Effet de l'administration anténatale de bétaméthasone avant 34 semaines d aménorrhées sur la morbidité néonatale des prématurés nés entre 34 et 36 semaines d aménorrhées plus 6 jours

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Clinical validation of a model predicting the risk of preterm delivery

International audienceObjectives: To validate a model predicting the risk of threatened preterm delivery and to establish the optimal threshold for this risk scoring system. Materials and methods: Two cohorts were studied: one of singleton pregnancies without preterm premature rupture of membranes (PPROM) and no cervical cerclage (cohort 1) and one of twin pregnancies without PPROM and no cervical cerclage (cohort 2). Patients were included from January 1st 2013 until December 31st 2013 by the Regional Perinatal Network of Ile de France with patients transferred because of threatened preterm delivery at 22 to 32 weeks of gestation. The individual probability of delivery within 48 hours of admission was calculated using the nomogram for every patient. Discrimination and calibration of the nomogram as well as the optimal threshold were determined using R studio. Results: The nomogram accurately predicted obstetric outcome. Discrimination and calibration were excellent, with an area under the curve (AUC) of 0.88 (95% CI 0.86-0.90) for cohort 1 and 0.73 (95% CI 0.66-0.80) for cohort 2. The optimal threshold would be 15% for cohort 1 and 10% for cohort 2. Using these thresholds, the performance characteristics of the nomogram were: sensitivity 80% (cohort 1) and 69% (cohort 2), negative predictive value 94.8% (cohort 1) and 91.3% (cohort 2). Use of the nomogram would avoid 253 unnecessary transfers in cohort 1. Conclusions: The nomogram was efficient and clinically relevant in our high risk population. A threshold set at 15% would help minimize the risk of preterm deliveries in singleton pregnancies and should reduce unnecessary, costly and stressful in utero transfer

Risk of preterm birth within 48 hours: Optimal threshold determination.

<p><b>On the left: In cohort 1</b>: To determine the best preterm risk threshold (minimization of false-negative and false-positive rates), one reliable statistical tool was used: MinROCdist. MinROCdist is the cut-off that minimizes the distance between the ROC curve and the upper left corner of the unit square. <b><i>On the right</i>: <i>In cohort 2</i>:</b> To determine the best preterm risk threshold (minimization of false-negative and false-positive rates), one reliable statistical tool was used: MinROCdist. MinROCdist is the cut-off that minimizes the distance between the ROC curve and the upper left corner of the unit square.</p

Pathologies maternelles chroniques et pertes de grossesse. Recommandations françaises

International audienceAim.-To review the available data on maternal chronic diseases and pregnancy losses.Material and Methods-We searched PubMed and the Cochrane library with pregnancy loss,stillbirth, intrauterine fetal demise, intrauterine fetal death, miscarriage and each maternaldiseases of this paper.Results-Antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anti-coagulant) should be measured in case of miscarriage after 10 WG confirmed by ultrasound(grade B) and an antiphospholipid syndrome should be treated by a combination of aspi-rin and low-molecular-weight heparin during a subsequent pregnancy (grade A). We donot recommend testing for genetic thrombophilia in case of first trimester miscarriage(grade B) or stillbirth (grade C). Glycemic control should be a goal before pregnancyfor women with pregestational diabetes to limit the risks of pregnancy loss (grade A)with a goal of prepregnancy HbA1c < 7%. Overt and subclinical hypothyroidisms should betreated by L-thyroxin during pregnancy to reduce the risks of pregnancy loss (grade A).Women who are positive for TPOAb should have TSH concentrations follow-up during pre-gnancy and subsequently treated by L-thyroxin if they develop subclinical hypothyroidism(grade B).Conclusions.-Prepregnancy management of most chronic maternal diseases, ideally throughprepregnancy multidisciplinary counseling, reduces the risks of pregnancy loss

Individual and obstetrical characteristics of the women included in the study (n = 481).

<p>Individual and obstetrical characteristics of the women included in the study (n = 481).</p

Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment

International audienceAutoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new-onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis. Four blood lymphocyte populations were significantly altered in AIHn patients at diagnosis compared with healthy subjects. Levels of mucosal-associated invariant T cells (MAIT), Type 1/Type 17 helper (Th1/ Th17) cells, clusters of differentiation (CD4) T cells, and invariant natural killer T cells were decreased, whereas MAIT granzyme B+ (GrB) cells were increased. A trend toward an increase of CD8+CD161+GrB+ cells was also observed. These alterations were not restored with standard immunosuppressive treatments. In the liver of AIHn patients, CD4, forkhead box P3 (Foxp3), and MAIT cell markers were enriched in the portal tract, and CD8, CD161, and GrB markers were enriched in the hepatic lobule. During remission, the hepatic lobule was clear of infiltrating T cells, but residual CD4 and MAIT cells were found in the portal tract, where Foxp3 was decreased, as previously described. In vitro, MAIT cells were functionally altered in AIH patients. Ex vivo MAIT cell activity (GrB) was linked to severe fibrosis. Conclusion: Our work proposes a global view of the lymphocyte alterations from diagnosis to remission phase in AIH patients. The absence of blood immune homeostasis restoration and the persistence of a CD4 infiltrate in the liver under standard immunosuppres-sion could form the basis of the high risk of relapse observed in AIH

Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment

International audienceAutoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new-onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis. Four blood lymphocyte populations were significantly altered in AIHn patients at diagnosis compared with healthy subjects. Levels of mucosal-associated invariant T cells (MAIT), Type 1/Type 17 helper (Th1/ Th17) cells, clusters of differentiation (CD4) T cells, and invariant natural killer T cells were decreased, whereas MAIT granzyme B+ (GrB) cells were increased. A trend toward an increase of CD8+CD161+GrB+ cells was also observed. These alterations were not restored with standard immunosuppressive treatments. In the liver of AIHn patients, CD4, forkhead box P3 (Foxp3), and MAIT cell markers were enriched in the portal tract, and CD8, CD161, and GrB markers were enriched in the hepatic lobule. During remission, the hepatic lobule was clear of infiltrating T cells, but residual CD4 and MAIT cells were found in the portal tract, where Foxp3 was decreased, as previously described. In vitro, MAIT cells were functionally altered in AIH patients. Ex vivo MAIT cell activity (GrB) was linked to severe fibrosis. Conclusion: Our work proposes a global view of the lymphocyte alterations from diagnosis to remission phase in AIH patients. The absence of blood immune homeostasis restoration and the persistence of a CD4 infiltrate in the liver under standard immunosuppres-sion could form the basis of the high risk of relapse observed in AIH

Impact of RAFT chain transfer agents on the polymeric shell density of magneto-fluorescent nanoparticles and their cellular uptake

International audienceThe impact of nanoparticle surface chemistry on cell interactions and especially cell uptake has become evident over the last few years in nanomedicine. Since PEG polymers have proved to be ideal tools for attaining stealthiness and favor escape from the in vivo mononuclear phagocytotic system, the accurate control of their geometry is of primary importance and can be achieved through reversible addition-fragmentation transfer (RAFT) polymerization. In this study, we demonstrate that the residual groups of the chain transfer agents (CTAs) introduced in the main chain exert a significant impact on the cellular internalization of functionalized nanoparticles. High-resolution magic angle spinning 1 H NMR spectroscopy and fluorescence spectroscopy permitted by the magneto-fluorescence properties of nanoassemblies (NAs) revealed the compaction of the PEG comb-like shell incorporating CTAs with a long alkyl chain, without changing the overall surface potential. As a consequence of the capability of alkyl units to self-assemble at the NA surface while hardly contributing more than 0.5% to the total polyelectrolyte weight, denser PEGylated NAs showed notably less internalization in all cells of the tumor microenvironment (tumor cells, macrophages and healthy cells). Interestingly, such differentiated uptake is also observed between pro-inflammatory M1-like and immunosuppressive M2-like macrophages, with the latter more efficiently phagocytizing NAs coated with a less compact PEGylated shell. In contrast, the NA diffusion inside multicellular spheroids, used to mimic solid tumors, appeared to be independent of the NA coating. These results provide a novel effort-saving approach where the sole variation of the chemical nature of CTAs in RAFT PEGylated polymers strikingly modulate the cell uptake of nanoparticles upon the organization of their surface coating and open the pathway toward selectively addressing macrophage populations for cancer immunotherapy