Downregulation of CDC42 inhibits the proliferation and stemness of human trophoblast stem cell via EZRIN/YAP inactivation.

Placental dysplasia increases the risk of recurrent spontaneous abortion (RSA). However, the underlying mechanism regulating placental development remains unclear. In this study, we showed that the expression of CDC42 was decreased in the villous tissue of RSA samples compared to healthy controls. Further examination demonstrated that CDC42 deficiency led to the differentiation of human trophoblast stem cells (hTSCs) and inhibited their proliferation. Genetic manipulation of YAP and EZRIN in hTSCs revealed that CDC42 regulates the stemness and proliferation of hTSCs; this is dependent on EZRIN, which translocates YAP into the nucleus. Moreover, the expression pattern of EZRIN, YAP, and Ki67 was also abnormal in the villous tissue of RSA samples, consistent with in vitro experiments. In summary, these findings suggest that the CDC42/EZRIN/YAP pathway plays an important role in placental development.

Dexmedetomidine reduced cytokine release during postpartum bleeding-induced multiple organ dysfunction syndrome in rats.

Dexmedetomidine (DEX) is an α 2-adrenergic agonist. It decreases the levels of norepinephrine release, resulting in a reduction of postsynaptic adrenergic activity. In the present study, the effects of DEX on postpartum bleeding-induced multiple organ dysfunction syndrome (BMODS) were studied in rats in which BMODS was induced by the combination of hypotension and clamping of the superior mesenteric artery. We evaluated the role of dexmedetomidine (DEX) in cytokine release during postpartum BMODS in rats. In summary, the present study demonstrated that DEX administration reduced IFN-r and IL-4 release and decreased lung injury during postpartum BMODS. It is possible that DEX administration decreased inflammatory cytokine production in BMODS by inhibiting inflammation and free radical release by leukocytes independent of the DEX dose.

Geographic variation in management of patients with placenta accreta spectrum: An international survey of experts (GPASS).

OBJECTIVE: To describe global geographic variations in the diagnosis and management of placenta accreta spectrum (PAS). METHODS: An international cross-sectional study was conducted among PAS experts practicing at medical institutions in member states of the United Nations. Survey questions focused on diagnostic evaluation and management strategies for PAS. RESULTS: A total of 134 centers participated. Participating centers represented each of the United Nations' designated regions. Of those, 118 (88%) reported practicing in a medium-volume or high-volume center. First-trimester PAS screen was reported in 35 (26.1%) centers. Respondents consistently implement guideline-supported care practices, including utilization of ultrasound as the primary diagnostic modality (134, 100%) and implementation of multidisciplinary care teams (115, 85.8%). Less than 10% of respondents reported routinely managing PAS without hysterectomy; these centers were predominantly located in Europe and Africa. Antepartum management and availability of mental health support for PAS patients varied widely. CONCLUSION: Worldwide, there is a strong adherence to PAS care guidelines; however, regional variations do exist. Comparing variations in care to outcomes will provide insight into the clinically significant practice variability.

The Risk of Postpartum Hemorrhage Following Prior Prelabor Cesarean Delivery Stratified by Abnormal Placentation: A Multicenter Historical Cohort Study.

Background: Prior prelabor cesarean delivery (CD) was associated with an increase in the risk of placenta previa (PP) in a second delivery, whether it may impact postpartum hemorrhage (PPH) independent of abnormal placentation. This study aimed to assess the risk of PPH stratified by abnormal placentation following a first CD before the onset of labor (prelabor) or intrapartum CD. Methods: This multicenter, historical cohort study involved singleton, pregnant women at 28 weeks of gestation or greater with a CD history between January 2017 and December 2017 in 11 public tertiary hospitals within 7 provinces of China. PPH was analyzed in the subsequent pregnancy between women with prior prelabor CD and women with intrapartum CD. Furthermore, PPH was analyzed in pregnant women stratified by complications with PP alone [without placenta accreta spectrum (PAS) disorders], complications with PP and PAS, complications with PAS alone (without PP), and normal placentation. We performed multivariate logistic regression to calculate adjusted odds ratios (aOR) and 95% CI controlling for predefined covariates. Results: Out of 10,833 pregnant women, 1,197 (11%) women had a history of intrapartum CD and 9,636 (89%) women had a history of prelabor CD. Prior prelabor CD increased the risk of PP (aOR 1.91, 95% CI 1.40-2.60), PAS (aOR 1.68, 95% CI 1.11-2.24), and PPH (aOR 1.33, 95% CI 1.02-1.75) in a subsequent pregnancy. After stratification by complications with PP alone, PP and PAS, PAS alone, and normal placentation, prior prelabor CD only increased the risk of PPH (aOR 3.34, 95% CI 1.35-8.23) in a subsequent pregnancy complicated with PP and PAS. Conclusion: Compared to intrapartum CD, prior prelabor CD increased the risk of PPH in a subsequent pregnancy only when complicated by PP and PAS.

Effect of blood pressure on reversible posterior leukoencephalopathy syndrome in pre-eclampsia or eclampsia.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a critical maternal complication in some pre-eclampsia (PE) and nearly all eclampsia patients; RPLS is associated with high blood pressure (BP). However, the effect of BP on RPLS and the different characteristics of RPLS in PE or eclampsia are largely unknown. We consecutively collected data from 69 patients who were diagnosed with RPLS in PE or eclampsia between 2013 and 2017. The BP and biochemical indicators at onset and post onset of RPLS were examined to explore their likely correlation with RPLS. We grouped patients into PE (n=40) and eclampsia (n=29) groups according to whether a seizure had occurred. Information regarding BP, clinical symptoms and imaging features was collected retrospectively to explore the differences between groups. BP measurements (moderate and severe hypertension, systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP) levels) and biochemical indicators (uric acid, lactate dehydrogenase (LDH), C-reactive protein and WBC) were higher at the onset of RPLS than post-onset of RPLS (P<0.001), whereas normal BP and serum albumin levels were lower (P<0.001). Moreover, the BP values (SBP, DBP and MAP) and LDH levels were significantly correlated with the degree of edema (Spearman's correlation, P<0.01). These results suggest that hypertension and LDH are likely factors in the development of RPLS in PE or eclampsia. Moreover, BP and LDH were closely related to the degree of brain edema, However, no significant differences were found between the PE and eclampsia groups with the exception of age and consciousness impairment.