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.

Patient blood management (PBM) in pregnancy and childbirth: literature review and expert opinion.

PURPOSE: Patient blood management [PBM] has been acknowledged and successfully introduced in a wide range of medical specialities, where blood transfusions are an important issue, including anaesthesiology, orthopaedic surgery, cardiac surgery, or traumatology. Although pregnancy and obstetrics have been recognized as a major field of potential haemorrhage and necessity of blood transfusions, there is still little awareness among obstetricians regarding the importance of PBM in this area. This review, therefore, summarizes the importance of PBM in obstetrics and the current evidence on this topic. METHOD: We review the current literature and summarize the current evidence of PBM in pregnant women and postpartum with a focus on postpartum haemorrhage (PPH) using PubMed as literature source. The literature was reviewed and analysed and conclusions were made by the Swiss PBM in obstetrics working group of experts in a consensus meeting. RESULTS: PBM comprises a series of measures to maintain an adequate haemoglobin level, improve haemostasis and reduce bleeding, aiming to improve patient outcomes. Despite the fact that the WHO has recommended PBM early 2010, the majority of hospitals are in need of guidelines to apply PBM in daily practice. PBM demonstrated a reduction in morbidity, mortality, and costs for patients undergoing surgery or medical interventions with a high bleeding potential. All pregnant women have a significant risk for PPH. Risk factors do exist; however, 60% of women who experience PPH do not have a pre-existing risk factor. Patient blood management in obstetrics must, therefore, not only be focused on women with identified risk factor for PPH, but on all pregnant women. Due to the risk of PPH, which is inherent to every pregnancy, PBM is of particular importance in obstetrics. Although so far, there is no clear guideline how to implement PBM in obstetrics, there are some simple, effective measures to reduce anaemia and the necessity of transfusions in women giving birth and thereby improving clinical outcome and avoiding complications. CONCLUSION: PBM in obstetrics is based on three main pillars: diagnostic and/or therapeutic interventions during pregnancy, during delivery and in the postpartum phase. These three main pillars should be kept in mind by all professionals taking care of pregnant women, including obstetricians, general practitioners, midwifes, and anaesthesiologists, to improve pregnancy outcome and optimize resources.

Nano-analytical characterization of endogenous minerals in healthy placental tissue: mineral distribution, composition and ultrastructure.

Despite its crucial role, the placenta is the least understood human organ. Recent clinical studies indicate a direct association between placental calcification and maternal and offspring health. This study reveals distinct characteristics of minerals formed during gestational ageing using cutting-edge nano-analytical characterization and paves the way for investigations focused on the identification of potential markers for disease risks in a clinical setting based on atypical placental mineral fingerprints.

Application of portable sleep monitoring devices in pregnancy: a comprehensive review.

Objective.The physiological, hormonal and biomechanical changes during pregnancy may trigger sleep disordered breathing (SDB) in pregnant women. Pregnancy-related sleep disorders may associate with adverse fetal and maternal outcomes including gestational diabetes, preeclampsia, preterm birth and gestational hypertension. Most of the screening and diagnostic studies that explore SDB during pregnancy were based on questionnaires which are inherently limited in providing definitive conclusions. The current gold standard in diagnostics is overnight polysomnography (PSG) involving the comprehensive measurements of physiological changes during sleep. However, applying the overnight laboratory PSG on pregnant women is not practical due to a number of challenges such as patient inconvenience, unnatural sleep dynamics, and expenses due to highly trained personnel and technology. Parallel to the progress in wearable sensors and portable electronics, home sleep monitoring devices became indispensable tools to record the sleep signals of pregnant women at her own sleep environment. This article reviews the application of portable sleep monitoring devices in pregnancy with particular emphasis on estimating the perinatal outcomes.Approach.The advantages and disadvantages of home based sleep monitoring systems compared to subjective sleep questionnaires and overnight PSG for pregnant women were evaluated.Main Results.An overview on the efficiency of the application of home sleep monitoring in terms of accuracy and specificity were presented for particular fetal and maternal outcomes.Significance.Based on our review, more homogenous and comparable research is needed to produce conclusive results with home based sleep monitoring systems to study the epidemiology of SDB in pregnancy and its impact on maternal and neonatal health.

Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization.

Exposure to nanoparticles (NPs) in pregnancy is increasingly linked to adverse effects on embryo-fetal development and health later in life. However, the developmental toxicity mechanisms of NPs are largely unknown, in particular potential effects on the placental secretome, which orchestrates many developmental processes pivotal for pregnancy success. This study demonstrates extensive material- and pregnancy stage-specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO2) and titanium dioxide (TiO2) NPs) and environmental NPs (diesel exhaust particles, DEPs). This includes a multitude of secreted inflammatory, vascular, and endocrine placental factors as well as extracellular vesicle (EV)-associated proteins. Moreover, conditioned media (CM) from NP-exposed explants induce pronounced anti-angiogenic and anti-vasculogenic effects, while early neurodevelopmental processes are only marginally affected. These findings underscore the potential of metal oxide NPs and DEPs for widespread interference with the placental secretome and identify vascular morphogenesis as a sensitive outcome for the indirect developmental toxicity of different NPs. Overall, this work has profound implications for the future safety assessment of NPs for industrial, commercial, or medical applications in pregnancy, which should consider placenta-mediated toxicity by holistic secretomics approaches to ensure the development of safe nanotechnologies.

A patient-reported outcome measure to identify occurrence and distress of post-surgery symptoms of WOMen with vulvAr Neoplasia (WOMAN-PRO) - a cross sectional study.

OBJECTIVE: The aim of the study was to describe the (a) symptom experience of women with vulvar intraepithelial neoplasia and vulvar cancer (vulvar neoplasia) during the first week after hospital discharge, and (b) associations between age, type of disease, stage of disease, the extent of surgical treatment and symptom experience. METHODS: This cross-sectional study was conducted in eight hospitals in Germany and Switzerland (Clinical Trial ID: NCT01300663). Symptom experience after surgical treatment in women with vulvar neoplasia was measured with our newly developed WOMAN-PRO instrument. Outpatients (n=65) rated 31 items. We used descriptive statistics and regression analysis. RESULTS: The average number of symptoms reported per patient was 20.2 (SD 5.77) with a range of 5 to 31 symptoms. The three most prevalent wound-related symptoms were 'swelling' (n=56), 'drainage' (n=54) and 'pain' (n=52). The three most prevalent difficulties in daily life were 'sitting' (n=63), 'wearing clothes' (n=56) and 'carrying out my daily activities' (n=51). 'Tiredness' (n=62), 'insecurity' (n=54) and 'feeling that my body has changed' (n=50) were the three most prevalent psychosocial symptoms/issues. The most distressing symptoms were 'sitting' (Mean 2.03, SD 0.88), 'open spot (e.g. opening of skin or suture)' (Mean 1.91, SD 0.93), and 'carrying out my daily activities' (Mean 1.86, SD 0.87), which were on average reported as 'quite a bit' distressing. Negative associations were found between psychosocial symptom experience and age. CONCLUSIONS: WOMAN-PRO data showed a high symptom prevalence and distress, call for a comprehensive symptom assessment, and may allow identification of relevant areas in symptom management.

[Urinary retention in young female patients]. / Blasenentleerungsstörung bei jungen Patientinnen.

INTRODUCTION: This practice case describes a 28-year-old female patient suffering from unclear residual urine formation. Urogynecologic examination reveals a severely hypercapacitated bladder with atonic detrusor. After ruling out other gynecologic and neurologic differential diagnoses, the diagnosis of Fowler syndrome was made. This is a painless residual urine formation with typical pelvic floor EMG with detrusor sphincter dyscoordination. Causal therapies do not exist. Sacral neuromodulation, percutaneous tibial nerve stimulation, or intermittent self-catheterization.

Prevalence of medically induced psychological trauma and its influence on women's health.

OBJECTIVE: The aim of the present study was three-fold. One, to assess the prevalence of medical traumatization in outpatients of a gynecologic department; two, to analyze the relationship of medical traumatization with adverse childhood events; and three, to investigate the extent to which medical traumatization affects the health outcomes of woman. METHODS: Between January and September 2022, a prospective cross-sectional study recruited patients of a gynecologic outpatient clinic at St. Gallen Cantonal Hospital in Switzerland. Medical trauma was a self-reported item. The presence of adverse childhood events was assessed using the Childhood Trauma Questionnaire. The severity of post-traumatic stress was evaluated using the Impact of Event Scale Revised questionnaire. RESULTS: In total, 227 patients were recruited. Medical trauma was reported by 20% of the interviewees and it was strongly associated with obesity (A = 0.005). Undergoing surgery was most commonly the source of psychological distress (5.7%) followed by delivery (4.8%), pregnancy loss (4.8%), and cancer diagnosis (4.0%). Yet, fewer than 1% of the patients reached the threshold suggesting post-traumatic stress disorder. CONCLUSIONS: We found no relationship between the medical trauma, adverse childhood events, cardiovascular disease, or substance abuse. The presence of medical trauma was associated with the patient's body mass index (calculated as weight in kilograms divided by the square of height in meters).

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.

Cordycepin (3'-deoxyadenosine), an inhibitor of mRNA polyadenylation, suppresses proliferation and activates apoptosis in human epithelial endometriotic cells in vitro.

BACKGROUND/AIMS: Endometriosis is a benign but chronic disorder associated with pelvic pain and infertility. Enhanced proliferation and reduced apoptosis susceptibility are characteristics of endometriosis. Cordycepin is a poly(A) polymerase inhibitor. It induces shortening of poly(A) tails, leading to destabilization of mRNAs and finally to proliferation inhibition and cell death in normal and tumor cells. The potential of cordycepin to block proliferation and survival of 11z human immortalized epithelial endometriotic cells was determined. METHODS: 11z cell cultures were treated with cordycepin. Cordycepin-induced inhibition of proliferation and alterations in protein expression and protein phosphorylation were determined by the methyl thiazolyl tetrazolium assay and immunoblot analysis, respectively. RESULTS: Cordycepin induced the rapid and significant upregulation of the cell cycle progression inhibitor p21 and the downregulation of the cell cycle progression promoter cyclin D(1), finally leading to the inhibition of the proliferation of 11z human epithelial endometriotic cells. Cordycepin reduced the phosphorylation of the p38 mitogen-activated protein kinase and the retinoblastoma protein. It also activated caspase-dependent, intrinsic apoptosis, as documented by the proteolytic cleavage of the caspase-9, caspase-3 and the poly(ADP ribose) polymerase 1 precursor. CONCLUSION: The mRNA polyadenylation inhibitor cordycepin inhibits proliferation and survival of endometriotic cells.

Frequency-domain near-infrared spectroscopy of the uterine cervix during regular pregnancies.

Preterm labor is a common obstetric complication. Clinical evaluation of cervical ripening to predict preterm labor is very inaccurate. We used frequency-domain near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of the optical properties (i.e., absorption and scattering of light) in the uterine cervix during regular pregnancies. Optical properties of uterine cervices were measured in 13 patients at various time points of regular pregnancies. For each gestational trimester, mean values with 95% confidence intervals were calculated for oxy-, deoxy-, and total hemoglobin concentration (O(2)Hb, HHb, tHb), tissue oxygen saturation and water content and statistically significant differences between the trimesters were determined. The wavelength-dependent scattering (scatter power) was calculated by an exponential fit. O(2)Hb, and tHb and the scatter power showed an increase as a function of the gestational age. Differences between the second and the third trimester were statistically significant. HHb and the water content showed no significant change over time. Our results show that FD-NIRS is a promising diagnostic tool for providing information about cervical content of hemoglobin, water, and extracellular matrix proteins. We propose this technology to assess the cervical ripening and eventually to predict preterm labor.

Optimal treatment for patients with ectopic pregnancies and a history of fertility-reducing factors.

PURPOSE: With most ectopic pregnancy (EP) cases now diagnosed and treated early, a major concern has become future reproductive outcome. The aim of this study was to evaluate long-term reproductive outcome after salpingotomy versus salpingectomy in patients with and without additional fertility-reducing factors. METHODS: As part of a prospective follow-up study, 261 patients underwent laparoscopic management of EP at our institution. History was taken specifically looking at preexisting risk factors for reduced fertility. Patients were then followed with regard to future reproductive events. RESULTS: Of 261 patients, 196 (75%) reported a subsequent desire for pregnancy. 145 patients had undergone salpingotomy and 51 salpingectomy. In patients without prior history of fertility-reducing factors, the subsequent intrauterine pregnancy rates were >90% for both salpingotomy and salpingectomy groups irrespective of the surgical approach. In patients with preexisting fertility-reducing factors, postoperative intrauterine pregnancy rates were 75% in the salpingotomy group, but only 40% in the salpingectomy group (p < 0.05), showing maximal effect for conservative surgery. CONCLUSION: Laparoscopic salpingotomy is of particular benefit for patients with additional fertility-reducing factors desirous of future pregnancy. Reproductive outcome is excellent in patients without such risk factor, irrespective of the surgical approach.

[Endometrial cancer - state of the art]. / Endometriumkarzinom - State of the Art.

Endometrial cancer is the most common genital malignant tumor in women in industrial countries. The typical symptoms are postmenopausal bleeding or metrorrhagia. Following anamneses, clinical examination and transvaginal sonography, histological confirmation is obtained by dilation and curettage. Hysterectomy, bilateral salpingo-oophorectomy and according to tumor stage pelvic and paraaortic lymphadenectomy are the mainstay of surgical treatment that is performed more and more often by laparoscopy. Adjuvant pelvic external beam radiation or vaginal brachytherapie are added if indicated. In certain situations adjuvant chemotherapy is necessary. Follow-up by clinical examination and transvaginal sonography are reasonable for the first few postoperative years.

Optical properties, physiologic parameters and tissue composition of the human uterine cervix as a function of hormonal status.

The influence of sex hormones on the human uterine cervix is likely to be important in the process of cervical ripening. Frequency domain near-infrared spectroscopy (FD-NIRS) was used to investigate non-invasively the changes in the optical properties that reflect physiologic parameters and tissue composition of the uterine cervix in the different phases of the menstrual cycle. Twenty premenopausal and nine postmenopausal women were examined. Optical properties of the uterine cervix were measured, and physiological parameters [concentration of water, oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb), total hemoglobin (tHb), oxygen saturation (StO(2)), water, and scattering power] were calculated. Analysis of variance (ANOVA) was used to test for statistical significance. The optical properties of the anterior cervical lip did not differ from those of the posterior lip. HHb was significantly lower in cervices during menstrual bleeding than during the follicular, luteal, or postmenopausal phases. The ratio of O(2)Hb to HHb was highly significantly increased by a factor of 2 when cervices during the menstrual bleeding were compared with those during the follicular, luteal, or postmenopausal phases. The scattering power was significantly lower during menstrual bleeding than during the follicular or postmenopausal phases. We demonstrated that withdrawal of sex hormones during menstrual bleeding is associated with a significant decrease in HHb and scattering power, with stable values of O(2)Hb, tHb, StO(2), and H(2)O compared with the values during the follicular, luteal or postmenopausal phases of the menstrual cycle. Cervical softening during menstrual bleeding seems to be different from cervical softening for labor.

Bipolar coagulation with the BiClamp forceps versus conventional suture ligation: a multicenter randomized controlled trial in 175 vaginal hysterectomy patients.

PURPOSE: To compare bipolar vessel sealing (BVS; BiClamp) versus conventional suture ligation in vaginal hysterectomy. METHODS: A multicenter, single-blind randomized controlled trial (RCT) was conducted at eight women's hospitals in Germany. One hundred and seventy-five patients with benign uterine disease underwent vaginal hysterectomy using BVS (n = 88) or conventional suture ligation (n = 87 controls). Data analysis was based on intention-to-treat. RESULTS: Postoperative pain (primary endpoint) was decreased in the BVS group, but not significantly. Intraoperative blood loss was significantly lower in this group, with <100 mL recorded in 79/88 versus 52/86 patients (P < 0.001). Hemoglobin decrease indicated non-significantly lower blood loss in the BVS group. Operating time was significantly shorter in the BVS group than in the controls (38.0 +/- 18.6 vs. 48.0 +/- 24.9 min; P = 0.001). On average, 7.8 sutures/operation were saved with bipolar coagulation (P < 0.0001). Ease of use ratings were significantly higher for BVS. Hospital stay was similar for both groups. Adverse event rates did not differ significantly. CONCLUSIONS: The BiClamp procedure proved superior or similar to conventional ligation, particularly with regard to intraoperative blood loss, operating time and postoperative pain, although statistical significance was not attained for postoperative pain. Moreover, BVS was easier to use and more cost effective.

Changes in tumour biological markers during primary systemic chemotherapy (PST).

BACKGROUND: The influence of primary systemic therapy (PST) on the expression of relevant therapeutic markers is still under investigation. PATIENTS AND METHODS: Corresponding "baseline" biopsies and post-chemotherapy surgical specimens from 87 patients treated with neoadjuvant anthracycline- or taxane-based chemotherapy were analysed for the expression of the oestrogen receptor (ER), the progesterone receptor (PR), the B-cell lymphoma protein 2 (Bcl-2), the v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (Her2/neu), the tumour protein p53 and the proliferation-related Ki-67 antigen. RESULTS: The pathological response rate was 70%. Twenty-three tumours (26%) changed hormone receptor classification after chemotherapy (7, ER; 16 PR). A significant change was also observed for Her2/neu status. Eleven tumours which were positive prior to PST down-regulated Her2/neu after chemotherapy. The median Ki-67 index decreased from 30% before to 13% after treatment (p<0.01). Minor changes were observed in the expression of Bcl-2 and p53 (9%). Only the reduction of Ki-67 was associated with pathological response to PST. CONCLUSION: Her2/neu status as well as ER and PR status should be re-evaluated on post-chemotherapy surgical specimens since changes can be observed.