Analysis of prehospital perimortem caesarean deliveries performed by Helicopter Emergency Medical Services in the Netherlands and recommendations for the future.

BACKGROUND: Prehospital perimortem caesarean delivery (PCD) is a rarely performed procedure. In this study, we aimed to examine all PCDs performed by the four Helicopter Emergency Medical Services in the Netherlands; to describe the procedures, outcomes, complications, and compliance with the recommended guidelines; and to formulate recommendations. METHODS: We performed a population-based retrospective cohort study of all consecutive maternal out-of-hospital cardiac arrests that underwent PCD in the prehospital setting between May 1995 and December 2019. Registered data included patient demographics, operator background, advanced life support interventions, and timelines. Resuscitation performance was evaluated according to the 2015 European Resuscitation Guidelines. RESULTS: Seven patients underwent a prehospital PCD. Three mothers died on the scene, while four were transported to a hospital but died in the hospital. Seven neonates were born by PCD. One neonate died on the scene and six were transported to a hospital. Three neonates were eventually discharged from the hospital. Among the three surviving neonates, the periods from dispatch to start of PCD were 13, 14, and 21 min. CONCLUSIONS: There was a low incidence of maternal perimortem caesarean deliveries in The Netherlands. Only some neonates survived after PCD. It is recommended that PCD be performed as quickly as possible. Due to the delay, the mother has a far lower chance of survival than the neonate. In fatal cases, autopsy is strongly recommended.

[Elective induction of labour at 39 weeks; better than expectant management in low-risk women]. / Electief inleiden van de baring bij 39 weken.

The ARRIVE trial has shown that elective induction of labour at 39 weeks improves maternal and foetal outcomes in comparison with expectant management. Caesarean sections, hypertensive disorders and neonatal ventilator support were all found to be reduced after elective induction. The trial was performed in an American nulliparous low-risk population. Several American professional organizations have now adapted their recommendation on elective induction in nulliparous low-risk women. These organizations now suggest informing women about the potential benefits, and offer elective induction in a model of shared decision-making. In the Netherlands there has been some reluctance amongst professionals to address this issue. This might be related to a conservative obstetric approach and the Dutch obstetric model with its three separate levels of care. Nevertheless, this subject should be addressed in a scientific, professional and unprejudiced way, given the evidence and potential implications for the large group of low-risk women and neonates in the Netherlands.

Methods and considerations concerning cardiac output measurement in pregnant women: recommendations of the International Working Group on Maternal Hemodynamics.

Cardiac output (CO), along with blood pressure and vascular resistance, is one of the most important parameters of maternal hemodynamic function. Substantial changes in CO occur in normal pregnancy and in most obstetric complications. With the development of several non-invasive techniques for the measurement of CO, there is a growing interest in the determination of this parameter in pregnancy. These techniques were initially developed for use in critical-care settings and were subsequently adopted in obstetrics, often without appropriate validation for use in pregnancy. In this article, methods and devices for the measurement of CO are described and compared, and recommendations are formulated for their use in pregnancy, with the aim of standardizing the assessment of CO and peripheral vascular resistance in clinical practice and research studies on maternal hemodynamics. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Raman spectra and structural peculiarities of TeO2-TeO3 mixed oxides.

Raman spectra of the mixed crystalline oxides of the (1 - x)TeO2 + xTeO3 (x = 0, », ½, 1) series were recorded and simulated by using the DFT calculations. Good agreement between observed and calculated Raman spectra makes it possible to establish unambiguous assignment for all prominent Raman lines. This result gives an insight into relations between structural peculiarities and observed spectral features for the crystals promising as nonlinear optical materials. Highlights • Several mixed TeO2-TeO3 crystals were synthesized by solid-state chemistry • DFT calculations well describe structures and phonon spectra of TeO2-TeO3 oxides • Raman lines can be assigned to internal vibrations of TeO4 and TeO6 polyhedrons • Observed Raman bands can be used as fingerprints of different structural units.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Validation of maternal cardiac output assessed by transthoracic echocardiography against pulmonary artery catheterization in severely ill pregnant women: prospective comparative study and systematic review.

OBJECTIVE: Most severe pregnancy complications are characterized by profound hemodynamic disturbances, thus there is a need for validated hemodynamic monitoring systems for pregnant women. Pulmonary artery catheterization (PAC) using thermodilution is the clinical gold standard for the measurement of cardiac output (CO), however this reference method is rarely performed owing to its invasive nature. Transthoracic echocardiography (TTE) allows non-invasive determination of CO. We aimed to validate TTE against PAC for the determination of CO in severely ill pregnant women. METHODS: This study consisted of a meta-analysis combining data from a prospective study and a systematic review. The prospective arm was conducted in Pretoria, South Africa, in 2003. Women with severe pregnancy complications requiring invasive monitoring with PAC according to contemporary guidelines were included. TTE was performed within 15 min of PAC and the investigator was blinded to the PAC measurements. Comparative measurements were extracted from similar studies retrieved from a systematic review of the literature and added to a database. Simultaneous CO measurements by TTE and PAC were compared. Agreement between methods was assessed using Bland-Altman statistics and intraclass correlation coefficients (ICC). RESULTS: Thirty-four comparative measurements were included in the meta-analysis. Mean CO values obtained by PAC and TTE were 7.39 L/min and 7.18 L/min, respectively. The bias was 0.21 L/min with lower and upper limits of agreement of -1.18 L/min and 1.60 L/min, percentage error was 19.1%, and ICC between the two methods was 0.94. CONCLUSIONS: CO measurements by TTE show excellent agreement with those obtained by PAC in pregnant women. Given its non-invasive nature and availability, TTE could be considered as a reference for the validation of other CO techniques in pregnant women. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. RESUMEN OBJETIVO: Las complicaciones del embarazo más graves se caracterizan por trastornos hemodinámicos serios, debido a los cuales existe la necesidad de sistemas validados de monitorización hemodinámica para mujeres embarazadas. Aunque la cateterización de la arteria pulmonar (CAP) mediante termodilución es el patrón de referencia clínico para la medición del gasto cardíaco (GC), este método se usa con poca frecuencia debido a su naturaleza invasiva. La ecocardiografía transtorácica (ETT) permite la determinación no invasiva del GC. El objetivo de este estudio fue validar la ETT frente al CAP para determinar el GC en mujeres embarazadas gravemente enfermas. MÉTODOS: Este estudio consistió en un metaanálisis que combinó datos de un estudio prospectivo y una revisión sistemática. El estudio prospectivo se llevó a cabo en Pretoria (Sudáfrica) en 2003. Se incluyeron mujeres con complicaciones graves en el embarazo que requerían una monitorización invasiva mediante CAP según las directrices de ese momento. Se realizó una ETT en un plazo de 15 minutos de haber realizado el CAP y el investigador no tuvo acceso a las mediciones del CAP. Las mediciones comparativas se extrajeron de estudios similares obtenidos a partir de una revisión sistemática de la literatura y se añadieron a una base de datos. Se compararon las mediciones simultáneas del GC mediante ETT y CAP. La concordancia entre métodos se evaluó a través del método estadístico de Bland-Altman y de coeficientes de correlación intraclase (CCI). RESULTADOS: Se incluyeron treinta y cuatro mediciones comparativas en el metaanálisis. Los valores medios del GC obtenidos mediante CAP y ETT fueron de 7,39 l/min y 7.18 l/min, respectivamente. El sesgo fue de 0,21 l/min, siendo los límites inferior y superior de la concordancia de -1,18 l/min y 1.60 l/min; el error porcentual fue del 19,1%, y el CCI entre ambos métodos fue de 0,94. CONCLUSIONES: Las mediciones del GC en mujeres embarazadas mediante ETT muestran una excelente concordancia con las obtenidas mediante CAP. Dada su naturaleza no invasiva y su disponibilidad, la ETT podría considerarse como referencia para la validación de otras técnicas relacionadas con el GC en mujeres embarazadas. : ,。(pulmonary artery catheterization,PAC)(cardiac output,CO),,。(transthoracic echocardiography,TTE)CO。PACTTECO。 : meta。2003。PAC。PAC 15 minTTE,PAC。,。TTEPACCO。Bland-Altman(intraclass correlation coefficients,ICC)。 : meta34。PACTTECO7.39 L/min7.18 L/min。-1.18 L/min、1.60 L/min0.21 L/min,19.1%,ICC0.94。 : TTECOPACCO。,TTECO。.

Fluorinated steroids do not improve outcome of isolated atrioventricular block.

INTRODUCTION: Congenital atrioventricular block (CAVB) is a rare disorder with a significant morbidity and mortality. Consensus regarding the prescription and efficacy of prenatal corticosteroids is lacking. This nationwide study was initiated to evaluate the effects of prenatal treatment with corticosteroids on the outcome of CAVB in The Netherlands. METHODS: All fetuses identified with isolated congenital AVB-II° or AVB-III° in any of the eight academic fetal heart centers of The Netherlands between 2003 and 2013 were included and reviewed. RESULTS: Fifty-six fetuses were included. Fourteen (25%) fetuses were treated with dexamethasone. We found no differences between the steroid-treated and untreated cases regarding in utero progression of the AVB (63% vs 67% respectively), survival to birth (86% vs 84%), pacemaker implantations (74% vs 58%) or long-term dilated cardiomyopathy (13% vs 17%). Steroid treated fetuses demonstrated more in utero growth restriction (38% vs 11%). CONCLUSION: No benefit from prenatal corticosteroid treatment was demonstrated for fetuses with isolated CAVB in this study. However, we found negative side effects. Our data provide no evidence to support the routine administration of corticosteroids for the treatment of fetal CAVB.

Hemodynamic effects of intravenous nicardipine in severely pre-eclamptic women with a hypertensive crisis.

OBJECTIVE: Nicardipine permits rapid control of blood pressure in women with severe pre-eclampsia (PE) and hypertensive crisis. Our objective was to investigate its maternal and fetal hemodynamic effects. METHODS: Ten severely pre-eclamptic pregnant women who required intravenous nicardipine for severe hypertension were included in this prospective observational trial. Maternal macrocirculation was assessed by transthoracic echocardiography. Maternal microcirculatory perfusion was examined sublingually with the sidestream dark field imaging technique. Fetal hemodynamics were assessed by Doppler examinations of the uteroplacental and fetal circulations. Maternal cardiac output, total vascular resistance, mitral E/A ratio and capillary heterogeneity index, uterine artery pulsatility index and fetal cerebroplacental ratio were considered primary outcomes. Paired measurements, obtained before administration of nicardipine infusion and after stabilization of blood pressure, were compared. RESULTS: Administration of nicardipine significantly reduced the mean arterial blood pressure (median difference, 26 mmHg; P = 0.002) and total vascular resistance (median difference, 791 dynes × s/cm(5) ; P = 0.002) in all included women. This induced a reflex tachycardia with consequent increase in cardiac output of 1.55 L/min (P = 0.004). There were no significant changes in the other determinants of maternal or fetal hemodynamic parameters. CONCLUSIONS: Nicardipine effectively reduces blood pressure through selective afterload reduction that triggers an increase in cardiac output, without affecting maternal diastolic function, or microcirculatory, uteroplacental or fetal perfusion. This hemodynamic response is uniform and predictable. Fetomaternal cardiovascular profiling can be achieved by combining transthoracic echocardiography with obstetric Doppler.

Microcirculation in women with severe pre-eclampsia and HELLP syndrome: a case-control study.

OBJECTIVE: To compare microcirculatory perfusion in women with severe pre-eclampsia against that in healthy pregnant women, and secondly in women with severe pre-eclampsia with or without HELLP syndrome (haemolysis, elevated liver enzymes, and low platelets). DESIGN: Case-control study. SETTING: University Hospital Rotterdam, the Netherlands. POPULATION: Twenty-three women with severe pre-eclampsia and 23 healthy pregnant controls, matched for maternal and gestational age. Out of the 23 women with severe pre-eclampsia, ten presented with HELLP syndrome. METHODS: Microcirculation was analysed sublingually by a non-invasive sidestream dark-field imaging device (SDF). MAIN OUTCOME MEASURES: Perfused vessel density (PVD), microcirculatory flow index (MFI), and heterogeneity index (HI) were calculated for both small vessels (∅ < 20 µm; capillaries) and non-small vessels (∅ > 20 µm; venules and arterioles). RESULTS: There were no significant differences between women with severe pre-eclampsia and healthy controls. Women with pre-eclampsia and HELLP syndrome showed a reduced PVD (P = 0.045), MFI (P = 0.008), and increased HI (P = 0.002) for small vessels, as compared with women with pre-eclampsia but without HELLP syndrome. CONCLUSIONS: Sidestream dark-field is a novel, promising technique in obstetrics that permits the non-invasive evaluation of microcirculation. We did not observe major differences in sublingual microcirculatory perfusion between women with severe pre-eclampsia and healthy pregnant controls. In women with severe pre-eclampsia, the presence of HELLP syndrome is characterised by impaired capillary perfusion.

Acidosis: A potential explanation for adverse fetal outcome in intrahepatic cholestasis of pregnancy. A case report.

BACKGROUND: Intrahepatic cholestasis of pregnancy is a cholestatic disorder with an increased risk for adverse perinatal outcome. The mechanism underlying intrauterine demise is poorly understood. CASE: A nulliparous woman with gestational age of 36 plus 6 weeks presented with suspected intrahepatic cholestasis. Continuous CTG monitoring evolved from a normal pattern towards a non-reassuring pattern. A male neonate was delivered by caesarean section. Apgar scores 0, 1 and 4 at 1, 5 and 10 min. Fetal cord gas analysis showed pH 6.98, base deficit -15 mmol/L. Blood results showed maternal serum bile acid concentration of 220 µmol/L. CONCLUSION: Our case suggests gradual evolution towards hypoxia and acidosis. It is unknown whether certain components in the bile acid concentrations might contribute to a fetal metabolic component of the acidosis.

Hemodynamic adaptation to pregnancy in women with structural heart disease.

BACKGROUND: Many women with structural heart disease reach reproductive age and contemplate motherhood. Pregnancy induces and requires major hemodynamic changes. Pregnant women with structural heart disease may have a reduced cardiac reserve. There are no longitudinal data on cardiovascular adaptation throughout pregnancy in women with structural heart disease. METHODS: Thirty-five women with structural heart disease were included in a prospective observational trial. Maternal hemodynamics were assessed before conception, during pregnancy and 6 months postpartum by transthoracic echocardiography. Uteroplacental perfusion was analyzed by obstetric Dopplers. Longitudinal evolution over time was analyzed as well as the long term influence of pregnancy on cardiac function. RESULTS: Cardiac output (CO), stroke volume (SV), left ventricular mass (LV mass) and E/E' ratio significantly increased and ejection fraction (EF) and fractional shortening (FS) decreased during pregnancy. There was a statistically significant difference in EF, FS and E/E' ratio before and after pregnancy. CONCLUSIONS: The characteristic pattern of hemodynamic adaptation to pregnancy is attenuated in women with structural heart disease. The pregnancy related volume load induces progression of diastolic dysfunction. Our data suggest a persistent reduction in systolic and diastolic cardiac functions after pregnancy in women with structural heart disease.

Maternal and fetal haemodynamic effects of nifedipine in normotensive pregnant women.

While nifedipine is commonly used for tocolysis, the controversy on its safety remains. So far, the haemodynamic effects on maternal and fetal circulations have not been well documented. Fifteen normotensive women who received 20 mg nifedipine were included in this prospective observational study. The maternal and fetal haemodynamic effects were analysed using maternal echocardiography and fetal Doppler ultrasonography. Nifedipine induced a significant afterload reduction in all women. It triggered a compensatory increase in cardiac output, which maintained blood pressure. These maternal changes had no influence on the uteroplacental and fetal circulations.

Fetal dilated cardiomyopathy caused by persistent junctional reciprocating tachycardia.

Ultrasound examination of a fetus at 32 weeks' gestation revealed dilated cardiomyopathy and a heart rate of 170 beats per minute. Prenatally, this mild tachycardia was not primarily suspected to be the cause of the myocardial changes. Postnatal electrocardiography revealed a persistent junctional reciprocating tachycardia (PJRT) and the diagnosis of tachycardia-induced cardiomyopathy (TICM) became apparent. After conversion to a sinus rhythm under digoxin and amiodarone, the cardiac changes regressed. PJRT is a rare form of supraventricular tachycardia. The prenatal findings in the condition have previously been described retrospectively, but it can only be diagnosed postnatally by its characteristic electrocardiographic properties. This case indicates that TICM can occur at lower heart rates than previously assumed. Even severe prenatal cardiomyopathy may be reversible once sinus rhythm has been restored.

Mesenchymal hamartoma of the liver: a benign tumor with deceptive prognosis in the perinatal period. Case report and review of the literature.

This article reports a case of perinatal mesenchymal hepatic hamartoma and reviews the literature on the subject. A fetus presented with polyhydramnios and a large multiloculated cystic abdominal mass at 33 weeks of gestation. The ultrasound appearance was most consistent with a mesenteric cyst. Prenatal drainage was considered, due to the size of the lesion. However, a conservative management was opted for. A female infant was born at 35 weeks by classical cesarean section. The immediate postnatal period was characterized by hemodynamic instability. Laparotomy revealed a pedunculated mesenchymal hamartoma of the liver, which could not completely be resected. The infant had an uneventful postoperative recovery and is doing well at 6 months of age. Hepatic mesenchymal hamartoma are rare benign tumors. Most cases are detected in early childhood. They usually present as a cystic rapidly growing abdominal mass. Prenatal diagnosis remains challenging. In children diagnosed in the perinatal period, the outcome seems worse and determined by the compressive effect of the mass.

Biphasic sarcomatoid carcinoma or carcinosarcoma of the breast: prognosis and therapy.

Biphasic sarcomatoid carcinoma of the breast represents only 0.2% of all breast cancer. Due to its rarity and repetitive reclassifications little is known about optimal treatment modalities. These tumours form a diagnostic and therapeutic challenge. The present report describes our experience with a case of biphasic sarcomatoid carcinoma of the breast and a review of the relevant literature is discussed.

A conserved retinoid X receptor (RXR) from the mollusk Biomphalaria glabrata transactivates transcription in the presence of retinoids.

Retinoid X receptors (RXR) are members of the nuclear receptor superfamily of ligand-activated transcription factors that have been characterized in a wide variety of metazoan phyla. They act as heterodimer partners of other nuclear receptors, and in vertebrates also activate transcription as homodimers in the presence of a ligand, 9-cis retinoic acid. In order to test the hypothesis that retinoic acid signaling pathways involving RXRs are present in the Lophotrochozoa, we have sought to isolate conserved members of this family from the platyhelminth parasite Schistosoma mansoni and its intermediate host, the mollusk Biomphalaria glabrata. Here we report that an RXR ortholog from B. glabrata (BgRXR) is better conserved, compared with mouse RXRalpha, both in the DNA-binding domain (89% identity) and in the ligand-binding domain (LBD) (81% identity), than are arthropod homologs. In EMSA, BgRXR binds to the direct repeat response element DR1 as a homodimer or as a heterodimer with mammalian RARalpha, LXR, FXR or PPARalpha. When transfected alone into mammalian cell lines, BgRXR transactivated transcription of a reporter gene from the Apo-A1 promoter in the presence of 9-cis retinoic acid or DHA. Constructs with the Gal4 DNA binding domain fused to the hinge and LBDs of BgRXR were used to show that ligand-dependent activation of transcription by BgRXR required its intact AF-2 activation domain, and that the LBD can form homodimers. Finally, the binding of 9-cis retinoic acid preferentially protected the LBD of BgRXR from degradation by trypsin in a proteolysis protection assay. Our results show that BgRXR binds and is activated by retinoids and suggest that retinoid signaling pathways are conserved in the Lophotrochozoa. The nucleotide sequence reported in this paper has been submitted to the GenBank/EBI Data Bank with accession no. AY048663.

PAQ: Partition Analysis of Quasispecies.

MOTIVATION: The complexities of genetic data may not be accurately described by any single analytical tool. Phylogenetic analysis is often used to study the genetic relationship among different sequences. Evolutionary models and assumptions are invoked to reconstruct trees that describe the phylogenetic relationship among sequences. Genetic databases are rapidly accumulating large amounts of sequences. Newly acquired sequences, which have not yet been characterized, may require preliminary genetic exploration in order to build models describing the evolutionary relationship among sequences. There are clustering techniques that rely less on models of evolution, and thus may provide nice exploratory tools for identifying genetic similarities. Some of the more commonly used clustering methods perform better when data can be grouped into mutually exclusive groups. Genetic data from viral quasispecies, which consist of closely related variants that differ by small changes, however, may best be partitioned by overlapping groups. RESULTS: We have developed an intuitive exploratory program, Partition Analysis of Quasispecies (PAQ), which utilizes a non-hierarchical technique to partition sequences that are genetically similar. PAQ was used to analyze a data set of human immunodeficiency virus type 1 (HIV-1) envelope sequences isolated from different regions of the brain and another data set consisting of the equine infectious anemia virus (EIAV) regulatory gene rev. Analysis of the HIV-1 data set by PAQ was consistent with phylogenetic analysis of the same data, and the EIAV rev variants were partitioned into two overlapping groups. PAQ provides an additional tool which can be used to glean information from genetic data and can be used in conjunction with other tools to study genetic similarities and genetic evolution of viral quasispecies.