Success Rate and Long-Term Effects of Embolization of Pelvic Arteries for the Treatment of Postpartum Hemorrhage

Introduction: Postpartum hemorrhage (PPH) is the leading cause of peripartal maternal mortality and accounts for 25% of all maternal deaths worldwide. The most common reasons of PPH are uterine atony, retained placenta, or placenta accreta spectrum. Treatment of PPH depends on the etiology and corresponds to a stepwise approach, which follows the German, Austrian and Swiss guideline for the diagnosis and therapy of PPH in Switzerland. In severe ongoing PPH, hysterectomy has been the ultima ratio for many decades. Nowadays, interventional embolization of the pelvic arteries (PAE) has become a popular alternative. Besides being a highly effective minimally invasive method, PAE avoids hysterectomy with consecutively reduced morbidity and mortality. However, data on the long-term effects of PAE on fertility and menstrual cycle are scarce. Methods: We performed a monocentric study consisting of a retro- and a prospective part including all women who had undergone a PAE between 2012 and 2016 at University Hospital Zurich. Descriptive characteristics of patients and efficacy of PAE defined as cessation of bleeding were analyzed retrospectively. In the prospective part, all patients were contacted for a follow-up questionnaire regarding menstruation and fertility after embolization. Results: Twenty patients with PAE were evaluated. Our data showed a success rate of PAE in 95% of patients with PPH; only 1 patient needed a second, then successful, PAE. No patient needed a hysterectomy or any other surgical intervention. In our study, an association between mode of delivery and identified etiology of PPH is observed. After spontaneous delivery (n = 6), the main reason of severe PPH was retained placenta (n = 4), while after cesarean section (n = 14), uterine atony was identified in most cases (n = 8). Regarding menstruation after embolization, all women reported regular menstruation after the breastfeeding period (100%). The majority reported a regular pattern with a shorter or similar duration (73%) and lower or similar intensity (64%). Dysmenorrhea decreased in 67% of patients. Four patients planned another pregnancy, of whom only one had become pregnant with assisted reproductive technology and ended up in a miscarriage. Discussion: Our study confirms the efficacy of PAE in PPH, thus obviating complex surgical interventions and associated morbidity. The success of PAE does not depend on the primary cause of PPH. Our results may encourage the prompt decision to perform PAE in the management of severe PPH in case of failure of conservative management and help physicians in the post-interventional counseling regarding menstruation patterns and fertility

First trimester abortion protocols by facility type in Switzerland and potential barriers to accessing the service

Simplified first-trimester abortion protocols are well established. However, data on the use of medical or surgical abortion protocols across Switzerland is lacking. We report protocol characteristics in abortion care for two different facility types, hospital vs private practices (office-based) in Switzerland. Furthermore, we investigate an association between protocol characteristics and the likelihood of following through with the abortion at the same facility. We also report abortion outcomes of an office-based cohort where doctors use simplified abortion protocols. This study consists of two parts. (i) Between April and July, 2019, we collected data regarding medical and surgical abortion protocols of institutions offering abortions, in a nationwide survey. We assessed whether the proportion of patients who followed through with the abortion (primary outcome) after first appointment was associated with predefined protocol characteristics, considered to complicate access to abortion services, using generalised estimating equations. (ii) We analysed abortion outcomes of six selected office-based facilities from January, 2008, to December, 2018, using simplified abortion protocols in accordance with the Worlds Health Organisation (WHO) guidelines. (i) We included a total of 39 institutions. Hospitals showed more protocol-based barriers to abortion access compared with office-based facilities. The odds of undergoing an abortion after the first appointment were increased using protocols with minimal barriers. Overall, office-based facilities applied higher gestational age limits, required fewer appointments, and administered mifepristone more often after the first visit than did hospitals. (ii) We included a total of 5274 patients with an incidence of complications requiring surgery of 2.5% in line with rates reported in published literature. Only a few hospitals provide abortion care with easy access to medical and surgical abortion, whereas most office-based facilities do. Access to abortion services is generally crucial, and should be provided in a single visit whenever clinically permissible

The Impact of Prepartum Platelet Count on Postpartum Blood Loss and Its Association with Coagulation Factor XIII Activity

BACKGROUND Postpartum hemorrhage is a leading cause of maternal morbidity and mortality worldwide. Contradictory information exists regarding the relevance of prepartum platelet count on postpartum hemorrhage. We have shown prepartum coagulation factor XIII to be associated with postpartum blood loss; however, little is known about the association of platelet count with factor XIII activity. Our objectives were, first, to evaluate the impact of prepartum platelet count on measured postpartum blood loss in the context of prepartum measurements of coagulation factors I, II, and XIII and, second, to evaluate the association of platelet count with coagulation factor XIII, both pre- and postpartum. MATERIAL AND METHODS This is a secondary analysis of a prospective cohort study (PPH 1,300 study) which analyzed the impact of prepartum blood coagulation factors on postpartum blood loss in 1,300 women. Blood loss was quantified using a validated technique. The impact of prepartum platelet count on measured blood loss was assessed by continuous outcome logistic regression; the association of platelet count with factor XIII activity by Spearman rank correlation. RESULTS Prepartum platelet count was significantly associated with measured postpartum blood loss: every one unit (G/L) increase in prepartum thrombocytes was associated with an odds ratio of 1.002 (95% confidence interval, 1.001-1.004, p = 0.005) to keep blood loss below any given cut-off level. This means that the probability of postpartum hemorrhage decreases with increasing prepartum platelet levels. Moreover, a significant association of platelet count with factor XIII activity was shown (Spearman rank correlation coefficient for prepartum values 0.228, p < 0.001, and for postpartum values 0.293, p < 0.001). DISCUSSION/CONCLUSION The significant association of prepartum platelet count and postpartum blood loss as well as the association of platelet count with blood coagulation factor XIII activity support the likely role of platelets in preventing postpartum hemorrhage and support the new guidelines for the treatment of postpartum hemorrhage in Germany, Austria, and Switzerland, which calls for optimizing platelet counts peripartally in case of postpartum hemorrhage. A possible effect of platelets on the level of circulating factor XIII cannot be ruled out and should prompt further investigation

Serum Pancreatic Stone Protein Reference Values in Healthy Pregnant Women: A Prospective Cohort Study

Background: In non-pregnant populations, pancreatic stone protein (PSP) has been reported to have a higher diagnostic performance for identifying severe inflammatory and infectious disease than other established biomarkers. Objective: To generate reference values for serum PSP in pregnancy and compare them to the values of the general healthy population. Design: A prospective cohort study. Setting: A single center. Population: Healthy women with singleton and multiple pregnancies. Methods: This is a prospective single-center cohort study. Between 2013 and 2021, samples of 5 mL peripheral blood were drawn from 440 healthy pregnant women. Therein, 393 cases were singletons and 47 were multiple pregnancies. Serum PSP levels were measured by specific enzyme-linked immunosorbent assay. The main outcome measures were serum PSP level (ng/mL) reference values in healthy pregnant women. Results: The mean PSP reference values in women with singleton pregnancies were 7.9 ± 2.6 ng/mL (95% CI; 2.69–13.03 ng/mL). The PSP values in women with multiple pregnancies (9.17 ± 3.06 ng/mL (95% CI; 3.05–15.28 ng/mL)) were significantly higher (p = 0.001). The PSP values in the first trimester (6.94 ± 2.53 ng/mL) were lower compared to the second (7.42 ± 2.21 ng/mL) and third trimesters (8.33 ± 2.68 ng/mL, p = 0.0001). Subgroup analyses in singletons revealed no correlations between PSP values, maternal characteristics, and pre-existing medical conditions. Conclusion: The PSP values in healthy pregnant women (4–12 ng/mL) were in the range of the reference values of the general healthy population (8–16 ng/mL). This insight blazes a trail for further clinical studies on the use of PSP as a potential novel biomarker for the early detection of pregnancy-related diseases such as chorioamnionitis

The Role of Pancreatic Stone Protein (PSP) as a Biomarker of Pregnancy-Related Diseases

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions

Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses

Background Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. Methods We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. Findings We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·91%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73–2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74–0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35–0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02–0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08–0·72) of 1412 cases with total bile acids of 40–99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52–10·50]; p=0·26), and versus 18 (3·44%; 2·05–5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83–105·30]; p<0·0001). Interpretation The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. Funding Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust

Naphthoquinone Derivatives Exert Their Antitrypanosomal Activity via a Multi-Target Mechanism

BACKGROUND AND METHODOLOGY: Recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. The lead of this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED(50) of 80 nM against Trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. A multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunctional mechanism of action. To disclose such a multitarget profile of B6, we exploited a chemical proteomics approach. PRINCIPAL FINDINGS: A functionalized congener of B6 was immobilized on a solid matrix and used to isolate target proteins from Trypanosoma brucei lysates. Mass analysis delivered two enzymes, i.e. glycosomal glycerol kinase and glycosomal glyceraldehyde-3-phosphate dehydrogenase, as potential molecular targets for B6. Both enzymes were recombinantly expressed and purified, and used for chemical validation. Indeed, B6 was able to inhibit both enzymes with IC(50) values in the micromolar range. The multifunctional profile was further characterized in experiments using permeabilized Trypanosoma brucei cells and mitochondrial cell fractions. It turned out that B6 was also able to generate oxygen radicals, a mechanism that may additionally contribute to its observed potent trypanocidal activity. CONCLUSIONS AND SIGNIFICANCE: Overall, B6 showed a multitarget mechanism of action, which provides a molecular explanation of its promising anti-trypanosomatid activity. Furthermore, the forward chemical genetics approach here applied may be viable in the molecular characterization of novel multitarget ligands

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI