Les pancréatites aiguës en réanimation pédiatrique : étude rétrospective monocentrique multi-sites française

Background: acute pancreatitis (AP) incidence has increased dramatically over the past years. New guidelines in 2018 were recently published in order to standardize the definition and management of AP. The aim of this study is to describe the management of children that were diagnosed with AP from the pediatric intensive care unit (PICU) in two French hospitals. Methods: this retrospective cohort study included children aged under 18 years old, who were admitted to the PICU of Robert-Debré hospital and Trousseau from 2006 to 2018 with a discharge diagnosis of AP. Data collected included management, severity and outcomes. We have also obtained data on clinical, biological and radiological presentation. Results: sixty patients were included, the median age was 8 [5-14] years and 75% had a co-morbidity mainly hematologic (26/60). Most of the AP were moderate (52%) or severe (45%). Hemodynamic failure was the main reason for PICU admission requiring a median fluid resuscitation of 56 ml/kg complemented by a median intravenous fluid therapy of 4 [2-5] ml/kg/h during the first 24 hours. Fasting has been instituted to 59 patients (98%) for a median of 4 [1-6] days, 54 patients (90%) received parenteral nutrition and 18 patients (30%) received enteral nutrition. Antibiotic therapy was given to 53 patients (88%) including 13% for curative therapy. The median length of stay in PICU was 4 [2-6] days. The mortality rate was 13%. Conclusion: this is the first French study which precisely described the management of patients with AP in PICU. It highlighted the differences with the new international guidelines. This study could improve the management of PA in PICU.Contexte : l’incidence de la pancréatite aiguë (PA) en pédiatrie est en augmentation. De nouvelles recommandations pédiatriques ont été publiées en 2018 afin de standardiser la définition et la prise en charge des PA. L’objectif de cette étude était de décrire la prise en charge des patients hospitalisés en unité de réanimation pédiatrique (URP) pour une PA au sein de deux centres français. Méthode : cohorte rétrospective monocentrique multi-sites regroupant des patients âgés de 0 à 18 ans hospitalisés en URP à l’hôpital Robert-Debré et Trousseau entre 2006 et 2018 pour une PA. Les traitements, la sévérité, l’étiologie, les données de la présentation clinique, biologique et de l’imagerie ont été relevés ainsi que les données d’évolution. Résultats : soixante patients ont été inclus avec un âge médian de 8 [5-14] ans dont 75% présentaient une co-morbidité principalement hématologique (26/60). La majorité des PA étaient modérées (52%) ou sévères (45%). Le principal motif d’admission était la défaillance hémodynamique nécessitant un volume médian de remplissage vasculaire de 56 ml/kg complété par une hydratation médiane de 4 [2-5] ml/kg/h. La mise à jeun concernait 59 patients (98%) pour une durée médiane de 4 [1-6] jours, une nutrition entérale a été administrée à 18 patients (30%) et une nutrition parentérale à 54 patients (90%). Une antibiothérapie a été administrée à 53 patients (88%) dont 8 (13%) à visée curative. Le délai médian d’hospitalisation en URP était de 4 [2-6] jours avec une mortalité à la sortie de 13%. Conclusion : cette première étude française sur les PA en URP permet d’analyser nos pratiques et de les comparer aux récentes recommandations internationales

Preschool-age children maintain a distinct memory CD4 + T cell and memory B cell response after SARS-CoV-2 infection

International audienceThe development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–reactive CD3 + CD4 + CD154 + T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4 + T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4 + T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2–reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner

Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.

BACKGROUND The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients. METHODS In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated. RESULTS The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup "SHH_3" (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received post-operative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively). CONCLUSIONS LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients

Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome

Background: The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients. Methods: In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated. Results: The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup "SHH_3"(86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively). Conclusions: LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients. © 2023 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children

International audienc