Questionnaire de connaissance de l’AJD pour les enfants et les adolescents ayant un diabète de type 1

Objectifs : Élaborer et valider un questionnaire de connaissance pour les enfants et les adolescents ayant un diabète de type 1 (DT1) et leurs parents. Patients et méthodes : Le questionnaire a été élaboré à partir d’un outil publié pour l’éducation initiale du diabète de type 1, les Cahiers de l’AJD, avec la participation de 1 576 jeunes de 10–20 ans ayant un DT1, 466 parents, 33 services de pédiatrie et huit maisons sanitaires de l’AJD (Aide aux jeunes diabétiques). À partir de 310 questions initiales de type Vrai-Faux, la sélection de 50 questions a été basée sur l’expertise de la commission pédagogique de l’AJD, la reproductibilité des questions (test-retest) et l’analyse statistique par méthode de variance minimum de Ward. Le questionnaire final a ensuite été administré à 2 933 jeunes de 10–20 ans (âge 14,1 + 2,5 ans, durée du diabète 5,5 ± 3,6 ans, HbA1c 8,25 ± 1,54 %) et 2 978 parents pour établir des références avec l’âge et évaluer les associations avec l’équilibre glycémique. Résultats : Le questionnaire est un reflet fidèle du programme d’éducation des Cahiers de l’AJD. Le questionnaire est faisable (temps de passage 5–15 min), reproductible et sensible : nombres moyens de bonnes réponses significativement différents entre filles et garçons (37,8 ± 5,7 vs 37,2 ± 6,0), entre mères et pères (40,3 ± 5,4 vs 38,5 ± 5,7) et pour des intervalles d’âge de un à deux ans. Le pourcentage de bons répondeurs est très variable d’une question à l’autre : il augmente avec l’âge pour 39 questions, mais ne varie pas pour 7 et diminue même pour 4. Les associations entre le nombre de bonnes réponses au questionnaire, l’équilibre glycémique et d’autres facteurs, font l’objet d’une autre publication. Conclusion : La publication du questionnaire de connaissance de l’AJD et des résultats pour chaque question en fonction de l’âge permet de disposer d’un outil et de références utilisables en clinique et en recherche pour l’évaluation des connaissances des jeunes de 10–20 ans ayant un DT1 et de leurs parents

Autoantibodies against podocytic UCHL1 are associated with idiopathic nephrotic syndrome relapses and induce proteinuria in mice

International audienc

Primary hyperoxaluria in adults and children: a nationwide cohort highlights a persistent diagnostic delay

International audienceABSTRACT Background Primary hyperoxalurias (PH) are extremely rare genetic disorders characterized by clinical heterogeneity. Delay in diagnosing these conditions can have detrimental effects on patient outcomes. The primary objective of this study is to assess the current diagnostic delay for PH. Methods This nationwide, observational and retrospective study included patients who received a genetic diagnosis of PH types 1, 2 and 3 between 1 January 2015 and 31 December 2019. Diagnostic delay was defined as the duration between the onset of symptoms and the time of genetic diagnosis. Results A total of 52 patients (34 children and 18 adults) were included in the study, with 40 PH1 (77%), 3 PH2 (6%) and 9 PH3 (17%). At the time of diagnosis, 12 patients (23%) required dialysis. Among the PH1 patients, the predominant symptom at onset in adults was renal colic (79% of cases), whereas symptoms in children were more diverse (renal colic in 17% of cases). The diagnostic delay was significantly shorter in children compared with adults [median (interquartile range)]: 1.2 (0.1–3.0) versus 30 (17–36) years, respectively (P < .0001). RNA interference was utilized in 23 patients (58%). Five individuals (13%) underwent double liver–kidney transplantation, and five (13%) received isolated kidney transplantation, with lumasiran therapy in four patients. For PH2 and PH3 patients, the diagnostic delay ranges from 0 to 3 years, with renal colic as first symptom in 33% of cases. Conclusion This extensive and recent cohort of PH underscores the considerable delay in diagnosing PH, particularly in adults, even in a country with a dedicated organization for enhancing the overall management of rare diseases. These findings reinforce the imperative for increased awareness among relevant specialties regarding the evaluation of urolithiasis

Characteristics and outcome of adults with severe autoimmune hemolytic anemia admitted to the intensive care unit: Results from a large French observational study

Adult'autoimmune hemolytic anemia (AIHA), which is often seen as a rare and "benign" autoimmune hematological disease, can be lifethreatening with an overall mortality rate from 8% to 20% depending on the series 1-3 and a short-term mortality rate that can be up to 30% in intensive care units (ICUs). 4 Factors associated with the need for ICU management of patients with severe AIHA remain partially unknown because only few data are available in the literature. 3-5 The aims of this retrospective observational multicenter study set up by the French reference center for adult immune cytopenias were to: (1) better describe the baseline characteristics and outcome of adults with severe AIHA admitted to an ICU, (2) investigate the factors associated with mortality in the ICU, and (3) identify factors at AIHA diagnosis associated with admission to an ICU. To be included in the study, patients had to (1) be ≥16 years old at the time of AIHA onset; (2) have a diagnosis of AIHA defined as hemoglobin level <12 g/dL, with ≥2 features of hemolysis among low haptoglobin level and/or elevated lactate dehydrogenase (LDH) level and/or elevated free bilirubin level, and a positive direct antiglobulin test (DAT) with no other cause of acquired or hereditary hemolytic anemia; and (3) at least one admission to an ICU specifically for AIHA management between January 2013 and December 2020. We excluded patients with nonautoimmune hemolytic anemia, DAT-negative AIHA and drug-induced immune hemolytic anemia and those admitted to the ICU for another reason than severity of AIHA. Baseline data in the ICU included the Charlson Comorbidity Index, the Knaus score, the Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Scor

Pediatr Nephrol

BACKGROUND: Pediatric ANCA vasculitis is a rare group of diseases with a scarcity of data in children. Annual incidence appeared to increase in the last several years, placing higher interest in the clinical and therapeutical outcomes of the disorder. Also, the growing use of rituximab questions the latest outcomes in these diseases. We therefore conducted a retrospective study to better understand the current characteristics, management, and the latest outcomes of the disorder. METHODS: We conducted a 9-year retrospective study of 46 children in 14 different centers across France to describe their clinical and laboratory presentations, therapeutic regimens, and kidney outcome. RESULTS: P-ANCA appeared to be a potential marker for higher relapse risk. Compared to adults, we found that ear-nose-throat presentations were frequent (45.7%) and more severe. Despite an evolution in the treatment management, kidney outcome remained poor with a substantial proportion of chronic kidney disease (54.8% at 1 year). Mortality stays low with 3 patients (6.5%) deceased at the end of our study. CONCLUSION: Clinical presentation was as previously described and time to diagnosis remains long. P-ANCA is a statistically significant marker for increased relapse risk. We observed a modification in the treatment regimens over the past several years with a growing use of rituximab and a decreasing use of cyclophosphamide. Despite these changes, kidney outcome remains poor and prospective studies should be conducted to assess the most appropriate therapeutic modality for each patient. A higher resolution version of the Graphical abstract is available as Supplementary information

Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome

International audienceBackground Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort.Methods We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular cis-expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts.Results Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3' untranslated region of HLA-DQB1 (P=9.3×10-23). Conditional analysis identified two additional independent risk alleles upstream of HLA-DRB1 (rs28366266, P=3.7×10-11) and in the 3' untranslated region of BTNL2 (rs9348883, P=9.4×10-7) within introns of HCG23 and LOC101929163 These three risk alleles were independent of the risk haplotype DRB1*07:01-DQA1*02:01-DQB1*02:02 identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1.Conclusions Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification