Higher Ustekinumab Levels in Maintenance Therapy are Associated with Greater Mucosal Healing and Mucosal Response in Crohn's Disease: An Experience of 2 IBD Centers.

BACKGROUND: Ustekinumab (UST), a human monoclonal antibody that binds the p40 subunit of interleukin 12 (IL-12) and IL-23, is licensed for induction and maintenance therapy of moderate to severe inflammatory bowel disease (IBD). To date, there is limited data published on any potential association between ustekinumab serum trough levels and mucosal healing in order to guide treatment strategies and appropriate dosing. AIM: This study aims to identify a relationship between maintenance ustekinumab serum trough levels and mucosal healing and/or response in patients with Crohn's disease in an observational cohort study. METHODS: Ustekinumab serum trough levels and antibody titres were analyzed in patients on maintenance drug using an ELISA drug-tolerant assay. Mucosal response (MR) was defined as ≥50% reduction in fecal calprotectin level (FC) and/or ≥50% reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD score). Mucosal healing (MH) was defined as FC ≤150 µg/mL and/or global SES-CD score ≤5. Median trough levels were analyzed using the Kruskal-Wallis test, and logistic regression was used to determine sensitivity and specificity of levels predicting mucosal response. RESULTS: Forty-seven patients on maintenance ustekinumab for Crohn's disease were included in this study. The majority were female (66%), with a median age of 40 years (21-78 years). The majority of patients were biologic-experienced (89.4%, n = 42). Patients with histologically confirmed Crohn's disease represented 100% (n = 47) of the cohort. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. Patients with mucosal healing (n = 30) had significantly higher mean serum ustekinumab levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). A serum ustekinumab trough level greater than 2.3 µg/mL was associated with MH, with a sensitivity of 100% and specificity of 90.6% (likelihood ratio 10.7). Similarly, for patients with MR (n = 40), we observed a higher mean serum ustekinumab trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). Furthermore, a serum ustekinumab trough level greater than 2.3 µg/mL was associated with a 10-fold increased likelihood of mucosal response vs mucosal nonresponse (sensitivity 100%, specificity 90.5%, likelihood ratio 10.5). CONCLUSION: This study demonstrates that higher ustekinumab serum trough levels are associated with a greater likelihood of achieving mucosal healing and mucosal response in patients with Crohn's disease regardless of prior biologic exposure. Further prospective studies are required to correlate target maintenance trough levels and the optimal time to dose-escalate in order to improve patient outcomes.

Meta-analysis: Impact of intragastric balloon therapy on NAFLD-related parameters in patients with obesity.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease affecting approximately 25% of adults in the western world. Intragastric balloon (IGB) is an endoscopic bariatric therapy -a therapeutic endoscopic tool that has shown promise in inducing weight loss. Its role in the treatment of NAFLD is yet to be established. AIM: To evaluate the effect of IGB as a treatment option in NAFLD. METHODS: We searched MEDLINE (PubMed) and EMBASE from inception to September 2022. We included studies evaluating the impact of IGB on obesity with the assessment of one or more liver-related outcomes and studies primarily evaluating the impact of IGB on NAFLD. We included comparative and non-comparative studies; primary outcomes were liver-related NAFLD surrogates. RESULTS: We included 19 studies with 911 patients. IGB demonstrated an effect on NAFLD parameters including NAFLD activity score (NAS): mean difference (MD): -3.0 [95% CI: -2.41 to -3.59], ALT: MD: -10.40 U/L [95% CI: -7.31 to -13.49], liver volume: MD -397.9 [95% CI: -212.78 to 1008.58] and liver steatosis: MD: -37.76 dB/m [95% CI: -21.59 to -53.92]. There were significant reductions in non-liver-related outcomes of body weight, BMI, glycated haemoglobin and HOMA-IR. CONCLUSION: Intragastric balloons may play an important role in addressing the treatment gap in NAFLD management.

Gender equality in academic gastroenterology: a review of gastroenterology literature over four decades.

BACKGROUND: Historically males have dominated the physician ranks, although in recent years, there has been an increase in the proportion of female doctors to redress this imbalance. With such attention being paid to gender equality in society, this study aimed to characterise the changing prevalence of female authorship of peer-reviewed published research with in the field of gastroenterology. AIMS: In order to quantitatively assess the growth of female gastroenterologists, we decided to examine the changing face of gender equality within the field of academic gastroenterology from 1971 to 2010. METHODS: All research published in the January and July issues of Gastroenterology from 1971 to 2010 was reviewed. The gender of the first author and last author (considered the senior author) of each study was recorded. Research was subsequently categorised by type: basic science research, clinical trials, and epidemiologic research. Data was analysed in 5-year time periods. RESULTS: Author gender could be identified from a total of 865 abstracts from 80 journal issues. In total, there were 120 (13.8%) female first authors and 91 (10.5%) female senior authors. Female first authorship has tripled since 1995, from 11% (1991-1995) to 32% (2006-2010). Female senior authorship has also tripled since 2000, from 7% (1996-2000) to 24% (2006-2010). DISCUSSION: Results demonstrated that there has been a significant increase in the prevalence of female authorship of published research in Gastroenterology since 1995. The increasing prevalence of females within the field of academic gastroenterology can therefore be extrapolated to demonstrate the growing numbers of female gastroenterologists in the entire field including clinical and academic gastroenterology.

EUS-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing metal stents in patients with malignant distal biliary obstruction: multicenter collaboration from the United Kingdom and Ireland.

BACKGROUND AND AIMS: EUS-guided choledochoduodenostomy (EUS-CDD) with an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with malignant distal biliary obstruction (MDBO). Our aim was to assess the efficacy, safety, and outcomes in patients with MDBO who underwent EUS-CDD with an EC-LAMS. METHODS: A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMSs at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 and November 2020 was undertaken. RESULTS: One hundred twenty patients (55% men) with a median age of 73 years (interquartile range, 17; range, 43-94) were included. The median follow-up period in 117 patients was 70 days (interquartile range, 169; range, 3-869), and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to ≤50% of original value within 14 days) was achieved in 94.8% of patients (92/97). The adverse event rate was 17.5% (n = 21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). CONCLUSIONS: EUS-CDD with EC-LAMSs at tertiary institutions within a regional hepatopancreatobiliary network for treatment of MDBO was effective in those where ERCP was not possible or was unsuccessful. When technical failures or adverse events occur, most patients can be managed with conservative or endoscopic therapy.

The optimal management of anti-drug antibodies to infliximab and identification of anti-drug antibody values for clinical outcomes in patients with inflammatory bowel disease.

PURPOSE: Secondary loss of response (LOR) to infliximab (IFX) commonly occurs. One cause is the development of anti-drug antibodies (ADAs). Evidence regarding the optimal management of ADAs is lacking. We aim to identify the best practice of management of ADAs to IFX to avoid discontinuation of therapy and to determine specific ADA cut-off values to determine pre-specified clinical outcomes. METHODS: This is a 3-year study of patients receiving IFX who developed ADAs > 8µg/ml. We reviewed the management strategies and subsequent outcomes in patients who developed ADAs. RESULTS: A total of 132 patients are included. Baseline characteristics include 54% male patients and mean age of 39.4 years. Fifty-two percent (n = 69) of patients discontinued IFX following the development of ADAs, 33.3% (n = 44) sited as secondary to LOR. Both an increase in IFX and adjustments to combination therapy were associated with lower rates of discontinuation of IFX vs no intervention (p value < 0.001, p value < 0.001). An increase in IFX resulted in a significant difference in ADAs/IFX trough levels pre- and post-intervention (p value < 0.001, p value = 0.032). ROC curve analysis yielded significant cut-off values for ADAs and treatment failure (ADA >16µg/ml, AUC 0.642, p value 0.003), steroid use (ADA >19 µg/ml, AUC 0.61, p value 0.048) development of infusion reactions (ADA> 37 µg/ml, AUC 0.68, p value 0.045) and switch to another biologic (ADA >45 µg/ml, AUC 0.739, p value <0.001). CONCLUSION: Both escalation of IFX and combination therapy resulted in lower rates of LOR. ROC curve analysis identified significant cut-off values for ADA trough levels and important clinical outcomes.

Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Measuring the value of endoscopic retrograde cholangiopancreatography activity: an opportunity to stratify endoscopists on the basis of their value.

INTRODUCTION: As finite healthcare resources come under pressure, the value of physician activity is assuming increasing importance. The value in healthcare can be defined as patient health outcomes achieved per monetary unit spent. Even though some attempts have been made to quantify the value of clinician activity, there is little in the medical literature describing the importance of endoscopists' activity. This study aimed to characterize the value of endoscopic retrograde cholangiopancreatography (ERCP) performance of five gastroenterologists. PATIENTS AND METHODS: We carried out a retrospective-prospective cohort study using the databases of patients undergoing ERCP between September 2014 and March 2017. We collected data from 1070 patients who underwent ERCP comparing value among the ERCPists at index ERCP. Procedure value was calculated using the formula Q/(T/C), where Q is the quality of procedure, T is the duration of procedure and C is the adjusted for complexity level. Quality and complexity were derived on a 1-4 Likert scale on the basis of American Society for Gastrointestinal Endoscopy criteria; time was recorded (in min) from intubation to extubation. Endoscopist time calculated from procedure time was considered a surrogate marker of cost as individual components of procedure cost were not itemized. RESULTS: In total, 590 procedures were analysed: 465 retrospectively over 24 months and 125 prospectively over 6 months. There was a 32% variation in the value of endoscopist activity in a more substantial retrospective cohort, with an even more considerable 73% variation in a smaller prospective arm. CONCLUSION: In an analysis of greater than 1000 ERCPs by a small cohort of experienced ERCPists, there was a wide variation in the value of endoscopist activity. Although the precision of estimating procedural costs needs further refinement, these findings show the ability to stratify ERCPists on the basis of the value their activity. As healthcare costs are scrutinized more closely, such value measurements are likely to become more relevant.

A randomized trial comparing winged versus conventional plastic stents for malignant bile duct strictures.

BACKGROUND AND STUDY AIMS: Stent insertion at endoscopic retrograde cholangiopancreatography (ERCP) is an established therapy for managing malignant biliary obstruction. Conventional plastic stents with a tubular design are most commonly used despite limited patency. Plastic stents with a winged design may theoretically increase the duration of stent patency. The aim of this study was to compare stent patency of the winged versus conventional plastic stents in patients with malignant biliary obstruction. PATIENTS AND METHODS: A prospective, randomized subject-blinded trial was conducted. Patients with malignant biliary obstruction were randomized (1:1) to either a 10 French winged stent or 7 or 10 French conventional plastic stent. Strictures greater than 1 cm distal to the hilum were included. Patients were followed clinically to determine the frequency of stent failure until surgery, death or study closure. RESULTS: Fifty-eight patients were enrolled. Following 9 exclusions, 49 patients were randomized to a winged (n = 23) or conventional stent (n = 26). Median time to stent failure was 89 (95 % CI 26-NA) vs 143 (95 % CI 33 - 266) days ( P  = 0.963) for the winged and conventional group, respectively. Stent failure for the winged group occurred in 11 (48 %) compared to 14 (54 %) in the conventional group. Median survival was 123 (95 % CI 81 - 189) vs 342 days (95 % CI 123 - 704) (p = 0.084) in the winged and conventional group respectively. There were no procedure related adverse events. CONCLUSIONS: Improvement in stent patency was not seen with the winged stent when compared to the conventional plastic stent.

Gastrointestinal Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy Specimens: Adequate Diagnostic Yield and Accuracy Can Be Achieved without On-Site Evaluation.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is the preferred method for biopsying the gastrointestinal tract, and rapid on-site cytological evaluation is considered standard practice. Our institution does not perform on-site evaluation; this study analyzes our overall diagnostic yield, accuracy, and incidence of nondiagnostic cases to determine the validity of this strategy. DESIGN: Data encompassing clinical information, procedural records, and cytological assessment were analyzed for gastrointestinal EUS-FNA procedures (n = 85) performed at Vancouver General Hospital from January 2012 to January 2013. We compared our results with those of studies that had on-site evaluation and studies that did not have on-site evaluation. RESULTS: Eighty-five biopsies were performed in 78 patients, from sites that included the pancreas, the stomach, the duodenum, lymph nodes, and retroperitoneal masses. Malignancies were diagnosed in 45 (53%) biopsies, while 24 (29%) encompassed benign entities. Suspicious and atypical results were recorded in 8 (9%) and 6 (7%) cases, respectively. Only 2 (2%) cases received a cytological diagnosis of 'nondiagnostic'. Our overall accuracy was 72%, our diagnostic yield was 98%, and our nondiagnostic rate was 2%. Our results did not significantly differ from those of studies that did have on-site evaluation. CONCLUSION: Our study highlights that adequate diagnostic accuracy can be achieved without on-site evaluation.

Therapeutic Endoscopic Ultrasound.

Endoscopic ultrasound (EUS) technology has evolved dramatically over the past 20 years, from being a supplementary diagnostic aid available only in large medical centers to being a core diagnostic and therapeutic tool that is widely available. Although formal recommendations and practice guidelines have not been developed, there are considerable data supporting the use of EUS for its technical accuracy in diagnosing pancreaticobiliary and gastrointestinal pathology. Endosonography is now routine practice not only for pathologic diagnosis and tumor staging but also for drainage of cystic lesions and celiac plexus neurolysis. In this article, we cover the use of EUS in biliary and pancreatic intervention, ablative therapy, enterostomy, and vascular intervention.

Propofol use in endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

Compared to standard endoscopy, endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are often lengthier and more complex, thus requiring higher doses of sedatives for patient comfort and compliance. The aim of this review is to provide the reader with information regarding the use, safety profile, and merits of propofol for sedation in advanced endoscopic procedures like ERCP and EUS, based on the current literature.

Impact of magnetic resonance enterography in the management of small bowel Crohn's disease.

INTRODUCTION: Magnetic resonance enterography (MRE) is a relatively new imaging modality that involves small bowel distension with orally administered fluid. Few studies have assessed its impact on patient management. AIM: The aim of this study was to determine whether MRE influenced the management of patients with established small bowel Crohn's disease (CD). MATERIALS AND METHODS: From a prospectively maintained database of patients with inflammatory bowel disease, we identified patients with small bowel CD who underwent MRE between January 2007 and December 2010. The results of the MRE and subsequent changes in patient management within 1 month were evaluated. RESULTS: Thirty women and 27 men with CD were included. Seven patients (12%) had a normal MRE. Forty-two of 57 (74%) patients had a change in management, and 41/50 (82%) patients with an abnormal MRE had changes in management (P<0.0008). After MRE, 20/42 (47%) patients had surgery and 22/42 (53%) had changes in medical treatment. Patients with stricturing disease had more surgical intervention (P=0.02), and patients with active disease on MRE had more medical intervention (P=0.0001). Patients with two or more abnormalities on MRE had more surgery compared with medical therapy (P=0.02). CONCLUSION: The majority of patients with small bowel CD had a change in management as a result of the MRE. Because of its high clinical impact on patient management, MRE should become one of the preferred methods of small bowel evaluation in CD. Specific MRE findings may help to stratify treatment options, however, further work is required to validate this.

Inter-endoscopist agreement in diagnosis of Barrett's oesophagus.

OBJECTIVE: To assess how interpretation of abnormalities at the oesophago-gastric junction (OGJ) when making a diagnosis of Barrett's oesophagus (BO) varies between endoscopists and to examine the impact of the endoscopy experience on these decisions. DESIGN/SETTING: Members of the Irish Society of Gastroenterology who regularly perform gastroscopy were invited to participate in a web based image assessment study. INTERVENTIONS: Questions were posed to ascertain level of endoscopy experience, and participants were asked to indicate the presence or absence of BO in 12 endoscopic images of the OGJ. OUTCOME MEASURES: Primary outcome was overall level of agreement in responses and relationship to endoscopy experience. RESULTS: The responses of 65 clinicians regularly performing gastroscopy were analysed. In 3/12 images, showing typical long segment BO, there was a strong consensus on the endoscopic diagnosis (>95% agreement). However, agreement was fair to poor (κ for multiple raters, 0.31) on the presence or absence of short BO segments at endoscopy. Minimal differences were observed between experienced endoscopists (individuals with >10 years' endoscopy experience) and less experienced counterparts in the threshold for BO diagnosis. Inter-endoscopist agreement overall was not significantly better within the more experienced group. CONCLUSION: The study demonstrates low interobserver agreement in endoscopic diagnosis of (short segment) BO, even among experienced endoscopists. Given the costs associated with endoscopic surveillance of BO, prompt efforts to promote consensus diagnosis and improve agreement are required as an important quality improvement measure in this area.