Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?

Contains fulltext : 57743.pdf (publisher's version ) (Open Access)OBJECTIVES: (1) To assess the recurrence rate of pre-eclampsia in women with this history before 34 weeks of pregnancy and thrombophilia. (2) To evaluate the effects of low-molecular-weight heparin (LMWH) on pregnancy outcome. METHODS: In a multicentre retrospective study subsequent pregnancies of women with a history of pre-eclampsia necessitating birth before 34 weeks and thrombophilia were analysed. Of 58 women, 26 received LMWH and aspirin (ASA) and 32 ASA (22) or no (10) medication in their subsequent pregnancies. RESULTS: In eight women treated with LMWH and ASA and in 16 women receiving ASA or no medication pre-eclampsia recurred in the subsequent pregnancy. (OR 0.55, 95% CI 0.15-1.31) There were no significant differences in birth weight or gestational age between both groups. CONCLUSIONS: The recurrence rate of pre-eclampsia in women with thrombophilic disorders is high in this small retrospective study. No positive effect was found for LMWH treatment. A multicentred randomised study has been started to reach an adequate number of patients to evaluate the influence of LMWH treatment

Modelling metastatic colonization of cholangiocarcinoma organoids in decellularized lung and lymph nodes

Cholangiocarcinoma (CCA) is a type of liver cancer with an aggressive phenotype and dismal outcome in patients. The metastasis of CCA cancer cells to distant organs, commonly lung and lymph nodes, drastically reduces overall survival. However, mechanistic insight how CCA invades these metastatic sites is still lacking. This is partly because currently available models fail to mimic the complexity of tissue-specific environments for metastatic CCA. To create an in vitro model in which interactions between epithelial tumor cells and their surrounding extracellular matrix (ECM) can be studied in a metastatic setting, we combined patient-derived CCA organoids (CCAOs) (n=3) with decellularized human lung (n=3) and decellularized human lymph node (n=13). Decellularization resulted in removal of cells while preserving ECM structure and retaining important characteristics of the tissue origin. Proteomic analyses showed a tissue-specific ECM protein signature reflecting tissue functioning aspects. The macro and micro-scale mechanical properties, as determined by rheology and micro-indentation, revealed the local heterogeneity of the ECM. When growing CCAOs in decellularized lung and lymph nodes genes related to metastatic processes, including epithelial-to-mesenchymal transition and cancer stem cell plasticity, were significantly influenced by the ECM in an organ-specific manner. Furthermore, CCAOs exhibit significant differences in migration and proliferation dynamics dependent on the original patient tumor and donor of the target organ. In conclusion, CCA metastatic outgrowth is dictated both by the tumor itself as well as by the ECM of the target organ. Convergence of CCAOs with the ECM of its metastatic organs provide a new platform for mechanistic study of cancer metastasis.</p

Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?

OBJECTIVES: (1) To assess the recurrence rate of pre-eclampsia in women with this history before 34 weeks of pregnancy and thrombophilia. (2) To evaluate the effects of low-molecular-weight heparin (LMWH) on pregnancy outcome. METHODS: In a multicentre retrospective study subsequent pregnancies of women with a history of pre-eclampsia necessitating birth before 34 weeks and thrombophilia were analysed. Of 58 women, 26 received LMWH and aspirin (ASA) and 32 ASA (22) or no (10) medication in their subsequent pregnancies. RESULTS: In eight women treated with LMWH and ASA and in 16 women receiving ASA or no medication pre-eclampsia recurred in the subsequent pregnancy. (OR 0.55, 95% CI 0.15-1.31) There were no significant differences in birth weight or gestational age between both groups. CONCLUSIONS: The recurrence rate of pre-eclampsia in women with thrombophilic disorders is high in this small retrospective study. No positive effect was found for LMWH treatment. A multicentred randomised study has been started to reach an adequate number of patients to evaluate the influence of LMWH treatment

Modelling metastatic colonization of cholangiocarcinoma organoids in decellularized lung and lymph nodes

Cholangiocarcinoma (CCA) is a type of liver cancer with an aggressive phenotype and dismal outcome in patients. The metastasis of CCA cancer cells to distant organs, commonly lung and lymph nodes, drastically reduces overall survival. However, mechanistic insight how CCA invades these metastatic sites is still lacking. This is partly because currently available models fail to mimic the complexity of tissue-specific environments for metastatic CCA. To create an in vitro model in which interactions between epithelial tumor cells and their surrounding extracellular matrix (ECM) can be studied in a metastatic setting, we combined patient-derived CCA organoids (CCAOs) (n=3) with decellularized human lung (n=3) and decellularized human lymph node (n=13). Decellularization resulted in removal of cells while preserving ECM structure and retaining important characteristics of the tissue origin. Proteomic analyses showed a tissue-specific ECM protein signature reflecting tissue functioning aspects. The macro and micro-scale mechanical properties, as determined by rheology and micro-indentation, revealed the local heterogeneity of the ECM. When growing CCAOs in decellularized lung and lymph nodes genes related to metastatic processes, including epithelial-to-mesenchymal transition and cancer stem cell plasticity, were significantly influenced by the ECM in an organ-specific manner. Furthermore, CCAOs exhibit significant differences in migration and proliferation dynamics dependent on the original patient tumor and donor of the target organ. In conclusion, CCA metastatic outgrowth is dictated both by the tumor itself as well as by the ECM of the target organ. Convergence of CCAOs with the ECM of its metastatic organs provide a new platform for mechanistic study of cancer metastasis.BN/Gijsje Koenderink La

[Foley catheter versus prostaglandin E2 gel for induction of labour at term: the PROBAAT study]

Objective To study the effectiveness and safety of induction of labour with a Foley catheter compared with vaginal prostaglandin E2 gel in full term pregnant women. Design Multicentre, randomised, open-label trial in 12 hospitals in the Netherlands between February 2009 and May 2010. Methods Women scheduled for induction of labour at full term singleton pregnancy in cephalic presentation, intact membranes, and an unripe cervix (Bishop score < 6) were enrolled by means of an on-line system. Participants were randomly allocated to induction of labour with a transcervical Foley catheter or vaginal prostaglandin E2 gel. The primary outcome was caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from induction to birth. Results A total of 824 women were allocated to induction of labour with a Foley catheter (n = 412) or prostaglandin E2 (n = 412). Caesarean section rates were comparable (23% versus 20%, RR 1.13, 95% CI 0.87 to 1.47). In the Foley catheter group fewer instrumental deliveries for foetal distress were performed (12% versus 18%, RR 0.68, 95% CI 0.49 to 0.95). Time to delivery (median hours (IQR)) was longer (29 (15-35) versus 18 (12-33)). Fewer mothers had suspected intrapartum infection (2% versus 4%, RR 0.41, 95% CI 0.17-0.98). Significantly fewer neonates were admitted toaneonatal ward after induction with a Foley catheter (12% versus 20%, RR 0.60, 95% CI 0.43 to 0.83). Conclusion In women with an unripe cervix at term, induction of labour with a Foley catheter does not reduce caesarean section rates, but there are fewer side-effects

[Foley catheter versus prostaglandin E2 gel for induction of labour at term: the PROBAAT study]

Item does not contain fulltextObjective To study the effectiveness and safety of induction of labour with a Foley catheter compared with vaginal prostaglandin E2 gel in full term pregnant women. Design Multicentre, randomised, open-label trial in 12 hospitals in the Netherlands between February 2009 and May 2010. Methods Women scheduled for induction of labour at full term singleton pregnancy in cephalic presentation, intact membranes, and an unripe cervix (Bishop score < 6) were enrolled by means of an on-line system. Participants were randomly allocated to induction of labour with a transcervical Foley catheter or vaginal prostaglandin E2 gel. The primary outcome was caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from induction to birth. Results A total of 824 women were allocated to induction of labour with a Foley catheter (n = 412) or prostaglandin E2 (n = 412). Caesarean section rates were comparable (23% versus 20%, RR 1.13, 95% CI 0.87 to 1.47). In the Foley catheter group fewer instrumental deliveries for foetal distress were performed (12% versus 18%, RR 0.68, 95% CI 0.49 to 0.95). Time to delivery (median hours (IQR)) was longer (29 (15-35) versus 18 (12-33)). Fewer mothers had suspected intrapartum infection (2% versus 4%, RR 0.41, 95% CI 0.17-0.98). Significantly fewer neonates were admitted toaneonatal ward after induction with a Foley catheter (12% versus 20%, RR 0.60, 95% CI 0.43 to 0.83). Conclusion In women with an unripe cervix at term, induction of labour with a Foley catheter does not reduce caesarean section rates, but there are fewer side-effects

Foley Catheter Versus Vaginal Prostaglandin E2 Gel for Induction of Labor at Term (PROBAAT Trial): An Open-Label, Randomized Controlled Trial EDITORIAL COMMENT

Obstetric

Foley catheter versus vaginal prostaglandin E2 gel for induction of labour at term (PROBAAT trial): an open-label, randomised controlled trial.

BACKGROUND: Induction of labour is a common obstetric procedure. Both mechanical (eg, Foley catheters) and pharmacological methods (eg, prostaglandins) are used for induction of labour in women with an unfavourable cervix. We aimed to compare the effectiveness and safety of induction of labour with a Foley catheter with induction with vaginal prostaglandin E2 gel. METHODS: We did an open-label, randomised controlled trial in 12 hospitals in the Netherlands between Feb 10, 2009, and May 17, 2010. We enrolled women with a term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix, an indication for induction of labour, and no prior caesarean section. Participants were randomly allocated by an online randomisation system to induction of labour with a 30 mL Foley catheter or vaginal prostaglandin E2 gel (1:1 ratio). Because of the nature of the intervention this study was not blinded. The primary outcome was caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from intervention to birth. All analyses were done on an intention-to-treat basis. We also did a meta-analysis that included our trial. The trial was registered with the Dutch trial registry, number NTR 1646. FINDINGS: 824 women were allocated to induction of labour with a Foley catheter (n=412) or vaginal prostaglandin E2 gel (n=412). Caesarean section rates were much the same between the two groups (23%vs 20%, risk ratio [RR] 1.13, 95% CI 0.87-1.47). A meta-analysis including our trial data confirmed that a Foley catheter did not reduce caesarean section rates. We recorded two serious maternal adverse events, both in the prostaglandin group: one uterine perforation and one uterine rupture. INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with a Foley catheter is similar to induction of labour with prostaglandin E2 gel, with fewer maternal and neonatal side-effects. FUNDING: None