Publications

This review offers information and practical guidance for professionals who care for patients with disorders of gut-brain interaction (DGBI). It summarizes evidence-based psychosocial approaches for adult and pediatric populations, organized into 4 sections: background, assessment, management, and training. The review begins by establishing a biopsychosocial framework, highlighting the bidirectional influences of biological and psychosocial factors on gut physiology and brain mechanisms. It then outlines key assessment strategies, including targeted patient interview questions and guidance on interpreting responses followed by empirically supported psychosocial treatments suitable for integrated and standalone care settings. The final section presents curriculum recommendations for providers in DGBI-specific psychosocial care. Emphasizing the brain-gut axis and the importance of the patient-provider relationship, this review underscores the need for accurate psychosocial assessment and contextually informed intervention. It concludes with future directions for training and research to enhance clinical outcomes in this complex and multifaceted domain.

BACKGROUND AND AIMS: Real-world data are needed to better understand the burden and outcomes of patients hospitalized with severe ulcerative colitis (UC).

METHODS: This retrospective cohort study analyzed US electronic health record (EHR) data with linked insurance claims to identify adults hospitalized for UC who received intravenous corticosteroids during an inpatient admission (index hospitalization) between January 1, 2014, and December 31, 2022, with ≥180 days of prior EHR activity. Results were analyzed for the overall cohort, in three subgroups: (1) no prior UC diagnosis in the EHR, (2) prior UC diagnosis without prior advanced therapy, and (3) prior UC with prior advanced therapy, and in a nested cohort of patients discharged without colectomy. Multivariable analyses assessed factors associated with colectomy before discharge.

RESULTS: Overall, we identified 9716 patients (mean [SD] age, 46.3 [17.4] years); 83.3% had a previous diagnosis of UC and 23.8% had prior biologic use for UC. During hospitalization, 13.1% received advanced therapy; 12.2% underwent colectomy. The rate of colectomy was 12.6% in subgroup 1, 9.2% in subgroup 2, and 19.6% in subgroup 3 (P < .0001). Prior UC diagnosis with prior advanced therapy use and abnormal/missing albumin labs were associated with higher risk of colectomy. The cumulative risk of colectomy <1 year after index hospitalization was 20.4% overall and 18.5%, 16.1%, and 32.7% in subgroups 1, 2, and 3, respectively. In the nested cohort (n = 4383), one-third received advanced therapy within 90 days; 38.4% experienced a UC-related hospitalization <1 year after index hospitalization.

CONCLUSION: These data from a large contemporary cohort elucidate the burden and outcomes for patients hospitalized with severe UC.

Gastrointestinal malignancies such as signet-ring cell carcinoma can mimic inflammatory bowel disease, leading to diagnostic uncertainty. We present the case of a 39-year-old woman who presented with cramping abdominal pain, watery diarrhea, and unintentional weight loss. Imaging revealed multifocal colonic strictures and pelvic ascites, initially suspected to represent Crohn's disease. Bidirectional endoscopy showed gastric edema and colonic strictures without typical inflammatory features. Following laparoscopic-assisted subtotal colectomy for progressive obstruction, histopathology revealed diffuse infiltration of signet-ring cells consistent with metastatic gastric adenocarcinoma. This case highlights the importance of maintaining a broad differential diagnosis when atypical features are present. Clinicians should maintain a high index of suspicion for malignancy in young patients with atypical strictures, especially when accompanied by systemic features such as weight loss or ascites, even when initial endoscopic biopsies are non-diagnostic.

PURPOSE: Studies show women are underrepresented in gastroenterology (GI). Understanding representation is crucial to improving representation. This study describes the geographic distribution of women in academic GI in the United States (US).

METHODS: We conducted a cross-sectional study of 224 US GI fellowship programs in 2023 by review of program websites and direct inquiry. Gender distribution of trainees and faculty across US regions was evaluated. Program characteristics were examined in univariate analyses. Logistic regression models assessed factors associated with women in leadership, adjusting for program type and region.

RESULTS: Women comprised 39.3% of 1,801 fellows and 30.2% of 3,899 GI faculty. Percentage of women fellows was highest in the West (50%), Northeast (38%), South (33%), and Midwest (33%), (p = 0.014). Median percentage of senior women faculty was highest in the Northeast (27%) (p = 0.009). Programs with women GI division chiefs had more women GI fellowship program directors (60% vs 40%, p = 0.001) and higher median percentage of women faculty (33% vs 26%, p = 0.016). The presence of a woman GI division chief was independently associated with having a woman GI fellowship program director (p = 0.008) and increased percentage of women faculty (p < 0.001).

CONCLUSION: Gender representation varied regionally, with some institutions lacking women faculty or trainees. Women in leadership are associated with greater faculty gender diversity, potentially impacting trainee recruitment, faculty retention, and patient care. The association between women GI division chiefs and increased women faculty and program directors highlights how leadership gender diversity may support recruitment and retention of women in academic GI.

BACKGROUND: Sucrose malabsorption and small intestinal bacterial overgrowth (SIBO) present with symptoms that overlap with those of disorders of gut-brain interaction (DGBI). Recent studies suggest that sucrose malabsorption is more prevalent than previously thought. This study aims to determine the prevalence of sucrose malabsorption based on 13C-sucrose breath test (SBT) in patients undergoing SIBO breath testing and assess whether symptoms distinguish sucrose malabsorption from SIBO.

METHODS: Three hundred patients referred for SIBO breath testing between August 2020 and March 2022 were recruited and asked to complete the Rome IV Questionnaire for bowel disorders, Irritable Bowel Syndrome Severity Score (IBS-SSS), and the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). After in person SIBO breath testing, they were provided an at-home 13C-SBT.

RESULTS: One-hundred-and-forty patients returned the SBT. Of the SIBO negative patients, 22% (25/113) were SBT positive. No statistically significant differences were found in predominant symptoms or Rome IV diagnoses (IBS, functional constipation, or functional diarrhea), bloating frequency, IBS-SSS, or PAGI-SYM Scores between SBT positive and SBT negative patients. SBT positive only patients (n = 24) reported less abdominal pain (p = 0.04) than abnormal SIBO test only patients (n = 23).

CONCLUSION: Sucrose malabsorption was present in 22% of SIBO negative patients, indicating that it is a possible contributor to DGBI symptoms. Symptom profile alone did not predict sucrose malabsorption, nor distinguish between sucrose malabsorption and SIBO. This emphasizes the importance of considering carbohydrate malabsorption syndromes, such as sucrose malabsorption, when evaluating patients with symptoms consistent with functional gastrointestinal disorders (FGID).

BACKGROUND & AIMS: Safe and effective treatment for irritable bowel syndrome with diarrhea (IBS-D) is needed. ORP-101 is a novel partial μ receptor agonist and full κ receptor antagonist designed to act peripherally without central nervous system exposure. This study evaluated the efficacy and safety of ORP-101 in IBS-D.

METHODS: In this randomized, double-blind, adaptive design placebo-controlled trial, eligible participants were randomized to receive ORP-101 50 mg, 100 mg, or placebo once daily for 12 weeks. As part of the adaptive design, the 50 mg ORP-101 dose was discontinued after interim analysis. The primary endpoint was composite response status of improvement in abdominal pain (improvement of 30% from baseline) and stool consistency (average daily stool consistency <5 on the Bristol Stool Form Scale, or 30% improvement in abdominal pain if no bowel movement) for 50% of days over 12-week treatment period.

RESULTS: 320 participants with IBS-D were randomized to ORP-101 50 mg (n=65), 100 mg (n=127), or placebo (n=128). The proportion of primary endpoint responders for ORP-101 50 mg, 100 mg, and placebo participants was 16.9%, 28.3%, and 21.9%, respectively (p= 0.79 for the three groups and p= 0.12 for ORP-101 100 mg vs. placebo). Secondary and exploratory endpoints favored ORP-101 100 mg vs placebo across multiple endpoints. ORP-101 was well tolerated, including in those without gallbladders.

CONCLUSION: In this phase II trial, ORP-101 100 mg did not achieve a statistically significant difference vs. placebo for the primary endpoint; however, it showed higher response across multiple key endpoints. Future studies will study ORP-101 in other chronic pain conditions.

BACKGROUND: Intestinal tissue levels of infliximab (IFX) in patients with inflammatory bowel disease (IBD) treated with subcutaneous (SC) therapy have not been previously assessed.

OBJECTIVE: To compare serum and colonic tissue IFX concentrations in IBD patients receiving SC versus intravenous (IV) IFX.

METHODS: This observational cross-sectional study included IBD patients on stable SC or IV IFX maintenance therapy undergoing routine follow-up colonoscopy. Clinical activity required elevated CDAI or Mayo score plus ≥ 1 biomarker (fecal calprotectin > 250 μg/g or CRP > 5 mg/L). Blood samples and two colonic biopsies were collected for serum and tissue IFX measurements.

RESULTS: Thirty-five patients were included. Serum and tissue IFX concentrations were significantly higher in the SC versus IV group (22 μg/mL vs. 9 μg/mL, p < 0.001; 25 μg/g vs. 10 μg/g, p = 0.002). Serum and colonic tissue IFX levels were positively correlated in both cohorts (IV: r = 0.42; p = 0.014; SC: r = 0.43; p = 0.001). Colonic tissue IFX concentrations were higher in patients with mild-moderate endoscopic activity than in those without active disease (p < 0.001). Serum and colonic tissue IFX levels both predicted sustained clinical remission, with optimal thresholds of 14.5 μg/mL (p = 0.015) and 17 μg/g (p < 0.005), respectively. Colonic tissue IFX showed higher predictive accuracy (AUROC 0.82, p = 0.01) than serum (AUROC 0.76, p = 0.045).

CONCLUSIONS: SC IFX achieved significantly higher serum and colonic tissue concentrations than IV IFX. Colonic tissue IFX levels demonstrated superior clinical relevance and may support future tissue-based therapeutic drug monitoring strategies in IBD.

BACKGROUND & AIMS: Infliximab is an established rescue therapy for patients with steroid-refractory acute severe ulcerative colitis (ASUC), yet optimal dosing strategies minimizing colectomy risk remain unclear. We aimed to develop a model-informed risk stratification algorithm to identify patients at high risk of colectomy within 90 days of initiating infliximab to support personalized dosing.

METHODS: We conducted a multicenter, retrospective population pharmacokinetics (popPK) and exposure-response study using data from patients with ASUC. A parametric time-to-event model was developed to characterize the 90-day colectomy risk. Patient characteristics and pharmacokinetic projections were evaluated as predictors. These modelling results informed the development of an algorithm for risk stratification and personalized infliximab rescue dosing.

RESULTS: Seven medical centers contributed data from 72 patients with ASUC, yielding a total of 152 infliximab serum concentrations. Eleven patients underwent colectomy within 90 days. The strongest predictor of colectomy was the clearance-normalized exposure between weeks 2 and 4 (area under the concentration-time curve, AUCw2-4 to Bayesian-forecasted infliximab clearance, CL), with an area under the receiver operating characteristic curve of 0.79 (95% confidence interval [CI], 0.52-1.00). The AUCw2-4/CL ratio was calculated by individualizing the popPK model using the patient's body weight, baseline C-reactive protein, and infliximab concentrations. Patients with a log-transformed AUCw2-4/CL ratio < 5.79 were classified as high risk for colectomy (sensitivity 83%, specificity 85%). Overall classification accuracy was 85% (95% CI, 74-92).

CONCLUSIONS: We developed a model-based dose-exposure-response framework to predict colectomy risk in ASUC. We integrated the algorithm into an interactive tool to enable individualized infliximab rescue therapy.

OBJECTIVES: There are limited data regarding adalimumab (ADM) clearance in inflammatory bowel disease (IBD). The aim of this study was to identify factors associated with ADM clearance and to assess its association with mucosal healing.

METHODS: This single-center, retrospective study included consecutive patients with IBD who received maintenance ADM therapy and underwent therapeutic drug monitoring (TDM) between January 2018 and May 2023. Drug clearance was determined using a nonlinear mixed-effect model with Bayesian priors. Mucosal healing was defined as an endoscopic Mayo score 1 or less; for ulcerative colitis, no ulcerations for patients with Crohn's disease, or a Rutgeerts score of i1 or less for patients with an ileocolonic resection for Crohn's disease and was evaluated within 3 months from TDM.

RESULTS: The study population consisted of 263 patients with IBD (74% Crohn's disease) who underwent a total of 515 TDM tests (388 proactive). Multivariable linear regression analysis identified that proactive TDM was associated with lower ADM clearance [beta coefficients (β): -0.173, 95% confidence interval (CI): -0.180 to -0.088, P < 0.001], while BMI (β: 0.125, 95% CI: 0.005-0.013, P < 0.001), prior biologic exposure (β: 0.087, 95% CI: 0.022-0.112, P = 0.004), and antibodies to ADM (β: 0.676, 95% CI: 0.628-0.750, P < 0.001) were associated with higher ADM clearance. Receiver operating characteristic analysis identified an ADM clearance threshold of 0.301 L/day (area under the receiver operating characteristic curve: 0.731; 95% CI: 0.654-0.808; P < 0.001; sensitivity: 61%; specificity: 78%) distinguishing patients with or without mucosal healing.

CONCLUSION: This study demonstrated that lower ADM clearance is associated with proactive TDM and mucosal healing in patients with IBD.