Magnetic blood purification-based soluble fms-like tyrosine kinase-1 removal in comparison with dextran sulfate apheresis and therapeutic plasma exchange.

BACKGROUND: Preeclampsia remains one of the most serious complications of pregnancy. Effective therapies are yet to be developed. Recent research has identified an imbalance of angiogenic and antiangiogenic factors as a root cause of preeclampsia. In particular, soluble fms-like tyrosine kinase-1 (sFlt-1) has been shown to bind the angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), reducing blood vessel growth. Increasing preclinical and clinical evidence suggests that removal of the sFlt-1 protein may benefit patients with early onset preeclampsia. sFlt-1 may be removed by conventional blood purification techniques, such as therapeutic plasma exchange (TPE) and dextran sulfate apheresis (DSA), or emerging technologies, including extracorporeal magnetic blood purification (MBP). METHODS: We compare the performance and selectivity of TPE, DSA, and MBP for the therapeutic removal of sFlt-1. For MPB, we employ magnetic nanoparticles functionalized with either sFlt-1 antibodies or the sFlt-1-binding partner, vascular endothelial growth factor (VEGF). RESULTS: We demonstrate that sFlt-1 removal by MBP is feasible and significantly more selective than TPE and DSA at comparable sFlt-1 removal efficiencies (MBP 96%, TPE 92%, DSA 78%). During both TPE and DSA, complement factors (incl. C3c and C4) are depleted to a considerable extent (-90% for TPE, -55% for DSA), while in MBP, complement factor concentrations remain unaltered. We further demonstrate that the removal efficacy of sFlt-1 in the MBP approach is strongly dependent on the nanoparticle type and dose and can be optimized to reach clinically feasible throughputs. CONCLUSIONS: Taken together, the highly selective removal of sFlt-1 and potential other disease-causing factors by extracorporeal magnetic blood purification may offer new prospects for preeclamptic patients.

Progesterone, cervical cerclage or cervical pessary to prevent preterm birth: a decision-making analysis of international guidelines.

OBJECTIVE: The aim of this study was to investigate guidelines on preterm birth, analyze decision-criteria, and to identify consensus and discrepancies among these guidelines. DESIGN: Objective consensus analysis of guidelines. SAMPLE: Ten international guidelines on preterm birth. METHODS: Relevant decision criteria were singleton vs. twin pregnancy, history, cervical length, and cervical surgery / trauma or Mullerian anomaly. Eight treatment recommendations were extracted. For each decision-making criteria the most commonly recommended treatment was identified, and the level of consensus was evaluated. MAIN OUTCOME MEASURES: Consensus and Discrepancies among recommendations. RESULTS: In a case of singleton pregnancies with no history of preterm birth and shortened cervix, most guidelines recommend progesterone. In singleton pregnancies with a positive history and shortened cervix, all guidelines recommend a cerclage as an option, alternative or conjunct to progesterone. The majority of the guidelines advise against treatment in twin pregnancies. CONCLUSIONS: A shortened cervix and a history of preterm birth are relevant in singleton pregnancies. In twins, most guidelines recommend no active treatment. Among international guidelines a shortened cervix and a history of preterm birth are relevant in singleton pregnancies. With no history of preterm birth and with a shortened cervix most guidelines recommend progesterone treatment.

Advances in prenatal diagnosis of fetal otocephaly by 3D imaging.

The case presented here shows the rare diagnosis of fetal otocephaly with lethal prognosis due to impossible airway management after birth. Otocephaly is characterised by fetal agnathia, microstomia and synotia. As in our case, otocephaly is usually not recognised until the third trimester and leads to challenging clinical situations and decision making.A woman in her 30s presented to our tertiary hospital at 27 weeks of gestation because of an unexplained polyhydramnios. 3D imaging illustrated the complex syndrome of otocephaly and helped understand the present disease patterns. After premature birth, palliative care was agreed on and the newborn was able to pass away peacefully in the arms of his parents.We recommend the implementation of 3D imaging into routine scans for the assessment of the fetal face and ears, especially in situations of unexplained polyhydramnios.

Accuracy of Point-of-care Ultrasound in Diagnosing Acute Appendicitis During Pregnancy.

INTRODUCTION: Acute appendicitis is the most common non-obstetrical surgical emergency in pregnancy. Ultrasound is the imaging tool of choice, but its use is complicated due to anatomical changes during pregnancy and depends on the clinician's expertise. In this study, our aim was to investigate the diagnostic accuracy of point-of-care ultrasound (POCUS) in suspected appendicitis in pregnant women. METHODS: We conducted a retrospective analysis of all pregnant women undergoing POCUS for suspected appendicitis between June 2010-June 2020 in a tertiary emergency department. The primary outcome was to establish sensitivity, specificity, and likelihood ratios of POCUS in diagnosing acute appendicitis, overall and for each trimester. We used histology of the appendix as the reference standard in case of surgery. If appendectomy was not performed, the clinical course until childbirth was used to rule out appendicitis. If the patients underwent magnetic resonance imaging (MRI), we compared readings to POCUS. RESULTS: A total of 61 women were included in the study, of whom 34 (55.7%) underwent appendectomy and in 30 (49.2%) an acute appendicitis was histopathologically confirmed. Sensitivity of POCUS was 66.7% (confidence interval [CI] 95% 47.1-82.7), specificity 96.8% (CI 95% 83.3-99.9), and positive likelihood ratio 20.7. Performance of POCUS was comparable in all trimesters, with highest sensitivity in the first trimester (72.7%). The MRI reading showed a sensitivity of 84.6% and a specificity of 100%. In the four negative appendectomies a MRI was not performed. CONCLUSION: Point-of-care ultrasound showed a high specificity and positive likelihood ratio in diagnosing acute appendicitis in pregnant women in all trimesters with suspected appendicitis. In negative (or inconclusive) cases further imaging as MRI could be helpful to avoid negative appendectomy.

The Role of Inorganics in Preeclampsia Assessed by Multiscale Multimodal Characterization of Placentae.

Preeclampsia is one of the most dangerous diseases in pregnancy. Because of the hypertensive nature of preeclampsia, placental calcifications are believed to be a predictor for its occurrence, analogous to their role in cardiovascular diseases. However, the prevalence and the relevance of calcifications for the clinical outcome with respect to preeclampsia remains controversial. In addition, the role of other inorganic components present in the placental tissue in the development of preeclampsia has rarely been investigated. In this work, we therefore characterized inorganic constituents in placental tissue in groups of both normotensive and preeclamptic patients (N = 20 each) using a multi-scale and multi-modal approach. Examinations included elemental analysis (metallomics), sonography, computed tomography (CT), histology, scanning electron microscopy, X-ray fluorescence and energy dispersive X-ray spectroscopy. Our data show that tissue contents of several heavy metals (Al, Cd, Ni, Co, Mn, Pb, and As) were elevated whereas the Rb content was decreased in preeclamptic compared to normotensive placentae. However, the median mineral content (Ca, P, Mg, Na, K) was remarkably comparable between the two groups and CT showed lower calcified volumes and fewer crystalline deposits in preeclamptic placentae. Electron microscopy investigations revealed four distinct types of calcifications, all predominantly composed of calcium, phosphorus and oxygen with variable contents of magnesium in tissues of both maternal and fetal origin in both preeclamptic and normotensive placentae. In conclusion our study suggests that heavy metals, combined with other factors, can be associated with the development of preeclampsia, however, with no obvious correlation between calcifications and preeclampsia.

Glutathione exposes sequential IgE-epitopes in ovomucoid relevant in persistent egg allergy.

SCOPE: Patients with persistent egg allergy have more immunoglobulin E (IgE) against sequential than conformational epitopes of ovomucoid (OVO). Here, we aimed to identify compounds capable to render sequential epitopes in egg. METHODS AND RESULTS: Glutathione was used for in vitro reduction of OVO and circular dichroism analyses were performed. Glutathione reduced OVO in a concentration-dependent manner. Egg white was analyzed for reduced proteins with a thiol probe and by MALDI-TOF/TOF. In unprocessed total egg white, several reduced proteins were detected by the thiol probe, among them reduced ovalbumin could be confirmed with MS analyses. Egg-allergics or sensitized controls were tested serologically (n = 19) for IgE against native and reduced OVO and in skin prick tests (n = 9). More patients had IgE against reduced than native OVO in Western blots. In skin prick test, five out of seven persistent egg-allergics and none of the controls reacted with reduced OVO. CONCLUSION: Reduced egg proteins are present in natural egg white. Glutathione, which is present in egg and furthermore is used as texture-improving additive in processed food, is capable of reducing OVO. Patients with persistent egg allergy reacted rather to reduce the native OVO. Hence, our data indicate that reduction is a novel natural and processing-associated principle, which contributes to the allergenicity of food.