Perianal Pediatric Crohn Disease Is Associated With a Distinct Phenotype and Greater Inflammatory Burden

Objectives: Data on the outcomes of children with perianal Crohn disease (pCD) are limited, although its presence is often used for justifying early use of biologics. We aimed to assess whether pCD in children is associated with more severe outcomes as found in adults. Methods: Data were extracted from the ImageKids database, a prospective, multicenter, longitudinal cohort study. The study enrolled 246 children at disease onset or thereafter. All patients underwent comprehensive clinical, endoscopic, and radiologic evaluation at enrollment;98 children had repeat evaluation at 18 months. Results: Of the 234 included patients (mean age 14.2 +/- 2.4 years;131 [56%] boys), 57 (24%) had perianal findings, whereas only 21 (9%) had fistulizing perianal disease. Children with pCD had reduced weight and height z scores compared with non-pCD patients (-0.9 vs -0.35, P = 0.03 and -0.68 vs -0.23, respectively;P = 0.04), higher weighted pediatric CD activity index (32 [interquartile range 16-50] vs 20 [8-37];P = 0.004), lower serum albumin (3.6 +/- 0.7 vs 4.5 +/- 0.8, P = 0.016), and higher magnetic resonance enterography global inflammatory score (P = 0.04). Children with pCD had more rectal (57% vs 38%, P = 0.04), and jejunal involvement (31% vs 11% P = 0.003) and a higher prevalence of granulomas (64% vs 23%, P = 0.0001). Magnetic resonance enterography-based damage scores did not differ between groups. Patients with skin tags/fissures only, had similar clinical, endoscopic, and radiologic characteristics as patients with no perianal findings. Conclusions: Pediatric patients with pCD with fistulizing disease have distinct phenotypic features and a predisposition to a greater inflammatory burden

Magnetic Resonance Enterography Cannot Replace Upper Endoscopy in Pediatric Crohn Disease: An Imagekids Sub-study

Objectives: Although magnetic resonance enterography (MRE) can accurately reflect ileal inflammation in pediatric Crohn disease (CD), there are no pediatric data on the accuracy of MRE to detect upper gastrointestinal tract (UGI) lesions. We aimed to compare MRE and esophagogastroduodenoscopy (EGD) in detecting the spectrum and severity of UGI disease in children. Methods: This is an ancillary study of the prospective multi-center ImageKids study focusing on pediatric MRE. EGD was performed within 2 weeks of MRE (at disease onset or thereafter) and explicitly scored by SES-CD modified for the UGI and physician global assessment. Local and central radiologists scored the UGI region of the MRE blinded to the EGD. Accuracy of MRE compared with EGD was examined using correlational coefficients (r) and area under receiver operating characteristic curves (AUC). Results: One hundred and eighty-eight patients were reviewed (mean age 14 +/- 1 years, 103 [55%] boys);66 of 188 (35%) children had macroscopic ulcerations on EGD (esophagus, 13 [7%];stomach, 34 [18%];duodenum, 45 [24%]). Most children had aphthous ulcers, but 10 (5%) had larger ulcers (stomach, 2 [1%];duodenum, 8 [4%]). There was no agreement between local and central radiologists on the presence or absence of UGI inflammation on MRE (Kappa=0.02, P - 0.71). EGD findings were not accurately detected by MRE, read locally or centrally (r=-0.03 to 0.11, P = 0.18-0.88;AUC - 0.47-0.55, P = 0.53-1.00).No fistulae or narrowings were identified on either EGD or MRE. Conclusions: MRE cannot reliably assess the UGI in pediatric CD and cannot replace EGD for this purpose

Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma:a prospective multicentre study

Objectives To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL) Methods Children with newly diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis. Results Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (kappa= 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging. Conclusions WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Retrospective Review of Current Nasojejunal Tube Insertion Practice

Repeated fluoroscopically guided nasojejunal tube (NJT) insertions, particularly in children, can pose health risks through increased radiation exposure. We analyzed frequency of NJT reinsertions and associated radiation exposure through retrospective evaluation of children <18 years at our institution who underwent fluoroscopically guided NJT insertions from 2007 to 2012. Age and weight, reinsertion frequency per patient, radiation dose (dose actual percentage [DAP]), time interval between, and indication for reinsertion were recorded. A total of 252 children (3 days to17 years, 11 months) had 449 NJT insertions. Reinsertions occurred in 105 (41.7%) patients with 14 (5.6%) having ≥5 reinsertions, and 67.6% of reinsertions occurring in patients <1 year. Mean DAP increased with frequency of reinsertion, along with age and weight. Most common indication for reinsertion was a pulled NJT (34.0%). Fluoroscopic NJT reinsertion was most frequent in younger, smaller patients. Self-guided, bedside NJT insertion, and/or earlier instigation of definitive nutritional therapy delivery should be considered