Publications

BACKGROUND AND AIMS: Acute severe ulcerative colitis (ASUC) is a life-threatening manifestation of ulcerative colitis. Diagnosis typically relies on the 1955 Truelove and Witts criteria. These do not incorporate treatment history with steroids or modern advanced therapies. This Delphi panel gathered expert opinion regarding potential criteria and approaches for diagnosing ASUC in contemporary practice, including current outpatient treatment with corticosteroids/advanced therapy.

METHODS: European, North-American and Asia-Pacific gastroenterologists participated in a four-round Delphi panel and consensus meeting, forming the Refined Evaluation Framework and INvEstigations for Diagnostics in ASUC (REFINED-ASUC) Working Group. Consensus was defined as ≥70% agreement/disagreement for Likert-scale, or ≥70% homogeneity for single-/multiple-choice responses.

RESULTS: Panelists agreed there is unmet need for ASUC criteria in contemporary practice. Consensus was obtained that ASUC diagnosis could be based around 3 'major' (C-reactive protein (CRP) ≥2 x upper limit of normal (ULN), ≥6 bowel movements/24 hours, ≥50% bowel movements with visible blood/24 hours) plus ≥2 'minor' criteria (low albumin, increased heart rate, nocturnal bowel movements, low hemoglobin, increased body temperature, or elevated leukocyte count) in patients treated with advanced therapy/corticosteroids. Patients on high-dose corticosteroids constitute a subgroup requiring different thresholds (CRP ≥1 x ULN, ≥33% bowel movements with visible blood/24 hours). Similar principles were agreed for untreated patients but without achieving consensus. Panelists agreed endoscopy should confirm ASUC diagnosis and exclude cytomegalovirus infection, and radiologic investigations to support excluding toxic megacolon.

CONCLUSIONS: This consensus provides new diagnostic criteria for ASUC in the modern therapeutic era, that can be applied to patients already in receipt of outpatient treatments. These criteria include additional clinical and laboratory parameters, for validation in prospective studies.

Liver damage in autoimmune hepatitis (AIH) is perpetrated by T-effector lymphocytes that are not adequately restrained by regulatory T cells (Tregs). The goal of AIH treatment is to control inflammation and induce disease remission through administration of immunosuppressive drugs including corticosteroids, azathioprine, and, in difficult-to-treat cases, mycophenolate mofetil or tacrolimus (TAC). Despite TAC being a potent immunosuppressant, its use has been hampered by a narrow therapeutic window and systemic toxicity. In this study, we have tested the effects of lipid-core nanoformulations encapsulating TAC (NC-TAC) as a novel drug delivery system that would enable potentially favorable immunomodulatory effects compared with unencapsulated TAC. NC-TAC properties were assessed in vitro, in CD4 T cells and Tregs isolated from the peripheral blood of AIH patients and controls; and in vivo through a model of T cell-mediated liver injury induced by Concanavalin-A (Con-A) in NOD/scid/gamma mice, pre-emptively reconstituted with human CD4 T lymphocytes. Compared to unencapsulated TAC, NC-TAC favored a regulatory phenotype in CD4 T cells of AIH patients, enhanced the suppressive function and preserved AIH Treg phenotype in the presence of an inflammatory stimulus. Systemic administration of NC-TAC ameliorated liver injury in vivo, as indicated by decreased ALT levels, reduced lymphocyte infiltration on histology, and an increased frequency of intrahepatic CD4+FOXP3+ lymphocytes. NC-TAC could therefore be considered as a novel drug delivery system to be possibly explored for the treatment of AIH, having a beneficial immunomodulatory profile and effectively favoring Treg immune responses.

BACKGROUND: Biologic therapies for patients with inflammatory bowel disease (IBD) were approved via large randomized controlled trials (RCTs) with strict criteria for patient enrollment. As newer IBD medications are approved, ongoing assessment is necessary to determine whether RCT eligibility criteria are too restrictive or adequately reflect real-world practice. Here, we investigate the trial-eligibility and clinical outcomes of patients with ulcerative colitis (UC) started on vedolizumab (VDZ) and ustekinumab (UST) therapy.

METHODS: This single-center retrospective cohort study at a large academic IBD referral center included patients with UC who received a new prescription for UST or VDZ between January 2020 and June 2023. The primary outcome assessed whether patients met trial eligibility using the inclusion and exclusion criteria from the UNIFI and GEMINI-1 RCTs. We also assessed treatment failure between the trial-eligible and ineligible groups.

RESULTS: Only 19/168 (11.3%) of patients with UC (n = 85 receiving VDZ; n = 83 receiving UST) were trial-eligible. The most common reasons for ineligibility were prior biologics and inadequate wash-out periods, the use of topical therapy, medical comorbidities and ongoing treatment with high doses of prednisone. Treatment failure was numerically higher in trial-ineligible compared to trial-eligible patients, though this difference was not statistically significant.

CONCLUSION: Most patients initiated on UST or VDZ would not have qualified for inclusion in their respective RCTs, largely due to current treatments. Revising trial eligibility criteria may be warranted to improve external validity and enable recruitment of a more diverse study population representative of real-world patients.

An intramural duodenal hematoma (IDH) is an uncommon clinical entity that can be an adverse event of therapeutic esophagogastroduodenoscopy (EGD). Herein, we present a case of a 60-year-old man who presented to the hospital with vomiting, diarrhea, and overt gastrointestinal bleeding with melena and small-volume hematemesis. EGD was pursued and revealed a bleeding duodenal ulcer that was therapeutically intervened upon to achieve hemostasis. After endoscopy, his hospital course was complicated by an intramural duodenal hematoma, which presented with abdominal pain and worsening anemia without recurrent overt gastrointestinal bleeding. After consultation with interventional radiology and surgery, he ultimately improved with supportive care and was discharged home without further endoscopic or procedural intervention. An IDH is an uncommon gastrointestinal pathology that should be considered after endoscopy in the setting of abdominal pain and anemia without overt bleeding. Conservative management often leads to successful outcomes, but multidisciplinary care should be considered in the setting of further adverse events.

BACKGROUND AND AIMS: Artificial intelligence (AI) may detect endoscopically active ulcerative colitis (UC) and streamline clinical trial enrollment. Here, we investigate the performance of a commercially available AI model, autoinflammatory bowel disease (AutoIBD)-UC (Virgo Surgical Video Solutions, Inc, San Francisco, Calif, USA), to detect moderate-to-severe UC in colonoscopy videos collected as part of routine clinical practice.

METHODS: AutoIBD-UC was applied to consecutive endoscopy videos between August 30, 2024, and October 17, 2024. Each video received an AutoIBD score (0-1); videos with scores above a predefined confidence threshold were flagged as possible moderate-to-severe UC. Flagged videos and medical records were reviewed to confirm UC diagnosis and grade Mayo endoscopic subscore (MES). Concurrently, research staff retrospectively reviewed all endoscopy reports to identify 3 cohorts: (1) 20 MES ≥2, (2) 20 non-UC inflammation, and (3) 20 screening colonoscopies. Sensitivity and specificity were calculated for all videos screened by AI. Median AutoIBD scores were compared by MES and disease extent.

RESULTS: AutoIBD-UC was applied to 2273 endoscopy videos. Twenty-one videos were flagged, 10 of which had MES ≥2. AutoIBD-UC flagged 9 of 20 videos in cohort 1 and all MES 3 videos. More procedures with extensive (4 of 8) or left-sided disease (5 of 7) were flagged compared with those with proctitis (0 of 5). Median AutoIBD-UC scores differed between MES 2 (0.437; interquartile range [IQR], 0.270-0.571) and MES 3 (0.690; IQR, 0.607-0.765; P = .006), and by disease extent: proctitis (0.224; IQR, 0.193-0.270), left-sided (0.571; IQR, 0.554-0.603), and extensive (0.506; IQR, 0.408-0.598; P = .021). The sensitivity of AutoIBD-UC was 0.47, and the specificity was 0.99.

CONCLUSIONS: AutoIBD-UC accurately detects moderate-to-severe UC with moderate sensitivity and high specificity. Larger studies are necessary to evaluate AutoIBD-UC's utility as a recruitment aid compared to standard practice.

BACKGROUND: There are limited data regarding the impact of body mass index (BMI) on pharmacokinetics in patients with inflammatory bowel disease (IBD) treated with vedolizumab (VDZ) or ustekinumab (UST). The aim of the study was to investigate the association of BMI with VDZ and UST concentrations in IBD.

METHODS: This single-center, retrospective study included consecutive patients with IBD who received intravenous (iv) VDZ or UST and underwent therapeutic drug monitoring (TDM) from November 2016 to March 2023. We assessed the correlation of BMI with drug concentrations using Spearman's rank test.

RESULTS: The study population consisted of 170 patients; 89 (52%) patients received iv VDZ [44% Crohn's disease (CD)] and 81 received UST (81% CD). There was an inverse correlation of baseline BMI [ρ: -0.321; 95% confidence interval (CI) -0.534 to -0.070; P = .011] and BMI at first TDM (ρ: -0.253; 95% CI, -0.462 to -0.018; P = .031) with UST concentration at first TDM. Regarding the latter, subgroup analyses revealed that this correlation referred only to patients with Crohn's disease (CD) (ρ: -0.293; 95% CI, -0.515 to -0.035; P = .023) or patients with IBD on standard UST dosing (ρ: -0.369; 95% CI, -0.616 to -0.055; P = .019). In contrast, there was no correlation of BMI with VDZ concentrations. Multivariable linear regression analysis identified higher BMI at first TDM as an independent variable associated with lower UST concentrations (B: -0.408; 95% CI, -0.930 to -0.217; P = .002).

CONCLUSION: This study demonstrated an inverse correlation between BMI and UST concentrations in patients with CD or patients with IBD on standard UST dosing, suggesting the need for closer TDM and dose adjustments to ensure optimal drug exposure in these patients with higher BMI.

BACKGROUND: The diagnosis of inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD), relies on clinical and pathological criteria. Non-invasive precision medicine tools to diagnose IBD and discriminate between UC and CD are needed to personalise management. Serum proteomics identified protein biomarkers capable of diagnosing IBD and differentiating CD from UC subtypes.

METHODS: We obtained serum samples from a retrospective study of 47 patients with IBD and non-IBD patients seen in a tertiary care paediatric gastroenterology clinic and applied SomaScan proteomics to measure 1305 proteins to discriminate between IBD and non-IBD and UC and CD. Four proteins were further validated by immunoassays in two retrospective cohorts of 295 and 105 individuals and multi-protein predictors were developed using Support Vector Machines (SVM).

FINDINGS: The SomaScan discovery phase identified 95 serum protein biomarkers (BH p < 0.01) that differentiated IBD from non-IBD and 70 proteins (p < 0.01) that distinguished UC from CD. Pathway analysis linked specific inflammatory processes and vascular functions to IBD and UC versus CD. An 8-protein classifier achieved an AUC of 0.95 for identifying IBD. Significant elevation of four key predictor proteins (MMP1, MMP3, Resistin, Haptoglobin) in IBD was validated by ELISA in the expanded cohort (N = 295). The 4-protein SVM predictor achieved an AUC of 0.86 and 0.90 for IBD discrimination in two independent cohorts. A separate 4-protein SVM predictor for differentiating UC from CD achieved an AUC of 0.93 in independent validation.

INTERPRETATION: Patients with paediatric-onset IBD have a unique serum protein signature associated with pro-inflammatory and vascular pathways. Additional studies are needed to determine whether these dysregulated proteins can be used in conjunction with traditional risk factors to support non-invasive biomarkers that identify IBD and discriminate between its subtypes.

FUNDING: Martin Schlaff, The Diane and Dorothy Brooks Foundation, The Manessis Family, Thomas and Lynn Kuzma, and The Hasso Serrano Foundation.

BACKGROUND: Postpartum pain management is an important part of maternal healthcare. Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are typically offered as first-line pharmacologic therapies for postpartum pain. There is a belief that NSAIDs may play a role in exacerbating inflammatory bowel disease (IBD); as a result, some obstetricians avoid NSAIDs for postpartum pain management in patients with IBD. However, data concerning the relationship between short-term NSAID use and IBD flares are inconsistent. The aim of this study was to assess whether hospital postpartum NSAID use is associated with postpartum IBD flare within 9 months from delivery.

METHODS: This single-center retrospective cohort study included patients with IBD, aged 18 years or older, who had singleton live births between January 1, 2016, and November 30, 2023. Chart review data for each eligible patient were collected for a 9-month postpartum period.

RESULTS: Among the 187 patients included in the study, there was no difference between NSAID-exposed and non-exposed patients in postpartum IBD flare: 10/114 (9%) vs. 10/73 (14%), respectively, P=0.335. Based on multivariate regression analysis, NSAID exposure was not associated with postpartum IBD flare, adjusted for active disease at conception and IBD flare during pregnancy: adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.2-1.7; P=0.327. The same was true for mode of delivery and inpatient opioid exposure: aOR 0.6, 95%CI 0.1-1.5; P=0.291.

CONCLUSIONS: Postpartum NSAID use for pain control is not associated with IBD flare 9 months after delivery. Large prospective studies are needed to confirm this finding.