Transfusion practices in postpartum hemorrhage: a population-based study.: Transfusion in Postpartum Haemorrhage

International audienceOBJECTIVE: To describe transfusion practices and anemia in women with postpartum hemorrhage (PPH), according to the clinical context. DESIGN: Population-based cohort study. SETTING: A total of 106 French maternity units (146 781 deliveries, December 2004 to November 2006). POPULATION: All women with PPH (n = 9365). METHODS: Description of the rate of red blood cell (RBC) transfusion in PPH overall and compared with transfusion guidelines. MAIN OUTCOME MEASURES: Transfusion practices and postpartum anemia by mode of delivery and cause of PPH in women given RBCs within 12 h after PPH. RESULTS: A total of 701 women received RBCs (0.48 ± 0.04% of all women and 7.5 ± 0.5% of women with PPH). Half the women with clinical PPH and hemoglobin lower than 7.0 g/dL received no RBCs. In the group with clinical PPH and transfusion within 12 h (n = 426), operative vaginal delivery was associated with a larger maximal hemoglobin drop, more frequent administration of fresh-frozen plasma (FFP) and pro-hemostatic agents [odds ratio (OR) 3.54, 95% confidence interval (95% CI) 1.12-11.18], transfusion of larger volumes of RBCs and FFP, a higher rate of massive RBCs transfusion (OR 5.22, 95% CI 2.12-12.82), and more frequent use of conservative surgery (OR 3.2, 95% CI 1.34-7.76), compared with spontaneous vaginal delivery. CONCLUSIONS: The RBC transfusion for PPH was not given in a large proportion of women with very low hemoglobin levels despite guidelines to the contrary. Operative vaginal delivery is characterized by higher blood loss and more transfusions than spontaneous vaginal delivery

Transglutaminase-dependent RhoA Activation and Depletion by Serotonin in Vascular Smooth Muscle Cells

The small G protein RhoA plays a major role in several vascular processes and cardiovascular disorders. Here we analyze the mechanisms of RhoA regulation by serotonin (5-HT) in arterial smooth muscle. 5-HT (0.1-10 microM) induced activation of RhoA followed by RhoA depletion at 24-72 h. Inhibition of 5-HT1 receptors reduced the early phase of RhoA activation but had no effect on 5-HT-induced delayed RhoA activation and depletion, which were suppressed by the 5-HT transporter inhibitor fluoxetine and the transglutaminase inhibitor monodansylcadaverin and in type 2 transglutaminase-deficient smooth muscle cells. Coimmunoprecipitations demonstrated that 5-HT associated with RhoA both in vitro and in vivo. This association was calcium-dependent and inhibited by fluoxetine and monodansylcadaverin. 5-HT promotes the association of RhoA with the E3 ubiquitin ligase Smurf1, and 5-HT-induced RhoA depletion was inhibited by the proteasome inhibitor MG132 and the RhoA inhibitor Tat-C3. Simvastatin, the Rho kinase inhibitor Y-27632, small interfering RNA-mediated RhoA gene silencing, and long-term 5-HT stimulation induced Akt activation. In contrast, inhibition of 5-HT-mediated RhoA degradation by MG132 prevented 5-HT-induced Akt activation. Long-term 5-HT stimulation also led to the inhibition of the RhoA/Rho kinase component of arterial contraction. Our data provide evidence that 5-HT, internalized through the 5-HT transporter, is transamidated to RhoA by transglutaminase. Transamidation of RhoA leads to RhoA activation and enhanced proteasomal degradation, which in turn is responsible for Akt activation and contraction inhibition. The observation of transamidation of 5-HT to RhoA in pulmonary artery of hypoxic rats suggests that this process could participate in pulmonary artery remodeling and hypertension

Nouvelle approche des fibroses par microscopie multiphotonique avec génération de second harmonique [New approach of fibrosis by multiphoton microscopy with second harmonic generation]

La fibrose est une réponse adaptative pathologique qui détruit non spécifiquement les tissus. Il s'agit d'un processus universel de réparation des tissus qui survient en réaction à de nombreux types d'agressions telles les contraintes mécaniques, les brûlures, les radiations ionisantes, l'ischémie, l'inflammation. Ces agressions concourent de manière intriquée à la physiopathologie des maladies infectieuses, tumorales ou auto-immunes, de l'hypertension artérielle et des maladies cardio-vasculaires. Le terme de fibrose décrit précisément l'accumulation nouvelle de protéines de la matrice extra-cellulaire selon un arrangement spatial fibrillaire caractéristique. Il s'agit essentiellement de molécules de collagènes de type I et III (voire de type II, V ou XI) synthétisées sous forme de triples hélices elles-mêmes assemblées en fibrilles par les cellules fibroblastiques. L'apparition des collagènes fibrillaires marque un changement qualitatif et quantitatif de composition des collagènes des tissus. Réciproquement, ces changements de la matrice extracellulaire influencent le phénotype des cellules qui y résident. Ainsi dans le rein normal, le collagène de type I n'existe que dans l'adventice artériel. Son apparition au sein des autres structures de cet organe marque une fibrose tubulo-interstitielle qui constitue le meilleur marqueur pronostic défavorable d'une évolution vers l'insuffisance rénale terminale, et ce quelle que soit la maladie causale. Ainsi, comme lors des fibroses compliquant les hépatopathies et les pneumopathies chroniques, les séquelles de brûlures ou d'abrasions cutanées-muqueuses ou encore le remodelage cardiaque et vasculaire, le réarrangement de la géométrie de la matrice extracellulaire altère l'organisation fonctionnelle du tissu considéré. De ce fait, ce processus de réparation a des effets fonctionnels délétères qui constituent un enjeu médical majeur. Les fibrilles de collagène ont des capacités d'auto-assemblage qui sont aussi catalysées et stabilisées ou au contraire empêchées par les enzymes de la matrice extracellulaire. Le développement de la fibrose ou sa régression dépend donc ainsi du bilan des équilibres biologiques de ces mécanismes. Il est donc crucial de caractériser les changements extracellulaires et cellulaires qui font du restutio ad integrum de l'architecture et de la fonction tissulaire un défi biomédical

Effect of a collector bag for measurement of postpartum blood loss after vaginal delivery: cluster randomised trial in 13 European countries

Objective To evaluate the effectiveness of the systematic use of a transparent plastic collector bag to measure postpartum blood loss after vaginal delivery in reducing the incidence of severe postpartum haemorrhage

Cardiac metabolic deregulation induced by the tyrosine kinase receptor inhibitor sunitinib is rescued by endothelin receptor antagonism

International audienceThe growing field of cardio-oncology addresses the side effects of cancer treatment on the cardiovascular system. Here, we explored the cardiotoxicity of the antiangiogenic therapy, sunitinib, in the mouse heart from a diagnostic and therapeutic perspective. We showed that sunitinib induces an anaerobic switch of cellular metabolism within the myocardium which is associated with the development of myocardial fibrosis and reduced left ventricular ejection fraction as demonstrated by echocardiography. The capacity of positron emission tomography with [ 18 F]fluorodeoxyglucose to detect the changes in cardiac metabolism caused by sunitinib was dependent on fasting status and duration of treatment. Pan proteomic analysis in the myocardium showed that sunitinib induced (i) an early metabolic switch with enhanced glycolysis and reduced oxidative phosphorylation, and (ii) a metabolic failure to use glucose as energy substrate, similar to the insulin resistance found in type 2 diabetes. Co-administration of the endothelin receptor antagonist, macitentan, to sunitinib-treated animals prevented both metabolic defects, restored glucose uptake and cardiac function, and prevented myocardial fibrosis. These results support the endothelin system in mediating the cardiotoxic effects of sunitinib and endothelin receptor antagonism as a potential therapeutic approach to prevent cardiotoxicity. Furthermore, metabolic and functional imaging can monitor the cardiotoxic effects and the benefits of endothelin antagonism in a theranostic approach

Placenta accreta spectrum - variations in clinical practice and maternal morbidity between UK and France : a population-based comparative study

SM’s DPhil was funded by the Medical Research Council. PACCRETA was funded by PACCRETA was funded by the French Health Ministry under its Clinical Research Hospital Program (grant number: AOR12156) and by the Angers University Hospital.Peer reviewedPublisher PD

Hémorragie du postpartum (profil épidémiologique et évaluation des pratiques d'anesthésie-réanimation en France)

La France se démarque par un ratio de mortalité maternelle par hémorragie du postpartum (HPP) élevé.Les objectifs de cette thèse étaient: 1/comparer les caractéristiques épidémiologiques de l'HPP entre la France et le Canada 2/décrire les pratiques d'anesthésie-réanimation dans l'HPP et évaluer leur adéquation par rapport aux recommandations chez les femmes décédées d'HPP et dans une population de femmes avec HPP.Les sources de données utilisées étaient: La base nationale canadienne de données hospitalières sur les séjours des patients, l'essai Pithagore6 et l'Enquête nationale confidentielle sur les morts maternelles.La comparaison du profil épidémiologique de l'HPP entre la France et le Canada montre que l'HPP n'est pas plus fréquente en France. Le recours plus fréquent à des traitements de seconde ligne suggère une incidence plus élevée de l'HPP sévère en France. Dans les décès maternels par HPP, certaines pratiques d'anesthésie-réanimation apparaissent comme inadéquates: le monitorage clinique et la mise en condition des patientes, la surveillance paraclinique, le protocole d'anesthésie générale et la stratégie transfusionnelle. La description en population des pratiques transfusionnelles dans l'HPP montre un recours insuffisant à la transfusion. Inversement des stratégies transfusionnelles dont l'efficacité n'est pas prouvée sont fréquemment appliquées.Ce travail suggère une sévérité importante de l'HPP en France, pouvant expliquer l'importance de la mortalité par HPP. Certaines pratiques d'anesthésie-réanimation apparaissant comme non-optimales pourraient être impliquées dans cette sévérité. L'association entre pratiques et sévérité de l'HPP reste à être étudiée.In France, the maternal mortality ratio due to postpartum hemorrhage (PPH) is higher than in other high resources countries. This situation remains partially unexplained. The objectives of this PhD thesis were: 1/ to compare PPH epidemiological characteristics between France and Canada, 2/ to describe anesthesia and intensive care practices in PPH and to compare them with guidelines, first in cases of maternal deaths from PPH and secondly in a large population of women with PPH. The data sources were: the Discharge Abstract Database from the Canadian Institute for Health Information, the Pithagore6 trial and the French Confidential Enquiry into Maternal Deaths. The comparison of PPH epidemiological profiles between France and Canada shows that PPH incidence is not higher in France. Second-line treatments in PPH management are more frequently performed, suggesting a higher incidence of severe PPH in France. Among maternal deaths from PPH, some practices in anesthesia and critical care management appear to be inadequate: clinical monitoring and laboratory assessment, protocol for general anesthesia and transfusion strategy. The description on transfusion practices in a large population of women with PPH shows that the use of blood products is not sufficient. Conversely, transfusion strategies with unproved efficacy are frequently used. These results suggest a higher rate of severe PPH in France, that may result in the higher maternal mortality due to PPH. Inadequate practices in anesthesia and critical care could be involved in this severity. But the association between specific components of anesthesia and critical care management and PPH severity remains to be exploredPARIS-JUSSIEU-Bib.électronique (751059901) / SudocSudocFranceF

Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster-randomised controlled trial.: Intervention to decrease severe postpartum haemorrhage

International audienceOBJECTIVE: Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical challenge. These are often considered to be associated with substandard initial care. Strategies to increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early management of PPH, would reduce the incidence of severe PPH. DESIGN: Cluster-randomised trial. POPULATION: 106 maternity units in six French regions. METHODS: Maternity units were randomly assigned to receive the intervention, or to have the protocol passively disseminated. The intervention combined outreach visits to discuss the protocol in each local context, reminders, and peer reviews of severe incidents, and was implemented in each maternity hospital by a team pairing an obstetrician and a midwife. MAIN OUTCOME MEASURES: The primary outcome was the incidence of severe PPH, defined as a composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, peripartum haemoglobin decrease of 4 g/dl or more, death. The main secondary outcomes were PPH management practices. RESULTS: The mean rate of severe PPH was 1.64% (SD 0.80) in the intervention units and 1.65% (SD 0.96) in control units; difference not significant. Some elements of PPH management were applied more frequently in intervention units-help from senior staff (P = 0.005), or tended to - second-line pharmacological treatment (P = 0.06), timely blood test (P = 0.09). CONCLUSION: This educational intervention did not affect the rate of severe PPH as compared with control units, although it improved some practices

Deletion of the myeloid endothelin-B receptor confers long-term protection from angiotensin II-mediated renal, retinal & vascular injury

International audienceThe endothelin system may be an important player in hypertensive end-organ injury as endothelin-1 increases blood pressure and is pro-inflammatory. The immune system is emerging as an important regulator of blood pressure and we have shown that the early hypertensive response to angiotensin-II infusion was amplified in mice deficient of myeloid endothelin-B (ETB) receptors (LysM-CreEdnrblox/lox). Hypothesizing that these mice would display enhanced organ injury, we gave angiotensin-II to LysM-CreEdnrblox/lox and littermate controls (Ednrblox/lox) for six weeks. Unexpectedly, LysM-CreEdnrblox/lox mice were significantly protected from organ injury, with less proteinuria, glomerulosclerosis and inflammation of the kidney compared to controls. In the eye, LysM-CreEdnrblox/lox mice had fewer retinal hemorrhages, less microglial activation and less vessel rarefaction. Cardiac remodeling and dysfunction were similar in both groups at week six but LysM-CreEdnrblox/lox mice had better endothelial function. Although blood pressure was initially higher in LysM-CreEdnrblox/lox mice, this was not sustained. A natriuretic switch at about two weeks, due to enhanced ETB signaling in the kidney, induced a hypertensive reversal. By week six, blood pressure was lower in LysM-CreEdnrblox/lox mice than in controls. At six weeks, macrophages from LysM-CreEdnrblox/lox mice were more anti-inflammatory and had greater phagocytic ability compared to the macrophages of Ednrblox/lox mice. Thus, myeloid cell ETB receptor signaling drives this injury both through amplifying hypertension and by inflammatory polarization of macrophages