Disease Extraintestinal Manifestations Research Articles

P881 Real-life vs trial access to biologic therapy differences: a 2019-2020 experience in an Italian tertiary IBD center

Abstract Background Inflammatory Bowel Diseases (IBD) are multifactorial diseases including Ulcerative Colitis (UC) and Crohn's Disease (CD). Up to 50% of IBD patients show a primary or secondary non-response to standard biological therapy. Hence, Randomized Clinical Trials (RCTs) represent a significant therapeutic opportunity for them. This study aims to describe the clinical characteristics of "trial IBD patients" vs. "real-life IBD". Methods We prospectively enrolled patients who started biologic therapy from August 2019 to August 2020. We divided patients into 3 sub-groups: (1) "real-life", patients treated according to clinical practice with biologic therapy that did not meet the inclusion and exclusion criteria for RCTs, (2) "real-life suitable for trial", patients potentially eligible in RCTs, but treated with standard of care, and (3) "trial", patients treated with drugs from 14 phases 2b and 3 studies actively recruiting in our center. Results We enrolled 134 patients (72 UC, 62 CD). "Real-life" patients were 41 in UC and 38 in CD, "real-life suitable for trial" were 6 in UC and 14 in CD, and "trial" were 25 in UC and 10 in CD. According to the existing inclusion and exclusion criteria, the study showed that 43% UC patients and 39% CD were suitable for enrollment in RCTs, however only 16% of CD were finally enrolled in RCTs. At the enrollment, patients were mainly excluded for topical therapy use, cancer, recent infections, low CDAI (<220) or SED-CD (<6), or presence of complication of diseases in CD or for limited extension of disease in UC. Both "trial" UC and CD patients presented more extraintestinal manifestations of disease, especially the articular ones (p<0,05) and a higher significant concomitant use of systemic corticosteroids (≤20mg/die (p < 0,05)). Percentages of patients treated previously with other biological drugs were superior in "trial" patients compared to "real-life" only in UC (88% vs 29%). We observed different baseline clinical disease activity scores in CD: the HBI of "real-life" patients was 4.8, and the HBI of "trial" patients was 9.1. In addition, patients enrolled in RCTs waited longer before accessing the proposed biological therapy. Conclusion This study highlights some differences between clinical practice and RCTs, particularly regarding criteria to start biologic therapy. Globally "trial patients" have more complex diseases that significantly impact their clinical status. Furthermore, RCTs use clinical scores (e.g. CDAI) as determinants for enrollment and decision-making, while endoscopy and radiological imaging are more widely used in clinical practice for decision making. These differences could cover the actual effectiveness of a new drug compared to the theoretical efficacy deriving from registration RCTs.

The association of inflammatory bowel disease with postoperative complications, re-admissions and emergency department visits following primary total hip arthroplasty.

Inflammatory bowel disease (IBD) is a systemic inflammatory disorder of the gut. Few studies have evaluated whether patients with a history of IBD have worse outcomes following primary total hip arthroplasty (THA). Therefore, the purpose of this study was to evaluate whether IBD is associated with increased: (1) medical complications; (2) readmissions; and (3) emergency department (ED) visits. Using a nationwide claims database, patients with IBD undergoing primary THA were identified and matched to a comparison group according to age, sex and the Charlson Comorbidity Index. Outcomes assessed included the development of 90-day medical complications, 90-day re-admissions and 90-day ED visit rates. A p-value <0.0001 was considered statistically significant. Patients with IBD had a greater incidence and odds ratio of total medical complications (31.90% vs. 11.47%; OR 2.89; p < 0.0001) compared with matched controls. IBD patients had significantly higher incidence and odds ratio of developing acute kidney injury (5.46 vs. 1.46%; OR 3.92; p < 0.0001), cerebrovascular accident (1.32 vs. 0.35%; OR 3.79; p < 0.0001), pneumonia (4.02 vs. 1.30%; OR 3.19; p < 0.0001), respiratory failure (1.21 vs. 0.41%; OR 2.94; p < 0.0001), deep vein thrombosis (0.89% vs. 0.30%; OR 2.93; p < 0.0001), and other adverse events. IBD patients also had higher incidence and odds ratio of 90-day re-admissions (4.20% vs. 3.23%; OR 1.31; p < 0.0001) and ED visits (6.56% vs. 3.99%; OR 1.69; p < 0.0001). This study found that patients with IBD are at increased risk of 90-day medical complications, re-admissions, and ED visits. Due to its systemic nature, surgeons operating on these patients should be aware of the disease's extra-intestinal manifestations, and the potential postoperative risks in IBD patients. Providers should use this investigation when educating patients on potential risks of elective THA.

Extraintestinal manifestations in infl ammatory bowel diseases in children, a modern view of the problem

Inflammatory bowel disease (IBD) is a group of severe systemic diseases with a multiple intestinal and extraintestinal manifestations (EIM). EIM can affect any organ systems, determine the course, therapy and prognosis of the underlying disease. The frequency of EIM (6–80%) differs significantly in studies depending on the cohort of patients (number, age of patients, IBD phenotype). In 6–10% of children EIM are the first symptoms of the disease. The classification of EIM most often depends on the activity of the disease in the intestine. The most commonly affected «target organs» in children and adults are joints, skin and mucous membranes, eyes, and the hepatobiliary system. Physical development delay is specific for children IBD, not always reversible. The article highlights the incidence of ulcerative colitis and Crohn’s disease EIM in children and adults, analyzes the basics of epidemiology, pathogenesis, clinical manifestations, approaches to the diagnosis and treatment of arthritis, growth disorders, mucocutaneous, ocular and hepatobiliary EIM of IBD in children. Therapy of EIM associated with IBD activity is aimed at controlling the underlying disease and includes a wide range of drugs, ФНОα antagonists are the most effective. The treatment protocols for other EIM are not standardized in either adult or pediatric practice and are significantly less successful.

Identifying Measures of Suboptimal Healthcare Interaction (SOHI) to Develop a Claims-Based Model for Predicting Patients with Inflammatory Bowel Disease at Risk for SOHI.

Understanding the demographic and clinical characteristics of patients with Inflammatory Bowel Disease (IBD) who are likely to experience poor disease outcomes may allow early interventions that can improve health outcomes. To describe demographic and clinical characteristics of patients with ulcerative colitis (UC) and Crohn's disease (CD) with the presence of at least one Suboptimal Healthcare Interaction (SOHI) event, which can inform the development of a model to predict SOHI in members with IBD based on insurance claims, with the goal of offering these patients some additional intervention. We identified commercially insured individuals with IBD between 01 January 2019 and 31 December 2019 using Optum Labs' administrative claims database. The primary cohort was stratified on the presence or absence of ≥1 SOHI event (a SOHI-defining data point or characteristic at a specific time point) during the baseline observation period. SOHI was deployed as the basis for the development of a model to predict which individuals with IBD were most likely to continue to have SOHI within a 1-year timeframe (follow-up SOHI) using insurance claims data. All baseline characteristics were analyzed descriptively. Multivariable logistic regression was used to examine the association of follow-up SOHI with baseline characteristics. Of 19,824 individuals, 6872 (34.7%) were found to have follow-up SOHI. Individuals with follow-up SOHI were more likely to have had similar SOHI events in the baseline period than those with non-SOHI. A significantly greater proportion of individuals with SOHI had ≥1 claims-based C-reactive protein (CRP) test order and ≥1 CRP lab results compared with non-SOHI. Individuals with follow-up SOHI were more likely to incur higher healthcare expenditures and resource utilization as compared with non-SOHI individuals. A few of the most important variables used to predict follow-up SOHI included baseline mesalamine use, count of baseline opioid fills, count of baseline oral corticosteroid fills, baseline extraintestinal manifestations of disease, proxy for baseline SOHI, and index IBD provider specialty. Individuals with SOHI are likely to have higher expenditures, higher healthcare resource utilization, uncontrolled disease, and higher CRP lab results as compared with non-SOHI members. Distinguishing SOHI and non-SOHI patients in a dataset could efficiently identify potential cases of poor future IBD outcomes.

Risk factors and outcomes of restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Retrospective study of 75 single center cases.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical gold standard in patients with ulcerative colitis (UC). Results are generally satisfactory but there is a significant rate of patients who experience postoperative complications. The aims of our study were to identify the pre- and intraoperative risk factors and their correlation with the reported outcomes. A retrospective study was conducted on the medical records of all consecutive patients undergoing restorative proctocolectomy with IPAA for UC in our center from 2010 to 2021. Pre- and intraoperative factors were examined and correlated with pouchitis, endoscopic pouchitis, pouch failure, anastomotic leak, postoperative complications classified according to Clavien-Dindo score and stoma outlet obstruction. A univariate and multivariate statistical analysis was performed. Out of 75 patients undergoing 3- or 2-stage IPAA surgery, the coexistence of extraintestinal clinical manifestations and preoperative topical rectal stump therapy for active proctitis were significantly associated with the occurrence of pouchitis (OR=4.4, p=0.03 and OR=7.6, p=0.01). Endoscopic pouchitis was found to be related to preoperative topical rectal therapy (OR=10.2, p=0.007), but not to extraintestinal manifestations of disease. Anastomotic leak was found to be significantly related to pouch failure (OR=22.7, p=0.007). Surgical indication for malignancy increased the risk for early complications (Clavien-Dindo >2) (OR=16.0, p=0.04). Young age was associated with the occurrence of outlet stoma obstruction in patients with recent IPAA surgery (OR=0.97, p=0.05). Based on observed results, an appropriate preoperative patient assessment aimed at detecting specific risk factors is crucial to identify early or prevent worse outcomes in patients undergoing IPAA surgery.

Updates on the diagnosis and management of celiac disease.

Celiac disease is a chronic autoimmune enteropathy affecting about 1% of the population. Gluten ingestion triggers an immune response in genetically susceptible patients, resulting in intestinal and extraintestinal disease manifestations. Current recommendations for diagnosis include serology for celiac-specific antibodies to transglutaminase, endomysium, and deamidated gliadin, and IgA serology. New highly accurate point-of-care tests can efficiently screen for celiac disease and improve the diagnostic timeframe. Definitive diagnosis is most commonly made via biopsy of the small bowel showing villous atrophy. A gluten-free diet with micronutrient supplementation is the only recommended treatment for celiac disease. Primary care providers must be able to recognize screening indications, refer patients appropriately, and provide proper patient education and follow-up.

Extraintestinal manifestation of inflammatory bowel disease and associated factors in pediatric patients

ObjectiveExtraintestinal manifestations in irritable bowel disease (IBD), Crohn's disease and ulcerative colitis are reported in different system of the body. We aimed to investigate the factors determining disease severity and evaluate extraintestinal manifestations in patients with irritable bowel disease based on disease activity scoring system. MethodsThis cross-sectional study was conducted on all patients with irritable bowel disease referred to clinic and gastroenterology ward of (XXX). Medical history, gastrointestinal complications and incidence of extraintestinal manifestations were recorded. Disease severity in ulcerative colitis was rated based on PUCAI (Pediatric Ulcerative Colitis Activity Index) score and in Crohn's disease was calculated based on PCDAI (Pediatric Crohn's Disease Activity Index) score. ResultsOf 73 children included in our study, 54.80% were diagnosed with ulcerative colitis and 45.20% were diagnosed with Crohn's disease. The most prevalent symptom was weight loss (81.81%), diarrhea (72.72%) and abdominal pain (69.69%) in Crohn's diseases and bloody diarrhea (80%), abdominal pain (77.5%) and weight loss (57.5%) in ulcerative colitis. The average of PCDAI score was 43.44 and PUCAI score was 35.62. The most prevalent extraintestinal manifestation of the disease was arthritis in 7 Crohn's disease patients (21.21%) and 5 patients (12.5%) with ulcerative colitis, oral plague in 5 patients (15.15%) with Crohn's disease and erythema nodosum in 2 patients (6.06%) with Crohn's disease. ConclusionThe severity of oral plaque was positively associated with the severity of the disease. There was no significant association among other parameters. Scoring systems, to determine the extraintestinal manifestation, should be standardized based on the scoring outcomes.

Physiological mechanisms of unexplained (functional) gastrointestinal disorders.

Functional gastrointestinal disorders (FGIDs) encompass a range of complex conditions with similar clinical characteristics and no overt pathology. Recent recognition of sub-clinical pathologies in FGIDs, in conjunction with physiological and biochemical abnormalities including increased intestinal permeability, microbial profile alterations, differences in metabolites and extra-intestinal manifestations of disease, call into question the designation of these conditions as 'functional'. This is despite significant heterogeneity in both symptom profile and specifics of reported physiological abnormalities hampering efforts to determine defined mechanisms that drive onset and chronicity of symptoms. Instead, the literature demonstrates these conditions are disorders of homeostatic imbalance, with disruptions in both host and microbial function and metabolism. This imbalance is also associated with extraintestinal abnormalities including psychological comorbidities and fatigue that may be a consequence of gastrointestinal disruption. Given the exploitation of such abnormalities will be crucial for improved therapeutic selection, an enhanced understanding of the relationship between alterations in function of the gastrointestinal tract and the response of the immune system is of interest in identifying mechanisms that drive FGID onset and chronicity. Considerations for future research should include the role of sex hormones in regulating physiological functions and treatment responses in patients, as well as the importance of high-level phenotyping of clinical, immune, microbial and physiological parameters in study cohorts. There is opportunity to examine the functional contribution of the microbiota and associated metabolites as a source of mechanistic insight and targets for therapeutic modulation.

P557 Increased risk of anastomotic leak in Crohn’s disease patients unable to complete preoperative mechanical bowel preparation

Abstract Background To assess the risk of postoperative anastomotic leak in Crohn’s disease patients unable to complete the preoperative mechanical bowel preparation (MBP): a prospective observational study from two referral centres in Germany and the Czech Republic. Methods Preoperative MBP was used routinely in all Crohn’s disease patients undergoing elective ileocolic or colorectal resections completed by the formation of an anastomosis since 6/2016. The MBP consisted of 2 L Polyethyleneglycol (PEG) solution combined with two doses of oral antibiotics Metronidazole and Paromomycin. The MBP was defined as incomplete when patients were not able to drink the whole amount of PEG solution due to side effects or complications. The primary endpoint was occurrence of anastomotic leak. The secondary endpoint was the incidence of postoperative intraabdominal septic complications (IASC) which were defined as an anastomotic leak, intraabdominal abscess or fistula and peritonitis. Results Between 6/2016 and 11/2019, 96 Crohn’s disease patients underwent elective ileocolic or colorectal resections after receiving preoperative MBP and oral antibiotics. Twenty-four (25%) developed complications of MBP, mostly vomiting; 17 patients (18%) were not able to complete MBP. The presence of extraintestinal disease manifestations (Hazard Ratio 4.8, p = 0.029), preoperative weight loss (HR 5.7, p = 0.019) and female sex (HR 13.3, p = 0.005) were associated with an increased probability not to be able to complete MBP. Postoperative anastomotic leak occurred in 2 patients (2%). The risk of anastomotic leak was significantly higher in patients unable to complete MBP (12%) as compared with patients with complete MBP (0%, p = 0.03). Postoperative IASC occurred in 7 patients (7%). Patient unable to complete preoperative MBP were at higher risk to develop IASC; however, the difference was not statistically significant (18% vs. 5%, p = 0.10) Conclusion The anastomotic leak rate is very low when preoperative mechanical bowel preparation and oral antibiotics have been used. However, patients not able to complete MBP might be at an increased risk.

Emerging leadership lecture: Inflammatory bowel disease in Asia: emergence of a "Western" disease.

More than a decade ago, inflammatory bowel disease (IBD) is rare in Asia. Today, the importance of IBD in Asia is exemplified by its rapidly increasing incidence, complicated disease behavior, and substantial morbidity. In the first large-scale population-based epidemiologic study in Asia, the incidence of IBD varied from 0.60 to 3.44 per 100,000. There has been a twofold to threefold increase in the incidence of IBD in several countries in Asia. Ulcerative colitis (UC) is more prevalent than Crohn's disease (CD), although CD incidence is rapidly increasing. A positive family history is much less common than in the West, as are extra-intestinal disease manifestations. Complicated and penetrating CD are common in Asia. These epidemiologic changes may relate to increased contact with the West, westernization of diet, improved hygiene, increasing antibiotics use, or changes in the gut microbiota. Asian patients with CD have altered gut microbiota compared with their healthy counterparts and Caucasian CD subjects. Mucosa-associated microbiota in IBD may differ geographically. In a population-based case-control study, breast-feeding, having pets, and better sanitary conditions were protective of IBD, suggesting that childhood environment plays an important role in modulating disease development. Genetic factors also differ between Asians and Caucasians. Nucleotide oligomerization domain-2 (NOD2) and autophagy variants were not associated with CD, but tumor necrosis factor superfamily gene-15 polymorphisms were strongly associated with CD in East Asians. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.

Differences in Clinical Manifestations of Inflammatory Bowel Disease Based on Gender

Introduction: Inflammatory bowel disease is a disease group with multiple intestinal and extra-intestinal manifestations. It is associated with multiple hepatobiliary and systemic inflammatory conditions. The gender-based differences in clinical manifestations of IBD remains sparsely studied. We evaluated the differences in intestinal and extra-intestinal disease manifestations in IBD patients based on gender. Methods: We studied a cohort of patients presenting to our inflammatory bowel disease clinic in 2013. All patients with histopathological findings of inflammatory bowel disease on colonoscopy were included in the study. Medical records were reviewed for demographic and clinical data. Chi-square test with Yates’ continuity correction and fisher’s exact test were used to evaluate categorical variables and Student’s t-test was used to evaluate continuous variables. Results: Two hundred seventy-five patient records were reviewed, and 257 patients were included in the study. There were 118 male and 139 female patients. Of them, 60 patients had classical extra-intestinal manifestations (blepharitis/iritis/scleritis/uveitis, primary sclerosing cholangitis, pyoderma gangreonosum, oligoarthropathies/arthritis, ankylosing spondylitis, autoimmune hepatitis), while 78 patients had associated systemic disorders (hypothyroidism, asthma, pulmonary fibrosis, allergic rhinitis, rheumatoid arthritis, sarcoidosis, osteoporosis, psoriasis). Some patients had multiple manifestations. Mood disorders were present in 22.48% of patients. In our cohort, there was a higher prevalence of extra-intestinal disorders associated with IBD and mood disorders in female patients. There was no difference in the severity of IBD or the prevalence of classical extra-intestinal manifestations of IBD. Conclusion: Our study showed increased prevalence of extra-intestinal diseases and mood disorders in female IBD patients. This is consistent with the current understanding that women in general have a higher prevalence of auto-inflammatory diseases. However, there was no statistical difference on the severity of intestinal disease or need for surgery. The gender-based differences in disease manifestations should be considered while treating patients with IBD.Table 1: Difference in IBD manifestation by gender

Inflammatory bowel disease in Asia: A systematic review

The incidence and prevalence of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are lower in Asia than in the West. However, across Asia the incidence and prevalence of IBD has increased rapidly over the last two to four decades. These changes may relate to increased contact with the West, westernization of diet, increasing antibiotics use, improved hygiene, vaccinations, or changes in the gut microbiota. Genetic factors also differ between Asians and the Caucasians. In Asia, UC is more prevalent than CD, although CD incidence is rapidly increasing in certain areas. There is a male predominance of CD in Asia, but a trend towards equal sex distribution for UC. IBD is diagnosed at a slightly older age than in the West, and there is rarely a second incidence peak as in the West. A positive family history is much less common than in the West, as are extra-intestinal disease manifestations. There are clear ethnic differences in incidence within countries in Asia, and an increased incidence in IBD in migrants from Asia to the West. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.

Campylobacter jejuniinfection of infant mice: Acute enterocolitis is followed by asymptomatic intestinal and extra-intestinal immune responses

Campylobacter (C.) jejuni is among the leading bacterial agents causing enterocolitis worldwide. Despite the high prevalence of C. jejuni infections and its significant medical and economical consequences, intestinal pathogenesis is poorly understood. This is mainly due to the lack of appropriate animal models. In the age of 3 months, adult mice display strong colonization resistance (CR) against C. jejuni. Previous studies underlined the substantial role of the murine intestinal microbiota in maintaining CR. Due to the fact that the host-specific gut flora establishes after weaning, we investigated CR against C. jejuni in 3-week-old mice and studied intestinal and extra-intestinal immunopathogenesis as well as age dependent differences of the murine colon microbiota. In infant animals infected orally immediately after weaning C. jejuni strain B2 could stably colonize the gastrointestinal tract for more than 100 days. Within six days following infection, infant mice developed acute enterocolitis as indicated by bloody diarrhea, colonic shortening, and increased apoptotic cell numbers in the colon mucosa. Similar to human campylobacteriosis clinical disease manifestations were self-limited and disappeared within two weeks. Interestingly, long-term C. jejuni infection was accompanied by distinct intestinal immune and inflammatory responses as indicated by increased numbers of T- and B-lymphocytes, regulatory T-cells, neutrophils, as well as apoptotic cells in the colon mucosa. Strikingly, C. jejuni infection also induced a pronounced influx of immune cells into extra-intestinal sites such as liver, lung, and kidney. Furthermore, C. jejuni susceptible weaned mice harbored a different microbiota as compared to resistant adult animals. These results support the essential role of the microflora composition in CR against C. jejuni and demonstrate that infant mouse models resemble C. jejuni mediated immunopathogenesis including the characteristic self-limited enterocolitis in human campylobacteriosis. Furthermore, potential clinical and immunological sequelae of chronic C. jejuni carriers in humans can be further elucidated by investigation of long-term infected infant mice. The observed extraintestinal disease manifestations might help to unravel the mechanisms causing complications such as reactive arthritis or Guillain-Barré syndrome.

Association of Age at Diagnosis and Ulcerative Colitis Phenotype

Ulcerative colitis (UC) primarily affects young adults; however, 12% of patients are diagnosed at an advanced age. Previous studies report that older patients are less likely to have pancolitis and more likely to have distal disease location. Our objective was to compare UC phenotype by age of diagnosis in a tertiary referral cohort. Retrospective database analysis. Demographics, disease extent, and EIM were compared by the following age of diagnosis groups: <17 years, 17-40 years, and >40 years. A total of 260 patients evaluated between July 1, 2004 and April 19, 2010 were included. Race, smoking history, extraintestinal manifestations of disease, and disease duration were significantly associated with age of diagnosis. As age of diagnosis increased, the proportion of non-white patients increased (p = 0.04), former smoking history increased (p < 0.001), extraintestinal manifestations of disease decreased (p < 0.017), and disease duration decreased (p < 0.0001). As age of diagnosis increased, there was a trend for a higher proportion of patients with proctitis and a decreased proportion of patients with pancolitis. Multivariable analysis adjusting for sex, race, smoking history, family history, and disease duration demonstrated that diagnosis at >40 years was associated with a decreased likelihood for pancolitis compared to younger cohorts (OR 0.43, 95% CI 0.24, 0.76). Diagnosis of ulcerative colitis after age 40 years was associated with decreased disease extent compared to younger age groups, even after adjustment for sex, race, smoking history, family history, and disease duration. Our results suggest that older patients have distinct clinical phenotypes.

Importance of host cell receptor specificity and immune responses in rotavirus pathogenesis

Rotavirus is the main cause of severe infantile gastroenteritis worldwide in humans and a significant animal pathogen. Major determinants of the tropism of rotaviruses for particular hosts and cells include the ability to utilise certain cell surface receptors and evade innate host immune responses. Extraintestinal disease manifestations resulting from rotavirus infection are also increasingly being recognised. For example, this virus plays a role in accelerating progression towards the onset of type 1 diabetes in genetically at-risk children and mice. It is important to evaluate the efficacy and safety of the current childhood vaccines for rotavirus disease occurring both in the gut and extraintestinally.

Risk Factors for High Dose Radiation Exposure in Crohnʼs Disease

Purpose: Diagnostic imaging is used frequently in patients with Crohn's disease (CD); therefore, CD patients may be exposed to high amounts of radiation from diagnostic imaging in their lifetime. Frequent exposure to radiation increases the incidence of malignancy. The aim of this study was to identify demographic and disease-specific characteristics that are associated with higher diagnostic radiation exposure in patients with CD. Methods: 106 patients with CD who were initiated on anti-TNF or immunomodulator therapy with at least one year of follow-up between 2004 and 2008 were included. All radiologic studies done 1 year before and 1 year after initiation of immunomodulators or anti-TNF therapy were recorded. The cumulative effective dose of radiation over the 2 years was calculated using standardized effective doses. Demographics, disease phenotype, disease duration, and presence of extraintestinal manifestations of disease (EIM) were extracted from a preexisting clinical database. The cohort was divided into quartiles by effective dose of radiation. Logistic regression analysis was performed to identify associations between demographic and disease-specific variables and cumulative effective dose of diagnostic radiation ≥55 mSv (top quartile effective dose of radiation). Results: 86% of the patients were <40 years old at diagnosis. 68% were female. 79% were Caucasian. 32%, 54%, and 14% had ileal, ileocolonic, and colonic disease, respectively. 27%, 34%, and 39% had inflammatory, stricturing, and penetrating disease, respectively. 29% had perianal disease and 29% had EIM. 64% were treated with anti-TNF agents and 38% with immunomodulators. 55% of patients were diagnosed with CD for less than 10 years prior to the study. Exposure to diagnostic radiation did not differ by age, sex, race, age at diagnosis or duration of disease, smoking status, presence of upper tract or perianal disease, presence of EIM or type of medical therapy initiated. Obstructing or penetrating disease was associated with higher exposure to diagnostic radiation (OR 4.84, 95% CI 1.07 to 21.98). There was also a trend to higher radiation exposure in patients with ileal or ileocolonic compared to patients with colonic disease (OR 5.2, 95% CI 0.59 to 45.87). Conclusion: Obstructing and penetrating CD is associated with higher diagnostic radiation exposure compared to patients with inflammatory disease behavior. Ileal and ileocolonic disease location compared to colonic disease location is also likely associated with higher radiation exposure. The use of ionizing radiation in the diagnostic evaluation of CD, especially in patients with complicated disease behavior and small bowel disease, should be minimized in an effort to reduce their lifetime exposure to radiation.

Prospective Evaluation of MR Enterography as the Primary Imaging Modality for Pediatric Crohn Disease Assessment

The objectives of this study were prospective evaluation of MR enterographic accuracy for detecting Crohn disease imaging features in pediatric patients, compared with a CT reference standard, as well as determination of MR enterographic accuracy for detecting active bowel inflammation and fibrosis using a histologic reference standard. The study group for this blinded prospective study included 21 pediatric subjects with known Crohn disease scheduled for clinical CT and histologic bowel sampling for symptomatic exacerbation. All subjects and their parents gave informed consent to also undergo MR enterography. CT and MR enterography examinations were independently reviewed by two radiologists and were scored for Crohn disease features. All bowel histology specimens were reviewed by a single pathologist for the presence of active mucosal inflammation and mural fibrosis, followed by correlation of imaging and histologic findings. All 21 subjects underwent MR enterography and histologic sampling, 18 of whom also underwent CT. MR enterography had high sensitivity for detecting Crohn disease imaging features (e.g., bowel wall thickening, mesenteric inflammation, lymphadenopathy, fistula, and abscess) compared with CT, with individual sensitivity values ranging from 85.1% to 100%. Of a total of 53 abnormal bowel segments with correlation of MRI and histologic findings, MR enterography showed 86.7% accuracy (90.0% sensitivity and 82.6% specificity) for detecting active inflammation (p < 0.001). The accuracy of MR enterography for detecting mural fibrosis overall was 64.9%, compared with histology, but increased to 83.3% (p < 0.05) for detecting fibrosis without superimposed active inflammation. MR enterography can substitute for CT as the first-line imaging modality in pediatric patients with Crohn disease, on the basis of its ability to detect intestinal pathologic abnormalities in both small and large bowel as well as extraintestinal disease manifestations. Additionally, MR enterography provides an accurate noninvasive assessment of Crohn disease activity and mural fibrosis and can aid in formulating treatment strategies for symptomatic patients and assessing therapy response.

Perioperative Factors During Ileal Pouch-Anal Anastomosis Predict Pouchitis

Pouchitis is the most common complication of IPAA. Identifying factors predictive of pouchitis may improve outcomes by modifying contributing factors and enhancing patient selection. The most objective means for confirming pouchitis is by histology because the clinical and endoscopic diagnoses rely on more subjective assessments. The importance of histological pouchitis in the absence of clinical or endoscopic findings is unknown. Prospectively collected data on patients with IPAA and pouch surveillance were evaluated. Patients who developed pouchitis, defined as symptoms of pouchitis confirmed by endoscopic biopsy (group B) were compared with those without any episode of clinical, endoscopic, or histological pouchitis (group A) for pre- and intraoperative factors and outcomes. Asymptomatic patients with histological pouchitis on surveillance biopsies (group C) were further compared with group A. Patients with Crohn's disease were excluded. Of the 673 patients with pouch biopsies, 422 (62.7%) were in group A, 161 (23.9%) in group B, and 90 (13.4%) in group C. Mean follow-up was 9.8 (±5.1), 12.4 (±5.4), and 13. (±4.7) years. Of the 43 preoperative factors evaluated, those associated with group B included leukocytosis (P < .001), rheumatologic extraintestinal disease (P < .001), disease proximal to splenic flexure (P = .001), pulmonary comorbidity (P = .004), prior steroid use (P = .006), and age at operation and diagnosis (P = .018 and .021). Of the 10 intraoperative factors evaluated, pouchitis was associated with S-pouch reconstruction (P < .001), transfusion (P < .001), and 2-stage instead of 3-stage operation (P = .05), all surrogates for operative complexity. On multivariate analysis, pulmonary comorbidity (OR 3.38, 95% CI 1.62-7.07), disease proximal to splenic flexure (OR 2.37, 95% CI 1.18-4.77), extraintestinal disease manifestations (OR 1.6, 95% CI 1.01-2.54), and S-pouch reconstruction (OR 1.59, 95% CI 0.99 - 2.54) were associated with pouchitis. Patients in group B had worse outcomes, including more strictures (P = .015), bowel obstructions (P = .019), fistulas (P = .18), and lower quality of life (P < .001). Group C patients had the same outcomes as those in group A and the finding was not predicted by the above-mentioned parameters. Patients with symptomatic, biopsy-confirmed pouchitis have worse long-term outcomes than those without pouchitis. This complication is associated with specific pre- and intraoperative factors. Histological pouchitis incidentally found on surveillance biopsy in asymptomatic patients is of no clinical relevance and does not influence outcome. Identification of these preoperative factors associated with the subsequent development of pouchitis will strengthen patient counseling and may facilitate risk stratification.

Inflammatory Bowel Disease in Military Aviators: 14 Cases With Return to Flying Duty

Inflammatory bowel disease, such as ulcerative colitis or Crohn's disease, is not a rare entity among military aviators. This relapsing inflammatory condition which may also affect extra intestinal organs can cause recurrent symptoms with considerable morbidity. The unpredictable nature of the disease, side effects of medications, and potential surgical procedures are obvious aeromedical concerns let alone the disease's extra-intestinal manifestations, some of which may result in sudden incapacitation. We present 14 military aviators who were diagnosed with inflammatory bowel disease and returned to flight duty after stabilization of symptoms. Mean follow-up period was 102 months (total of 1,429 months) without any adverse effects on flight safety. Only 4 aviators were grounded for a cumulative duration of 35 months during that period. We believe that because adequate disease control is readily feasible in most cases, safe return to flight duty within a short period is reasonable in uncomplicated cases.

Impact of Age at Diagnosis and Ulcerative Colitis Disease Extent

Purpose: Ulcerative colitis (UC) primarily affects young adults; however 12% of patients are diagnosed at an advanced age. Previous studies report that older patients are less likely to have pancolitis and more likely to have distal disease location. However, no studies have classified patients using the Montreal classification system. Our objective was to compare UC phenotype by age of diagnosis in a tertiary referral cohort. Methods: The Inflammatory Bowel Disease Program's Clinical Database prospectively documents demographic, extraintestinal manifestations of disease (EIM), and Montreal classification of disease for all UC patients at each clinic visits. Demographics, disease extent, and EIM were compared by the following age of diagnosis groups: <17 years, 17-40 years, 41-59 years, ≥60 years. Results: 270 patients evaluated at a tertiary referral center between July 1, 2004 and April 19, 2010 were included. Mean age of diagnosis was 29.8 years. 8% (n=22) were diagnosed under age 17, 62% (n=167) were diagnosed between 17 and 40 years of age, 24% (n=64) were diagnosed between age 41 and 59, and 6% (n=17) were diagnosed at age ≥ 60. Gender, race, and family history of inflammatory bowel disease did not differ by age at diagnosis. 82%, 71%, 47%, and 18% of patients diagnosed at <17, 17-40, 41-59, and ≥60 years of age were never smokers (p<0.001). Mean disease duration from time of diagnosis was 16.7, 11.1, 8.2, and 5.5 years in patients diagnosed at <17, 17-40, 41-59, and ≥60 years respectively (p<0.001). As age of diagnosis increased, there was a trend for an increased proportion of patients with proctitis and a decreased proportion of patients with pancolitis (see Table). Conclusion: After adjustment for smoking history, patients diagnosed at 60 or older were less likely to develop pancolitis compared to younger cohorts (OR 0.78, 95% CI 0.49, 1.23); however the finding was not statistically significant. Adjusting for disease duration, did not affect the odds of developing pancolitis (data not shown).Table: [1272] Ulcerative colitis disease extent by age at diagnosis