Faculty Bibliography

BACKGROUND: Infliximab and ustekinumab are used to treat Crohn's disease (CD). Neurologic side effects have rarely been described with either agent.We report a case of a 75-year-old female with fibromyalgia and inflammatory bowel disease with subsequent development of sporadic Creutzfeldt- Jakob disease (sCJD) after initiation of biologic therapy. CASE: The patient was diagnosed with ulcerative colitis (UC) in 1992 and treated with 5-ASA, 6- MP, and steroids. She stopped medication shortly thereafter but symptoms returned in November 2016 requiring hospitalization. She was treated with IV steroids, but transitioned to infliximab due to suboptimal response. In February 2017, she exhibited flushing, dizziness, and muscle spasms after an infusion. Infliximab antibody levels were >'100 U/mL. Prior to transitioning therapies, a colonoscopy was performed and noted improved colitis, but biopsies showed granulomas and her diagnosis was changed to CD. A CT enterography revealed disease limited to the colon. A plan to treat the patient with ustekinumab was made in July 2017. Of note, during several office visits, the patient demonstrated hand tremor, imbalance, and widened gait she believed to have started around the time of her adverse reaction to infliximab in February 2017. The symptoms were initially thought to be related to steroid exposure, however tapering of steroids did not lead to improvement. Despite many attempts, the patient declined neurological evaluation. The symptoms worsened throughout the duration of ustekinumab therapy, and in February 2018, the patient sustained a left distal radius fracture after a fall. She agreed to a neurological evaluation in May 2018 and was found to have several focal cerebellar deficits. EEG was nonspecific. Brain MRI was notable for symmetrically increased signal within the caudate nucleus, putamen, and thalami, and prominent ventricles compatible with cerebral and cerebellar volume loss-findings suggestive of sCJD. A lumbar puncture revealed normal 14-3-3 protein in the CSF, but real-time quaking induced conversion was found to be positive. Following a goals of care discussion the patient was transitioned to home hospice. DISCUSSION: Trials demonstrating the efficacy of infliximab report an excellent safety profile, with rare reports of neurologic side effects. These include optic neuritis, confusion, paresthesias, and gait instability thought to be due to TNF-a blockade leading to extensive demyelination throughout the central and peripheral nervous system. Trials demonstrating the efficacy of ustekinumab also report a positive safety profile with rare neurologic side effects. We found 4 case reports of severe neurologic diseases including one case of primary progressive multiple sclerosis, amyotrophic lateral sclerosis, and 2 cases of reversible posterior leukoencephalopathy syndrome throughout treatment. These occurred in patients receiving treatment doses for either psoriasis or CD. To our knowledge, there have been no preceding case reports of sCJD development following either infliximab or ustekinumab. With respect to the onset of sCJD in our reported case, the temporal onset of symptoms succeeding the patient's infusion reaction to infliximab and commencement of ustekinumab therapy does raise the possibility of an association, however it may be a mere coincidence. Further research into the possible long-term neurologic effects of infliximab and ustekinumab is warranted

Background/UNASSIGNED:Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy. Methods/UNASSIGNED:This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days. Results/UNASSIGNED:A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55). Conclusions/UNASSIGNED:Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI.

Background: Te Accreditation Council for Graduate Medical Education (ACGME) has identifed six core competencies in which trainees are expected to demonstrate profciency. Milestones have been developed to provide a framework for evaluating trainee performance within these competencies. We used an objective structured clinical examination (OSCE) focused on inflammatory bowel disease (IBD) to assess the milestones in gastroenterology (GI) fellows. METHODS: Ten second-year fellows from six GI fellowship programs participated in a four case OSCE. In the "Transition of CareTM case the fellow was to assess a patient's readiness on the planned transition from child-centered to adult-centered care. In the "Shared Decision MakingTM case the fellow was to evaluate a patient with Crohn's disease who would beneft from combination therapy. In the "ER FlareTM case the fellow was to triage and suggest management of a flaring ulcerative colitis patient. In the "IBS in IBDTM case the fellow was asked to discuss irritable bowel syndrome in the context of quiescent IBD. Previously validated OSCE checklists were used to assess the GI fellows' performance using a 3-and 5-point behaviorally-anchored Likert Scale. Checklists were scored by the standardized patient. Checklist items were mapped to appropriate ACGME milestones by a GI medical educator. Scores within each milestone were normalized on a scale from 0-9 as utilized by the ACGME in the Next Accreditation System milestone initiative. Fellows were provided feedback on their performance. RESULTS: Te majority of fellows scored between 6 and 9 in the milestones assessing patient care (PC), medical knowledge (MK), interpersonal and communication skills (ICS), professionalism (Prof), and systems-based practice (SBP). Composite average scores for all participants were as follows: PC1 7. 7, PC2 6. 9, MK1 6. 9, MK2 7. 0, ICS1 7. 4, Prof1 7. 6, Prof3 6. 9, and SBP4 6. 4. Fellows scored highest in the "Shared Decision MakingTM case and scored lowest in the "Transitions of CareTM case. CONCLUSION(S): In this OSCE GI fellows performed well in the majority of milestones evaluated, however areas of less optimal performance were identifed, providing areas for future focus in fellow training. Te OSCE is a well-validated standardized tool for evaluating trainees, and with appropriate mapping of checklists to ACGME milestones, it can serve as an objective method to assess GI fellows' progress in the core competencies

Background: Nearly one-half of Crohn's disease patients require bowel resection within the frst 10 years of disease (1). Small bowel obstruction (SBO) is the most common indication for surgery in Crohn's patients, followed by abscess and presence of fstulizing disease (2). Tere are little data regarding pharmacologic treatment of Crohn's-associated SBO with corticosteroids. In particular, the safety and efcacy of corticosteroids in treating inflammation in the setting of acute Crohn's SBO remains unclear. METHODS: Our group performed a retrospective chart review of patients admitted with Crohn's-disease associated SBO to our institution. Key variables examined included use of corticosteroids, length of stay, infectious complications, and short-term requirement for surgery. Inclusion criteria included adults (>18 years) who were not pregnant and carried a known diagnosis of Crohn's disease. Using the i2b2 search engine, patients admitted with the ICD10 diagnoses for Crohn's disease and a primary diagnosis of SBO were included. Analysis of outcomes was performed comparing patients who received steroids versus those who did not using t-statistics and chi-square analysis. RESULTS: Between 2015 and 2017, ffy-seven patients met inclusion criteria. Te majority (n=32, 56%) received no corticosteroids for the preceding three months nor during the admission for SBO, while the minority (n=25, 44%) did receive steroids. Te mean age of patients (45+/-19 years vs 46+/-18 years, P=0.92), and duration of Crohn's disease (14+/-13 years vs 14+/-12 years, P=0.93) did not differ between groups. C-reactive peptide (CRP) on admission did not differ between groups (23.9+/-17 vs 46.6+/-78, P=0.49). Eleven patients (19%) required surgery related to Crohn's disease during or within the three months following admission. Tere was no difference in requirement for surgery between groups. In multivariable logistic regression, the only factor associated with requirement for surgery was duration of Crohn's disease (P<0.05). Tere was no difference in duration of nasogastric tube placement, time to PO challenge, or length of hospital stay. Tere were no mortalities in either group and no difference in infectious complications afer discharge. CONCLUSION(S): Tese results suggest that corticosteroids are not associated with improved outcomes in patients with Crohn's associated SBO. Length of stay is not decreased due to use of corticosteroids. Te study is limited by its retrospective design and small sample size. However, future case-control or randomized clinical trials can examine the use of corticosteroids during acute Crohn's-associated SBO

Background: Patients with inflammatory bowel disease (IBD) have many unique health maintenance needs and ofen require therapy necessitating close monitoring. Gastroenterologists ofen serve as the primary care provider for these patients and therefore must be familiar with the health maintenance needs of IBD patients. In this study, we investigated whether implementing a multi-modal educational intervention could improve providers' rates of addressing healthcare maintenance measures. METHODS: A retrospective chart review was performed in 2013-2014 on 208 IBD patients to determine adherence to performance practice measures. From February-April 2016, fellows received a recurring in-service lecture and an IBD clinic note template outlining the 2011 healthcare maintenance recommendations by the American Gastroenterological Association. An iBook was also introduced, which provided a comprehensive overview of IBD practice guidelines. Retrospective chart review was then performed 1 year aferwards. For each patient, performance measures were assessed in both pre-and post-intervention notes in the following categories: vaccinations, bone health, therapy-specifc maintenance, tobacco cessation, and cancer screening. Each performance measure was given a score of 0 (not addressed), 1 (addressed), or N/A (irrelevant to subject). Te primary outcome was improvement in rates of adherence to performance measures. Te adherence rates for pre-and post-intervention groups were compared using a chi-squared test. RESULTS: A total of 208 pre-intervention clinic visits and 40 post-intervention visits were included for analysis. Afer the interventions, the rate of healthcare maintenance measures addressed overall increased from 37% to 52% (P<.001) (Figure 1). Tere were statistically signifcant improvements in addressing bone health (29% to 63%, P<.001), vaccination (33% to 47%, P<.001), and therapy-specifc measures (53% to 74%, P=.01). Tere were no statistically signifcant changes in addressing cancer screening (66% to 58%, P=.19) or smoking (23% to 30%, P=.59). CONCLUSION(S): Te use of multiple educational interventions to enhance delivery of IBD healthcare maintenance resulted in improved adherence to healthcare maintenance measures. Targeted educational programs and a multi-modal approach may be an effective method for teaching GI fellows and reinforcing the importance of addressing these measures to optimize the care of their IBD patients

Patients with inflammatory bowel disease (IBD) are well known to be at increased risk of venous thromboembolism. Systemic thrombotic events are rare, but likely more common among IBD patients as well. We describe a case of Crohn's colitis complicated by spontaneous pulmonary vein thrombosis eventually resulting in systemic embolism and acute mesenteric ischemia. A 25-year-old female with stricturing Crohn's colitis presented to the emergency department with one week of back pain and pleuritic chest pain. She was initially diagnosed with Crohn's disease three years prior, when she presented with large bowel obstruction requiring emergent transverse colostomy. Infliximab was begun after surgery, and she achieved complete clinical remission. She continued to feel well until the present illness. Upon hospital admission, a computed tomography (CT) scan revealed multiple right sided pulmonary emboli as well as a large pulmonary vein thrombus extending into the left atrium. Echocardiogram revealed no evidence of right heart strain. Anticoagulation was initiated with unfractionated heparin, and the patient was eventually transitioned to apixaban. On the evening prior to anticipated discharge, she developed sudden onset fever and epigastric pain. A CT scan of the abdomen revealed acute thrombosis of the superior mesenteric artery. The patient underwent emergent laparotomy with thrombectomy, initially without small bowel resection. Subsequent second-look laparotomy revealed 75cm of ischemic small bowel, which was resected. The patient continued to have fever and abdominal pain, however, and further exploration revealed necrosis of the entire remaining small bowel, which was resected leaving only a duodenal stump. The patient was eventually transferred to another center for consideration of intestinal transplant. Pulmonary vein thrombosis is an extremely rare condition usually precipitated by intrathoracic neoplasm or thoracic surgery, particularly lung transplantation. There is an associated risk of pulmonary hypertension as well as systemic arterial embolization. To our knowledge, this is the first reported case of spontaneous pulmonary vein thrombosis with IBD as the inciting factor. Due to the risk of catastrophic complications from systemic embolism, rapid diagnosis and treatment are essential. Anticoagulation alone may not be sufficient in all cases, and thrombectomy may be considered if the thrombus does not resolve with medical management

Introduction: Patients with inflammatory bowel disease (IBD) have many unique health maintenance needs and often require therapy necessitating close monitoring. Gastroenterologists often serve as the primary care provider for these patients and therefore must be familiar with the health maintenance needs of IBD patients. In this study, we investigated whether implementing a multimodal educational intervention could improve providers' rates of addressing healthcare maintenance measures. Methods: A retrospective chart review was performed in 2013-2014 on 208 IBD patients to determine adherence to performance practice measures. From February-April 2016, fellows received a recurring in-service lecture and an IBD clinic note template outlining the 2011 healthcare maintenance recommendations by the American Gastroenterological Association. An iBook was also introduced, which provided a comprehensive overview of IBD practice guidelines. Retrospective chart review was then performed 1 year afterwards. For each patient, performance measures were assessed in both pre- and post-intervention notes in the following categories: vaccinations, bone health, therapy-specific maintenance, tobacco cessation counseling, and cancer screening. Each performance measure was given a score of 0 (not addressed), 1 (addressed), or N/A (irrelevant to subject). The primary outcome was improvement in rates of adherence to performance measures. The adherence rates for pre- and post-intervention groups were compared using a chi-squared test. Results: A total of 208 pre-intervention clinic visits and 40 post-intervention visits were included for analysis. After the interventions, the rate of healthcare maintenance measures addressed overall increased from 37% to 52% (p < .001) (Figure 1). There were statistically significant improvements in addressing bone health (29% to 63%, p < .001), vaccination (33% to 47%, p < .001), and therapy-specific measures (53% to 74%, p=.01). There were no statistically significant changes in addressing cancer screening (66% to 58%, p=.19) or smoking (23% to 30%, p=.59). Conclusion: The use of multiple educational interventions to enhance delivery of IBD healthcare maintenance resulted in improved adherence to healthcare maintenance measures. Targeted educational programs and a multi-modal approach may be an effective method for teaching GI fellows and reinforcing the importance of addressing these measures to optimize the care of their IBD patients