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Background: Acute bleeding requires fast and targeted therapy. Therefore, knowledge of the patient's potential to form a clot is crucial. Point-of-care testing (POCT) provides fast and reliable information on coagulation. Structural circumstances, such as person-bound sample transport, can prolong the reporting of the results. The aim of the present study was to investigate the diagnostic quality and accuracy between POCT INR diagnostics and standard laboratory analysis (SLA) as well as the time advantage between a pneumatic tube and a personal-based transport system. Methods: Two groups of haemorrhagic patients (EG: emergency department; OG: delivery room; each n = 12) were examined in the context of bleeding emergencies using POCT and SLA. Samples were transported via a pneumatic tube system or by a personal transport service. Results: INR results between POCT and SLA showed a high and significant correlation (EG: p < 0.001; OG: p < 0.001). POCT results were reported significantly more quickly (EG: 1.1 vs. 39.6 min; OG: 2.0 vs. 75.0 min; p < 0.001) and required less time for analysis (EG: 0.3 vs. 24.0 min; OG: 0.5 vs. 45.0 min; p < 0.001) compared to SLA. The time for transportation with the pneumatic tube was significantly shorter (8.0 vs. 18.5 min; p < 0.001) than with the personal-based transport system. Conclusion: The results of the present study suggest that POCT may be a suitable method for the emergency diagnosis and may be used as prognostic diagnostic elements in haemotherapy algorithms to initiate targeted haemotherapy at an early point in time.
Objective: To assess the effect of cesarean section (CS) timing, elective versus unplanned, on the residual myometrial thickness (RMT) and CS scars. Methods: This is a prospective single-blinded observational cohort study with 186 observations. Patients indicated to undergo first singleton CS were preoperatively recruited. Exclusion criteria were history of repeated CS, vertical hysterotomy, diabetes, and additional uterine surgeries. Sonographic examination was performed for assessing the RMT ratio, the presence of a niche, fibrosis, and the distance from the scar to the internal os (SO) 1 year after CS. Power analysis was performed with 0.05 α, 0.1 β, and all statistical analyses were conducted with Stata®. Results: Wilcoxon rank-sum test for the association between CS timing, RMT ratio and SO showed Z values of −0.59 and −4.94 (P = 0.553 and P < 0.001), respectively. There was no association between CS timing and niches and fibrosis (P > 0.99 and P = 0.268, respectively). Linear regression between SO and the extent of cervical dilatation showed a −0.45 β (95% confidence interval −0.68 to −0.21) and a 10.22-mm intercept (P < 0.001). Conclusion: RMT is independent of the timing of CS, but the SO distance shows a negative linear relationship with the cervical dilatation.
Objective: To assess the effect of cesarean section (CS) timing, elective versus unplanned, on the residual myometrial thickness (RMT) and CS scars. Methods: This is a prospective single-blinded observational cohort study with 186 observations. Patients indicated to undergo first singleton CS were preoperatively recruited. Exclusion criteria were history of repeated CS, vertical hysterotomy, diabetes, and additional uterine surgeries. Sonographic examination was performed for assessing the RMT ratio, the presence of a niche, fibrosis, and the distance from the scar to the internal os (SO) 1 year after CS. Power analysis was performed with 0.05 α, 0.1 β, and all statistical analyses were conducted with Stata®. Results: Wilcoxon rank-sum test for the association between CS timing, RMT ratio and SO showed Z values of −0.59 and −4.94 (P = 0.553 and P < 0.001), respectively. There was no association between CS timing and niches and fibrosis (P > 0.99 and P = 0.268, respectively). Linear regression between SO and the extent of cervical dilatation showed a −0.45 β (95% confidence interval −0.68 to −0.21) and a 10.22-mm intercept (P < 0.001). Conclusion: RMT is independent of the timing of CS, but the SO distance shows a negative linear relationship with the cervical dilatation.
Introduction: Cesarean section (CS) rates are increasing worldwide. One constant indication is the breech presentation at term. By offering external cephalic version (ECV) and vaginal breech delivery CS rates can be further reduced. Objective: This study aimed to analyze the ECV at 38 weeks of gestation with the associate uptake rate, predicting factors, success rate, and complications at a tertiary healthcare provider in Germany specializing in vaginal breech delivery. Methods: We conducted a prospective cohort study with retrospective data acquisition. All women with a singleton fetus in breech presentation presenting after 34 weeks of gestation for counseling between 2013 and 2017 were included. ECV impact factors were analyzed using logistic regression. Results: A total of 1,598 women presented for breech birth planning. ECV was performed on 353 patients. The overall success rate was 22.4%. A later week of gestation (odds ratio [OR] 1.69), an abundant amniotic fluid index (AFI score) (OR 5.74), fundal (OR 3.78) and anterior (OR 0.39) placental location, and an oblique lie (OR 9.08) were significantly associated with successful ECV in our population. No major complications were observed. The overall vaginal delivery rates could be increased to approximately 14% with ECV. Conclusion: The demand for alternative birth modes other than CS for breech birth is high in the area of Frankfurt, Germany. Our study offers evidence of the safety of ECV at 38 weeks. Centers with expertise in vaginal breech delivery and ECV can reduce CS-rates. To further establish vaginal breech delivery and ECV as alternate options, the required knowledge and skill should be implemented in the revised curricula.
Preeclampsia (PE), a gestational hypertensive disease originating from the placenta, is characterized by an imbalance of various cellular processes. The cell cycle regulator p21Cip1/CDKN1A (p21) and its family members p27 and p57 regulate signaling pathways fundamental to placental development. The aim of the present study was to enlighten the individual roles of these cell cycle regulators in placental development and their molecular involvement in the pathogenesis of PE. The expression and localization of p21, phospho-p21 (Thr-145), p27, and p57 was immunohistochemically analyzed in placental tissues from patients with early-onset PE, early-onset PE complicated by the HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome as well as late-onset PE compared to their corresponding control tissues from well-matched women undergoing caesarean sections. The gene level was evaluated using real-time quantitative PCR. We demonstrate that the delivery mode strongly influenced placental gene expression, especially for CDKN1A (p21) and CDKN1B (p27), which were significantly upregulated in response to labor. Cell cycle regulators were highly expressed in first trimester placentas and impacted by hypoxic conditions. In support of these observations, p21 protein was abundant in trophoblast organoids and hypoxia reduced its gene expression. Microarray analysis of the trophoblastic BeWo cell line depleted of p21 revealed various interesting candidate genes and signaling pathways for the fusion process. The level of p21 was reduced in fusing cytotrophoblasts in early-onset PE placentas and depletion of p21 led to reduced expression of fusion-related genes such as syncytin-2 and human chorionic gonadotropin (β-hCG), which adversely affected the fusion capability of trophoblastic cells. These data highlight that cell cycle regulators are important for the development of the placenta. Interfering with p21 influences multiple pathways related to the pathogenesis of PE.
Doppler examination of the umbilical artery and the fetal middle cerebral artery is evaluated predominantly in pregnancies with fetuses in cephalic presentation and never has been elucidated in breech presentation. Evidence on the accuracy of fetal weight estimation in dependence of the fetal presentation is controversial. Nevertheless, clinical decisions including recommendations for a cesarean section or labor induction based on these examinations are applied to pregnancies with fetuses in breech presentation. The objective of this study was to investigate the influence of the fetal presentation on fetal weight estimation accuracy, umbilical artery and middle cerebral artery resistance indices (RI) in a prospective case control study. Ultrasound examinations in 305 uncomplicated term pregnancies (153 vertex presentations, 152 breech) were investigated. Non-parametric variables were compared using Pearson’s chi2 test and Wilcoxon chi2 test, depending on variable scaling. Fetal weight estimation accuracy was not significantly different between vertex presentation group (VP) (6.97%) and breech presentation group (BP) (7.96%, p = 0.099). Fetal head circumference measurements were significantly larger in BP (350 mm vs. 341 mm in VB, p > 0.0001) while abdominal circumferences were significantly smaller (VP: 338 mm, BP: 331 mm, p = 0.0039) and weight estimation was not significantly different. Umbilical artery RIs were not significantly different between VP (54.5) and BP (55.3, p = 0.354). Fetal middle cerebral artery RIs also showed no significant differences (VP: 71.2, BP: 70.7, p = 0.335). Our study shows that fetal Doppler (RI) and weight estimation ultrasound originally calibrated in cephalic pregnancies are applicable to pregnancies with fetuses in breech presentation.
Vaginal breech delivery is becoming an extinct art although national guidelines underline its safety and vaginal breech delivery in an upright position has been shown to be a safe birth mode option. In order to spread clinical knowledge and be able to implement vaginal breech delivery into obstetricians’ daily practice, we need to gather knowledge from facilities who teach specialized obstetrical management. Methods: We performed a prospective cohort study on 140 vaginal deliveries out of breech presentation solely-managed by seven newly-trained physicians and compared fetal outcome as well as rates of manual assistance in respect to preexisting experience. Results: Fetal morbidity rate measured with a modified PREMODA score was not significantly different in three sub-cohorts sorted by preexisting expertise levels of managing obstetricians (experience groups EG, EG0: 2, 5%; EG1: 3, 7.5%; EG2: 1, 1.7%; p = 0.357). Manual assistance rate was significantly higher in EG1 (low experience level in breech delivery and only in dorsal position) compared to EG0 and EG2 (EG1 28, 70%; EG0: 14, 25%; EG2: 21, 35%; p = 0.0008). Conclusions: Our study shows that vaginal breech delivery with newly-trained obstetricians is a safe option whether or not they have advanced preexisting expertise in breech delivery. These data should encourage implementing vaginal breech delivery in clinical routine.
Impact of Docetaxel on blood-brain barrier function and formation of breast cancer brain metastases
(2019)
Background: Breast cancer (BC) is the most frequent malignant tumor in females and the 2nd most common cause of brain metastasis (BM), that are associated with a fatal prognosis. The increasing incidence from 10% up to 40% is due to more effective treatments of extracerebral sites with improved prognosis and increasing use of MRI in diagnostics. A frequently administered, potent chemotherapeutic group of drugs for BC treatment are taxanes usually used in the adjuvant and metastatic setting, which, however, have been suspected to be associated with a higher incidence of BM. The aim of our study was to experimentally analyze the impact of the taxane docetaxel (DTX) on brain metastasis formation, and to elucidate the underlying molecular mechanism.
Methods: A monocentric patient cohort was analyzed to determine the association of taxane treatment and BM formation. To identify the specific impact of DTX, a murine brain metastatic model upon intracardial injection of breast cancer cells was conducted. To approach the functional mechanism, dynamic contrast-enhanced MRI and electron microscopy of mice as well as in-vitro transendothelial electrical resistance (TEER) and tracer permeability assays using brain endothelial cells (EC) were carried out. PCR-based, immunohistochemical and immunoblotting analyses with additional RNA sequencing of murine and human ECs were performed to explore the molecular mechanisms by DTX treatment.
Results: Taxane treatment was associated with an increased rate of BM formation in the patient cohort and the murine metastatic model. Functional studies did not show unequivocal alterations of blood-brain barrier properties upon DTX treatment in-vivo, but in-vitro assays revealed a temporary DTX-related barrier disruption. We found disturbance of tubulin structure and upregulation of tight junction marker claudin-5 in ECs. Furthermore, upregulation of several members of the tubulin family and downregulation of tetraspanin-2 in both, murine and human ECs, was induced.
Conclusion: In summary, a higher incidence of BM was associated with prior taxane treatment in both a patient cohort and a murine mouse model. We could identify tubulin family members and tetraspanin-2 as potential contributors for the destabilization of the blood-brain barrier. Further analyses are needed to decipher the exact role of those alterations on tumor metastatic processes in the brain.
Preeclampsia (PE) remains a leading cause of maternal and perinatal mortality and morbidity worldwide. Its pathogenesis has not been fully elucidated and no causal therapy is currently available. It is of clinical relevance to decipher novel molecular biomarkers. RITA (RBP-J (recombination signal binding protein J)-interacting and tubulin-associated protein) has been identified as a negative modulator of the Notch pathway and as a microtubule-associated protein important for cell migration and invasion. In the present work, we have systematically studied RITA’s expression in primary placental tissues from patients with early- and late-onset PE as well as in various trophoblastic cell lines. RITA is expressed in primary placental tissues throughout gestation, especially in proliferative villous cytotrophoblasts, in the terminally differentiated syncytiotrophoblast, and in migrating extravillous trophoblasts. RITA’s messenger RNA (mRNA) level is decreased in primary tissue samples from early-onset PE patients. The deficiency of RITA impairs the motility and invasion capacity of trophoblastic cell lines, and compromises the fusion ability of trophoblast-derived choriocarcinoma cells. These data suggest that RITA may play important roles in the development of the placenta and possibly in the pathogenesis of PE.
Introduction: Vaginal delivery out of a breech presentation in pregnancies at term are being re-implemented into clinical practice. Still, recommendations regarding exclusion criteria leading to caesarean sections are based on expert opinions, not on evidence-based guidelines. The difference in perinatal outcome and course of delivery in births with babies in frank breech position and babies in incomplete or complete breech presentation never has been investigated in a large patient cohort.
Objective: To compare perinatal outcome of vaginally intended breech deliveries between births out of frank breech position and incomplete/complete breech presentation.
Design: Prospective cohort study.
Sample: 884 women at term with a singleton in frank breech presentation (FB) and 284 women with incomplete or complete breech presentation (CB) intending vaginal birth between January 2004 and December 2018.
Methods: Maternal and fetal outcome was compared between groups using Pearson’s Chi Square test. Birth duration parameters were analysed using logistic regression.
Results: There were no differences in cesarean section rates (FB: 25.1%, CB 22.2%, p = 0.317). Short-term fetal morbidity did not differ between groups (FB: 2.5%, CB: 2.8%, p = 0.761). In vaginal deliveries the necessity to perform manual assistance was significantly more frequent in deliveries of infants in CB (FB: 39.9%, CB: 51.6%, p = 0.0013). Cord loops (FB: 10.1%, CB: 18.0%, p = 0.0004) and cesarean sections necessary because of cord prolapses (FB: 1.4%, CB 8.1%, p = 0.005) were significantly more often in deliveries with babies in CB.
Conclusion: This study provides evidence, that perinatal morbidity is not associated with the fetal leg posture in vaginally intended breech deliveries. The higher risk for the need of manual assistance during vaginal birth in deliveries of babies out of complete or incomplete breech presentation suggests that obstetrical departments re-implementing the vaginal breech in their repertoire might start with births of babies out of frank breech presentation.