Faculty Bibliography

BACKGROUND:Venous thromboembolism (VTE) is a significant cause of morbidity and mortality among patients with inflammatory bowel disease (IBD). However, data on national trends remain limited. AIMS/OBJECTIVE:To assess national trends in VTE-associated hospitalisations among patients with IBD as well as risk factors for, and mortality associated with, these events METHODS: Using the U.S. Nationwide Inpatient Sample from 2000-2018, temporal trends in VTE were assessed using the National Cancer Institute's Joinpoint Regression Program with estimates presented as the average annual percent change (AAPC) with 95% confidence intervals (CIs). RESULTS:Between 2000 and 2018, there were 4,859,728 hospitalisations among patients with IBD, with 128,236 (2.6%) having a VTE, and 6352 associated deaths. The rate of VTE among hospitalised patients with IBD increased from 192 to 295 cases per 10,000 hospitalisations (AAPC 2.4%, 95%CI 1.4%, 3.4%, p < 0.001), and remained significant when stratified by ulcerative colitis (UC) and Crohn's disease as well as by deep vein thrombosis and pulmonary embolism. On multivariable analysis, increasing age, male sex, UC (aOR: 1.30, 95%CI 1.26, 1.33), identifying as non-Hispanic Black, and chronic corticosteroid use (aOR: 1.22, 95%CI 1.16, 1.29) were associated with an increased risk of a VTE-associated hospitalisation. CONCLUSION/CONCLUSIONS:Rates of VTE-associated hospitalisations are increasing among patients with IBD. Continued efforts need to be placed on education and risk reduction.

Introduction: Strictures in Crohn's disease (CD) increase the likelihood of requiring surgery, which is costly and invasive. In the last two decades, endoscopic therapies including endoscopic balloon dilation (EBD) and endoscopic stricturotomy (ESt) have emerged as effective and less invasive therapies for CD strictures.1 ESt in particular is advantageous for longer, fibrotic strictures, or strictures adjacent to anatomic structures requiring precision, and has shown a high rate of surgery-free survival.2-4 We therefore assessed the cost-effectiveness of ESt as compared to surgical resection for CD strictures.
Method(s): A microsimulation state-transition model compared ESt to surgical resection for patients with primary or anastomotic CD strictures. Our primary outcome was quality-adjusted life years (QALYs) over ten years, and strategies were compared at a willingness to pay (WTP) of $100,000/QALY from a societal perspective. Costs (2022 $US) and ICERs were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty.
Result(s): The surgery strategy cost more than 2.5 times the endoscopic stricturotomy strategy, but resulted in nine higher QALYs per 100 persons (Table). Overall, surgery had an ICER of $308,787/QALY, making ESt more cost-effective. The median number of endoscopic stricturotomies was 4 in the ESt strategy and 0 in the surgery strategy; the median number of surgeries was 0 and 2 respectively. One-way sensitivity analyses showed that quality of life after ESt as compared to that after surgery, probabilities of requiring repeated interventions, and surgical mortality and cost were the most influential parameters in our model (Figure). Probabilistic sensitivity analyses favored ESt in 65.5% of iterations.
Conclusion(s): Endoscopic stricturotomy is cost-effective for managing primary or anastomotic Crohn's disease strictures. Post-intervention quality of life and probabilities of requiring repeated interventions exert most influence on cost-effectiveness; the decision between ESt and surgery should be made considering patients' risk and quality of life preferences. (Figure Presented)

Introduction: As the inflammatory bowel disease (IBD) patient population ages, there will be an increasing number of individuals requiring advanced therapies. Although older age is thought to be associated with immunosenescence, there are data suggesting that older adults may be at higher risk for antibody development as the result of biologic use.
Method(s): Using a large commercial laboratory database (Prometheus Laboratories), we extracted infliximab (IFX) dosing as well as antibody to infliximab (ATI) levels for all individuals using this assay from 2015-2021. Our primary outcome was the presence of ATI (titer >3.1 U/mL). Frequencies were recorded as categorical variables with chi-square analysis used, and multivariable logistic regression was employed to assess the impact of IFX dose, age (< 60 years-old v. >=60 years-old), and IBD subtype on the development of ATI.
Result(s): Overall, there were 22,197 unique specimens, with 3,028 (13.6%) having ATI. When stratified by age, individuals >=60 years-old developed ATI 18.1% (473/2,612) of the time as compared to 15.0% (2,555/17,030) for individuals < 60 years of age (p< 0.01, Figure). Among all individuals with IFX dose < 10mg q8 weeks, older adults (>=60 years of age) were more likely to develop ATI as compared to younger adults (22.8% vs. 16.2%, respectively, p< 0.01); however, when IFX dose was >=10mg/kg q8 weeks, age >= 60 years-old was no longer significantly associated with the development of ATI (9.9% if < 60 years-old vs. 10.6% if >=60 years-old) on univariable analysis. Overall, older adults were less likely to receive IFX doses >=10mg/kg q8 weeks (38.4% in older adults vs. 49.7% in younger adults; p< 0.01). On multivariable analysis, age >=60 years-old (adjOR 1.35, 95%CI 1.20-1.51), IFX dose >= 10mg/kg q8 weeks (adjOR 0.53, 95%CI 0.49-0.57) and having ulcerative colitis as compared to Crohn's disease (adjOR 1.44, 95%CI 1.33-1.57) were independently associated with the development of ATI.
Conclusion(s): Older adults with IBD develop ATI more frequently than younger adults when adjusting for IFX dose and IBD subtype. However, when IFX dose >=10mg/kg q8 weeks, ATI was significantly less likely to develop among older adults, and occurred in a similar proportion of younger individuals. Further education is needed, highlighting that older adults with IBD are more likely to develop ATI as compared to younger adults, particularly when using lower doses of IFX, and that higher doses may decrease this likelihood. (Figure Presented)

Introduction: Infliximab (IFX) has been efficacious in reducing colectomy rates among patients with moderate-to severe ulcerative colitis, but predictors of colectomy within 30 days of IFX among patients with acute severe ulcerative colitis (ASUC) are less established.
Method(s): We performed a single-center retrospective analysis of patients who received at least one dose of IFX while admitted between 2011-2022. We assessed demographic, clinical and laboratory predictors of colectomy within 30 days of first IFX dose. Multivariable and time-to-event analysis using Kaplan-Meier with log-rank statistics were used to assess risk factors for colectomy within 30 days.
Result(s): A majority of the 172 patients hospitalized with ASUC who received IFX received 10 mg/kg (87.79%). Overall, 22/172 patients (12.79%) underwent colectomy within 30 days of first IFX dose. On univariable analysis, age, sex, race, ethnicity, BMI and smoking status were not associated with risk of colectomy. Higher initial CRP was significantly associated with 30-day risk of colectomy (106.17 vs. 65.10 mg/dL among patients who did not undergo colectomy; p< 0.01), as was a decrease of CRP <=50% prior to discharge (p< 0.01). Lower initial albumin [< 3 (36.36%), 3.0-3.5 (40.91%), >3.5 g/dL (22.73%)] was associated with our primary outcome (p=0.046), as was a higher number of bowel movements in a 24-hour period prior to discharge (5.6 vs. 3.9 among patients who did not undergo colectomy; p=0.0256). On multivariable analysis, higher initial CRP (aOR 1.01, 95% CI 1.00 - 1.02), <=50% change in CRP after first dose of IFX (aOR 9.00, 95% CI 2.43 - 33.29) and higher number of bowel movements in a 24-hour period prior to discharge (aOR 1.24, 95% CI 1.01- 1.52) remained significantly associated with risk of colectomy when adjusting for relevant covariables (Table). On Kaplan-Meier analysis, initial CRP >100 mg/ dL, albumin < 3 g/dL and change in CRP <=50% prior to discharge were significantly associated with decreased time to colectomy (Figure).
Conclusion(s): Among patients with ASUC, higher CRP, decrease of CRP <=50% and higher number of bowel movements prior to discharge were associated with increased risk of colectomy within 30-days of receiving IFX. Initial CRP >100 mg/dL, albumin < 3 g/dL and decrease of <=50% in CRP prior to discharge were associated with decreased time to colectomy. These results can identify patients at highest risk and impact clinical decision-making regarding need for and timing of colectomy in patients with ASUC receiving IFX. (Table Presented)

Introduction: Inflammatory bowel disease (IBD), comprised of Ulcerative Colitis (UC) and Crohn's Disease (CD), is caused by a combination of environmental factors, immune dysregulation, and genetic susceptibility. Other immune-mediated phenomena, like hypothyroidism, have also been observed in this population. Thus, we sought to explore clinical characteristics and outcomes among IBD patients with hypothyroidism compared to IBD patients without hypothyroidism.
Method(s): In a retrospective chart review from a large, tertiary, academic medical center, baseline demographics and clinical data were extracted for patients diagnosed with either UC or CD and having at least one thyroid stimulating hormone (TSH) measurement from prior to 2016. Based on the presence of a documented hypothyroidism ICD-10 code, patients were then divided into two groups, those with IBD alone and those with both IBD and hypothyroidism, as described in Figure. Individual charts were then further examined for disease characteristics, biomarkers, healthcare utilization, medication use, and other comorbidities from 2016 to 2022. Demographic and clinical variables were then compared between the two groups, as seen in Table.
Result(s): We identified 166 adult IBD patients (CD 53%, UC 47%). The mean age was 62.9 years. Among these patients, 116 patients (69.9%) had IBD and hypothyroidism. The most common causes of hypothyroidism were Hashimoto, subclinical, and acquired hypothyroidism. No differences were noted in race, smoking status, or BMI. IBD disease location, behavior, and prevalence of extra-intestinal manifestations did not significantly differ between the two study groups. Both groups had similar number of colonoscopies, hospitalizations, as well as comparable medication use (SSRI/SNRI, steroids, 5-ASA, immunomodulators, biologics). However, patients with IBD and hypothyroidism had higher rates of anemia (p=0.03), hypoalbuminemia (p=0.007), and CRP elevations (p=0.002). Furthermore, patients with both IBD and hypothyroidism had a greater median number of emergency department visits (p=0.039) and axial radiography (p=0.002).
Conclusion(s): IBD patients with hypothyroidism experience a more severe disease course with higher biomarkers of inflammation and healthcare utilization than those without hypothyroidism despite similar IBD phenotype and therapy exposures. This highlights a potential subgroup of IBD patients who may be at risk for increased disease severity and associated poor outcomes. (Table Presented)

Introduction: Obesity is associated with an increased risk of colorectal neoplasia, but this relationship has not been studied in patients with inflammatory bowel disease (IBD). Both IBD and obesity induce a chronic inflammatory state, so the combination of the two could have an additive or synergistic effect on risk of colorectal neoplasia. Given the increased baseline incidence of dysplasia among IBD patients, identifying modifiable risk factors, such as obesity, could have a significant impact on long term cancer-related outcomes.
Method(s): We performed a retrospective case-control study of IBD colitis patients at an academic IBD Center between January 2006 and February 2022. Demographic and disease-related data, known risk factors for dysplasia, and median BMI during the follow-up period were obtained. Only patients with at least 5 years of colonoscopy reports were included. A case was defined as any patient with biopsy proven dysplasia-indefinite, low-grade, or high-grade-during the study period. A control was defined as any patient with absence of biopsy-proven dysplasia. Obesity was defined as BMI of 30 or greater. Univariate analysis was performed using T-test for continuous variables and chi-square for categorical variables. Multivariate analysis was performed using logistic regression to model dysplasia risk.
Result(s): 106 cases had biopsy-proven colorectal dysplasia (64 IND, 36 LGD, 10 HGD); 125 controls had no dysplasia. Number of colonoscopies (p < 0.001) IBD subtype ulcerative colitis (p = 0.016), maximum histologic severity (p = 0.127), pseudopolyps (p = 0.162), IBD duration (p = 0.098), sex (p = 0.18), age (p < 0.001), smoking history (p = 0.048), prior dysplasia (p < 0.001), and obesity (p < 0.001) were associated with dysplasia on univariate analysis. On multivariable regression, number of colonoscopies (OR 1.26, 95% CI 1.08 - 1.48, p = 0.004), prior dysplasia (OR 3.98, 95% CI 1.23 - 12.86, p = 0.021), and obesity (OR 2.90, 95% CI 1.21 - 6.95, p = 0.017) were each independently associated with increased dysplasia risk. (Figure)
Conclusion(s): Patients with IBD have an increased risk of colorectal neoplasia, but a variety of comorbid states may exacerbate this risk. Notably, we identified obesity as an independent risk factor for dysplasia. Further research is needed to determine whether this risk functions synergistically with IBD or just as an independent risk factor. Furthermore, targeted weight-loss interventions may reduce the incidence of dysplasia among patients with IBD. (Table Presented)

Introduction: Nearly a quarter of older adults with inflammatory bowel disease (IBD) require surgery. Patients with IBD are at risk for complications postoperatively and this risk is increased in older adults. However, little is known about the risk factors leading to these complications.We assessed risk factors associated with adverse postoperative outcomes among older adults who underwent IBD-related surgery, as well as evaluated trends in emergency vs. elective surgery in this population.
Method(s): Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified adults >=60 years of age who underwent an IBD-related intestinal resection from 2005-2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or what we identified as serious complications listed in NSQIP.
Result(s): In total, 9,640 intestinal resections were performed among older adults with IBD from 2005-2019, with 48.3% having undergone resection for Crohn's disease (CD), and 51.7% for ulcerative colitis (UC). Nearly 37% experienced an adverse outcome, with the most common complication being infection (20.21%). From 2005 to 2015, there was no decrease in the number of emergent cases among older adults. On univariate analysis, higher rates of adverse postoperative outcomes were seen with increasing age (p< 0.001), with nearly 50% of those >=80 years of age having an adverse outcome. Patients who underwent an emergency surgery had a higher likelihood of postoperative complications (66.86%; p< 0.001). On multivariable analysis, albumin <=3 (aOR 1.99; 95%CI 1.69-2.33), the presence of two or more comorbidities (aOR, 1.50; 95%CI 1.27-1.76), totally dependent functional status as compared to those partially dependent or independent (aOR, 7.28; 95%CI 3.14-21.2), and emergency surgery (aOR, 1.70; 95% CI 1.36-2.11) significantly increased the odds of an adverse outcome. (Figure)
Conclusion(s): Overall 37% of older adults with IBD experienced an adverse outcome as a result of IBD-related surgery. Limited functional health status, low preoperative serum albumin levels, and those undergoing emergent surgery were associated with a significantly higher risk. This is particularly important as the number of older adults with IBD is increasing, with a persisting number of emergency cases over time. Given the high rate of surgery in this population, future research should focus on preoperative rehabilitation, nutritional optimization, and timely surgery to improve outcomes. (Table Presented)

PURPOSE OF THE REVIEW/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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.