Clinical characteristics and sequelae of intrapartum hypertension : a retrospective cohort study

Background: In a significant proportion of pregnant women, elevated blood pressure may first present during the intrapartum period. This phenomenon, intrapartum hypertension, is often overlooked as blood pressure during delivery is attributed to labour pain, analgesic agents and haemodynamic changes. Thus the true prevalence and clinical significance of intrapartum hypertension remains unknown. This study sought to define the prevalence of intrapartum hypertension in previously normotensive women, identify associated clinical characteristics, and its impact on maternal and fetal outcomes. Methods: In this single-center retrospective cohort study, all available partograms were reviewed over a 1-month period at an outer metropolitan hospital in Sydney (Campbelltown Hospital). Women with diagnosed hypertensive disorders of pregnancy during the incident pregnancy were excluded. A total of 229 deliveries were included in the final analysis. Intrapatum hypertension (IH) was defined as two or more systolic blood pressure (SBP)⩾140 mmHg or diastolic blood pressure (DBP)⩾90 mmHg during the intrapartum. Demographic data at the time of the first antenatal visit for the incident pregnancy as well as final maternal outcomes (intrapartum and post-partum) and fetal outcomes were collected. Statistical analyses were carried out using SPSSv27 with adjustments for baseline variables. Results: Amongst 229 deliveries, 32 women (14%) had intrapartum hypertension. Older maternal age (p = 0.02), higher body mass index (p < 0.01) and higher diastolic blood pressure at the first antenatal visit (p = 0.03) were associated with intrapartum hypertension. A longer second stage of labour (p = 0.03), intrapartum non-steroidal anti-inflammatory medications (p < 0.01) and epidural anaesthesia (p = 0.03) were associated with intrapartum hypertension, while IV syntocin for labour induction was not. Women with intrapartum hypertension had a longer inpatient admission following delivery (p < 0.01), and elevated postpartum BP (p = 0.02) with discharge on antihypertensive medications (p < 0.01). Intrapartum hypertension was not associated with poor fetal outcomes, though subgroup analyses showed that women who had at least a single elevated blood pressure reading during the intrapartum experienced poorer fetal outcomes. Conclusion: In previously normotensive women, 14% developed intrapartum hypertension during delivery. This was associated with postpartum hypertension, longer maternal admission and discharge with antihypertensive medications. There was no difference in fetal outcomes

High-sensitivity troponin T and C-reactive protein have different prognostic values in hemo- and peritoneal dialysis populations : a cohort study

Background--Dialysis patients have an exceedingly high mortality rate. Biomarkers may be useful tools in risk stratification of this population. We evaluated the prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) and CRP (C-reactive protein) in predicting adverse outcomes in stable hemodialysis and peritoneal dialysis (PD) patients. Variability in hs-cTnT was also examined. Methods and Results--A retrospective cohort study included 574 dialysis patients (hemodialysis 347, PD 227). Outcomes examined included mortality and major adverse cardiovascular events, with median follow-up of 3.5 years. hs-cTnT was an independent predictor of both outcomes in hemodialysis and PD patients. Increased risk only became significant when hs-cTnT reached quintile 3 ( > 49 ng/L). Area under the receiver operating curve analysis showed that the addition of hs-cTnT to clinical parameters significantly improved its prognostic performance for mortality in PD patients (P=0.002). CRP was an independent predictor of both outcomes in PD patients only. Only CRP in the highest quintile ( > 16.8 mg/L) was associated with increased risk. hs-cTnT remained relatively stable for the whole follow-up period for hemodialysis patients, whereas for PD patients, hs-cTnT increased by 23.63% in year 2 and 29.13% in year 3 compared with baseline (P < 0.001). Conclusions--hs-cTnT and CRP are useful tools in predicting mortality and major adverse cardiovascular events in hemodialysis and PD patients. Given that hs-cTnT levels increase over time in PD patients, interval monitoring may be valuable for risk assessment. In contrast, hs-cTnT in hemodialysis patients has little interval change and progress monitoring is not indicated

Antihypertensive methyldopa, labetalol, hydralazine, and clonidine reversed tumour necrosis factor-α inhibited endothelial nitric oxide synthase expression in endothelial-trophoblast cellular networks

Medications used to control hypertension in pregnancy also improve trophoblast and endothelial cellular interaction in vitro. Tumour necrosis factor-α (TNF-α) inhibits trophoblast and endothelial cellular interactions and simultaneously decreases endothelial nitric oxide synthase (eNOS) expression. This study investigated whether antihypertensive medications improved these cellular interactions by modulating eNOS and inducible nitric oxide synthase (iNOS) expression. Human uterine myometrial microvascular endothelial cells (UtMVECs) were pre-incubated with (or without) low dose TNF-α (0.5 ng/ml) or TNF-α plus soluble fms-like tyrosine kinase-1 (sFlt-1) (100 ng/ml). The endothelial cells were cultured on Matrigel. After endothelial cellular networks appeared, trophoblast derived HTR-8/SVneo cells were co-cultured in the presence of clinically relevant doses of methyldopa, labetalol, hydralazine or clonidine for 24 hours. Cells were retrieved from the Matrigel to extract mRNA and eNOS and iNOS expression were examined by quantitative PCR. Methyldopa, labetalol, hydralazine and clonidine reversed the inhibitory effect of TNF-α on eNOS mRNA expression. After pre-incubating endothelial cells with TNF-α and sFlt-1, all the medications except methyldopa lost their effect on eNOS mRNA expression. In the absence of TNF-α, antihypertensive medications did not change eNOS expression. The mRNA expression of iNOS was not affected by TNF-α or any medications. This study shows that selected antihypertensive medications used in the treatment of hypertension in pregnancy increase eNOS expression in vitro when induced by the inflammatory TNF-α. The antiangiogenic molecule sFlt-1 may antagonise the potential benefit of these medications by interfering with the NOS pathway

Behavioral treatment of obesity.

ABSTRACT Behavioral treatment is an approach used to help individuals develop a set of skills to achieve a healthier weight. It is more than helping people to decide what to change; it is helping them identify how to change. The behavior change process is facilitated through the use of self-monitoring, goal setting, and problem solving. Studies suggest that behavioral treatment produces weight loss of 8-10% during the first 6 mo of treatment. Structured approaches such as meal replacements and food provision have been shown to increase the magnitude of weight loss. Most research on behavioral treatment has been conducted in university-based clinic programs. Although such studies are important, they tell us little about the effectiveness of these approaches in settings outside of specialized clinics. Future research might focus more on determining how these behavioral techniques can be best applied in a real-world setting. Am J Clin Nutr 2005; 82(suppl):230S-5S

High-Sensitivity Troponin T and C-Reactive Protein Have Different Prognostic Values in Hemo- and Peritoneal Dialysis Populations: A Cohort Study

Background-—Dialysis patients have an exceedingly high mortality rate. Biomarkers may be useful tools in risk stratification of this population. We evaluated the prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) and CRP (C-reactive protein) in predicting adverse outcomes in stable hemodialysis and peritoneal dialysis (PD) patients. Variability in hs-cTnT was also examined. Methods and Results-—A retrospective cohort study included 574 dialysis patients (hemodialysis 347, PD 227). Outcomes examined included mortality and major adverse cardiovascular events, with median follow-up of 3.5 years. hs-cTnT was an independent predictor of both outcomes in hemodialysis and PD patients. Increased risk only became significant when hs-cTnT reached quintile 3 (>49 ng/L). Area under the receiver operating curve analysis showed that the addition of hs-cTnT to clinical parameters significantly improved its prognostic performance for mortality in PD patients (P=0.002). CRP was an independent predictor of both outcomes in PD patients only. Only CRP in the highest quintile (>16.8 mg/L) was associated with increased risk. hs-cTnT remained relatively stable for the whole follow-up period for hemodialysis patients, whereas for PD patients, hs-cTnT increased by 23.63% in year 2 and 29.13% in year 3 compared with baseline (P<0.001). Conclusions-—hs-cTnT and CRP are useful tools in predicting mortality and major adverse cardiovascular events in hemodialysis and PD patients. Given that hs-cTnT levels increase over time in PD patients, interval monitoring may be valuable for risk assessment. In contrast, hs-cTnT in hemodialysis patients has little interval change and progress monitoring is not indicated. ( J Am Heart Assoc. 2018;7:e007876. DOI: 10.1161/JAHA.117.007876.

Quantification of placental change in mouse models of preeclampsia using magnetic resonance microscopy

Abnormal development of the placenta is postulated to be central to the aetiology of preeclampsia. This study investigates changes in placental histopathology in mouse models of preeclampsia compared to the morphology using magnetic resonance microscopy (MRM) (11.7 T) of intact ex vivo tissue followed by 3D analysis of the image data. Here, C57BL/6JArc pregnant mice were subject to either normal pregnancy (n=3), or to one of two experimental models of preeclampsia; TNF-α infusion  (n=3) or reduced uterine perfusion pressure(RUPP) (n=3). Placental tissue was collected at gestational day (gd) 17, fixed in formalin and incubated with Magnavist™ contrast agent, and high resolution images (50 μm × 50 μm × 50 μm voxels) obtained by magnetic resonance imaging at 11.74 T. Visual segmentation into placental subregions and three dimensional (3D) reconstruction followed by volume analysis was performed with Amira™ 3D analysis software. The significance of differences between treatment groups in total and regional volumes was assessed. In a single placenta the volumes measure by standard histology were compared. Three placentas from each animal were imaged, segmented into anatomical regions and 3D reconstructions generated. Total placental volume, labyrinth and decidual volume were not significantly different between groups. The junctional zone volume was found to be significantly larger in the RUPP animals (18.5±1.5 mm3) compared to TNF-α infused animals (15.8±1.5) or control animals (15.0±0.7, P<0.01). However, the decidual/junctional zone volume was smaller in the TNF-a compared to control animals (P<0.05). Placental structural change in experimental models of preeclampsia is able to be visualized and quantified using MRM and 3-D analysis. These techniques could prove to be a powerful tool in examining changes in placental morphology

Menopausal hormone therapy is associated with having high blood pressure in postmenopausal women : observational cohort study

Background: The relationship between menopausal hormone therapy (MHT) and cardiovascular risk remains controversial, with a number of studies advocating the use of MHT in reducing risk of cardiovascular diseases, while others have shown it to increase risk. The aim of this study was to determine the association between menopausal hormone therapy and high blood pressure. Methods and Findings: A total of 43,405 postmenopausal women were included in the study. Baseline data for these women were sourced from the 45 and Up Study, Australia, a large scale study of healthy ageing. These women reported being postmenopausal, having an intact uterus, and had not been diagnosed with high blood pressure prior to menopause. Odds ratios for the association between MHT use and having high blood pressure were estimated using logistic regression, stratified by age (<56 years, 56-61 years, 62-70 years and over 71 years) and adjusted for demographic and lifestyle factors. MHT use was associated with higher odds of having high blood pressure: past menopausal hormone therapy use: <56 years (adjusted odds ratio 1.59, 99% confidence interval 1.15 to 2.20); 56-61 years (1.58, 1.31 to 1.90); 62-70 years (1.26, 1.10 to 1.44). Increased duration of hormone use was associated with higher odds of having high blood pressure, with the effect of hormone therapy use diminishing with increasing age. Conclusions: Menopausal hormone therapy use is associated with significantly higher odds of having high blood pressure, and the odds increase with increased duration of use. High blood pressure should be conveyed as a health risk for people considering MHT use

Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds

O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis

Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia&nbsp;in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc&nbsp;from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy : the TURRIFIC randomised trial

BackgroundSevere early onset (less than 34weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders.Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach.MethodsWe have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300mg bd) with that of UDCA tablets (up to 2000mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool.DiscussionOur study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial.Trial identifiersAustralian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36.EudraCT number: 2018-004011-44.IRAS: 272398.NHMRC registration: APP1152418 and APP117853.Peer reviewe