Objectives and Study

Primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed under the age of 6 years (i.e.VEO-IBD) may have unique characteristics and disease course. We aimed to analyze the characteristics and natural history of children with VEO PSC-IBD and compare them to children diagnosed with PSC-IBD at an older age.

Methods

This was a multicenter, retrospective, study evaluating patients diagnosed with both IBD and PSC before (VEO-PSC-IBD) or after the age of 6 years (PSC-IBD), followed at 14 centers affiliated with the Porto IBD Interest group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every six months thereafter for a minimum follow-up of 12 months. Outcomes were analyzed at 1, 3 and 5 years

Results

A total of 69 children with both IBD and PSC were included: 28 with VEO PSC-IBD [median age 5.2 years, 21 UC (75%)] and 41 with PSC-IBD [median age 15.7 years, 34 UC (83%)]. Most patients with UC presented with extensive disease at diagnosis (89% in VEO PSC-UC vs. 89% in PSC-UC, p=0.72). Both groups presented most often with mild intestinal disease at diagnosis (mean PUCAI of VEO IBD-PSC 34±16, vs 31±19 of IBD-PSC, p=0.11). A higher number of VEO-IBD-PSC patients were diagnosed with autoimmune SC than older children [24 (86%) vs. 27 (66%) PSC-IBD, p=0.04], whereas no other differences were found for PSC-related variables. The risk of developing biliary strictures and starting vancomycin after ursodehoxicolic acid was lower in the VEO-PSC-IBD group (Log-rank p=0.02 and p=0.02), while no difference was found for portal hypertension and liver transplantation at 5-year follow-up. No cases of cholangiocarcinoma or death were found.

Conclusions

IBD-PSC has similar baseline characteristics whether diagnosed as VEOIBD or thereafter. However, a milder disease course in terms of biliary complications and the need for PSC-related therapy escalation characterize the VEOIBD subcohort.

Objectives and Study

Pediatric inflammatory bowel disease increases globally, but the incidence has been reported to stabilize in adults. Differences in incidence across geographic regions and time suggest that environmental factors are important in the etiology. We therefore aimed to study whether the incidence is still increasing, and whether there is a regional difference in incidence.

Methods

We analyzed data from those born in Norway from 2004-2012 identified in the Medical Birth Registry (n=541 000). Diagnostic codes indicative for IBD were retrieved from the nationwide Norwegian Patient Registry by end of 2020, and ≥2 ICD-10 codes K50, K51 and K523 defined the cases. We studied geographical differences based on the county of birth, comparing five geographical regions of Norway by latitude. Hazard ratios were adjusted for sex, maternal characteristics (age, parity, education, smoking status) and perinatal factors (mode of delivery, birthweight, preterm birth).

Results

We identified 799 cases by the end of 2020: 465 had Crohn’s disease, 293 had ulcerative colitis and 41 IBD-U. The cumulative incidence was similar for those born in 2010-2012 compared to 2004-2006, but somewhat higher for those born in 2007-2009 (Figure).

The risk of IBD was higher in the Northern (adjusted HR 2.27, 95%CI 1.49-3.44) and Mid region (HR 1.92, 1.28-2.89) compared to the southernmost region. Also for the two regions closest to the southernmost the risk was somewhat higher (HR 1.46 and 1.55, respectively, both p=0.05). The regional difference was driven mainly by differences in Crohns disease, though also ulcerative colitis had higher incidence in the Northern region (HR 2.50, 1.36-4.59).

Conclusions

The data might indicate that the increasing incidence in pediatric IBD observed in our high-income and high-incidence country is stabilizing. The difference from north to south within a homogenous population is likely driven by environmental factors that are differently distributed.

Objectives and Study

Ecological observations suggest socioeconomic status (SES) in childhood affects the risk of later inflammatory bowel disease (IBD). While individual-level analyses have been inconsistent, they have mostly lacked refined assessments of SES exposure. We aimed to comprehensively study the association between early-life SES and later IBD.

Methods

This study included 117,493 participants from the Norwegian MoBa and Swedish ABIS cohorts, followed from birth (1997–2009) until the end of 2021. IBD diagnoses were identified through national registers. Questionnaire and register data from birth provided data on measures of SES, including maternal and paternal educational level, maternal and paternal occupational status, and household income level. Cox model was used to estimate hazard ratios (HRs) mutually adjusted for other exposures (Model I) and confounders, e.g., IBD heredity (Model II). Cohort-specific estimates were pooled using a random-effects model.

Results

A total of 451 participants (ABIS, n=113; MoBa, n=338) were diagnosed with IBD over 2,026,362 person-years (PYR) of follow-up (incidence; ABIS, 31/100,000 PYR; MoBa, 20/100,000 PYR). Low maternal educational level in early life was associated with an increased risk of later IBD (pooled mutually adjusted HR [aHR]=1.50; 95%CI=1.08–2.08). In adjusted models, maternal unemployment status and high household income level were non-significant factors linked to IBD (Figure 1), particularly Crohn’s disease (data not shown). Results were largely consistent across ABIS and MoBa.

Figure 1. Measures of early-life socioeconomic status and risk of inflammatory bowel disease. Model I, mutually adjusted for other exposures. Model II, additionally adjusted for sex, exclusive breastfeeding duration, parental IBD, parental origin, maternal age, maternal comorbidity (type 1 diabetes, rheumatoid arthritis, thyroid disease), and maternal smoking during pregnancy.

Conclusions

This prospective Scandinavian cohort study showed an association between early-life SES, including maternal educational level, and subsequent IBD. Further studies are needed to assess what modifiable factors that may mediate the link between early-life SES and later IBD.

Objectives and Study

Preterm neonates are at risk for late-onset sepsis (LOS), the leading cause of morbidity and mortality at neonatal intensive care units (NICUs). Considering the frequent use of antibiotics, we hypothesize that fungi play an important role in preterm intestinal physiology, and that this may contribute to E.coli-induced LOS development.

Methods

Preterm neonates (n=20) from two Dutch NICUs who were diagnosed with E. coli caused LOS (n=10) were matched to healthy preterm neonates (n=10) based on birth center, birth weight and antibiotic use. Longitudinal mycobiome profiles were determined with Internal Transcribed Spacer-1 (ITS1) sequencing on isolated fecal DNA. A gradient boosting model identified fungal amplicon sequence variants most predictive for E.coli-induced LOS. Consequently, the possible role of Candida parapsilosis (Cp) was studied in the preterm intestine using human fetal colonoids and mucosal immune cells derived from fetal intestinal tissues (18-21 weeks of gestation). Cp-induced epithelial barrier loss was assessed by trans epithelial resistance (TEER). E.coli translocation was determined by basolateral E.coli concentrations after 6 hours of infection. Inflammatory responses were measured by cytokine levels, using cytokine bead array.

Results

C.parapsilosis was determined as most predictive for E.coli-induced LOS. When colonoid monolayers (n=5 donors) were exposed to Cp derived conditioned media (CDM) for 5 days, relative TEER levels were decreased by 22% (p=0.016). Additional 6 hour E.coli infection, showed an increased trend of relative E.coli translocation after a 5 days Cp CDM exposure (n=4). Inflammatory epithelial IL8 responses (n=3) towards Cp CDM were increased basolaterally compared to control. When exposed to living Cp for 24 hours, the inflammatory response of mucosal immune cells was prominently characterized by increased IL1β cytokine secretion compared to control (n=4, p=0.008).

Conclusions

Our results suggest that increased abundance of intestinal C.parapsilosis in preterm neonates could precede E.coli LOS by potentially mediating intestinal barrier dysfunction and pro-inflammatory responses.

Objectives and Study

Eosinophilic esophagitis (EoE) is an increasingly common cause of esophageal symptoms in children and adolescents, significantly impacting physical health and quality of life. In the past decade, EoE prevalence has rapidly risen throughout the Western world. We aimed to describe trends in EoE incidence in the pediatric population.

Methods

A retrospective population-based study was conducted in a 2.6 million-member health maintenance organization in Israel. The cohort included all patients with newly diagnosed EoE based on their electronic medical records. Data were analyzed for the years 2014-2021. To assess whether changes in incidence can be explained by a general increase in the use of endoscopies, we compared the trends in EoE incidence rate to the trends of the number of esophagogastroduodenoscopies (EGDs) tests performed during the same time in the general pediatric population.

Results

During the study period (5.6 million person-years), the overall pediatric incidence rate of EoE diagnosis increased by 101% from 6.2 per 100,000 in 2014 to 12.5 per 100,000 person-years in 2021. During the same period, the rate of pediatric patients undergoing EGDs increased slightly by 17% from 277 per 100,00 person-years to 324 per 100,000 person-years. There was an Increase rate of EoE diagnosis in all age groups. The most dominant group was adolescents, whose incidence rate increased from 6.3 to 15.5 per 100,000 person-years. The prevalence in 2021 among children and adolescents was 56.5 for 100,000.

Conclusions

The incidence of EoE increased twofold in our cohort between the years 2014-2021. The minor increase in the rate of EGDs performed in the same period implies that the increased incidence rate is genuine and not related to increased healthcare utilization.

Objectives and Study

Multispectral optoacoustic tomography (MSOT) is capable to non-invasively visualize endogenous and exogenous chromophores in various human tissues. The intravenous application of indocyanine green (ICG), a clinical approved fluorescent dye, already allows for mapping of lymphatic and vascular networks. We present a translational study, reaching from phantom experiments to a human clinical trial, for intraluminal detection of ICG for non-radiant bed-side evaluation of the gastrointestinal passage.

Methods

The optoacoustic properties of a blended standardized breakfast with and without ICG at different concentrations and pH levels were characterized in 3D-printed custom-made agarose phantom models. In a clinical study (clinicaltrial.gov ID NCT05160077) n=10 healthy subjects received a standardized breakfast with and without ICG on two different days and were imaged with MSOT over 8 hours and 24 hours after intake at four gastrointestinal segments (gastric antrum, terminal ileum, transverse colon and sigmoid colon). Three consecutive stool samples were collected to confirm the presence of ICG in the faeces by fluorescence imaging.

Results

Phantom experiments with blended breakfasts demonstrated the capability of MSOT for detection of ICG and its stability over a wide range of concentrations (1.06 µM – 212.15 µM) and pH (<1 – 7). In humans, spectrally unmixed MSOT ICG signals were visually detected in the terminal ileum from 1.5 hours onwards. Quantified ICG signals increased 2.5 hours after food intake with a maximum after 5.5 hours in comparison to consistently lower background signals after ingestion of normal breakfast (all P<0.05). In the sigmoid colon increased ICG signals were recorded 24 hours after ICG ingestion (P=0.0008, Figure 1). Spectrally unmixed ICG signals of ICG were verified in three consecutive stool samples by fluorescence imaging.

Conclusions

The oral application of ICG and its visualization with MSOT allows for non-invasive radiation-free characterisation of the gastrointestinal transit. This opens news possibilities for the assessment of functional and anatomical gastrointestinal diseases.