Explore the vast range of titles available.

IntroductionReports of benefit from HSCT were tempered by the ASTIC trial which failed its ambitious primary endpoint and reported high toxicity. Subsequent reports suggest that HSCT achieves complete mucosal healing in 50%, and that toxicity relates to the cyclophosphamide dose.DesignA UK multi-site RCT comparing low intensity HSCT with standard of care (SOC) in patients with active CD at endoscopy (SESCD ulcer score ≥ 2) refractory to 2 biologic classes. Planned recruitment was 99 patients randomised 2:1 to HSCT versus SOC. The primary endpoint was centrally read endoscopic remission (SESCD ulcer subscore of 0) without requirement for surgery or death at week 48.ResultsThe trial was halted due to unexpected SAE after 23 patients (13 HSCT, 10 SOC) had been randomised. The coronavirus pandemic prevented some outcome assessments. Patients had advanced disease: mean (SD) CD duration 13.9 (7) years; CDAI at baseline 337.5 (182.4) with 20 (91%) having undergone surgery and 9 (43%) having a stoma. All patients contributed to the safety analysis. The primary outcome using central reading was available for 7/10 HSCT and 6/9 SOC patients. Absence of endoscopic ulceration without surgery or death was reported in 3/7 (43%) HSCT patients compared to 0/9 (0%) SOC patients. Centrally read SESCD (mean (SD)) was 11.8 (8.7) and 10.1 (5.7) at baseline compared to 2.8 (2.9) and 18.7 (9.1) at week 48 in the HSCT and SOC groups respectively. Clinical remission (CDAI <150) occurred in 57% and 0% of patients in the HSCT and SOC groups at week 48. SAE were more frequent after HSCT (39 in 13 (100%) patients) than SOC (15 in 4 (40%) patients). Importantly, 10 SUSARs were reported in 6 HSCT patients including 3 cases of delayed renal failure due to thrombotic microangiopathy (TMA). Two patients in the HSCT arm died.ConclusionHSCT using a low intensity regimen results in meaningful reduction in endoscopic disease activity with some patients experiencing resolution of ulceration. However, the incidence of serious adverse events makes the regimen used in this trial unsuitable for future clinical use.This project (15/178/09) is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, NIHR or the Department of Health and Social Care.

Background and ObjectivesPoint prevalence studies have reported higher carriage rates of C. difficile in IBD patients compared with the general population, but longitudinal prospective data are lacking. The objectives of this observational study were to investigate and molecularly characterise isolates of C. difficile, collected prospectively on a monthly basis over a one-year period among IBD outpatients and healthy controls (HC).MethodsAt enrolment, recruited participants had established diagnoses of UC (n=16) and Crohn’s disease (n=6) and reported no recent hospitalisation or exposure to antibiotics. PCR ribotype and toxin status (cytotoxigenic culture) were determined for all +ive stool cultures. All participants underwent a monthly telephone interview to identify potential risk factors for C. difficile acquisition (changes in medications, exposure to antibiotics, clinic attendances, hospitalisation) and to assess for disease activity (Harvey-Bradshaw Index and Simple Clinical Activity Colitis Index).ResultsTwo patients underwent physician-initiated laboratory testing of C. difficile during the sample collection phase, although no participants developed or were treated for C. difficile infection. C. difficile was cultured from 29/223 samples (13%) representing 16/22 patients and 1 of 5 HC with concurrent antibiotic exposure in 6/29 visits (20%). Of the toxin +ive isolates (n=25; 078, 005, 302 and 015), 72% (n=21) were PCR ribotype 078. Toxigenic negative ribotypes included 023, 026 and 656. Of those toxin +ive isolates, 9 samples (36%) were associated with relapsing IBD of which 7/9 were ribotype 078. Multiple stool specimens also tested +ive for different ribotypes in 3 patients with UC, all of whom were taking regular immunosuppressants. WGS studies of the 078 isolates revealed marked genetic similarity, with only 3 of the 21 isolates varying by 1 or more nucleotides when compared to the 078 reference genome, suggesting there may have been a common source for cross-transmission.ConclusionsThe high prevalence of PCR ribotype 078 in this IBD outpatient cohort is consistent with the recent emergence of this strain in the community. These results reinforce the importance of testing all in-and outpatients with an apparent flare or relapsing IBD for carriage of toxigenic C. difficile to inform optimal management strategies. Future research is needed to understand the predominance of 078 isolates in IBD, particularly in the context of clinical relapse.

Background/Aims: The normal intestinal epithelium is increasingly being recognised as an important component of the mucosal innate protection against microorganisms. Human neutrophil defensins 1–3 (HNP 1–3) and lysozyme are components of the systemic innate immunity. The aim of this study was to investigate the expression of HNP 1–3 and lysozyme in normal and active inflammatory bowel disease (IBD) mucosa. Methods: Mucosal tissue sections were studied by immunohistochemistry using antibodies to neutrophil defensins 1–3 and lysozyme. Extracts of purified intestinal epithelial cells were used for immunoblotting studies and antimicrobial activity against the phoP negative strain of Salmonella typhimurium. Results: Surface epithelial cells strongly immunoreactive for neutrophil defensins and lysozyme were seen in active ulcerative colitis and Crohn's disease (but not normal or inactive IBD) mucosal samples. Many of these cells coexpressed both of the antimicrobial proteins. Immunoblotting studies confirmed the expression of neutrophil defensins in extracts of purified ulcerative colitis epithelial cells, which also demonstrated antimicrobial activity. Conclusion: HNP 1–3 and lysozyme are expressed in surface enterocytes of mucosa with active IBD and they may play an important role in intestinal host defence against luminal microorganisms.