Search

Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years.

Documenting bacteremia at the onset of fever in immunosuppressed children is challenging; therefore, it leads to the early administration of broad-spectrum antibiotics. We aimed to analyse the evolution of antibiotic resistance profiles of bacterial bloodstream infections (BSI) and gut colonisations in a large cohort of immunocompromised children carrying a central venous catheter, in comparison with a prior, similar study conducted in our centre from 2014 to 2017. A retrospective, observational cohort study was conducted from January 2018 to December 2021, in a tertiary centre for paediatric immuno-haematology and oncology. Empirical antibiotic therapy was adapted to the immunosuppression risk group and prior bacterial colonisation. There was a mean of 6.9 BSI/1000 patient bed days. Multidrug-resistant bacteria (MDRB) associated BSI accounted for 35/273 (12.8%). The incidence of MDRB gum/gut colonisation and MDRB associated BSI increased annually and correlated with the level of immunosuppression (p = 0.024). One third (34.7%) of the BSI episodes were not associated with neutropenia. As compared to the previous study, an alarming emergence of MDRB responsible for gut colonisations and BSI in immunosuppressed children was reported over the last four years. The degree of immunosuppression directly correlates with the risk of having an MDRB gut colonisation or MDRB BSI.

Background: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents and young adults (AYAs) after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, AYAs and adults after a first allogeneic HSCT for AML. Methods: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (Results: With a median follow-up of 4.37 years (min-max 0.18 – 14.73 years), the probability of 2 year-overall survival (OS) was 71.4% in children, 61.1% in AYAs and 62.9% in adults (p=0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for AYAs and 29.4% for adults - p=0.0254, and 7.0% for children, 10.6% for AYAs and 14.2% for adults, pConclusion: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that AYAs AML patients should be treated with chemotherapy-based MAC regimen and bone marrow as stem cells source.

Allogenic hematopoietic stem cell transplantation (aHSCT) remains the treatment of choice for some malignant hemopathies in children, albeit with the risk of long-term consequences, including chronic kidney disease (CKD).In our single tertiary referral center, we retrospectively assessed the long-term renal outcome in a cohort of children and adolescents who had undergone aHSCT for malignant hemopathies between 2003 and 2017. We distinguished glomerular and tubular dysfunctions and assessed the accuracy of the most common formula(s) to estimate glomerular filtration rate (GFR) during standard clinical follow-up.Among the 166 patients who had received aHSCT, 61 underwent kidney functional assessment 1 to 10 years post-transplantation. Twenty-seven patients (44.3%) had a CKD with glomerular impairment, including 20 patients with a GFR 90 mL/min/1.73 mIn conclusion, our study shows that CKD represents an important long-term sequela for children and adolescents who undergo aHSCT for malignant hemopathies, either with glomerular dysfunction or with the more insidious tubular dysfunction which could potentially impact growth. These patients could benefit from specialized long-term nephrology follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.

Introduction A child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013–2014 influenza season, despite cord blood transplantation and antiviral treatments. Methods Conventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens. Results The patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status. Conclusions Conventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed.

Apres la rudesse de la desindustrialisation, dans les annees 2000, NewcastleGastehead a tente de repositionner son projet de ville dans le registre culturel. Alors que l’on assistait au renouvellement d’une sensibilite au maritime, le reamenagement des quais centraux (projet Quayside) avait ete pense pour creer une vitrine metropolitaine du Tyneside. Cependant, une quinzaine d’annees apres, ce tournant culturel n’a pas pris l’ampleur esperee et a notamment subi la crise de 2008. Les grands projets des annees 2000 sont en partie rejetes par la population. Le patrimoine alors considere comme une « ressource territoriale », est aujourd’hui au cœur de l’ancrage des habitants sur le territoire. Cet article revient sur l’evolution des dynamiques patrimoniales du Tyneside.

Because of the increased hemolytic rate, a significant proportion of patients with sickle cell disease (SCD) are prone to develop cholelithiasis. The present study investigated the role of several genetic factors (UGT1A1 promoter (TA)One hundred and fifty-eight children (2-18 yr old) regularly followed at the University Hospital of Lyon (France) were included. A multivariate Cox model was used to test the associations between cholelithiasis and the different parameters analyzed.We confirmed that alpha-thalassemia and low basal reticulocyte (RET) count were independent protective factors for cholelithiasis while 7/7, 8/8 and 7/8 UGT1A1 (TA)Our findings demonstrate that UGT1A1 (TA)

Resume Objectifs. Evaluer la fonction musculaire d’un groupe de patientes fibromyalgiques et la comparer a celle d’une population feminine de reference. Methodes. Seize patientes fibromyalgiques et 87 sujets sains feminins sedentaires ou sportifs de loisir ont execute un protocole experimental compose de quatre epreuves. La premiere evaluait le moment de force isocinetique concentrique maximum des muscles extenseurs et flechisseurs du genou dominant. Un dynamometre de Colin autorisait une mesure de la force manuelle isometrique. La resistance musculaire a la fatigue s’appreciait lors d’une epreuve isocinetique de flexion–extension des genoux : le sujet enchainait 30 contractions concentriques d’intensite maximale a la vitesse angulaire de 180 °/s. La derniere epreuve evaluait l’endurance musculaire statique a l’aide de tests exigeant le maintien d’une position donnee. Resultats. Toutes les variables musculaires apparaissaient reduites chez les sujets fibromyalgiques. Ce deficit, deja manifeste pour les efforts anaerobiques, s’accentuait lors des efforts en aerobie. Le deficit moyen correspondait a 39 % ( p p p Conclusion. L’exploration combinee des trois filieres energetiques confirme l’alteration generale de la fonction musculaire du sujet fibromyalgique. Cette etude suggere cependant une perturbation preferentielle des composantes oxydatives.

Ontogenesis of oxytocin (OT) and vasopressin (VP) gene expression and function were investigated in murine thymus. OT and VP transcripts were detected in the thymus on embryonic days 13 and 15, respectively. Corresponding messenger RNAs were evidenced in thymic epithelial cells by in situ hybridization with a neurophysin probe. From all OT and VP receptors, only OTR was expressed by all T-cell subsets, while V1bR was found in double positive and single positive CD8 cells. In fetal thymic organ cultures, OTR antagonist d[D-Tyr(Et)2, Thr4]OVT increased early apoptosis of CD8 cells, while V1bR antagonist (Sanofi SSR149415) inhibited T-cell differentiation, and favored CD8 T-cell commitment.

Rehabilitation of verbal short-term memory (vSTM) deficits in aphasic patients has been the focus of very few studies, despite the fact that their incidence in aphasia is high and that they further handicap residual language functioning. The few existing treatment studies on vSTM deficits have shown mitigated results and targeted attentional/ executive aspects of working memory rather than passive short-term storage capacity.

An enzyme-linked immunoassay has been recently set up for direct measurement of the binding capacity of plasma fibronectin to gelatin. This binding capacity could be completely inhibited in vitro by an eight-fold excess of gelatin, of Haemaccel®, but not of Geloplasma®. On the contrary, the levels of immunoreactive fibronectin measured by laser nephelometry did not change, in presence of 10 to 1000 μg ml−1 of gelatin, of Haemaccel or of Geloplasma. When infused into normal volunteers, Haemaccel provoked a strong and immediate inhibition of the plasma fibronectin binding capacity to gelatin. This inhibition was dose-dependent and maximal after infusion of 500 ml of Haemaccel. Twenty-four hours after this infusion, there was a progressive recovery of the gelatin-binding capacity, which was almost completely achieved 96 h later. The formation of complexes between Haemaccel and fibronectin was demonstrated by gel filtration chromatography and by affinity chromatography. Immunoreactive plasma fibronectin levels remained unchanged up to 24 h after infusion of 500 ml of Haemaccel. A transient decline to 50% of its initial value then occurred the second day after the infusion. Therefore, a delay existed between the formation of fibronectin-Haemaccel complexes and their elimination from the bloodstream. This delay decreased when smaller volumes of Haemaccel were infused, which strongly suggests that plasma fibronectin is cleared by means of Haemaccel and does not seem to play a role of opsonin in these conditions. Besides, after Haemaccel infusion, the recovery time of the gelatin binding function of plasma fibronectin most probably reflects the blood turnover of this domain of the molecule. The production rate of new fibronectin molecules appears to be about 90 μg ml−1 day−1, which corresponds to a half-recovery time of about 40 h.