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Brandon M Shore,1 Bharati Kochar,2,3 Hans H Herfarth,4,5 Edward L Barnes4,5 1Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA; 3The Mongan Institute, Boston, MA, USA; 4Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 5Center for Gastrointestinal Biology and Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACorrespondence: Edward L Barnes, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Campus Box #7080, 130 Mason Farm Road, Chapel Hill, NC, 27599-7080, USA, Tel +1 919-962-3112, Fax +1 919-966-6842, Email edward_barnes@med.unc.eduAbstract: The population of older patients with inflammatory bowel disease (IBD) is expected to continue to increase in the coming decades, which necessitates and improved understanding of the critical issues faced by patients in this population. Although restorative proctocolectomy with IPAA remains the surgical procedure of choice for the majority of patients with medically refractory ulcerative colitis (UC) and UC-related dysplasia, the evidence surrounding surgery for older patients UC remains sparse. In particular, comparisons of outcomes among older and younger patients undergoing IPAA and comparisons between older patients undergoing IPAA and those undergoing proctocolectomy with end ileostomy remain an understudied and important issue, as evidence in this area will be used to guide patient-centered surgical choices among older patients who require colectomy for UC. In this narrative review, we review the available literature regarding IPAA for older patients, as well as the pre-, peri-, and postoperative factors that may influence outcomes in this population.Keywords: pouchitis, surgery, older age, ulcerative colitis, J-pouch

Inflammaging, a state of chronic, progressive low-grade inflammation during aging, is associated with several adverse clinical outcomes, including frailty, disability, and death. Chronic inflammation is a hallmark of aging and is linked to the pathogenesis of many aging-related diseases. Anti-inflammatory therapies are also increasingly being studied as potential anti-aging treatments, and clinical trials have shown benefits in selected aging-related diseases. Despite promising advances, significant gaps remain in defining, measuring, treating, and integrating inflammaging into clinical geroscience research. The Clin-STAR Inflammation Research Interest Group was formed by a group of transdisciplinary clinician-scientists with the goal of advancing inflammaging-related clinical research and improving patient-centered care for older adults. Here, we integrate insights from nine medical subspecialties to illustrate the widespread impact of inflammaging on diseases linked to aging, highlighting the extensive opportunities for targeted interventions. We then propose a transdisciplinary approach to enhance understanding and treatment of inflammaging that aims to improve comprehensive care for our aging patients., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Purpose of Review: The prevalence of IBD in older adults is rapidly growing. Older adults with IBD are underrepresented in research and clinical trials and yet at great risk for adverse events. Therefore, understanding advanced aged associated constructs in older adults can be critical to improving the management of older adults with IBD., Recent Findings: In this review, we present recent studies on frailty in IBD. We identify 4 major themes in the literature: studies that describe frailty in patients with IBD, studies that report on consequences of frailty, studies of frailty as a risk stratification modality, and studies of frailty as an exposure and outcome. In reviewing the literature, we discuss the heterogeneity that exists and outline future directions to ensure appropriate applications for frailty in the field of IBD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patient concerns and preferences are important in the management of inflammatory bowel disease (IBD: Crohn's disease [CD], ulcerative colitis). In the absence of contemporary data, we aimed to determine patient concerns and preferences and establish if there are demographic or disease-related differences., Methods: We surveyed patients with IBD at Massachusetts General Hospital between July and September 2023. The Rating Form of Inflammatory Bowel Disease Patient Concerns (RFIPC) and a set of supplemental questions rated on a visual analog scale (0-100 mm) were administered to patients and compared by age, disease type, sex, and surgery status. Additionally, a survey administered to treating providers gathered insight into the difference between patient and provider perceptions of concerns., Results: A total of 350 patients and 30 providers completed the survey. The mean age was 47 years; 50% were female, 49% had CD, and 80% were on advanced IBD therapy. Effects of medication (median = 54), energy level (median = 53), and having an ostomy bag (median = 52) were rated highest by patients. Older patients rated most disease complication and treatment-related concerns similar to younger adults; those aged 35-59 years had the greatest level of concern for most questions. Sex, disease activity, and prior surgical history also impacted patients' concerns. Providers perceived patients' worries as higher than those rated by patients themselves., Conclusions: A shared decision-making model targeting the achievement of disease remission and addressing concerns rated highly by patients is important to meet the goal of care for patients with IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Gut bacteria are implicated in inflammatory bowel disease (IBD), but the strains driving these associations are unknown. Large-scale studies of microbiome evolution could reveal the imprint of disease on gut bacteria, thus pinpointing the strains and genes that may underlie inflammation. Here, we use stool metagenomes of thousands of IBD patients and healthy controls to reconstruct 140,000 strain genotypes, revealing hundreds of lineages enriched in IBD. We demonstrate that these strains are ancient, taxonomically diverse, and ubiquitous in humans. Moreover, disease-associated strains outcompete their healthy counterparts during inflammation, implying long-term adaptation to disease. Strain genetic differences map onto known axes of inflammation, including oxidative stress, nutrient biosynthesis, and immune evasion. Lastly, the loss of health-associated strains of Eggerthella lenta was predictive of fecal calprotectin, a biomarker of disease severity. Our work identifies reservoirs of strain diversity that may impact inflammatory disease and can be extended to other microbiome-associated diseases., Competing Interests: Declaration of interests K.E.B. is a consultant for OM1 and Bristol Myers Squibb. B.K. has served on the advisory board for Pfizer, Inc. R.J.X. is a co-founder of Celsius Therapeutics and Jnana Therapeutics, a member of the scientific advisory board of Nestle, a consultant to Novartis, and a member of the board of directors at Moonlake Immunotherapeutics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite the growing proportion of older adults with inflammatory bowel disease (IBD), their lived experience is not well understood. IBD literature is generally focused on younger adults, and few studies are qualitative. Older adults may report well-being differently than younger adults, so it is important that we learn about their goals and priorities with a chronic disease., Objective: The study sought to understand the lived experience of older adults with IBD and explore their perceptions and priorities., Methods: We conducted in-depth interviews with patients ≥60 years of age with IBD to evaluate the impact and perception of IBD in the context their overall health and life. We used a hybrid inductive-deductive thematic analysis of our transcripts to identify underlying patterns., Results: We achieved thematic saturation after 22 interviews. We produced 4 major themes: (1) having IBD at an older age, (2) financial ramifications of IBD at an older age, (3) expectations for a meaningful life, and (4) unmet needs. Prominent subthemes included (1) ageism, loss of autonomy, and barriers to healthcare; (2) retirement and insurance issues; (3) redefining quality of life and gratitude; and (4) social isolation and navigating daily life with IBD., Conclusions: Having IBD later in life presents unique challenges. Physicians treating older patients should consider age-sensitive communication, susceptibility to social isolation, and practices for healthy aging in the context of IBD. Patient priorities for further investigation include more representation in the media and educational material tailored for older adults with IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Older adults with ulcerative colitis [UC] have greater morbidity than younger adults. The goal of this study was to investigate differences in the management and outcomes of older and younger patients hospitalised with severe UC., Methods: We conducted a retrospective cohort study of patients hospitalised for acute severe ulcerative colitis requiring intravenous steroids. We compared outcomes of adults aged ≥65 years with outcomes of younger patients. Primary study outcomes included frequency and timing of medical and surgical rescue therapy during the hospitalisation, postoperative complications, frailty, and mortality outcomes up to 1 year following the hospitalisation., Results: Our cohort included 63 older adults [≥65 years] and 137 younger adults [14-64 years]. Despite similar disease severity at hospitalisation, older adults were half as likely to receive medical rescue therapy (odds ratio 0.45, 95% confidence interval [CI] 0.22-0.91). This difference was more striking among the frailest older adults. Older patients were similarly likely to undergo surgery but were more likely to undergo urgent or emergent procedures [50%] compared with younger patients [13%] [p <0.004]. The fraction of older adults at high risk for frailty increased from 33% pre-hospitalisation to 42% post-hospitalisation. Nearly one-third [27.8%] of older adults died within 1 year of hospitalisation, with half the deaths among older adults being attributable to UC or complications of UC., Conclusions: In comparison with younger patients, older adults had lower frequency use of medical rescue therapy, higher rates of emergency surgery, and increased mortality within 1 year. Further research is needed to optimise care pathways in this population., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Despite the growing prevalence of older adults with inflammatory bowel diseases (IBD), polypharmacy, an important geriatric construct, is poorly understood. We described polypharmacy and its implications in older adults with IBD., Methods: In a cross sectional study of adults ≥ 60 years with IBD, we obtained medication lists from the medical record and patients. We assessed medications by the Beer's criteria, anti-cholinergic burden and drug-drug interactions. We constructed multi-variate logistic regression models to assess association between polypharmacy with low quality-of-life, controlling for age, sex, IBD-type, number of comorbidities and depression., Results: In 100 adults ≥ 60 years with IBD, with a median age of 68 years, 56% met criteria for remission by a validated disease activity index. Polypharmacy, defined as ≥ 5 concomitant medications, was noted in 86% of the cohort and 45% had severe polypharmacy, defined as ≥ 10 concomitant medications. In this cohort, 48% were on ≥ 1 medication that met Beer's criteria for potentially inappropriate in older adults and 24% had a cumulative anti-cholinergic drug burden score of ≥ 3, the threshold for serious adverse events attributed to anti-cholinergic burden. Serious drug-drug interactions were found in 26% with 7% involving an IBD medication. Controlling for potential confounders, polypharmacy, defined both numerically (OR 22.79, p < 0.01) and by medication appropriateness (OR 1.95, p < 0.01), was significantly associated with low quality of life., Conclusion: Polypharmacy is prevalent in older adults with IBD and independently associated with low quality of life. Describing polypharmacy can guide de-prescription strategies tailored to GI clinic for older adults with IBD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Antibiotics are a cornerstone in management of intra-abdominal abscesses in Crohn's disease (CD). Yet, the optimal route of antibiotic administration is poorly studied. We aimed to compare surgical and nonsurgical readmission outcomes for patients hospitalized for intra-abdominal abscesses from CD discharged on oral (PO) or intravenous (IV) antibiotics., Methods: Data for patients with CD hospitalized for an intra-abdominal abscess were obtained from 3 institutions from January 2010 to December 2020. Baseline patient characteristics were obtained. Primary outcomes of interest included need for surgery and hospital readmission within 1 year from hospital discharge. We used multivariable logistic regression models and Cox regression analysis to adjust for abscess size, history of prior surgery, history of penetrating disease, and age., Results: We identified 99 patients discharged on antibiotics (PO = 74, IV = 25). Readmissions related to CD at 12 months were less likely in the IV group (40% vs 77% PO, P = .01), with the IV group demonstrating a decreased risk for nonsurgical readmissions over time (hazard ratio, 0.376; 95% confidence interval, 0.176-0.802). Requirement for surgery was similar between the groups. There were no differences in time to surgery between groups., Conclusions: In this retrospective, multicenter cohort of CD patients with intra-abdominal abscess, surgical outcomes were similar between patients receiving PO vs IV antibiotics at discharge. Patients treated with IV antibiotics demonstrated a decreased risk for nonsurgical readmission. Further prospective trials are needed to better delineate optimal route of antibiotic administration in patients with penetrating CD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Inflammatory bowel diseases (IBD) affect >3 million Americans and are associated with tremendous economic burden. Direct patient-level financial impacts, financial distress, and financial toxicity are less well understood. We aimed to summarize the literature on patient-level financial burden, distress, and toxicity associated with IBD in the United States., Methods: We conducted a literature search of US studies from 2002 to 2022 focused on direct/indirect costs, financial distress, and toxicity for patients with IBD. We abstracted study objectives, design, population characteristics, setting, and results., Results: Of 2,586 abstracts screened, 18 articles were included. The studies comprised 638,664 patients with IBD from ages 9 to 93 years. Estimates for direct annual costs incurred by patients ranged from $7,824 to $41,829. Outpatient costs ranged from 19% to 45% of direct costs, inpatient costs ranged from 27% to 36%, and pharmacy costs ranged from 7% to 51% of costs. Crohn's disease was associated with higher costs than ulcerative colitis. Estimates for indirect costs varied widely; presenteeism accounted for most indirect costs. Severe and active disease was associated with greater direct and indirect costs. Financial distress was highly prevalent; associated factors included lower education level, lower household income, public insurance, comorbid illnesses, severity of IBD, and food insecurity. Higher degrees of financial distress were associated with greater delays in medical care, cost-related medication nonadherence, and lower health-related quality of life., Discussion: Financial distress is prevalent among patients with IBD; financial toxicity is not well characterized. Definitions and measures varied widely. Better quantification of patient-level costs and associated impacts is needed to determine avenues for intervention., (Copyright © 2023 by The American College of Gastroenterology.)

Background & Aims: Prior studies have suggested that proton pump inhibitor (PPI) use is associated with increased risk of dementia; however, these have been limited by incomplete assessment of medication use and failure to account for confounders. Furthermore, prior studies have relied on claims-based diagnoses for dementia, which can lead to misclassification. We investigated the associations of PPI and histamine-2 receptor antagonist (H2RA) use with dementia and cognitive decline., Methods: We conducted a post hoc analysis of ASPirin in Reducing Events in the Elderly (ASPREE), a randomized trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities. Baseline and recent PPI and H2RA use were determined according to review of medications during annual in-person study visits. Incident dementia was defined according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, criteria. Secondary endpoints include cognitive impairment, no dementia (CIND) and changes in cognition. Associations of medication use with dementia and CIND outcomes were examined using Cox proportional hazards models. Changes in cognitive test scores were examined using linear mixed-effects models., Results: Baseline PPI use vs nonuse was not associated with incident dementia (multivariable hazard ratio, 0.88; 95% confidence interval, 0.72-1.08), CIND (multivariable hazard ratio, 1.00; 95% confidence interval, 0.92-1.09), or with changes in overall cognitive test scores over time (multivariable B, -0.002; standard error, 0.01; P = .85). Similarly, no associations were observed between H2RA use and all cognitive endpoints., Conclusions: In adults ≥65 years of age, PPI and H2RA use were not associated with incident dementia, CIND, or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs)., Methods: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality., Results: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48)., Conclusions: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic inflammatory conditions of the pouch are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC)., Aims: We aimed to investigate the relationship between acute pouchitis within 180 days of the final stage of IPAA surgery (very early pouchitis) and the future development of chronic antibiotic dependent pouchitis (CADP) and Crohn's-like disease of the pouch (CLDP)., Methods: We performed a retrospective cohort study, evaluating patients who underwent proctocolectomy with IPAA between January 1, 2004 and December 31, 2016. Multivariable logistic regression was used to evaluate the relationship between very early pouchitis and the development of CADP and CLDP., Results: Among 626 patients undergoing IPAA for UC, 137 (22%) developed very early pouchitis, 75 (12%) developed CADP, and 59 (9%) developed CLDP in a median follow-up of 5.18 years (interquartile range 0.94-10.8 years). Very early pouchitis was associated with a significant increase in the odds of developing CADP (adjusted odds ratio [aOR3.65, 95% CI 2.19-6.10) as was primary sclerosing cholangitis (aOR 3.97, 95% CI 1.44-11.0). Very early pouchitis was associated with increased odds for developing CLDP (aOR 2.77, 95% CI 1.54-4.98) along with a family history of inflammatory bowel disease (aOR 2.10, 95% CI 1.11-3.96)., Conclusion: In this cohort, very early pouchitis was associated with an increased risk of developing CADP and CLDP. These findings highlight very early pouchitis as a unique risk factor for chronic inflammatory conditions of the pouch and the need for future studies evaluating potential strategies for secondary prophylaxis strategies in this population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: This review summarizes the most recent literature on older adults with inflammatory bowel diseases (IBD). Additionally, we review geriatric syndromes that may be pertinent to the management of older adults with IBD., Recent Findings: Traditionally chronological age has been used to risk stratify older adults with IBD, however physiologic status, including comorbidities, frailty, and sarcopenia, are more closely associated with clinical outcomes for older adults. Delaying care for and undertreating older adults with IBD based upon advanced chronologic age alone is associated with worse outcomes, including increased mortality. Treatment decisions should be made considering physiologic status, with an understanding of the differential risks associated with both ongoing disease and treatment. As such, there is an increasing recognition of the impact geriatric syndromes have on older adults with IBD, which need to be further explored., Summary: Older adults with IBD are less likely to receive advanced therapies and timely surgery. They are also more likely to have adverse outcomes despite having similar disease courses to younger adults with IBD. Focusing on biological age as opposed to chronological age can shift this trajectory and improve quality of care for this growing population of patients with IBD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: There are limited data on comparative risk of infections with various biologic agents in older adults with inflammatory bowel diseases (IBDs). We aimed to assess the comparative safety of biologic agents in older IBD patients with varying comorbidity burden., Methods: We used data from a large, national commercial insurance plan in the United States to identify patients 60 years and older with IBD who newly initiated tumor necrosis factor-α antagonists (anti-TNF), vedolizumab, or ustekinumab. Comorbidity was defined using the Charlson Comorbidity Index (CCI). Our primary outcome was infection-related hospitalizations. Cox proportional hazards models were fitted in propensity score-weighted cohorts to compare the risk of infections between the different therapeutic classes., Results: The anti-TNF, vedolizumab, and ustekinumab cohorts included 2,369, 972, and 352 patients, respectively, with a mean age of 67 years. The overall rate of infection-related hospitalizations was similar to that of anti-TNF agents for patients initiating vedolizumab (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.84-1.04) and ustekinumab (0.92, 95% CI 0.74-1.16). Among patients with a CCI of >1, both ustekinumab (HR: 0.66, 95% CI: 0.46-0.91, p-interaction <0.01) and vedolizumab (HR: 0.78, 95% CI: 0.65-0.94, p-interaction: 0.02) were associated with a significantly lower rate of infection-related hospitalizations compared with anti-TNFs. No difference was found among patients with a CCI of ≤1., Discussion: Among adults 60 years and older with IBD initiating biologic therapy, both vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations than anti-TNF therapy for those with high comorbidity burden., (Copyright © 2022 by The American College of Gastroenterology.)

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis., Aims: We aimed to investigate whether a shorter period between pouch creation and restoration of fecal flow through an IPAA was associated with an increased risk of development of pouchitis within the first 2 years after IPAA., Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. We used Kaplan-Meier testing and Cox Proportional Hazards Modeling to evaluate the relationship between the time between restoration of fecal continuity and time to subsequent development of pouchitis, adjusting for other clinical and demographic factors., Results: We identified 624 patients who underwent proctocolectomy with IPAA for UC, of whom 246 (39%) developed pouchitis within the first 2 years after IPAA. There was no difference when comparing the median time to restoration of continuity among those patients who developed pouchitis and those who did not (49 days vs. 49 days, p = 0.85) or in multivariable analysis. Primary sclerosing cholangitis (Hazard Ratio [HR] 2.14, 95% CI 1.12-4.08), family history of inflammatory bowel disease (HR 1.49, 95% CI 1.08-2.06), and delayed pouch creation (HR 0.75, 95% CI 0.57-1.00) were significantly associated with time to development of pouchitis., Conclusion: Although a staged approach to IPAA may have benefits in the surgical management of UC, the timing interval between pouch creation and restoration of continuity did not impact the subsequent development of early pouchitis in this cohort., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: We aimed to compare the risk of frailty in older adults with incident inflammatory bowel disease (IBD) and matched non-IBD comparators and assess the association between frailty and future hospitalizations and mortality., Methods: In a cohort of patients with incident IBD ≥60 years of age from 2007 to 2016 in Sweden identified using nationwide registers, we defined frailty using Hospital Frailty Risk Score. We compared prevalence of frailty in patients with IBD with age, sex, place of residency- and calendar year-matched population comparators. In the IBD cohort, we used Cox proportional hazards modeling to examine the associations between frailty risk and hospitalizations or mortality., Results: We identified 10,590 patients with IBD, 52% female with a mean age of 71 years of age, matched to 103,398 population-based comparators. Among patients with IBD, 39% had no risk for frailty, 49% had low risk for frailty, and 12% had higher risk for frailty. Mean Hospital Frailty Risk Score was 1.9 in IBD and 0.9 in matched comparators (P &lt; .01). Older adults with IBD at higher risk for frailty had a 20% greater risk for mortality at 3 years compared with those who were not frail. Compared with nonfrail older patients with IBD, patients at higher risk for frailty had increased mortality (hazard ratio [HR], 3.22, 95% confidence interval [CI], 2.86-3.61), all-cause hospitalization (HR, 2.42; 95% CI, 2.24-2.61), and IBD-related hospitalization (HR, 1.50; 95% CI, 1.35-1.66). These associations were not attenuated after adjusting for comorbidities., Conclusions: Frailty is more prevalent in older adults with IBD than in matched comparators. Among older patients with IBD, frailty is associated with increased risk for hospitalizations and mortality., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose of the Review: Sarcopenia is the loss of muscle quantity and strength. It is highly prevalent in patients with inflammatory bowel disease (IBD) and is associated with periods of ongoing inflammation. This review will summarize the prior work in the field and highlight areas for future research., Recent Findings: The presence of sarcopenia has been associated with adverse outcomes in different populations. Most recently, sarcopenia has been associated with adverse postoperative outcomes and an increased likelihood of surgery in IBD. Despite this, significant heterogeneity among these studies limits the ability to draw definitive conclusions., Summary: The importance of sarcopenia in inflammatory bowel disease (IBD) is only beginning to be recognized. Future studies assessing it utility both as a risk stratification tool and a modifiable factor in IBD are needed., Competing Interests: Conflict of Interest Statement All the authors have no relevant conflicts of interest to declare ASF reports the following disclosures: consulting for GuidePoint, Janssen, LEK, M3 and Schlesinger BK reports the following disclosures: advisory board for Pfizer, Inc TK and SC have no disclosures

Objectives: Polypharmacy and frailty are two common geriatric conditions. In community-dwelling healthy older adults, we examined whether polypharmacy is associated with frailty and affects disability-free survival (DFS), assessed as a composite of death, dementia, or persistent physical disability., Methods: We included 19,114 participants (median age 74.0 years, IQR: 6.1 years) from ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. Frailty was assessed by a modified Fried phenotype and a deficit accumulation Frailty Index (FI). Polypharmacy was defined as concomitant use of five or more prescription medications. Multinomial logistic regression was used to examine the cross-sectional association between polypharmacy and frailty at base line, and Cox regression to determine the effect of polypharmacy and frailty on DFS over five years., Results: Individuals with polypharmacy (vs. <5 medications) were 55% more likely to be pre-frail (Relative Risk Ratio or RRR: 1.55; 95%Confidence Interval or CI:1.44, 1.68) and three times more likely to be frail (RRR: 3.34; 95%CI:2.64, 4.22) according to Fried phenotype. Frailty alone was associated with double risk of the composite outcome (Hazard ratio or HR: 2.16; 95%CI: 1.56, 2.99), but frail individuals using polypharmacy had a four-fold risk (HR: 4.24; 95%CI: 3.28, 5.47). Effect sizes were larger when frailty was assessed using the FI., Conclusion: Polypharmacy was significantly associated with pre-frailty and frailty at baseline. Polypharmacy-exposed frailty increased the risk of reducing disability-free survival among older adults. Addressing polypharmacy in older people could ameliorate the impact of frailty on individuals' functional status, cognition and survival., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background & Aims: Although colonoscopies for dysplasia surveillance are standard of care in patients with long-standing ulcerative colitis (UC), there is a paucity of data on the yield of surveillance colonoscopies in those older than 75 years of age., Methods: We conducted a multicenter retrospective cohort study including patients with UC who underwent ≥1 colonoscopy at age ≥75 years. The primary outcome was diagnosis of dysplasia (visible or random) and colorectal cancer. Multivariable regression adjusted for relevant confounders examined the predictors of polypoid or non-polypoid dysplasia or colorectal cancer., Results: The primary cohort included 211 patients with UC who underwent 635 colonoscopies after age ≥75 years. A total of 83 patients (39.3%) patients had dysplasia or cancer detected. Among colonoscopies, 123 (19.4%) identified visible dysplasia, 23 (3.6%) had random dysplasia (1 high-grade dysplasia found in each group, respectively), and 5 (0.8%) had colon cancer. In multivariable analysis, prior adenoma or colon cancer below age 75 tears (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07-3.96), flat dysplasia before 75 years (OR, 2.78; 95% CI, 1.05-7.44), and older age (80-84 years (OR, 2.29; 95% CI, 1.20-4.38), ≥85 years (OR, 3.54; 95% CI, 1.27-9.82) were associated with detection of dysplasia or cancer. Only 1 patient was noted to have a procedure-related complication., Conclusions: Patients with long-standing UC without prior dysplasia may have a low yield on continued endoscopic surveillance at age ≥75 years. A targeted approach to surveillance may be appropriate in older individuals with UC., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Despite the increased numbers of older adults with inflammatory bowel diseases (IBDs), there are few studies regarding the safety and effectiveness of IBD treatments in older adults. The aim of this study was to compare the safety and effectiveness of anti-tumor necrosis factor (TNF)-α agents and vedolizumab in older adults with IBD., Methods: We conducted a retrospective cohort study using an active comparator, new-user design for adults age 65 years and older with IBD initiating anti-TNF-α agents and vedolizumab in the Medicare claims database from 2014 to 2017. The primary safety outcome was infection-related hospitalization (excluding intra-abdominal and perianal abscesses). Co-primary outcomes to estimate effectiveness were IBD-related hospitalization, IBD-related surgery, and new corticosteroid use 60 days or more after biologic initiation. We performed propensity score weighting to control for confounding and estimated adjusted hazard ratios and 95% confidence intervals using standardized morbidity ratio-weighted variables., Results: We identified 1152 anti-TNF-α new users and 480 vedolizumab new users. The median age was 71 years in both cohorts and 11% were age 80 years or older. Crohn's disease patients comprised 54% of the anti-TNF-α cohort and 57% of the vedolizumab cohort. There was no significant difference in demographics, health care utilization, or frailty in both cohorts. More than half of both cohorts had a Charlson comorbidity index of 2 or higher. Vedolizumab users had a decreased risk of infection-related hospitalization (adjusted hazard ratio, 0.47; 95% confidence interval, 0.25-0.86). There was no significant difference in the outcomes approximating effectiveness., Conclusions: Older IBD patients treated with vedolizumab had a lower risk of infection-related hospitalization compared with those initiating anti-TNFs. We observed no difference in effectiveness defined by hospitalizations, surgery, or new corticosteroid use., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The gut microbiome is increasingly recognized to play a role in cognition and dementia. Antibiotic use impacts the gut microbiome and has been linked with chronic disease. Despite these data, there is no evidence supporting an association between long-term antibiotic use in adults and cognitive function. We conducted a prospective population-based cohort study among 14,542 participants in the Nurses' Health Study II who completed a self-administered computerized neuropsychological test battery between 2014-2018. Multivariate linear regression models were used to assess if chronic antibiotic use in midlife was associated with cognitive impairment assessed later in life. Women who reported at least 2 months of antibiotic exposure in midlife (mean age 54.7, SD 4.6) had lower mean cognitive scores seven years later, after adjustment for age and educational attainment of the spouse and parent, with a mean difference of -0.11 standard units for the global composite score (Ptrend <0.0001), -0.13 for a composite score of psychomotor speed and attention (Ptrend <0.0001), and -0.10 for a composite score of learning and working memory (Ptrend <0.0001) compared with non-antibiotic users. These differences were not materially changed after multivariate adjustment for additional risk factors, including comorbid conditions. As a benchmark, the mean difference in score associated with each additional year of age was (-0.03) for global cognition, (-0.04) for psychomotor speed and attention, and (-0.03) for learning and working memory; thus the relation of antibiotic use to cognition was roughly equivalent to that found for three to four years of aging. Long-term antibiotic use in midlife is associated with small decreases in cognition assessed seven years later. These data underscore the importance of antibiotic stewardship, especially among aging populations., Competing Interests: I have rea the journal’s policy and the authors of this manuscript have the following competing interests: Dr Chan served as a consultant for Bayer Pharma AG, Pfizer Inc., and Boehringer Ingelheim. Dr. Kochar served on an advisory board to Pfizer. This study was not funded by Bayer Pharma AG, Boehringer Ingelheim, or Pfizer Inc. No other conflict of interest exists. The other authors declare that they have no conflicts of interest.

The number of Americans 65 years or older in 2060 will be more than double what it was in 2014. Approximately 40% of patients seen in gastroenterology (GI) and hepatology practices in the United States are 60 years or older. Adapting care delivery models, curating data on shifting risk-benefit decisions with geriatric syndromes, understanding appropriate assessments, and focusing on tailored implementation strategies are challenges that are actively confronting us as we provide care for a burgeoning population of older adults. Limited availability of geriatric specialists results in an onus of specialists caring for older adults, such as gastroenterologists, to innovate and develop tailored, comprehensive, and evidence-based care for adults in later life stages. In this article, we present the 5M framework from geriatrics to achieve age-friendly healthcare. The 5Ms are medications, mind, mobility, multicomplexity, and what matters most. We apply the 5M framework to 2 chronic conditions commonly encountered in clinical GI practice: inflammatory bowel diseases and cirrhosis. We highlight knowledge gaps and outline future directions to expand evidence-based care and advance the creation of age-friendly GI care., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA., Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis., Results: Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02-7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11-2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45-1.08)., Discussion/conclusion: Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC., Competing Interests: Edward L. Barnes has served as a consultant for AbbVie, Gilead, Pfizer, Takeda, and Target RWE. Bharati Kochar has served as a consultant for Pfizer. Michael D. Kappelman has served as a consultant for Abbvie, Takeda, Janssen, and Eli Lilly and has received research support from Abbvie and Janssen. Millie D. Long has served as a consultant for AbbVie, UCB, Takeda, Janssen, Pfizer, Salix, Valeant, and Target Pharmasolutions and has received research support from Pfizer and Takeda. Hans H. Herfarth has served as a consultant for Alivio, AMAG, Finch, Gilead, Lycera, Merck, Otsuka, Pfizer, PureTech, and Seres and research support from Pfizer and Artizan Biosciences. Joshua Hudson, Scott Esckilsen, Mark Koruda, and Robert S. Sandler have no relevant disclosures or conflicts of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Inflammatory bowel diseases (IBD), consisting of Crohn's disease and ulcerative colitis, are chronic remitting, relapsing inflammatory conditions of the gastrointestinal tract. While traditionally a disease of younger ages, the number of older adults with IBD is rising rapidly. Patients with IBD often experience geriatric syndromes at earlier ages. Older adults with IBD have poorer disease and treatment-related outcomes compared with younger adults with IBD. Applying the principles of geriatrics to understanding a chronic disease in older adults may improve health span. Better tools are needed to stratify IBD patients who are at high risk for adverse events. Frailty is a geriatric construct that may approximate biologic age. Frailty is a complex, multi-dimensional syndrome that leads to increased vulnerability to stress and decline of reserve across multiple physiologic systems. In this review, we present the leading conceptual models of frailty and discuss the applications of frailty in immune-mediated diseases. We also review chronic conditions where frailty has been applied successfully as a tool for risk stratification. Finally, we discuss in the detail the growing body of literature highlighting the relationship between frailty and IBD, the epidemiology of frailty in IBD, and ramifications of frailty in IBD., Competing Interests: Conflict of interest statement: BK: Advisory Board for Pfizer ARO: none ANA: scientific advisory board member for Abbvie, Gilead and Kyn Therapeutics, research funding from Pfizer CSR: none, (© The Author(s), 2021.)

Background: Home infusions (HIs) for biologic medications are an option for inflammatory bowel disease (IBD) patients in the United States. We aimed to describe the population receiving HIs and report patient experience with HIs., Methods: We conducted a retrospective cohort study in the Quintiles-IMSLegacy PharMetrics Adjudicated Claims Database from 2010 to 2016 to describe the population receiving infliximab (IFX) and vedolizumab (VDZ) HIs and determine predictors for an urgent/emergent visit post-HIs. We then administered a cross-sectional survey to IBD Partners Internet-based cohort participants to assess knowledge and experience with infusions., Results: We identified claims for 11 892 conventional IFX patients, 1573 home IFX patients, 438 conventional VDZ patients, and 138 home VDZ patients. There were no differences in demographics or median charges with IFX home and conventional infusions. Home VDZ infusions had a greater median charge than conventional VDZ infusion. Less than 4% of patients had an urgent/emergent visit post-HIs. Charlson comorbidity index > 0 (odds ratio [OR]: 1.95; 95% confidence interval [CI], 1.01-3.77) and Medicaid (OR: 3.01; 95% CI, 1.53-5.94) conferred significantly higher odds of urgent/emergent visit post-HIs. In IBD Partners, 644 IBD patients responded; 56 received HIs. The majority chose HIs to save time and preferred HIs to conventional infusions. Only 2 patients reported an urgent/emergent visit for HI-related problems., Conclusions: HI appears to be safe in IBD patients receiving IFX and VDZ. However, patients with fewer resources and more comorbidities are at increased risk for an urgent/emergent visit post-HIs. The overall patient experience with HI is positive. Expansion of HIs may result in decreased therapy-related logistic burden for carefully selected patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: The development of chromoendoscopy (CE) and high definition endoscopy (HDE) has improved detection of subtle colonic dysplasia in patients with inflammatory bowel diseases (IBDs). The role of random biopsies for dysplasia surveillance is unclear., Methods: We reviewed patients with IBD who underwent a CE or HDE colonoscopy and had colonic dysplasia detected. Detection of dysplasia was classified as either visible or random and graded as low grade dysplasia (LGD), high grade dysplasia (HGD), or indefinite for dysplasia. Multivariable regression adjusted for relevant confounders examined the predictors of dysplasia detectable on random biopsies alone., Results: The study included 300 patients (203 ulcerative colitis, 97 Crohn's disease with colonic involvement) contributing 442 colonoscopies; the mean disease duration was 24.5 years; 7.2% had primary sclerosing cholangitis (PSC). Three hundred sixty-two colonoscopies (82%) had only visible dysplasia, 52 (12%) had only random dysplasia, and 28 (6%) had both visible and random dysplasia. Longer disease duration (odds ratio, 1.04; 95% CI, 1.01-1.07), active inflammation (odds ratio, 2.89; 95% CI, 1.26-6.67), and concomitant PSC (odds ratio, 3.66; 95% CI, 1.21-11.08) were associated with detecting dysplasia on random biopsies compared with visible lesions. Patients with random dysplasia (21%) or both random and visible dysplasia (21%) were more likely to undergo surgical resection compared with those with only visible dysplasia (5%; P < 0.001) and have subsequent development of colorectal cancer (15%, 7%, 1%, respectively; P < 0.0001)., Conclusion: Nearly one fifth of dysplasia detected in patients with IBD was found on random biopsies. Patients with high risk characteristics may benefit from continuing the practice of random biopsies during surveillance examinations., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery. 1 Although up to 80% of patients can develop pouchitis symptoms, 2 , 3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease 4-6 ; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The epidemiology of meningitis is unknown in inflammatory bowel disease (IBD) patients., Goals: We aimed to determine the incidence of and risk factors for meningitis in IBD patients., Study: We conducted a retrospective cohort and nested case-control study in the Quintiles IMS Legacy PharMetrics Adjudicated Claims Database from January 2001 to June 2016. We matched IBD patients to those without IBD on age, sex, enrollment, and region. Meningitis was defined as one code for meningitis associated with an emergency department visit or hospitalization. Meningitis risk was calculated with incidence rate ratios. In a nested case-control study of IBD patients, predictors for meningitis were determined with multivariable conditional logistic regression models., Results: We identified 50,029 patients with Crohn's disease (CD) and 59,830 patients with ulcerative colitis (UC) matched to 296,801 non-IBD comparators. There were 85 CD patients, 77 UC patients, and 235 comparators with meningitis. CD patients had 2.17 times the rate of meningitis and UC patients had 1.63 times the rate of meningitis as non-IBD comparators. After adjusting for relevant covariates among those with IBD, treatment with mesalamine was associated with a significantly lower odds of a meningitis claim (odds ratio: 0.40, 95% confidence interval: 0.26-0.62). Having at least one comorbidity was associated with a significantly higher odds of a meningitis claim (odds ratio: 2.21, 95% confidence interval: 1.76-2.77)., Conclusions: Although the overall rate of meningitis is low, IBD patients are at an increased risk compared with non-IBD comparators. Comorbidities are a risk factor for meningitis in IBD patients. Pneumococcal and meningococcal vaccinations should be discussed., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Vaping, or e-cigarettes, heat nicotine and other chemicals to create a vapor that is inhaled. The practice has gained rapid popularity with 41 million people globally reporting regular or occasional use. Although tobacco smoking is well-known to increase esophageal acid exposure by augmenting the number of reflux events, the effects of vaping on the gastrointestinal tract have not yet been elucidated. Our objective is to report a case of severe esophagitis associated with vaping, which is the first in the literature to our knowledge., Case Presentation: A 25-year-old male with a history of well-controlled gastro-esophageal reflux disease presented to the emergency room for evaluation of one week of severe odynophagia. He had been treated with a proton-pump inhibitor for several years with good effect. Approximately two months prior to presentation, he started vaping tetrahydrocannabinol and nicotine with recent heavy daily use. He denied any alcohol or non-steroidal anti-inflammatory drug use. We performed esophagogastroduodenoscopy that revealed Los Angeles Grade C esophagitis (involving ≥ 1 mucosal breaks continuous between tops of ≥ 2 mucosal folds, < 75% circumferential). Histopathological analysis of esophageal biopsies demonstrated granulation tissue with acute and chronic inflammation. Periodic acid-Schiff-diastase staining was negative and immunohistochemical stains for herpes simplex virus and cytomegalovirus were negative. There was no evidence of eosinophilic esophagitis. We treated him with intravenous PPI and analgesics until he was able to tolerate oral intake. He was counseled extensively on vaping cessation and reported complete resolution of symptoms after 2 months., Conclusion: This patient's presentation illustrates a serious gastrointestinal consequence of vaping, the long-term consequences of which warrant additional studies. Like smoking, the mechanism of injury in vaping may be, at least in part, due to the effects of nicotine. As prevalence of vaping continues to rise, clinicians should be aware of this complication and carefully solicit a patient's vaping history as a simple denial of "smoking" can be misleading.

We report utilization patterns and characteristics of patients treated with biologic anti-inflammatory agents in a large commercially insured patient population in the United States. We identified adult (age ≥18 years) patients receiving biologic anti-inflammatory agents between 1 January 2012 and 31 March 2019 across the five Research Partners in the Biologic and Biosimilars Collective Intelligence Consortium's Distributed Research Network. We examined the number of incident use episodes for each biologic, as well as patient demographic and clinical characteristics. Curated data and analytic tools from the Food and Drug Administration's Sentinel System were used to perform the analyses. We identified 90,360 incident episodes of tumor necrosis factor-alpha inhibitors (TNFi) and 70,506 incident episodes of non-TNFi medications. Adalimumab was the most common TNFi drug (47% of all TNFi episodes) and showed a steady increase in utilization during the study period compared to other TNFi agents. Rituximab was the most commonly initiated non-TNFi medication (44% of non-TNFi episodes). Other non-TNFi agents, namely, ustekinumab, vedolizumab, and secukinumab, demonstrated notable increases in utilization over time. Biosimilar use was limited; we observed 653 incident episodes for infliximab-dyyb and 39 incident episodes for infliximab-abda. As more biologics enter the market, greater variation in the use of biologics with similar indications and between biologic originators and biosimilars is anticipated. Because information on efficacy and safety at the time of drug approval is limited, post-marketing surveillance and research is needed to monitor medication safety and evaluate effectiveness between biologic drugs using real-world data., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Background: The effect of immunosuppressive treatment for immune-mediated diseases on risk of the novel coronavirus disease 2019 (COVID-19) has not been established. We aimed to define the effect of targeted biologic and immunomodulator therapy on risk of COVID-19 in a multi-institutional cohort of patients with inflammatory bowel disease (IBD)., Methods: We identified patients 18 years and older who received care for IBD at Partners Healthcare between January 2019 and April 2020. The primary outcome was development of COVID-19 defined as a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. Multivariable regression models were used to examine the effect of immunosuppression on risk of COVID-19 and its outcomes., Results: In a cohort of 5302 IBD patients, 39 (0.7%) developed COVID-19. There was no difference in age, sex, or race between IBD patients with and without COVID-19. The rate of COVID-19 was similar between patients treated with immunosuppression (0.8%) compared with those who were not (0.64%; P = 0.55). After adjusting for age, sex, race, and comorbidities, use of immunosuppressive therapy was not associated with an increased risk of COVID-19 (odds ratio, 1.73; 95% confidence interval, 0.82-3.63). The presence of obesity was associated with a higher risk of COVID-19 (odds ratio, 8.29; 95% confidence interval, 3.72-18.47). There were 7 hospitalizations, 3 intensive care unit stays, and 1 death. Older age and obesity but not immunosuppressive treatment were associated with severe COVID-19 infection., Conclusions: The use of systemic immunosuppression was not associated with an increased risk of COVID-19 in a multi-institutional cohort of patients with IBD., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)