Prenatal detection of right aortic arch.

PURPOSE: To examine an unselective population of fetuses with right aortic arch (RAA) and suggest perinatal management. Second, to evaluate the importance and possible implication of fetal MRI in those cases. METHODS: Retrospective study of 36 patients with RAA diagnosed prenatally between 2006 and 2017 in a tertiary referral center. RESULTS: 32 fetuses were diagnosed with RAA and 4 with double aortic arch (DAA). 7 (19, 5%) cases had intracardiac abnormalities. Tetralogy of the Fallot was the most frequent one. Other extracardiac malformations were observed in 11/36 (30, 6%). Karyotype was available in 16 (44, 5%) cases. Two had 22q11.2 microdeletion, two trisomy 21, and one 20p12.2 duplication. Two needed surgery for respiratory symptoms. A newborn was identified with epilepsy, Lennox-Gastaud syndrome and Pallister-Killian syndrome postnatally and another one with showed hyperreflexia and premature closer of the fontanelle. Three feticides were performed for pregnancy termination in one case with 22q11 deletion, trisomy 21, and partial agenesis of corpus callosum. CONCLUSION: RAA can be detected by fetal echocardiography and it is associated with other cardiac or non-cardiac abnormalities, 22q11 microdeletion, trisomy 21, and other chromosomal abnormalities. karyotyping should be offered in any case of RAA, irrespective of co-existing malformations. Fetal MRI is a promising diagnostic tool for assessment of congenital cardiovascular abnormalities and extracardiac anomalies.

Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in ectopic endometrium of endometriosis patients.

BACKGROUND: Current evidence suggests that endometrial-derived stem cells, spilled in the peritoneal cavity via retrograde menstruation, are key players in the establishment of endometriotic lesions. The aim of this study was to determine the presence and distribution of the stemness-related factors OCT4, SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis. METHODS: Immunohistochemical analysis was used to determine stromal and epithelial expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP) endometrium (n = 69) and endometriotic tissue (n = 90) and in control endometrium (n = 50). Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was performed in paired samples of EP endometrium and endometriotic tissue. Co-immunofluorescence staining was performed for OCT4 and SOX15. For statistical analyses we used unpaired t-test, Fisher combination test and Spearman test. For paired analyses, paired t-test and McNemar test were used. RESULTS: We detected a significant correlation between the expression of the established stem cell marker OCT4 and the stemness-related markers SOX15 (p < 0.001) and TWIST1 (p = 0.002) but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A concordant expression of OCT4 and SOX15 in the same sample was observed in epithelial cells of the endometriotic tissue (71.7%). The expression of stemness-related factors was not associated with proliferative or secretory phase of the menstrual cycle in endometriosis patients but was found to be differentially expressed during the menstrual cycle in the control group. Increased expression of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001) and unpaired analysis (p = 0.040, p < 0.001 and p = 0.001). CONCLUSION: Our findings support the hypothesis that upregulation of stem cell-related factors contribute to the establishment of endometriotic lesions. TRIAL REGISTRATION: The study was approved by the institutional review board (545/2010 on 6th of May 2014) of the Medical University of Vienna ( http://ethikkommission.meduniwien.ac.at/fileadmin/ethik/media/dokumente/register/alle_2010.pdf ).

Velamentous cord insertion as a risk factor for obstetric outcome: a retrospective case-control study.

PURPOSE: Velamentous umbilical cord insertion (VCI) is associated with adverse pregnancy outcomes. Literature lacks data on Doppler. We aimed to evaluate obstetric outcomes and results of uterine and umbilical artery Doppler flowmetry associated with VCI. MATERIALS AND METHODS: In a retrospective case-control study, 108 singleton pregnancies with VCI were age- and body mass index-matched to 108 singleton pregnancies without VCI. The main outcome parameters were obstetric outcome, pregnancy-related complications, uterine artery flowmetry at the second-trimester screening, and umbilical artery flowmetry before delivery. Statistical analysis was accomplished using Pearson's Chi-square test or Fisher's exact test, and the Mann-Whitney U test, where appropriate. RESULTS: Pregnancies with VCI revealed a significantly higher PI in the umbilical artery during the last measurement before delivery (1.00 ± 0.25 vs. 0.90 ± 0.10; p = 0.001). Gestational age at this measurement did not differ between the groups. Fetal malformations and intrauterine fetal death were more common in pregnancies with VCI (12.7 vs. 0 %; p < 0.001, and 6.5 vs. 0 %; p = 0.014, respectively). Patients with VCI delivered significantly earlier (36.2 ± 4.5 vs. 38.4 ± 2.6; p < 0.001). CONCLUSION: Higher rates of (early) preterm delivery were found in pregnancies with VCI. Fetuses with VCI also suffered from malformations and IUFD more frequently. The last pulsatility index value in the umbilical artery, before delivery, was significantly higher in pregnancies with VCI, which is of uncertain clinical value.

Enhanced epithelial to mesenchymal transition (EMT) and upregulated MYC in ectopic lesions contribute independently to endometriosis.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose polarity and cell-to-cell contacts and acquire the migratory and invasive abilities of mesenchymal cells. These abilities are thought to be prerequisites for the establishment of endometriotic lesions. A hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in epithelial cells. TWIST1, a transcription factor that represses E-cadherin transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription factor, and its close relative SLUG have similar properties to TWIST1 and are thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by an estrogen response cis-acting element (ERE) in its promoter, is associated with proliferation in endometriosis. The role of EMT and proliferation in the pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC expression. METHODS: CDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42 ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples, were collected during the same surgical procedure. We evaluated TWIST1 and MYC protein expression by immunohistochemistry (IHC) in the epithelial and stromal tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched samples were analyzed from the same patient. Concordant expression of TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed. RESULTS: We found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p < 0.001) in endometriosis, while CDH1 expression was concordantly reduced in these samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also significantly enhanced in ectopic endometrium compared to eutopic tissues (p = 0.008). We found exclusive expression of either TWIST1 or MYC in the same samples (p = 0.003). CONCLUSIONS: Epithelial TWIST1 is overexpressed in endometriosis and may contribute to the formation of endometriotic lesions by inducing epithelial to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found exclusive expression of either TWIST1 or MYC in the same samples, indicating that EMT and proliferation contribute independently of each other to the formation of endometriotic lesions.

To Predict the Requirement of Pharmacotherapy by OGTT Glucose Levels in Women with GDM Classified by the IADPSG Criteria.

The aim of this study was to assess the association between OGTT glucose levels and requirement of pharmacotherapy in GDM patients classified by the IADPSG criteria. This study included 203 GDM patients (108 managed with lifestyle modification and 95 requiring pharmacotherapy). Clinical risk factors and OGTT glucose concentrations at 0 (G0), 60 (G60), and 120 min (G120) were collected. OGTT glucose levels were significantly associated with the later requirement of pharmacotherapy (ROC-AUC: 71.1, 95% CI: 63.8-78.3). Also, the combination of clinical risk factors (age, BMI, parity, and pharmacotherapy in previous gestation) showed an acceptable predictive accuracy (ROC-AUC: 72.1, 95% CI: 65.0-79.2), which was further improved when glycemic parameters were added (ROC-AUC: 77.5, 95% CI: 71.5-83.9). Random forest analysis revealed the highest variable importance for G0, G60, and age. OGTT glucose measures in addition to clinical risk factors showed promising properties for risk stratification in GDM patients classified by the recently established IADPSG criteria.

Comprehensive study of angiogenic factors in women with endometriosis compared to women without endometriosis.

OBJECTIVE: Endometriosis is a benign gynaecological disease, affecting women during their reproductive years. Angiogenesis represents a crucial step in the pathogenesis of endometriosis, because endometriotic lesions require neovascularization. In this study several angiogenesis-related genes have been studied in the context of endometriosis. Some of the analyzed angiogenic factors as well as their interactions were studied the first time regarding a possible association with endometriosis. STUDY DESIGN: This case-control study consisted of 205 biopsies of 114 patients comprising 61 endometriosis patients and 53 control patients. Among them in 29 cases paired samples were obtained. VEGFA, VEGFR2, HIF1A, HGF, NRP1, PDGFB, FGF18, TNFα, TGFB2, EPHB4, EPO and ANG mRNA expression was analyzed by qRT-PCR in ectopic tissue samples, in eutopic endometrium of women with and without endometriosis, and in unaffected peritoneum of women with and without endometriosis. RESULTS: VEGFR2, HIF1A, HGF, PDGFB, NRP1 and EPHB4 are overexpressed in ectopic lesions compared to eutopic tissues. VEGFR2, HGF, PDGFB, NRP1, and EPHB4 showed highest mRNA levels in peritoneal implants, in contrast HIF1A showed the highest expression in ovarian endometriomas. Correlation analyses of angiogenic factors in ectopic lesions revealed the strongest associations between VEGFR2, PDGFB, and EPHB4. We further showed a significant upregulation of VEGFR2, HIF1A and EPHB4 in eutopic endometrium of women with endometriosis compared to that of controls and a trend towards upregulation of HGF. Additionally, a significant downregulation for HIF1A, HGF and EPHB4 was observed in unaffected peritoneal tissues of women with endometriosis compared to controls. CONCLUSION: We identified new genes (EPHB4 and NRP1) that may contribute to angiogenesis in endometriosis beside known factors (VEGFA, VEGFR2, HIF1A, HGF, and PDGFB). Correlation studies revealed the putative importance of EBHB4 in association with endometriosis. Our analyses support preliminary reports that angiogenic factors seem to be differently expressed in peritoneal implants, ovarian endometriomas and deep infiltrating endometriosis. Our observation that angiogenic factors are differently expressed in the unaffected peritoneum of women with endometriosis compared to women without endometriosis underlines the importance of the peritoneum in the establishment of endometriosis.

Pain perception during outpatient cystoscopy: a prospective controlled study.

OBJECTIVE: Rigid cystoscopy is a common diagnostic tool in the assessment of lower urinary tract symptoms, but it is an invasive procedure which can cause distress. Data exist about pain perception during cystoscopy in male patients but only a few data are available in women. The purpose of this study was to investigate pain perception in urogynecologic patients during cystoscopy and compare it with pain perception during urodynamics. We also investigated the difference between anticipated and actual pain perception. STUDY DESIGN: A cooperative, non-randomized cohort study was performed including 109 women with pelvic floor dysfunction scheduled for outpatient cystoscopy or urodynamic testing. Patients completed a questionnaire and a visual analog scale (VAS, 0-10 cm) before and after examination. Patients were called one day after examination and asked about pain and their general state of health. According to power calculation, a sample size of 52 patients per group was needed to detect a 2 cm difference in pain scores on the VAS - judged as a clinically significant - with 95% power and a two-sided significance level of 0.05. RESULTS: In 57 patients undergoing cystoscopy versus 52 patients undergoing urodynamics, the main pain scores on VAS were 1.9 cm for cystoscopy and 1.2 cm for urodynamics (p=0.03). Patients in both groups anticipated more pain than they actually experienced: 2.7±2.4 before versus 1.9±1.8 after cystoscopy (p<0.01) and 2.1±2.4 before versus 1.2±1.6 after urodynamics (p<0.01). CONCLUSION: Patients experience cystoscopy as more painful than urodynamics. Patients anticipate both cystoscopy and urodynamics to be more painful than they actually are.

Effective management and intrauterine treatment of congenital cytomegalovirus infection: review article and case series.

OBJECTIVE: Human Cytomegalovirus (CMV) infection during pregnancy is the most frequent viral cause of intrauterine infection and responsible for various cerebral and other ultrasound abnormalities of the fetus. It is the leading infectious cause of mental retardation and sensorineural deafness in affected newborns and infants. We present three cases of primary cytomegalovirus infection in pregnancy and demonstrate three different scenarios of the disease with regard to clinical outcome and therapy options. We first report on CMV related phospho- and glycoprotein-specific antibody reactivities in amnion fluid that have not been reported earlier in literature. CASE PRESENTATION: Case 1: A 33-year-old Gravida II Para I was referred for primary CMV infection at 15 weeks gestation presenting with a history of fever. HIG therapy was performed resulting in good neonatal outcome. Case 2: A 23-year-old Gravida I was referred for targeted ultrasound at 23 weeks of gestation presenting with intrauterine growth retardation, multiple fetal hepatic echodensities and thickened placenta. Termination of pregnancy was initiated. Case 3: A 29-year-old Gravida II Para I was referred for primary CMV infection at 16 weeks gestation presenting with no clinical symptoms of CMV. HIG therapy was performed, resulting in good neonatal outcome. CONCLUSION: We want to stress the potential benefit of an off label use of CMV-specific hyperimmune globulin (HIG) therapy, present an algorithm for the management of affected pregnancies and review current literature on this issue.