism. This means they require adaptability. In the usual description of the mechanisms of scaffolding, scaffold proteins are considered as reactors where molecules involved in a cascade of reactions are simultaneously bound with the right orientation to meet and interact. This description is not realistic: (i) it is not verified by experiments and (ii) timing and orientation constraints make it complex which seems to contradict the required adaptability. A scaffold protein, Ste5, is used in the MAPK pathway of Saccharomyces Cerevisiae for the cell to provide a specific response to stimuli. The massive amount of data available for this pathway makes it ideal to investigate the actual mechanisms of scaffolding. Here, a complete treatment of the chemical reactions allows the computation of the distributions of all the proteins involved in the MAPK pathway when the cell receives various cues. These distributions are compared to several experimental results. It turns out that the molecular mechanisms of scaffolding are much simpler and more adaptable than previously thought in the reactor model. Scaffold proteins bind only one molecule at a time. Then, their membrane recruitment automatically drives specific, amplified and localized signal transductions. The mechanisms presented here, which explain how the membrane recruitment of a protein can produce a drastic change in the activity of cells, are generic and may be commonly used in many biological processes

Increased membrane affinity of the C1 domain of protein kinase Cdelta components for the lack of involvement of its C2 Domain in membrane recruitment

[[sponsorship]]生物醫學科學研究所,應用科學研究中心[[note]]已出版;[SCI];有審查制度;具代表性[[note]]http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Drexel&SrcApp=hagerty_opac&KeyRecord=0021-9258&DestApp=JCR&RQ=IF_CAT_BOXPLO

Interfacial membrane properties modulate protein kinase C activation: role of the position of acyl chain unsaturation

We studied the effects of the addition of a series of 1,2- dioctadecenoyl-sn-glycerol-3-phosphoethanolamines to vesicles composed of 1- palmitoyl-2-oleoylphosphatidylserine and 1-palmitoyl-2- oleoylphosphatidylcholine on the activity and membrane binding of protein kinase C (PKC). The three phosphatidylethanolamines (PEs) were dipetroselinoyl-PE, dioleoyl-PE, and divaccenoyl-PE, which have double bonds in positions 6, 9, and 11, respectively. These lipids represent a group of structurally homologous compounds whose physical properties have been compared. We also used a fluorescent probe, 4-[(n-dodecylthio)methyl]-7- (N,N-dimethylamino)coumarin to measure the relative interfacial polarities of LUVs containing each of the three PEs. We find dipetroselinoyl-PE allows the least access of the fluorescent probe to the membrane. This is also the lipid that shows the lowest activation of PKC. The activity of PKC was found to correlate best with the interfacial properties of the three PEs rather than with the curvature energy of the membrane. The results show the sensitivity of the activity of PKC to small changes in lipid structure