Device-assisted enteroscopy performance measures in the United Kingdom: DEEP-UK quality improvement project.

BACKGROUND: Device-assisted enteroscopy (DAE) has become a well-established diagnostic and therapeutic tool for the management of small-bowel pathology. We aimed to evaluate the performance measures for DAE across the UK against the quality benchmarks proposed by the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We retrospectively collected data on patient demographics and DAE performance measures from electronic endoscopy records of consecutive patients who underwent DAE for diagnostic and therapeutic purposes across 12 enteroscopy centers in the UK between January 2017 and December 2022. RESULTS: A total of 2005 DAE procedures were performed in 1663 patients (median age 60 years; 53% men). Almost all procedures (98.1%) were performed for appropriate indications. Double-balloon enteroscopy was used for most procedures (82.0%), followed by single-balloon enteroscopy (17.2%) and spiral enteroscopy (0.7%). The estimated depth of insertion was documented in 73.4% of procedures. The overall diagnostic yield was 70.0%. Therapeutic interventions were performed in 42.6% of procedures, with a success rate of 96.6%. Overall, 78.0% of detected lesions were marked with a tattoo. Patient comfort was significantly better with the use of deep sedation compared with conscious sedation (99.7% vs. 68.5%; P<0.001). Major adverse events occurred in only 0.6% of procedures. CONCLUSIONS: Performance measures for DAE in the UK meet the ESGE quality benchmarks, with high diagnostic and therapeutic yields, and a low incidence of major adverse events. However, there is room for improvement in optimizing sedation practices, standardizing the depth of insertion documentation, and adopting marking techniques to aid in the follow-up of detected lesions.

Unveiling Distinct Proteomic Signatures in Complicated Crohn's Disease That Could Predict the Disease Course.

Crohn's disease (CD) is characterized by a chronic, progressive inflammation of the gastrointestinal tract often leading to complications, such as strictures and fistulae. Currently, there are no validated tools anticipating short- and long-term outcomes at an early stage. This investigation aims to elucidate variations in protein abundance across distinct CD phenotypes with the objective of uncovering potential biomarkers implicated in disease advancement. Serum samples collected from 30 CD patients and 15 healthy age-matched controls (HC) were subjected to depletion of highly abundant proteins and to a label-free mass spectrometry analysis. Twenty-four proteins were shown to be significantly different when comparing CD with HC. Of these, WD repeat-containing protein 31 (WDR31), and proteins involved in the acute inflammatory response, leucine-rich alpha-2-glycoprotein (LRG1) and serum amyloid A1 (SAA1), were more abundant in the aggressive subgroup. Against standard biomarkers, a positive correlation between SAA1 and WDR31 and C-reactive protein (CRP) was found. In this study, a unique serum biomarker panel for aggressive CD was identified, which could aid in predicting the disease course.

Updates in the diagnosis and management of non-ampullary small-bowel polyposis.

Advances in endoscopic instruments and techniques changed the strategy of diagnosis and management for non-ampullary small-bowel polyposis. In patients with Peutz-Jeghers syndrome, gastrointestinal surveillance using capsule endoscopy should commence no later than eight years old. Small bowel polyps >15 mm should be treated to prevent intussusception. Recently, endoscopic ischemic polypectomy and endoscopic reduction of intussusception were described. In patients with familial adenomatous polyposis, the first endoscopic screening using a lateral viewing and a longer endoscope to check the proximal jejunum should be performed around 25 years. Some experts recommend a first duodenal examination with a first colonoscopy (13 years). The surveillance intervals for duodenal polyposis should be adjusted individually. ESGE recommended the resection of every adenoma larger than 1 cm. Cold snare polypectomy has the potential to change the threshold of size for endoscopic resection. In patients with Juvenile polyposis syndrome, small bowel involvement seems infrequent and mostly located in the duodenal part. There is no indication for distal small bowel investigation.

Patterns of emergency admission for IBD patients over the last 10 years in Lothian, Scotland: a retrospective prevalent cohort analysis.

OBJECTIVE: It is unclear how the compounding prevalence of inflammatory bowel disease (IBD) has translated into the causes and rates of hospitalisation, particularly in an era of increased biologic prescribing. We aimed to analyse these trends in a population-based IBD cohort over the last 10 years. DESIGN: The Lothian IBD registry is a complete, validated, prevalent database of IBD patients in NHS Lothian, Scotland. ICD-10 coding of hospital discharge letters from all IBD patient admissions to secondary care between 1 January 2010 and 31 December 2019 was interrogated for admission cause, with linkage to local/national data sets on death and prescribed drugs. RESULTS: Fifty-seven per cent (4673/8211) of all IBD patients were admitted to secondary care for >24 h between 1 January 2010 and 31 December 2019. In patients <40 years, IBD was the commonest reason for admission (38% of admissions), whereas infection was the most common cause in those >60 years (19% of admissions). Three per cent (243/8211) of IBD patients accounted for 50% of the total IBD bed-days over the study period. Age-standardised IBD admission rates fell from 39.4 to 25.5 admissions per 100,000 population between 2010 and 2019, an average annual percentage reduction of 3% (95% CI -4.5% to -2.1%, p < 0.0001). Non-IBD admission rates were unchanged overall (145-137 per 100,000 population) and specifically for serious (hospitalisation) and severe (ITU admission or death) infection over the same period. CONCLUSION: Despite compounding prevalence and increased biologic use, IBD admission rates are falling. The cause of admission varies with age, with infection the predominant cause in older patients.

Are we addressing the top 10 research priorities in IBD?

BACKGROUND: Since publication of the top 10 research priorities in inflammatory bowel disease (IBD) based on the James Lind Alliance Priority Setting Partnership, the question remains whether this has influenced the IBD-research landscape. This study aimed to create an overview of the current distribution of research interests of trials in the UK. METHODS: The ClinicalTrials.gov database and European Union Clinical Trials Register were screened for clinical trials set up from 9 August 2016 to 16 November 2019 in the UK involving adult patients with IBD. RESULTS: Of 20 non-industry-sponsored studies, a quarter investigated treatment strategies considering efficacy, safety and cost-effectiveness (priority 1). Four evaluated the role of diet (priorities 3 and 7). Development/assessment of biomarkers for patient stratification (priority 2) and fatigue (priority 8) were subject of three studies. IBD-related pain and control of diarrhoea/incontinence were each subject of 2 studies (priorities 4 and 6). The effect of gut microbiota (priority 10) and optimal strategy for perianal Crohn's disease (priority 5) was the focus of 2 studies each. One study evaluated surgery for terminal ileal Crohn's disease (priority 9). Of 63 industry-sponsored studies, 59 focused on priority 1. CONCLUSIONS: This study presents an impression of the breadth of the IBD-research landscape in the UK, in light of the top 10 research priorities published in 2016. Optimal treatment strategy has been the most studied research priority by academic and industry-sponsored trials. Fewer studies focused on patient-reported outcomes. It remains debatable to what extent the current research landscape adequately represents all stakeholders' viewpoints on needs for expanded knowledge in IBD, particularly the patients' perspective.

Serum Interleukin (IL)-23 and IL-17 Profile in Inflammatory Bowel Disease (IBD) Patients Could Differentiate between Severe and Non-Severe Disease.

Interleukin (IL)-17 and IL-23 are crucial for mediating gut mucosal inflammation in inflammatory bowel disease (IBD), which has led to new therapeutic strategies. We assessed the relevancy of IL-17 and IL-23 serum levels as potential biomarkers towards severe IBD discrimination and disease-related complications. Sixty-two patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) were included. Serum IL-17 and IL-23 were measured by sandwich enzyme-linked immunosorbent assays (ELISA). IL-23 and fecal calprotectin (FCal) were significantly higher in severe CD (p < 0.001) and UC (p < 0.001 and p = 0.001, respectively), compared to mild or moderate. Elevated C-reactive protein (CRP) was correlated with severe disease only in CD (p = 0.008), whereas for UC, disease severity was associated with increased IL-17 values (p < 0.001). Diagnostic role of IL-23 was superior to FCal in discriminating between severe and mild to moderate CD (p < 0.001). IL-23 levels were also significantly higher in CD patients with intestinal complications (p = 0.04). Both IL-17 and IL-23 correlate with IBD severity, and IL-23 might be a promising novel biomarker for severe CD. Identifying the dominant IL pathway involved in IBD severity could serve as guidance for clinical decision-making on biologic therapy.

Effectiveness and Safety of Adalimumab Biosimilar SB5 in Inflammatory Bowel Disease: Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naïve SB5 Observational Cohorts.

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6-15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2-12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up.

Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Tofacitinib is a Janus kinase inhibitor (JAKi) recently approved for the treatment of moderate to severe ulcerative colitis (UC) based on robust efficacy and safety data derived from OCTAVE clinical trials. Evidence on the outcomes of tofacitinib therapy in real-world UC patients is needed, as a number of these patients would be deemed ineligible for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe UC patients. METHODS: We searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30 May 2018 and 24 January 2021. Pooled induction (8-14 weeks) and maintenance (16-26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models. RESULTS: Nine studies were included, comprising 830 patients, of which 81% were previously treated with anti-tumour necrosis factor (TNF) and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% confidence interval, 41-60%) and 37% (26-45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31-50%) and 29% (23-36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%). CONCLUSION: Tofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.

Normalization of Fecal Calprotectin Within 12 Months of Diagnosis Is Associated With Reduced Risk of Disease Progression in Patients With Crohn's Disease.

BACKGROUND & AIMS: The level of fecal calprotectin (FC) correlates with endoscopic evidence of inflammation in Crohn's disease (CD). A treat-to-target algorithm for patients with CD, that incorporates FC, outperforms a treatment strategy based on symptoms alone in the induction of mucosal healing at 12 months. We investigated whether normalization of FC within 12 months of diagnosis of CD is associated with a reduction in disease progression. METHODS: We performed a retrospective cohort study at a tertiary IBD centre in the United Kingdom. We identified all incident cases of CD diagnosed from 2005 through 2017. Patients with a FC measurement ≥250 µg/g at diagnosis who also had at least 1 follow-up FC measurement within the first 12 months of diagnosis and >12 months of follow up were included. The last FC measurement within 12 months of diagnosis was used to determine normalization (cut-off <250 µg/g). The primary endpoint was time to first disease progression (composite of progression in Montreal disease behavior B1 to B2/3, B2 to B3, or new perianal disease; CD-related surgery; or CD-related hospitalization). Cox proportional hazards regression analysis was used to determine independent factors associated with time to first disease progression. RESULTS: A total of 375 patients out of 1389 incident cases were included, with a median follow up of 5.3 years (interquartile range, 3.1-7.4 years). Normalization of FC within 12 months of diagnosis was confirmed in 43.5% of patients. Patients with normalized levels of FC had a significantly lower risk of composite disease progression (hazard ratio [HR], 0.36; 95% CI, 0.24-0.53; P < .001). They also had a lower risk of reaching any of the separate progression endpoints (progression in Montreal behavior or new perianal disease HR, 0.22; 95% CI, 0.11-0.45; P < .001; hospitalization HR, 0.33; 95% CI, 0.21-0.53; P <.001; surgery HR, 0.39; 95% CI, 0.19-0.78; P = .008) CONCLUSIONS: Normalization of FC within 12 months of diagnosis is associated with a reduced risk of progression of CD.

What is the Impact of the Proportion of Solid Necrotic Content on the Number of Necrosectomies during EUS-Guided Drainage using Lumen-Apposing Metallic Stents of Pancreatic Walled-off Necrosis ?

BACKGROUND AND AIMS: The fully-covered, lumen apposing metal stents are designed for one step placement, facilitating the direct endoscopic necrosectomy into the walled-off pancreatic necrosis. However, the prediction of the number of necrosectomy sessions in these patients is not known. This study evaluated the association between the proportion of solid necrotic material inside walled-off necrosis, as assessed during the endosonography placement of a lumen apposing metal stent, and the number of necrosectomies subsequently required. METHODS: Patients from three tertiary medical centers with symptomatic walled off pancreatic necrosis (pain, infection, gastric/biliary obstruction) at more than 4 weeks after onset of acute pancreatitis were retrospectively analysed. Proportion of solid necrotic debris was estimated during endosonography procedure of lumen apposing metal stents placement. Necrosectomy was performed when obstruction or inflammation occurred subsequently. Lumen apposing metal stents were removed after clearance of necrotic content. RESULTS: In 46 patients with successful lumen apposing metal stents placement, necrosectomy was performed in 39 patients (72.78%). Performance of 3 or more necrosectomies was significantly associated with more than 50% pancreatic necrosis (p=0.032), but not with walled-off pancreatic necrosis size or location. Necrotic infection during lumen apposing metal stents stenting was associated with hypoalbuminemia, but not with necrosectomy requirement. Clinical success after a median follow-up of 13.37 months was 87%. CONCLUSIONS: Walled-off pancreatic necrosis with more than 50% solid necrotic content were associated with more necrosectomy procedures, requiering longer endoscopy time, intravenous sedations, and higher costs.

Small molecule drugs in the treatment of inflammatory bowel diseases: which one, when and why? - a systematic review.

In the 'treat-to-target' era of inflammatory bowel disease (IBD) management, small molecule drugs (SMDs) represent a promising alternative to biomolecular drugs. Moreover, increasing failure rates of anti-tumor necrosis factor α agents have contributed to the development of new molecules with different mechanisms of action and bioavailability. This review focuses on the positioning of new, orally targeted therapies in the treatment algorithm of both Crohn's disease (CD) and ulcerative colitis (UC), with special consideration to their efficacy and safety. We performed a comprehensive search of PubMed and clinical trial registries to identify randomized controlled trials assessing SMDs in adult patients with moderate-to-severe IBD, irrespective of previous exposure to other biologics. In this review, we included 15 double-blind, placebo-controlled trials that assessed the efficacy and safety of Janus kinase inhibitors, sphingosine-1-phosphate modulators (S1P), SMAD blockers, phosphodiesterase 4 inhibitors and α-4 antagonists. The primary endpoints in UC were achieved for tofacitinib in the phase III OCTAVE study and AJM-300, with a favorable safety profile. S1P receptor agonists, such as etrasimod and ozanimod, demonstrated favorable results in induction studies. For CD, filgotinib and upadacitinib also met the primary outcome criteria. Available data have demonstrated so far that SMDs have an advantageous safety and efficacy profile. However, their use in a clinical setting will eventually require a personalized, mechanism-based therapeutic approach.

Depression and suicide ideation in chronic hepatitis C patients untreated and treated with interferon: prevalence, prevention, and treatment.

Interferon-based therapies were until recently the standard of care in chronic hepatitis C (CHC), despite their side effects. We aimed to review the available data on the depression and suicide in CHC patients receiving or not antiviral therapy based on interferon treatment. A PubMed search was performed, identifying relevant papers published between 1991 and January 2015 concerning major depressive disorders and suicidal risk in patients under interferon. A total of 21 relevant papers were retrieved. Prospective studies reported depression as the most common side effect of interferon, with an incidence peak between weeks 8 and 12 of therapy. Suicide risk was analyzed in 7 of the reviewed articles, and case reports of attempted suicide were discussed. Moreover, studies have shown that pretreatment with serotonin reuptake inhibitors is a good strategy for the prevention of interferon-induced depression.