Mucosal Integrity Testing Can Detect Differences in the Rectums of Patients with Inflammatory Bowel Disease Compared to Controls: A Pilot Study.

BACKGROUND: While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in disease initiation and progression. Currently, there is no convenient way to measure this in vivo. AIMS: Our aim is to determine whether a mucosal integrity (MI) testing device that has been used to measure MI in the esophagus can also be used to measure barrier function in the colon during colonoscopy. METHODS: Mucosal integrity testing was measured in patients with IBD (n = 17) and controls (n = 7) during colonoscopy. During the procedure, an MI catheter was passed down the working channel of the colonoscope and placed along the mucosal wall to measure MI in the rectum, left, transverse, and right colon. In patients with IBD, MI measurements and biopsies were taken in areas which appeared inflamed when present. We then determined if there was a significant difference in MI between patients with IBD and controls. RESULTS: MI was significantly higher in the rectum of patients with IBD (CD and UC combined) versus control colons [767 (618-991) vs. 531 (418-604) ohms, P < 0.01]. There were no significant differences in MI among patients with IBD versus controls in the right, transverse, or left colon. Within the IBD group, there were no significant differences in MI between inflamed versus non-inflamed rectums. There was no correlation between quality of life scores or endoscopic severity with MI, though this study was likely underpowered to detect these differences. CONCLUSION: Rectal MI is significantly higher in patients with IBD versus controls. Future studies are needed to determine how this information can be used clinically.

Safety and Efficacy of Vedolizumab Versus Tumor Necrosis Factor α Antagonists in an Elderly IBD Population: A Single Institution Retrospective Experience.

BACKGROUND: Vedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population. AIMS: Here, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD. METHODS: This retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes. RESULTS: 212 cases were identified-108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p < 0.001). CONCLUSIONS: In a cohort of IBD patients over age 60, vedolizumab showed no statistically significant differences in infection, hospitalization, or surgical intervention-free survival as compared to anti-TNF. Vedolizumab was discontinued less frequently than anti-TNF. Patients on vedolizumab had higher rates of endoscopic remission and response.

Inpatient Management of Inflammatory Bowel Disease-Related Complications.

Despite advances in therapeutic options, a sizeable proportion of patients with inflammatory bowel disease require hospitalization or surgery during their lifetime. While current treatment guidelines for the management of ulcerative colitis and Crohn's disease cover the spectrum of disease severity and behavior, management of acute complications of inflammatory bowel disease can present unique challenges that are not always addressed in these guidelines. In this review, the authors provide a comprehensive summary of the existing literature focused on management of patients hospitalized with complications of inflammatory bowel disease. Proposed management algorithms are provided to guide clinicians through common scenarios to determine the most appropriate interventions - escalation of medical therapies, non-surgical therapeutic interventions (drainage of intra-abdominal abscess or endoscopic balloon dilation) or surgery. Prevention of complications is proposed through a multi-disciplinary approach that involves surgeons, dieticians, radiologists, pathologists and infectious disease consultants.

Depressive Symptoms Predict Anti-tumor Necrosis Factor Therapy Noncompliance in Patients with Inflammatory Bowel Disease.

BACKGROUND: Noncompliance in use of anti-tumor necrosis factor (anti-TNF) therapy in patients with moderate-to-severe inflammatory bowel disease (IBD) can be a factor in medication failure. Few studies have evaluated the contribution of depressive symptoms to medication noncompliance in anti-TNF therapies. METHODS: A retrospective chart review was performed in a single-center tertiary care IBD center for patients with Crohn's disease and ulcerative colitis starting anti-TNF therapy over a 2-year period. Medication noncompliance was defined as interruption of medication (not filling anti-TNF prescription if injectable or not getting infliximab infusion for 30 days beyond needed date for continuation) due to patient-driven circumstances. Depressive symptoms were evaluated at baseline using the well-validated Patient Health Questionnaire-9 (PHQ-9), with PHQ-9 ≥ 10 indicative of at least moderate depressive symptoms. Statistical analysis was performed using Cox proportional hazards regression controlling for age, sex, psychiatric history, and disease. RESULTS: A total of 246 patients (75 with ulcerative colitis, 171 with Crohn's disease) were started on anti-TNF therapy. Seventy-nine patients (32%) had a prior psychiatric diagnosis reported in the medical record. Thirty-three patients (13%) were noncompliant in follow-up. Sixty patients (24%) had at least moderate depressive symptoms at baseline (PHQ ≥ 10). Depressive symptoms at baseline were significantly associated with noncompliance in follow-up (hazards ratio 2.28, CI 1.1-4.6, p < 0.05). CONCLUSION: Depressive symptoms at baseline were associated with medication noncompliance of anti-TNF therapies at follow-up when controlling for age, sex, disease type, and history of psychiatric disease.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Background: Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. Methods: We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Results: Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Conclusions: Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

A patient education intervention improved rates of successful video visits during rapid implementation of telehealth.

INTRODUCTION: The need to rapidly implement telehealth at large scale during the COVID-19 pandemic led to many patients using telehealth for the first time. We assessed the effect of structured pre-visit preparatory telephone calls on success of telehealth visits and examined risk factors for unsuccessful visits. METHODS: A retrospective cohort study was carried out of 45,803 adult patients scheduled for a total of 64,447 telehealth appointments between March and July 2020 at an academic medical center. A subset of patients received a structured pre-visit phone call. Demographic factors and inclusion of a pre-visit call were analysed by logistic regression. Primary outcomes were non-completion of any visit and completion of phone-only versus audio-visual telehealth visits. RESULTS: A pre-visit telephone call to a subset of patients significantly increased the likelihood of a successful telehealth visit (OR 0.54; 95% CI: 0.48-0.60). Patients aged 18-30 years, those with non-commercial insurance or those of Black race were more likely to have incomplete visits. Compared to age 18-30, increasing age increased likelihood of a failed video visit: 31-50 years (OR 1.31; 95% CI: 1.13-1.51), 51-70 years (OR 2.98; 2.60-3.42) and >70 years (OR 4.16; 3.58-4.82). Those with non-commercial insurance and those of Black race (OR 1.8; 95% CI 1.67-1.92) were more likely to have a failed video visit. DISCUSSION: A structured pre-call to patients improved the likelihood of a successful video visit during widespread adoption of telehealth. Structured pre-calls to patients may be an important tool to help reduce gaps in utilization among groups.

A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn's Disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder that may affect any part of gastrointestinal tract with extra-intestinal manifestations and associated immune dysregulation. To characterize heterogeneity in CD, we profiled single-cell transcriptomics of 170 samples from 65 CD patients and 18 non-inflammatory bowel disease (IBD) controls in both the terminal ileum (TI) and ascending colon (AC). Analysis of 202,359 cells identified a novel epithelial cell type in both TI and AC, featuring high expression of LCN2, NOS2, and DUOX2, and thus is named LND. LND cells, confirmed by high-resolution in-situ RNA imaging, were rarely found in non-IBD controls, but expanded significantly in active CD. Compared to other epithelial cells, genes defining LND cells were enriched in antimicrobial response and immunoregulation. Moreover, multiplexed protein imaging demonstrated that LND cell abundance was associated with immune infiltration. Cross-talk between LND and immune cells was explored by ligand-receptor interactions and further evidenced by their spatial colocalization. LND cells showed significant enrichment of expression specificity of IBD/CD susceptibility genes, revealing its role in immunopathogenesis of CD. Investigating lineage relationships of epithelial cells detected two LND cell subpopulations with different origins and developmental potential, early and late LND. The ratio of the late to early LND cells was related to anti-TNF response. These findings emphasize the pathogenic role of the specialized LND cell type in both Crohn's ileitis and Crohn's colitis and identify novel biomarkers associated with disease activity and treatment response.

The Importance of Monitoring the Postpartum Period in Moderate to Severe Crohn's Disease.

BACKGROUND: Prior research demonstrates Crohn's disease patients often do well in pregnancy; however, less is known about the risk of flare in the postpartum period. METHODS: A retrospective chart review was conducted at a tertiary care inflammatory bowel disease center. All pregnant women with Crohn's disease who were followed in the postpartum period, defined as 6 months after delivery, were included. Statistical analysis included χ 2 analysis, Wilcoxon rank sum test, and logistic regression analysis. The primary outcome of interest was rate of flare in the postpartum period. RESULTS: There were 105 patients included in the study, with a majority (68%) on biologic medication during pregnancy. Thirty-one patients (30%) had a postpartum flare at a median of 9 weeks (range 2-24 weeks). Twenty-five patients (81%) had their postpartum flare managed in the outpatient setting with medications (only 4 of these patients required prednisone). 6 of 31 patients (19%) were hospitalized at a median of 4 weeks (range 2-26 weeks) after delivery, requiring intravenous corticosteroids or surgery. In multivariable regression, there was no significant increase in risk of postpartum flare with increasing maternal age, flare during pregnancy, or steroid or biologic use during pregnancy. Smoking during pregnancy increased risk of postpartum flare (odds ratio, 16.2 [1.72-152.94], P < 0.05). CONCLUSION: In a cohort of Crohn's disease patients, 30% experienced a postpartum flare despite being on medical therapy, but most were able to be managed in the outpatient setting.

Demographic Factors Associated With Successful Telehealth Visits in Inflammatory Bowel Disease Patients.

BACKGROUND: This study evaluated synchronous audiovisual telehealth and audio-only visits for patients with inflammatory bowel disease (IBD) to determine frequency of successful telehealth visits and determine what factors increase the likelihood of completion. METHODS: Data were collected from March to July 2020 in a tertiary care adult IBD clinic that was transitioned to a fully telehealth model. A protocol for telehealth was implemented. A retrospective analysis was performed using electronic medical record (EMR) data. All patients were scheduled for video telehealth. If this failed, providers attempted to conduct the visit as audio only. RESULTS: Between March and July 2020, 2571 telehealth visits were scheduled for adult patients with IBD. Of these, 2498 (99%) were successfully completed by video or phone. Sixty percent were female, and the median age was 41 years. Eighty six percent of the population was white, 8% black, 2% other, and 4% were missing. Seventy-five percent had commercial insurance, 15% had Medicare, 5% had Medicaid, and 5% had other insurance. No significant factors were found for an attempted but completely failed visit. Using a multivariate logistic regression model, increasing age (odds ratio, 1.80; 95% CI, 1.55-2.08; P < 0.05), noncommercial insurance status (odds ratio, 1.89; 95% CI, 1.61-2.21; P < 0.05), and black race (odds ratio, 2.07; 95% CI, 1.38-3.08; P < 0.05) increased the likelihood of a video encounter failure. CONCLUSIONS: There is a high success rate for telehealth within an IBD population with defined clinic protocols. Certain patient characteristics such as age, race, and health insurance type increase the risk of failure of a video visit.

Functional Medicine Approach to Patient Care Improves Sleep, Fatigue, and Quality of Life in Patients With Inflammatory Bowel Disease.

Background: A Functional Medicine program was developed at an inflammatory bowel disease (IBD) center with the goal of integrating strategies to address modifiable lifestyle factors and to complete a 6-week elimination diet under the direction of a trained Functional Medicine dietitian and Functional Medicine providers. Methods: From January 2019 to November 2019, patients with controlled, but persistent, symptoms from IBD were offered enrollment. Each of the 5 visits incorporated an educational session focused on nutrition followed by a session focusing on modifiable lifestyle factors. The patients were placed on a supervised 6-week elimination diet. At each visit, patients completed the SIBDQ (Short Inflammatory Bowel Disease Questionnaire), FSS (Fatigue Severity Scale), PSQI (The Pittsburgh Sleep Quality Index), and MSQ (Medical Symptoms Questionnaire). Statistical analysis was performed using the Wilcoxon matched pairs signed-rank test. Results: Nineteen patients enrolled (2 men: 1 ulcerative colitis [UC], 1 Crohn's disease [CD]; 17 women: 3 UC, 14 CD). 15 patients completed all modules. There was improvement in all patient-reported outcomes (PROs) (FSS, P < .001; PSQI, P < .001; SIBDQ, P < .001; MSQ, P < .001). Every patient who completed the last session demonstrated weight loss. Conclusions: The psychoemotional roots to immune disease states, particularly IBD, are complicated and often not addressed in traditional care. We are just beginning to understand the impact of nutrition, sleep, stress, movement, and relationships on IBD. In this cohort, utilizing Functional Medicine as an adjunct to traditional care resulted in improvement in all PROs.

Tofacitinib Adherence and Outcomes in Refractory Inflammatory Bowel Disease.

Background: Tofacitinib has been approved for moderate-to-severe ulcerative colitis and studied in Crohn's disease. Understanding medication adherence to oral medications in severe disease is essential. Methods: We retrospectively reviewed adherence and real-world outcomes of inflammatory bowel disease patients who initiated tofacitinib at a single care center. Adherence was measured by proportion of days covered. Results: Sixty-three patients were identified. All patients failed at least one prior biologic therapy. Mean proportion of days covered was 95.7% for ulcerative colitis and 93.1% for Crohn's disease. Significant clinical and endoscopic response was seen. Conclusion: Adherence was high in a cohort with highly refractory disease.

Gastroenterologist-Lead Management of Iron Deficiency Anemia in Inflammatory Bowel Disease Is Effective, Safe, and May Increase Quality of Life.

BACKGROUND: The effectiveness and safety of gastroenterologist (GI)-lead treatment of iron deficiency anemia (IDA) in inflammatory bowel disease (IBD) have not been well-studied. METHODS: A retrospective chart review of patients with IBD, IDA, and evidence of treatment with iron at a tertiary IBD center was conducted. RESULTS: In 351 patients, hemoglobin and quality of life scores increased significantly after treatment with iron. Twelve of 341 patients treated with intravenous iron had an adverse effect. Twenty-seven patients required a hematology referral. CONCLUSION: GIs should consider treating patients with IBD and IDA with intravenous iron as it is safe and effective.

A Single Center Experience With Long-Term Ustekinumab Use and Reinduction in Patients With Refractory Crohn Disease.

BACKGROUND: Ustekinumab was approved for moderate and severe Crohn's disease (CD) in 2016, but little is known about long-term outcomes. METHODS: A retrospective study evaluated all patients with CD treated with ustekinumab, including patients with reinduction. C-reactive protein (CRP), Harvey-Bradshaw Index (HBI), Short Inflammatory Bowel Disease (SIBDQ), and endoscopy outcomes were collected prospectively. RESULTS: Ninety-six patients received ustekinumab, resulting in improvement in CRP, HBI, and SIBDQ scores with 68% endoscopic improvement/remission. Thirty-four patients underwent reinduction, resulting in improved HBI and CRP. CONCLUSIONS: Ustekinumab in refractory CD results in significant clinical and endoscopic improvement and reinduction may be a viable option to recapture response.

Does Reverse Causality Underlie the Temporal Relationship Between Depression and Crohn's Disease?

BACKGROUND: Studies suggest that there is a temporal relationship between depression and Crohn's disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression-CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective-cognitive dimension of depression. METHODS: We studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective-cognitive index of depression. Crohn's disease status and the affective-cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data. RESULTS: The results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective-cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse. CONCLUSIONS: The hypothesis that an affective-cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.

Risk Factors for Medication Nonadherence to Self-Injectable Biologic Therapy in Adult Patients With Inflammatory Bowel Disease.

BACKGROUND: In inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), nonadherence to biologic therapy increases risk of disease flare. The aim of this study was to identify risk factors for nonadherence. METHODS: This was a single-center retrospective study evaluating patients with IBD treated at a tertiary care center and prescribed self-injectable biologic therapy using the center's specialty pharmacy. Adherence was defined using medication possession ratio (MPR). Nonadherence was defined as MPR <0.86. RESULTS: Four hundred sixty patients (n = 393 with CD and n = 67 with UC) were evaluated with mean MPR (interquartile range) equaling 0.89 (0.48-1). Overall, 69% of patients were adherent (defined as MPR ≥0.86), 66% of patients with CD and 87% of patients with UC. In univariate analysis, several factors increased risk of nonadherence: CD diagnosis, insurance type, psychiatric history, smoking, prior biologic use, and narcotic use (P < 0.05). In multivariable analysis, Medicaid insurance (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.85-15.6) and CD diagnosis (OR, 2.8; 95% CI, 1.3-6.0) increased risk of nonadherence. In CD, as the number of risk factors increased (narcotic use, psychiatric history, prior biologic use, and smoking), the probability of nonadherence increased. Adherence was 72% in patients with 0-1 risk factors, decreasing to 62%, 61%, and 42% in patients with 2, 3, and 4 risk factors, respectively (P < 0.05). CONCLUSIONS: This study identified risk factors for nonadherence to biologic therapy. In patients with CD, the probability of nonadherence increased as the number of risk factors increased.

Management of Pouchitis and Other Common Complications of the Pouch.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the preferred surgical treatment for refractory or complicated ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Pouchitis is the most common complication of this procedure and can occur in about 50% of patients. Treatment of pouchitis depends on the phenotype of disease. Pouchitis can be classified as acute, chronic/refractory, or secondary pouchitis, which includes pouchitis occurring due to Crohn's disease (CD). CD of the pouch is becoming an increasingly recognized problem, and management is challenging. This article reviews the literature and offers treatment recommendations regarding management of pouchitis and CD of the pouch.

The Gastroenterologist's Role in Management of Perianal Fistula.

Perianal fistula occurs frequently in the Crohn disease population. Therapy for fistulas has changed through the years from primarily surgical management to multidisciplinary management among gastroenterologists, radiologists, and surgeons. Gastroenterologists play a role in assisting with diagnosis through endoscopic ultrasound and assessment of luminal disease activity, providing medical therapy including biologic therapy and antibiotics, and coordinating the multidisciplinary care with surgical and radiologic colleagues.