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Background The optimal endoscopic target in early Crohn’s disease (CD) that limits long-term disease complications is unknown. Methods We analysed medical records from patients who had follow-up data since the end of CALM. Patients with Crohn’s disease endoscopic index of severity (CDEIS) scores at the end of CALM were included. The primary outcome was a composite of major adverse outcomes reflecting CD progression: new internal fistula/abscess, stricture, perianal fistula/abscess, CD hospitalisation, or CD surgery since the end of CALM. We compared median CDEIS and per cent improvement from baseline CDEIS. Youden index analysis was used to identify optimal CDEIS cut-off score associated with CD progression. Kaplan–Meier and Cox regression methods were used to compare rates of progression by different CDEIS targets. Multivariable models were adjusted for age, prior surgery, and stricturing behaviour. Results 110 patients with median age 28 (IQR 22–38) years, disease duration 0.2 (0.1–0.5) years, and median follow up of 3.1 (1.9–4.4) years were included. Eleven per cent had a history of stricture, 5.5% history of surgery, and 52% were originally in the tight control arm of the CALM study. Median CDEIS score at end of CALM was 3 (0–5.4) and 32 (29%) patients had disease progression. Baseline median CDEIS score was similar between those with and without progression [10.9 (7.5–15.5) vs. 11.9 (8–17.5)]. Median CDEIS score at the end of CALM was higher among those with progression [1.3 (0–5.1) vs. 4.9 (3–9.1), p < 0.001)]. Patients within higher quartiles of CDEIS score had higher rates of progression over time (Figure 1). Patients without disease progression had a greater median decrease in CDEIS score from baseline to end of CALM [90% (60–100%) vs. 50% (30–80%), p < 0.001]. The optimal CDEIS score cut-off was 2 with sensitivity 84%, specificity 60% and NPV 90% for progression. Patients with CDEIS ≤ 2 had less progression over time compared with patients with > 50% improvement from baseline CDEIS (not reaching CDEIS ≤ 2) and those not meeting either endpoint (Figure 2). On adjusted analysis, CDEIS score ≤ 2 was associated with a decreased risk of progression (aHR 0.23, 95% CI 0.09–0.56). Conclusion In early CD, a CDEIS score ≤ 2 is optimal cut-off associated with a lower risk of disease progression.

BACKGROUND: Tight control (TC) for Crohn’s disease (CD), using symptoms plus biomarkers (faecal calprotectin, C-reactive protein) to direct adalimumab (ADA) treatment, was associated with improved outcomes and considered cost effective (from United Kingdom setting) compared to clinical management (CM) in a 48-week (wk) multicenter, randomized controlled trial (CALM). AIMS: This study aims to evaluate the cost-effectiveness (CE) of TC vs CM from Canadian perspective. METHODS: The CE of TC versus CM was assessed in a Canadian setting. An ordered probit regression estimated CDAI-based health state (remission: CDAI

Endoscopic and deep remission at 1 year prevents disease progression in early Crohn's disease : long-term data from CALM

Summary Background PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. Methods This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18–65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNFα treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7·5 mg, 22·5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks. Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score ≤2 with no individual subscore >1 and rectal bleeding subscore ≤1) at week 12. The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted. This study is registered with ClinicalTrials.gov, number NCT01620255. Findings Between Nov 2, 2012, and Feb 4, 2016, we screened 587 patients; 357 were eligible and randomly assigned to receive placebo (n=73) or PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70). Remission rates at week 12 were significantly greater in three of four active-treatment groups than in the placebo group (2·7% [two of 73]): 7·5 mg (11·3% [eight of 71]), 22·5 mg (16·7% [12 of 72]), 75 mg (15·5% [11 of 71]), and 225 mg (5·7% [four of 70]). These rates corresponded to a stratum-adjusted (anti-TNFα-naive and anti-TNFα-experienced) risk difference versus placebo of 8·0% for 7·5 mg (90% CI 1·9 to 14, p=0·0425), 12·8% for 22·5 mg (5·6 to 19·9, p=0·0099), 11·8% for 75 mg (4·8 to 18·8, p=0·0119), and 2·6% for 225 mg (−1·2 to 6·4, p=0·1803). Four of 73 (5·5%) patients had a serious adverse event in the placebo group, ten of 71 (14·1%) in the 7·5 mg group, one of 70 (1·4%) in the 22·5 mg group, three of 73 (4·1%) in the 75 mg group, and three of 70 (4·3%) in the 225 mg group. No safety signal was observed for the study drug. Interpretation PF-00547659 was safe and well tolerated in this patient population, and better than placebo for induction of remission in patients with moderate to severe ulcerative colitis. The greatest clinical effects were observed with the 22·5 mg and 75 mg doses. Funding Pfizer.

Administration of nonselective beta-blockers in prophylaxis of first variceal bleeding is not suitable for all patients. Thus, we evaluated endoscopic variceal band ligation (EVBL) in primary prevention of bleeding in patients with cirrhosis and large esophageal varices. A total of 73 consecutive patients with liver cirrhosis and large esophageal varices without a history of gastrointestinal bleeding were randomized to receive either EVBL or propranolol and were followed for up to 18 months. Forty patients underwent EVBL and 33 patients received propranolol. Variceal bleeding occurred in 2 patients in the EVBL (5%) and in 2 patients in the propranolol group (6%, NS). The 18 month actuarial risk for first variceal bleed was 5% in the EVBL (95% CI, 0-12%) and 20% in the propranolol group (95% CI, 0-49%, NS). The actuarial probability of death at 18 months of follow-up was 5% (95% CI, 0-11%) in the EVBL group and 7% (95% CI, 0-17%, NS) in the propranolol arm. In conclusion, EVBL was an effective and safe alternative to propranolol in primary prophylaxis of bleeding in patients with large esophageal varices.

Purpose To evaluate the effects of secondary deployment of expanded polytetrafluoroethylene (ePTFE)–covered stent grafts in the treatment of dysfunctional transjugular intrahepatic portosystemic shunts (TIPSs) in comparison with other common approaches (conventional angioplasty or implantation of bare metal stents). Materials and Methods A retrospective review of 121 dysfunctional bare metal TIPS presenting between 2000 and 2004 was conducted. The group was divided into four subgroups according to the type of intervention: conventional angioplasty (52 cases; 43%), bare metal stent deployment (35 cases; 28.9%), nondedicated ePTFE-covered stent-graft deployment (15 cases; 12.4%), and dedicated ePTFE-covered stent-graft deployment (19 cases; 15.7%). In all four groups, the primary patency after the specific intervention was calculated and mutually compared. Results Primary patency rates after 12 and 24 months were 49.7% and 25.3%, respectively, in conventional angioplasty; 74.9% and 64.9%, respectively, with bare metal stents; 75.2% and 64.5%, respectively, with nondedicated ePTFE-covered stent grafts; and 88.1% and 80.8%, respectively, with dedicated ePTFE-covered stent grafts. Conclusions In the treatment of dysfunctional TIPS, better patency after the intervention was obtained by deploying dedicated ePTFE-covered stent grafts in comparison with conventional angioplasty, bare metal stents, and nondedicated ePTFE-covered stents.

The aim of the study was to determine the prevalence and detailed data concerning the incidence of spontaneous bacterial peritonitis in the Czech Republic. Ninety-nine patients with liver cirrhosis and ascites were examined. Spontaneous bacterial peritonitis was diagnosed in 35 patients (35.4%). It was revealed more often in patients with alcoholic aetiology of cirrhosis whose anamnesis involved sub-febrile or febrile states and the deterioration of ascites. Elevated serum leucocyte counts and increased levels of C-reactive protein can contribute to the diagnosis. A low level of total protein and albumin in ascites predisposes to the increase of this infection. The reduction of the platelet count in a set of patients with spontaneous bacterial peritonitis indicates the influence of portal hypertension in the aetiology of the disease.

BACKGROUND & AIMS: Tofacitinib, an orally administered Janus kinase inhibitor, blocks signaling through γ-chain-containing cytokines (interleukins 2, 4, 7, 9, 15, and 21). We performed a phase 2 trial to measure its efficacy in patients with moderate-to-severe active Crohn's disease. METHODS: Patients (N = 139; age, ≥18 y) with moderate-to-severe active Crohn's disease were assigned randomly to groups given 1 mg (n = 36), 5 mg (n = 34), or 15 mg (n = 35) tofacitinib or placebo (n = 34), twice daily for 4 weeks, at 48 centers in 12 countries. The primary end point was the proportion of clinical responders at week 4 (decrease from baseline in the Crohn's Disease Activity Index score of ≥70 points [Response-70]). Secondary end points included clinical remission (Crohn's Disease Activity Index score of

We describe the successful creation of a transjugular intrahepatic portosystemic shunt (TIPS) in a patient with complete situs inversus using a simple modification of the standard TIPS technique.

The purpose of the study was to evaluate the long-term clinical efficacy of Doppler sonography in revealing failure of transjugular intrahepatic portosystemic shunts (TIPS).During a 5-year period, 1192 Doppler examinations were performed in 216 patients with TIPS. No regular follow-up shunt venography was performed. Doppler examinations were retrospectively compared with the results of shunt revisions. Sonograms with negative findings were compared with the patients' clinical status so that the number of false-negative sonographic findings leading to an episode of shunt failure (recurrence of gastrointestinal bleeding or ascites) could be ascertained. Sonographic parameters assessed included diameter, velocity, flow volume, and congestion index of the portal vein; and shunt velocities.Doppler sonography revealed shunt occlusion in 25 of 26 angiographically proven cases (sensitivity, 96%). The combination of velocity criteria (peak intrashunt velocityor =250 cm/sec, maximum velocity in the portal third of the shuntor =50 cm/sec, or maximum portal vein velocity less than or equal to two thirds of the baseline value) revealed shunt stenosis in 103 of 110 cases (sensitivity, 94%). Doppler sonography missed a significant shunt stenosis that led to an episode of gastrointestinal bleeding or ascites recurrence in only seven cases. The congestion index of the portal vein showed significant differences between patent and malfunctioning shunts (p0.001).Doppler sonography is an effective primary imaging method for long-term follow-up of patients with TIPS.