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INTRODUCTION: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy. METHODS AND ANALYSIS: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia. TRIAL REGISTRATION N

BACKGROUND: Intestinal ultrasound (IUS) is a valuable tool for assessment of Crohn's disease (CD). However, there is no widely accepted luminal disease activity index. AIMS: To identify appropriate IUS protocols, indices, items, and scoring methods for measurement of luminal CD activity and integration of IUS in CD clinical trials. METHODS: An expert international panel of adult and paediatric gastroenterologists (n = 15) and radiologists (n = 3) rated the appropriateness of 120 statements derived from literature review and expert opinion (scale of 1-9) using modified RAND/UCLA methodology. Median panel scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 were considered inappropriate, uncertain and appropriate ratings respectively. The statement list and survey results were discussed prior to voting. RESULTS: A total of 91 statements were rated appropriate with agreement after two rounds of voting. Items considered appropriate measures of disease activity were bowel wall thickness (BWT), vascularity, stratification and mesenteric inflammatory fat. There was uncertainty if any of the existing IUS disease activity indices were appropriate for use in CD clinical trials. Appropriate trial applications for IUS included patient recruitment qualification when diseased segments cannot be adequately assessed by ileocolonoscopy and screening for exclusionary complications. At outcome assessment, remission endpoints including BWT and vascularity, with or without mesenteric inflammatory fat, were considered appropriate. Components of an ideal IUS disease activity index were identified based upon panel discussions. CONCLUSIONS: The panel identified appropriate component items and applications of IUS for CD clinical trials. Empiric evidence, and development and validation of an IUS disease activity index are needed.

INTRODUCTION: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy. METHODS AND ANALYSIS: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia. TRIAL REGISTRATION N

Purpose: This study was designed to compare the radiation dose in abdominal dual-energy (DE) and single-energy (SE) acquisitions obtained in clinical practice with a second-generation DE computed tomography (DECT) and to analyze the dose variation in comparison with an SE ac- quisition performed with a 64-row SECT (SECT). Methods: A total of 130 patients divided into 2 groups underwent precontrast and portal abdominal 128-row CT examination. In group A, DE portal acquisition was performed using a detector configuration of 2 40 0.6 mm, tube A at 80 kVp and a reference value of 559 mAs, tube B at 140 kVp and a reference value of 216 mAs, pitch 0.6, and online dose modulation; group B underwent SE portal acqui- sition using a detector configuration of 64 0.6 mm, 120 kVp and a reference value of 180 mAs, pitch 0.75, and online dose modulation. Group C consisted of 32 subjects from group A previously studied with 64-row SECT using the following parameters: detector configuration 64 0.6 mm, 120 kVp and a reference value of 180 mAs, pitch 0.75, and online dose modulation. In each group, the portal phase dose-length product and radiation dose (mSv) were calculated and normalized for a typical abdominal acquisition of 40 cm. Results: After normalization to standard 40-cm acquisition, a dose-length product of 599.0 T 133.5 mGy I cm (range, 367.5 T 1231.2 mGy I cm) in group A, 525.9 T 139.2 mGy I cm (range, 215.7Y882.8 mGy I cm) in group B, and 515.9 T 111.3 mGy I cm (range, 305.5Y687.2 mGy I cm) in group C was calculated for portal phase acquisition. A significant radiation dose increase (P G 0.05) was observed in group A (10.2 T 2.3 mSv) compared with group B (8.9 T 2.4) and group C (8.8 T 1.9 mSv). No significant difference (P 9 0.05) was reported between SE 64- and 128-row acquisitions. A significant positive cor- relation between radiation dose and body mass index was observed in each group (group A, r2 = 0.59, P G 0.0001; group B, r2 = 0.35, P G 0.0001; group C, r2 = 0.2