Congenital pulmonary adenomatoid malformation: Indication and management of fetal shunting in our center

Objective: Congenital pulmonary adenomatoid malformations (CPAM) are increasingly diagnosed in recent years thanks to the expert hands and the technology of ultrasonography used in antenatal diagnosis. The purpose was to examine a series of cases referred to our fetalmaternal tertiary center for lung disease and to present the natural course, treatment and outcome of antenatally diagnosed cystic lung disease. Material and Methods: We proposed a retrospective study (October 2003 to September 2016) in a single center. Prenatal and postnatal data of fetus, with suspected CPAM, where analyzed. Results: We studied 34 cases. One child was excluded post-natally because at birth diagnosis of esophageal duplication was made. Mean gestational age at the diagnosis was 22 weeks (range 21 to 28). Thoracoamniotic shunting was performed in 9 cases. In 8 cases, it was an intra-cystic drain and in 1 case, a pleuroamniotic drain. Mean gestational age for drainage was 25 weeks (range 22 to 28). Mean gestational age at delivery was 38 weeks. All patients underwent postnatal radiological assessment. Anatomical surgical resection was performed in all cases: immediately at birth in 7 symptomatic cases, in the first year of life for 1 case that became symptomatic and 1 patient died immediately at birth due to severe respiratory distress. Conclusion: Antenatally diagnosed CPAM have an excellent prognosis. We propose invasive prenatal thoracoamniotic shunting in rare cases with unequivocal fetal compromise (i.e., polydramnios and hydrops)

Time-to-birth prediction models and the influence of expert opinions

Preterm birth is the leading cause of death among children under five years old. The pathophysiology and etiology of preterm labor are not yet fully understood. This causes a large number of unnecessary hospitalizations due to high--sensitivity clinical policies, which has a significant psychological and economic impact. In this study, we present a predictive model, based on a new dataset containing information of 1,243 admissions, that predicts whether a patient will give birth within a given time after admission. Such a model could provide support in the clinical decision-making process. Predictions for birth within 48 h or 7 days after admission yield an Area Under the Curve of the Receiver Operating Characteristic (AUC) of 0.72 for both tasks. Furthermore, we show that by incorporating predictions made by experts at admission, which introduces a potential bias, the prediction effectiveness increases to an AUC score of 0.83 and 0.81 for these respective tasks

PP2A/B55 and Fcp1 regulate Greatwall and Ensa desphorylation during mitotic exit

Entry into mitosis is triggered by activation of Cdk1 and inactivation of its counteracting phosphatase PP2A/B55. Greatwall kinase inactivates PP2A/B55 via its substrates Ensa and ARPP19. Both Greatwall and Ensa/ARPP19 are regulated by phosphorylation, but the dynamic regulation of Greatwall activity and the phosphatases that control Greatwall kinase and its substrates are poorly understood. To address these questions we applied a combination of mathematical modelling and experiments using phospho-specific antibodies to monitor Greatwall, Ensa/ARPP19 and Cdk substrate phosphorylation during mitotic entry and exit. We demonstrate that PP2A/B55 is required for Gwl dephosphorylation at the essential Cdk site Thr194. Ensa/ARPP19 dephosphorylation is mediated by the RNA Polymerase II carboxy terminal domain phosphatase Fcp1. Surprisingly, neither Fcp1 nor PP2A appear to essential to dephosphorylate the bulk of mitotic Cdk1 substrates following Cdk1 inhibition. Taken together our results suggest a hierarchy of phosphatases coordinating Greatwall, Ensa/ARPP19 and Cdk substrate dephosphorylation during mitotic exit

Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics

DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to ‘sloppy’ transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences

A cluster randomized trial of a transition intervention for adolescents with congenital heart disease: rationale and design of the CHAPTER 2 study

BACKGROUND: The population of adolescents and young adults with congenital heart disease (CHD) is growing exponentially. These survivors are at risk of late cardiac complications and require lifelong cardiology care. However, there is a paucity of data on how to prepare adolescents to assume responsibility for their health and function within the adult health care system. Evidence-based transition strategies are required. METHODS: The Congenital Heart Adolescents Participating in Transition Evaluation Research (CHAPTER 2) Study is a two-site cluster randomized clinical trial designed to evaluate the efficacy of a nurse-led transition intervention for 16–17 year olds with moderate or complex CHD. The primary endpoint is excess time to adult CHD care, defined as the time interval between the final pediatric cardiology appointment and the first adult CHD appointment, minus the recommended time interval between these appointments. Secondary endpoints include the MyHeart score (CHD knowledge), Transition Readiness Assessment Questionnaire score, and need for catheter or surgical re-intervention. Participants are enrolled in clusters based on week of attendance in the pediatric cardiology clinic. The intervention consists of two one-hour individualized sessions between a cardiology nurse and study participant. Session One focuses on knowledge of the participant’s CHD, review of their cardiac anatomy and prior interventions, and potential late cardiac complications. Session Two focuses on self-management and communication skills through review and discussion of videos and role-play. The study will recruit 120 participants. DISCUSSION: Many adolescents and young adults experience a gap in care predisposing them to late cardiac complications. The CHAPTER 2 Study will investigate the impact of a nurse-led transition intervention among adolescents with CHD. Fidelity of the intervention is a major focus and priority. This study will build on our experience by (i) enrolling at two tertiary care programs, (ii) including a self-management intervention component, and (iii) evaluating the impact of the intervention on time to ACHD care, a clinically relevant outcome. The results of this study will inform pediatric cardiology programs, patients and policy makers in judging whether a structured intervention program provides clinically meaningful outcomes for adolescents and young adults living with CHD. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT0172333

Évaluation d’un outil de mesure avec affichage de la norme en temps réel pour les biométries fœtales

International audienceObjectifs: La plupart des appareils à ultrasons comprennent un outil permettant l’affichage en temps réel de la valeur standard de la mesure biométrique prise. Notre hypothèse était que cet outil influence l’échographiste au fur et à mesure des mesures, en induisant une normalisation, donc une tendance vers le 50e centile. L’objectif de cette étude était d’évaluer l’impact d’un affichage en temps réel de la valeur standard dans le dépistage par échographie prénatale.Méthode: Nous avons mené une étude observationnelle, prospective, contrôlée et ouverte incluant tous les patients ayant subi une échographie prénatale au 2ème ou 3ème trimestre aux Hôpitaux Universitaires de Strasbourg entre décembre 2017 et juin 2018. Les critères d’exclusion étaient la présence d’une anomalie morphologique fœtale ou d’une anomalie caryotypique. L’outil testé était l’affichage en temps réel à l’écran de l’âge gestationnel, dont la mesure correspond au 50e centile. Les mesures ont été rétrospectivement transformées en Z-scores. Le principal point final était de comparer la distribution des scores Z entre les groupes.Résultats: Nous avons inclus 3551 examens échographiques: 696 effectués avec l’outil et 2796 effectués sans. Cinquante-neuf scans ont été exclus en raison d’anomalies morphologiques. Il n’y avait pas de différence statistiquement significative entre les distributions Z-scores des mesures effectuées avec ou sans l’outil, quel que soit le paramètre étudié. Il n’y avait pas non plus de différence dans la détection des mesures pathologiques: en dessous du 10e centile ou au-dessus du 90e centile.Conclusion: L’utilisation d’un tel outil ne semble pas nuire au dépistage biométrique, mais ne semble pas non plus utile

Vanishing Gastroschisis with a Favorable Outcome after a 3-Year Follow-Up: A Case Report and Literature Review

Vanishing gastroschisis (VG) is a severe complication of gastroschisis with a high mortality rate. We report here a case of VG with a favorable outcome after a 3-year follow-up. A 26-year-old primigravida woman was referred to Strasbourg University Hospital because her fetus was diagnosed with an isolated gastroschisis at 13-week gestation. The ultrasound evolution was marked by a progressive closure of the abdominal wall defect from 19-week gestation and the appearance of dilated intra-abdominal loops. The child was born with a closed abdominal wall except a small remnant at the level of the former gastroschisis orifice. Explorative laparotomy revealed extensive midgut atresia with only 50 cm of remaining midgut. A jejunocolic anastomosis was performed. The child is now 3 years old and has a favorable outcome with only 2 nights a week of parenteral nutrition. A total of 39 cases of VG type D from Perrone et al. classification are described in the literature from 1991 to 2019, among which 19 (48.7%) are alive at the time of publication but only 4 cases are described with a long-term follow-up of 3 years or more. This is the fifth case described with a favorable evolution after 3-year follow-up

Premières tentatives de quantification des flux de macro déchets plastiques en Seine

International audienceMacroplastiques, bassin de la Seine, barrages flottants, taux de fuite CHAPÔ Le projet MacroPLAST, soutenu et financé par le ministère de la transition écologique et solidaire, est issu de la mise en oeuvre de la Directive Cadre de Surveillance du Milieu Marin, qui initie diverses actions relatives aux macrodéchets marins afin de réduire à la source leurs quantités en mer et sur le littoral. CONTEXTE Pas un jour ne passe sans la diffusion d'images chocs de la pollution marine à travers le monde par le plastique. Bien que le plus grand nombre de fragments soient des microplastiques ( 5 mm). Les stocks à la surface des océans sont estimés à 300 000 tonnes alors que des modèles statistiques à l'échelle mondiale prédisent des flux entrant de l'ordre de 1-10 millions de tonnes/an (Eriksen et al., 2014; Jambeck et al., 2015). Les fonds océaniques pourraient quant à eux constituer la destination finale des plastiques (Galgani et al., 2000). Alors que les déchets plastiques ne représentent que 10% de l'ensemble des déchets générés par les activités humaines, leur durée de vie (siècles à millénaires) en fait les déchets les plus représentés dans des zones très éloignées de leur origine, i.e. les grandes agglomérations urbaines (Barnes et al., 2009). Ce n'est que très récemment que la communauté scientifique a pris conscience que 1) les fleuves et rivières sont des vecteurs majeurs de la pollution plastique des continents vers les océans (le chiffre de 80 % des déchets provenant des continents est souvent cité), et 2) les macroplastiques sont des gisements de microplastiques secondaires dont le réel impact écologique est à peine connu aujourd'hui. Encore plus que pour les microplastiques, les connaissances concernant les flux de macroplastiques dans les eaux de rivière ainsi que leur dynamique de transfère et leurs sources sont très lacunaires. Pourtant, elles sont essentielles pour calibrer les modèles statistiques de flux de plastiques en mer à l'échelle mondiale. Dans ce contexte, le projet MacroPLAST, financé par le Ministère de la Transition Écologique et Solidaire, a pour objectif d'évaluer les flux de macrodéchets déversés en mer à l'échelle du bassin de la Seine. Bien que l'ensemble des déchets soit considéré (débris plastiques, métalliques, bois manufacturés, verre), l'étude s'oriente principalement sur les macroplastiques. Cette synthèse présente les résultats obtenus ou en cours d'obtention dans le cadre des programmes de recherche PIREN-Seine, OPUR et MacroPLAST. Ils proviennent en partie de la thèse de Rachid Dris (Dris, 2016) complétés des données récentes de l'ORDIF (Observatoire Régional des Déchets d'Île de France) et du site sinoe.org (ADEME). VERS LES PREMIERES ESTIMATIONS DE FLUX DE MACROPLASTIQUES EN SEINE L'estimation des flux de déchets peut être abordée selon deux approches : une approche de modélisation conceptuelle (AMC) et une approche expérimentale (AE). La première considère un taux de fuite de déchets plastiques dans l'environnement constituant une quantité de déchets mal gérés dépendante de la pression anthropique (Jambeck et al., 2015). Elle a l'avantage d'être globale et d'intégrer toutes les tailles de plastique