High Perceived Stress is Associated With Increased Risk of Ulcerative Colitis Clinical Flares.

BACKGROUND & AIMS: Although perceived stress (PS) has been associated with symptomatic flares in inflammatory bowel disease, clinical and physiological measures associated with perceived stress and flare are not known. The aim of this study was to identify physiological factors associated with perceived stress in ulcerative colitis (UC) subjects, and their relationship with flare. METHODS: Patients with UC in clinical remission (Simple Colitis Clinical Activity Index [SCCAI] score <5) underwent clinical and behavioral assessments, morning salivary cortisol measurements, autonomic nervous system activity testing (heart rate variability, electrodermal activity) at baseline with patient-reported SCCAI every 2 weeks over 1 to 2 years and fecal calprotectin at time of flare. Clinical flares (SCCAI ≥5) and biochemical flares (SCCAI ≥5 with fecal calprotectin ≥250 µg/g) were evaluated. RESULTS: One hundred ten patients with UC were enrolled, with mean follow-up of 65.6 weeks. Patients with UC with higher and lower PS were determined. Although the high PS group had 3.6 times higher odds of a clinical flare than the low PS group, no significant differences in biochemical flares were observed between the low and high PS groups. The high vs low PS group differed in tonic sympathetic arousal as indexed by significantly greater baseline electrodermal activity (4.3 vs 3.4 microsiemens; P = .026) in the high PS group, but not in terms of heart rate variability and morning cortisol levels. Increased fecal calprotectin was associated with cardioautonomic measures, suggesting lower parasympathetic activity. CONCLUSIONS: Increased PS assessed at baseline is associated with tonic sympathetic arousal and greater odds of clinical flares in patients with UC.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study.

BACKGROUND & AIMS: We compared the safety and effectiveness of tumor necrosis factor α (TNF-α) antagonists vs vedolizumab vs ustekinumab in patients with Crohn's disease (CD) in a multicenter cohort (CA-IBD). METHODS: We created an electronic health record-based cohort of adult patients with CD who were initiating a new biologic agent (TNF-α antagonists, ustekinumab, vedolizumab) from 5 health systems in California between 2010 and 2017. We compared the risk of serious infections (safety) and all-cause hospitalization and inflammatory bowel disease-related surgery (effectiveness) between different biologic classes using propensity score (PS) matching. RESULTS: As compared with TNF-α antagonists (n = 1030), 2:1 PS-matched, ustekinumab-treated patients with CD (n = 515) experienced a lower risk of serious infections (hazard ratio [HR], 0.36; 95% CI, 0.20-0.64), without any difference in the risk of hospitalization (HR, 0.99; 95% CI, 0.89-1.21) or surgery (HR, 1.08; 95% CI, 0.69-1.70). Compared with vedolizumab (n = 221), 1:1 PS-matched, ustekinumab-treated patients with CD (n = 221) experienced a lower risk of serious infections (HR, 0.20; 95% CI, 0.07-0.60), without significant differences in risk of hospitalization (HR, 0.76; 95% CI, 0.54-1.07) or surgery (HR, 1.42; 95% CI, 0.54-3.72). Compared with TNF-α antagonists (n = 442), 2:1 PS-matched, vedolizumab-treated patients with CD (n = 221) had a similar risk of serious infections (HR, 1.53; 95% CI, 0.84-2.78), hospitalization (HR, 1.32; 95% CI, 0.98-1.77), and surgery (HR, 0.63; 95% CI, 0.27-1.47). High comorbidity burden, concomitant opiate use, and prior hospitalization were associated with serious infections and hospitalization in biologic-treated patients with CD. CONCLUSION: In a multicenter cohort of biologic-treated patients with CD, ustekinumab was associated with a lower risk of serious infections compared with TNF-α antagonists and vedolizumab, without any differences in risk of hospitalization or surgery. The risk of serious infections was similar for TNF-α antagonists vs vedolizumab.

Functional brain rewiring and altered cortical stability in ulcerative colitis.

Despite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC), N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC < IBS < HC) and increased eigenvector centrality in the visual network (UC > IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. None of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.

Pneumococcal Vaccination Recommendation and Completion Rates Among Patients With Inflammatory Bowel Disease and Barriers to Vaccination.

BACKGROUND: Guidelines for inflammatory bowel disease (IBD) patients receiving immunosuppression encouraged both the pneumococcal polysaccharide vaccine (PPSV23) and the pneumococcal conjugate vaccine (PCV13). We aimed to evaluate which pneumococcal vaccines are recommended and administered, and to understand provider and IBD patient knowledge regarding pneumococcal vaccinations. METHODS: We performed a retrospective, cross-sectional analysis of 357 adult IBD patients on immunosuppression in our health care system. Patient demographics and clinical characteristics were collected. The primary outcome was rate of documented vaccinations recommended by providers; the secondary outcome was rate of receipt of the vaccines. We identified factors associated with receipt of any pneumococcal vaccine through multivariable logistic regression. We also performed provider and IBD patient surveys to understand provider and patient knowledge regarding pneumococcal vaccines. We used χ 2 and Fisher exact tests to assess survey responses. RESULTS: Fifty seven percent of IBD patients had any pneumococcal vaccination recommended and 35% had recommendations for both PPSV23 and PCV13. Forty percent received any pneumococcal vaccine and 18% received both vaccines. In multivariable analyses, increasing age (adjusted odds ratio: 1.03, 95% CI: 1.01-1.05) was associated with receipt of any pneumococcal vaccine, after adjusting for gender, race, insurance, disease activity, and time seen in our gastroenterology clinics. In the survey study, on average, 59% of providers correctly answered questions regarding pneumococcal vaccination indications. CONCLUSION: In our health care system, while recommendation for any pneumococcal vaccination was >50%, receipt of both PPSV23 and PCV13 was low. Simplified vaccine regimens (ie, PCV20) will likely improve vaccination rates.

Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) alter their dietary behaviors to reduce disease-related symptoms, avoid feared food triggers, and control inflammation. This study aimed to estimate the prevalence of avoidant/restrictive food intake disorder (ARFID), evaluate risk factors, and examine the association with risk of malnutrition in patients with IBD. METHODS: This cross-sectional study recruited adult patients with IBD from an ambulatory clinic. ARFID risk was measured using the Nine-Item ARFID Screen. Nutritional risk was measured with the Patient Generated-Subjective Global Assessment. Logistic regression models were used to evaluate the association between clinical characteristics and a positive ARFID risk screen. Patient demographics, disease characteristics, and medical history were abstracted from medical records. RESULTS: Of the 161 participants (Crohn's disease, 45.3%; ulcerative colitis, 51.6%; IBD-unclassified, 3.1%), 28 (17%) had a positive ARFID risk score (≥24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Active symptoms (odds ratio, 5.35; 95% confidence interval, 1.91-15.01) and inflammation (odds ratio, 3.31; 95% confidence interval, 1.06-10.29) were significantly associated with positive ARFID risk. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P < .01). CONCLUSIONS: Avoidant eating behaviors are common in IBD patients, even when in clinical remission. Patients who exhibit active symptoms and/or inflammation should be screened for ARFID risk, with referrals to registered dietitians to help monitor and address disordered eating behaviors and malnutrition risk.

Recommendations on the Appropriate Management of Steroids and Discharge Planning During and After Hospital Admission for Moderate-Severe Ulcerative Colitis: Results of a RAND Appropriateness Panel.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

Effect of Obesity on Risk of Hospitalization, Surgery, and Serious Infection in Biologic-Treated Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

INTRODUCTION: Obesity is variably associated with treatment response in biologic-treated patients with inflammatory bowel diseases (IBD). We evaluated the association between obesity and risk of hospitalization, surgery, or serious infections in patients with IBD in new users of biologic agents in a large, multicenter, electronic health record (EHR)-based cohort (CA-IBD). METHODS: We created an EHR-based cohort of adult patients with IBD who were new users of biologic agents (tumor necrosis factor [TNF-α] antagonists, ustekinumab, and vedolizumab) between January 1, 2010, and June 30, 2017, from 5 health systems in California. Patients were classified as those with normal body mass index (BMI), overweight, or obese based on the World Health Organization classification. We compared the risk of all-cause hospitalization, IBD-related surgery, or serious infections among patients with obesity vs those overweight vs those with normal BMI, using Cox proportional hazard analyses, adjusting for baseline demographic, disease, and treatment characteristics. RESULTS: Of 3,038 biologic-treated patients with IBD (69% with Crohn's disease and 76% on TNF-α antagonists), 28.2% (n = 858) were overweight, and 13.7% (n = 416) were obese. On a follow-up after biologic initiation, obesity was not associated with an increased risk of hospitalization (adjusted hazard ratio [aHR] vs normal BMI, 0.90; [95% confidence interval, 0.72-1.13]); IBD-related surgery (aHR, 0.62 [0.31-1.22]); or serious infection (aHR, 1.11 [0.73-1.71]). Similar results were observed on stratified analysis by disease phenotype (Crohn's disease vs ulcerative colitis) and index biologic therapy (TNF-α antagonists vs non-TNF-α antagonists). DISCUSSION: In a multicenter, EHR-based cohort of biologic-treated patients with IBD, obesity was not associated with hospitalization, surgery, or serious infections. Further studies examining the effect of visceral obesity on patient-reported and endoscopic outcomes are needed.

What's New in the Postoperative Management of Crohn's Disease?

Patients with Crohn's disease (CD) often require surgical resection due to complications, such as strictures and abscesses, or disease refractory to medical therapy. To understand the evolving management of patients with CD after surgery, we outline the risk factors for postoperative recurrence, advances in postoperative endoscopic evaluation and characterization of recurrence, noninvasive methods of assessing postoperative recurrence, use of postoperative prophylactic medical therapy including newer biologics, and novel surgical methods to reduce postoperative recurrence. The Rutgeerts score (RS) was developed to predict progression of disease based on endoscopic appearance postoperatively and to guide medical therapy. However, this scoring system groups ileal and anastomotic lesions into the same category. A modified RS was developed to separate lesions isolated to the anastomosis and those in the neo-terminal ileum to further understand the role of anastomotic lesions in CD progression. Additional scoring systems have also been evaluated to better understand these differences. In addition, noninvasive diagnostic methods, such as small bowel ultrasound, have high sensitivity and specificity for the detection of postoperative recurrence and are being evaluated as independent methods of assessment. Studies have also shown a reduction in endoscopic recurrence with postoperative anti-TNFα therapy. However, preoperative exposure to anti-TNFα therapy may impact postoperative response to these medications, and therefore, determining optimal postoperative prophylaxis strategy for biologic-experienced patients requires further exploration. Lastly, new surgical modalities to reduce postoperative recurrence are currently being investigated with preliminary data suggesting that an antimesenteric functional end-to-end anastomosis (Kono-S) may decrease postoperative recurrence.

The Role of Resilience in Irritable Bowel Syndrome, Other Chronic Gastrointestinal Conditions, and the General Population.

BACKGROUND & AIMS: Resilience is the ability to adapt positively to stress and adversity. It is a potential therapeutic target as it is reduced in irritable bowel syndrome (IBS) compared to healthy controls and associated with worse symptom severity and poorer quality of life. The aim of this study was to examine if these findings are generalizable by comparing resilience between IBS versus the general population and other chronic gastrointestinal (GI) conditions. METHODS: Participants in the general population completed an online survey containing questionnaires measuring demographics, diagnosis of IBS and other GI conditions, symptom severity, psychological symptoms, resilience, and early adverse life events (EALs). IBS was defined as having a physician diagnosis of IBS and/or meeting Rome criteria without co-morbid GI disease. All others were included in the general population group. The chronic GI conditions group included those with inflammatory bowel disease, celiac disease and/or microscopic colitis. RESULTS: Resilience was lower in IBS (n = 820) than the general population (n = 1026; p < 0.001) and associated with worse IBS symptom severity (p < 0.05). Global mental health affected resilience differently in IBS compared to the general population (all p's < 0.05). EALs were associated with decreased ability to bounce back from adversity in both IBS and the general population (p < 0.001). Resilience scores were similar in IBS and other chronic GI conditions that present with similar symptoms. CONCLUSIONS: Resilience is lower compared to the general U.S. population but does not appear to be specific to IBS as it is comparable to other chronic GI conditions. Low resilience negatively affects symptom severity and mental health and thus, may serve as a novel therapeutic target.

Rates of inflammatory bowel disease in Hispanics comparable to non-Hispanic Whites: results of a cohort study.

PURPOSE: Previous studies have suggested that inflammatory bowel disease (IBD) occurs at higher rates among non-Hispanic Whites (NHWs) compared to other ethnicities; however, Hispanics as the largest minority in the United States remain underrepresented in IBD research and we hypothesize that they have similar rates of IBD. We examined the epidemiology, demographics, clinical presentation, and treatment of IBD in a predominantly Hispanic cohort in Los Angeles (LA) County. METHODS: This was a retrospective cohort study based at Olive View-UCLA Medical Center, one of the three major safety-net hospitals in LA County. Electronic medical records from 2015 to 2018 were queried, and biopsy-proven cases of IBD (n = 170) were identified. Outcomes included the incidence and prevalence of IBD, disease distribution, treatment, and IBD-related surgery. RESULTS: The incidence of IBD among Hispanics was 175 (95% confidence interval [CI] 127-240) and 113 (95% CI 62-200) for NHWs per 100,000 person-years. Prevalence of IBD per 100,000 people was 418 (95% CI 341-512) for Hispanics and 557 (95% CI 431-739) for NHWs. Notably, the proportion of Hispanic IBD patients with a history of smoking was 21.5% vs 50.8% in NHWs (p = 0.011). There were no significant differences between the two groups with regard to Montreal classification, pharmacotherapy, or IBD-related surgery. CONCLUSIONS: In one of the largest US studies of Hispanics with IBD, and the only one to have both clinical and histopathologic confirmation as inclusion criteria, we found the incidence and prevalence of IBD among Hispanics to be higher than previously recognized and comparable to NHWs. Additionally, Hispanic IBD patients had lower rates of smoking compared to NHWs.

The IBD-associated long noncoding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation.

The inflammatory bowel diseases (IBD) are a complex set of chronic gastrointestinal inflammatory conditions arising from the interplay of genetic and environmental factors. This study focuses on noncoding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon γ-antisense 1 (IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of patients with actively inflamed IBD versus healthy controls. This study builds on these observations, demonstrating that the second splice variant is specifically altered, and this alteration even stratifies within inflamed patients. With the use of a CRISPR-based overexpression system, IFNG-AS1 was selectively overexpressed directly from its genomic loci in T cells. An unbiased mRNA array on these cells identified a large increase in many inflammatory cytokines and a decrease in anti-inflammatory cytokines after IFNG-AS1 overexpression. Media from T cells overexpressing IFNG-AS1 elicited an inflammatory signaling cascade in primary human peripheral blood mononuclear cells, suggesting the potential functional importance of IFNG-AS1 in IBD pathophysiology. The significance of these results is amplified by studies suggesting that a single-nucleotide polymorphism in IFNG-AS1, rs7134599, was associated with both subtypes of patients with IBD independently of race.NEW & NOTEWORTHY Long noncoding RNAs are an emerging field of inflammatory bowel disease (IBD) research. This study mechanistically analyzes the role of a commonly upregulated gene in IBD and shows IFNG-AS1 as a mediator of an inflammatory signaling cascade.

IBD in the Elderly: Management Challenges and Therapeutic Considerations.

PURPOSE OF REVIEW: Elderly patients with inflammatory bowel disease (IBD) are increasing in prevalence as our population ages and the incidence of IBD increases. The purpose of this review is to describe the management challenges in elderly IBD patients, including comorbid conditions and therapeutic considerations unique to the elderly population. RECENT FINDINGS: The elderly experience coexisting comorbidities that complicate IBD management. The disease course and potential side effects of treatments can impact the elderly IBD patient differently than younger IBD patients. The duration for colorectal cancer surveillance (CRC) also remains controversial and should be individualized to determine when discontinuation is appropriate. Given greater safety considerations in the elderly IBD population, treatment targets and management goals require a more personalized approach in the elderly, taking into account coexisting comorbidities, inflammatory burden, and functional limitations.

Tethered capsule endomicroscopy for microscopic imaging of the esophagus, stomach, and duodenum without sedation in humans (with video).

BACKGROUND AND AIMS: Patients with many different digestive diseases undergo repeated EGDs throughout their lives. Tethered capsule endomicroscopy (TCE) is a less-invasive method for obtaining high-resolution images of the GI mucosa for diagnosis and treatment planning of GI tract diseases. In this article, we present our results from a single-center study aimed at testing the safety and feasibility of TCE for imaging the esophagus, stomach, and duodenum. METHODS: After being swallowed by a participant without sedation, the tethered capsule obtains cross-sectional, 10 µm-resolution, optical coherence tomography images as the device traverses the alimentary tract. After imaging, the device is withdrawn through the mouth, disinfected, and reused. Safety and feasibility of TCE were tested, focusing on imaging the esophagus of healthy volunteers and patients with Barrett's esophagus (BE) and the duodenum of healthy volunteers. Images were compared with endoscopy and histopathology findings when available. RESULTS: Thirty-eight patients were enrolled. No adverse effects were reported. The TCE device swallowing rate was 34 of 38 (89%). The appearance of a physiologic upper GI wall, including its microscopic pathology, was visualized with a tissue coverage of 85.4% ± 14.9% and 90.3% ± 6.8% in the esophagus of BE patients with and without endoscopic evidence of a hiatal hernia, respectively, as well as 84.8% ± 7.4% in the duodenum. A blinded comparison of TCE and endoscopic BE measurements showed a strong to very strong correlation (r = 0.7-0.83; P < .05) for circumferential extent and a strong correlation (r = 0.77-0.78; P < .01) for maximum extent (Prague classification). TCE interobserver correlation was very strong, at r = 0.92 and r = 0.84 (P < .01), for Prague classification circumferential (C) and maximal (M) length measurements, respectively. CONCLUSIONS: TCE is a safe and feasible procedure for obtaining high-resolution microscopic images of the upper GI tract without endoscopic assistance or sedation.

Increasing Rates of Bowel Resection Surgery for Stricturing Crohn's Disease in the Biologic Era.

BACKGROUND: The era of biologics is associated with declining rates of surgery for Crohn's disease (CD), but the impact on surgery for stricturing CD is unknown. Our study aimed to assess nationwide trends in bowel resection surgery for obstruction in CD since the introduction of infliximab for CD in 1998. METHODS: Using the Nationwide Inpatient Sample, we performed a nationwide analysis, identifying patients hospitalized for CD who underwent bowel resection for an indication of obstruction between 1998 and 2020 (era of biologics). Longitudinal trends in all CD-related resections and resection for obstruction were evaluated. Multivariable logistic regression identified patient and hospital characteristics associated with bowel resection surgery for obstruction. RESULTS: Hospitalizations for all CD-related resections decreased from 12.0% of all hospitalizations in 1998 to 6.9% in 2020, while hospitalizations for CD-related resection for obstructive indication increased from 1.3% to 2.0%. The proportion of resections for obstructive indication amongst all CD-related bowel resections increased from 10.8% in 1998 to 29.1% in 2020. In the multivariable models stratified by elective admission, the increasing year was associated with risk of resection for obstructive indication regardless of urgency (nonelective model: odds ratio, 1.01; 95% CI, 1.00-1.02; elective model: odds ratio, 1.06; 95% CI, 1.04-1.08). CONCLUSIONS: In the era of biologics, our findings demonstrate a decreasing annual rate of CD-related bowel resections but an increase in resection for obstructive indication. Our findings highlight the effect of medical therapy on surgical rates overall but suggest limited impact of current medical therapy on need of resection for stricturing disease.

In our nationwide analysis, rates of bowel resection for patients with Crohn's disease have declined since the approval of infliximab in 1998. However, rates of resection for obstruction in patients with Crohn's disease continue to increase.

Recent trends and risk factors associated with Clostridioides difficile infections in hospitalized patients with inflammatory bowel disease.

BACKGROUND: Clostridioides difficile infections (CDIs) are common among patients with inflammatory bowel disease (IBD) and can mimic and exacerbate IBD flares, thus warranting appropriate testing during flares. AIMS: To examine recent trends in rates of CDI and associated risk factors in hospitalized IBD patients, which may better inform targeted interventions to mitigate the risk of infection. METHODS: This is a retrospective analysis using the Nationwide Readmissions Database from 2010 to 2020 of hospitalized individuals with Crohn's disease (CD) or ulcerative colitis (UC). Longitudinal changes in rates of CDI were evaluated using International Classification of Diseases codes. Multivariable logistic regression evaluated the association between patient- and hospital-related factors and CDI. RESULTS: There were 2,521,935 individuals with IBD who were hospitalized at least once during the study period. Rates of CDI in IBD-related hospitalizations increased from 2010 to 2015 (CD: 1.64%-3.32%, p < 0.001; UC: 4.15%-5.81%, p < 0.001), followed by a steady decline from 2016 to 2020 (CD: 3.15%-2.27%, p < 0.001; UC: 5.04%-4.27%, p < 0.001). In multivariable models, CDI was associated with the Charlson-Deyo comorbidity index, public insurance, and hospital size. CDI was associated with increased mortality. CONCLUSIONS: Rates of CDI among hospitalized patients with IBD had initially increased, but have declined since 2015. Increased comorbidity, large hospital size, public insurance, and urban teaching hospitals were associated with higher rates of CDI. CDI was associated with increased mortality in hospitalized patients with IBD. Continued vigilance, infection control, and treatment of CDI can help continue the trend of declining infection rates.

Microbial and Metabolite Signatures of Stress Reactivity in Ulcerative Colitis Patients in Clinical Remission Predict Clinical Flare Risk.

BACKGROUND: Stress reactivity (SR) is associated with increased risk of flares in ulcerative colitis (UC) patients. Because both preclinical and clinical data support that stress can influence gut microbiome composition and function, we investigated whether microbiome profiles of SR exist in UC. METHODS: Ninety-one UC subjects in clinical and biochemical remission were classified into high and low SR groups by questionnaires. Baseline and longitudinal characterization of the intestinal microbiome was performed by 16S rRNA gene sequencing and fecal and plasma global untargeted metabolomics. Microbe, fecal metabolite, and plasma metabolite abundances were analyzed separately to create random forest classifiers for high SR and biomarker-derived SR scores. RESULTS: High SR reactivity was characterized by altered abundance of fecal microbes, primarily in the Ruminococcaceae and Lachnospiraceae families; fecal metabolites including reduced levels of monoacylglycerols (endocannabinoid-related) and bile acids; and plasma metabolites including increased 4-ethyl phenyl sulfate, 1-arachidonoylglycerol (endocannabinoid), and sphingomyelin. Classifiers generated from baseline microbe, fecal metabolite, and plasma metabolite abundance distinguished high vs low SR with area under the receiver operating characteristic curve of 0.81, 0.83, and 0.91, respectively. Stress reactivity scores derived from these classifiers were significantly associated with flare risk during 6 to 24 months of follow-up, with odds ratios of 3.8, 4.1, and 4.9. Clinical flare and intestinal inflammation did not alter fecal microbial abundances but attenuated fecal and plasma metabolite differences between high and low SR. CONCLUSIONS: High SR in UC is characterized by microbial signatures that predict clinical flare risk, suggesting that the microbiome may contribute to stress-induced UC flares.

Impact of malnutrition and nutrition support in hospitalised patients with inflammatory bowel disease.

BACKGROUND: Malnutrition is prevalent in patients with inflammatory bowel disease (IBD) and has been associated with worse clinical outcomes. AIMS: This observational study examines trends in protein-calorie malnutrition (PCM) amongst hospitalised IBD and non-IBD patients, and the association between (1) malnutrition and (2) nutrition support and hospitalisation outcomes. METHODS: We queried the Nationwide Readmissions Database from 2010 to 2018 for hospitalisations with and without IBD. Amongst patients with IBD and concurrent PCM, we identified those who received nutrition support. Multivariable Cox proportional hazards and Kaplan-Meier analyses evaluated the associations between PCM and nutrition support and readmission and mortality. Multiple linear regression described the association between compared variables and length of stay (LOS) and total hospitalisation costs. RESULTS: This study included 1,216,033 patients (1,820,023 hospitalisations) with Crohn's disease (CD), 832,931 patients (1,089,853 hospitalizations) with ulcerative colitis (UC) and 240,488,656 patients (321,220,427 hospitalisations) without IBD. Admitted IBD patients were 2.9-3.1 times more likely to have PCM than non-IBD patients. IBD patients with PCM had a higher risk of readmission and mortality, as well as longer LOS and higher hospitalisation costs. Nutrition support (parenteral and enteral) was associated with a reduced risk of readmission, but higher mortality increased LOS and higher total hospitalisation costs. CONCLUSIONS: Malnutrition in hospitalised IBD patients remains an important contributor to readmission, mortality, LOS and healthcare costs. Providing nutrition support to IBD patients may reduce the risk of readmission. Further studies are needed to evaluate the role of nutrition support amongst hospitalised IBD patients to optimise disease and healthcare outcomes.

Machine Learning-based Characterization of Longitudinal Health Care Utilization Among Patients With Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with increased health care utilization. Forecasting of high resource utilizers could improve resource allocation. In this study, we aimed to develop machine learning models (1) to cluster patients according to clinical utilization patterns and (2) to predict longitudinal utilization patterns based on readily available baseline clinical characteristics. METHODS: We conducted a retrospective study of adults with IBD at 2 academic centers between 2015 and 2021. Outcomes included different clinical encounters, new prescriptions of corticosteroids, and initiation of biologic therapy. Machine learning models were developed to characterize health care utilization. Poisson regression compared frequencies of clinical encounters. RESULTS: A total of 1174 IBD patients were followed for more than 5673 12-month observational windows. The clustering method separated patients according to low, medium, and high resource utilizers. In Poisson regression models, compared with low resource utilizers, moderate and high resource utilizers had significantly higher rates of each encounter type. Comparing moderate and high resource utilizers, the latter had greater utilization of each encounter type, except for telephone encounters and biologic therapy initiation. Machine learning models predicted longitudinal health care utilization with 81% to 85% accuracy (area under the receiver operating characteristic curve 0.84-0.90); these were superior to ordinal regression and random choice methods. CONCLUSION: Machine learning models were able to cluster individuals according to relative health care resource utilization and to accurately predict longitudinal resource utilization using baseline clinical factors. Integration of such models into the electronic medical records could provide a powerful semiautomated tool to guide patient risk assessment, targeted care coordination, and more efficient resource allocation.