The risk of subsequent surgery following bowel resection for Crohn's disease in a national cohort of 19 207 patients.

AIM: Surgery is required for most patients with Crohn's disease (CD) and further surgery may be necessary if medical treatment fails to control disease activity. The aim of this study was to characterize the risk of, and factors associated with, further surgery following a first resection for Crohn's disease. METHODS: Hospital Episode Statistics from England were examined to identify patients with CD and a first recorded bowel resection between 2007 and 2016. Multivariable logistic regression was used to examine risk factors for further resectional surgery within 5 years. Prevalence-adjusted surgical rates for index CD surgery over the study period were calculated. RESULTS: In total, 19 207 patients (median age 39 years, interquartile range 27-53 years; 55% women) with CD underwent a first recorded resection during the study period. 3141 (16%) underwent a further operation during the study period. The median time to further surgery was 2.4 (interquartile range 1.2-4.6) years. 3% of CD patients had further surgery within 1 year, 14% by 5 years and 23% by 10 years. Older age (≥58), index laparoscopic surgery and index elective surgery (adjusted OR 0.65, 95% CI 0.54-0.77; 0.77, 0.67-0.88; and 0.77, 0.69-0.85; respectively) were associated with a reduced risk of further surgery by 5 years. Prior surgery for perianal disease (1.60, 1.37-1.87), an extraintestinal manifestation of CD (1.51, 1.22-1.86) and index surgery in a high-volume centre for CD surgery (1.20, 1.02-1.40) were associated with an increased risk of further surgery by 5 years. A 25% relative and 0.3% absolute reduction in prevalence-adjusted index surgery rates for CD was observed over the study period. CONCLUSIONS: Further surgery following an index operation is common in CD. This risk was particularly seen in patients with perianal disease, extraintestinal manifestations and those who underwent index surgery in a high-volume centre.

Venous Thromboembolism Following Discharge from Hospital in Patients Admitted for Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Patients admitted to hospital with inflammatory bowel disease[IBD] are at increased risk of venous thromboembolism[VTE]. This study aims to identify IBD patients at increased VTE risk on hospital discharge and to develop a risk scoring system to recognise them. METHODS: Hospital episode statistics data were used to identify all patients admitted with IBD as an emergency or electively for surgery. All patients with VTE within 90 days of hospital discharge were identified. A multilevel logistic regression model was used to identify patient- and admission-level factors associated with VTE. A scoring system to identify patients at higher risk for VTE was constructed. RESULTS: A total of 201 779 admissions in 101 966 patients were included. The rate of VTE within 90 days was 17.2 per 1000 patient-years at risk and was highest in patients admitted as an emergency who underwent surgery[36.9]. VTE was associated with: female sex (odds ratio 0.65 [95% confidence interval 0.53-0.80], p <0.001); increasing age [49-60 years] (4.67 [3.36-6.49], p <0.001); increasing length of hospital stay [>10 days] (3.80 [2.80-5.15], p <0.001); more than two hospital admissions in previous 3 months (2.23 [1.60-3.10], p <0.001); ulcerative colitis (1.48 [1.21-1.82], p <0.001); and emergency admission including surgery (1.59 [1.12-2.27], p = 0.010); or emergency admission not including surgery (1.59 [1.08-2.35], p = 0.019) compared with elective surgery. A score >12 in the VTE scoring system gave a positive predictive value [PPV] of VTE of 1%. The area under the curve [AUC] was 0.714 [95% CI 0.70-0.73]. CONCLUSION: IBD patients admitted to hospital with a prolonged length of stay, increasing age, male sex, or as an emergency were at increased risk of VTE following discharge. Higher-risk patients were identifiable by a VTE risk scoring system.

The risk of later surgery at the anastomotic site following right hemicolectomy for Crohn's disease in a national cohort of 12 230 patients.

BACKGROUND: Crohn's disease (CD) has a high-risk of bowel resection and later surgery for recurrent disease. Recent guidelines recommend colonoscopy 6-12 months following surgery to reduce further surgical intervention through medical therapy intensification. AIMS: To investigate the risk of further surgery at the anastomosis following right hemicolectomy for CD. METHODS: Hospital Episode Statistics were used to identify patients with CD and a right hemicolectomy between 2007 and 2016. Adherence to post-resection colonoscopy guidance timing and risk of further surgery at the anastomosis were examined. Cox proportional hazards models assessed risk factors for further surgery. RESULTS: 12 230 patients were identified: 45% male; median age 36 (IQR 26-49) years. Median follow-up was 5.9 (IQR 3.6-8.6) years: totalling 74 960 person-years. Median time to further surgery was 2.9 (IQR 1.2-5.3) years. By 5 years 9% and by 10 years 16.9% of those with sufficient follow-up had at least one further surgery involving the anastomotic site. Older, less deprived patients and those whose index surgery took place on an elective admission had a reduced risk of further surgery. The annual number of right hemicolectomies increased over the study from 1063 to 1317, driven by the increasing prevalence of CD. Overall, 78% of patients did not have a colonoscopy, as recommended, within 6-12 months following index resection. CONCLUSIONS: Further surgery involving the anastomotic site remains common following index right hemicolectomy for CD. Post-surgical colonoscopy was only undertaken in 22% of patients within suggested timeframes. Increased colonoscopy may lead to a reduced need for surgery if early optimisation of medical therapy is undertaken for recurrence.

Identification and Characterization of Inhibitors of a Neutral Amino Acid Transporter, SLC6A19, Using Two Functional Cell-Based Assays.

SLC6A19 (B0AT1) is a neutral amino acid transporter, the loss of function of which results in Hartnup disease. SLC6A19 is also believed to have an important role in amino acid homeostasis, diabetes, and weight control. A small-molecule inhibitor of human SLC6A19 (hSLC6A19) was identified using two functional cell-based assays: a fluorescence imaging plate reader (FLIPR) membrane potential (FMP) assay and a stable isotope-labeled neutral amino acid uptake assay. A diverse collection of 3440 pharmacologically active compounds from the Microsource Spectrum and Tocriscreen collections were tested at 10 µM in both assays using MDCK cells stably expressing hSLC6A19 and its obligatory subunit, TMEM27. Compounds that inhibited SLC6A19 activity in both assays were further confirmed for activity and selectivity and characterized for potency in functional assays against hSLC6A19 and related transporters. A single compound, cinromide, was found to robustly, selectively, and reproducibly inhibit SLC6A19 in all functional assays. Structurally related analogs of cinromide were tested to demonstrate structure-activity relationship (SAR). The assays described here are suitable for carrying out high-throughput screening campaigns to identify modulators of SLC6A19.