Abstract
Background and Aims
Few population-based cohort studies have assessed the disease course of ulcerative colitis UC in the era of biological therapy and widespread use of immunomodulators. The ...aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.
Methods
In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.
Results
A total of 717 patients were included in the study. During follow-up, 43 6% patients underwent a colectomy and 163 23% patients were hospitalised. Of patients with limited colitis distal to the left flexure, 90 21% progressed to extensive colitis. In addition, 92 27% patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio HR: 0.5 95% CI: 0.3–0.8. Overall, patients were treated similarly in both geographical regions; 80 11% patients needed biological therapy and 210 29% patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation HR: 0.5 95% CI: 0.3–0.8.
Conclusions
Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.
Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which ...bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC).
In healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103
DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD).
Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients. Video Abstract.
Cytokine storm can result from cancer immunotherapy or certain infections, including COVID-19. Though short-term immune-related adverse events are routinely described, longer-term immune consequences ...and sequential immune monitoring are not as well defined. In 2006, six healthy volunteers received TGN1412, a CD28 superagonist antibody, in a first-in-man clinical trial and suffered from cytokine storm. After the initial cytokine release, antibody effect-specific immune monitoring started on Day + 10 and consisted mainly of evaluation of dendritic cell and T-cell subsets and 15 serum cytokines at 21 time-points over 2 years. All patients developed problems with concentration and memory; three patients were diagnosed with mild-to-moderate depression. Mild neutropenia and autoantibody production was observed intermittently. One patient suffered from peripheral dry gangrene, required amputations, and had persistent Raynaud’s phenomenon. Gastrointestinal irritability was noted in three patients and coincided with elevated γδT-cells. One had pruritus associated with elevated IgE levels, also found in three other asymptomatic patients. Dendritic cells, initially undetectable, rose to normal within a month. Naïve CD8
+
T-cells were maintained at high levels, whereas naïve CD4
+
and memory CD4
+
and CD8
+
T-cells started high but declined over 2 years. T-regulatory cells cycled circannually and were normal in number. Cytokine dysregulation was especially noted in one patient with systemic symptoms. Over a 2-year follow-up, cognitive deficits were observed in all patients following TGN1412 infusion. Some also had signs or symptoms of psychological, mucosal or immune dysregulation. These observations may discern immunopathology, treatment targets, and long-term monitoring strategies for other patients undergoing immunotherapy or with cytokine storm.
Background Colonoscopy has a miss rate for adenomas that may partly relate to poor visualization of the colonic surface. Dynamic position changes during colonoscope withdrawal can improve luminal ...distension. Objective To assess whether position changes also improve adenoma and polyp detection. Design Randomized crossover clinical trial. Setting Academic endoscopy unit. Patients This study involved 130 patients who presented for routine colonoscopy. Intervention Examination either entirely in the left lateral position followed by position changes (cecum to hepatic flexure, left lateral; transverse colon, supine; splenic flexure and descending colon, right lateral) or vice versa. After both examinations, polyps were removed for histopathology. Main Outcome Measurements Proportion of patients with ≥1 polyp or adenoma detected between the hepatic flexure and the sigmoid-descending colon junction. Luminal distension was measured on a scale of 1 to 5: 1, total collapse; 5, fully distended. Results At least 1 adenoma was detected in 34% of patients in colon areas in which the patient position differed from left lateral (transverse colon, splenic flexure, descending colon) compared with 23% examined with the patient in the left lateral position alone ( P = .01). At least 1 polyp was detected in 52% of patients with position changes versus 34% of patients examined in the left lateral position alone ( P < .001). Adenoma and polyp detection were positively correlated with an improved distension score (correlation coefficient, 0.12; P < .001). Adenomas were detected in 16% of colon areas with adequate distension scores (4 and 5) compared with 7% of those with borderline or nondiagnostic scores (1-3; P < .001). Limitations Single-operator study. Conclusion Dynamic position changes during colonoscope withdrawal significantly improved polyp and adenoma detection. (Clinical trial registration number: NCT00234650 )
Abstract
Introduction
Anti-SARS-CoV-2 vaccine clinical trials did not include patients with immune-mediated conditions such as inflammatory bowel disease IBD. We aimed to describe the implementation ...of anti-SARS-CoV-2 vaccination among IBD patients, patients’ concerns, and the side effect profile of the anti-SARS-CoV-2 vaccines, using real-world data.
Methods
An anonymous web-based self-completed survey was distributed in 36 European countries between June and July 2021. The results of the patient characteristics, concerns, vaccination status, and side effect profile were analysed.
Results
In all 3272 IBD patients completed the survey, 79.6% had received at least one dose of anti-SARS-CoV-2 vaccine, and 71.7% had completed the vaccination process. Patients over 60 years old had a significantly higher rate of vaccination p < 0.001. Patients’ main concerns before vaccination were the possibility of having worse vaccine-related adverse events due to their IBD 24.6%, an IBD flare after vaccination 21.1%, and reduced vaccine efficacy due to IBD or associated immunosuppression 17.6%. After the first dose of the vaccine, 72.4% had local symptoms and 51.4% had systemic symptoms five patients had non-specified thrombosis. Adverse events were less frequent after the second dose of the vaccine and in older patients. Only a minority of the patients were hospitalised 0.3%, needed a consultation 3.6%, or had to change IBD therapy 13.4% after anti-SARS-CoV-2 vaccination.
Conclusions
Although IBD patients raised concerns about the safety and efficacy of anti-SARS-CoV-2 vaccines, the implementation of vaccination in those responding to our survey was high and the adverse events were comparable to the general population, with minimal impact on their IBD.
Introduction. Previous epidemiological studies suggest a higher rate of pancolonic disease in South Asians (SA) compared with White Europeans (WE). The aim of the study was to compare colectomy rates ...for ulcerative colitis (UC) in SA to those of WE. Methods. Patients with UC were identified from a national administrative dataset (Hospital Episode Statistics, HES) between 1997 and 2012 according to ICD-10 diagnosis code K51 for UC. The colectomy rate for each ethnic group was calculated as the proportion of patients who underwent colectomy from the total UC cases for that group. Results. Of 212,430 UC cases, 73,318 (35.3%) were coded for ethnicity. There was no significant difference in the colectomy rate between SA and WE (6.93% versus 6.90%). Indians had a significantly higher colectomy rate than WE (9.8% versus 6.9%, p<0.001). Indian patients were 21% more likely to require colectomy for UC compared with WE group (OR: 1.21, 95% CI: 1.04–1.42, and p=0.001). Conclusions. Given the limitations in coding, the colectomy rate in this cohort was higher in Indians compared to WE. A prospectively recruited ethnic cohort study will decipher whether this reflects a more aggressive phenotype or is due to other confounding factors.
Background and Aims:
To investigate the long-term efficacy of endoscopic dilatation of Crohn’s anastomotic strictures and to identify risk and protective factors associated with the need for repeat ...dilatation or surgery.
Methods:
A total of 54 patients who had endoscopic balloon dilatations for anastomotic Crohn’s strictures between 2004 and 2009, with follow-up until June 2014, were identified from a single tertiary center. The primary end points were repeat dilatation or surgical resection, and the impact of radiology, medical therapy, and endoscopic data on these outcomes was analysed with Cox proportional hazards analysis.
Results:
A total of 151 dilatations were performed on patients with a median age of 52 years interquartile range (IQR), 46–62 years. The median duration from the first to the second dilatation was 6 years (IQR, 5–7 years). The median disease duration was 28 years (IQR, 19–32 years). At endoscopy, disease activity was reported in 50/54 (92%) cases, with a median Rutgeerts grading of i2 (range, i0–i4). A median of two (IQR 1–9) dilatations was required, with a time to repeat dilatation of 23 months (IQR 7.2–56.9). Escalation of medical therapy was adopted in 22/54 patients (41% of the study population). On multivariate analysis, only combination therapy (anti-TNFα and immunomodulator) was significantly associated with the (decreased) need for repeated dilatation hazard ratio (HR) 0.23; 95% CI, 0.07–0.67; p = 0.01. Anastomotic resections were performed in 10 (18%) patients, with a Rutgeerts score of i4 at initial endoscopic balloon dilatation being associated with this outcome (HR 4.55; 95% CI 1.08–19.29; p = 0.04) on multivariate analysis.
Conclusion:
Endoscopic balloon dilatation of Crohn’s anastomotic strictures is safe and effective in the long term. We demonstrate that active disease predicts for future surgery, while escalation of medical therapy may decrease the need for repeat dilatation.
Epidemiological associations have implicated factors associated with Westernization, including the Western diet, in the development of inflammatory bowel disease (IBD). The role of diet in IBD ...etiopathogenesis, disease control and symptom management remains incompletely understood. Few studies have collected data on the dietary habits of immigrant populations living with IBD. Our aim was to describe the dietary practices and beliefs of British South Asians with IBD.
A 30-item questionnaire was developed and consecutively administered to 255 British South Asians with IBD attending gastroenterology clinics in the United Kingdom.
Fifty-one percent of participants believed diet was the initiating factor for their IBD and 63% felt diet had previously triggered disease relapse. Eighty-nine percent avoided certain dietary items in the belief that this would prevent relapse. The most commonly avoided foods and drinks were spicy and fatty foods, carbonated drinks, milk products, alcohol, coffee, and red meat. A third of patients had tried a whole food exclusion diet, most commonly lactose- or gluten-free, and this was most frequently reported amongst those with clinically active IBD (P= 0.02). Almost 60% of participants avoided eating the same menu as their family, or eating out, at least sometimes, to prevent IBD relapse.
British South Asians with IBD demonstrate significant dietary beliefs and food avoidance behaviors with increased frequency compared to those reported in Caucasian IBD populations. Studies in immigrant populations may offer valuable insights into the interaction between diet, Westernization and cultural drift in IBD pathogenesis and symptomatology.
Background and Aim
A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease ...unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years.
Methods
The Epi‐IBD study is a prospective population‐based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow‐up period.
Results
Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow‐up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4–12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow‐up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5‐aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU.
Conclusions
In a population‐based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow‐up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.
Background:
Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a ...real-world study of linaclotide in the UK.
Methods:
This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded.
Results:
In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1–77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks −77.0 (−96.3, −57.7); p < 0.001; n = 124 and baseline to 52 weeks −70.7 (−95.0, −46.5); p < 0.001; n = 76. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%).
Conclusion:
Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice.
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