Functional abdominal pain disorders and patient- and parent- reported outcomes in children with inflammatory bowel disease in remission

BACKGROUND: Chronic abdominal pain occurs frequently in pediatric patients with inflammatory bowel disease (IBD) in remission. AIMS: To assess the prevalence and factors associated with Functional Abdominal Pain Disorders among IBD children in remission (IBD-FAPD). METHODS: Patients with IBD for > 1 year, in clinical remission for ≥ 3 months were recruited from a National IBD network. IBD-FAPDs were assessed using the Rome III questionnaire criteria. Patient- or parent- reported outcomes were assessed. RESULTS: Among 102 included patients, 57 (56%) were boys, mean age (DS) was 15.0 (± 2.0) years and 75 (74%) had Crohn's disease. Twenty-two patients (22%) had at least one Functional Gastrointestinal Disorder among which 17 had at least one IBD-FAPD. Past severity of disease or treatments received and level of remission were not significantly associated with IBD-FAPD. Patients with IBD-FAPD reported more fatigue (peds-FACIT-F: 35.9 ± 9.8 vs. 43.0 ± 6.9, p = 0.01) and a lower HR-QoL (IMPACT III: 76.5 ± 9.6 vs. 81.6 ± 9.2, p = 0.04) than patients without FAPD, and their parents had higher levels of State and Trait anxiety than the other parents. CONCLUSIONS: Prevalence of IBD-FAPD was 17%. IBD-FAPD was not associated with past severity of disease, but with fatigue and lower HR-QoL

Modeling Immunization To Infliximab in Children With Crohn’s Disease Using Population Pharmacokinetics: A Pilot Study

International audienceBackground - Antidrug antibodies (ADAs) dramatically increase infliximab clearance and are responsible for underexposure to the drug, leading to treatment failure. This pilot study aimed at developing a population pharmacokinetic model to detect and describe an early increase in infliximab clearance due to ADA. Methods - Twenty children with Crohn's disease (CD) were followed for 1 year or until treatment failure. Infliximab trough concentration, ADA, C-reactive protein (CRP), and Paediatric Crohn's Disease Activity Index (PCDAI) were recorded at each visit. A time-varying clearance population pharmacokinetic model was built to detect and describe an increase in infliximab clearance, independent from ADA testing. Factors associated with clearance variation and the relationships between infliximab concentrations, clearance variation, and clinical response were investigated. Results - The model detected important increases in clearance in 4 patients. These patients had suboptimal early response, with higher mean PCDAI (P = 0.0086) and CRP (P = 0.028) compared with other patients. Two of them had detectable ADA. Clearance increase as described by the model and lower infliximab trough concentration at week 2 were associated with poorer outcomes in a multivariate Cox model (P = 0.001 and P = 0.0048, respectively). Conclusions - Being able to detect an increase in infliximab clearance, this model could allow the early detection of immunization to infliximab and therefore could help with dose adjustment in patients with CD. Moreover, the results suggest that clearance variations could be used as a predictive marker of clinical response. These findings need to be confirmed in a larger cohort, however, and predictive factors of clearance increase have to be investigated

Exocrine pancreatic insufficiency in a child with Netherton syndrome

International audienc

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

International audienceInfliximab is an anti-tumor necrosis factor monoclonal antibody approved in chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD) and ulcerative colitis (UC). Infliximab pharmacokinetics is variable between patients, but influence of the underlying disease was never assessed. This study aimed at assessing this influence using a cohort of patients monitored in a single center and with the same assay. Infliximab trough concentrations were determined on samples collected between weeks 0 and 22 after treatment initiation in 218 patients treated for RA, PsA, AS, CD or UC. Infliximab pharmacokinetics was analyzed by a one-compartment population model with first-order elimination rate constant. In AS patients, volume of distribution (V) and elimination clearance (CL) were 5.4 L and 0.24 L/day, respectively. In CD and UC patients, V was 49% and 52% higher than in AS, respectively, and CL was 47% and 60% higher than in AS, respectively. In RA patients, CL was 49% higher than in AS patients. Simulations showed that without methotrexate, a 3 mg/kg dosing regimen would lead only 16% of RA patients to reach the target concentration (2.5 mg/L) at week 22, whereas target concentrations would be reached in approximately half of RA patients cotreated with methotrexate, as well as half of CD (3.5 mg/L) and UC (3.7 mg/L) patients. The suboptimality of approved dosing regimens supports the development of dosing optimization based on concentration measurements

Vaccination coverage of children with inflammatory bowel disease after an awareness campaign on the risk of infection

International audienceBACKGROUND: Children with inflammatory bowel disease are at risk of vaccine-preventable diseases mostly due to immunosuppressive drugs. AIM: To evaluate coverage after an awareness campaign informing patients, their parents and general practitioner about the vaccination schedule. METHODS: Vaccination coverage was firstly evaluated and followed by an awareness campaign on the risk of infection via postal mail. The trial is a case-control study on the same patients before and after the awareness campaign. Overall, 92 children were included. A questionnaire was then completed during a routine appointment to collect data including age at diagnosis, age at data collection, treatment history, and vaccination status. RESULTS: Vaccination rates significantly increased for vaccines against diphtheria-tetanus-poliomyelitis (92% vs. 100%), Haemophilus influenzae (88% vs. 98%), hepatitis B (52% vs. 71%), pneumococcus (36% vs. 57%), and meningococcus C (17% vs. 41%) (p\textless0.05). Children who were older at diagnosis were 1.26 times more likely to be up-to-date with a minimum vaccination schedule (diphtheria-tetanus-poliomyelitis, pertussis, H. influenzae, measles-mumps-rubella, tuberculosis) (p=0.002). CONCLUSION: Informing inflammatory bowel disease patients, their parents and general practitioner about the vaccination schedule via postal mail is easy, inexpensive, reproducible, and increases vaccination coverage. This method reinforces information on the risk of infection during routine visit

A European Survey on Digestive Perianastomotic Ulcerations, a Rare Crohn-like Disorder Occurring in Children and Young Adults

International audienceObjectives: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat.Methods: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU.Results: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1–23] months, and first symptoms occurred 39 [22–106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19–67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%).Conclusions: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology

Management of Central Venous Catheters in Children and Adults on Home Parenteral Nutrition: A French Survey of Current Practice

Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study

Background and Aims: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases {[}VEO-IBD]. The present study aimed at defining how next-generation sequencing {[}NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network {[}ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD {[}n = 185] or an anamnesis suggestive of a monogenic disorder {[}n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing {[}WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results: Molecular diagnosis was achieved in 66/207 children {[}32\%]: 61\% with small bowel inflammation, 39\% with colitis and perianal lesions, and 18\% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD

Avtomatika i telemechanika

(Abridged) The Maunakea Spectroscopic Explorer (MSE) is an end-to-end science platform for the design, execution and scientific exploitation of spectroscopic surveys. It will unveil the composition and dynamics of the faint Universe and impact nearly every field of astrophysics across all spatial scales, from individual stars to the largest scale structures in the Universe. Major pillars in the science program for MSE include (i) the ultimate Gaia follow-up facility for understanding the chemistry and dynamics of the distant Milky Way, including the outer disk and faint stellar halo at high spectral resolution (ii) galaxy formation and evolution at cosmic noon, via the type of revolutionary surveys that have occurred in the nearby Universe, but now conducted at the peak of the star formation history of the Universe (iii) derivation of the mass of the neutrino and insights into inflationary physics through a cosmological redshift survey that probes a large volume of the Universe with a high galaxy density. MSE is positioned to become a critical hub in the emerging international network of front-line astronomical facilities, with scientific capabilities that naturally complement and extend the scientific power of Gaia, the Large Synoptic Survey Telescope, the Square Kilometer Array, Euclid, WFIRST, the 30m telescopes and many more