Crohn's Patients Research Articles

3158 Sacral Osteomyelitis Secondary to Crohn's Disease

INTRODUCTION: Increased ostomy output and abdominal pain can be concerning symptoms for patients with underlying gastrointestinal pathology such as Inflammatory Bowel Disease (IBD). While the acute etiology is often directly related to said underlying condition, alternative causes should remain on the differential diagnosis. The following is a case of sacral osteomyelitis as a result of direct extension from the gastrointestinal tract. CASE DESCRIPTION/METHODS: A 43 year old male with Crohn's disease complicated by recurrent fistula/abscess status post multiple colectomies with ileostomy and blind colostomy presented from a rehabilitation facility due to increased non-bloody watery ileostomy output and abdominal pain. He also presented with chronic rectal ulcers that appeared stable with scant purulent drainage. Vital signs were notable for hypotension and tachycardia that responded to fluids and empiric vancomycin and imipenem. Labs were notable for significantly elevated inflammatory markers, negative stool infectious panel, negative clostridium difficile, negative lactoferrin, white blood cell count of 23.9, and negative blood/urine cultures. Ileoscopy revealed colonization of the ileum and no source of high ostomy output was identified. Ileal biopsy revealed acute Crohn's enteritis. MRI pelvis fistula protocol revealed S5 osteomyelitis which was confirmed clinically by visualization in the OR. However, bone biopsy was negative in the setting of empiric antibiotic therapy. Patient was treated with approximately six weeks of vancomycin and ceftriaxone. He then followed up with Infectious Disease and had resolution of the infection and significant improvement in rectal ulcer drainage. DISCUSSION: Determination of the source of infection in patients with IBD can be challenging due to the inflammatory nature of the disease. Patients often present with systemic symptoms and non-specific complaints that could be mistakenly attributed to the underlying chronic disease. In any patient with fistulizing Crohn's presenting with sepsis, clinicians should have a high level of suspicion for osteomyelitis, especially in chronically debilitated patients with non-healing wounds. If routine infectious evaluation is unrevealing, clinicians should consider musculoskeletal infections due to direct extension from organic intra-abdominal processes. A broad differential diagnosis should be maintained for these Crohn's patients as multiple organ systems may be affected both directly and indirectly.

Five Anabolic Steroids in the Treatment of Inflammatory Bowel Disease

Abstract Crohn's disease (CD) and ulcerative colitis (UC), the constituents of Inflammatory Bowel Disease (IBD), are the most destructive benign diseases of young adults. Two-hundred thousand young men and women in North America will have major bowel resection annually, half to experience a premature death and many an increased risk of colorectal cancer. New cases in the youngest quadrille are appearing at a 0.5 percent rate per year. Adalimumab, the last pharmaceutical TNF-inhibitor drug approved for IBD was 17 years ago. Adalimumab's failure rate is 40 percent by year two, 60 percent by year five, and the 12-year German study questions whether there is any long-term gain in quality of life at all. The problems to date in understanding and treating IBD are that no one has identified the cause, no specific biomarkers are recognized, no alternatives to overtly toxic medications and no alternatives exist for inevitable surgical resections. That has changed. There are now serum hormonal biomarkers that are highly predictive of flairs in Crohn's diseases; the first being the nuclear membrane Estrogen Receptor-beta/Estrogen Receptor-alpha ratio. The second being bioavailable testosterone measured as the Free Androgen Index. Causation is clearly demarcated to hormonal dysregulation at the Hypothalamic-Pituitary-Gonadal Axis suppressing testosterone production. Five inexpensive, generic, FDA approved anabolic steroid medications have been successfully used to treat IBD, albeit, not the recognized standard of care. Here is the future of medicine: After initial medical information intake, measure Gender Specific Medicine biomarkers of gonadal hormones (causation) and then treat to normalize these biomarkers. Admixtures of anabolic steroids should reset the biomarkers and reduce the autoimmune, inflammatory, and systemic aspects of disease. Remission may be attainable with even the most resistant Crohn's and Ulcerative Colitis patients as observed in the Case Reports.

Chyme Reinfusion Is Associated with Lower Rate of Postoperative Ileus in Crohn's Disease Patients After Stoma Closure.

The rate of postoperative ileus following stoma closure is high in patients with Crohn's disease and temporary enterostomy. To evaluate the effect of chyme reinfusion on postoperative outcomes including ileus in these patients. Patients were screened from January 2012 to December 2017 and divided into chyme reinfusion group (n = 33) and non-chyme reinfusion group (n = 84). The following 30-day postoperative outcomes were evaluated. Univariate and multivariate analyses and propensity score matching were performed to identify risk factors for these postoperative outcomes. The incidence of postoperative ileus was significantly lower in the chyme reinfusion than in non-chyme reinfusion group, which had been confirmed by the results after matching (3/26 vs 11/26, p = 0.012). The rate of postoperative diarrhea was significantly lower in the chyme reinfusion group compared with non-chyme reinfusion group, whereas the difference was not significant after matching (2/26 vs 6/26, p = 0.191). Additionally, the postoperative length of stay was significantly shorter in the chyme reinfusion than in non-chyme reinfusion group before and after propensity score matching. In the multivariate analysis, chyme reinfusion was an independent protective factor for postoperative ileus (odds ratio 0.218; 95% confidence interval 0.05-0.95; p = 0.042) and for postoperative length of stay (coefficient - 0.191; 95% confidence interval - 0.350 to - 0.032, p = 0.019). Chyme reinfusion was associated with lower rate of postoperative ileus and shorter length of stay following stoma closure in Crohn's patients with temporary ileostomy. Further randomized clinical trial between patients with or without chyme reinfusion was needed to confirm these conclusions.

Elevated Levels of Alveolar Nitric Oxide May Indicate Presence of Small Airway Inflammation in Patients with Inflammatory Bowel Disease.

Pulmonary manifestations of inflammatory bowel disease (IBD), albeit not rare, are largely overlooked in clinical practice. The role of exhaled nitric oxide (eNO) as an established biological marker of airway inflammation compels us to use it as a tool to investigate the exact nature of these manifestations. Fractional eNO (FeNO) was measured in multiple flows, and with the use of a mathematical model, alveolar concentration of NO (CANO) and bronchial flux of NO (JawNO) were assessed in 27 patients with IBD [17 with Crohn's disease (CD) and 10 with ulcerative colitis (UC)] and in 39 healthy controls. Carefully selected criteria were used to exclude patients or healthy controls that presented factors considered to be correlated with eNO measurements. Disease activity was measured in Crohn's patients using the CD activity index (CDAI) score and in UC using the partial Mayo score. CANO was significantly higher in the IBD group, compared to the control group (p < 0.0001). FeNO was significantly increased in patients with IBD (p = 0.023), while there was no statistical significance found regarding levels of JawNO in patients with IBD (p = 0.106), both compared to controls. There was no significant correlation between any eNO component and markers of disease activity. Alveolar concentration of NO is elevated in patients with IBD, regardless of disease activity. This may suggest that subclinical small airway inflammation is present in patients with IBD, even those with mild or inactive disease.

P068 The utility of contrast-enhanced trans-abdominal ultrasound in the assessment of ileal Crohn's disease

BACKGROUND: While ileo-colonoscopy remains the gold standard for luminal evaluation of Crohn’s ileitis, repeated colonoscopies to reassess disease activity can be inconvenient (prep, lost time from work) and put the patient at additional procedure risk and increase health care cost. MRI and CT enterography can be used to assess ileal disease, but the tests involve contrast use, radiation exposure, and are lengthy and costly. Contrast-enhanced ultrasound (CEUS) has been promoted in Europe and Asia as a promising tool for assessment of disease activity with lower cost and no radiation exposure. METHODS: This is a prospective study currently enrolling patients with active Crohn's ileitis. All patients underwent evaluation with ileo-colonoscopy and serum inflammatory marker (CRP). Subsequently, all patients underwent CEUS by an independent radiologist who was blinded to the endoscopy results. Ultrasound contrast agent sulfur hexafluoride with gas-filled microbubbles was used (4.8 mL of IV Lumason, Bracco Diagnostics Inc), with real-time visualization of bowel wall microvascularization and perienteric tissue. Bowel wall thickness was measured and a time-signal intensity curve was obtained after calculating the peak enhancement and area under the curve. Prior groups (1) used a cut off point of 18.2 dB for moderate activity and 23.0 dB for severe activity. CEUS findings were compared to the endoscopic findings to assess for correlation in assessing disease activity and severity. RESULTS: Four male patients (age 22–65, 3 AA and one Caucasian) with symptomatic Crohns ileitis were enrolled in our study thus far. Patient A had moderate inflammation on CEUS with a peak intensity of 22 dB correlating with Rutgeerts i3 ileitis (large ulcers) above the ileoclonic anastomosis. Patient B had severe inflammation on CEUS with a peak intensity of 27 dB that correlated with moderate to severe ileitis with an inflammatory stricture on endoscopy. Patient C and D both had mild enhancement of distal ileum with a peak intensity of 17 dB; correlating with the findings of aphthous and larger ulcers on endoscopy. Only the 2 patients with a peak intensity of 27 dB had elevated CRP. CONCLUSION(S): In our limited experience, CEUS correlates with endoscopic findings of active ileitis and disease severity in Crohn's patients. With further patients enrollment and follow up, we aim to confirm this finding and to assess whether CEUS imaging can also evaluate inactive ileitis in treated Crohn's patients.

P098 Anti-TNF biologic therapy does not increase postoperative morbidity in pediatric Crohn's patients

BACKGROUND: Limited knowledge exists as to what impact preoperative biologic therapy has on post-operative complications in pediatric patients undergoing abdominal surgery for Crohn's disease (CD). Therefore, we sought to determine the 30-day postoperative infectious complication rate among pediatric CD patients who received biologic therapy within 12 weeks of an abdominal operation. METHODS: A retrospective chart review was performed on pediatric (&lt;18 years of age) CD patients who underwent an abdominal operation between 1/1/2008 and 12/31/2017. Patients were grouped according to whether they received an anti-TNF (infliximab, adalimumab, certolizumab pegol) or no biologic therapy within 12 weeks prior to the operation. The primary outcome was a the overall 30-day postoperative infectious complication rate. Secondary outcomes included 30-day readmission rate and return to the operating room (ROR). RESULTS: A total of 69 pediatric CD patients met inclusion criteria (n = 54 anti-TNF therapy, n = 15 received no biologic therapy). There were no differences between the anti-TNF and no biologic cohorts with respect to demographics or CD characteristics. No significant differences in overall 30-day postoperative infectious complications existed between patients exposed to anti-TNF agents and those with no preoperative exposure, or in its subcategories of surgical infectious complications and non-surgical infectious complications. There was also no difference in the rate of ileus, readmission, or ROR. CONCLUSION(S): Preoperative exposure to anti-TNF biologic therapy does not add to overall or infectious 30-day postoperative morbidity in pediatric CD patients.

P100 Study of endoscopic findings in children with chronic diarrhea attending Alexandria university children's hospital

BACKGROUND: Chronic diarrhea is a major problem worldwide with high morbidity and mortality. METHODS: The medical records were revised for: clinical presentation, clinical examination, laboratory investigation and endoscopic findings RESULTS: Forty patients were included in the study. The mean age of the patients was 3 and half years. Patients from rural areas were more than from urban regions. Sixty-five percent of the patients were males and thirty-five percent were females. Mucoid diarrhea was the most common type of diarrhea. Failure to thrive was evident in abetalipoproteinemia and Crohn's patients. Fecal calprotectin above 150 mg/kg is highly specific and sensitive for inflammatory bowel disease. Eosinophilic enterocolitis was the most common disease (57.5%) followed by celiac disease (15%) then ulcerative colitis (12.5%). CONCLUSION(S): Management of patients with chronic diarrhea should be initiated and followed in a specialized Pediatric GIT unit since it requires experience and close clinical, endoscopic and pathological assessment.

Performance of Surveillance MR Enterography (MRE) in Asymptomatic Children and Adolescents With Crohn's Disease.

MR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established. To determine whether MRE imaging features are associated with clinical recurrence. Retrospective. Pediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified. 1.5T including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, diffusion-weighted, and contrast-enhanced multiphase T1 -weighted gradient recalled echo sequences. MREs were reviewed by three radiologists independently for mural thickening, T2 -weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's-related treatment escalation, surgery, or hospitalization. Fisher's exact test, Wald chi-square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features. Of 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T2 -weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786). MRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6-month period, indicating a potential role for surveillance imaging to assess for subclinical active disease. 3 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;50:1955-1963.

Preclinical evaluation of EPHX2 inhibition as a novel treatment for inflammatory bowel disease.

Epoxyeicosatrienoic acids (EETs) are signaling lipids produced by cytochrome P450 epoxygenation of arachidonic acid, which are metabolized by EPHX2 (epoxide hydrolase 2, alias soluble epoxide hydrolase or sEH). EETs have pleiotropic effects, including anti-inflammatory activity. Using a Connectivity Map (CMAP) approach, we identified an inverse-correlation between an exemplar EPHX2 inhibitor (EPHX2i) compound response and an inflammatory bowel disease patient-derived signature. To validate the gene-disease link, we tested a pre-clinical tool EPHX2i (GSK1910364) in a mouse disease model, where it showed improved outcomes comparable to or better than the positive control Cyclosporin A. Up-regulation of cytoprotective genes and down-regulation of proinflammatory cytokine production were observed in colon samples obtained from EPHX2i-treated mice. Follow-up immunohistochemistry analysis verified the presence of EPHX2 protein in infiltrated immune cells from Crohn’s patient tissue biopsies. We further demonstrated that GSK2256294, a clinical EPHX2i, reduced the production of IL2, IL12p70, IL10 and TNFα in both ulcerative colitis and Crohn's disease patient-derived explant cultures. Interestingly, GSK2256294 reduced IL4 and IFNγ in ulcerative colitis, and IL1β in Crohn's disease specifically, suggesting potential differential effects of GSK2256294 in these two diseases. Taken together, these findings suggest a novel therapeutic use of EPHX2 inhibition for IBD.

Profile of Consecutive Fecal Calprotectin Levels in the Perioperative Period and Its Predictive Capacity for Early Endoscopic Recurrence in Crohn's Disease.

The perioperative behavior of fecal calprotectin and whether it predicts early postoperative endoscopic recurrence of Crohn's disease are unknown. We aimed to compare the perioperative profiles of fecal calprotectin between patients with Crohn's disease and patients without Crohn's disease undergoing intestinal resection and to identify the association between consecutive fecal calprotectin levels and endoscopic recurrence 3 months after surgery in patients with Crohn's disease. This was a prospective observational study. This study was conducted in a tertiary referral hospital. One hundred fourteen consecutive patients (90 Crohn's disease, 24 non-Crohn's disease) who underwent resection were recruited. Univariate and multivariate analyses were performed to identify variations and risk factors. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves. The fecal calprotectin levels on preoperative day 14 and postoperative days 14, 21, 28, 60, and 90 were higher in the Crohn's disease group than they were in non-Crohn's disease group (p < 0.05). Twenty patients (22.2%) developed endoscopic recurrence 3 months after resection. The trend for fecal calprotectin change (Δfecal calprotectin) from preoperative day 14 to postoperative day 14 was opposite in the recurrence and nonrecurrence groups. Multivariate analysis showed that this change was a predictive factor of early endoscopic recurrence (p < 0.05). ΔFecal calprotectin was more accurate at predicting early endoscopic recurrence than was fecal calprotectin at single time points with a cutoff value of 240 μg/g. This is a single-center trial with a limited cohort of patients. The perioperative fecal calprotectin levels were higher in patients with Crohn's disease than they were in the control group. The change in fecal calprotectin levels from preoperative day 14 to postoperative day 14 could serve as a practical predictive index for early postoperative endoscopic recurrence. See Video Abstract at http://links.lww.com/DCR/A796.

Early Postoperative Anti-TNF Therapy Does Not Increase Complications Following Abdominal Surgery in Crohn's Disease.

The impact of postoperative anti-TNF therapy on infectious complications following Crohn's disease surgery remains controversial. Use of anti-TNF therapy 2-4weeks postoperatively appears safe, but safety of use within 2weeks is unknown. We sought to evaluate the effect of anti-TNF therapy initiated within 2weeks of abdominal surgery in patients with Crohn's disease. We conducted a retrospective review of adult Crohn's disease patients undergoing abdominal surgery between 2004 and 2011. Infectious and non-infectious complications were compared between patients exposed to anti-TNF therapy within 2weeks or between 2 and 4weeks postoperatively and to those without exposure using chi-squared and regression analysis. Three hundred thirty-one abdominal surgeries were included; 241 were without anti-TNF exposure, 46 received postoperative anti-TNF within 2weeks of surgery, and 44 received anti-TNF therapy 2-4weeks after surgery. Patients who received anti-TNF therapy within 2weeks of surgery, those initiated between 2 and 4weeks of surgery, and those who did not receive anti-TNF therapy within 4weeks of surgery had no significant difference in rates of infectious complications (22%, 32%, 33%, p = 0.332). Rates of non-infectious complications (4%, 9%, 14%, p = 0.143), mortality (0%, 0%, 3%, p = 0.105), hospital readmission (17%, 16%, 15%, p = 0.940), and reoperation (11%, 11%, 16%, p = 0.563) were also similar between groups. Use of early anti-TNF therapy within 2weeks or between 2 and 4weeks following abdominal surgery did not increase risk of postoperative surgical infections in Crohn's patients.

Anti-TNF biologic therapy does not increase postoperative morbidity in pediatric Crohn's patients

IntroductionLimited knowledge exists as to what impact preoperative biologic therapy has on postoperative complications in pediatric patients undergoing abdominal surgery for Crohn's disease (CD). Therefore, we sought to determine the 30-day postoperative infectious complication rate among pediatric CD patients who received biologic therapy within 12 weeks of an abdominal operation. MethodsA retrospective chart review was performed on pediatric (<18 years of age) CD patients who underwent an abdominal operation between 1/1/2008 and 12/31/2017. Patients were grouped according to whether they received an anti-TNF (infliximab, adalimumab, certolizumab pegol) or no biologic therapy within 12 weeks prior to the operation. The primary outcome was the overall 30-day postoperative infectious complication rate. Secondary outcomes included 30-day readmission rate and return to the operating room (ROR). ResultsA total of 69 pediatric CD patients met inclusion criteria (n = 54 anti-TNF therapy, n = 15 received no biologic therapy). There were no differences between the anti-TNF and no biologic cohorts with respect to demographics or CD characteristics. No significant differences in overall 30-day postoperative infectious complications existed between patients exposed to anti-TNF agents and those with no preoperative exposure, or in its subcategories of surgical infectious complications and nonsurgical infectious complications. There was also no difference in the rate of ileus, readmission, or ROR. ConclusionsPreoperative exposure to anti-TNF biologic therapy does not add to overall or infectious 30-day postoperative morbidity in pediatric CD patients. Level of evidenceIII. Type of studyRetrospective review.

Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple surgical approach.

Rectal flap advancement is still a part of therapeutic management of anal fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal flap advancement and to determine predictive factors for failure, with a special focus on CD METHOD: The patients' details, the characteristics of the fistula and the main clinical and therapeutic events were prospectively assessed among patients who underwent rectal flap advancement. All patients had a partial-thickness rectal flap advancement. Failure of primary rectal flap advancement was defined as the occurrence of at least one of the following: abscess, discharge, visible external opening, further drainage procedure. The rates of failure of rectal flap and the predictive factors of failure were assessed. Eighty-seven patients (34 patients with CD) were included. The median (interquartile range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were 15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at 3, 6, 12 and 24months respectively. These data were comparable in Crohn's patients. Those with a supralevator fistula [hazard ratio2.53 (1.01-7.71), P=0.0476] and patients who had fewer than two fistula drainages before rectal flap [hazard ratio3.19 (1.40-8.23), P=0.005] were associated with higher rectal flap failure rates. In CD patients, the absence of biological therapy at referral was predictive of failure. Rectal flap advancement is a satisfactory option for the therapeutic management of anal fistula, including CD populations. Fistula drainage is needed before performing this surgical technique.

Prevalence of Non-Alcoholic Steatohepatitis (NASH) in Individuals With Crohnʼs Disease: A Population-Based National Study

Introduction: Previous studies have suggested a possible association between Crohn's Disease (CD) and non-alcoholic steatohepatitis (NASH). However, this link is controversial since most of these studies have been limited by small sample sizes. We sought to examine the association between Crohn's disease and NASH using a large population based database. Methods: We queried a commercial database (Explorys Inc., Cleveland, OH), an aggregate of Electronic Health Record (EHR) data from 26 major integrated healthcare systems in the US from 1999 to June 2018. We identified an aggregated patient cohort of eligible patients with diagnoses of Crohn's Disease and NASH based on Systemized Nomenclature of Medical terminology (SNOMED-CT) codes, excluding patients with autoimmune liver disease, viral liver disease, and alcoholic liver disease. We calculated the prevalence of NASH in patients with and without Crohn's disease and performed univariate analyses to assess the prevalence of conditions co-morbid to both Crohn's disease and NASH. Results: A total of 34,605,400 individuals were included in the study period between June, 2013 and June, 2018. Of these, 153,810 (0.44%) had a diagnosis of Crohn's disease and 27,170 (0.08%) had a diagnosis of NASH. Of the individuals with Crohn's disease, 520 also had a diagnosis of NASH (0.34%) [Odds Ratio (OR): 5.4 (p< 0.0001)]. Compared to individuals with Crohn's disease and without NASH, individuals with Crohn's disease and NASH had higher prevalence of HTN, 71% vs 43% (OR 3.2, p<0.0001), HLD 65% vs 33% (OR 3.9, p<0.0001), metabolic disease 90% vs 58% (OR 6.8, p<0.0001), diabetes 52% vs 21% (OR 4.0, p<0.0001), obesity 60% vs 20% (OR 5.8, p<0.0001), and morbid obesity 29% vs 5.9% (OR 6.5; p< 0.0001). Crohn's patients with NASH had increased prevalence of azathioprine use at 15% compared to 8.8% (OR 1.9; p< 0.0001), and TNF-alpha inhibitors at 23% compared to 16% in subjects with Crohn's disease and without NASH (OR 1.6; p< 0.0001). Conclusion: In this large population-based study, the overall prevalence of NASH in Crohn's disease patients was 0.34% compared to 0.08% in the general population. Patients with Crohn's disease and NASH had higher rates of metabolic risk factors and higher rates of use of immunomodulators and anti-TNF-alpha agents.854_A Figure 1 No Caption available.854_B Figure 2 No Caption available.

The Use of Dual Energy Computed Tomography in Evaluating Crohnʼs Disease Activity

Introduction: The extent and severity of activity in Crohn's patients is critical for determining optimal treatment. Clinical, endoscopic, laboratory (eg fecal calprotectin (FC), erythrocyte sedimentation rate (ESR), and C-Reactive protein (CRP)) and imaging are the methods used for this assessment. Activity on imaging correlates with the degree of enhancement of involved segments measured by Hounsfield units on CT or by signal intensity on MRI. Dual energy CTE (DECTE) can provide iodine density within a region of interest and therefore may more accurately identify the most inflamed portion of affected bowel. Our study attempts to evaluate if this added information influences clinical decision making. Methods: Clinical and imaging studies in 20 Crohn's disease patients undergoing DECTE between 2014-2017 with laboratory data within 3 months before or after DECTE were reviewed. Clinically active disease was defined as the presence of active inflammation on pathology, a Harvey-Bradshaw Index (HBI) of 5 or greater, or elevated biomarkers (ESR, CRP, FC). Inactive disease was defined as lack of activity in any of these three categories. Independently, iodine maps from DECTE studies were assessed for maximum, minimum iodine density, pattern of distribution (transmural or submucosal) and amount of abnormal bowel. Active disease on DECTE was present when minimum iodine density in a region exceeded 2.5mgI. Results: Of the 20 patients, 17 were determined to have clinically active disease. 4/17 of active patients exhibited activity solely on pathology; 4/17 had evidence of activity on HBI alone; 2/17 patients only demonstrated elevated biomarkers; and 7/17 expressed activity in two or more categories. 3/20 patients demonstrated no evidence of activity in any categories. Maximum and minimum iodine density of affected bowel were 4±0.75 (2.7-5.4) mg/mL and 2.78±0.53(2.2-3.9) mg/mL, respectively. Iodine density of normal-appearing small bowel was 1.47±0.27(1.2-2) mg/mL. The maximum and minimum iodine density of affected bowel differed significantly from normal bowel (P<0.0001). Conclusion: Our study demonstrates that DECTE has advantages over conventional CT by pinpointing regions of active inflammation within affected bowel.

Risk factors for anastomotic recurrence after primary ileocaecal resection in Crohn's disease.

Ileocaecal resection is the most common operation performed in Crohn's disease. Our study aimed to identify the risk factors for anastomotic recurrence following primary ileocaecal resection. We retrospectively analysed data from all Crohn's disease surgical patients in a single colorectal unit between 2006 and 2016, including all patients who underwent primary ileocaecal resection. We defined anastomotic recurrence as the postoperative need for endoscopic dilatation of the ileocolic anastomosis or neoterminal ileal resection, and used Cox regression to determine the risk factors for such recurrence. In total, 101 patients underwent primary ileocaecal resection during the study period. Nine (8.9%) patients were excluded because of follow-up less than 1 year and 12 (13.0%) patients had anastomotic recurrence. The median follow-up was 4.7 (1.3-10.8) years. At 3 years, 93.1% of patients required no neoterminal ileal resection or dilatation of the ileocolic anastomosis. Urgent primary ileocaecal resection [hazard ratio (HR)=4.98, 95% confidence interval (CI)=1.45-17.11, P=0.011], stapled anastomosis (HR=20.34, 95% CI=5.06-81.77, P<0.001) and need for postoperative corticosteroid treatment after the primary ileocaecal resection (HR=3.58, 95% CI=1.03-12.40, P=0.044) emerged as significant risk factors for anastomotic recurrence. Urgent surgery and postoperative corticosteroid need represented risk factors for anastomotic recurrence. Hand-sewn anastomosis with an opening of the bowel's antimesenteric border seems to be a safe choice for ileocaecal resection.

Chronotype, social jet lag, sleep debt and food timing in inflammatory bowel disease

The preference of the sleep/wake cycle can be grouped into categories or chronotypes. Inflammatory bowel disease (IBD) has been linked to poor sleep quality which correlates with disease severity. Social jet lag (SJL) is the difference between sleep timing on work and free days and is a marker for circadian misalignment which has been linked to increased inflammation. We investigated whether chronotype, SJL, sleep debt (SD), and food timing were associated with an IBD specific complications and a lower quality of life. Overall, 191 subjects (115 IBD subjects and 76 healthy controls (HC)) completed the Pittsburgh Sleep Quality Index (PSQI), Morningness-Eveningness Questionnaire (MEQ), Munich ChronoType Questionnaire (MCTQ), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and a structured Food Timing Questionnaire. Later chronotype (by MEQ) was associated with a worse SIBDQ (r = −0.209; P < 0.05). SJL was increased in IBD at 1.32 h ± 1.03 vs. 1.05 h ± 0.97 in HC, P < 0.05, when adjusted for age. SJL (>2 h) was present in 40% of severe/complicated Crohn's patients (fistulizing or structuring Crohn's or history of Crohn's related surgery) compared to only 16% of uncomplicated Crohn's patients (P < 0.05). Sleep debt was increased in IBD subjects compared to HC at 21.90 m ± 25.37 vs. 11.49 m ± 13.58, P < 0.05. IBD subjects with inconsistent breakfast or dinner times had lower SIBDQ scores (4.78 ± 1.28 vs. 5.49 ± 1.02, P < 0.05; 4.95 ± 0.31 vs. 5.42 ± 0.32, P < 0.05 respectively). In summary, later chronotype, and markers of circadian misalignment (social jet lag, sleep debt, and inconsistent meal timing) were associated with IBD disease specific complications and/or lower quality of life.

Abstract 4476: Role of MAP-Kinase suppressor in IBD

Abstract BACKGROUND &amp; AIMS: Endogenous suppressor of Mitogen Activated Kinase Pathway (MAPK) are considered cancer suppressors. In this regard , Sprouty (SPRY) proteins that are endogenous suppressor of receptor tyrosine kinase signaling are reported to be tumor suppressors in various cancers, whereas we discovered that SPRY2 augments Epithelial Mesenchymal Transition (EMT) in colorectal cancer (CRC) [Oncogene, 2016 Jun 16; 35(24): 3151-62]. Significance of SPRY proteins in Inflammatory Bowel Disease (IBD) is not clearly understood. MATERIALS &amp; METHODS: Biopsies from Crohn's Colitis patients were assessed for SPRY, Beta-catenin, Occludin and ZO1 expression. Tight junction profiler was employed to assess expression of integrin proteins in CaCO2 colon cancer cell line. SPRY was suppressed in colon cancer cells by siRNA and CRISPR/Cas9 technology and changes were assessed by immunoblotting, real time PCR, phase-contrast and confocal microscopy. Spry1 and Spry2 floxed mice were utilized to dissect SPRY functions in mesenchymal cells. RESULTS: SPRY, E-cadherin, Beta-catenin and Occludin mRNA transcripts were significantly different in IBD patients (p&amp;lt;0.05). No significant changes in ZO1 mRNA transcripts were noted. Suppression of SPRY significantly decreased expression of several integrins in CaCO2 cells (p&amp;lt;0.05) . Treatment of CaCO2 cells with Dextran Sodium Sulfate (DSS) significantly altered SPRY, Beta-catenin, Occludin and ZO1 expressions that was reversed by SPRY suppression. Spry1-/- and Spry2-/- double mutant murine embryonic fibroblasts (MEFs) demonstrated restoration of several epithelial markers which protected cells from DSS-induced changes. CONCLUSIONS: SPRY expression in colonic epithelium regulates IBD. SPRY has prognostic value in IBD. Citation Format: Sharad Khare, Qiong Zhang. Role of MAP-Kinase suppressor in IBD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4476.

PFOA and ulcerative colitis

IntroductionPFOA (perfluoroctanoic acid) is a perfluoroalkyl substance (PFAS). Although use in the US has been phased out, PFOA persists indefinitely in the environment, and is present in the serum of virtually all people in industrialized countries. Approximately 6 million Americans drink water comtaminated with PFOA above EPA-recommended levels. In a previous cohort study (n = 32,000), we found a strong positive exposure-response relation between PFOA serum levels and subsequent ulcerative colitis (UC) in a high-exposed population from the mid-Ohio valley, but no association with Crohn's disease. In the present study we aimed to determine if UC cases had higher levels of PFOA than did controls or Crohn's disease patients. MethodsWe measured PFOA and three other PFAS in the serum of 114 UC patients, 60 Crohn's disease patients, and 75 controls, within a year of diagnosis. We conducted regression analyses to assess the association of the PFAS with diagnosis. ResultsThe mean age of subjects was 17 years. The mean year of diagnosis was 2007. Mean levels of PFAS were similar to US levels. Mean log PFOA level in UC patients was 38% higher (p = 0.01) than the combined group of Crohn's disease and controls. In contrast, the three other PFASs were significantly higher in controls and Crohn's patients than UC patients. The odds ratio for UC per one unit of log PFOA was 1.60 (95% CI 1.14–2.24), but the trend by quintiles was not monotonic (1, 0.84, 40.98, 33.36, 2.86). ConclusionWe found higher serum PFOA in UC cases compared to Crohn's disease patients or controls, in contrast to other PFAS. Our research is limited by not knowing if the elevated PFOA preceded UC in this population.

Sa1822 - Steroid and Opioid use Among Crohn's Patients before and after Initiation of Ustekinumab

Sa1822 - Steroid and Opioid use Among Crohn's Patients before and after Initiation of Ustekinumab