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Introduction The best way to deliver a term breech infant is still a much discussed topic among obstetricians. The question whether nulliparity should be considered an exclusion criterion for an intended vaginal breech delivery is not fully answered. Objective We compared maternal and neonatal outcome of intended vaginal breech deliveries of nulliparous versus multiparous women at term. Study design We conducted a prospective case-control study between January 2004 and December 2016. 1046 women expecting singletons at term with favorable pelvic measurements were enrolled in the study. Results Neonatal morbidity and mortality was not significantly different in deliveries of nulliparous (n = 647) versus multiparous (n = 399) women. Nulliparous women had a significantly higher rate of a cesarean section during labor than multiparous women. Maternal birth-injury rates and the use of epidural anesthesia were significantly higher comparing vaginal births of nulliparous (n = 384) versus multiparous (n = 331) women. Conclusion Nulliparity seems not be an exclusion criterion for intended vaginal breech birth at term. It is still important to inform the women of an increased risk of a cesarean section during labor. A clinical management built on this evidence might reduce negative implications for future pregnancies.

Preeclampsia is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, chemerin was introduced as a novel adipokine inducing insulin resistance in vitro and in vivo. In the current study, we investigated serum concentrations of chemerin by ELISA in control and preeclampsia patients during pregnancy (n=37, preeclampsia: n=37) and 6 months after delivery (n=35, preeclampsia: n=36). Furthermore, the association between chemerin and markers of renal function, glucose and lipid metabolism, as well as inflammation was studied in pregnant patients. Median maternal chemerin concentrations were significantly elevated in preeclampsia patients (249.5 [range: 123.1-366.9] μg/l) as compared to controls (204.8 [138.5-280.8] μg/l) (p0.001). Furthermore, chemerin serum levels positively correlated with blood pressure, creatinine, free fatty acids, cholesterol, triglycerides (TG), leptin, adiponectin, and C-reactive protein in univariate analyses. In multivariate analyses, TG and leptin remained independently associated with circulating chemerin. Interestingly, median chemerin concentrations 6 months after delivery remained significantly higher in former preeclampsia patients (196.0 [119.8-368.7] μg/l) as compared to controls (152.2 [102.8-216.4] μg/l). Taken together, maternal chemerin serum concentrations are significantly increased in preeclampsia during and after pregnancy. Furthermore, TG and leptin are independent predictors of circulating chemerin during pregnancy.

INTRODUCTION: In the clinical routine, the diagnosis of preeclampsia is often challenging. Not all pregnant women with signs and symptoms of preeclampsia develop the disease. Recently, the assessment of the sFlt-1/PlGF ratio in the serum of pregnant women has been proposed as an aid in the diagnosis of preeclampsia. PATIENTS AND METHODS: In a retrospective, monocentric case-control study, we reviewed 30 cases of patients who presented with the clinical symptoms of hypertensive disorders of pregnancy in the delivery ward. Next to the standard diagnostic algorithm for preeclampsia, the sFlt-1/PlGF ratio was determined using the automated Elecsys ® platform. RESULTS: In 12/30 cases (40%), the diagnosis of a hypertensive pregnancy disorder was confirmed with an sFlt1/PlGF ratio of >85. In 18/30 (60%) cases, a ratio

the v2-test and v2-for-trend. Results: In the first study, 50 patients were treated with labetalol. Of these 37 (74%) responded and 13 (26%) did not, despite dose maximisation. From the non-responders 10 (77%) were admitted with severe pre-eclampsia whilst from the responders only 1 was admitted (3%) (v2-p < 0.001). A prediction model for the response to labetalol was created. The area under the receiver operating characteristic curve was 0.9626 and this was confirmed in the validation study. Using the prediction model to guide treatment, the PE rate fell from 20% to 10% and 6%, respectively over the three phases of the study (v2 for trend p < 0.001). Conclusion: Maternal demographics and haemodynamics can provide a sensitive prediction tool to anticipate the response to labetalol in hypertensive pregnancies, with a subsequent reduction in severe pre-eclampsia rates

Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.

Fragestellung: Maligne Keimzelltumoren des Ovars machen etwa 3 – 5% der bosartigen Ovarialtumoren aus; die haufigsten Entitaten sind das Dysgerminom, das immature Teratom sowie der Dottersacktumor. Die Diagnose wird meist im Kindes- oder Jugendalter gestellt, wobei eine genaue praoperative Zuordnung allein auf der Basis von Tumormarkern wie AFP, hcG, LDH, Ca-125, CA 19 – 9, SCC und NSE nicht moglich ist. Es existieren keine exakten bildmorphologischen Kriterien fur die haufig eingesetzten bildgebenden Verfahren (Sonografie, CT, MRT). Methodik: Es wurde eine retrospektive Analyse von 6 Patientinnen mit verschiedenen Keimzelltumoren durchgefuhrt, die im gynakologischen Tumorzentrum der Universitatsklinik Leipzig im Zeitraum von 2002 – 2014 erfasst wurden. Neben Patientencharakteristika, den Operationsverlaufen, den histopatholgischen Befunden (Makro- und Mikroskopie) und den adjuvanten Therapien wurden insbesondere die praoperativen bildgebenden Verfahren vergleichend ausgewertet sowie das Follow-up erfasst. Ergebnisse: Bildmorphologisch lasst sich eine deutliche Unterscheidung zu benignen ovariellen Veranderungen (Zysten (ggf. eingeblutet), Zystadenofibromen, Endometriose) und zu typischen Ovarialkarzinomen darstellen. Die einzelnen Keimzelltumoren zeigen sowohl spezifische Muster in der Bildgebung als auch den Tumormarkern. Die Spezifika der praoperativen Befunde werden durch die makroskopische Beurteilung der Praparate durch den Pathologen bestatigt. Schlussfolgerung: Die kombinierte Betrachtung der Befunde aus Sonografie ggf. der kontrastmittel-verstarkten Computertomografie und des Tumormarkerpanels erlaubt eine praoperative Spezifizierung der Tumorentitat und eine optimierte Planung des operativen Vorgehens. Darauf basierend wird ein einfacher diagnostischer Algorithmus vorgeschlagen.

Background Preeclampsia is a devastating complication of pregnancy affecting both mother and fetus. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is a potential therapeutic target in preeclampsia. We evaluated the safety and efficacy of treating women with very preterm preeclampsia using a plasma-specific dextran sulfate (PSDS) column to remove circulating sFlt-1. Methods This was an open study of up to three extra-corporeal PSDS-apheresis treatments in 10 women with very preterm preeclampsia to determine the extent of sFlt-1 and proteinuria reduction, and its safety for mother and fetus. Results Six patients with very preterm preeclampsia (mean gestational age 29 + 2 weeks) underwent one PSDS-apheresis treatment; three were treated twice, and one for three times. The apheresis volumes ranged from 400 to 1500 ml. Mean starting sFlt-1 concentration was 18,342 pg/mL (range 8243–35,301 pg/mL) with a 17% mean reduction per treatment (range 6–28%). Mean starting protein: creatinine (P/C) ratio was 6.4 g/g (range 0.4–16.9 g/g); mean reduction per treatment was 39% (range 88% reduction to 30% increase). Among women treated multiple times, pregnancy continued on average for 11 days (range 7–19 days). The most common side effect during treatment was transient blood pressure reduction ( ∼ 10–20 mmHg), managed by withholding antihypertensive therapies before treatment, saline prehydration, and reducing blood flow through the apheresis column. There were no adverse effects to fetuses or neonates. Conclusions Therapeutic apheresis reduces circulating sFlt-1 and proteinuria in women with very preterm preeclampsia, enabling pregnancy to continue. A controlled trial is needed to determine whether apheresis to remove sFlt-1 safely prolongs pregnancy.

Preeclampsia (PE) is a serious cardiovascular complication in pregnancy, which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Fibroblast growth factor (FGF)-21 was recently introduced as a novel adipokine improving glucose metabolism in vitro and in vivo.We investigated serum FGF-21 levels in patients with PE (n=51) as compared to healthy, age-matched controls (n=51) during and 6 months after pregnancy. Furthermore, association of FGF-21 with markers of renal function, glucose and lipid metabolism, as well as inflammation, was elucidated in all individuals.Median maternal FGF-21 serum concentrations adjusted for body mass index and gestational age at blood sampling were significantly, almost 3-fold increased in PE patients (309.6 ng/l) as compared to healthy, age-matched pregnant women (105.2 ng/l) (p0.001). Furthermore, FGF-21 concentrations were independently and positively correlated with triglycerides whereas an independent and negative association was observed with glomerular filtration rate and low density lipoprotein (LDL) cholesterol in pregnant women. Moreover, FGF-21 serum levels significantly decreased in former PE patients 6 months after pregnancy approaching levels found in control patients.Maternal FGF-21 serum concentrations are significantly increased in PE during pregnancy. Furthermore, triglycerides, glomerular filtration rate, and LDL cholesterol are independent predictors of circulating FGF-21 in pregnant women.

Preeclampsia (PE) contributes to maternal and fetal morbidity and mortality worldwide. Moreover, it is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, growth arrest specific protein (Gas) 6 has been introduced as a novel metabolic risk factor with anti-angiogenic, pro-atherogenic, and pro-adipogenic properties. In the current study, we investigated serum concentrations of Gas6 in patients with PE (n=51) as compared to healthy, age-matched controls (n=51) during and 6 months after pregnancy. Furthermore, association of Gas6 with markers of renal function, glucose and lipid metabolism, as well as inflammation, was assessed in all individuals. Median maternal Gas6 serum levels adjusted for body mass index and gestational age at blood sampling were significantly increased in PE patients (5.7 μg/l) as compared to healthy, age-matched pregnant women (4.6 μg/l) (p

Winkler et al raise an interesting point that perhaps lowering of soluble fms-like tyrosine kinase 1 (sFlt-1) may not have been the sole reason for the therapeutic benefit noted in our study,1 and that lowering other substances such as low-density lipoprotein cholesterol by dextran sulfate cellulose (DSC) apheresis may have contributed to the benefit we observed. In addition, Winkler et al contend that the therapeutic benefit noted in a prior study by Wang et al2 that used heparin-mediated extracorporeal low-density lipoprotein precipitation (HELP) apheresis may have been caused by lowering of low-density lipoprotein cholesterol. We agree with Winkler et al that we cannot conclude lowering sFlt-1 was the sole reason for the therapeutic benefit. Future clinical studies using specific apheretic columns (eg, sFlt-1 antibody columns) are needed to directly answer the contributing role of sFlt-1 in mediating preeclamptic signs and symptoms. We would like to point out that although lipid abnormalities frequently accompany …

Background— Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia. Removing sFlt-1 may benefit women with very preterm ( Methods and Results— We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dose-dependent fashion. Finally, we performed multiple apheresis treatments in 3 additional women with very preterm (gestational age at admission 28, 30, and 27+4 weeks) preeclampsia and elevated circulating sFlt-1 levels. Dextran sulfate apheresis lowered circulating sFlt-1, reduced proteinuria, and stabilized blood pressure without apparent adverse events to mother and fetus. Pregnancy lasted for 15 and 19 days in women treated twice and 23 days in a woman treated 4 times. In each, there was evidence of fetal growth. Conclusions— This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting.

Preeclampsia (PE) is associated with facets of the metabolic syndrome and an increased future metabolic and cardiovascular risk for mother and newborn. Recently, zinc-α2-glycoprotein (ZAG) has been proposed as a new adipokine involved in the pathogenesis of obesity.In the current study, we investigated ZAG serum levels in PE patients as compared to healthy gestational age-matched controls.We quantified serum concentrations of ZAG in patients with PE (no.=37) as compared to healthy gestational age-matched controls (no.=37) by enzyme-linked immunosorbent assay. Furthermore, association of this adipokine with renal function, glucose and lipid metabolism, as well as inflammation was studied.Median serum ZAG levels were 1.4-fold higher in PE patients (58.8 mg/l) as compared to controls (41.9 mg/l) (p0.01). Furthermore, circulating ZAG was positively correlated to systolic and diastolic blood pressure, creatinine, triglycerides, and leptin in univariate analyses. In multiple regression analysis, creatinine remained independently associated with ZAG.We demonstrate that maternal ZAG serum concentrations are significantly increased in PE. Furthermore, renal function is an independent predictor of circulating ZAG.

In the clinical routine, the diagnosis of preeclampsia is often challenging. Not all pregnant women with signs and symptoms of preeclampsia develop the disease. Recently, the assessment of the sFlt-1/PlGF ratio in the serum of pregnant women has been proposed as an aid in the diagnosis of preeclampsia.In a retrospective, monocentric case-control study, we reviewed 30 cases of patients who presented with the clinical symptoms of hypertensive disorders of pregnancy in the delivery ward. Next to the standard diagnostic algorithm for preeclampsia, the sFlt-1/PlGF ratio was determined using the automated Elecsys® platform.In 12/30 cases (40%), the diagnosis of a hypertensive pregnancy disorder was confirmed with an sFlt1/PlGF ratio of85. In 18/30 (60%) cases, a ratio85 excluded the diagnosis of preeclampsia at the time of presentation and allowed an adaptation of the patient's surveillance programme.In the clinical setting of "suspected preeclampsia", determination of the sFlt-1/PlGF ratio can serve as an aid in the diagnosis of hypertensive disorders in pregnancy. The reliable exclusion of the diagnosis "preeclampsia" can help in an appropriate and cost-effective management of patients with signs and symptoms of the disease.

6-Aminonicotinamide (6-AN), an antimetabolite of nicotinamide, damages the astrocytes and oligodendrocytes through a blockade of the pentose phosphate pathway. Both types of glia cells become hydropic. A third type of glia cell, described by Vaughn and Peters, the multipotential glia, is affected to a lesser extent. These cells phagocytize and form pseudopodia after treatment with 6-AN. Thus the multipotential glia cells are ‘marked’ by the action of 6-AN, since they are obviously less dependent on the pentose phosphate pathway in the carbohydrate metabolism.

Light- and electron-microscopie studies were performed in glia cells and neurons of the cerebellum of 12-day-old rats until 48 following intraperitoneal application of 8 mg/kg 6-aminonicotinamide (6-AN), an antimetabolite of nicotinamide that inhibits the oxidative pentose-phosphate pathway. Particularly sensitive were the neuroblasts of the external granular layer. The migration of the neuroblasts was clearly reduced. Parts of the internal granular layer were damaged, while the Purkinje cells and astrocytes remained unchanged. Oligodendrocytes and astrocytes showed vacuolar degeneration. Swelling of the myelin sheath occurred in the form of a status spongiosus. 48 h after 6-AN injection some mitoses and phagocytic cells were found in the internal granular layer.

6-Aminonicotinamide (6-AN), an antimetabolite of nicotinamide, damages the astrocytes and oligodendrocytes through a blockade of the pentose phosphate pathway. Both types of glia cells become hydropic. A third type of glia cell, described by VAUGHN and PETERS, the multipotential glia, is affected to a lesser extent. These cells phagocytize and form pseudopodia after treatment with 6-AN. Thus the multipotential glia cells are 'marked' by the action of 6-AN, since they are obviously less dependent on the pentose phosphate pathway in the carbohydrate metabolism.

Light- and electron-microscopie studies were performed in glia cells and neurons of the cerebellum of 12-day-old rats until 48 following intraperitoneal application of 8 mg/kg 6-aminonicotinamide (6-AN), an antimetabolite of nicotinamide that inhibits the oxidative pentose-phosphate pathway. Particularly sensitive were the neuroblasts of the external granular layer. The migration of the neuroblasts was clearly reduced. Parts of the internal granular layer were damaged, while the Purkinje cells and astrocytes remained unchanged. Oligodendrocytes and astrocytes showed vacuolar degeneration. Swelling of the myelin sheath occurred in the form of a status spongiosus. 48 h after 6-AN injection some mitoses and phagocytic cells were found in the internal granular layer.