Despite incredible growth in systems of care and rapidly expanding therapeutic options for people with inflammatory bowel disease, there are significant barriers that prevent patients from benefiting from these advances. These barriers include restrictions in the form of prior authorization, step therapy, and prescription drug coverage. Furthermore, inadequate use of multidisciplinary care and inflammatory bowel disease specialists limits patient access to high-quality care, particularly for medically vulnerable populations. However, there are opportunities to improve access to high-quality, patientcentered care. This position statement outlines the policy and advocacy goals that the American Gastroenterological Association will prioritize for collaborative efforts with patients, providers, and payors.

Abstract INTRODUCTION Inflammatory bowel disease (IBD) is a chronic inflammatory condition that may result in malnutrition and alteration of body composition, such as the development of sarcopenia. Sarcopenia is a known component of frailty, which is a driver of poor health outcomes and a significant independent predictor of mortality in patients with IBD. The purpose of this study was to determine whether grip strength, as a predictor of sarcopenia and frailty, is associated with clinical symptoms, endoscopic disease activity and disease-related disability in patients with IBD. METHODS This is a prospective cohort study performed at a single tertiary care center. Outpatient adults aged 18 to 89-years-old with a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD), were consented and enrolled at the time of an outpatient colonoscopy. Study participants were asked to complete two paper surveys addressing clinical symptoms and IBD Disability Index. Grip strength measurements were obtained using a Jamar dynamometer and adjusted for age and sex by Z-score calculation. RESULTS There was a total of 74 patients, with a mean age of 47.06 years, 51.4% male and 48.6% female with a diagnosis of either UC (38%) or CD (62%). The mean disease duration was 15.7 years (0.5-50.7). Mean hand grip Z-score amongst all patients was lower in patients not in clinical remission compared to those in clinical remission (–0.160 vs 0.480, p = 0.025), though in subgroup analysis based on diagnosis, statical significance only maintained in the CD, but not the UC group (-0.230 vs 0.610, p=0.044; 0.020 vs 0.340, p=0.544 respectively). Mean hand grip Z-score was not associated with IBD Disability Index (–0.070 vs 0.250, p= 0.669) or endoscopic disease activity (UC 0.210 vs 0.070, p=0.513; CD –0.108 vs 0.274, p=0.638). CONCLUSION Low hand grip strength is associated with clinical disease activity in patients with CD but not UC. Our study does not suggest hand grip strength to be associated with IBD-related disability or endoscopic disease activity in either patients with UC or CD. Data on clinical outcomes at 6-months will be collected. DISCUSSION From the findings in our study, hand grip measurements alone may not be the best predictor of disease activity or related disability. There is a lack of validated diagnostic criteria for sarcopenia and frailty in the IBD population and additional diagnostic modalities may be required. While our study suggests that hand grip may be correlated with clinical disease activity in patients with CD, additional studies with a large population size and wider representation of disease severity, such as including hospitalized IBD populations, are needed to further validate these findings.

BACKGROUND & AIMS:Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS:We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS:In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS:In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

The three types of IFN have roles in antimicrobial immunity and inflammation that must be properly balanced to maintain tissue homeostasis. For example, IFNs are elevated in the context of inflammatory bowel disease and may synergize with inflammatory cytokines such as TNF-α to promote tissue damage. Prior studies suggest that in mouse intestinal epithelial cells (IECs), type III IFNs are preferentially produced during viral infections and are less cytotoxic than type I IFN. In this study, we generated human IEC organoid lines from biopsies of ileum, ascending colon, and sigmoid colon of three healthy subjects to establish the baseline responses of normal human IECs to types I, II, and III IFN. We found that all IFN types elicited responses that were qualitatively consistent across intestinal biopsy sites. However, IFN types differed in magnitude of STAT1 phosphorylation and identity of genes in their downstream transcriptional programs. Specifically, there was a core transcriptional module shared by IFN types, but types I and II IFN stimulated unique transcriptional modules beyond this core gene signature. The transcriptional modules of type I and II IFN included proapoptotic genes, and expression of these genes correlated with potentiation of TNF-α cytotoxicity. These data define the response profiles of healthy human IEC organoids across IFN types, and they suggest that cytotoxic effects mediated by TNF-α in inflamed tissues may be amplified by a simultaneous high-magnitude IFN response.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

BACKGROUND:The IBD disability index (IBDDI) has been shown to be valid and reliable. We compared the distributional and predictive properties of the IBDDI, when collected from five populations of people living with IBD- from Winnipeg, Chicago, Toronto, Hong Kong, and Jerusalem.METHODS:People with IBD from five jurisdictions were invited to complete a survey including the IBDDI, the World Health Organization Disability Assessment Scale, the Work and Social Adjustment Scale, the IBDQ, the Kessler-6 distress scale, and the Stanford presenteeism scale. Between sites, we compared the correlation between IBDDI and the other 4 measures of disability/quality of life/distress, and the association between IBDDI and presenteeism and having been hospitalized in the past year.RESULTS:There were 1121 participants from Winnipeg, 511 from Chicago, 147 from Toronto, 97 from Hong Kong, and 96 from Jerusalem. The majority had Crohn's disease. Although the mean IBDDI score varied by site, the correlation between IBDDI and each of the other 4 measures of disability/QOL/distress was nearly identical. Similarly, the regression coefficient showing the association between IBDDI and presenteeism was nearly identical in all sites, and the risk ratios showing the association between hospitalization and high IBDDI was similar in all sites.CONCLUSION:The correlation between IBDDI and different measures of disability/QOL/distress was similar across all sites. There is strong evidence of the association between IBD-related disability and presenteeism, and between hospitalization and high IBD-related disability, and that the associations are the same across different populations. The severity of disability that an individual with a given IBDDI score has is directly comparable across populations.

The unprecedented response to the COVID-19 coronavirus pandemic disrupted the health care community. Consequently, the American Gastroenterological Association (AGA) adapted and expanded its policy priorities to meet the evolving needs of members and patients. To inform these efforts, the AGA launched a needs assessment survey to better understand the impact of COVID-19 on gastroenterology and hepatology (GI) providers in clinical practice. The findings were used to develop timely resources for the GI community, inform advocacy efforts, and advance a robust legislative agenda that resulted in support for COVID-19–related legislative and regulatory protections for the GI community. Here, we summarize the survey findings and describe the AGA's programmatic responses to the COVID-19 pandemic, focusing on its advocacy and legislative efforts. Furthermore, we share how these experiences continue to actively inform ongoing support for the GI community during COVID-19, including vaccine administration. Finally, we discuss how these experiences with COVID-19 help provide a model for rapid assessment and targeted response for future public health crises. The AGA developed and distributed the COVID-19 Needs Assessment survey during July and August 2020 via e-mail to AGA members. We assessed a range of topics that included feedback on providers' experiences with resumption of elective procedures, growth and implementation of telehealth, access to personal protective equipment (PPE), impacts of COVID-19 on financial feasibility and security, and utilization of governmental COVID-19 relief programs. In total, there were 432 respondents, and response rates to individual questions varied. Of those who reported practice type, 40% were in single-specialty practice, 33% in academic practice, 13% in hospital-based practice, and 12% in multispecialty group practice. When respondents were asked about the impacts on their GI practices without substantive future federal grants and loans, 42% of the 313 respondents indicated their practices would be "smaller (than pre–COVID-19 levels) and financially unhealthy." Respondents also indicated utilization of several COVID-19–related financial assistance programs. The applications and receipts of aid for different programs are depicted in Figure 1. Thirty-five percent of respondents did not apply for any federal grants, loans, or funds. A majority of respondents were concerned about reduced procedure volume upon resuming elective endoscopy. Of 358 respondents, more than 95% predicted a return to lower endoscopic volume than before COVID. Moreover, one-fourth of respondents predicted that a return to pre-COVID levels would take more than 12 months. There were 352 responses to questions relating to management of PPE resources. They rated a significant degree of difficulty (responses of "extremely difficult," "very difficult," or "difficult") across the following PPE-related challenges: utilization rates (57%), sourcing (55%), regulatory/external interventions (38%), and staff compliance/adherence (24%). These respondents cited using multiple approaches for PPE conservation that included re-use tactics (72%), staff education (70%), increased inventory security (52%), and policy changes (39%). When asked how PPE resources compared to the 2 weeks before the survey, the majority (62%) noted "no change," with 18% indicating "worse" (resources continue to decline) and 20% indicating "better" (some PPE needs addressed). Utilization and type of telemedicine services varied. Respondents noted using the following options for the majority of their telemedicine visits (multiple responses possible): electronic health record (EHR) integrated (26%), non–EHR integrated (27%), patient registration based (19%), commercial Centers for Medicare and Medicaid Services–allowed third party (eg, Zoom or Skype, 18%), audio only (18%), or asynchronous (ie, online patient portal or e-mail, 11%). Respondents cited multiple barriers that contributed to limited utilization of telemedicine. When asked about converting in-person to telemedicine visits, 324 respondents indicated significant difficulty ("extremely difficult," "very difficult," or "difficult") related to commercial payer reimbursement (53%), patient engagement/interest and ability to participate (50%), technology or equipment (48%), Medicare reimbursement (45%), and interstate regulations on health care delivery (39%). In response to the COVID-19 pandemic, the AGA spearheaded several initiatives to address the immediate needs of gastroenterologists. First, members of the Clinical Guidelines Committee and the Clinical Practice Update Committees convened to form the Rapid Review Working Group for COVID-19 to develop evidence-based recommendations to guide the use of PPE and preprocedure COVID-19 testing for endoscopic procedures.1Sultan S. Lim J. Altayar O. et al.AGA rapid recommendations for gastrointestinal procedures during the COVID-19 pandemic.Gastroenterology. 2020; 159: 739-758Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar, 2Sultan S. Altayar O. Siddique S.M. et al.AGA Institute rapid review of the gastrointestinal and liver manifestations of COVID-19, meta-analysis of international data, and recommendations for the consultative management of patients with COVID-19.Gastroenterology. 2020; 159: 320-334Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar, 3Sultan S. Siddique S.M. Altayar O. et al.AGA Institute rapid review and recommendations on the role of pre-procedure SARS-CoV-2 testing and endoscopy.Gastroenterology. 2020; 159: 1935-1948Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The AGA used rigorous GRADE methodology and systematic reviews to state a much stronger position to show the potential benefits and harms of policies on patient care. This allowed the AGA to use the working group's guidance to advocate more effectively for resources on Capitol Hill. Second, the AGA engaged in virtual member outreach to better understand the concerns and barriers for gastroenterology practices and members affected by the pandemic. These most frequently took the form of presidential town hall meetings where AGA leaders engaged members to hear about their challenges with practice finances, resumption of endoscopy, and timely provision of patient care. These stories provided our members of Congress with concrete examples of how their constituents were affected by the pandemic and further supported our requests for additional resources. Third, the AGA advanced existing gastroenterology advocacy priorities within COVID-19 advocacy efforts. One such effort succeeded in the incorporation of legislation to close the Medicare colonoscopy loophole within COVID-19 relief legislation. The fix to the loophole will be implemented in 2022 and will gradually phase out the coinsurance for Medicare beneficiaries by 2030. AGA also advocated for HR 7077/S 3877, the Community Solutions for COVID–19 Act, to improve access to testing and treatment for minority communities that have been disproportionately affected by the pandemic. This legislation aligned with the AGA's Equity Project, a broader multiyear effort to use advocacy to eliminate health disparities in GI care.4Carr R.M. Quezada S.M. Gangarosa et al.From intention to action: operationalizing AGA diversity policy to combat racism and health disparities in gastroenterology.Gastroenterology. 2020; 159: 1637-1647Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Although this bill was not specific to gastroenterology, it was an important step toward reducing health disparities for our patients and improving overall patient care. AGA members increased their engagement as a result of the organization's focus on pandemic-related policy. Through the online AGA Advocacy Center, members sent a record number of letters to their members of Congress: 1296 letters by 364 members regarding reimbursement cuts and 3047 letters by 944 members regarding COVID-19 relief. The outreach made by AGA members was instrumental to achieving success in our legislative endeavors. The response to COVID-19 also bolstered existing advocacy programs, including 84% growth in the AGA Congressional Advocates Program (CAP). The CAP was reestablished in 2018 and is a grassroots civic engagement program for AGA members to learn about GI-related advocacy, engage with their peers, and foster relationships with local representatives. In addition, AGA's September Advocacy Day went virtual in 2020, leading to a record turnout of 75 members conducting 76 meetings with members of Congress from 26 states. Similarly, a record number of AGA members joined cardiologists, rheumatologists, and other specialists in the Alliance of Subspecialty Medicine's Virtual Advocacy Day in November 2020. Finally, AGA members also increased engagement via the AGA Political Action Committee (PAC). AGA PAC is the voluntary bipartisan political arm of AGA and the only PAC dedicated to gastroenterology, supporting candidates who align with our public policy priorities, such as access to care, fair reimbursement, and National Institutes of Health research. The AGA supported a number of legislative and regulatory initiatives in 2020, directly addressing COVID-19 and continuing to support ongoing GI priorities. The legislative agenda related to the COVID-19 pandemic is presented in Table 1.Table 1Legislative Agenda for COVID-19 ReliefTopicIssueLegislative or Regulatory SolutionCurrent StatusFinancial reliefAGA members faced financial burdens during the pandemic, with 70% of members indicating that they would be financially unhealthy and 41% that they would need to downsize without reliefExpand financial relief programs for providers, such as the Provider Relief Fund, Paycheck Protection Program, and Medicare Accelerated and Advanced Payment ProgramAdditional flexibilities have been enacted to ease provider access to relief.Supplementary funding for the Paycheck Protection Program, Provider Relief Fund, and other federal loan programs has been secured.Continue to advocate for a steady stream of funding for relief programs to ensure practices and providers remain viable.TelehealthIncreased use for telehealth is important for access to patient care and ongoing medical services during the pandemicSupport HR 6644, which expands telehealth beyond the pandemic and requires ERISA plans to reimburse at Medicare's rates.CMS to continue payment parity for audio-only telehealth.Secured Medicare payment parity for audio-only E/M visits.Continue to work with policy makers and payers to reimburse for telehealth services at the same payment rate after the public health emergency.ReimbursementGI practices are struggling financially during the pandemic. However, proposed changes to RVU allocation projected that GIs would face 4% cuts in reimbursement.Congress should intervene to prevent cuts to physicians in 2021Congress mitigated 10% across-the-board budget neutrality cuts for 2021. For most clinicians, Congressional action greatly reduced the cuts. For GIs, the 4% cut that was expected was largely negated. However, the exact impact depends on the diversity of services offered by a practice.Next steps are to halt 4% PAYGO cuts set to go in effect October 1, 2021.Provider reliefGIs, like other physicians, have been deployed to serve on the front lines of the COVID-19 pandemicExpand medical liability protections for health care workers treating COVID-19 patients (HR 7059).Provide flexibility for foreign-born physicians to continue to practice in the US and maintain the workforce (HR 2895/S 948, HR 6788/S 3599).Support health care workerss by providing loan forgiveness (HR 6720).Congress added 2000 additional GME slots as part of the omnibus/supplemental bill that was passed at the end of 2020. This was the first time since 1997 that GME has been increased.Continue to advocate for these policies that reduce regulatory, financial, and institutional burdens placed on health care professionals during the public health emergency.Digestive disease and cancer researchResearch facilities have had to halt research because of the pandemic and relief is needed to resume cutting-edge researchInclude $15.5 billion in supplemental funding to NIH to support COVID-19 research and research that was disrupted due to the pandemicAdvocated for supplemental funding to be included in the Biden administration's stimulus legislation: status pendingCMS, Centers for Medicare and Medicaid Services; E/M, evaluation and management; ERISA, Employee Retirement Income Security Act; GME, graduate medical education; NIH, National Institutes of Health; RVU, relative value units. Open table in a new tab CMS, Centers for Medicare and Medicaid Services; E/M, evaluation and management; ERISA, Employee Retirement Income Security Act; GME, graduate medical education; NIH, National Institutes of Health; RVU, relative value units. Efforts included supporting CMS' payment parity for audio-only telehealth visits, supporting HR 6720 (Student Loan Forgiveness for Frontline Health Workers Act), and delaying the proposed 5% cut to Medicare physician payments for 2021. The AGA championed the Removing Barriers to Colorectal Cancer Screening Act, which removed the cost-sharing burden associated with polypectomy during screening colonoscopy and was ultimately incorporated within the successful passing of the Consolidated Appropriations Act. The AGA continued advocacy for the successful increase in federal funding for GI research at the National Institutes of Health and the Department of Defense. It also supported reform of the Stark Law and Antikickback Statute at the Department of Health and Human Services and reform of the prior authorization process by assisting in the introduction of bills in both the House and the Senate. The AGA Government Affairs committee continues to work closely with AGA members on how best to support the pandemic response and recovery efforts. For example, the AGA endorses the Building COVID-19 Vaccine Confidence Act and the COVID-19 Prevention and Awareness Act of 2021. These bills fund vaccine promotion efforts among vulnerable populations and those at increased risk for COVID-19–related complications, including people with liver disease or those using immune-modifying medications. The new year and presidential administration have wrought several changes that the AGA continues to track. These include a new open enrollment period for health insurance exchanges to support people who are uninsured or have lost employer-sponsored coverage and extending regulations allowing telehealth services for all Medicare patients. The AGA supports efforts to make access to vital care and technology services permanently available for patients and practices. Later this year, the Supreme Court is expected to rule on whether the Affordable Care Act is constitutional. The AGA will advocate for legal provisions to ensure access to specialty care, colon cancer screening, and protections for people with preexisting conditions. Finally, the AGA will support programs anticipated in the next stimulus package that support small businesses that have benefited AGA members previously. The public health emergency has prompted the AGA to reevaluate its processes and develop new methods to rapidly meet the needs of its members. This adaptability is important to codify for future crises, which could similarly result in major changes in the health care landscape and pose a significant threat to gastroenterology practices and care of patients with digestive disease. The lessons learned from the COVID-19 experience to date have demonstrated the importance of the key steps below, which are also summarized in Figure 2.1.Conduct members' needs assessments. These should be performed routinely and iteratively. They can take the form of membership surveys that allow for quantitative analysis, as well as open discussion on the AGA community or during webinars and town hall meetings for more qualitative and narrative feedback. As public health emergencies evolve, the concerns and needs of our members will change, so it is important for assessments to be conducted on an ongoing basis. This will allow us to ensure that advocacy efforts and legislative development remain in pace with members' needs.2.Employ a collaborative approach. As new areas of interest emerge within the AGA in response to evolving crises, working groups and task forces will emerge to address new areas of interest. Advocacy efforts should utilize developing AGA efforts to work collaboratively on legislative action items that can improve patient care. Similarly, a collaborative approach with other specialties who face similar barriers to practice is important. The AGA's close relationships with sister GI societies, physician organizations, and other health advocacy groups remain vital in staying up to date on the latest movements on Capitol Hill and provide opportunities to act on shared priorities.3.Engage members in advocacy. Members of Congress are much more likely to take action on legislation if a constituent meets with them or contacts them directly. When urgent legislative action is needed, the AGA should continue to encourage member engagement through the Congressional Advocates Program and other existing structures, including Advocacy Day and the PAC. To initially address the COVID-19 pandemic, the AGA adjusted its priorities based on both data-driven and qualitative feedback from its members. This resulted in the development of pragmatic clinical resources, increased member engagement through virtual technology, and the advancement of new and existing advocacy priorities. In addition, by continuing to strengthen member-based advocacy, the AGA helped secure tangible COVID-19 and GI-focused legislative and regulatory successes. Because the COVID-19 pandemic continues to present challenges for GI physicians and their patients, the AGA is committed to continuing its engagement with members for input, collaboration with other key stakeholders, and support of advocacy efforts. We are optimistic that by continuing to develop this approach, the AGA will continue to support its members and the patients they serve in any future disruptions in care.

BACKGROUND AND AIMS Poor sleep quality in Crohn's disease (CD) is associated with histologic activity and clinical relapse. We sought to characterize sleep dysfunction and determine the effect of poor sleep quality on risk for hospitalization and surgery. METHODS Clinical data were collected for CD subjects including the Pittsburgh Sleep Quality Index (PSQI) and Harvey-Bradshaw index (HBI). The PSQI score and a brief medical history were obtained for control subjects. The PSQI and HBI correlation was tested at an initial clinic visit and at follow-up. Crohn's disease subjects with and without poor sleep were compared for risk of hospitalization or surgery by Kaplan-Meier and Cox proportional hazards. RESULTS Ninety-two CD and 82 control subjects were included. Crohn's disease and control subjects shared similar baseline characteristics and PSQI (8.3 vs 7.8, P = 0.31), and 77% of the CD population had PSQI >5. Crohn's disease subjects with PSQI >5 more often had inflammatory phenotypes and reported increased benzodiazepine and psychiatric medication use. Crohn's disease subjects with PSQI >5 also reported more night awakenings due to pain and bathroom use. The PSQI correlated with HBI (r = 0.256, P = 0.014), and ΔPSQI on follow-up correlated with ΔHBI (r = 0.47, P = 0.002). Cox proportional hazards model for hospitalization or surgery showed that PSQI >8 was predictive of surgery or hospitalization (hazards ratio 5.37; 95% confidence interval, 1.39-27.54). CONCLUSION There is a high burden of poor sleep quality in CD, which is associated with risk for adverse outcomes. Sleep quality may identify CD patients at risk for complications and have prognostic value in CD.

anastomosis in 3%.Median total QWLQ score was 71 , and the subscale 'problems due to the health situation' showed the lowest median score .QWLQ showed adequate convergent validity with SIBDQ (r=0.70,p<0.001),EQ-5D-5L (r= 0.47, p<0.001) and MFI (r=-0.48,p<0.001).Lower median QWLQ scores were found in patients with active disease (53 versus 83, p<0.001) and in patients who reported work impairment due to their disease (56 versus 86, p<0.001).QWLQ scores were not significantly different in CD versus UC patients (72 versus 70, p=0.58).Conclusion: Convergent validity of the QWLQ was adequate and supported by correlations with validated quality of life and fatigue questionnaires in IBD patients.Active disease and work impairment due to IBD were associated with lower QWLQ scores.QWLQ could potentially be used to identify patients who might benefit from specific support programs to improve their work ability. Mo1828

Background and Aims: When colon polyps are removed in the setting of inflammatory bowel disease (IBD) involving the large intestine, biopsy sampling of the flat mucosa surrounding such polyps have been recommended, but there are no data to support this practice. Methods: We reviewed endoscopic and pathologic findings in IBD patients who had dysplastic polyps removed and biopsy sampling of the adjacent flat mucosa. We assessed risk for subsequent neoplasia based on the presence or absence of dysplasia in the peri-polyp flat mucosa and based on number and grade of index polypoid lesions. Kaplan-Meier survival analysis was performed. Results: Fifty-six IBD patients (68% ulcerative colitis [UC]) underwent 102 colonoscopies, in which 129 dysplastic polyps were resected. Five hundred three biopsy procedures of the surrounding flat mucosa were performed (mean, 3.9 biopsy samples per polyp), of which 16 (3.2%) were dysplastic. Thirty-four patients (21 UC) had follow-up in a median of 1.7 years (range,.02-15) and 147 colonoscopies. The presence of dysplasia in peri-polyp biopsy specimens during index colonoscopy was not associated with risk of developing high-grade dysplasia (HGD) or cancer (Pearson chi(2) test = .19). The size and number of dysplastic polyps were not predictive of neoplastic outcomes, but the probability of developing subsequent advanced neoplasia for polypoid low-grade dysplasia was 18%, 29%, and 40% by 1, 3, and 5 years, respectively, and for polypoid HGD was 50%, 60%, and 70% by 1, 3, and 5 years, respectively (hazard ratio, 7.0; standard error, 4.8). Conclusions: In patients with IBD-associated colitis, biopsy sampling of the mucosa adjacent to discrete dysplastic polypoid lesions are low yield and do not predict findings in follow-up examinations. However, the grade of dysplasia of the polyp itself is predictive of subsequent advanced neoplasia.

Background: Sleep quality is frequently disturbed in patients with inflammatory bowel disease (IBD).Sleep physiology and IBD pathophysiology involve overlapping immunologic and cell signaling relationships.While active IBD promotes poor sleep, prior studies showed that poor sleep can predict clinical relapse.We investigated whether poor sleep quality is a risk factor for hospitalization or surgery in Crohn's disease (CD).Methods: We performed a cross-sectional study of adult patients with CD recruited from an ambulatory clinic in a tertiary care IBD center.Study subjects completed a questionnaire that included the validated Pittsburgh Sleep Quality Index (PSQI)."Poor sleep" was defined as a PSQI score >8.Clinical disease activity was simultaneously measured by Harvey-Bradshaw Index (HBI) with "clinical remission" defined as HBI <5.Additional data extracted from the medical records included medical history, medications, and demographics.The subjects were followed until inpatient admission for CD activity or CD related surgery.A multivariate Cox regression was performed to determine risk factors for the combined outcome of hospitalization or surgery.Results: 92 patients were followed over a mean of 258 days.While similar in baseline characteristics for age, sex, BMI, and smoking status, patients with poor sleep quality had significantly higher HBI scores at baseline (table 1).A multivariate Cox regression (table 2) including, "poor sleep", current steroid use, current smoking, any prior surgery, "clinical remission", body mass index, age, alcohol use, and female sex showed that "poor sleep" (HR 5.37, 95% CI 1.39 -27.54) and current steroid use (HR 4.31,) portended increased risk for hospitalization or surgery (table 2).Female sex conferred a lower risk for the outcome (HR 0.28, 95% CI 0.07 -0.94).Conclusion: Poor sleep quality measured by the PSQI is a risk factor for hospitalization or surgery in Crohn's disease, independent of clinical disease activity.Sleep quality may represent a modifiable risk factor for disease complications, and present an opportunity for further individualizing clinical management of patients with CD.

Wearable activity monitors allow individuals to track physical characteristics, including sleep patterns. Sleep dysfunction in inflammatory bowel disease (IBD) is associated with inflammatory activity and risk for clinical disease relapse. Passive measurement of sleep by a wearable device can identify patterns of sleep dysfunction. We investigated whether remotely measured sleep quality by a wearable device is associated with clinical disease activity. Patients with Crohn’s disease (CD) or ulcerative colitis (UC) were recruited from an ambulatory clinic at a tertiary care IBD centre. Medical history was collected from medical records. Each patient received a Fitbit Charge HR (San Francisco, CA) and a smart phone application. Data from the devices included “sleep fragmentation”, awakening events per hour in bed, “restlessness”, restless events per hour in bed, and “sleep efficiency”, time sleeping divided by time in bed. The average of up to seven days of data was then calculated. “Clinically active” was defined as Harvey-Bradshaw Index of > 4 for CD or Simple Clinical Colitis Activity Index of 1 for UC. Each parameter was compared between disease states, then logistic regression for the outcome of clinically active disease. Multivariate analysis included age, sex, diagnosis, and comorbid sleep disorder with each sleep parameter. 38 patients (26 CD, 12 UC) were followed for an average of 8.87 nights. There were no significant differences between CD and UC for age, male sex, or clinically active disease, though there was a difference in the presence of comorbid sleep disorders (Table 1). Baseline characteristics and sleep parameters. A change in average sleep fragmentation by 0.1 was not predictive of clinically active disease in the univariate model, but was predictive in the multivariate model (OR 1.78 (95% CI 1.004–3.11), p = 0.02) (Table 2). Multivariate logistic regression for clinically active disease. While restlessness (OR 1.14 (95% CI 0.34–3.82), p = 0.82) and sleep efficiency (OR 0.019 (95% CI 8x10–5–4.41), p = 0.14) were not predictive. Worse sleep fragmentation measured by a wearable activity tracking device is associated with increased odds of clinical disease activity in IBD. Changes in sleep fragmentation patterns may have utility in a remote patient monitoring system as an early indicator of clinical disease activity.

Introduction The use of cyclosporine (CyA) as rescue therapy for patients with acute severe ulcerative colitis (ASUC) who fail IV steroids is well established. Traditionally, this treatment is followed by maintenance therapy with thiopurines. Tofacitinib is an oral Janus Kinase inhibitor that was recently approved as a first class drug for the treatment of moderate to severe ulcerative colitis (UC). We describe the use of tofacitinib as maintenance therapy after induction with CyA for a patient with ASUC. Case presentation We describe a case of a 26-year-old man with a history of pan-colitis UC diagnosed in 2014. His past medical history is also significant for primary sclerosing cholangitis (PSC) and autoimmune hepatitis. He had previously failed therapy with mesalamine and vedolizumab. When he presented to our center, he was on infliximab (10mg/kg) every 4 weeks, azathioprine and allopurinol. He was unable to be weaned off steroids and continued to have up to 10 bowel movements daily with urgency and hematochezia. In addition, he suffered from steroid-related adverse effects, including vertebral fractures and central adiposity. Stool was positive for infection with C. difficile and Campylobacter, so he was treated with antibiotics. Due to severe medically-refractory colitis in the setting of a high steroid burden, he was admitted and treatment with IV CyA was started for induction of remission. By day 9, the patient achieved clinical remission and was later discharged on oral CyA as well as azathioprine, hydrocortisone enemas and prednisone 10 mg/day. After 8 weeks of therapy, he was still in clinical remission with normal CRP. CyA and azathioprine were stopped, and he was started on tofacitinib 10 mg BID. Prednisone (5 mg/day) was later weaned off. At his last follow-up visit after 23 weeks on tofacitinib, the patient was still in steroid-free remission. Discussion Despite an expanding choice of agents, the number of maintenance therapy options for patients recovering from ASUC remains limited. Tofacitinib has demonstrated a significant efficacy in patients with severe colitis, including the challenging group of patients resistant to prior therapies. This makes the combination with CyA as a bridging therapy for ASUC very appealing. This is the first demonstration of the effectiveness and safety of this novel combination.

Current evidence suggests the etiology of inflammatory bowel diseases (IBD) involves the confluence of host genetic, environmental, and microbial factors that lead to chronic, and often refractory, disease in susceptible individuals. The involvement of microbial triggers in IBD, including Crohn's disease (CD), is increasingly evident with supporting data provided with advancements in metagenomic sequencing that have identified perturbations in microbial structure and function-broadly termed dysbiosis-in CD patients compared with healthy subjects. This concept is supported by the finding germ-free animals with CD genetic susceptibility fail to develop disease; demonstrating microorganisms are necessary but not sufficient for CD. The vast majority of CD microbiome research has focused on the complex bacterial communities and microbiome dysbiosis in the gut with 16S metagenomic sequencing. However, emerging data capturing eukaryotes suggest fungal opportunistic pathogens are also associated with IBD pathogenesis and chronicity. This hypothesis is further supported by historical observations that CD patient populations display elevated antibodies against fungal targets, even evident before disease diagnosis. This review discusses the current findings in the field, followed by historical and metagenomic evidence for fungal pathogens in the development and recurrence of CD in adult and pediatric populations.

Sleep quality is frequently disturbed in patients with inflammatory bowel disease (IBD). Sleep physiology and IBD pathophysiology involve overlapping immunologic and cell signalling relationships. While active IBD promotes poor sleep, prior studies showed that poor sleep can predict clinical relapse. We investigated whether poor sleep quality is a risk factor for hospitalisation or surgery in Crohn's disease (CD). We performed a cross-sectional study of adult patients with CD recruited from an ambulatory clinic in a tertiary care IBD centre. Study subjects completed a questionnaire that included the validated Pittsburgh Sleep Quality Index (PSQI). "Poor sleep" was defined as a PSQI score >8. Clinical disease activity was simultaneously measured by Harvey-Bradshaw Index (HBI) with "clinical remission" defined as HBI <5. Additional data extracted from the medical records included medical history, medications, and demographics. The subjects were followed until inpatient admission for CD activity or CD-related surgery. A multivariate Cox regression was performed to determine risk factors for the combined outcome of hospitalisation or surgery. 92 patients were followed over a mean of 258 days. While similar in baseline characteristics for age, sex, BMI, and smoking status, patients with poor sleep quality had significantly higher HBI scores at baseline. Baseline characteristics of patients by sleep quality. Poor sleep quality was defined as a Pittsburg Sleep Quality Index score of greater than 8. Pittsburg Sleep Quality Index = PSQI, Body Mass Index = BMI, Harvey-Bradshaw Index = HBI. Prognostic factors associated with Crohn's disease-related hospitalisation or surgery. Pittsburg Sleep Quality Index = PSQI, Body Mass Index = BMI, Harvey-Bradshaw Index = HBI) A multivariate Cox regression including, "poor sleep", current steroid use, current smoking, any prior surgery, "clinical remission", body mass index, age, alcohol use, and female sex showed that "poor sleep" (HR 5.37, 95% CI 1.39 – 27.54) and current steroid use (HR 4.31, 95% CI 1.15 – 16.50) portended increased risk for hospitalisation or surgery. Female sex conferred a lower risk for the outcome (HR 0.28, 95% CI 0.07 – 0.94). Poor sleep quality measured by the PSQI is a risk factor for hospitalisation or surgery in Crohn's disease, independent of clinical disease activity. Sleep quality may represent a modifiable risk factor for disease complications, and present an opportunity for further individualising clinical management of patients with CD.

Background and Aims: Mucosal appearance on endoscopy is an important indicator of inflammatory burden and determines prognosis in ulcerative colitis (UC). Inflammation induces tryptophan metabolism along the kynurenine pathway (KP) and yields immunologically relevant metabolites. We sought to examine whether changes in serum tryptophan metabolites and tissue expression of KP enzymes are associated with UC endoscopic and histologic disease severity. Methods: Serum and mucosal samples were prospectively obtained at colonoscopy in patients with UC. Mayo disease activity scores, demographics, smoking status, medications, and outcomes were collected. Serum tryptophan metabolites were analyzed using ultra-high performance liquid chromatography (uHPLC), and gas chromatography-mass spectrometry (GC-MS), and enzyme expression was determined by quantitative real-time polymerase chain reaction. Metabolite and enzyme levels were compared by endoscopic subscore, clinical disease activity, time to surgery, and hospitalization. Results: This study included 99 patients with Mayo endoscopic subscores 0-3. Kynurenic acid/tryptophan ratio (KYNA/T) and expression of indolamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase, kynurinase, and kynurenine monooxygenase correlated positively with endoscopic subscore. Adjusting for age of diagnosis, smoking status, disease extent, and medications yielded significant odds of endoscopic inflammation with increasing KYNA/T (OR 1.0015, P = 0.0186) and IDO1 expression (OR 1.0635, P = 0.0215). The highest tertile ratio of KYNA/T had shorter time to surgery (P = 0.009) and hospitalization (P = 0.01) than the lowest. Conclusions: Increasing KYNA/T is closely associated with endoscopic inflammation and predictive of disease outcomes in patients with UC. These findings identify this novel metabolic association and further support the role of the KP in regulating mucosal inflammation in UC.

Background: Patients with Crohn's disease (CD) commonly report symptoms of heartburn, however the prevalence, predisposing factors, and relationship between heartburn and CD are not known. We assessed the prevalence of heartburn in patients with CD and investigated the association between gastro-oesophageal reflux disease (GORD) and CD manifestations, treatment, and sleep quality. Methods: We recruited patients (pts) with CD from an ambulatory clinic at a tertiary care inflammatory bowel disease center. Pts completed a survey that included the validated GORD Health Related Quality of Life (GORD-HRQL) instrument and Pittsburgh Sleep Quality Index (PSQI). We abstracted clinical data from medical records including medical history, CD classification, medications, and Harvey-Bradshaw Index (HBI). Simple statistical analysis was performed for univariate associations, followed by multivariate logistic regression analysis. Results: 111 pts with CD were included in the analysis. The mean age was 42 years, mean body mass index (BMI) was 26.31, and the population was 60.4% female. The most common Montreal classification was A2 (59.5%), L3 (55.0%, 9.9% L4), and B1 (50.5%). 63.9% of pts with CD reported heartburn. Pts with and without heartburn were of similar age, sex, smoking status, location of disease, and disease behavior. Pts with heartburn had a higher mean BMI and less frequent alcohol use (Table 1). Female sex (OR 3.06 (95% CI 1.18–7.90), p=0.02), BMI (OR 1.12 (1.03–1.22), p=0.01), alcohol use (OR 0.47 (0.24–0.90), p=0.02), current steroid use (OR 3.70 (1.17–11.67), p=0.03), and history of ileocecectomy (IC) (OR 4.27 (1.41–12.89), p=0.01) were associated with heartburn (Table 2). Pts with heartburn reported less satisfaction with their current condition (p=0.005), worse sleep (PSQI mean 7.35 v. 4.63, p<0.001), and higher mean HBI (2.54 v. 1.20, p=0.017). Pts within 5 years of IC had a similar rate of heartburn as those whose surgery was more than five years prior, but of less severity (GORD-HRQL 4.30 v. 12.05, p=0.02). Table 1. Characteristics of patients reporting heartburn symptoms compared to patients that do not report heartburn symptoms Table 2. Multivariate analysis of factors to predict the presence of heartburn symptoms in Crohn's disease determined by logistic regression OR = Odds Ratio; CI = Confidence Interval. Conclusions: Heartburn in CD is associated with poor sleep quality and increased disease activity. In addition, we newly identified prior IC as a risk factor for heartburn in CD, which may reflect motility alterations due to surgery or fibrosis in these pts. Further investigation into heartburn in CD pts and its management is warranted.

The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a lack of dense granules in platelets. HPS types 1 and 4 are associated with a granulomatous enterocolitis that is phenotypically indistinguishable from Crohn's disease. We present two cases of HPS-associated Crohn's disease phenotype in which the patients were refractory to standard medical management. The pathophysiology of HPS is mediated by single-gene defects that alter endosome trafficking, and we hypothesize that this mechanism leads to the observed association with a CD phenotype.