The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon.

Crohn's disease (CD) is a chronic gastrointestinal disease that is increasing in prevalence worldwide. CD is multifactorial, involving the complex interplay of genetic, immune, and environmental factors, necessitating a system-level understanding of its etiology. To characterize cell-type-specific transcriptional heterogeneity in active CD, we profiled 720,633 cells from the terminal ileum and colon of 71 donors with varying inflammation status. Our integrated datasets revealed organ- and compartment-specific responses to acute and chronic inflammation; most immune changes were in cell composition, whereas transcriptional changes dominated among epithelial and stromal cells. These changes correlated with endoscopic inflammation, but small and large intestines exhibited distinct responses, which were particularly apparent when focusing on IBD risk genes. Finally, we mapped markers of disease-associated myofibroblast activation and identified CHMP1A, TBX3, and RNF168 as regulators of fibrotic complications. Altogether, our results provide a roadmap for understanding cell-type- and organ-specific differences in CD and potential directions for therapeutic development.

Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study.

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.

Prevalence and Appropriateness of Polypharmacy in Older Adults with Inflammatory Bowel Diseases.

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.

A Narrative Review of Financial Burden, Distress, and Toxicity of Inflammatory Bowel Diseases in the United States.

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.

Managing the older adult with inflammatory bowel disease: is age just a number?

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.

Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials.

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.

Very Early Pouchitis Is Associated with an Increased Likelihood of Chronic Inflammatory Conditions of the Pouch.

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.

Risk of Infections With Ustekinumab and Tofacitinib Compared to Tumor Necrosis Factor α Antagonists in Inflammatory Bowel Diseases.

BACKGROUND & AIMS: The comparative safety of therapies is important to inform relative positioning within the therapeutic algorithm. Tumor necrosis factor α antagonists (anti-TNF) are associated with an increased risk of infections. Whether there is a similar increase with ustekinumab (UST) or tofacitinib has not been established. METHODS: We identified patients with Crohn's disease or ulcerative colitis from a national commercial health insurance plan in the United States between 2008 and 2019. Infectious outcomes were ascertained for patients newly initiating anti-TNF, UST, or tofacitinib therapy. Cox proportional hazards models were fit in propensity score-weighted cohorts to compare rates between patients treated with UST or tofacitinib and anti-TNF therapy. RESULTS: Our study included 19,096, 2420, and 305 patients with inflammatory bowel disease initiating anti-TNF, UST, and tofacitinib therapy, respectively. Over follow-up on-treatment, 7% and 44% of anti-TNF patients had infection-related hospitalizations and developed infections, respectively, compared with 4% and 32% of UST patients and 6% and 41% of tofacitinib patients. In the weighted Cox analysis, UST was associated with a significantly lower risk of infection (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.86-0.99) compared with anti-TNF therapy. There was a trend towards a reduction in infection-related hospitalizations (HR, 0.84; 95% CI, 0.66-1.03). The risk of infections (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05) were similar between patients on tofacitinib and anti-TNF. CONCLUSIONS: UST is associated with reduced risk of infections compared to anti-TNF biologics in inflammatory bowel disease, whereas no difference was observed between tofacitinib and anti-TNF therapy.

Yield and Predictors of Surveillance Colonoscopies in Older Adults With Long-standing Ulcerative Colitis.

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.

Prevalence and Implications of Frailty in Older Adults With Incident Inflammatory Bowel Diseases: A Nationwide Cohort Study.

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 < .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.

Vedolizumab Is Associated With a Lower Risk of Serious Infections Than Anti-Tumor Necrosis Factor Agents in Older Adults.

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.

Comorbidity Influences the Comparative Safety of Biologic Therapy in Older Adults With Inflammatory Bowel Diseases.

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.

Inflammatory Bowel Disease Patients Who Respond to Treatment with Anti-tumor Necrosis Factor Agents Demonstrate Improvement in Pre-treatment Frailty.

BACKGROUND: Frailty may be a risk factor for complications in inflammatory bowel diseases (IBD) patients. We examined the impact of treatment on IBD patients who were frail prior to treatment and identified predictors of post-treatment change in frailty. METHODS: In an electronic health record-based cohort of IBD patients initiating anti-tumor necrosis factor (TNF)-α agents, we applied a validated claims-based frailty index to determine frailty in the 1 year prior to and after treatment initiation. We characterized treatment non-response using a composite outcome of IBD-related hospitalization, surgery, change in therapy, or initiation of systemic steroids. We constructed multivariable logistic regression models to identify determinants of post-treatment frailty. RESULTS: The 1210 patients initiating anti-TNF therapy had a median age of 30 years; 20% were ≥ 50 years. In the first year after anti-TNF initiation, 40% were non-responders. Many more treatment non-responders were frail in the year following treatment compared with treatment responders (27% vs 7%, p < 0.001). Pre-treatment frailty (OR 2.01, 95% CI 1.35-3.00) and prior IBD-related hospitalization (OR 1.63, 95% CI 1.15-2.30) were independently predictive of higher likelihood of post-treatment frailty. Therapy response was associated with a lower likelihood (OR 0.24, 95% CI 0.16-0.34) of post-treatment frailty. Nearly 85% of patients who were frail prior to treatment demonstrated improvement in frailty following treatment CONCLUSIONS: Response to anti-TNF therapy is an important determinant of post-treatment frailty in patients with IBD. Our findings suggest that effectively treating inflammatory states in older patients with IBD may improve frailty.

Comparative Risk of Thrombotic and Cardiovascular Events with Tofacitinib and Anti-TNF Agents in Patients with Inflammatory Bowel Diseases.

BACKGROUND: Tofacitinib and inflammatory bowel disease (IBD) have been associated with increased risks for thromboembolic and cardiovascular events, but drug attributable risk is unknown. METHODS: We conducted a retrospective cohort study in a US claims database. We identified patients with IBD by International Classification of Disease (ICD) codes, stipulated 180 days of continuous enrollment prior to tofacitinib or anti-tumor necrosis factor (TNF) initiation to determine new users. Primary outcomes were ICD codes for venous thromboembolism (VTE) and cardiovascular (CV) events. We constructed propensity score (PS)-weighted Cox proportional hazard models to estimate hazard ratios (HRs) and time-to-event outcomes comparing tofacitinib and anti-TNF. We conducted a subgroup analysis of patients ≥ 50 years. RESULTS: We identified 305 patients with IBD initiating tofacitinib and compared them with 19,096 initiating anti-TNFs. After weighting, balance was achieved across all demographic covariates. VTE occurred in 5% of patients treated with tofacitinib and 4% of anti-TNF users; in a PS-weighted cohort, tofacitinib did not confer a significantly elevated VTE risk compared with anti-TNF therapy (HR: 1.72, 95% CI: 0.74-3.01). A major CV event (MACE) occurred in 2% of tofacitinib users and 1% of anti-TNF users; tofacitinib also did not confer a significantly elevated risk for MACE (HR: 2.50, 95% CI: 0.37-6.18). Those with a Charlson comorbidity index ≥ 2 had greater risks for thromboembolic and cardiovascular events. Similar findings were noted in patients ≥ 50 years. CONCLUSIONS: In this large, active comparator, study, we demonstrate that tofacitinib was not associated with a higher risk of adverse thrombotic events compared with anti-TNFs in patients with IBD.

Relationship Between Stages of Ileal Pouch-Anal Anastomosis, Timing of Restoration of Fecal Continuity, and Pouchitis.

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.

Pretreatment Frailty Is Independently Associated With Increased Risk of Infections After Immunosuppression in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Infections are an important adverse effect of immunosuppression for treatment of inflammatory bowel diseases (IBDs). However, risk of infection cannot be sufficiently determined based on patients' ages or comorbidities. Frailty has been associated with outcomes of patients with other inflammatory diseases. We aimed to determine the association between frailty and risk of infections after immunosuppression for IBD. METHODS: We performed a cohort study of 11,001 patients with IBD, using a validated frailty definition based on International Classification of Disease codes to identify patients who were frail vs fit in the 2 years before initiation of an anti-tumor necrosis factor (TNF) or immunomodulator therapy, from 1996 through 2010. Our primary outcome was an infection in the first year after treatment. We constructed multivariable logistic regression models, adjusting for clinically pertinent confounders (age, comorbidities, steroid use, and combination therapy) to determine the association between frailty and posttreatment infections. RESULTS: There were 1299 patients treated with an anti-TNF agent and 2676 patients treated with an immunomodulator. In this cohort, 5% of patients who received anti-TNF therapy and 7% of patients who received an immunomodulator were frail in the 2 years before immunosuppression. Frail patients were older and had more comorbidities. Higher proportions of frail patients developed infections after treatment (19% after TNF and 17% after immunomodulators) compared with fit patients (9% after TNF and 7% after immunomodulators; P < .01 for frail vs fit in both groups). Frail patients had an increased risk of infection after we adjusted for age, comorbidities, and concomitant medications (anti-TNF adjusted odds ratio, 2.05 [95% confidence interval, 1.07-3.93] and immunomodulator adjusted odds ratio, 1.81 [95% confidence interval, 1.22-2.70]). CONCLUSIONS: Frailty was associated with infections after immunosuppression in patients with IBD after we adjust for age and comorbidities. Systematic assessment and strategies to improve frailty might reduce infection risk in patients with IBD.

Creation of a Case-Finding Definition for Identifying Patients With Acute Pouchitis in Administrative Claims Data.

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 disease4-6; 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.

Patients With Inflammatory Bowel Diseases Are at Higher Risk for Meningitis.

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.

Vaping-associated esophagitis.

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.