Uterine massage for preventing postpartum hemorrhage at cesarean delivery: Which evidence?

BACKGROUND: Cesarean delivery could be complicated by postpartum hemorrhage (PPH), the first cause of maternal death. OBJECTIVES: To evaluate the efficacy of uterine massage in preventing postpartum hemorrhage at cesarean delivery. DATA SOURCES: Electronic databases from their inception until October 2017. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included all RCTs comparing uterine massage alone or as part of the active management of labor before or after delivery of the placenta, or both, with non-massage in the setting of cesarean delivery. DATA COLLECTION AND ANALYSIS: The primary outcome was PPH, defined as blood loss >1000 mL. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference (MD) or relative risk (RR) with 95% confidence interval (CI). RESULTS: Only 3 RCTs comparing uterine massage vs no uterine massage were found. The quality of these 3 trials in general was very low with high or unclear risk of bias. All of them included only women in the setting of spontaneous vaginal delivery and none of them included cesarean delivery, and therefore the meta-analysis was not feasible. CONCLUSIONS: There is not enough evidence to determine if uterine massage prevents postpartum hemorrhage at cesarean delivery

Which criteria should be used for starting pharmacologic therapy for management of gestational diabetes in pregnancy? Evidence from randomized controlled trials

Introduction: There is inconclusive evidence to support any specific criteria for starting pharmacologic therapy after diet in women with gestational diabetes mellitus (GDM). We aimed to analyze the most used criteria for starting pharmacologic treatment for patients with GDM. Material and methods: Electronic databases were searched from their inception to September 2017. We included all the randomized controlled trials (RCTs) of GDM managed initially by diet and exercise reporting criteria for starting pharmacologic therapy. RCTs in women with pregestational diabetes were excluded. Data regarding glucose values used for starting pharmacologic therapy were extracted and carefully reviewed. Results: We included 15 RCTs (4307 women) in the meta-analysis. For fasting glucose target, 8/14 (57%) used a value lower or equal to 90 mg/dL and the remainder used values 50% of the values higher than the target values and another one (7%) used >30%. Conclusion: The majority of RCTs (87%) used very tight criteria of either 1 or 2 values over the target values in the 1 or 2-week period for starting pharmacologic treatment for patients with GDM; more than 50% used 2 values. Key Message Pharmacologic therapy should be considered in women with gestational diabetes when, despite an adequate diet and exercise, 1 or 2 blood glucose values are over the target values of 90mg/dL fasting or 120mg/dL 2-hour postprandial over 1 or 2 weeks

Fetal brain hemodynamics in pregnancies at term: correlation with gestational age, birthweight and clinical outcome

Introduction: The primary aim of this study was to ascertain the strength of association between cerebral blood flow assessed in anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries and the following clinical outcomes: small for gestational age (SGA), induction of labor (IOL) for oligohydramnios and caesarean section (CS) for nonreassuring fetal status (NRFS) during labor. Material and methods: Retrospective analysis of prospectively collected data on consecutive singleton pregnancies from 40 0/7 to 41 6/7 week of gestation. UA, ACA, MCA, PCA pulsatility index (PI) were measured from 40 weeks of gestations. Furthermore, the ratios between cerebral blood flow and UA (CPR, ACA/UA and PCA/UA) were calculated and correlated with the observed outcomes. Results: Two hundred twenty-four singleton pregnancies were included in the study. Mean PI of either ACA (p = .04), MCA (p = .008), and PCA (p = .003) were lower in the SGA compared to non-SGA group; furthermore, mean PCA PI was significantly lower than MCA PI (p = .04). Furthermore, CPR (p = .016), ACA/UA (p = .02), and PCA/UA (p = .003) were significantly lower in the SGA group compared to controls. UA, ACA, MCA, and PCA PI were higher in women undergoing IOL for oligohydramnios compared to controls. Logistic regression analysis showed that CPR and PCA/UA ratio were independently associated with SGA. SGA, ACA PI, and ACA/UA were independently associated with CS for NRFS. Finally, birthweight centile, were independently associated with IOL oligohydramnios. Despite this, the predictive accuracy of Doppler in detecting any of the explored outcome was only poor to moderate. Conclusion: Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor. However, the predictive accuracy of Doppler at term is only poor to moderate, thus advising against its use in clinical practice as a standalone screening test for adverse perinatal outcome in pregnancies at term. Key Message Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor

Effectiveness of seminal plasma in in vitro fertilization treatment: A systematic review and meta-analysis

BACKGROUND: With in vitro fertilization (IVF) techniques, only 20-25% of the transferred embryos lead to a pregnancy. OBJECTIVE: To evaluate the beneficial effects of seminal plasma (SP) or semen applied at the time of oocyte aspiration or embryo transfer. SEARCH STRATEGY: Electronic databases were searched from their inception up to August 2017. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) evaluating the effects of SP or semen in IVF treatment. Trials were considered if women were exposed to any kind of SP or semen (either SP/semen injection or sexual intercourse) around the time of oocyte pickup and embryo transfer. DATA COLLECTION AND ANALYSIS: The primary outcome was clinical pregnancy rate (CPR). MAIN RESULTS: Eight RCTs on women undergoing IVF (2128 in total) were included in the meta-analysis. Women randomized in the intervention group had a significantly higher CPR compared with controls (30.0 versus 25.1%; RR 1.20; 95% CI, 1.04-1.39). No significant differences were found in the secondary outcomes, including livebirth rate, biochemical pregnancy, miscarriage, multiple pregnancies, and birth weight. The subgroup analyses (four RCTs, 780 participants), including only those RCTs in which prepared undiluted SP was injected just after oocyte pickup, conformed with the overall analysis for the primary outcome (46.3 versus 37.2%; RR 1.23; 95% CI, 1.05-1.45). AUTHORS' CONCLUSION: Because intravaginal or intracervical SP application around the time of oocyte pickup is associated with higher CPR, local application SP may be considered as a potential treatment to improve implantation. TWEETABLE ABSTRACT: SP at the time of oocyte pickup is associated with higher CPR

Vaginal Cleansing before Cesarean Delivery

OBJECTIVE: To assess the efficacy of vaginal cleansing before cesarean delivery in reducing postoperative endometritis. DATA SOURCES: MEDLINE, Ovid, EMBASE, Scopus, Clinicaltrials.gov, and Cochrane Library were searched from their inception to January 2017. METHODS OF STUDY SELECTION: Selection criteria included all randomized controlled trials comparing vaginal cleansing (ie, intervention group) with a control group (ie, either placebo or no intervention) in women undergoing cesarean delivery. Any method of vaginal cleansing with any type of antiseptic solution was included. The primary outcome was the incidence of endometritis. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of relative risk (RR) with 95% CI. TABULATION, INTEGRATION, AND RESULTS: Sixteen trials (4,837 women) on vaginal cleansing immediately before cesarean delivery were identified as relevant and included in the review. In most of the included studies, 10% povidone-iodine was used as an intervention. The most common way to perform the vaginal cleansing was the use of a sponge stick for approximately 30 seconds. Women who received vaginal cleansing before cesarean delivery had a significantly lower incidence of endometritis (4.5% compared with 8.8%; RR 0.52, 95% CI 0.37-0.72; 15 studies, 4,726 participants) and of postoperative fever (9.4% compared with 14.9%; RR 0.65, 95% CI 0.50-0.86; 11 studies, 4,098 participants) compared with the control group. In the planned subgroup analyses, the reduction in the incidence of endometritis with vaginal cleansing was limited to women in labor before cesarean delivery (8.1% compared with 13.8%; RR 0.52, 95% CI 0.28-0.97; four studies, 440 participants) or those with ruptured membranes (4.3% compared with 20.1%; RR 0.23, 95% CI 0.10-0.52; three studies, 272 participants). CONCLUSION: Vaginal cleansing immediately before cesarean delivery in women in labor and in women with ruptured membranes reduces the risk of postoperative endometritis. Because it is generally inexpensive and a simple intervention, we recommend preoperative vaginal preparation before cesarean delivery in these women with sponge stick preparation of povidone-iodine 10% for at least 30 seconds. More data are needed to assess whether this intervention may be also useful for cesarean deliveries performed in women not in labor and for those without ruptured membranes

Overexpression of neuroglobin promotes energy metabolism and autophagy induction in human neuroblastoma SH-SY5Y cells

Neuroglobin (NGB) is an O2-binding globin mainly expressed in the central and peripheral nervous systems and cerebrospinal fluid. Previously, it was demonstrated that NGB overexpression protects cells from hypoxia-induced death. To investigate processes promoted by NGB overexpres-sion, we used a cellular model of neuroblastoma stably overexpressing an NGB-FLAG construct. We used a proteomic approach to identify the specific profile following NGB overexpression. To evaluate the role of NGB overexpression in increasing energetic metabolism, we measured oxygen consumption rate (OCR) and the extracellular acidification rate through Seahorse XF technology. The effect on autophagy induction was evaluated by analyzing SQSTM1/p62 and LC3-II expres-sion. Proteomic analysis revealed several differentially regulated proteins, involved in oxidative phosphorylation and integral mitochondrial proteins linked to energy metabolism. The analysis of mitochondrial metabolism demonstrated that NGB overexpression increases mitochondrial ATP production. Indeed, NGB overexpression enhances bioenergetic metabolism, increasing OCR and oxygen consumption. Analysis of autophagy induction revealed an increase of LC3-II together with a significant decrease of SQSTM1/p62, and NGB-LC3-II association during autophagosome formation. These results highlight the active participation of NGB in several cellular processes that can be upregulated in response to NGB overexpression, playing a role in the adaptive response to stress in neuroblastoma cells

Anti-inflammatory activity of a cb2 selective cannabinoid receptor agonist: Signaling and cytokines release in blood mononuclear cells

The endocannabinoid system (ECS) exerts immunosuppressive effects, which are mostly mediated by cannabinoid receptor 2 (CBR2), whose expression on leukocytes is higher than CBR1, mainly localized in the brain. Targeted CBR2 activation could limit inflammation, avoiding CBR1-related psychoactive effects. Herein, we evaluated in vitro the biological activity of a novel, selective and high-affinity CBR2 agonist, called JT11, studying its potential CBR2-mediated anti-inflammatory effect. Trypan Blue and MTT assays were used to test the cytotoxic and anti-proliferative effect of JT11 in Jurkat cells. Its pro-apoptotic activity was investigated analyzing both cell cycle and poly PARP cleavage. Finally, we evaluated its impact on LPS-induced ERK1/2 and NF-kB-p65 activation, TNF-α, IL-1β, IL-6 and IL-8 release in peripheral blood mononuclear cells (PBMCs) from healthy donors. Selective CB2R antagonist SR144528 and CBR2 knockdown were used to further verify the selectivity of JT11. We confirmed selective CBR2 activation by JT11. JT11 regulated cell viability and proliferation through a CBR2-dependent mechanism in Jurkat cells, exhibiting a mild pro-apoptotic activity. Finally, it reduced LPS-induced ERK1/2 and NF-kB-p65 phosphorylation and pro-inflammatory cytokines release in human PBMCs, proving to possess in vitro anti-inflammatory properties. JT11 as CBR2 ligands could enhance ECS immunoregulatory activity and our results support the view that therapeutic strategies targeting CBR2 signaling could be promising for the treatment of chronic inflammatory diseases