Incidence of chest X-ray abnormalities early in the third trimester of twin pregnancy and its relationship with the subsequent development of preeclampsia.

AIM: To clarify the incidence of abnormal findings on chest X-ray (CXR) early in the third trimester of twin pregnancy and its relationship with the development of preeclampsia and preeclampsia-related diseases. METHODS: This was a retrospective cohort study conducted among women with twin pregnancies who underwent chest radiography for preoperative screening early in the third trimester and delivered at our center at >34 weeks' gestation from 2013 to 2017. The primary outcome was the incidence of positive CXR findings, defined either as cardiomegaly or blunting of the costophrenic angle. The secondary outcome was the incidence of maternal complications, including preeclampsia; hemolytic, elevated liver enzymes, and low platelet syndrome; eclampsia; cerebrovascular disease; and placental abruption. We evaluated the significance of positive CXR findings, in addition to confounding factors, in the subsequent development of preeclampsia. RESULTS: During the study period, 358 twin pregnancies were identified, and 330 were finally enrolled. The incidence of positive CXR findings was 18.2%. The incidence of preeclampsia in the CXR-positive group was 36.7% (22/60), which was significantly higher than that in the CXR-negative group (7.0% [19/270]) (p < 0.01). Moreover, positive CXR findings were independently associated with subsequent preeclampsia (adjusted odds ratio: 9.15, 95% confidence interval: 4.13-20.3). CONCLUSION: In twin pregnancies, the incidence of CXR abnormalities early in the third trimester was 18.2%, even without the development of hypertension. This should be considered a significant risk factor for subsequent preeclampsia.

Diagnosis, Management, and Therapy of Fetal Ovarian Cysts Detected by Prenatal Ultrasonography: A Report of 36 Cases and Literature Review.

BACKGROUND: Fetal ovarian cysts are the most frequently diagnosed intra-abdominal cysts; however, the evidence for perinatal management remains controversial. METHODS: We retrospectively reviewed cases of fetal ovarian cysts diagnosed by prenatal ultrasonography at our institution between January 2010 and January 2020. The following were investigated: gestational age at diagnosis, cyst size, appearance, prenatal ultrasound findings, and postnatal outcomes. Prior to 2018, expectant management was applied in all cases; after 2018, in utero aspiration (IUA) of simple cysts ≥40 mm was performed. RESULTS: We diagnosed 29 and seven simple and complex cysts, respectively. Fourteen patients had simple cysts with a maximum diameter <40 mm, and two of them progressed to complex cysts during follow-up; however, when the diameter was limited to <35 mm, no cases showed progression to complex cyst. Fifteen of the simple cysts were ≥40 mm; three progressed to complex cysts, and two of them were confirmed to be ovarian necrosis. In four patients who underwent IUA, the ovaries could be preserved. CONCLUSIONS: IUA is a promising therapy for preserving ovaries with simple cysts ≥40 mm in diameter; however, the indications for fetal surgery and the appropriate timing of intervention require further study.

Complement activation by an angiogenic imbalance leads to systemic vascular endothelial dysfunction: A new proposal for the pathophysiology of preeclampsia.

The underlying mechanism of preeclampsia by which an angiogenic imbalance results in systemic vascular endothelial dysfunction remains unclear. Complement activation directly induces endothelial dysfunction and is known to be involved in preeclampsia; nevertheless, the association between complement activation and angiogenic imbalance has not been established. This study aimed to evaluate whether angiogenic imbalance affects the expression and secretion of inhibitory complement factor H (CFH) in endothelial cells, resulting in complement activation and systemic vascular endothelial dysfunction. Viability of human umbilical vein endothelial cells (HUVECs) was assessed upon CFH knockdown by targeted-siRNA, and were incubated with complement factors. HUVECs were also treated with placental growth factor (PlGF) and/or soluble fms-like tyrosine kinase 1 (sFlt1), and CFH expression and secretion were measured. These cells were evaluated by cell viability assay and cell surface complement activation was quantified by immunocytochemical assessment of C5b-9 deposition. HUVECs transfected with CFH-siRNA had significantly lower viability than that of control cells. Moreover, the expression and secretion of CFH were significantly increased upon PlGF treatment compared with PlGF + sFlt1 combo. HUVECs treated with PlGF had less C5b-9 deposition and higher viability than HUVECs treated with PlGF + sFlt1. In summary, CFH was found to be essential for endothelial cell survival by inhibiting complement activation. An angiogenic imbalance, including decreased PlGF and increased sFlt1, suppresses CFH expression and secretion, resulting in complement activation on the surface of endothelial cells and systemic vascular endothelial dysfunction.

Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library.

INTRODUCTION: Preeclampsia therapy has not been established, except for the termination of pregnancy. The aim of this study was to identify a potential therapeutic agent from traditional Japanese medicine (Kampo) using the drug repositioning method. MATERIALS AND METHODS: We screened a library of 74 Kampo to identify potential drugs for the treatment of preeclampsia. We investigated the angiogenic effects of these drugs using human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were performed to measure the levels of placental growth factor (PlGF) in conditioned media treated with 100 µg/mL of each drug. We assessed whether the screened drugs affected cell viability. We performed tube formation assays to evaluate the angiogenic effects of PlGF-inducing drugs. PlGF was measured after administering 10, 50, 100, and 200 µg/mL of the candidate drug in the dose correlation experiment, and at 1, 2, 3, 6, 12, and 24 h in the time course experiment. We also performed tube formation assays with the candidate drug and 100 ng/mL of soluble fms-like tyrosine kinase 1 (sFlt1). PlGF production by the candidate drug was measured in trophoblastic cells (BeWo and HTR-8/SVneo). The Mann-Whitney U test or one-way analyses of variance followed by the Newman-Keuls post-hoc test were performed. P-values < 0.05 were considered significant. RESULTS: Of the 7 drugs that induced PlGF, Tokishakuyakusan (TS), Shoseiryuto, and Shofusan did not reduce cell viability. TS significantly facilitated tube formation (P = 0.017). TS administration increased PlGF expression in a dose- and time-dependent manner. TS significantly improved tube formation, which was inhibited by sFlt1 (P = 0.033). TS also increased PlGF production in BeWo (P = 0.001) but not HTR-8/SVneo cells (P = 0.33). CONCLUSIONS: By using the drug repositioning method in the in vitro screening of the Kampo library, we identified that TS may have a therapeutic potential for preeclampsia. Its newly found mechanisms involve the increase in PlGF production, and improvement of the antiangiogenic state.

Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.

This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group, n = 14) and CAM without fetal infection (CAM-f[-] group, n = 31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all, p > 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21-13.7] µg/ml) than in the CAM-f(-) (3.61 [2.71-4.65] µg/ml) or control group (3.39 [2.81-3.93] µg/ml; p < 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 µg/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera and LRG mRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p < 0.01). In vitro experiments using a fetal liver-derived cell line (WRL68) showed that the expression of LRG mRNA was significantly increased after interleukin (IL)-6, IL-1ß, and tumor necrosis factor- alpha (TNF-α) stimulation (p < 0.01); the induction was considerably stronger following IL-6 and TNF-α stimulation (p < 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG production in utero.

The Role of Preoperative and Postoperative Transversus Abdominis Plane and Rectus Sheath Block in Patients Undergoing Total Laparoscopic Hysterectomy.

PURPOSE: This study was performed to assess the efficacy of a preoperative and postoperative transversus abdominis plane (TAP) and rectus sheath (RS) block compared with no TAP and RS block in patients undergoing total laparoscopic hysterectomy (TLH). DESIGN: Prospective observational cohort study. METHODS: From January 2014 to December 2017, 195 women undergoing TLH were categorized into three groups based on their perioperative analgesia: no TAP + RS block (n = 88), preoperative TAP + RS block + systemic analgesia (n = 68), and postoperative TAP + RS block + systemic analgesia (n = 39). We evaluated use of nonsteroidal anti-inflammatory drugs (NSAIDs) and NSAID consumption within the first 12 hours postoperatively and the numerical rating scale score at 0, 12, and 24 hours postoperatively. FINDINGS: Women with a preoperative TAP + RS block had a significantly lower utilization rate of NSAIDs within the first 12 hours postoperatively (54.4% vs 75.0%; P = .007), lower postoperative flurbiprofen dose (45.5 vs 62.0 mg; P = .048), and lower numerical rating scale score at 12 hours postoperatively (1.63 vs 2.20; P = .002) compared with women with no TAP + RS block. CONCLUSIONS: A preoperative TAP + RS block provided superior postoperative analgesia in patients undergoing TLH and reduced analgesic consumption during the first 12 hours postoperatively.