Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: The impact of thiopurine de-escalation while on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. METHODS: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score ≥3 and fecal calprotectin >150 µg/g or increase in Mayo endoscopic subscore ≥1 from baseline), fecal calprotectin remission (<150 µg/g), C-reactive protein remission (<5 mg/L), centrally read endoscopic remission (Mayo endoscopic subscore = 0), histologic remission (Nancy index = 0), histo-endoscopic remission, and adverse events. RESULTS: In total, 62 patients were randomized to continue (n = 20) or withdraw (n = 42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 µg/mL, interquartile rate [IQR], 12.3-18.5 µg/mL versus 15.9 µg/mL, IQR, 10.1-22.7 µg/mL, respectively, P = 0.36). The continue group had significantly higher fecal calprotectin remission (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6-146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3-33.8; P = .03) predicted clinical relapse after thiopurine withdrawal. CONCLUSIONS: Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic, and histo-endoscopic activity. Histologic activity and prior anti-tumor necrosis factor exposure may predict disease relapse on thiopurine withdrawal for patients using vedolizumab for UC. Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Biological Agents in the Treatment of Crohn's Disease: A Propensity Score-Matched Analysis From the Prospective Persistence Australian National IBD Cohort (PANIC3) Study.

INTRODUCTION: Comparative effectiveness research provides data on the relative benefits and risks between treatments. In Crohn's disease (CD), however, there are few head-to-head studies comparing advanced therapies and none with long-term follow-up. Real-world effectiveness, defined by treatment persistence, obtained from prospective population-based patient cohorts, may help determine the best sequencing and positioning of biological agents. METHODS: We analyzed the prospectively collected population-based Australian national Pharmaceutical Benefits Scheme dispensing data registry (2005-2019) for CD. There is no mandated biological agent prescribing order, and all citizens and permanent residents are eligible for treatment irrespective of insurance status. Propensity score matching was performed to reduce selection bias. RESULTS: There were 2,029 lines of therapy in 1,446 patients (median age 43 years, interquartile range 34-58, 44% male patients) over the 15-year period with 5,618 patient-years of follow-up. Per line of therapy, 915/2,029 (45.1%) patients used adalimumab, 722/2,029 (35.6%) used infliximab, 155/2,029 (7.6%) used vedolizumab, and 237/2,029 (11.7%) used ustekinumab. When used in biological agent-naive patients, there was no difference in persistence between any agent ( P > 0.05). Used after first line in biological agent-experienced CD, ustekinumab had significantly better persistence than non-ustekinumab biological agents ( P = 0.0018), vs anti-tumor necrosis factor (TNF) alpha therapy ( P = 0.006) or vedolizumab ( P < 0.001). Ustekinumab persistence was unaffected by prior biological agent exposure ( P = 0.51). After anti-TNF use, ustekinumab had superior persistence to an alternative anti-TNF agent ( P = 0.033) and to vedolizumab ( P = 0.026). Using a propensity score-matched analysis adjusted for age, immunomodulator use, and bio-exposed status, ustekinumab had superior persistence to anti-TNF ( P = 0.01). Multivariate predictors of worse persistence were the use of a non-ustekinumab biological agent (adjusted hazard ratio 2.10, P < 0.001), and bio-experienced status (adjusted hazard ratio 1.23, P < 0.001). DISCUSSION: This large national prospective database with nonhierarchical prescribing of biological agents did not identify superior persistence of any agent in bio-naive CD. However, for patients with bio-experienced CD, persistence was greater with ustekinumab.

High prevalence of Crohn disease and ulcerative colitis among older people in Sydney.

OBJECTIVES: To determine the age-standardised prevalence of inflammatory bowel disease (IBD) in a metropolitan area of Sydney, with a focus on its prevalence among older people. DESIGN, SETTING: Population-based epidemiological study of people with IBD in the City of Canada Bay, a local government area in the inner west of Sydney, during 1 March 2016 - 10 November 2016. PARTICIPANTS: Patients diagnosed with confirmed IBD according to the Copenhagen or revised Porto criteria. MAIN OUTCOME MEASURES: Crude prevalence of IBD, including Crohn disease and ulcerative colitis; age-standardised prevalence of IBD, based on the World Health Organization standard population; prevalence rates among people aged 65 years or more. RESULTS: The median age of 364 people with IBD was 47 years (IQR, 34-62 years); 185 were women (50.8%). The crude IBD prevalence rate was 414 cases (95% CI, 371-456 cases) per 100 000 population; the age-standardised rate was 348 cases (95% CI, 312-385 cases) per 100 000 population. The age-standardised rate for Crohn disease was 166 cases (95% CI, 141-192 cases) per 100 000 population; for ulcerative colitis, 148 cases (95% CI, 124-171 cases) per 100 000 population. The IBD prevalence rate in people aged 65 years or more was 612 cases (95% CI, 564-660 cases) per 100 000, and for those aged 85 years or more, 891 cases (95% CI, 833-949 cases) per 100 000; for people under 65, the rate was 380 cases (95% CI, 342-418 cases) per 100 000. CONCLUSIONS: We found that the prevalence of confirmed IBD in a metropolitan sample was highest among older people. Challenges for managing older patients with IBD include higher rates of comorbid conditions, polypharmacy, and cognitive decline, and the immunosuppressive nature of standard therapies for IBD.

Thiopurines and their optimization during infliximab induction and maintenance: A retrospective study in Crohn's disease.

BACKGROUND AND AIM: Combining therapy with a thiopurine is favored when commencing infliximab in Crohn's disease; however, the optimal 6-thioguanine nucleotide (TGN) level and how long to continue thiopurines after induction are uncertain. We aimed to compare outcomes after induction and during maintenance in combination therapy versus infliximab monotherapy in Crohn's and to examine whether TGN levels were associated with outcomes. METHODS: Crohn's patients induced with infliximab with or without concomitant thiopurines were retrospectively identified. Response to induction and clinical outcomes in subsequent 6-month maintenance semesters were analyzed. A TGN level ≥235 pmol/8 × 108 red blood cells was considered therapeutic. RESULTS: In 89 patients, response to induction was higher in combination therapy than monotherapy (74 vs 47%, P = 0.04). This benefit was only seen in patients with a therapeutic TGN (odds ratio 3.72, confidence interval 1.07-13.0, P = 0.04). Combination therapy during induction yielded a three times longer time to subsequent need for treatment escalation or treatment failure compared with monotherapy (29 vs 9 months, P = 0.01), with both therapeutic and subtherapeutic TGNs independent predictors on multivariate analysis. Among 370 semesters, there was no difference in outcomes between combination therapy and monotherapy (P = 0.42), nor when combination semesters were stratified by therapeutic versus subtherapeutic TGN (P = 0.56). In semester 1 only, a significantly higher remission rate was observed with therapeutic compared with subtherapeutic TGN (76% vs 33%, P = 0.02). CONCLUSIONS: Combination therapy dosed with an optimized thiopurine was superior to infliximab monotherapy for induction of response, durability of response, and clinical outcomes in the first 6 months following induction. Thereafter, combination therapy yielded no clinical advantage, supporting consideration of thiopurine withdrawal on a case-by-case basis.

Major Abdominal and Perianal Surgery in Crohn's Disease: Long-term Follow-up of Australian Patients With Crohn's Disease.

BACKGROUND: Most patients with Crohn's disease still require surgery despite significant advances in medical therapy, surveillance, and management strategies. OBJECTIVE: The purpose of this study was to assess surgical strategies and outcomes in Crohn's disease, including surgical recurrence and emergency surgery. DESIGN: This was a multicenter, retrospective review of a prospectively collected database. SETTINGS: A specialist-referred cohort of patients with Crohn's disease between 1970 and 2009 was studied. PATIENTS: Included were 972 patients with Crohn's disease who were referred to the Sydney Inflammatory Bowel Disease cohort database. MAIN OUTCOME MEASURES: Main outcomes of interest were the rates of major abdominal and perianal surgery between decades (1970-1979, 1980-1989, 1990-1999, and 2000-2009), indications for surgery, types of procedure performed, rate of elective and emergency surgery, risk of surgical recurrence, and predictive factors for surgery. RESULTS: Between 1970 and 2009, the overall risks of surgery within 5, 10, and 15 years of diagnosis were 31.7%, 43.3%, and 48.4%. The median time to first surgery from time of diagnosis was 2 years (range, 0-31 years). A total of 6.7% of patients required emergency surgery within 5 years of diagnosis. In total, 8.8% of patients required emergency surgery within 15 years. The overall risk of surgical recurrence was 35.9%. The risk of major abdominal surgery significantly decreased between 2000 and 2009 when compared with the 1970 to 1979 period (OR = 0.49 (95% CI, 0.34-0.70). However, the rate of perianal surgery significantly increased (OR = 5.76 (95% CI, 2.54-13.06)). The main indications for surgery were enteric stricture or obstruction, perianal disease, and intra-abdominal fistulas/abscess. Of the 972 patients over 4 decades, only 11 patients (1.1%) were diagnosed with colorectal cancer. LIMITATIONS: This was a specialist-referred cohort, not a population-based study. CONCLUSIONS: The rate of major abdominal surgery has decreased, with surgery reserved for more severe and complicated disease. The natural history of patients with more complicated Crohn's disease and severe phenotypes puts them at higher risk of surgical recurrence and emergency surgery. There has been no reduction in emergency surgery rates and there has been an increase in surgical recurrence despite the reduction in surgical rate morbidity. See Video Abstract at http://links.lww.com/DCR/A483.

Epidemiology and outcomes of primary sclerosing cholangitis with and without inflammatory bowel disease in an Australian cohort.

BACKGROUND & AIMS: Epidemiological data on primary sclerosing cholangitis (PSC) outside the Northern hemisphere are limited. Similarly, the impact of inflammatory bowel disease (IBD) on PSC outcomes remains unclear. We aimed to study the epidemiology and outcomes of PSC patients with and without IBD in an Australian cohort. METHODS: We retrospectively studied PSC patients attending two tertiary referral hospitals over 20 years. Diagnosis of PSC was made according to international guidelines by positive cholangiography and/or liver biopsy (for small duct PSC) with supporting clinical and laboratory evidence. RESULTS: Of 208 PSC patients (61% male) were studied (2271patient-years follow-up). The median age of PSC diagnosis was similar for PSC-IBD and PSC-only patients (40 years vs 42 years, P = .35). All 33 deaths occurred in PSC-IBD patients while there were no deaths in PSC-only patients (21% vs 0%, P < .01). However, there were no significant differences in liver transplantation (PSC-only 25% vs PSC-IBD 31%, P = .45) and transplant-free survival between PSC-only and PSC-IBD patients (P = .43). On multivariate Cox regression, only elevated international normalized ratio (INR) was associated with a greater risk of death or liver transplant (HR 2.0, 95% CI 1.1-3.6, P = .02). Development of gastrointestinal malignancy was higher in the PSC-IBD group compared to PSC-only group (22% vs 2%, P < .01). CONCLUSION: Australian PSC patients have similar characteristics compared to European and North American cohorts. IBD is a significant predictor of gastrointestinal malignancies. Deaths were more common in PSC-IBD but overall transplant-free survival remained similar in PSC-IBD and PSC-only groups. An elevated INR was an independent predictor of death or liver transplantation.

Inflammatory Bowel Disease Environmental Risk Factors: A Population-Based Case-Control Study of Middle Eastern Migration to Australia.

BACKGROUND & AIMS: The incidences of the inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC) are increasing, indicating gene-environment interactions. Migrants from low-IBD-prevalence countries to a high-prevalence country may help identify the relative contribution of environmental risk factors compared with native Caucasians. METHODS: This prospective case-control study evaluated IBD environmental risk factors of Middle Eastern migrants (MEM) in Australia compared with matched Caucasian IBD subjects, MEM controls, Caucasian controls, and controls in the Middle East using adjusted odds ratios (aOR). RESULTS: A total of 795 subjects were recruited: 154 MEM cases (75 CD; 79 UC), 153 MEM controls, 162 Caucasian cases (85 CD; 77 UC), 173 Caucasian controls, and 153 controls in Lebanon. Smoking increased CD risk in MEM and Caucasians and reduced UC risk in Caucasians (aOR, 0.77; 95% CI, 0.41-0.98) but not MEM (aOR, 1.45; 95% CI, 0.80-2.62). Antibiotic use reduced the risk of MEM CD (aOR, 0.27; 95% CI, 0.11-0.67) and UC (aOR, 0.38; 95% CI, 0.18-0.80), but increased the risk in Caucasians (CD: aOR, 5.24; 95% CI, 2.13-12.90; and UC: aOR, 6.82; 95% CI, 2.67-17.38). Most hygiene markers (rural dwelling, pet ownership, pet feeding, and farm animal contact) reduced CD and UC risk in MEM (P < .05). In contrast, in Caucasians these hygiene markers lacked significance. Other significant risk factors include IBD family history, appendectomy, tonsillectomy, and breastfeeding. CONCLUSIONS: Differential IBD environmental risk factors exist between migrants and native Caucasians, indicating a dynamic interplay between environmental factors and IBD risk for immigrants that is distinct to those factors most relevant in native Caucasians.

Treatment endpoints in ulcerative colitis: Does one size fit all?

A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician's subjective assessment of symptoms. However, choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy. The treatment endpoints for ulcerative colitis (UC), recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) consensus have changed somewhat over time. The latest STRIDE-II consensus advises immediate (clinical response), intermediate (clinical remission and biochemical normalisation) and long-term treatment (endoscopic healing, absence of disability and normalisation of health-related quality of life, as well as normal growth in children) endpoints in UC. However, achieving deeper levels of remission, such as histologic normalisation or healing of the gut barrier function, may further improve outcomes among UC patients. Generally, all medical therapy should seek to improve short- and long-term mortality and morbidity. Hence treatment endpoints should be chosen based on their ability to predict for improvement in short- and long-term mortality and morbidity. Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient. In addition, changing therapy that has achieved partial response may lead to worse outcomes, with failure to recapture response on treatment reversion. Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians, or may have strong opinions re certain therapies. Potential benefits and harms of therapies, incremental benefits of achieving deeper levels of remission, as well as uncertainties of the same, need to be discussed with individual patients, and a treatment endpoint agreed upon with the clinician. Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission, such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.

Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study.

Background: Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. Objectives: We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. Design: This is a retrospective, multicentre study of patients admitted with ASUC. Methods: CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. Results: CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). Conclusion: CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.

Cytomegalovirus reactivation in acute severe ulcerative colitis Cytomegalovirus (CMV) is a highly prevalent virus that may result in concominant reactivation in patients with acute severe ulcerative colitis and potentially worsen their outcomes. Our study aims to determine the impact of presence of CMV in patients with acute severe ulcerate colitis requiring hospitalisation and its association with outcomes including risk of surgical resection of colon, length of hospital stay, readmission rate, as well as effect of outcomes amongst those treated with antivirals for CMV. Our results did not find a significant association between detection of CMV on surgical risk, though outcomes including longer hospital stays, higher readmission rate were found. Antiviral use was not associated with lower risk of surgery but was found to prolong time to surgery. Given that our study was based on retrospective data, further prospective studies will be required to examine the benefit of antiviral use in outcomes for those with concominant CMV and acute severe ulcerative colitis. We conclude from our study that while having concomitant CMV with acute severe uclerative colitis may not necessarily increase risk for surgery, patients may still have worse outcomes in other areas therefore the detection of CMV should be considered a significant and clinically relevant result.

Determining efficacy of dynamic multimedia bowel preparation instructions versus standard instructions on adenoma detection and patient reported measures (DIGICLEAN trial): a study protocol for a multicentre, colonoscopist-blinded, randomised controlled trial.

INTRODUCTION: Colonoscopy plays important roles in bowel cancer screening and treatment. Poor bowel preparation occurs in 20-25% of colonoscopies. This negatively impacts adenoma and sessile serrated lesion detection rates, procedural time, requirement for repeat colonoscopies, healthcare costs and likelihood of patient withdrawal from screening programmes. It is unclear whether a combination of multimedia modalities can improve bowel preparation quality, adenoma detection rates and patient-reported measures in those undergoing colonoscopy assessment. METHODS: The DIGICLEAN trial is a prospective, parallel, multicentre, colonoscopist-blinded, randomised controlled trial. The trial will enrol 1294 participants aged 45 years and older who are indicated for a colonoscopy as an outpatient with a positive faecal occult blood test, iron deficiency anaemia or rectal bleeding. Participants will be randomised into the interventional arm, where bowel preparation instructions are delivered via a web-based application which uses scheduled short messaging service, regular patient survey assessment, email and videos; or the control arm, where routine standard written, verbal or emailed instructions are administered. The web-based application will assess patient-reported bloating, constipation and dietary adherence leading up to the colonoscopy. Depending on patient responses, additional aperients may be encouraged digitally in the interventional arm with same instructions made available in written format for the control arm. Patient-reported measures will be collected in both arms the day after the procedure using the validated Newcastle ENDOPREM questionnaire. In some sites, participants will undergo digital pre-anaesthetic screening as well. The co-primary endpoints are the adenoma detection rates and patient-reported measures taken after the colonoscopy. ETHICS AND DISSEMINATION: Ethics approval for this study was obtained from the Western Sydney Local Health District Human Research Ethics Committee (2022/ETH00059). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000747729.

Adolescents and young adults communicating with gastroenterologists: variation in inflammatory bowel disease clinical communication.

OBJECTIVES: This study explored the variation in emerging adults' communication with gastroenterologists around the management of inflammatory bowel disease (IBD). METHODS: Nineteen emerging adults with IBD aged 18-25 and seven gastroenterologists participated in the study. Outpatient specialist consultations of consenting participants were audio-recorded and transcribed. Transcribed consultations were analysed in terms of the linguistic structure of the consultations and the gastroenterologist-patient role relationship. RESULTS: Variations in the emerging adults' communication with their gastroenterologists stem partly from variation in their ability, opportunity, or need to contribute to the different phases of the consultation and partly from variations in the gastroenterologists' style of communication. Gastroenterologists differed in the construction of their role relationship with the patient, resulting in variations in employing empowering strategies including eliciting, exploring, and clarifying the patient's concerns, sharing clinical reasoning, and validating the patient experience. Variations were also observed in the length of appointments and the gastroenterologists' assessment and addressing of adherence issues. Techniques used by the gastroenterologist varied (1) from simply confirming adherence, to a comprehensive assessment of the patient's understanding of their management plan and their feedback, and (2) from use of persuasion to values calibration. CONCLUSIONS: Evidence-based consumer interventions and communication guidelines for clinicians are needed to address the identified variations in providing care to emerging adults living with chronic conditions.

Giant laterally spreading tumors of the duodenum: endoscopic resection outcomes, limitations, and caveats.

BACKGROUND: Giant hemicircumferential and greater nonampullary duodenal adenomas or laterally spreading tumors (LSTs) may be amenable to safe endoscopic resection, but little data exists on outcomes or risk stratification. DESIGN: We interrogated a prospectively maintained database of all patients who underwent endoscopic resection between January 2008 and November 2010. The resection technique was standardized. Major complications were defined as perforation, bleeding requiring readmission with hemoglobin drop of more than 20 g/L, or other substantial deviations from the usual clinical course. Outcomes were analyzed in 2 groups: giant lesions (>30 mm) and conventional duodenal polyps (<30 mm in diameter). Statistical evaluation was performed by using a χ(2) test. RESULTS: A total of 50 nonampullary duodenal polyps and LSTs were resected from 46 patients (23 men, mean age 59.4 years, range 35-83 years). Nineteen were giant hemicircumferential and greater LSTs (mean size 40.5 mm, range 30-80 mm), and 31 were less than 30 mm in diameter (mean size 14.5 mm, range 5-25 mm). Intraprocedural bleeding occurred more frequently in giant lesions (57.8% vs 19.3%, P = .005) and was treated with a combination of soft coagulation and endoscopic clips with hemostasis achieved in all cases. Major complications, mostly bleeding related, occurred in 5 patients (26.3%) with giant lesions and 1 patient (3.2%) with a smaller lesion (P = .014). There were no deaths. LIMITATION: Retrospective observational study in a tertiary center. CONCLUSIONS: Endoscopic resection of giant nonampullary duodenal LSTs is a successful treatment. However, it is hazardous and associated with significantly higher complication rates, primarily bleeding, when compared with conventional duodenal polypectomy. Safer and more effective hemostatic tools are required in this high-risk location.

Circumferential location predicts the risk of high-grade dysplasia and early adenocarcinoma in short-segment Barrett's esophagus.

BACKGROUND: Whether early Barrett's neoplasia has a predilection for particular spatial locations in shorter segment disease is currently unknown. Anatomic factors may play a role in lesion location because of differing levels of mucosal acid exposure. OBJECTIVE: To identify high-risk lesion locations, which has important implications for surveillance strategies. DESIGN: We interrogated a prospectively maintained database of patients who underwent endoscopic resection (ER) for Barrett's neoplasia at 2 Australian tertiary centers. Lesions targeted for ER were characterized and their location in the distal esophagus was noted as on a clock face. A Z test of proportions was used to test for deviation from uniformity in the distribution of lesions. SETTING: Two Australian tertiary centers. PATIENTS: Patients who underwent ER for Barrett's neoplasia. MAIN OUTCOME MEASUREMENTS: Lesion location in the distal oesophagus, resected specimen histology. RESULTS: A total of 146 consecutive patients had ER for biopsy-proven high-grade dysplasia or esophageal adenocarcinoma. A total of 75 patients had Barrett's segment length of 5 cm or less and a visible lesion. Five patients had 2 visible lesions giving a total of 80 lesions. ER of 66 lesions (82.5%) led to the identification of advanced pathology: 37 high-grade dysplasia (46%), 24 mucosal adenocarcinoma (30%), 5 submucosal adenocarcinoma (6%). Of a total of 80 lesions, 43 (53.8%) (95% CI, 42.9%-64.7%) were centered within the 2- to 5-o'clock arc, comprising 25% of the circumference. This area also accounted for 36 (54.5%) of the 66 lesions with advanced histology (95% CI, 42.5%-66.5%). All confidence intervals lie wholly above the 25% expected in a uniform circular distribution (P < .05). LIMITATIONS: Observational study in a tertiary center. CONCLUSIONS: In Barrett's maximal segments of 5 cm or less, the 2- to 5-o'clock arc, accounts for approximately 50% of macroscopically visible lesions and associated early neoplasia. This finding has important implications for surveillance strategies.

Dual biologic therapy with ocrelizumab for multiple sclerosis and vedolizumab for Crohn's disease: A case report and review of literature.

BACKGROUND: Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases, including Crohn's disease (CD). CASE SUMMARY: This case report and narrative review demonstrate the potential safety of dual biologic therapy (DBT) in a 45-year-old female with two separate immune-mediated diseases. She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab, and she had been recently diagnosed with CD after presenting with diarrhoea. The CD diagnosis was confirmed radiologically, endoscopically, histologically, and biochemically. The patient received treatment with vedolizumab, a gut-specific inhibitor of the α4ß7 integrin on leukocytes. No adverse reactions were observed for the duration of treatment. The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated. CONCLUSION: DBT may be a safe and effective option for the treatment of refractory disease or multiple immune-mediated diseases. Newer biologics, which have improved safety profiles and gut specificity, may provide promising avenues for treatment. However, caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties, side effects, and efficacy profiles. Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019, but treatment decisions should be made in a multidisciplinary setting. Further research from controlled trials is needed to better understand the safety profile of DBT in CD. The immunopathological mechanisms underlying DBT also remain to be clarified.

Review of exclusive enteral therapy in adult Crohn's disease.

BACKGROUND: Exclusive enteral nutrition (EEN) is a potentially effective but underused therapy for Crohn's disease (CD) in adults. It is first-line induction treatment for paediatric patients but remains a second-line or third-line therapy in adults. OBJECTIVE: To analyse the evidence for EEN in adult patients with CD, and summarise this in a narrative review. METHODS: In April/May 2020 and July 2021, a literature search was performed using the Medical Subject Headings (MeSH) terms: 'Crohn's disease', 'CD', 'inflammatory bowel disease', 'IBD', 'exclusive enteral nutrition', 'enteral nutrition', 'EEN', in PubMed, Scopus, Cochrane. Additional studies were obtained from references of search result articles as well as general reading. Studies with adult patients with CD treated with EEN were selected. 79 articles of relevance were found. Where data in adults were lacking, data from paediatric studies as extrapolated with care. RESULTS: EEN in adult patients been shown to improve clinical, biomarker, endoscopic and radiologic measures of disease activity. EEN avoids the potential adverse effects of recurrent corticosteroids for induction such as metabolic derangements and opportunistic infections. EEN has also demonstrated benefits among adult patients with fistulising and stricturing CD. It may avoid surgery in such patients. Preoperative EEN has also been shown to reduce postoperative complications and recurrence. There appears to be benefits in combing EEN with antitumour necrosis factor agents, however, benefits of combination therapy with other biologics are less clear. A major drawback of EEN therapy in adults has been poor compliance. More palatable polymeric formulations improved patient education and dietitian support may overcome this. Evidence in adults is limited to small studies, often with suboptimal control arms and lack of blinding. Larger scale studies with improved study design are needed to confirm these beneficial effects. CONCLUSION: Despite limitations in evidence EEN should be considered in treating adults with CD.

Depression, anxiety and stress among patients with inflammatory bowel disease during the COVID-19 pandemic: Australian national survey.

BACKGROUND: The global COVID-19 pandemic has impacted on the mental health of individuals, particularly those with chronic illnesses. We aimed to quantify stress, anxiety and depression among individuals with Inflammatory bowel disease (IBD) in Australia during the pandemic. METHODS: An electronic survey was made available to IBD patients Australia-wide from 17 June to 12 July 2020. Respondents with an underlying diagnosis of IBD and over 18 years of age were included. A validated questionnaire (Depression, Anxiety, Stress Score-21, DASS21) was used to assess depression, anxiety and stress. Data on potential predictors of depression, anxiety and stress were collected. RESULTS: 352 participated in the survey across Australia. 60.5% of respondents fulfilled DASS criteria for at least moderate depression, anxiety or stress. 45% reported a pre-existing diagnosis of depression and/or anxiety. Over 2/3 of these respondents reported worsening of their pre-existing depression/anxiety due to the current pandemic. Of those without a pre-existing diagnosis of anxiety or depression, high rates of at least moderate to severe depression (34.9%), anxiety (32.0%) and stress (29.7%) were noted. Younger age (OR 0.96, 95% CI 0.94 to 0.98, p<0.001), lack of access to an IBD nurse (OR 1.81, 95% CI 1.03 to 3.19, p=0.04) and lack of education on reducing infection risk (OR 1.99, 95% CI 1.13 to 3.50, p=0.017) were associated with significant stress, anxiety and/or depression. CONCLUSION: High prevalence of undiagnosed depression, anxiety and stress was identified among respondents. Improved access to IBD nurse support and greater attention to education are modifiable factors that may reduce depression, anxiety and/or stress among patients with IBD during the pandemic.

Early thiopurine maintenance is associated with reduced proximal disease progression and colectomy rate in ulcerative colitis.

BACKGROUND: Thiopurines effectively maintain remission in ulcerative colitis patients. Whether early initiation of thiopurines after ulcerative colitis diagnosis decreases proximal disease progression and colectomy rates is not known. METHODS: We conducted a cohort study of ulcerative colitis subjects recruited from 1970 to 2009. Early thiopurine maintenance was defined as commencement of azathioprine or mercaptopurine within 5 years of diagnosis and maintenance for at least 6 months. Propensity score matching was conducted to correct for confounders influencing early thiopurine introduction. Outcomes of interest were colectomy rate and endoscopic proximal disease extension. RESULTS: 982 consecutive ulcerative colitis subjects (12 879 patient-years) were recruited with 116 requiring colectomy. Thiopurines initiation and maintenance increased over time with median time to thiopurine commencement decreasing from 23 years in the first decade to 2 years in the last decade (P < 0.0001). Multivariate analysis showed that early thiopurine maintenance significantly decreased the need for colectomy [hazard ratio, 0.13; 95% confidence interval (CI):0.03-0.55; P = 0.006]. The number of subjects needed to be treated to reduce one colectomy at 5 and 10 years was 18 (95% CI, 16- 36) and 12 (95% CI, 11-25). After propensity score matching, early thiopurine maintenance was significantly associated with decreased colectomy (hazard ratio, 0.10; 95% CI, 0.03-0.43; P = 0.002) and proximal progression of disease extent (hazard ratio, 0.26; 95% CI, 0.10-0.78; P = 0.015). CONCLUSION: Early thiopurine maintenance for >6 months is significantly associated with reduced colectomy and proximal progression of disease extent in ulcerative colitis.

Ulcerative Colitis and Cytomegalovirus Infection: From A to Z.

Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.