Etude descriptive de la mortalité des patients traités par hormone de croissance synthétique dans l enfance après la prise en charge d'un cancer (données de l étude SAGhE en France)

L étude Safety and Appropriateness of Growth hormone treatments in Europe complète les résultats des études précédentes concernant le devenir à long terme des patients traités par hormone de croissance (GH) dans l enfance. L objectif de mon travail est la description de la mortalité et de ses causes chez les patients traités par GH dans les suites d un cancer en France.Les critères d inclusion sont : traitement par GH recombinante entre 1985 et 1997 et âge supérieur à 18 ans au 31 décembre 2007. Parmi eux, 1100 enfants ont été traités dans les suites d un cancer. Les données du RNIPP, du RNIAM et du CépiDC ont été recueillies pour évaluer le statut vital et les causes de décès.Le suivi médian de notre population est 17.2 ans. L âge théorique moyen est 28.7ans. Les tumeurs initiales les plus fréquentes sont les tumeurs du système nerveux central (56.9%) et les leucémies (22.7%) 170 patients sont décédés (15.5% de la population initiale) : 64% en lien avec la tumeur initiale et 24.1% en lien avec un nouveau cancer, parmi lesquels 50 % de tumeurs cérébrales (principalement gliomes et astrocytomes) et 21.7% d ostéosarcomes. Les rétinoblastomes sont les tumeurs initiales les plus fréquemment associées au décès lié à une seconde tumeur (62%), suivi par les leucémies (37.5%), les gliomes et astrocytomes (24%) et les médulloblastomes (21%). Les traitements par GH sont prescrits aux patients à faible potentiel tumoral évolutif mais le pronostic global reste préoccupant et un décès sur 4 est secondaire à une seconde tumeur. Des études comparant le devenir à long terme de patients traités par GH à celui de patients non traités devront compléter les données actuelles.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Risk of Diabetes Treated in Early Adulthood After Growth Hormone Treatment of Short Stature in Childhood

International audienc

Whole Goat Milk-Based Formula versus Whey-Based Cow Milk Formula: What Formula Do Infants Enjoy More?—A Feasibility, Double-Blind, Randomized Controlled Trial

(1) Background: While goat milk formula (GMF) is an alternative to cow milk formula (CMF), infants’ preferences for one over the other have not been formally assessed. Specifically, our aim in this study was to determine whether infants experience fewer feeding behavior problems with whole milk-based GMF than with conventional whey-based CMF. (2) Methods: This was a multicenter, double-blind, randomized controlled trial with two-arm parallel assignment conducted in six pediatricians’ offices in or near Paris, France, between June 2018 and 31 December 2021. Overall, 64 healthy infants (≤4 months old), predominantly formula-fed, were randomly assigned to either the whole milk-based GMF (n = 33) or whey-based CMF (n = 31) arm. Parents completed the Baby Eating Behavior Questionnaire (BEBQ) and the modified QUALIN questionnaire to evaluate infant feeding behavior and quality of life (psychomotor and socioemotional development), respectively, at inclusion (1 to 5 days before milk delivery) and the final visit (day 28 ± 3 after milk delivery). Informed consent was obtained for all recruited patients, and an ethical committee approved the study. (3) Results: Changes in BEBQ Enjoyment of Food and Slowness in Eating subscale scores from inclusion to final visit did not differ between arms. However, there were significant improvements in subscale scores for Food Responsiveness (GMF: 0.15 ± 1; CMF: −0.48 ± 0.81; p = 0.010) and General Appetite (GMF: 0.26 ± 1.2; CMF: −0.48 ± 0.88; p = 0.012), and modified QUALIN (GMF: 4.6 ± 9.4; CMF: −0.40 ± 7.6; p = 0.03) scores in favor of the GMF group. (4) Conclusions: In this double-blind, randomized controlled trial, GMF-fed infants exhibited a greater general appetite than CMF-fed infants, possibly due to differences in the composition of these formulas (i.e., protein and lipid profiles). In addition, GMF-fed infants enjoyed a better quality of life. There was no difference in food enjoyment between groups. These findings suggest that whole-milk-based GMF could be an attractive alternative to whey-based CMF. Clinical trial registration: NCT03488758 (clinicaltrials.gov)

Outcomes of hybrid closed‐loop insulin delivery activated 24/7 versus evening and night in free‐living prepubertal children with type 1 diabetes: A multicentre, randomized clinical trial

International audienceAims: To assess the safety and efficacy of hybrid closed-loop (HCL) insulin delivery 24/7 vs. only evening and night (E/N), and on extended 24/7 use, in free-living children with T1D.Materials and methods: Pre-pubertal children (n = 122; 49F/73M, age: 8.6 ± 1.6, diabetes duration: 5.2 ± 2.3 years, insulin pump use: 4.6 ± 2.5 years, HbA1c: 7.7 ± 0.7%/61 ± 5 mmol/mol) from 4 centers were randomized for 24/7 vs. E/N activation of the Tandem Control-IQ system for 18 weeks. Afterwards, all children used the activated system 24/7 for 18 more weeks. Primary outcome was %time spent in 70-180 mg/dL glucose range (TIR).Results: HCL was active 94.1% and 51.1% of time on 24/7 and E/N modes, respectively. TIR from baseline increased more on 24/7 vs. E/N: 52.9 ± 9.5 to 67.3 ± 5.6 (+14.4%, 95CI: 12.4-16.7%) vs. 55.1 ± 10.8 to 64.7 ± 7.0 (+9.6%, 95CI: 7.4-11.6%), p = 0.001. Mean %time below range was similarly reduced from 4.2 and 4.6 to 2.7, and mean %time above range more on 24/7 mode: 41.9 to 30.0 (-11.9%, 95CI: 9.7-14.6%) vs. 39.8 to 32.6 (-7.2%, 95CI: 5.0-9.9%), p = 0.007. TIR increased through the whole range of baseline levels and always more with 24/7 use. The results were maintained during extension phase in those initially on 24/7 use and improved in those with initial E/N use up to those with 24/7 use. Neither ketoacidosis nor severe hypoglycemia occurred.Conclusions: Our study demonstrates the safety and efficacy of Tandem Control-IQ system in free-living children with T1D for both E/N and 24/7 use. 24/7 use shows better outcomes, sustained for up to 36 weeks with no safety issue. This article is protected by copyright. All rights reserved

Hybrid Closed Loop Overcomes the Impact of Missed or Suboptimal Meal Boluses on Glucose Control in Children with Type 1 Diabetes Compared to Sensor-Augmented Pump Therapy

International audienceBackground: It is unclear whether hybrid closed-loop (HCL) therapy attenuates the metabolic impact of missed or suboptimal meal insulin bolus compared with sensor-augmented pump (SAP) therapy in children with type 1 diabetes in free-living conditions. Methods: This is an ancillary study from a multicenter randomized controlled trial that compared 24/7 HCL with evening and night (E/N) HCL for 36 weeks in children between 6 and 12 years old. In the present study, the 60 children from the E/N arm underwent a SAP phase, an E/N HCL for 18 weeks, then a 24/7 phase for 18 weeks, extended for 36 more weeks. The last 28-30 days of each of the four phases were analyzed according to meal bolus management (cumulated 6817 days). The primary endpoint was the percentage of time that the sensor glucose was in the target range (TIR, 70-180 mg/dL) according to the number of missed boluses per day. Findings: TIR was 54% ± 10% with SAP, 63% ± 7% with E/N HCL, and steadily 67% ± 7% with 24/7 HCL. From the SAP phase to 72 weeks of HCL, the percentage of days with at least one missed meal bolus increased from 12% to 22%. Estimated marginal (EM) mean TIR when no bolus was missed was 54% (95% confidence intervals [CI] 53-56) in SAP and it was 13% higher (95% CI 11-15) in the 24/7 HCL phase. EM mean TIR with 1 and ≥2 missed boluses/day was 49.5% (95% CI 46-52) and 45% (95% CI 39-51) in SAP, and it was 15% (95% CI 14-16) and 17% higher (95% CI 6-28), respectively, in the 24/7 HCL phase (P < 0.05 for all comparisons vs. SAP). Interpretation: HCL persistently improves glycemic control compared with SAP, even in case of meal bolus omission. ClinicalTrials.gov (NCT03739099)

Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway

International audienceHoloprosencephaly (HPE) is the most common congenital cerebral malformation in humans, characterized by impaired forebrain cleavage and midline facial anomalies. It presents a high heterogeneity, both in clinics and genetics. We have developed a novel targeted next-generation sequencing (NGS) assay and screened a cohort of 257 HPE patients. Mutations with high confidence in their deleterious effect were identified in approximately 24% of the cases and were held for diagnosis, whereas variants of uncertain significance were identified in 10% of cases. This study provides a new classification of genes that are involved in HPE. SHH, ZIC2, and SIX3 remain the top genes in term of frequency with GLI2, and are followed by FGF8 and FGFR1. The three minor HPE genes identified by our study are DLL1, DISP1, and SUFU. Here, we demonstrate that fibroblast growth factor signaling must now be considered a major pathway involved in HPE. Interestingly, several cases of double mutations were found and argue for a polygenic inheritance of HPE. Altogether, it supports that the implementation of NGS in HPE diagnosis is required to improve genetic counseling