Haase J.K.,University College Cork |
Didelot X.,Imperial College London |
Lecuit M.,French Institute of Health and Medical Research |
Lecuit M.,Necker Enfants Malades University Hospital |
And 7 more authors.
Environmental Microbiology | Year: 2014
Listeria monocytogenes is ubiquitously prevalent in natural environments and is transmitted via the food chain to animals and humans, in whom it can cause life-threatening diseases. We used Multilocus Sequence Typing (MLST) of ~2000 isolates of L.monocytogenes to investigate whether specific associations existed between clonal complexes (CCs) and the environment versus diseased hosts. Most CCs (72%) were not specific for any single source, and many have been isolated from the environment, food products, animals as well as from humans. Our results confirm that the population structure of L.monocytogenes is largely clonal and consists of four lineages (I-IV), three of which contain multiple CCs. Most CCs have remained stable for decades, but one epidemic clone (CC101) was common in the mid-1950s and very rare until recently when it may have begun to re-emerge. The historical perspective used here indicates that the central sequence types of CCs were not ancestral founders but have rather simply increased in frequency over decades. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.
Lebranchu Y.,University of Tours |
Snanoudj R.,Necker Enfants Malades University Hospital |
Toupance O.,University Hospital |
Weestel P.-F.,University Hospital |
And 11 more authors.
American Journal of Transplantation | Year: 2012
Calcineurin inhibitors improve acute rejection rates and short-term graft survival in renal transplantation, but their continuous use may be deleterious. We evaluated the 5-year outcomes of sirolimus (SRL) versus cyclosporine (CsA) immunosuppressive treatment. This observational study was an extension of the SPIESSER study where deceased donor kidney transplant recipients were randomized before transplantation to a SRL- or CsA-based regimen and followed up 1 year. Data from 131 (63 SRL, 68 CsA) out of 133 patients living with a functional graft at 1 year were collected retrospectively at 5 years posttransplant. Seventy percent of CsA patients versus 54% of SRL patients were still on the allocated treatment at 5 years (p = 0.091), most discontinuations in each group being due to safety issues. In intent-to-treat, mean MDRD eGFR was higher with SRL: 54.2 versus 45.3 mL/min with CsA (p = 0.019); SRL advantage was greater in on-treatment analyses. Therewere no differences for patient survival (p=0.873), graft survival (p=0.121) and acute rejection (p = 0.284). Adverse events were more frequent with SRL (80% vs. 60%, p = 0.015). Results confirmed the high SRL discontinuation rate due to adverse events. Nevertheless, a benefit was evidenced on renal function in patients (more than 50%) still on treatment at 5 years. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
Tsai Y.-H.,Institute Pasteur Paris |
Tsai Y.-H.,French Institute of Health and Medical Research |
Tsai Y.-H.,University Paris Diderot |
Disson O.,Institute Pasteur Paris |
And 9 more authors.
PLoS Pathogens | Year: 2013
Listeria monocytogenes (Lm) is an invasive foodborne pathogen that leads to severe central nervous system and maternal-fetal infections. Lm ability to actively cross the intestinal barrier is one of its key pathogenic properties. Lm crosses the intestinal epithelium upon the interaction of its surface protein internalin (InlA) with its host receptor E-cadherin (Ecad). InlA-Ecad interaction is species-specific, does not occur in wild-type mice, but does in transgenic mice expressing human Ecad and knock-in mice expressing humanized mouse Ecad. To study listeriosis in wild-type mice, InlA has been "murinized" to interact with mouse Ecad. Here, we demonstrate that, unexpectedly, murinized InlA (InlAm) mediates not only Ecad-dependent internalization, but also N-cadherin-dependent internalization. Consequently, InlAm-expressing Lm targets not only goblet cells expressing luminally-accessible Ecad, as does Lm in humanized mice, but also targets villous M cells, which express luminally-accessible N-cadherin. This aberrant Lm portal of entry results in enhanced innate immune responses and intestinal barrier damage, both of which are not observed in wild-type Lm-infected humanized mice. Murinization of InlA therefore not only extends the host range of Lm, but also broadens its receptor repertoire, providing Lm with artifactual pathogenic properties. These results challenge the relevance of using InlAm-expressing Lm to study human listeriosis and in vivo host responses to this human pathogen. © 2013 Tsai et al.
PubMed | Necker Enfants Malades University Hospital, Marseille University Hospital Center, Paris-Sorbonne University, Aix - Marseille University and 10 more.
Type: | Journal: The Journal of allergy and clinical immunology | Year: 2016
Most children with primary immunodeficiencies (PIDs) now reach adulthood. However, few studies have evaluated their health status and health-related quality of life (HRQoL).To investigate long-term morbidity, the French Reference Center for PIDs initiated a prospective multicenter cohort: the French Childhood Immune Deficiency Long-term Cohort. The data collected were used to assess the physical health condition of patients who reached adulthood and the effect on their quality of life.Patients were asked to complete health status questionnaires. Aseverity score (grade 1 [mild] to grade 4 [life-threatening]) was assigned to each health condition. The HRQoL of patients was compared with age- and sex-matched French normal values by using the 36-item Short-Form Survey (SF-36) HRQoL questionnaire.Among 329 participants, the mean age at evaluation was 27.6years, with a 21-year mean follow-up after diagnosis; 43% reported at least 1 grade 4 health condition, and 86% reported at least 1 grade 3 (severe) or 4 health condition. Twenty-five (7.6%) patients had been treated for cancer. Compared with the French normal values, adults with PIDs scored significantly lower for all HRQoL domains. HRQoL was strongly associated with the burden of health conditions. The association with grade 4 or grade 3-4 health conditions was highly significant for all physical and mental domains.Adults with PIDs diagnosed during childhood experienced a heavy burden of health conditions, which affected their HRQoL. Our results emphasize the need to closely monitor this vulnerable population.
Lecuit M.,Institute Pasteur Paris |
Lecuit M.,French Institute of Health and Medical Research |
Lecuit M.,University of Paris Descartes |
Lecuit M.,Necker Enfants Malades University Hospital |
And 2 more authors.
Trends in Microbiology | Year: 2013
The human virome is the viral component of the microbiome. Its composition, and interindividual and temporal variability are not precisely known. Its impact on human health has received less attention than that of the bacterial microbiome, but is likely to be equally important, both in homeostasis and disease. Here we review the recent advances in this field and the questions that arise in the context of our rapidly increasing knowledge regarding the composition and function of the human virome. With the ever-extending use of next-generation sequencing (NGS) on a variety of clinical samples, rapid progress on the composition of the human virome and its impact upon human health are to be expected in the coming years. © 2013.
PubMed | Necker Enfants Malades University Hospital, University of Angers, French Center For Pediatric Stroke Service Of Medecine Physique Et Of Readaptation Pediatrique, French Polynesia Hospital and 2 more.
Type: Journal Article | Journal: Expert review of neurotherapeutics | Year: 2016
Over the last decade considerable advances have been made in the identification, understanding and management of pediatric arterial ischemic stroke. Such increasing knowledge has also brought new perspectives and interrogations in the current acute and rehabilitative care of these patients. Areas covered: In developed countries, focal cerebral arteriopathy is one of the most common causes of arterial ischemic stroke in childhood and imaging features are well characterized. However, there are ongoing debates regarding its underlying mechanisms, natural evolution and proper management. The implementation of thrombolytic therapy in acute pediatric stroke has been shown to be efficient in anecdotal cases but is still limited by a number of caveats, even in large tertiary centers. Finally, neonatal stroke represents a unique circumstance of possible early intervention before the onset of any neurological disability but this appears meaningful only in a selective group of neonates. Expert commentary: While perinatal stroke, a leading cause of cerebral palsy, appears to be multifactorial, a large number of childhood ischemic stroke are probably essentially triggered by infectious factors leading to vessel wall damage. Current research is aiming at better identifying risk factors in both conditions, and to define optimal acute and preventive therapeutic strategies in order to reduce significant long-term morbidity.
Gaspar H.B.,University College London |
Hammarstrom L.,Karolinska Institutet |
Mahlaoui N.,Necker Enfants Malades University Hospital |
Borte M.,University of Leipzig |
And 4 more authors.
Journal of Clinical Immunology | Year: 2014
Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency and is a paediatric emergency. Delay in recognising and detecting SCID can have fatal consequences and also reduces the chances of a successful haematopoietic stem cell transplant (HSCT). Screening for SCID at birth would prevent children from dying before HSCT can be attempted and would increase the success of HSCT. There is strong evidence to show that SCID fulfills the internationally-established criteria for a condition to be screened for at birth. There is also a test (the T-cell receptor excision circle (TREC) assay) that is now being successfully used in an increasing number of US states to screen for SCID in routine newborn Guthrie samples. Concerted lobbying efforts have highlighted the need for newborn screening (NBS) for SCID, and its implementation is being discussed in Europe both at EU and individual country level, but as yet there is no global mandate to screen for this rare and frequently lethal condition. This paper summarizes the current evidence for, and the success of SCID NBS, together with a review of the practical aspects of SCID testing and the arguments in favour of adding SCID to the conditions screened for at birth. © 2014 Springer Science+Business Media.
Souberbielle J.-C.,Necker Enfants Malades University hospital |
Cavalier E.,University of Liège |
Cormier C.,Cochin University Hospital
Annales d'Endocrinologie | Year: 2015
The aim of this article is to discuss the diagnostic approach of an increased serum PTH concentration in a normocalcemic, normophosphatemic patient. Detection of this biological presentation is frequent in routine practice all the more that PTH reference values established in vitamin D replete subjects with a normal renal function are used by the clinical laboratories. The first step in this diagnostic approach will be to rule out a cause of secondary hyperparathyroidism (SHPT). Among these, the most frequent are vitamin D deficiency, very low calcium intake, impaired renal function, malabsorptions, drugs interfering with calcium/bone metabolism, such as lithium salts and antiresorptive osteoporosis therapies, hypercalciuria due to a renal calcium leak. If no cause of SHPT are evidenced, the diagnosis of normocalcemic primary hyperparathyroidism (PHPT) should be considered. A calcium load test is a very useful tool for this diagnosis if it shows that serum PTH is not sufficiently decreased when calcemia rises frankly above the upper normal limit. In a normocalcemic patient with hypercalciuria and a high serum PTH concentration, a thiazide challenge test may help to differentiate SHPT due to a renal calcium leak from normocalcemic PHPT. Beyond the discussion of this diagnostic flowchart, we also discuss some points about the merits and the difficulties of measuring and interpreting ionized calcemia and 24-h calciuria. © 2015 Elsevier Masson SAS.
Lapillonne A.,University of Paris Descartes |
Lapillonne A.,Necker Enfants Malades University Hospital |
Lapillonne A.,Baylor College of Medicine |
Kermorvant-Duchemin E.,University of Paris Descartes |
Kermorvant-Duchemin E.,Necker Enfants Malades University Hospital
Journal of Nutrition | Year: 2013
Significant efforts have been made to improve the nutritional support of preterm infants in neonatal intensive care units(NICUs) to avoid cumulative nutritional deficits, reduce postnatal growth restriction, and promote optimal long-term development. The objective of this systematic review was to compare the characteristics and results of all surveys published in the past 10 y (2002-2012) that used a questionnaire to survey at least 2 NICUs receiving preterm infants with an intention to treat with parenteral nutrition (PN) and that reported information on at least 1 macronutrient. A total of 6 surveys were identified, which were conducted in the United States (n = 2) or Europe (n = 4). There was wide variability in the responserate (23-100%), with a higher response rate in the smaller studies (81-100%; 8-64 respondents) compared with the larger studies (23-58%; 296-809 respondents). Large differences were observed in the nutritional protocols both among the NICU sin the individual surveys and between surveys. PN was initiated on the first day of life (DOL) by only 24-54%of respondents(4 surveys) and within the second DOL by 67-94%of respondents (5 surveys). Lipids were initiated before the third DOL for46-96% of respondents (3 surveys). The results of this systematic review suggest that continuous education is needed and that greater efforts are required to disseminate and implement guidelines. Repeated surveys are needed to highlight trends inclinical practices and level of compliance of NICUs with existing guidelines. © 2013 American Society for Nutrition.
Neuzillet C.,French Institute of Health and Medical Research |
Neuzillet C.,University Paris Diderot |
Neuzillet C.,Henri Mondor University Hospital |
Tijeras-Raballand A.,AAREC Filia Research |
And 10 more authors.
Pharmacology and Therapeutics | Year: 2015
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second cause of cancer-related death in 2030. PDAC is the poorest prognostic tumor of the digestive tract, with 80% of patients having advanced disease at diagnosis and 5-year survival rate not exceeding 7%. Until 2010, gemcitabine was the only validated therapy for advanced PDAC with a modest improvement in median overall survival as compared to best supportive care (5-6 vs 3 months). Multiple phase II-III studies have used various combinations of gemcitabine with other cytotoxics or targeted agents, most in vain, in attempt to improve this outcome. Over the past few years, the landscape of PDAC management has undergone major and rapid changes with the approval of the FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens in patients with metastatic disease. These two active combination chemotherapy options yield an improved median overall survival (11.1 vs 8.5 months, respectively) thus making longer survival a reasonably achievable goal. This breakthrough raises some new clinical questions about the management of PDAC. Moreover, better knowledge of the environmental and genetic events that underpin multistep carcinogenesis and of the microenvironment surrounding cancer cells in PDAC has open new perspectives and therapeutic opportunities. In this new dynamic context of deep transformation in basic research and clinical management aspects of the disease, we gathered updated preclinical and clinical data in a multifaceted review encompassing the lessons learned from the past, the yet unanswered questions, and the most promising research priorities to be addressed for the next 5 years. © 2015 Elsevier Inc.