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Umbilical vein varix is associated with a high incidence of fetal anomalies and perinatal complications. There are two types of umbilical vein varix: fetal intra‐abdominal and extra‐abdominal. Herein, a case is reported of severe fetal anemia with extra‐abdominal umbilical vein varix. A 33‐year‐old primigravida was referred to our hospital for fetal growth restriction, fetal cardiomegaly, and decreased fetal movements at 26 weeks' gestation. A Doppler assessment showed an elevated middle cerebral artery peak systolic velocity at 2.2 MoM, suggesting fetal anemia. Umbilical vein varix had caused intermittent turbulent flow, provoking hemolytic anemia. Intrauterine transfusion improved fetal circulatory failure and anemia and prolonged gestational period. At 33 weeks' gestation, the patient underwent cesarean delivery due to nonreassuring fetal status. Pathological analysis revealed focal loss of vascular smooth muscle of the umbilical vein. Extra‐abdominal umbilical vein varix has been reported in 14 cases including this case. The antenatal diagnosis rate is reported to be 79%; fetal heartbeat abnormalities and fetal deaths were reported as 50% and 14%, respectively. Eighty‐six percent of patients had intra‐umbilical cord thrombosis, but currently this is the only case of hemolytic anemia. Furthermore, extra‐abdominal umbilical vein varix may present as fetal hydrops with anemia. During ultrasound examination of fetal anemia, umbilical cord screening should be performed with caution. [ABSTRACT FROM AUTHOR]

Background: Uterine atony is the leading cause of severe postpartum hemorrhage (PPH); however, the underlying cause of intractable atonic PPH unresponsive to conventional treatments (such as uterotonics and intrauterine balloon tamponade) remains unclear.Objectives: The aim of this study was to investigate whether intractable atonic PPH is associated with the type of bleeding (arterial or nonarterial) and its location, along with variations in the size and shape of the uterine cavity after delivery.Study design: This retrospective study included women who had undergone a dynamic computed tomography (CT) scan for the management of severe PPH at Kyoto University Hospital between April 2011 and March 2017. Patients' electronic medical records were reviewed, and relevant clinical information was collected. The presence of contrast extravasation (CE) on CT images in the early phase (40 s) was regarded as active arterial bleeding. Bleeding sites and size of the uterine cavity were evaluated using an xyz coordinate system. The size of the uterine cavity was compared between groups with CE into the upper and lower parts of the uterine body.Results: Of the 60 women assessed for eligibility, 30 were included in the current analysis. Contrast extravasation was detected in 19 women, with 14 showing CE in the early phase. The presence of CE in the early phase was significantly associated with the need for transarterial embolization (Fisher's exact test, p = .0017). The upper and lower parts of the uterine cavity were 97.4 ± 2.7 mm (mean ± standard error of the mean) and 87.2 ± 3.5 mm in length, respectively. The maximum anteroposterior diameters of the upper and lower parts of the uterine cavity were 23.1 ± 2.6 and 76.0 ± 3.0 mm, respectively, and the largest transverse diameters were 67.3 ± 1.9 and 81.1 ± 2.3 mm, respectively. The group that showed CE into the upper uterine cavity had significantly larger qualitative parameters of the upper uterine cavity compared to the group with CE into the lower uterine cavity. The gate from the lower uterine cavity toward the upper uterine cavity was narrow (anteroposterior diameter of 22.6 ± 2.0 mm, transverse diameter of 40.7 ± 3.3 mm), and the intrauterine balloon was always found in the lower uterine cavity on the CT scan. The upper uterine body was characterized by a flat oval-shaped cavity (xy plane), thick uterine wall, and lack of uniformity among bleeding sites (z  =  62.4 ± 14.8 mm). In contrast, the lower uterine cavity was a circular shape (xy plane) with thin walls, and bleeding sites were located at lateral sides around the level of the internal os (z =  -18.8 ± 4.9 mm).Conclusions: Atonic PPH has a significant subtype, named "PRACE," which is characterized by PPH, resistance to treatment, and arterial CE. The need for embolization can be predicted by the presence of arterial bleeding and its location, along with the shape of the uterine cavity. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate epidemiological and clinical aspects of severe postpartum hemorrhage (PPH) in Japan. Methods: We used national health insurance claims from 2011 to 2014 provided by the Ministry of Health, Labour and Welfare. The data included randomly selected claims that covered 10% of all inpatients in October, a so-called sampling dataset (covering 1/120 inpatients per year). We extracted claims for transfused blood, and further narrowed down the claims by names of diseases linked to PPH. As most referral obstetric facilities have adopted the diagnosis procedure combination (DPC)-based payment system while small-scale obstetric facilities have not (non-DPC facilities), the claims were also analyzed separately for DPC and non-DPC facilities. We assessed the incidence and causes of PPH, transfusion volume of red blood cells (RBC) and fresh frozen plasma (FFP), and surgical hemostatic management. Results: The number of PPH cases that required blood transfusion in the sampling dataset was 29, 29, 32, and 36 in 2011, 2012, 2013, and 2014, respectively. The leading cause of PPH was uterine atony followed by placental abruption. Although no specific trends were observed for the volume of transfused RBC (1467 ± 234 ml in 2014), there was a steady increase in the rate of FFP utilization in non-DPC facilities from 37% to 79% over the 4-year sampling period. Intrauterine balloon tamponade emerged in 2014. Conclusion: This nationwide survey indicates that the annual incidence of severe PPH is increasing. Furthermore, FFP has become more prevalent in small-scale obstetric facilities. [ABSTRACT FROM AUTHOR]

A caesarean section (CS) is a major risk factor for a venous thromboembolism, and enoxaparin, a low-molecular-weight heparin, has been widely used for thromboprophylaxis. However, it remains unclear whether an enoxaparin thromboprophylaxis has an acceptable safety profile when given early after CS compared to delayed administration, especially in the presence of an epidural catheter. This study aimed to survey cases in which enoxaparin administration was performed within 24 hours of CS and to evaluate patient outcomes with or without epidural anaesthesia. The number of eligible cases were 578: 328 patients received an epidural anaesthesia (epidural group), and 250 did not (non-epidural group). In both groups, no patient developed a spinal epidural haematoma. A wound or a subcutaneous bleeding occurred in 22 (6.7%) and 20 (8.0%) cases in the epidural and non-epidural groups, respectively. One patient developed a mild pulmonary embolism, and one case of asymptomatic deep vein thrombosis was detected. An enoxaparin administration within 24 hours of CS appears to be reasonable, regardless of an epidural anaesthesia. Impact statement What is already known on this subject? A venous thromboembolism (VTE) after a caesarean section (CS) remains a significant cause of maternal morbidity and mortality. Therefore, a thromboprophylaxis using enoxaparin, a low-molecular-weight heparin, has been widely recommended and accepted. However, there is no consensus regarding the optimal timing to initiate an enoxaparin administration after CS in the presence of an epidural catheter. What do the results of this study add? This is the largest study that has collected cases receiving enoxaparin within 24 hours of a CS. Irrespective of the presence of an epidural catheter, no patient developed a spinal epidural haematoma after an early administration of enoxaparin. Furthermore, the incidence of haemorrhagic complications did not increase. What are the implications of these findings for clinical practice and/or further research? Given the significant incidence of VTE after CS and the extremely low frequency of spinal epidural haematomas, it can be justified to initiate thromboprophylaxis with enoxaparin soon after CS. However, appropriately designed, large clinical trials are necessary to examine the safety and efficacy of an early enoxaparin administration after CS. Based on such studies, the starting time of thromboprophylaxis after a CS should be decided. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role of beta‐human chorionic gonadotropin (HCG) level and its change prior to methotrexate (MTX) treatment as predictors of treatment success and to access the posttreatment observation period for ectopic tubal pregnancy. Methods: Clinical data of 41 females treated with MTX for tubal pregnancies were reviewed and analyzed retrospectively. Results: Among 41 patients, 34 achieved complete resolution without surgery. No statistically significant difference was observed in the presence of hemorrhagic ascites, serum progesterone levels, or diameters of adnexal mass between the MTX success and failure groups. Serum HCG levels on the day of MTX administration (day 1) were significantly lower in the MTX success group. Moreover, % HCG change per day, which represents the increment ratio of HCG prior to MTX treatment, was significantly lower in the MTX success group. Receiver operating characteristic (ROC) curves demonstrated that the treatment success was predicted by % HCG change per day less than +12.6% per day with a sensitivity of 87% and a specificity of 71%. The duration from treatment to complete recovery was strongly correlated with day 1 HCG levels. Conclusions: Pretreatment HCG change is a significant predictor of therapeutic success of MTX treatment, and the treatment period may be predicted from initial HCG levels. [ABSTRACT FROM AUTHOR]

Background: Premature rupture of membranes occurring in previable midtrimester patients is associated with perinatal mortality, and optimal therapeutic methods are yet to be established.Objective: This study's objective was to investigate whether an elastomeric sealant, which has been used as a hemostatic agent for arterial anastomosis, could plug the uterine endocervical canal to prevent leakage of intrauterine fluid in an ex vivo model.Methods: The elastomeric sealant or fibrin glue was applied to the cervix of uteri removed for benign gynecological disease (n = 4). Normal saline was administered into the ex vivo uterine cavity through a catheter using a pressure infusion bag. Intrauterine pressure was measured using a digital pressure gauge, and the pressure at which normal saline started leaking out of the uterine cervix was compared between both the sealants.Results: No fluid leakage was observed with the elastomeric sealant until the pressure exceeded 20 kPa (150 mmHg), while the leakage onset pressure with fibrin sealant was 6.6 ± 1.8 kPa (50 ± 14 mmHg). The threshold leak pressure where the onset of liquid flow was initiated was significantly different between both the sealants (p < .0001).Conclusions: Intracervical elastomeric sealant exhibited powerful fluid leakage prevention in an ex vivo model. The sealant would have potential to prevent the leakage of amniotic fluid in pregnancies with previable premature rupture of membranes. [ABSTRACT FROM AUTHOR]

Background: Defective decidual endovascular trophoblast invasion and subsequent impaired spiral artery remodeling is highly associated with the pathogenesis of preeclampsia (PE). Since there are scant and conflicting data regarding the function of Wnt5a signaling in extravillous trophoblasts (EVT), the aim of this study was to investigate whethere impaired Wnt5a signaling affects the invasive and tube forming capabilities of EVT.Methods: Expression levels of Wnt ligands were compared between first trimester chorionic villi of women who later developed PE and women with unaffected pregnancies using publicly available microarray data (GSE12767). Wnt5a expression was examined in placentas using quantitative RT-PCR, Western blot analysis and immunohistochemistry. The function of Wnt5a signaling in EVT was investigated in an immortalized first trimester EVT cell line, HTR-8/SVneo, using small-interfering RNAs, recombinant human Wnt5a (rhWnt5a), and inhibitors of JNK or PKC.Results: Microarray data analysis of the first trimester placentas showed that, among Wnt ligands, Wnt5a expression was significantly lower in women who later developed PE. The mRNA and protein expression levels of Wnt5a were significantly decreased in PE placentas compared with normal term placentas. Wnt5a knockdown significantly suppressed invasion and tube formation of HTR-8/SVneo cells, while the addition of rhWnt5a augmented the cell migration, invasion, and tube formation. Repression of Wnt5a/PKC signaling in HTR-8/SVneo cells inhibited cell invasion, but did not alter cell tube formation. In contrast, inhibition of Wnt5a/JNK signaling attenuated rhWnt5a-induced invasion and tube formation capabilities.Conclusions: These findings suggest that impaired Wnt5a signaling is associated with poor placentation and subsequent PE. [ABSTRACT FROM AUTHOR]

Problem: Excisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin protein, may be a barrier to ascending pathogens during pregnancy. We thus hypothesized that hyposecretion of cervical MUC5B is associated with preterm birth after cervical excisional surgery. Method of study: This prospective nested case‐control study (Study 1) included pregnant women who had previously undergone cervical excisional surgery across 11 hospitals. We used proteomics to compare cervicovaginal fluid at 18–22 weeks of gestation between the preterm and term birth groups. In another case‒control analysis (Study 2), we compared MUC5B expression in nonpregnant uterine tissues between 15 women with a history of cervical excisional surgery and 26 women without a history of cervical surgery. Results: The abundance of MUC5B in cervicovaginal fluid was significantly decreased in the preterm birth group (fold change = 0.41, p =.035). Among the 480 quantified proteins, MUC5B had the second highest positive correlation with gestational age at delivery in the combined preterm and term groups. The cervicovaginal microbiome composition was not significantly different between the two groups. Cervical length was not correlated with gestational age at delivery (r = 0.18, p =.079). Histologically, the MUC5B‐positive area in the nonpregnant cervix was significantly decreased in women with a history of cervical excisional surgery (0.85‐fold, p =.048). The distribution of MUC5B‐positive areas in the cervical tissues of 26 women without a history of cervical excisional surgery differed across individuals. Conclusions: This study suggests that the primary mechanism by which cervical excisional surgery causes preterm birth is the hyposecretion of MUC5B due to loss of the cervical glands. [ABSTRACT FROM AUTHOR]