Preventing postpartum hemorrhage: A network meta-analysis on routes of administration of uterotonics.

1. OBJECTIVE: To perform a network meta-analysis to specify the route of administration that maximises the effectiveness of each of the available prophylactic uterotonics without increasing the risk for side effects. 2. DATA SOURCES: Literature searches on 12th September 2022 included: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. The reference lists of the retrieved study records were also searched. 3. STUDY ELIGIBILITY CRITERIA: Population: Randomized controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. INTERVENTIONS: Systemically administered prophylactic uterotonics of any route and dose for primary postpartum hemorrhage prevention. Comparison: Any other prophylactic uterotonic, or a different route or dose of a given uterotonic, or placebo, or no treatment. Outcomes (primary): postpartum hemorrhage ≥ 500 mL and ≥ 1000 mL. 4. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias and trustworthiness assessments were performed, according to Cochrane's guidance. Direct, indirect and network meta-analyses were conducted, and results were summarized either as risk ratio or mean difference with 95% confidence intervals for dichotomous and continuous outcomes, respectively. The certainty of generated evidence was assessed according to the GRADE approach. Cumulative probabilities were calculated and the surface under the cumulative ranking curve was used to create a ranking of the available drugs. 5. RESULTS: One hundred eighty-one studies involving 122,867 randomised women were included. Most studies were conducted in hospital settings in lower-middle income countries and involved women delivering vaginally. When compared with intramuscular oxytocin, carbetocin (RR 0.58, 95 % CI 0.40-0.84) and oxytocin (RR 0.75, 95 % CI 0.59-0.97) by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination (RR 0.71, 95 % CI 0.56-0.91) are probably more effective in preventing primary postpartum hemorrhage. Intramuscularly administered oxytocin and carbetocin by an intravenous bolus have a favourable side effects profile. 6. CONCLUSIONS: Generated evidence was generally moderate and global inconsistency was low. Carbetocin and oxytocin by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination are probably the top uterotonics for primary postpartum hemorrhage prevention. Large scale studies exploring different routes of administration for available prophylactic uterotonics, and women's views should be conducted.

MicroRNAs Can Influence Ovarian Cancer Progression by Dysregulating Integrin Activity.

Ovarian cancer is a deadly disease that affects thousands of women worldwide. Integrins, transmembrane receptors that mediate cell adhesion and signaling, play important roles in ovarian cancer progression, metastasis, and drug resistance. Dysregulated expression of integrins is implicated in various cellular processes, such as cell migration, invasion, and proliferation. Emerging evidence suggests that microRNAs (miRNAs) can regulate integrin expression and function, thus affecting various physiological and pathological processes, including ovarian cancer. In this article, we review the current understanding of integrin-mediated cellular processes in ovarian cancer and the roles of miRNAs in regulating integrins. We also discuss the therapeutic potential of targeting miRNAs that regulate integrins for the treatment of ovarian cancer. Targeting miRNAs that regulate integrins or downstream signaling pathways of integrins may provide novel therapeutic strategies for inhibiting integrin-mediated ovarian cancer progression.

Advantages and Limitations of Ultrasound as a Screening Test for Ovarian Cancer.

Ovarian cancer (OC) is the seventh most common malignancy diagnosed among women, the eighth leading cause of cancer mortality globally, and the most common cause of death among all gynecological cancers. Even though recent advances in technology have allowed for more accurate radiological and laboratory diagnostic tests, approximately 60% of OC cases are diagnosed at an advanced stage. Given the high mortality rate of advanced stages of OC, early diagnosis remains the main prognostic factor. Our aim is to focus on the sonographic challenges in ovarian cancer screening and to highlight the importance of sonographic evaluation, the crucial role of the operator΄s experience, possible limitations in visibility, emphasizing the importance and the necessity of quality assurance protocols that health workers have to follow and finally increasing the positive predictive value. We also analyzed how ultrasound can be combined with biomarkers (ex. CA-125) so as to increase the sensitivity of early-stage OC detection or, in addition to the gold standard examination, the CT (Computed tomography) scan in OC follow-up. Improvements in the performance and consistency of ultrasound screening could reduce the need for repeated examinations and, mainly, ensure diagnostic accuracy. Finally, we refer to new very promising techniques such as liquid biopsies. Future attempts in order to improve screening should focus on the identification of features that are unique to OC and that are present in early-stage tumors.

Intrauterine Growth Restriction Due to Gestational Diabetes: From Pathophysiology to Diagnosis and Management.

Intrauterine growth restriction (IUGR) represents a condition where the fetal weight is less than the 10th percentile for gestational age, or the estimated fetal weight is lower than expected based on gestational age. IUGR can be caused by various factors such as maternal, placental or fetal factors and can lead to various complications for both the fetus and the mother, including fetal distress, stillbirth, preterm delivery, and maternal hypertension. Women with gestational diabetes are at an increased risk of developing IUGR. This article reviews the different aspects of gestational diabetes in addition to IUGR, the diagnostic methods available for IUGR detection, including ultrasound and Doppler studies, discusses the management strategies for women with IUGR and gestational diabetes and analyzes the importance of early detection and timely intervention to improve pregnancy outcomes.

Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications.

As the leading cause of neonatal morbidity and mortality, preterm birth is recognized as a major public health concern around the world. The purpose of this review is to analyze the connection between infections and premature birth. Spontaneous preterm birth is commonly associated with intrauterine infection/inflammation. The overproduction of prostaglandins caused by the inflammation associated with an infection could lead to uterine contractions, contributing to preterm delivery. Many pathogens, particularly Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Actinomyces, Candida spp., and Streptococcus spp. have been related with premature delivery, chorioamnionitis, and sepsis of the neonate. Further research regarding the prevention of preterm delivery is required in order to develop effective preventive methods with the aim of reducing neonatal morbidity.

Ovarian Cancer and Glutamine Metabolism.

Cancer cells are known to have a distinct metabolic profile and to exhibit significant changes in a variety of metabolic mechanisms compared to normal cells, particularly glycolysis and glutaminolysis, in order to cover their increased energy requirements. There is mounting evidence that there is a link between glutamine metabolism and the proliferation of cancer cells, demonstrating that glutamine metabolism is a vital mechanism for all cellular processes, including the development of cancer. Detailed knowledge regarding its degree of engagement in numerous biological processes across distinct cancer types is still lacking, despite the fact that such knowledge is necessary for comprehending the differentiating characteristics of many forms of cancer. This review aims to examine data on glutamine metabolism and ovarian cancer and identify possible therapeutic targets for ovarian cancer treatment.

Inflammatory Molecules Responsible for Length Shortening and Preterm Birth.

It is estimated that inflammation at the placental-maternal interface is directly responsible for or contributes to the development of 50% of all premature deliveries. Chorioamnionitis, also known as the premature rupture of the amniotic membrane in the mother, is the root cause of persistent inflammation that preterm newborns experience. Beyond contributing to the onset of early labor, inflammation is a critical element in advancing several conditions in neonates, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity and periventricular leukomalacia. Notably, the immune systems of preterm infants are not fully developed; immune defense mechanisms and immunosuppression (tolerance) have a delicate balance that is easily upset in this patient category. As a result, premature infants are exposed to different antigens from elements such as hospital-specific microbes, artificial devices, medications, food antigens and hypoxia/hyperoxia. This has detrimental implications for preterm deliveries of less than 28 weeks because they have not yet evolved the mechanisms to tolerate maternal and self-antigens.

What is already done by different societies in reduction of maternal mortality? Are they successful at all?

Maternal mortality represents a major issue for every health system, especially in developed countries that aim on creating protocols to retain a declining pattern. With the appropriate medical supplies and training, some of these countries have made a remarkable progress in preventing maternal morbidity and mortality. On the contrary, developing countries have still made little or even no progress. Identifying determinants and designing strategies is of great importance in order to overcome such difficulties. The aim of this study is to identify the main causes of maternal mortality in the different societies.

Pregnancy and COVID-19.

Evidence indicates that SARS-CoV-2 infection increases the likelihood of adverse pregnancy outcomes. Modifications in the circulatory, pulmonary, hormonal, and immunological pathways induced by pregnancy render pregnant women as a high-risk group. A growing body of research shows that SARS-CoV-2 infection during pregnancy is connected to a number of maternal complications, including pneumonia and intensive care unit (ICU) hospitalization. Miscarriages, stillbirth, preterm labor, as well as pre-eclampsia and intrauterine growth restriction are also among the most often documented fetal implications, particularly among expecting women who have significant COVID-19 symptoms, often affecting the timing and route of delivery. Thus, prevention of infection and pharmacological treatment options should aim to minimize the aforementioned risks and ameliorate maternal, obstetric and fetal/neonatal outcomes.

Cancer Treatment and Immunotherapy during Pregnancy.

BACKGROUND/AIM: Immunotherapy has, in recent years, witnessed an expansion in its indications for the treatment of cancer. Coupled with the fact that, nowadays, even more women choose to postpone parenthood, thus increasing their chances of having some kind of malignancy during pregnancy, more and more women are eligible for receiving immunotherapy during this period of their lives. The cases of cancer diagnosed during pregnancy is an ever-increasing trend nowadays. MATERIALS AND METHODS: The oncologists and clinicians treating women often face a range of ethical and therapeutic dilemmas due to the particularity of the patient's conditions. The primary concern is the protection of the mother, firstly, and then the fetus (through adjustments to the various treatment regimens) if possible. RESULTS AND CONCLUSIONS: Oncological drugs, radiation therapy, surgery, or a combination of all the above methods are selected, depending on the case. In this project, we studied the oncology drugs used for various types of gestational cancer, their appropriateness and timing, as well as their possible effects on the parent and embryo upon their administration. Various studies have shown that the administration of oncological drugs should be postponed until at least after the first trimester of pregnancy.

Myomectomy during pregnancy; diagnostical dilemmas: two case reports and a systematic review of the literature.

Myomectomy in pregnancy, until this day, remains very controversial. We present two cases of successful antepartum myomectomies performed in the second trimester of gestation. In both cases, the initial suspected origin of these tumours was the ovaries. However, as it was shortly after confirmed, since both women underwent laparotomy, the diagnosis of these masses was uterine fibroids. Both cases resulted on the live birth of two healthy infants via caesarean section. Secondarily, we conducted a thorough review of current data of myomectomies performed during pregnancy, including the characteristics and diagnosis of the myomas of pregnant women, the surgical details and complications, along with the outcomes of these gestations. Overall, the analysis of cases published in international literature, suggests that the surgical removal of myomas during pregnancy can be considered safe, given certain indications and considerations. Our review comprises of 71 women undergoing excision of fibroids during pregnancy. Only three cases ended in a miscarriage while the remaining 68 resulted in a second or third trimester delivery. However, the data concerning the safety of the procedure are scarce and originate mostly from case reports. Thus, conclusions on the exact maternal and obstetrical complication rates cannot be drawn.

Prenatal diagnosis of aberrant right subclavian artery: a literature review.

The primary aim of this review is to estimate the prevalence of ARSA both in euploid fetuses as well as in fetuses with Down Syndrome. Secondary objectives were to estimate the association of ARSA with cardiac anomalies and chromosomal defects, especially trisomy 21 and 22q11 deletion (DiGeorge Syndrome). The incidence of ARSA in normal population varies from 0.35% to 3.5%, based on different studies. Since the first reported association between ARSA and trisomy 21 in 2015 until today, several studies have emerged to confirm different degrees of this correlation. Indeed, ARSA appears to be a clinically useful prenatal ultrasound marker for trisomy 21. Particularly, most recent studies concluded that ARSA as a non-isolated finding can be used as screening for Down syndrome. However, when ARSA is an isolated finding, various studies proved that there is no significant correlation with Down syndrome. Apart from these, ARSA appears to be associated with other chromosomal abnormalities, such as 22q11 deletion, cardiac defects and other morphological anomalies. As a conclusion ARSA should be characterized as isolated or non-isolated, as the non - isolated ARSA appears to be a clinically useful marker of Down syndrome and thus, additional testing is required when diagnosed.

The Relevance of Notch Signaling in Cancer Progression.

The Notch signaling pathway controls normal embryonic development and tissue homeostasis of many cell types. It regulates cell proliferation, fate, differentiation, and cell death by short-range signaling between nearby cells that come in contact. The Notch pathway has also been critically involved in the pathobiology of a variety of malignancies, regulating cancer initiation and development, as well as early stages of cancer progression, by adjusting conserved cellular programs. Fibroblasts, an essential for tumor growth component of stroma, have also been affected by Notch regulation. Sequencing Notch gene mutations have been identified in a number of human tumors, revealing information on the progression of specific cancer types, such as ovarian cancer and melanoma, immune-associated tumors such as myeloid neoplasms, but especially in lymphocytic leukemia. Activation of the Notch can be either oncogenic or it may contain growth-suppressive functions, acting as a tumor suppressor in other hematopoietic cells, hepatocytes, skin, and pancreatic epithelium.

Network-based protein structural classification.

Experimental determination of protein function is resource-consuming. As an alternative, computational prediction of protein function has received attention. In this context, protein structural classification (PSC) can help, by allowing for determining structural classes of currently unclassified proteins based on their features, and then relying on the fact that proteins with similar structures have similar functions. Existing PSC approaches rely on sequence-based or direct three-dimensional (3D) structure-based protein features. By contrast, we first model 3D structures of proteins as protein structure networks (PSNs). Then, we use network-based features for PSC. We propose the use of graphlets, state-of-the-art features in many research areas of network science, in the task of PSC. Moreover, because graphlets can deal only with unweighted PSNs, and because accounting for edge weights when constructing PSNs could improve PSC accuracy, we also propose a deep learning framework that automatically learns network features from weighted PSNs. When evaluated on a large set of approximately 9400 CATH and approximately 12 800 SCOP protein domains (spanning 36 PSN sets), the best of our proposed approaches are superior to existing PSC approaches in terms of accuracy, with comparable running times. Our data and code are available at https://doi.org/10.5281/zenodo.3787922.

Multicentric studies of the fetal neurobehavior by KANET test.

Assessment of fetal neurobehavior and detection of neurological impairment prenatally has been a great challenge in perinatal medicine. The evolution of four-dimensional (4D) ultrasound not only enabled a better visualization of fetal anatomy but also allowed the study of fetal behavior in real time. Kurjak Antenatal Neurodevelopmental Test (KANET) was developed for the assessment of fetal neurobehavior and the detection of neurological disorders, based on the assessment of the fetus by application of 4D ultrasound in the same way that a neonate is assessed postnatally. KANET is a method that has been applied for the past 10 years and studies show that it is a strong diagnostic tool and can be introduced into everyday clinical practice. We present all data from studies performed up to now on KANET.

Fetal loss following second trimester amniocentesis. Who is at greater risk? How to counsel pregnant women?

OBJECTIVE: The purpose of this retrospective observational cohort study was to determine the impact of certain risk factors on fetal loss, after mid-trimester amniocentesis. MATERIAL AND METHODS: Six thousand seven-hundred and fifty-two (6752) consecutive amniocenteses with known pregnancy outcome performed during a 7-year period (2004-2010) were included in this study. Different maternal-, fetal- and procedure-related factors were evaluated in this study. RESULTS: During this 7-year period, 6752 cases who underwent amniocentesis, with complete data available were evaluated for the outcome and risk factors mentioned. Total fetal loss rate (FLR) up to the 24th week was 1.19%. Risk factors associated with increased risk of fetal loss after amniocentesis were maternal age (OR:2.0), vaginal spotting (OR:2.2) and serious bleeding (OR:3.5) during pregnancy, history of 2nd trimester termination of pregnancy (OR:4.0), history of more than three spontaneous (OR:3.0) or surgical first trimester abortions (OR:2.1), fibromas (OR:3.0) and stained amniotic fluid (OR:6.1). CONCLUSIONS: Amniocentesis is a safe-invasive procedure for prenatal diagnosis with total FLR of 1.19% in our institution during the study period. The present study has emphasized the significance of certain risk factors for adverse outcome and therefore the need to individualize the risk.

The role of cervical length measurement at 11-14 weeks for the prediction of preterm delivery.

OBJECTIVE: To determine whether cervical length (CL) measurement at 11?14 weeks is predictive of preterm delivery (PTD). METHODS: This was a prospective study of a low-risk population of 1113 women, who underwent CL measurement at 11-14 weeks. Mean CL was calculated for deliveries at >37, <37 and <34 weeks. Cut-off limits of 27 mm and 30 mm were used to examine the predictive value of CL. RESULTS: Mean +/- SD CL for the entire study population was 40.6 +/- 5.5 mm. CL was analyzed for term and PTD (<37 weeks) and further analyzed for deliveries at 34-37 and <34 weeks. Mean CL was 38.9 +/- 5.5 mm for PTD and 40.8 +/- 5.5 mm for deliveries >37 weeks (p=0.001). Receiver operating characteristic analysis showed small predictive value of CL for PTD <37 weeks (sensitivity = 63.3% and specificity = 51.1%, area under the curve (AUC)=0.60, 95% CI: 0.54-0.66) (p=0.001) and did not show any predictive value for PTD <35 weeks (AUC=0.55, 95% CI: 0.43-0.67, p=0.355) or PTD <32 weeks (AUC=0.51, 95% CI: 0.30-0.74, p=0.851). CONCLUSION: CL at 11-14 weeks does not appear to be predictive of PTD. Statistical analysis of CL did not show any predictive value for PTD <35 weeks, or <32 weeks and although it showed a predictive value for PTD at <37 weeks, the sensitivity was very low.