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Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels and anti-drug antibodies, is a promising strategy that can be used to optimize inflammatory bowel disease therapeutics. It is based on the premise that there is a relationship between drug exposure and outcomes, and that considerable inter-individual variability exists in how patients metabolize the drug (pharmacokinetics) and the magnitude and duration of response to therapy (pharmacodynamics). Therefore, the American Gastroenterological Association has prioritized clinical guidelines on the role of TDM in the management of inflammatory bowel disease. To inform these clinical guidelines, this technical review was developed in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework for interventional and prognostic studies, and focused on the application of TDM for biologic therapy, specifically anti-tumor necrosis factor−α agents, and for thiopurines. Focused questions address the benefits and risks of a strategy of reactive TDM (in patients with active inflammatory bowel disease) to guide treatment changes compared with empiric treatment changes, and the benefits and risks of a strategy of routine proactive TDM (during routine clinical care in patients with quiescent disease) compared with no routine TDM. Additionally, the review addresses the benefits and risks of routine measurement of thiopurine methyltransferase enzyme activity or genotype before starting thiopurine therapy compared with empiric weight-based dosing and explores the performance of different trough drug concentrations for anti−tumor necrosis factor agents and thiopurines to inform clinical decision making when applying TDM in a reactive setting. Due to a paucity of data, this review does not address the role of TDM for more recently approved biologic agents, such as vedolizumab or ustekinumab.

Endoscopy is essential for the diagnosis and management of patients with inflammatory bowel diseases. Endoscopic procedures are used to make the initial diagnosis of inflammatory bowel disease (IBD), distinguish Crohn’s disease from ulcerative colitis, evaluate disease extent and disease activity, assess response to therapy, survey for dysplasia, and provide endoscopic treatment. This review focuses on the purpose of different endoscopic procedures including upper and lower endoscopy, and capsule endoscopy as well as balloon enteroscopy in the evaluation and management of patients with IBD in the United States.

Background Managing patients with inflammatory bowel disease requires multidisciplinary coordination. Technological advances have enhanced access to care for patients and improved physician interactions. The primary aim of our project was to convene diverse institutions and specialties through a multisite virtual conferencing platform to discuss complex patient management. Methods The case conference is designed to include multiple institutions to exchange ideas, review evidence-based data, and provide input on the management of patients with Crohn's disease and ulcerative colitis. Technology is supplied and coordinated by an information technology specialist and Chorus Call, Inc., an international teleconferencing service provider. The Inflammatory Bowel Disease Live Interinstitutional Interdisciplinary Videoconference Education (IBD LIVE) initiative is accredited by the University of Pittsburgh Medical Center (UPMC) Center for Continuing Education in the Health Sciences for 1 AMA PRA Category 1 Credit per weekly session. Results IBD LIVE began in 2009 comprising only adult gastroenterology and pediatric gastroenterology from UPMC Presbyterian and Children's Hospitals. Participation steadily increased from 5 sites in 2010 to 11 sites in 2014. Maximum attendance for a single conference was 73 participants with a median of 48. The Continuing Medical Education scores (1 = worst to 5 = best) have a high median overall score (4.6, range 3.2-5.0) with positive responses with regard to the degree to which the conference changed practice. Conclusions IBD LIVE has been successful and continues to grow. Implementation of the Crohn's and Colitis Foundation of America Virtual Preceptor Program using the IBD LIVE platform will provide expanded national physician access to this professional education activity.

Use of the immunomodulators thiopurines and methotrexate (MTX) in the treatment of inflammatory bowel disease (IBD), i.e., Crohn's disease and ulcerative colitis (UC), is considered to be good clinical practice. However, despite being administered to a considerable number of IBD patients over the years, questions remain about the most rational treatment regimens of azathioprine (AZA), 6-mercaptopurine (6-MP), and MTX, and results from a range of recent studies necessitate increased attention to how to optimize the use of these immunomodulators. First and foremost, it is of utmost importance to define the subgroup of IBD patients in need of immunomodulators, including those in need of combination therapy with biologic agents, especially because some side effects may be rather severe. Second, colorectal cancer is observed more often in IBD patients than in the background population. However, a recent nationwide Dutch study pointed to a preventive effect of thiopurines. Finally, the need for an appropriate approach to the discontinuation of immunomodulators is emphasized. Since controversy continues regarding the most appropriate use of immunomodulators, this paper is focusing on pharmacokinetics, pharmacogenetics, and therapeutic blood testing, as well as the occurrence of adverse events, when using AZA, 6-MP, and MTX in an attempt to determine a more up-to-date and rational treatment regimen in IBD.

Imaging is a central component of the diagnostic process in inflammatory bowel diseases. This review summarizes the recent progress of various most commonly used imaging modalities including computed tomography enterography, magnetic resonance enterography and capsule endoscopy. Advantages and disadvantages of each imaging protocol in suspected and established inflammatory bowel diseases are reviewed and brought into context in proposed diagnostic algorithms.

Budesonide is a synthetic corticosteroid characterized by enhanced topical potency and limited systemic bioavailability. Its use in ulcerative colitis (UC) was limited to rectal preparations until recently when the new oral budesonide formulation incorporating the multi-matrix system technology was introduced. The purpose of this review is to evaluate the current role of oral and rectal budesonide in managing UC patients Areas covered: In this paper, we described the chemical structure and pharmacologic characteristics of the different oral and rectal budesonide preparations, provided a summary of the published trials that evaluated the efficacy and safety of budesonide in UC, and discussed the current status of its use in this population Expert opinion: Budesonide is effective in inducing remission in a subset of patients with mild-moderate UC. Nevertheless, the current evidence suggests inferiority of oral budesonide to 5-aminosalisylates (5-ASA) and systemic steroids, whereas rectal applications are comparable to other rectal steroid preparations, but still inferior to rectal 5-ASA. In clinical practice, several issues need clarification including, its exact position in the line of induction agents; the role of combining budesonide and 5-ASAs; the role of combining oral and rectal budesonide; and the role of budesonide in maintenance therapy.

Methotrexate (MTX) is an established therapy for patients with steroid-dependent Crohn's disease (CD). MTX is also frequently used in combination with anti-TNF agents to suppress anti-drug antibody formation. It has been suggested in the past that MTX lacks any clinical effectiveness in patients with ulcerative colitis (UC); however, newer data at least partially contradict this assumption. The following review will discuss recent data for the use of MTX in CD, UC and in combination with anti-TNF agents.

summary Background & aims: Conjugated linoleic acid (CLA) has demonstrated efficacy as an immune modulator and anti-inflammatory compound in mouse and pig models of colitis. We investigated the immunoregulatory efficacy of CLA in patients with mild to moderate Crohn’s disease (CD). Methods: Thirteen patients with mild to moderately active CD were enrolled in an open-label study of CLA (6 g/d orally) for 12 weeks. Peripheral blood was collected at baseline, 6 and 12 weeks after treatment initiation for isolation of peripheral blood mononuclear cells for functional analyses of lymphoproliferation and cytokine production. Disease activity was calculated using the CD activity index (CDAI) and quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Results: CLA significantly suppressed the ability of peripheral blood CD4þ and CD8þ T cell subsets to produce IFN- g, TNF-a and IL-17 and lymphoproliferation at week 12. There was a statistically significant drop in CDAI from 245 to 187 (P ¼ 0.013) and increase in IBDQ from 141 to 165 (P ¼ 0.017) on week 12. Conclusion: Oral CLA administration was well tolerated and suppressed the ability of peripheral blood T cells to produce pro-inflammatory cytokines, decreased disease activity and increased the quality of life of patients with CD.

Growing evidence demonstrates the adverse effects of narcotics in inflammatory bowel disease (IBD). We sought to study the relationship between narcotic use, objective measures of disease activity, and other associated factors in hospitalized patients with IBD.We performed a retrospective cohort study of all adult IBD patients admitted to a general medical or surgical ward service at a United States tertiary care center over a 1-year period. We collected demographic and disease-specific information, inpatient narcotic use, and disease activity measurements from endoscopic and radiologic reports. Bivariate comparisons were made between characteristics and narcotic use. Logistic regression was used to evaluate the independent effects of characteristics on narcotic use.A total of 117 IBD patients were included. Narcotics were given to 70.1% of hospitalized patients. Factors significantly associated with any inpatient narcotic use: Crohn's disease (CD); P ≤ 0.01, duration of IBD, P = 0.02, prior psychiatric diagnosis, P = 0.02, outpatient narcotic use, P ≤ 0.01, current smoking, P ≤ 0.01, prior IBD-specific surgery, P0.02, and prior IBD / irritable bowel syndrome (IBS) diagnosis, P = 0.02. Narcotic use was not significantly associated with disease severity on computed tomography (CT) scan or endoscopy. On multivariate analysis, smoking (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.21-15.6) and prior outpatient narcotic use (OR 5.41, 95% CI 1.54-19.0) were independently associated with inpatient narcotic use.A majority of patients with IBD are prescribed narcotics during hospitalization in spite of data on increased complications. Risk factors for narcotic use include CD and associated factors (disease duration, surgeries), substance abuse (outpatient narcotics and smoking), psychiatric diagnoses, and IBD-IBS.

For more than a decade, methotrexate has been known to be an effective therapeutic agent in the treatment of steroid-dependent active Crohn’s disease. However, international data on medication utilization suggest that this drug is rarely used in clinical practice for an indication of Crohn’s disease. This review investigates the potential reasons for the underuse of methotrexate in patients with inflammatory bowel diseases.

Background: Obesity is a significant public health threat to children in the United States. The aims were to: 1) Determine the prevalence of obesity in a multicenter cohort of children with inflammatory bowel disease (IBD); 2) Evaluate whether overweight and obese status is associated with patient demographics or disease characteristics. Methods: We used data from the ImproveCareNow Collaborative for pediatric IBD, a multicenter registry of children with IBD, collected between April 2007 and December 2009. Children ages 2–18 years were classified into body mass index (BMI) percentiles. Bivariate analyses and multivariate logistic regression were used to compare demographic and disease characteristics by overweight (BMI >85%) and obese (BMI >95%) status. Results: The population consisted of 1598 children with IBD. The prevalence of overweight/obese status in pediatric IBD is 23.6%, (20.0% for Crohn's disease [CD] and 30.1% for ulcerative colitis [UC] and indeterminate colitis [IC]). African American race (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.10–2.48) and Medicaid insurance (OR 1.67, 95% CI 1.19–2.34) were positively associated with overweight/obese status. Prior IBD-related surgery (OR 1.73, 95% CI 1.07–2.82) was also associated with overweight and obese status in children with CD. Other disease characteristics were not associated with overweight and obesity in children with IBD. Conclusions: Approximately one in five children with CD and one in three with UC are overweight or obese. Rates of obesity in UC are comparable to the general population. Obese IBD patients may have a more severe disease course, as indicated by increased need for surgery. Sociodemographic risk factors for obesity in the IBD population are similar to those in the general population. (Inflamm Bowel Dis 2010;)

Background: Capsule endoscopy (CE) is performed to assess inflammatory bowel disease (IBD). We aimed to define the results of CE in subtypes of IBD and to determine whether CE results in management changes. Methods: A retrospective cohort study was performed of all CEs for IBD at a tertiary care center from 2003–2009. Descriptive statistics were used to compare IBD-specific medications, surgeries, and imaging studies in the 3 months prior and 3 months after CE. Results: Of 907 CEs performed from 2003–2009, 128 were for an indication of symptomatic IBD and 124 capsules left the stomach (86 for Crohn's disease [CD], 15 for indeterminate colitis [IC], 23 for pouchitis). Only 22.1% of CEs done for CD were normal, as compared to 53.3% for IC and 34.8% for pouchitis. Severe findings in CD consisted of multiple aphthae/ulcers (22.1%), stenosis (8.1%), and stenosis with immediate retention (17.4%). In CD, 61.6% had a change in medication in the 3 months after the CE, with 39.5% initiating a new IBD medication, most commonly budesonide or corticosteroids. In the 3 months following CE, 12.8% of patients with CD underwent surgery. Severe findings on CE in patients with CD, as compared to no/minimal findings, resulted in significant differences in medication changes (73.2% versus 51.1%, P = 0.04), addition of medications (58.5% versus 22.2%, P < 0.01), and surgeries (21.9% versus 4.4%, P = 0.01). Conclusions: CE results in management changes in the majority of cases of symptomatic IBD, regardless of the subtype of IBD. (Inflamm Bowel Dis 2011;)

Adipocytes of peripancreatic and intrapancreatic adipose tissue secret adipocytokines such as leptin, adiponectin, and resistin. For resistin, a role as an early predictor of peripancreatic necrosis and clinical severity in acute pancreatitis has been reported. It was the aim of this study to investigate whether the adipocytokine visfatin is able to serve as an early marker predicting peripancreatic necrosis and clinical severity.A total of 50 patients (20 females and 30 males) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and APACHE-II (Acute Physiology and Chronic Health Evaluation II) score. Pancreatic and peripancreatic necrosis were quantified by the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Visfatin was measured at admission and daily for 10 days by enzyme-linked immunosorbent assay (ELISA).Visfatin values were significantly and positively correlated with clinical severity (APACHE-II score and Ranson score) and with clinical end points such as death and need for interventions. Admission visfatin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver operator characteristics that admission visfatin concentration provides a positive predictive value of 93.3% in predicting the extent of peripancreatic necrosis (area under the curve (AUC): 0.89, P0.001, sensitivity: 93.3%, specificity: 81.8%, likelihood ratio: 5.1, post-test probability: 93%) by using a cutoff value of 1.8 ng/ml.Admission visfatin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Visfatin may have potential for clinical use as a new and diagnostic serum marker.

To determine whether polyp detection rates are reduced as time progresses through half and full-day endoscopy shifts.Polyp detection on colonoscopy may be reduced during colonoscopies performed later in the day.Retrospective analysis of screening colonoscopies performed by attending physicians only between August 2003 and August 2005 at University of North Carolina Hospitals. The primary outcome was detection of any polyp. The secondary outcome was adenoma detection. Both were assessed by time of day and shift type.A total of 3421 eligible screening colonoscopies, performed by 20 attending gastroenterologists, were analyzed. Polyp detection rate for colonoscopies initiated before 9 AM was 48.6%, versus 34.0% for those initiated after 4:00 PM (P=0.04). On multivariate analysis, each hour of the day was associated with reduced odds of polyp detection [adjusted odds ratio (OR) 0.93, 95% confidence interval (CI) 0.89-0.98 for any polyp; adjusted OR: 0.94, 95% CI: 0.89-0.98 for adenoma]. When evaluated by physician shift, the odds of polyp detection were reduced in the last 1.5 hours compared with the first 1.5 hours of the shift, regardless of the length or timing of the shift (AM shift: OR: 0.63, 95% CI: 0.41-0.96; PM shift: OR: 0.79, 95% CI: 0.42-1.46; and full-day shift: OR: 0.67, 95% CI: 0.44-1.00).Polyp detection by attending tertiary-care gastrointestinal physicians is reduced as time progresses during both half and full-day endoscopy shifts. These findings have implications for future quality improvement interventions.

In the absence of overt structural abnormalities, the diagnostic approach to chronic abdominal pain can be challenging. Occupational particulate inhalation causing injury to an organ other than the lung is rare. We report a case of inadvertent glass microparticulate ingestion causing chronic abdominal pain with altered local and systemic inflammatory responses.

OBJECTIVES: Peripancreatic necrosis determines clinical severity in acute pancreatitis. Early markers predicting peripancreatic necrosis and clinical severity are lacking. Because adipocytes of peripancreatic adipose tissue secret highly active adipocytokines, the aim of the study was to investigate whether adipocytokines are able to serve as early markers predicting peripancreatic necrosis and clinical severity. METHODS: A total of 50 patients (20 women, 30 men) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and the APACHE (Acute Physiology And Chronic Health Evaluation) II score. Pancreatic and peripancreatic necrosis were quantified by using the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Adiponectin, leptin, and resistin were measured at admission and daily for at least 10 days by enzyme-linked immunosorbent assay. RESULTS: In contrast to admission C-reactive protein values, admission resistin values were significantly correlated with clinical severity and even with clinical end points such as death and need for interventions. Admission resistin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver-operator characteristics that admission resistin concentration provides a positive predictive value of 89% in predicting the extent of peripancreatic necrosis (area under the curve, 0.8; P=0.002; sensitivity, 80%; specificity, 70%) by using a cutoff value of 11.9 ng/ml. CONCLUSIONS: Admission resistin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Resistin may have potential for clinical use as a new and diagnostic serum marker.

Methotrexate, which was initially developed in 1948 for the treatment of leukemia, has been used clinically for nearly 60 years as low- and high-dose therapy in other diseases including certain lymphomas, Wegeners’ disease, psoriasis, and rheumatoid arthritis. In inflammatory bowel diseases (IBDs) methotrexate’s clinical efficacy has been established for steroid-dependent Crohn’s disease (CD) in adults and also in children refractory or intolerant to thiopurine therapy.1–5 The effectiveness of intramuscularly (i.m.) administered methotrexate 25 mg once weekly in steroid-dependent CD is well documented. In the North American Crohn’s Study Group’s landmark trial, 39.4% of the patients receiving methotrexate (25 mg, i.m./week) were in clinical remission as defined by the Crohn’s Disease Activity Index (CDAI)

Due to further technical developments in recent years, magnet resonance imaging (MRI) is now recognized as one of the primary diagnostic imaging modalities in the field of Internal Medicine. This review describes relevant indications for MRI in the different subspecialties of Internal Medicine and compares the diagnostic yield of MRI to other established modalities such as computed tomography and ultrasound.

A severe flare of colitis in patients with IBD treated with immunosuppressive therapy may be complicated by an underlying CMV infection. The aim of this pilot study was to investigate the diagnostic efficacy of quantitative polymerase chain reaction (PCR) to detect CMV DNA in stool samples of IBD patients. Twenty-one patients with a severe flare of IBD, incompletely responding or refractory to either steroids or immunosuppressive agents, were included in the study. Nineteen patients completed the study according to the protocol undergoing an endoscopy with biopsies and collection of stool samples. Biopsy and stool samples were qualitatively and quantitatively analyzed for CMV DNA using real-time PCR. Thirty-two percent (6/19) of the patients had detectable CMV DNA in colonic biopsies and in five (83%) of those patients CMV DNA was detected in the stool. Thirteen patients had negative findings for CMV DNA in biopsy and stool samples. The sensitivity, specificity, and accuracy of the PCR-based stool test for detection of CMV DNA compared to PCR-based detection of CMV in mucosal biopsies were 83, 93, and 90%, respectively. The pilot study suggests a high accuracy of this non-invasive testing method to detect CMV DNA in stool samples as compared to mucosal biopsies. This approach may offer a non-endoscopic testing modality for underlying CMV infection in patients with a severe flare of IBD, which could also be applied more broadly to determine the prevalence of CMV infections in patients with IBD.

In a survey comprising 1,176 patients with inflammatory bowel disease (IBD) we recently showed that azathioprine (AZA) beyond 4 years is beneficial in ulcerative colitis (UC) patients and in a subset of Crohn's disease (CD) patients. Here, we show for the first time that azathioprine responsiveness depends on body mass index (BMI). The relationship is reciprocal in UC and CD, with a better outcome in UC patients with a BMI 25. These observations are particularly interesting considering the evolving concept of a relationship between fatty metabolism and immune regulation. Additionally, we show that CD patients, but not UC patients, respond better to AZA when it is started in clinical remission. This observation may support data favouring a "hit hard and early" regime in CD. Finally, we were able to demonstrate a decrease in the incidence of CD-related complications requiring surgery through treatment with AZA

To evaluate the efficacy and safety of purine analogs (azathioprine, 6-mercaptopurine (6-MP)) in the prevention of postoperative recurrence in Crohn's disease (CD). We searched MEDLINE, the Cochrane Library, and EMBASE. The primary end points, clinical and endoscopic recurrence at 1 and 2 years, and safety were analyzed by the methods of Peto and Der Simonian and Laird. Four controlled trials enrolled 433 patients and compared azathioprine (n=3) or (6-MP) (n=1) with control arms (placebo with or without antibiotic induction therapy or mesalamine). In the overall analysis, purine analogs were more effective than control arms in preventing clinical recurrence at 1 year (mean difference, 95% confidence interval (CI): 8, 1-15%, P=0.021, number needed to treat (NNT)=13) and 2 years (mean difference, 95% CI: 13%, 2-24%, P=0.018, NNT=8). In sensitivity analyses, the efficacy of purine analogs was superior to that of placebo for the prevention of clinical and endoscopic recurrence at 1 year (mean differences, 95% CI: 13, 1.8-25%, P=0.025, NNT=7, and 23%, 9-37%, P=0.0016, NNT=4, respectively). At 1 year, in the overall analysis, purine analogs were more effective than control arms were in preventing severe (i2-4) endoscopic recurrence (mean difference, CI 95%: 15, 1.8-29%, P=0.026, NNT=7), but they were not effective in the prevention of very severe (i3-4) recurrence. The rate of adverse events leading to drug withdrawal was higher in thiopurine-treated patients than in control arms (17.2 vs. 9.8%, respectively, P=0.021). Purine analogs are more effective than placebo in preventing both clinical and endoscopic postoperative recurrence in CD, but they are associated with a higher rate of adverse events leading to drug withdrawal

Gastroenterologists often encounter situations when the clinical and pathophysiological features that typically distinguish functional from organic disorders overlap. This "blurring of boundaries" can occur with post-infectious irritable bowel syndrome (PI-IBS), a subset of IBS and a newly described entity IBD-IBS. The key associating features include pain and usually diarrheal symptoms that are disproportionate to the observed pathology, microscopic inflammation, and often a co-association with psychological distress. A previous initiating gastrointestinal infection is required for PI-IBS and assumed for IBD-IBS. Using this perspective we discuss the clinical and pathophysiological features of PI-IBS and IBD-IBS and the growing evidence for the overlapping features of these two disorders in terms of alteration of gut flora, immune dysregulation, and role of stress. A unifying model of PI-IBS and IBD-IBS is proposed that may have important clinical and research implications. It obligates us to reframe our understanding of illness and disease from the dualistic biomedical model into a more integrated biopsychosocial (BPS) perspective.

Background: The therapy for posttransplant IBD is clinically challenging. Patients receiving liver transplants are immunosuppressed to prevent rejection, but via an unknown mechanism develop de novo IBD in spite of receiving some of the same medications used for therapy in traditional IBD. In the published literature most of the patients who developed de novo IBD were treated with traditional corticosteroids. Exposure to systemic corticosteroids increases risks of infection, diabetes mellitus, and osteoporosis among other complications. Budesonide, a luminally active steroid with low systemic absorption, is an established therapeutic agent for IBD that should receive special considerations as first-line therapy in this patient population. Methods: We describe 3 cases of de novo IBD after liver transplantation. None of these patients had a history of IBD prior to their transplant. All 3 were treated with oral budesonide in lieu of systemic corticosteroids. Additionally, a Medline MeSH search was performed using the terms “inflammatory bowel disease” and “liver transplant” as part of a systematic review of the literature. Results: All 3 cases of de novo post transplant IBD went into clinical remission with oral budesonide. The Medline search ultimately revealed 19 case reports, case series or retrospective reviews on de novo post liver transplant IBD. Most reports focused on the diagnosis and risk factors and did not have an emphasis on therapy. Conclusions: Given the track record for budesonide in traditional IBD, and its documented efficacy and systemic steroid-sparing benefit, in our opinion this drug should be considered first-line therapy for de novo posttransplant IBD. (Inflamm Bowel Dis 2008;14:1695–1700)

Background Environmental factors are likely to be involved in the pathogenesis of inflammatory bowel disease (IBD), as the incidence of both Crohn's disease (CD) and ulcerative colitis (UC) increased with improved living standards in Europe after World War II. On the basis of earlier reports suggesting that hygienic standards may also play a role in the pathogenesis of IBD, we investigated the influence of hepatitis A seroprevalence as an indicator for poorer hygienic conditions and worm infestations in IBD. Methods Hepatitis A seroprevalence was examined in patients with UC and CD. Patients with minor endocrinological disorders served as controls. All patients were questioned about immunizations, parasitic infections (worms), contact with animals, living on a farm, and ever traveling abroad. Patients were excluded for active hepatitis A immunization or recent passive immunization. Results are presented as Mantel-Haenszel odds ratios with 95% confidence interval, adjusted for age group. Results The sample included 307 patients (73 CD, 48 UC, and 186 controls). Hepatitis A seroprevalence was strongly associated with age older than 50 years. Age adjusted Mantel-Haenszel odds ratios were 0.25 (0.09-0.71) for UC and 0.75 (0.38-1.46) for CD versus controls. For parasitic infections, the odds ratios were 1.15 (0.52-2.53) for UC and 0.34 (0.13-0.89) for CD. Conclusion We were able to demonstrate a negative association of hepatitis A infection with UC only. In contrast, a novel finding was a strong protective effect of worm infestations for the occurrence of CD, but not UC.

HISTORY AND CLINICAL FINDINGS: A 26-year-old man was admitted urgently because of breathing-related pain in the left thorax. This pain had started 3 months before, but had at first improved spontaneously. He had lost 13 kg during those weeks and had no recollection of any injury. Physical examination was unremarkable except for slight pain on upper-abdominal pressure and a palpably enlarged spleen. INVESTIGATIONS: All laboratory tests were normal, including the Quick value (100%), partial thromboplastin time (38 sec) and hemoglobin (14.2 g/dl). Chest radiogram showed a high left diaphragm. Abdominal sonography revealed a 12 x 10 cm moderately echogenic tumour in the spleen, extending from the splenic hilus to the upper splenic pole. Contrast-enhanced computed tomography demonstrated a hypodense tumour from which 300 ml of old blood were removed by needle puncture. Biopsy of the wall of the haematoma revealed pseudocystic transformation. TREATMENT AND COURSE: The pseudocyst again filled with blood in a few days. A drain was inserted and remained for 32 days. Six installations of alcohol achieved complete obliteration of the cystic haematoma, which did not recur. CONCLUSION: Splenic haematoma should be considered in the differential diagnosis of pain in the lower left thorax, even in the absence of a history of injury. Sonographically such a haematoma my imitate a solid tumor. Obliteration of the cavity by alcohol installation can be a successful alternative to surgical treatment.

1.1 Introduction Ulcerative colitis is a life long disease arising from an interaction between genetic and environmental factors, but observed predominantly in the developed countries of the world. The precise aetiology is unknown and therefore medical therapy to cure the disease is not yet available. Within Europe there is a North–South gradient, but the incidence appears to have increased in Southern and developing countries in recent years.1,2 Patients may live with a considerable symptom burden despite medical treatment (66% describe interference with work and 73% with leisure activities3) in the hope that the aetiology of ulcerative colitis will shortly be revealed and a cure emerges. Although this is conceivable in the next decade, clinicians have to advise patients on the basis of information available today. Despite randomized trials there will always be many questions that can only be answered by the exercise of judgement and opinion. This leads to differences in practice between clinicians, which may be brought into sharp relief by differences in emphasis between countries. The Consensus endeavours to address these differences. The Consensus is not meant to supersede the guidelines of different countries (such as those from the UK,4 or Germany5), which reach broadly the same conclusions since they are, after all, based on the same evidence. Rather, the aim of the Consensus is to promote a European perspective on the management of ulcerative colitis (UC) and its dilemmas. Since the development of guidelines is an expensive and time-consuming process, it may help to avoid duplication of effort in the future. A European Consensus is also considered important because an increasing number of therapeutic trials recruit from Central and Eastern European countries where practice guidelines have yet to be published. This document sets out the current European Consensus on the diagnosis and management …

The main goal of the therapy of inflammatory bowel diseases is the induction and maintenance of disease remission. Whereas the standard medical approach is guided by the clinical symptoms and concurrent therapy of the patients ('step-up' approach), a new evolving concept for patients with Crohn's disease is trying to modify the disease course by treating intestinal inflammation early and very aggressively with anti-TNF therapy and immunosuppressive agents, such as azathioprine ('top-down' approach). This review discusses the background of this new approach in Crohn's disease and places the first available clinical results of 'top-down' therapy into perspective with available data on potential adverse effects, the natural course and the therapeutic goal of mucosal healing in Crohn's disease.

Summary Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 µg/mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1β, IL-6, IL-12 tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in supernatants were analysed by the beadlyte® cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3·2 with acteoside versus 5·2 with phosphate-buffered saline (PBS) (P