Background Inflammatory bowel disease (IBD) is associated with significant psychosocial, economic, and physical burden on patients. IBD care in the United States results in significant healthcare expenditure with recurring emergency department (ED) care and hospital admissions. Despite advances in therapy and improved access to specialty care, there is still room for improvement in cost-efficient care. Specialty medical homes and interdisciplinary care models have emerged as ways to improve medical care, patient outcomes, and quality of life, as well as improve the impact of healthcare costs. There is limited real-world data on cost in the United States, with many articles citing cost estimates from models.Methods We analyzed real-world data from our tertiary care center with a focus on recurrent ED visits by IBD patients. Descriptive statistics were used for a cost analysis of multiple ED visits by IBD patients. Patients with >= 4 visits to the ED in a 6-month period were described as SuperUsers and were included in a separate analysis. The cost of hospitalization was also included.Results Total cost associated with all ED visits from SuperUsers were $72 999.57 with an average of $6636.32 per patient. When the patients were admitted, the total cost of ED visits and hospitalizations was $721 461.52, with an average of $65 587.41 per patient.Conclusions ED utilization by IBD patients with or without hospitalization is expensive and is typically driven by a cohort of SuperUsers. More work needs to be done to improve cost-effectiveness in IBD care, including reducing the frequency of ED visits. Inflammatory bowel disease patients with uncontrolled disease may have frequent visits to the emergency department and/or multiple hospitalizations. This results in expensive care with worse outcomes. Healthcare professionals and patients should work together to optimize care for better outcomes.

INTRODUCTION: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question. METHODS: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension. RESULTS: We analyzed 416 patients with IBD (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in patients with hypoalgesic IBD when compared with other patients with IBD and healthy controls. Patients with hypoalgesic IBD were also more likely to be homozygous for this polymorphism when compared with other patients with IBD and healthy controls. Hypoalgesic CD (30% vs 12%, P = 0.004) and hypoalgesic UC (32% vs 15%, P = 0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals (n = 50), rs6795970 homozygotes (n = 11) also demonstrated reduced abdominal discomfort to rectal balloon distension. DISCUSSION: These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.

Supplementary Figure 1 from NKX3.1 Homeodomain Protein Binds to Topoisomerase I and Enhances Its Activity

Numerous factors influence healthcare resource utilization (HRU) in inflammatory bowel disease (IBD). We previously demonstrated an association between the presence of certain IBD-related symptoms and HRU. We conducted a longitudinal study to identify the clinical variables and IBD-related symptoms predictive of HRU. This investigation utilized clinical encounters at an IBD center within a tertiary care referral center between 10/29/2015–12/31/2019. Participants were assessed over two time points (index and follow-up office visits) separated by a minimum of 6 months. Demographics, endoscopic disease severity, totals and sub-scores of surveys assessing for IBD-related symptoms, HRU, and substance use, and IBD-related medications. HRU was defined as any IBD-related emergency room visit, hospitalization, or surgery during the 6 months prior to follow-up appointment. We identified patients exhibiting HRU (at follow-up) and computed descriptive statistics and contingency table analyses of index appointment clinical data to identify predictors of HRU. Multivariable logistic regression models were fit incorporating significant demographic and clinical factors. 162 consecutively enrolled IBD patients (mean age 44.0 years; 99f:63 m; 115 Crohn’s disease [CD], 45 ulcerative colitis [UC], 2 indeterminate colitis) were included. 121 patients (74.7 In this longitudinal study, abdominal pain was the only clinical variable that demonstrated an association with future HRU (even when considering other symptoms and key variables such as disease activity, IBD-medications, and psychiatric comorbidities (i.e., anxious or depressed state). These findings reinforce the importance of regularly screening for and effectively treating abdominal pain in IBD.

Introduction: Hypoalgesic or silent inflammatory bowel disease (IBD) is a poorly understood condition that has been associated with poor clinical outcomes. There is evidence that lifestyle factors, including diet, exercise, and substance use can influence inflammatory activity and symptoms in IBD. It is unclear, though, whether these issues impact pain experience in IBD. We performed this study to evaluate the potential relationship between several key lifestyle factors and silent IBD. Methods: We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in 2 patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: (a) active IBD without pain (silent IBD) and (b) active IBD with pain. We also evaluated the relative incidence of characteristics related to diet, exercise, sexual activity, and substance abuse. Results: One hundred and eighty IBD patients had active disease and 69 (38.3%) exhibited silent IBD. Silent IBD patients exhibited incidences of disease type, location, and severity as pain-perceiving IBD patients. Silent IBD patients were more likely to be male and less likely to exhibit anxiety and/or depression or to use cannabis, analgesic medication, or corticosteroids. There were no significant differences in dietary, exercise-related, or sexual activities between silent and pain-perceiving IBD patients. Conclusions: Silent IBD was associated with reduced incidence of substance and analgesic medication use. No relationships were found between silent IBD and diet, exercise, or sexual activity, though specific elements of each require further dedicated study.

Lifestyle factors, including diet, exercise, substance use, and sexual activity, have been shown to influence risk of inflammation and complications in inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Little is known about their potential role in abdominal pain generation in IBD. We performed this study to evaluate for relationships between lifestyle factors and abdominal pain in quiescent IBD (QP-IBD). We performed a retrospective analysis utilizing data from our institution’s IBD Natural History Registry (January 1, 2017–December 31, 2022). Endoscopic evaluation, concurrent laboratory studies and surveys were completed by participants. Demographic and clinical data were also abstracted. We identified 177 consecutive patients with quiescent disease (105 females:72 males; 121 with CD:56 with UC) for participation in this study, 93 (52.5

Background:Polysubstance use (PSU), the simultaneous use of 2 or more substances of abuse, is common in inflammatory bowel disease (IBD). Preliminary studies suggest it may be associated with poor outcomes. This prospective study evaluated the impact of PSU on disease activity and healthcare resource utilization in IBD.Methods:This study was conducted in a tertiary IBD center between October 29, 2015, and December 31, 2019. Participants were assessed over 2 time points (index and follow-up outpatient appointments) separated by a minimum of 6 months. Demographics, endoscopic disease activity, and surveys assessing symptoms, healthcare resource utilization and substance use (tobacco, alcohol, marijuana, cocaine, methamphetamine, heroin, opioid, or benzodiazepine) were abstracted. We identified PSU during the index appointment and computed descriptive statistics and contingency table analyses, and multivariate logistic regression models at follow up to evaluate outcomes.Results:162 consecutively enrolled IBD patients were included. Seventy-five patients (46%) were polysubstance users at the index appointment. The most common cohorts were utilizing tobacco and alcohol (n=40) or tobacco and opioids (n=13). On bivariate and multivariate analyses, PSU during the index visit was positively associated with emergency department (ED) visits (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.24-5.07; P=0.01) and negatively associated with extraintestinal manifestations (OR 0.37, 95%CI 0.18-0.74; P=0.005). Age, sex, disease activity, disease subtype and IBD-related symptoms were not associated with PSU.Conclusions:IBD patients exhibiting PSU had increased risk of future ED visits. This study highlights the risks of PSU and reinforces the importance of appropriate substance use screening.

Classical MCL (cMCL) constitutes 6-8% of all B cell NHL.Despite recent advances, MCL is incurable except with allogeneic stem cell transplant.Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes.We treated 13 bMCL patients with combined epigenetic and immunotherapy treatment consisting of vorinostat, cladribine and rituximab (SCR).We report an increased OS greater than 40 months with several patients maintaining durable remissions without relapse for longer than 5 years.This is remarkably better then current treatment regimens which in bMCL range from 14.5-24 months with conventional chemotherapy regimens.We demonstrate that the G/A870 CCND1 polymorphism is predictive of blastic disease, nuclear localization of cyclinD1 and response to SCR therapy.The major resistance mechanisms to SCR therapy are loss of CD20 expression and evasion of treatment by sanctuary in the CNS.These data indicate that administration of epigenetic agents improves efficacy of anti-CD20 immunotherapies.This approach is promising in the treatment of MCL and potentially other previously treatment refractory cancers.

COVID-19 vaccine hesitancy varies across the USA. Data on COVID-19 vaccine hesitancy in patients with inflammatory bowel disease (IBD) are lacking. We assessed COVID-19 vaccine hesitancy and its associated variables in patients with IBD. We evaluated voluntary patient survey responses during routine clinical visits to our IBD center. Data collected included demographic and clinical characteristics. Descriptive statistics, univariate and multivariate analyses were performed to evaluate significant associations with COVID-19 vaccine hesitancy. A total of 239 individuals completed the survey. Over a third of respondents (35.6%) expressed hesitancy toward receiving the COVID-19 vaccine due to vaccine safety concerns (49.4%) and efficacy (23.5%), while others reported non-specific concerns (34.1%). On univariate analysis, Crohn’s disease (OR 2.33 CI 1.28–4.25 p = 0.0056), use of biologic medications (OR 1.93 CI 1.16–3.23, p = 0.012), previous self-reported vaccine refusal (OR 8.13 CI 2.90–22.82 p = 0.0001), earlier date of survey administration (OR 2.01 CI 1.17–3.44 p = 0.011), and self-reported COVID infection (OR 2.55 CI 1.16–5.61 p = 0.0056) were more likely to be associated with COVID-19 vaccine hesitancy. On multivariate analysis, patient age, previous vaccine refusal and date of survey administration were more likely to be associated with COVID-19 vaccine hesitancy. Over one-third of patients with IBD expressed COVID-19 vaccine hesitancy. Vaccine safety and efficacy were the most common reasons. Younger age, previous vaccine refusal and earlier date of survey were more likely to be associated with hesitancy. Our findings suggest that there is room for targeted education to improve COVID-19 vaccine uptake in patients with IBD.

Several symptoms have been connected to increased healthcare resource utilization (HRU) in the context of inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC). This study was designed to investigate the prevalence of IBD-associated symptoms and to determine whether any are independently associated with HRU. We undertook a retrospective analysis of data related to consecutive IBD patient encounters from a tertiary care referral center between 1/1/2015 and 8/31/2019. Demographics, clinical activity, endoscopic severity, IBD-related symptom scores, anxiety and depression scores, and other key clinical data were abstracted. Four hundred sixty-seven IBD patients [247f.: 220 m; 315 CD, 142 UC and 11 indeterminate colitis] were included in this study. The most common symptoms were fatigue (83.6%), fecal urgency (68.2%) and abdominal pain (63.5%). Fatigue, abdominal pain, anxiety or depression, corticosteroids, and opioids were each positively associated with HRU, while NSAID and mesalamine use were inversely associated on bivariate analysis. The only factor that demonstrated a statistically significant association with HRU in the whole cohort on multivariable analysis was abdominal pain. Abdominal pain is independently associated with HRU and should be specifically screened for in IBD patients to identify individuals at risk of undergoing expensive interventions. This study also reinforces the importance of optimizing diagnostic and therapeutic management of abdominal pain in IBD.

Introduction: “Silent,” or painless, chronic pancreatitis (CP) exists when patients with diagnostic features of CP describe no abdominal pain. It is a poorly understood phenomenon but it is important as it may go unnoticed until serious complications arise, including pancreatic insufficiency, diabetes, and even cancer. The aim of this study was to better characterize the silent CP patient and investigate potential risk factors associated with this condition. Methods: We performed a retrospective analysis using data from a single tertiary care center between 2018-2021. 286 patients were identified using ICD-10 codes (“other chronic pancreatitis”-K86.1 and “exocrine pancreatic insufficiency”-K86.81). Two expert reviewers assessed each patient. Patients were included if they demonstrated feature(s) of CP including parenchymal (atrophy, calcifications +/- scarring) and/or ductal (stricture +/- dilation) changes on CT, MRI, or EUS imaging. Patients were excluded if their pain was attributed to a cause other than CP or if they underwent prior pancreaticobiliary surgery. Patients were categorized as having painful or silent CP, based upon documentation from at least two clinic visits. Patient demographics, CP etiology, presence of pancreatic duct stent & diabetes, substance use, and pain medication usage were abstracted. Descriptive statistics, bivariate and logistic regression analyses (utilizing variables with a p< 0.1 on bivariate analysis) were performed to characterize the study cohort and evaluate for independent associations with silent CP. Results: 117 patients with CP were included in this study (mean age 57.2 years, 61.5% male). 23 patients (19.7%) had silent CP (Table). Patients with silent CP were older, more likely male, more likely diabetic, and less likely to use opioids or any pain medications. On multivariate analysis, older age (OR 1.06, 95% CI 1.01-1.11, p=0.03), male sex (OR 5.38, 95% CI 1.38-20.96, p=0.02), and opioid use (OR 0.18, 95% CI 0.03-0.96, p=0.04) were associated with silent CP. Conclusion: Silent CP is relatively common and affected patients are older, more likely male, and less likely to use opioids. This suggests there may be inherent differences in visceral pain perception contributing to this clinical phenotype. Future studies should focus on evaluating larger cohorts longitudinally to confirm our findings and to more carefully investigate the underlying pathophysiology of silent CP, as well as to evaluate clinical outcomes of this condition. Table 1. - Multivariate Analysis for Association Between Clinical Characteristics and Silent vs Painful Chronic Pancreatitis Clinical Characteristic Odds Ratio 95% Confidence Interval P Value Age 1.060 1.010 1.110 0.027 Male Sex 5.376 1.383 20.964 0.015 Diabetes 2.430 0.774 7.610 0.128 Current Opioid Use 0.176 0.032 0.956 0.044 Any Current Pain Medication Use 0.860 0.241 23.070 0.816

Objectives We aimed to evaluate the incidence, predisposing factors and impacts of polysubstance use (PSU) (ie, the concurrent use or abuse of two or more drugs or substances) in inflammatory bowel disease (IBD). Methods Data of patients enrolled between 1 January 2015 and 31 August 2019 from a single tertiary care referral center were retrospectively collected. Patients' baseline and clinical characteristics and their antidepressant and/or anxiolytic medications were abstracted. Associations between PSU and patients' characteristics were analyzed. Multivariate logistic regression models were fit, incorporating significant clinical factors. Results Altogether 315 patients with IBD (166 women, 149 men; 214 with Crohn's disease and 101 ulcerative colitis) were enrolled. Of them, 66 (21.0%) exhibited PSU (CD 21.5%, UC 19.8%); 37.5% had moderate to severe disease activity, 34.3% with extraintestinal manifestations (EIM), 41.6% with an anxious or depressed state and 69.8% had used healthcare resources in the prior 12 months. Moreover, 71.2% used two substances, while 27.3% used three substances. In the total cohort, EIM (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14-3.34, P = 0.019) and antidepressant or anxiolytic use (OR 2.51, 95% CI 1.45-4.39, P < 0.001) were positively associated with PSU on multivariate analysis. PSU was associated with increased rate of IBD-associated imaging (57.6% vs 47.0%, P < 0.05). Conclusions PSU is common in IBD. EIM, antidepressant and/or anxiolytic use and imaging studies were independently associated with PSU. This study reinforces the importance of screening patients with IBD for substance use, particularly those with EIM and using antidepressants and/or anxiolytics.

We aimed to evaluate the incidence, predisposing factors and impacts of polysubstance use (PSU) (ie, the concurrent use or abuse of two or more drugs or substances) in inflammatory bowel disease (IBD). Data of patients enrolled between 1 January 2015 and 31 August 2019 from a single tertiary care referral center were retrospectively collected. Patients’ baseline and clinical characteristics and their antidepressant and/or anxiolytic medications were abstracted. Associations between PSU and patients’ characteristics were analyzed. Multivariate logistic regression models were fit, incorporating significant clinical factors. Altogether 315 patients with IBD (166 women, 149 men; 214 with Crohn's disease and 101 ulcerative colitis) were enrolled. Of them, 66 (21.0%) exhibited PSU (CD 21.5%, UC 19.8%); 37.5% had moderate to severe disease activity, 34.3% with extraintestinal manifestations (EIM), 41.6% with an anxious or depressed state and 69.8% had used healthcare resources in the prior 12 months. Moreover, 71.2% used two substances, while 27.3% used three substances. In the total cohort, EIM (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14-3.34, P  = 0.019) and antidepressant or anxiolytic use (OR 2.51, 95% CI 1.45-4.39, P  < 0.001) were positively associated with PSU on multivariate analysis. PSU was associated with increased rate of IBD-associated imaging (57.6% vs 47.0%, P  < 0.05). PSU is common in IBD. EIM, antidepressant and/or anxiolytic use and imaging studies were independently associated with PSU. This study reinforces the importance of screening patients with IBD for substance use, particularly those with EIM and using antidepressants and/or anxiolytics.

BACKGROUND:Management of inflammatory bowel disease (IBD) patients can be very challenging. Nurse navigators (NNs) have demonstrated great promise for coordinating care of complex disorders but little is known about their impact on the setting of IBD. We undertook this study to evaluate how the introduction of a NN in a dedicated IBD clinic would influence several outcomes related to patient care.METHODS:A retrospective chart review was performed evaluating Penn State IBD clinic patients receiving care a year before and after the introduction of a dedicated NN to the clinic. No-show rates, new appointments in less than 21 days, total clinic visits per month, and patient enrolment in our IBD registry and biorepository were measured prior to and after hiring of the NN between 2 providers. Each provider and their composite data were statistically compared using univariate analysis.RESULTS:After hiring the NN, there was a statistically significant decrease in combined no-show rates (P=0.02). There was no significant difference in the combined average number of new appointments in less than 21 days (P=0.62) or total clinic visits per month (P=0.09). Enrolment in the database and biorepository increased (from 83% to 90%). Finally, 97% were satisfied with the NN's services, and 94% were satisfied with the IBD education they provided.CONCLUSIONS:Hiring a NN in our clinic was associated with high patient satisfaction, reduced no-show rates, and increased research participation. Thus, incorporation of a NN can improve care in an IBD-centered gastroenterology clinic.

Introduction: Cannabis use is common in the setting of inflammatory bowel disease (IBD). Patients frequently use cannabis to treat IBD-associated symptoms, and there is evidence that cannabis and its derivatives are helpful for this purpose. However, it is unclear how the symptom profiles of active IBD cannabis users and nonusers compare and how these symptoms may relate to their underlying disease state and/or complications. Materials and Methods: We performed a retrospective cohort study using a consented IBD natural history registry from a single tertiary care referral center between January 1, 2015 and August 31, 2020. We asked patients about current cannabis use and frequency. We also abstracted demographic and clinical characteristic information, including endoscopic severity, and totals and subscores of surveys assessing IBD characteristics, presence of anxiety/depression, and IBD-associated symptoms. We compared clinical and demographic factors of cannabis users and nonusers and developed a logistic regression model to evaluate for independent associations with cannabis use. Results: Three hundred eighty-three IBD patients met the inclusion criteria (206 females, 177 males; 258 Crohn's disease [CD], 118 ulcerative colitis, and 7 indeterminate colitis). Thirty patients (7.8%) were active cannabis users, consuming it for an average of 2.7 times per week. Cannabis users were more likely to report abdominal pain (83.3% vs. 61.7%), gas (66.7% vs. 45.6%), tenesmus (70.0% vs. 47.6%), and arthralgias (53.3% vs. 20.3%) compared to those that did not use cannabis (p<0.05 for each). Incidence of moderate-severe endoscopic inflammation was similar between cannabis users and nonusers, while CD-associated complications were more common in nonusers (39.1% vs. 69.7%, p<0.05). The only factor that demonstrated a significant association with cannabis use on multivariable analysis was arthralgia (p<0.01). Discussion: Active IBD cannabis users were more likely to report a variety of symptoms, including abdominal pain, gas, tenesmus, and arthralgias. However, they did not demonstrate more frequent active disease or IBD-associated complications, suggesting that other nonluminal factors influence their symptoms and/or decision to use cannabis. These findings demonstrate the importance of evaluating for extraintestinal contributors to symptom burden in IBD cannabis users, as well as the ongoing need to develop safer and more effective methods for recognizing and managing abdominal pain and other symptoms in this setting.

Background: Psychiatric disorders, including anxiety and depression, are significantly more common in patients with inflammatory bowel disease (IBD). We established an integrated psychiatry clinic for IBD patients at our tertiary center IBD clinic to provide patients with critical, but frequently unavailable, coordinated mental health services. We undertook this study to evaluate the impact of this service on psychiatric outcomes, quality of life, and symptom experience. Methods: We performed a longitudinal prospective study comparing patients who had been cared for at our integrated IBD-psychiatry clinic to those who had not. We abstracted demographic and clinical information as well as contemporaneous responses to validated surveys. Results: Thirty-six patients cared for in the IBD psychiatry clinic were compared to a control cohort of 35 IBD patients. There was a significant reduction in the Hospital Anxiety and Depression Scale (HADS) depression score over time in the study cohort (p = 0.001), though not in the HADS anxiety score. When compared to the control group, the study cohort showed a significant reduction in the HADS depression score. No significant differences were observed in the Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, or Short IBD Questionnaire. Conclusions: This is the first study to evaluate the impact of an integrated psychiatry clinic for IBD patients. Unlike their control counterparts, individuals treated in this clinic had a significant reduction in the mean HADS depression score. Larger scale studies are necessary to verify these findings. However, this study suggests that use of an integrated psychiatry IBD clinic model can result in improvement in mental health outcomes, even in the absence of significant changes in IBD activity.