The enteric nervous system relays psychological stress to intestinal inflammation.

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-ß2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.

Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.

Humoral immune response and safety of SARS-CoV-2 vaccination in very early onset inflammatory bowel disease.

Children with very early onset inflammatory bowel disease (VEO-IBD) may respond differently to coronavirus disease 2019 (COVID-19) immunization compared to healthy children or other patients with IBD. We recruited children with VEO-IBD <6 years of age and younger following receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Demographics, IBD characteristics, medication use, adverse events (AEs) and IBD exacerbations were collected. Blood draws (optional) were obtained for measurement of antireceptor binding domain (RBD) IgG antibodies following vaccination. Of 41 participants, none required emergency department visit or hospitalization due to AE, and only one experienced IBD exacerbation. Detectable antibody was present in 19/19 participants who provided blood sample; 6/7 participants (86%) had durable humoral response 12 months postvaccination. Children with VEO-IBD experience robust humoral immune response to COVID-19 immunization. Severe AEs were rare. These findings provide reassurance that children with VEO-IBD respond well and safely to SARS-CoV-2 vaccination.

Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome.

BACKGROUND & AIMS: Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized. METHODS: To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days. RESULTS: Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition. CONCLUSIONS: These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).

Humoral Immune Response and Safety of SARS-CoV-2 Vaccination in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

Pediatric Cholelithiasis in the United States: National Hospitalization Trends, 2006 to 2019.

OBJECTIVES: Previous studies have shown increasing hospitalizations for pediatric cholelithiasis, but recent trends are unknown. We conducted a national study of pediatric cholelithiasis to characterize recent hospitalization rate trends. METHODS: Retrospective repeated cross-sectional analysis of pediatric (age < 18 years) cholelithiasis-associated hospitalizations combining data from the 2006 through 2019 Kids' Inpatient Database releases. The primary outcome of interest was the national hospitalization rate (per 100,000 children). We examined rates stratified by age group and sex and characterized hospitalization outcomes and characteristics for pediatric cholelithiasis. RESULTS: Twenty-nine thousand one hundred two hospital records representing 42,282 gallstone-associated hospitalizations were identified. The hospitalization rate declined from 12.9 [95% confidence interval (CI): 12.6-13.2] in 2006 to 9.1 (95% CI: 8.8-9.3) in 2019. Consistent with the literature, hospitalizations occurred most often among teenagers (71%) and individuals with female sex (72%). The proportion of hospitalizations at freestanding children's hospitals increased significantly (from 18.2% to 35.1%). Finally, the proportion of hospitalizations involving a potentially medical predisposing condition increased significantly. CONCLUSIONS: The estimated US hospitalization rate for pediatric cholelithiasis declined by 30% between 2006 and 2019. Female patients and teenagers had the largest decline, and hospitalizations increasingly occurred at freestanding children's hospitals. Potential explanations include potential changes in delivery of care as well as changes in population disease burden.

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

Factors Affecting Initial Humoral Immune Response to SARS-CoV-2 Vaccines Among Patients With Inflammatory Bowel Diseases.

INTRODUCTION: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD. METHODS: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level. RESULTS: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0-3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4-7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1-0.8) and ustekinumab (OR 0.2, 95% CI 0.05-0.8) was associated with decreased odds of lacking antibody response. DISCUSSION: Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.

COVID-19 Vaccine Perceptions Among Patients With Chronic Disease in a Large Gastroenterology and Hepatology Practice.

INTRODUCTION: To assess beliefs about safety, effectiveness, and delivery of the coronavirus disease 2019 (COVID-19) vaccine among chronic Gastroenterology and Hepatology patients at an academic health system. METHODS: We asked about vaccine beliefs, vaccine concerns, and preferred location to receive the COVID-19 vaccine. RESULTS: A total of 1,215 patients responded (response rate: 37%). Most patients believed that vaccines are safe, effective, and that they would take the COVID-19 vaccine at a medical office or pharmacy. However, we identified important sociodemographic factors associated with vaccine hesitancy. DISCUSSION: Patients have high level of trust in the COVID-19 vaccine and are likely to follow their specialist physician recommendations.

Community stakeholder preferences for evidence-based practice implementation strategies in behavioral health: a best-worst scaling choice experiment.

BACKGROUND: Community behavioral health clinicians, supervisors, and administrators play an essential role in implementing new psychosocial evidence-based practices (EBP) for patients receiving psychiatric care; however, little is known about these stakeholders' values and preferences for implementation strategies that support EBP use, nor how best to elicit, quantify, or segment their preferences. This study sought to quantify these stakeholders' preferences for implementation strategies and to identify segments of stakeholders with distinct preferences using a rigorous choice experiment method called best-worst scaling. METHODS: A total of 240 clinicians, 74 clinical supervisors, and 29 administrators employed within clinics delivering publicly-funded behavioral health services in a large metropolitan behavioral health system participated in a best-worst scaling choice experiment. Participants evaluated 14 implementation strategies developed through extensive elicitation and pilot work within the target system. Preference weights were generated for each strategy using hierarchical Bayesian estimation. Latent class analysis identified segments of stakeholders with unique preference profiles. RESULTS: On average, stakeholders preferred two strategies significantly more than all others-compensation for use of EBP per session and compensation for preparation time to use the EBP (P < .05); two strategies were preferred significantly less than all others-performance feedback via email and performance feedback via leaderboard (P < .05). However, latent class analysis identified four distinct segments of stakeholders with unique preferences: Segment 1 (n = 121, 35%) strongly preferred financial incentives over all other approaches and included more administrators; Segment 2 (n = 80, 23%) preferred technology-based strategies and was younger, on average; Segment 3 (n = 52, 15%) preferred an improved waiting room to enhance client readiness, strongly disliked any type of clinical consultation, and had the lowest participation in local EBP training initiatives; Segment 4 (n = 90, 26%) strongly preferred clinical consultation strategies and included more clinicians in substance use clinics. CONCLUSIONS: The presence of four heterogeneous subpopulations within this large group of clinicians, supervisors, and administrators suggests optimal implementation may be achieved through targeted strategies derived via elicitation of stakeholder preferences. Best-worst scaling is a feasible and rigorous method for eliciting stakeholders' implementation preferences and identifying subpopulations with unique preferences in behavioral health settings.

Variation Among Patients With Crohn's Disease in Benefit vs Risk Preferences and Remission Time Equivalents.

BACKGROUND & AIMS: Patients with Crohn's disease (CD) must make decisions about their treatment. We aimed to quantify patients' preferences for different treatment outcomes and adverse events. We also evaluated the effects of latent class heterogeneity on these preferences. METHODS: An online stated-preference survey was completed by 812 individuals with CD in the Crohn's and Colitis Foundation Partners cohort (IBD Partners). Patients were given information on symptoms and severity of active disease; duration of therapy with corticosteroids; and risks of serious infection, cancer and surgery. Patients were asked to assume that their treatment was not working and to choose an alternative therapy. The primary outcome was remission-time equivalents (RTE) of a given duration of symptom severity or treatment-related risk. Latent class choice models identified groups of patients with dominant treatment-outcome preferences and associated patient characteristics with these groups. RESULTS: Latent class analysis demonstrated 3 distinct groups of survey responders whose choices were strongly influenced by avoidance of active symptoms (61%), avoidance of corticosteroid use (25%), or avoidance of risks of cancer, infection or surgery (14%) when choosing a therapy. Class membership was correlated with age, sex, mean short CD activity index score and corticosteroid avoidance. RTEs in each latent class differed significantly from the mean RTEs for the overall sample, although the symptom-avoidant class most closely approximated the overall sample. CONCLUSIONS: In an online survey of patients with CD, we found substantial heterogeneity in preference for medication efficacy and risk of harm. Physicians and regulators should therefore not assume that all patients have mean-value preferences-this could result in significant differences in health-technology assessment models.

Mongersen and SMAD-7 Inhibition, Not a Lucky 7 for Patients With IBD: When Trial Design Is as Important as Disease Therapy.

The phase II mongersen (GED-0301) trial produced unparalleled success rates in Crohn's disease and generated much hope for a crippling disease. Unfortunately, the subsequent phase III trial was terminated early because of a lack of efficacy. We discuss the differences in trial design that may have contributed to these disparate findings and how these findings may serve as a lesson in subsequent therapeutic trials in Crohn's disease.

Comparing the Noncomparable: The Need for Equivalence Measures That Make Sense in Health-Economic Evaluations.

BACKGROUND: The popularity of quality-adjusted life years (QALYs) has been resistant to concerns about validity and reliability. Utility-theoretic outcome equivalents are widely used in other areas of applied economics. Equivalence values can be derived for time, money, risk, and other metrics. These equivalence measures preserve all available information about individual preferences and are valid measures of individual welfare changes. OBJECTIVE: The objective of this study was to derive alternative generalized equivalence measures from first principles and illustrate their application in an empirical comparative-effectiveness example. METHODS: We specify a general-equilibrium model incorporating neoclassical utility functions, health production function, severity-duration preferences, and labor-market tradeoff function. The empirical implementation takes advantage of discrete-choice experiment methods that are widely accepted in other areas of applied economics and increasingly in health economics. We illustrate the practical significance of restrictive QALY assumptions using comparative-effectiveness results based on both QALYs and estimates of welfare-theoretic time-equivalent values for anti-tumor necrosis factor and prolonged corticosteroid treatments for Crohn's disease in three distinct preference classes. RESULTS: The QALY difference between the two treatments is 0.2 months, while time-equivalent values range between 0.5 and 1.3 months for aggregate and class-specific differences. Thus, the QALY-based analysis understates welfare-theoretic values by 60%-85%. CONCLUSION: These results suggest that using disease-specific equivalence values offer a meaningful alternative to QALYs to compare global outcomes across treatments. The equivalence values approach is consistent with principles of welfare economics and offers several features not represented in QALYs, including accounting for preference nonlinearities in disease severity and duration, inclusion of preference-relevant nonclinical healthcare factors, representing preferences of clinically-relevant patient subpopulations, and including utility losses related to risk aversion.

Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis.

The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that mice with an intestinal epithelial cell (IEC)-specific deletion of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3(ΔIEC) mice) exhibited extensive dysregulation of IEC-intrinsic gene expression, including decreased basal expression of genes associated with antimicrobial defence. Critically, conventionally housed HDAC3(ΔIEC) mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3(ΔIEC) mice showed significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 has a central role in maintaining intestinal homeostasis. Re-derivation of HDAC3(ΔIEC) mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis and intestinal barrier function were largely restored in the absence of commensal bacteria. Although the specific mechanisms through which IEC-intrinsic HDAC3 expression regulates these complex phenotypes remain to be determined, these data indicate that HDAC3 is a critical factor that integrates commensal-bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis.

Increased Mortality Rates With Prolonged Corticosteroid Therapy When Compared With Antitumor Necrosis Factor-α-Directed Therapy for Inflammatory Bowel Disease.

OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that compromise quality of life and may increase mortality. This study compared the mortality risk with prolonged corticosteroid use vs. antitumor necrosis factor-α (anti-TNF) drugs in IBD. METHODS: A retrospective cohort study was conducted among Medicaid and Medicare beneficiaries from 2001 to 2013 with IBD prescribed either >3,000 mg of prednisone or equivalent within a 12-month period or new initiation of anti-TNF therapy, each treated as time-updating exposures. The primary outcome was all-cause mortality. Secondary outcomes included common causes of death. Marginal structural models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for anti-TNF use relative to corticosteroids. RESULTS: Among patients with CD, 7,694 entered the cohort as prolonged corticosteroid users and 1,879 as new anti-TNF users. Among patients with UC, 3,224 and 459 entered the cohort as prolonged CS users and new anti-TNF users, respectively. The risk of death was statistically significantly lower in patients treated with anti-TNF therapy for CD (21.4 vs. 30.1 per 1,000 person-years, OR 0.78, 0.65-0.93) but not for UC (23.0 vs. 30.9 per 1,000 person-years, OR 0.87, 0.63-1.22). Among the CD cohort, anti-TNF therapy was also associated with lower rates of major adverse cardiovascular events (OR 0.68, 0.55-0.85) and hip fracture (OR 0.54, 0.34-0.83). CONCLUSIONS: Compared with prolonged corticosteroid exposure, anti-TNF drug use was associated with reduced mortality in patients with CD that may be explained by lower rates of major adverse cardiovascular events and hip fracture.

Radiofrequency Ablation Is Associated With Decreased Neoplastic Progression in Patients With Barrett's Esophagus and Confirmed Low-Grade Dysplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) with low-grade dysplasia (LGD) can progress to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) has been shown to be an effective treatment for LGD in clinical trials, but its effectiveness in clinical practice is unclear. We compared the rate of progression of LGD after RFA with endoscopic surveillance alone in routine clinical practice. METHODS: We performed a retrospective study of patients who either underwent RFA (n = 45) or surveillance endoscopy (n = 125) for LGD, confirmed by at least 1 expert pathologist, from October 1992 through December 2013 at 3 medical centers in the United States. Cox regression analysis was used to assess the association between progression and RFA. RESULTS: Data were collected over median follow-up periods of 889 days (interquartile range, 264-1623 days) after RFA and 848 days (interquartile range, 322-2355 days) after surveillance endoscopy (P = .32). The annual rates of progression to HGD or EAC were 6.6% in the surveillance group and 0.77% in the RFA group. The risk of progression to HGD or EAC was significantly lower among patients who underwent RFA than those who underwent surveillance (adjusted hazard ratio = 0.06; 95% confidence interval: 0.008-0.48). CONCLUSIONS: Among patients with BE and confirmed LGD, rates of progression to a combined end point of HGD and EAC were lower among those treated with RFA than among untreated patients. Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for LGD.

Mortality associated with medical therapy versus elective colectomy in ulcerative colitis: a cohort study.

BACKGROUND: Ulcerative colitis (UC) can be treated with surgery or medications. Patients often must choose between long-term immunosuppressant therapy or total colectomy. Whether one of these treatment approaches has a mortality benefit is uncertain. OBJECTIVE: To determine whether patients with advanced UC treated with elective colectomy have improved survival compared with those treated with medical therapy. DESIGN: Retrospective matched cohort study. SETTING: Data from all 50 states for Medicaid beneficiaries (2000 to 2005), Medicare beneficiaries (2006 to 2011), and dual-eligible persons (2000 to 2011). PATIENTS: 830 patients with UC pursuing elective colectomy and 7541 matched patients with UC pursuing medical therapy. MEASUREMENTS: The primary outcome was time to death. Cox proportional hazards models were used to compare the survival of patients with advanced UC treated with elective colectomy or medical therapy. The models controlled for significant comorbid conditions through matched and adjusted analysis. RESULTS: The mortality rates associated with elective surgery and medical therapy were 34 and 54 deaths per 1000 person-years, respectively. Elective colectomy was associated with improved survival compared with long-term medical therapy (adjusted hazard ratio [HR], 0.67 [95% CI, 0.52 to 0.87]), although this result did not remain statistically significant in all sensitivity analyses. Post hoc analysis by age group showed improved survival with surgery in patients aged 50 years or older with advanced UC (HR, 0.60 [CI, 0.45 to 0.79]; P = 0.032 for age-by-treatment interaction). LIMITATIONS: Retrospective nonrandomized analysis is subject to residual confounding. The source cohort was derived from different databases throughout the study. Sensitivity and secondary analyses had reduced statistical power. CONCLUSION: Elective colectomy seemed to be associated with improved survival relative to medical therapy among patients aged 50 years or older with advanced UC. PRIMARY FUNDING SOURCE: National Institutes of Health and Agency for Healthcare Research and Quality.