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International audience; BackgroundThe optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose–effect relationship for two regimens of intravenous tranexamic acid vs placebo.MethodsWomen experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin–antiplasmin levels and in the plasmin peak time.ResultsIn the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68–118] for D-dimer level at 120 min and 56% [25–87] for the plasmin–antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13–63] [P=0.003 vs placebo]; plasmin–antiplasmin: –2% [–32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32–84] [P=0.06 vs placebo]; plasmin–antiplasmin: 13% [18–43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid.ConclusionsFibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic–pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage.

Pre-viable premature rupture of membranes (pre-viable PROM) is a rare event occurring in less than 1% of pregnancies. Nevertheless, it can be responsible for severe maternal complications, the risk of which needs to be balanced with the possibility to prolong the pregnancy up to viable gestational age. Maternal sepsis was reported in 1%-5% of women who received conservative management and prophylactic antibiotics, but information on maternal mortality is lacking. Our objective was to identify maternal deaths in women who had pre-viable PROM, describe the characteristics of the women, explore preventability factors within the care they received, and estimate the lethality of pre-viable PROM.We identified all maternal deaths associated with pre-viable PROM from the 2001-2015 French National Confidential Enquiry into Maternal Deaths (NCMM). Data on women's characteristics and the care they received were extracted from the ENCMM database. The lethality was determined after estimating the total number of pregnant women with pre-viable PROM from the national hospital discharge database.Between 2001 and 2015, we identified seven maternal deaths associated with pre-viable PROM, representing 0.6% of all maternal deaths over this period (ie, maternal mortality ratio 0.06/100 000 live births). Six maternal deaths were attributed to sepsis after genital infection by Gram-negative bacilli and one to postpartum hemorrhage due to placenta accreta. Four of these seven cases were considered preventable. The main preventability factors were delayed diagnosis, delayed fetal extraction, and inappropriate antibiotic treatment. The estimated lethality was 4.5/10 000 women with pre-viable PROM.Maternal death associated with pre-viable PROM is rare but possible. Most of these deaths seem preventable, with areas for improvement related to earlier diagnosis and better treatment of uterine infections, which can evolve rapidly.

General Relativity (GR) exists in different formulations. They are equivalent in pure gravity but generically lead to distinct predictions once matter is included. After a brief overview of various versions of GR, we focus on metric-affine gravity, which avoids any assumption about the vanishing of curvature, torsion or non-metricity. We use it to construct an action of a scalar field coupled non-minimally to gravity. It encompasses as special cases numerous previously studied models. Eliminating non-propagating degrees of freedom, we derive an equivalent theory in the metric formulation of GR. Finally, we give a brief outlook to implications for Higgs inflation., 49 pages, 5 figures, 3 appendices; v2: minor improvements and references added, matches published version

Resume La grossesse et le post-partum sont des periodes ou le risque d’embolie pulmonaire est augmente du fait d’une hypercoagulabilite, d’une stase veineuse et de traumatismes vasculaires eventuels. La physiopathologie de l’embolie pulmonaire fait intervenir une redistribution de la perfusion responsable d’hypoxemie et dans les formes graves une hypertension arterielle pulmonaire responsable de dilatation et d’ischemie du ventricule droit. Certaines parturientes (syndrome des antiphospholipides, mutation du facteur V ou du facteur II) sont particulierement a risque. Ce risque peut etre apprecie a l’aide de score (Dargaud, Strathege) qui permet d’adapter la strategie de prevention. Le seuil des D-dimeres permettant d’eliminer le diagnostic augmente avec l’evolution de la grossesse. La realisation d’un angioscanner thoracique est possible, malgre la grossesse, de meme que l’IRM. Le traitement repose sur les HBPM qui ne passent pas la barriere placentaire. Les antivitamines K sont contre-indiques au cours de la grossesse. La fibinolyse au cours des formes graves est exceptionnelle mais possible ainsi que le recours a l’ECMO.