BackgroundThiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors.AimTo investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse.MethodsThis was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively.Results237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4–8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035).Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007).ConclusionThiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

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Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II cells (A549). To study in vitro the direct influence of alveolar type II cells on mechanical stretch. Methods A549 were treated with different doses of lipopolysaccharide (LPS), 0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, and then A549 were lengthened 5%, 15%, 30% using a FLEXCELL tension unit 4000, a vacuum-driven device that applies strain to cells, which were cultured in six-well plates coated with collagen-I, and 12 cycles/min for 4 hours. Apoptosis was measured using the flow cytometry method that measures annexin V and propidium iodide (PI) staining. The morphological changes of apoptotic cells were observed by transmission electron microscope. Results Apoptosis could be induced in alveolar type II cells (A549) by mechanical stretch. The percentage of annexin V + PI cells increased after being treated with cyclic stretch for 4 hours by 5%, 15%, 30% in all groups. The morphological features of apoptotic cells demonstrated by transmission electron microscope were as follows: shrinkage of the cell, chromatin condensation and aggregation under the nuclear membrane as a crescent or lump, membrane-encapsulated nuclear fragment or cell organ formed by invagination of the cell membrane, and apoptotic body formation followed by vacuolization. Conclusion Apoptosis induced by mechanical stretch and LPS is dose dependent. Mechanical stretch aggravates apoptosis especially in cells treated with LPS. Annexin V and PI double staining is a specific, sensitive, and quantitative method for analyzing apoptotic cells. It is also helpful to clarify the protective mechanism of low-volume ventilation in ARDS. Acknowledgement The study was funded by the 'One Hundred People' project of Shanghai Sanitary Bureau (03-77-20).

provided stool for FC concentration analysis and the study was terminated once the last recruited patient reached a follow up period of 365 days. Remission was defined as a Crohn's disease activity index (CDAI) of < 150. Relapse was defined as either a need for escalation of medical therapy, surgery for active CD or progression of disease phenotype using the Montreal classification. The study was approved by the West of Scotland Research Ethics Service (REC reference 10/ S0704/1). The Receiver Operating Characteristic (ROC) curve of relapse by 12 months, based on FC value at baseline, was calculated. Kaplan-Meier curves of time to relapse, some of which were longer than 12 months, were based on the resulting best FC cut-off value for predicting relapse (with patients who had not relapsed being censored at end of follow-up) and compared using the log-rank tests. Results 98 patients were recruited. One patient was lost to follow up, 1 died and the care of 3 patients was transferred to another centre, before either relapsing or being followed up for 12 months. Of the 93 remaining patients 11 (12%) had relapsed by 12 months. The median FC was lower for non-relapsers, 96 µg/g (IQR 39-237), than for relapsers, 328 µg/g (IQR 189-574), (p = 0.008). The area under the ROC curve to predict relapse using FC was 74.8% ( Figure 1). A cut-off FC value of 240 µg/g to predict relapse of quiescent Crohn's disease over the course of one year was associated with a sensitivity of 72.7% and specificity of 74.3%. Negative predictive value was high at 95.3% and positive predictive value was 27.6%. There was a significant difference in time to relapse for those with the first FC value below or above 240 µg/g (p = 0.011). Conclusion In this prospective dataset, FC appears to be a useful, non-invasive tool to help identify quiescent Crohn's disease patients at a low risk of relapse over the ensuing 12 months. A FC value of 240 µg/g was deemed the best cut-off value in our patients.

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