Dual bolus intravenous contrast injection technique for multiregion paediatric body CT.

OBJECTIVES: Optimal vascular and parenchymal enhancement for multi-region paediatric body computed tomography (CT) has many challenges. A variety of approaches are currently employed, associated with varying image quality and radiation dose implications. We present a dual bolus intravenous (DBI) contrast technique for single-acquisition imaging of the chest, abdomen and pelvis, with evaluation of multi-compartmental vascular enhancement. METHODS: A DBI regime was designed for use with a programmable dual head pump injector. A larger initial bolus (two-thirds volume) is followed by a smaller bolus (one-third volume) before imaging the chest, abdomen and pelvis in a single acquisition, 45-65 seconds from the start of initial injection. Flow rates and second bolus timing were tailored to patient weight and contrast volume, using five weight categories. Multi-compartmental vascular opacification was graded and image quality was assessed in a cohort of 130 patients. RESULTS: The DBI technique resulted in concordant multi-compartmental (thoracic aortic, pulmonary arterial, abdominal aortic and portal venous) vascular enhancement. Early splenic parenchymal enhancement artefacts and alterations to renal enhancement were observed. CONCLUSION: We present a weight-stratified dual bolus intravenous contrast technique to improve image quality in paediatric multi-region body CT. KEY POINTS: • In children, optimal vascular and parenchymal enhancement in multi-region CT is challenging. • A dual bolus contrast technique offers concordant arterial and portal venous opacification. • Adaptation to patient size is achieved by stratification into five weight categories. • Dose penalties of 'overlap' and 'dual phase' imaging techniques can be avoided.

MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T cell responses.

Although intestinal epithelial cells (IECs) can express major histocompatibility complex class II (MHC II), especially during intestinal inflammation, it remains unclear if antigen presentation by IECs favours pro- or anti-inflammatory CD4+ T cell responses. Using selective gene ablation of MHC II in IECs and IEC organoid cultures, we assessed the impact of MHC II expression by IECs on CD4+ T cell responses and disease outcomes in response to enteric bacterial pathogens. We found that intestinal bacterial infections elicit inflammatory cues that greatly increase expression of MHC II processing and presentation molecules in colonic IECs. Whilst IEC MHC II expression had little impact on disease severity following Citrobacter rodentium or Helicobacter hepaticus infection, using a colonic IEC organoid-CD4+ T cell co-culture system, we demonstrate that IECs can activate antigen-specific CD4+ T cells in an MHC II-dependent manner, modulating both regulatory and effector Th cell subsets. Furthermore, we assessed adoptively transferred H. hepaticus-specific CD4+ T cells during intestinal inflammation in vivo and report that IEC MHC II expression dampens pro-inflammatory effector Th cells. Our findings indicate that IECs can function as non-conventional antigen presenting cells and that IEC MHC II expression fine-tunes local effector CD4+ T cell responses during intestinal inflammation.

Severe paediatric ulcerative colitis: incidence, outcomes and optimal timing for second-line therapy.

BACKGROUND: Despite the predominance of extensive disease in children with ulcerative colitis, data concerning severe paediatric ulcerative colitis are sparse. We reviewed rates and predictors of response to intravenous-corticosteroid therapy in a single-centre cohort with long-term follow-up. METHODS: 99 children (49% males; age 2-17 years) were hospitalised (1991-2000) for treatment of severe ulcerative colitis (90% extensive; 49% new onset ulcerative colitis). Clinical, laboratory and radiographic data were reviewed. A population-based subset was used to assess incidence. Predictors of corticosteroid response were analysed using univariate and multivariate analyses at days 3 and 5 of therapy. Colectomy rates were calculated using Kaplan-Meier survival analyses. RESULTS: 28% (95% CI, 23 to 34%) of children with ulcerative colitis resident in the Greater Toronto Area required admission for intravenous corticosteroid therapy, of whom 53 (53%; 95% CI, 44 to 63%) responded. Several predictors were associated with corticosteroid failure, but in multivariable modelling only C-reactive protein [OR = 3.5 (1.4 to 8.4)] and number of nocturnal stools [OR = 3.2 (1.6 to 6.6)] remained significant at both days 3 and 5. The Pediatric Ulcerative Colitis Activity Index (PUCAI), Travis and Lindgren's indices strongly predicted non-response. Radiographically, the upper range of colonic luminal width was 40 mm in children younger than 11 years versus 60 mm in older patients. Cumulative colectomy rates at discharge, 1 year and 6 years were 42%, 58% and 61%, respectively. CONCLUSIONS: Children with ulcerative colitis commonly experience at least one severe exacerbation. Response to intravenous corticosteroids is poor. The PUCAI, determined at day 3 (>45 points) should be used to screen for patients likely to fail corticosteroids and at day 5 (>70 points) to dictate the introduction of second-line therapies.