Maternal and Fetal Risks in Higher Multiple Cesarean Deliveries

The professionalization of women has shifted family planning to increased maternal ages. This has increased the use of assisted reproduction. Therefore, the tolerance toward suboptimal outcome of pregnancy decreases, and self-determined decision-making is on the rise. Once women have made the decision for elective cesarean section in their first pregnancy, subsequent pregnancies may result in multiple cesarean deliveries. This chapter analyzes the risks associated with higher multiple cesarean deliveries, such as bleeding and transfusion, adhesions, bowel and urinary tract injury, and uterus rupture. It also discussed the risks for vaginal birth following cesarean (VBAC) following multiple cesareans. Also there are neonatal risks involved, and women may require specific obstetric anesthesia. The chapter will analyze the risks for the offspring and the mother depending on the number of previous cesarean sections. This may enable detailed counseling of parents before a higher multiple repeat cesarean section is performed

The Surgical Technique of Caesarean Section: What is Evidence Based?

Caesarean section is the most frequent obstetric operation which is associated with increased maternal morbidity and mortality. Although these risks are low, affected women may suffer from severe consequences and this may affect subsequent pregnancies and deliveries. A variety of surgical approaches have been described, however, on low evidence level. The objective of this chapter is therefore to systematically search the literature and analyse the available evidence including preoperative workup, prophylactic antibiotics, skin disinfection, preoperative bladder catheterization as well as details of the individual steps of the actual operation itself such as skin incision types, preparation of soft tissue and womb, removal of the placenta, cervical dilatation and stitching of the womb, peritoneum, rectus muscle, fascia, subcutaneous fat, and skin. We systematically searched for meta-analysis, systematic reviews, and big studies and evaluated the evidence for each individual step

Human umbilical cord-derived mesenchymal stem cells utilise activin-A to suppress interferon-gamma production by natural killer cells

Following allogeneic hematopoietic stem cell transplantation (HSCT), interferon (IFN)-γ levels in the recipient's body can strongly influence the clinical outcome. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are lucrative as biological tolerance inducers in HSCT settings. Hence, we studied the molecular mechanism of how UC-MSCs influence natural killer (NK) cell-mediated IFN-γ production. Allogeneic NK cells were cultured in direct contact with UC-MSCs or cell free supernatants from MSC cultures (MSC conditioned media). We found that soluble factors secreted by UC-MSCs strongly suppressed IL-12/IL-18-induced IFN-γ production by NK cells by reducing phosphorylation of STAT4, NF-κB as well as T-bet activity. UC-MSCs secreted considerable amounts of Activin-A, which could suppress IFN-γ production by NK cells. Neutralisation of Activin-A in MSC conditioned media significantly abrogated their suppressive abilities. Till date, multiple groups have reported that prostaglandin (PG)-E2 produced by MSCs can suppress NK cell functions. Indeed, we found that inhibition of PGE2 production by MSCs could also significantly restore IFN-γ production. However, the effects of Activin-A and PGE2 were not cumulative. To the best of our knowledge, we are first to report the role of Activin-A in MSC mediated suppression of IFN-γ production by NK cells.DFG/SFB738/A5Hannover Biomedical Research School (HBRS)DFG/REBIRTHNiedersächsische Krebsgesellschaf

Repeated freezing procedures preserve structural and functional properties of amniotic membrane for application in ophthalmology

For decades, the unique regenerative properties of the human amniotic membrane (hAM) have been successfully utilized in ophthalmology. As a directly applied biomaterial, the hAM should be available in a ready to use manner in clinical settings. However, an extended period of time is obligatory for performing quality and safety tests. Hence, the low temperature storage of the hAM is a virtually inevitable step in the chain from donor retrieval to patient application. At the same time, the impact of subzero temperatures carries an increased risk of irreversible alterations of the structure and composition of biological objects. In the present study, we performed a comprehensive analysis of the hAM as a medicinal product; this is intended for a novel strategy of application in ophthalmology requiring a GMP production protocol including double freezing– thawing cycles. We compared clinically relevant parameters, such as levels of growth factors and extracellular matrix proteins content, morphology, ultrastructure and mechanical properties, before and after one and two freezing cycles. It was found that epidermal growth factor (EGF), transforming growth factor beta 1 (TGF-ß1), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), hyaluronic acid, and laminin could be detected in all studied conditions without significant differences. Additionally, histological and ultrastructure analysis, as well as transparency and mechanical tests, demonstrated that properties of the hAM required to support therapeutic efficacy in ophthalmology are not impaired by dual freezing. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Influence of selected factors on serum AFP levels in pregnant women in terms of prenatal screening accuracy — literature review

Alpha-fetoprotein (AFP) is one of the biochemical components of the triple (T-3) and quadruple (T-4) test used so far in prenatal screening mainly for trisomy 21 (T21) and neural tube defects (NTDs). Based on many years of experience and data collected during these studies, a variety of factors have been identified that can affect a pregnant woman's serum AFP level, and thus the risk assessment of trisomy 21 (T21) and neural tube defects. These include both unaccounted for purely medical data (e.g., from baseline information about the patient, assisted reproduction methods used, comorbidities and emerging pregnancy pathologies) and errors made during statistical analysis. Since the triple or quadruple test is usually performed between 15 and 20 weeks of pregnancy, most scientific studies are based solely on results from this period of pregnancy — limited data are available for the first and third trimesters of pregnancy. In the era of new improved screening tests, AFP has the potential to become an independent marker for pregnancy well-being evaluation

Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity

Background: Mesenchymal stem cells (MSCs) are increasingly considered to be used as biological immunosuppressants in hematopoietic stem cell transplantation (HSCT). In the early reconstitution phase following HSCT, natural killer (NK) cells represent the major lymphocyte population in peripheral blood and display graft-vs-leukemia (GvL) effects. The functional interactions between NK cells and MSCs have the potential to influence the leukemia relapse rate after HSCT. Until date, MSC-NK cell interaction studies are largely focussed on bone marrow derived (BM)-MSCs. Umbilical cord derived (UC)-MSCs might be an alternative source of therapeutic MSCs. Thus, we studied the interaction of UC-MSCs with unstimulated allogeneic NK cells.Results: UC-MSCs could potently suppress NK cell cytotoxicity in overnight cultures via soluble factors. The main soluble immunosuppressant was identified as prostaglandin (PG)-E2. Maximal PGE2 release involved IL-1β priming of MSCs after close contact between the NK cells and UC-MSCs. Interestingly, blocking gamma-secretase activation alleviated the immunosuppression by controlling PGE2 production. IL-1 receptor activation and subsequent downstream signalling events were found to require gamma-secretase activity.Conclusion: Although the role of PGE2 in NK cell-MSC has been reported, the requirement of cell-cell contact for PGE2 induced immunosuppression remained unexplained. Our findings shed light on this puzzling observation and identify new players in the NK cell-MSC crosstalk.DFG/SFB738/A5Hannover Biomedical Research School (HBRS)REBIRTH Cluster of ExcellenceNiedersächsische Krebsgesellschaft e.V