Global Longitudinal Strain Predicts Outcomes in Patients with Reduced Left Ventricular Function Undergoing Transcatheter Edge-to-Edge Mitral Repair.

BACKGROUND: The timing and selection of optimal candidates for mitral transcatheter edge-to-edge valve repair remains to be fully determined, especially in cases with severely depressed left ventricular ejection fraction (LVEF). The objective of this study is to evaluate the prognostic value of myocardial strain (LVGLS) in this setting. METHODS: Retrospectively, 172 consecutive patients with LVEF ≤40% and severe MR treated with MitraClip were included. Four groups were generated according to the LVEF (<30% or ≥30%) and median LVGLS. The primary end-point was cardiovascular mortality. RESULTS: Procedural success was high (96.5%) and complications were rare. At one-year follow-up, 82.5% of patients maintained MR grade ≤2, 79.2% were at a NYHA class ≤II and a reduction of 80% in heart failure admissions was observed in all groups. Interestingly, among patients with a more depressed LVEF, LVGLS was found to be an independent predictor for cardiovascular mortality (HR: 3.3; 95% CI: 1.1-10, p = 0.023). CONCLUSIONS: Mitral valve repair with MitraClip is safe and it improves the mid-term functional class of patients regardless of LVEF. LVGLS can help in the selection of optimal candidates and timing for this procedure, as well as in the recognition of those patients with worse prognoses.

Current findings in endometrial microbiome: impact on uterine diseases.

Microbiome or microbiota is essential to regulate many mammalian physiological processes, including reproduction. Like other organs or tissues, the upper female reproductive tract used to be considered as devoid of microorganisms; however, a non-infection-related bacterial community was discovered in the uterus from humans and other mammals, and its composition is related to reproductive success. The dysbiosis of endometrial microbiota is associated with benign and malign uterine diseases. Hence, this review addressed the current knowledge about uterine microbiota alterations and their association with common endometrial diseases, including endometrial polyposis, endometriosis, uterine myomatosis, endometrial hyperplasia, and endometrial cancer. There is a specific bacterial community in the endometrium in the most-analyzed uterine diseases. However, the constant finding consists in a reduced abundance of Firmicutes and Lactobacillus, while there is an increased abundance of Proteobacteria (such as Escherichia coli and Enterococcus), Bacteroidetes (Prevotella, for example), and Actinobacteria (as Gardnerella), in contrast to healthy endometrium. Besides, we discussed the future usefulness of the endometrial microbiota components as biomarkers to diagnose uterine diseases and their probable clinical outcomes. In addition, we analyzed their potential use as probiotics since they could provide an alternative or complement to existing therapies.

Gestational Weight Gain Influences the Adipokine-Oxidative Stress Association during Pregnancy.

INTRODUCTION AND OBJECTIVE: The weight gained during pregnancy could determine the immediate and future health of the mother-child dyad. Excessive gestational weight gain (EGWG) due to abnormal adipose tissue (AT) accumulation is strongly associated with adverse perinatal outcomes as gestational diabetes, macrosomia, obesity, and hypertension further in life. Dysregulation of adipokine, AT dysfunction, and an imbalance in the prooxidant-antioxidant systems are critical features in altered AT accumulation. This study was aimed to investigate the association between adipokines and oxidative stress markers in pregnant women and the influence of the GWG on this association. METHODS: Maternal blood samples were obtained in the third trimester of pregnancy (n = 74) and serum adipokines (adiponectin, leptin, and resistin), oxidative damage markers: 8-oxo-2'-deoxyguanosine (8-oxodG), lipohydroperoxides (LOOH), malondialdehyde (MDA), and carbonylated proteins (CP), and glucose a metabolic marker were measured. RESULTS: Women with EGWG had low adiponectin levels than women with adequate weight gain (AWG) or insufficient weight gain (IWG). Multiple linear regression models revealed a positive association between adiponectin and 8-oxodG in women with AWG (B = 1.09, 95% CI: 164-222, p = 0.027) and IWG (B = 0.860, 95% CI: 0.199-1.52, p = 0.013) but not in women with EGWG. In women with EGWG, leptin was positively associated with LOOH (p = 0.018), MDA (p = 0.005), and CP (p = 0.010) oxidative markers. CONCLUSION: Our findings suggest that concurrent mechanisms regulate adipokine production and oxidative stress in pregnant women and that this regulation is influenced by GWG, probably due to an excessive AT accumulation.

The sFlt-1/PlGF ratio as a triage tool to identify superimposed preeclampsia in women with chronic hypertension in emergency rooms.

OBJECTIVES: Assess the usefulness of the sFlt-1/PlGF ratio for the differential diagnosis of uncontrolled chronic hypertension vs. superimposed preeclampsia. STUDY DESIGN: We performed a cross-sectional study from 2015 to 2017 and 42 women with initial diagnosis of superimposed preeclampsia were enrolled in the emergency room. After a 12 week follow up patients were grouped as superimposed preeclampsia (Group A) and uncontrolled chronic hypertension (Group B) according to the American College of Obstetricians and Gynecologist criteria. A group of 33 healthy women paired by gestational age were included as controls (Group C). Maternal serum levels of sFlt-1 and PlGF were measured at enrollment, and the ratios of the groups were compared. MAIN OUTCOME MEASURES: Superimposed preeclampsia vs. uncontrolled chronic hypertension. RESULTS: After follow-up, group distribution was 30 women in Group A, 12 women in Group B, and 25 women in Group C. The sFlt-1/PlGF ratio was higher in women with superimposed preeclampsia than in women with uncontrolled chronic hypertension (215.5 vs. 9.65, p < 0.001). The control group displayed lower ratio values (3.66, p < 0.001). The sFlt-1 concentration was higher in Group A than in Group B (7564 vs. 1281 pg/mL, p < 0.001) and the PlGF level was lower in Group A (34.39 vs. 169 pg/mL, p < 0.001). CONCLUSIONS: The sFlt-1/PlGF ratio exhibits good performance for the differential diagnosis of superimposed preeclampsia vs. uncontrolled chronic hypertension.

Placental Microarray Profiling Reveals Common mRNA and lncRNA Expression Patterns in Preeclampsia and Intrauterine Growth Restriction.

Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributors to perinatal morbidity and mortality. These pregnancy disorders are associated with placental dysfunction and share similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lncRNAs from pregnant women from four study groups: PE, IUGR, PE-IUGR, and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP (n = 461; 314 mRNAs: 252 up-regulated and 62 down-regulated; 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP (n = 39), including 9 lncRNAs with a high correlation degree (p < 0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification, and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of PE and IUGR.

Brain Differences Associated with Self-Injurious Thoughts and Behaviors: A Meta-Analysis of Neuroimaging Studies.

This meta-analysis aims to evaluate whether the extant literature justifies any definitive conclusions about whether and how SITBs may be associated with brain differences. A total of 77 papers (N = 4,903) published through January 1, 2019 that compared individuals with and without SITBs were included, resulting in 882 coordinates. A pooled meta-analysis assessing for general risk for SITBs indicated a lack of convergence on structural differences. When all types of control groups were considered, functional differences in the left posterior cingulate cortex (PCC), right amygdala, left hippocampus, and right thalamus were significant using multi-level kernel density analysis (pcorrected < 0.05) but nonsignificant using activation-likelihood estimation. These results suggest that a propensity for internally-oriented, emotional processing coupled with under-active pain processing could potentially underlie SITBs, but additional research is needed to test this possibility. Separate analyses for types of SITBs suggested that the brain differences associated with deliberate self-harm were consistent with the overall findings. Checkered moderator effects were detected. Overall, the meta-analytic evidence was not robust. More studies are needed to reach definitive conclusions about whether SITBs are associated with brain differences.

Virtual reality suicide: Development of a translational approach for studying suicide causes.

Causal knowledge is crucial for understanding and preventing suicide. Unfortunately, we have little direct knowledge about suicide causes because we cannot conduct experiments that seek to make suicide more likely. In such situations, translational approaches can provide valuable, though tentative, information. We sought to establish a new translational approach by developing a laboratory approximation of suicide with new virtual reality (VR) technologies. Such an approach would allow researchers to tentatively investigate the causes of suicide by conducting experiments that introduce purported causes of suicide and observe their effects on VR suicide rates. Across three studies (total N = 498), results indicated that our two VR suicide scenarios (jumping from heights; shooting oneself) were safe; rated as unpleasant, realistic, and suicide-relevant; associated with several relevant predictors of VR suicide completion, including male sex, suicidal desire, suicidal capability, agitation, and prior suicidality; associated with reasons for not engaging in VR suicide that are similar to the reasons people give for not engaging in actual suicide; and produced 5% completion rates under neutral conditions and 25% completion rates after reward/avoid manipulations. We hope that future work further improves this approach and applies it to more directly test ideas about suicide causes and suicide prevention.

Macrophage Populations in Visceral Adipose Tissue from Pregnant Women: Potential Role of Obesity in Maternal Inflammation.

Obesity is associated with inflammatory changes and accumulation and phenotype polarization of adipose tissue macrophages (ATMs). Obese pregnant women have alterations in adipose tissue composition, but a detailed description of macrophage population is not available. In this study, we characterized macrophage populations in visceral adipose tissue (VAT) from pregnant women with normal, overweight, and obese pregestational weight. Immunophenotyping of macrophages from VAT biopsies was performed by flow cytometry using CD45 and CD14 as markers of hematopoietic and monocyte linage, respectively, while HLA-DR, CD11c, CD163, and CD206 were used as pro- and anti-inflammatory markers. Adipocyte number and size were evaluated by light microscopy. The results show that pregnant women that were overweight and obese during the pregestational period had adipocyte hypertrophy. Two different macrophage populations in VAT were identified: recruited macrophages (CD45⁺CD14⁺), and a novel population lacking CD45, which was considered to be a resident macrophages subset (CD45−CD14⁺). The number of resident HLA−DRlow/− macrophages showed a negative correlation with body mass index (BMI). Both resident and recruited macrophages from obese women expressed higher CD206 levels. CD11c expression was higher in resident HLA-DR⁺ macrophages from obese women. A strong correlation between CD206 and CD11c markers and BMI was observed. Our findings show that being overweight and obese in the pregestational period is associated with adipocyte hypertrophy and specific ATMs populations in VAT.

New Insights into the Role of Matrix Metalloproteinases in Preeclampsia.

Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs) exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects.

The paternal polymorphism rs5370 in the EDN1 gene decreases the risk of preeclampsia.

OBJECTIVE: To evaluate whether the maternal, paternal or the combined maternal/paternal contribution of SNP rs5370 of the EDN1 gene is associated with preeclampsia and drove its expression in placenta. STUDY DESIGN: This case-control study included 61 preeclamptic patients and their partners and 49 healthy pregnant women and their partners. The population was sub-divided into three groups: women-only, men-only and combined (women/men). The analysis included genotyping of rs5370 in mothers and fathers and evaluating the expression profile of the EDN1 gene in placenta. Comparisons of categorical variables were performed using chi-square and/or Fisher's exact tests. The intergroup comparisons were analysed with the Mann-Whitney U test. The association between the polymorphism and the disease was evaluated through multivariate regression analysis. Spearman's correlation was performed to test the relationship between pre-gestational history and clinical features of the affected patients with EDN1 gene expression. RESULTS: The analysis of paternal risk factors associated with preeclampsia revealed no differences between groups. A negative association between SNP rs5370 and preeclampsia was found in men group (OR 0.42; CI 95% 0.18-0.94, p=0.034) but not in women or combined groups. The adjustment for paternal protective factors increased the observed negative association, and the opposite was observed in the presence of paternal risk factors. The expression of the EDN1 gene in the placenta was significantly higher in the group of cases and was not associated with the rs5370 polymorphism. CONCLUSION: The paternal rs5370 polymorphism decreases the risk for preeclampsia and is not associated with placental expression of the EDN1 gene.