Journal of Crohn's and Colitis - Articles in Press

Reply to Dr. Chiodini's and Dr. Chamberlin's letters - Corrected Proof

Herbert J. Van Kruiningen — 2012-02-03

I write today to address the points of confusion expressed by Dr. Chiodini and Dr. Chamberlin in their letters. The animal studies referred to were referenced at the end of the paragraph on “Transmission of Crohn's disease to animals”—see Ref. 1 published in 1999. Nowhere in the 1999 paper nor in the present manuscript do I mention using bacterial cultures as inoculum as was done in our earlier work. Yes, it was a different method—the inoculum was fresh triturated diseased tissue.

Fibromuscular dysplasia mimicking Crohn's disease over a period of 23years - Corrected Proof

W. Dolak, J. Maresch, F. Kainberger, F. Wrba, Ch. Müller — 2012-02-02

Abstract: Rare diseases with similar clinical presentation as more frequent gastrointestinal disorders might be challenging in the diagnostic and therapeutic management. In this case we report on a 47-year-old woman who was thought to suffer from Crohn's disease. Symptoms, macroscopic and histological aspects of the gastrointestinal tract, treatment response and clinical course had encouraged the wrong diagnosis over a period of 23years. After the patient died in the context of a sudden clinical deterioration, fibromuscular dysplasia of the aorta was finally unmasked by post-mortem examination as underlying cause of all symptoms attributed to Crohn's disease. Re-evaluation of former diagnostic procedures revealed subtle aspects of fibromuscular dysplasia, even in biopsy samples from 23years ago. This first case report of fibromuscular dysplasia of the aorta documents a rare pitfall in the diagnostic workup of a frequent clinical presentation in gastroenterology.

Synchronous colorectal carcinoma in segmental colitis associated with diverticulosis - Corrected Proof

Antonio Tursi — 2012-02-02

Segmental colitis associated with diverticulosis (SCAD) is a chronic disease affecting colonic regions harboring diverticula, with sparing of the rectum and right colon. Although rare, its prevalence is now increasing in clinical practice. The course of the disease is generally benign, but in some cases it may be complicated and require surgery.

Chronic hepatitis C, inflammatory bowel disease and interferon therapy - Corrected Proof

Cumali Efe, Emir Charles Roach, Tugrul Purnak, Ersan Ozaslan — 2012-02-02

Dear Sir, Interferon (IFN) alpha, in a combination with ribavirin, is currently the standard therapy for chronic viral hepatitis C (HCV). IFN-β1 alpha is also another kind of interferon which is commonly used in the treatment of multiple sclerosis. Both of these treatment modalities have been associated with various side effects, including the reactivation of autoimmune thyroid and liver diseases. Also, the exacerbation of preexisting inflammatory bowel disease (IBD) including, Crohn's disease and ulcerative colitis (UC) or the de novo induction of these entities, have been reported. Similarly, in February 2011 issue of Journal of Crohn's and Colitis, Tuna et al. reported a case of multiple sclerosis that developed UC during the course of IFN therapy. With this regard, we would like to present two cases, portraying the spectrum of the effects of INF during the treatment of HCV.

Adherence of gastroenterologists to European Crohn's and Colitis Organisation Consensus on Crohn's disease: A real-life survey in Spain - Corrected Proof

J. Hinojosa, J.P. Gisbert, F. Gomollón, A. López San Román — 2012-01-30

Abstract: Background: There is no information as to the extent by which Spanish gastroenterologists adhere to Crohn's disease (CD) management guidelines. The objective of this study was to evaluate the degree of adherence of Spanish gastroenterologists to the European Crohn's and Colitis Organisation (ECCO) guidelines and to determine whether differences in adherence exist between gastroenterologists specialized in inflammatory bowel diseases (GSIBDs) and general gastroenterologists (GGs).Methods: This was a prospective, nation-wide, questionnaire-based survey covering aspects related to diagnosis, treatment, follow-up, and safety considered by the physicians in their daily management of CD, as well as demographic traits seen in clinical practice.Results: The overall degree of adherence to guidelines by both GSIBDs and GGs was high. However, the use of imaging techniques in diagnosis, follow-up, and in relapsed patients differed between the two groups. In the diagnosis of perianal disease, GSIBDs used magnetic resonance and surgical exploration under anesthesia more frequently than GGs. In terms of therapeutic choices, the adherence to guidelines was good in both groups. However, GSIBDs showed significantly higher adherence in some areas: thiopurines were used less in refractory cases and methotrexate was used more commonly in corticoid-dependent, azathioprine-intolerant patients, and in patients under biological treatment. Request for infection studies and vaccinations at diagnosis or prior to treatment was more common among GSIBDs.Conclusions: Guideline adherence among Spanish gastroenterologists is high. However, there are significant differences between IBD-specialized (more adherent in general) and non-specialized gastroenterologists.

Clumsy analogy yields melodramatic conclusion: MAP are not weapons of mass destruction - Corrected Proof

Judith Eve Lipton — 2012-01-30

It is histrionic and misleading to compare research on MAP and Crohn's Disease to the fruitless search for weapons of mass destruction in Iraq prior to the US invasion. The comparison is odious for several reasons.

Vitamin D as a therapy for colitis: A systematic review - Corrected Proof

Imogen Nicholson, A. Mark Dalzell, Wael El-Matary — 2012-01-30

Abstract: Background and aim: The effect of vitamin D supplementation on immune disorders has been a topical research focus. The aim of this systematic review was to examine the current evidence of the effect of vitamin D supplementation as a therapy for colitis.Methods: The following databases were searched: MEDLINE, Pubmed, Scopus, Web of Knowledge, Cinicaltrials.gov and the Cochrane Central Register of Controlled Trials using the terms ‘inflammatory bowel disease’ ‘Crohn's disease’ ‘ulcerative colitis’ ‘colitis’ [and] ‘vitamin D’. Both human and animal studies published in English language were examined. The reference lists of included studies and review articles were manually searched for any relevant studies.Results: Four studies were included in this systematic review. All reported an improvement in disease activity with vitamin D supplementation. The only high quality human study reported a non-significant reduction of relapse rate for Crohn's disease. No major adverse effects of vitamin D supplementation were reported.Conclusions: Although there is some evidence that supplemental vitamin D, as an adjunctive treatment, may help in controlling colitis, this evidence is not enough to justify using vitamin D in treating inflammatory bowel disease (IBD). Large high quality placebo-controlled randomised controlled trials are needed to explore a possible benefit of using vitamin D in treating IBD.

Cutaneous sarcoidosis in a patient with ulcerative colitis on infliximab - Corrected Proof

Kum C. Fok, Watson W.S. Ng, Christopher J.A. Henderson, Susan J. Connor — 2012-01-30

Abstract: The advance of anti-tumour necrosis factor (TNF) therapy had dramatically changed the treatment algorithm of inflammatory bowel disease (IBD). This had significantly improved the quality of life for patients with Crohn's disease (CD) and ulcerative colitis (UC).1 However, side-effects of anti-TNF treatment were unavoidable with paradoxical inflammation (for example leucocytoclastic vasculitis and psoriasis) being well-known phenomena of anti-TNF therapy.2 We report a case of infliximab induced cutaneous sarcoidosis in a patient with ulcerative colitis and review the literature.

Infliximab-induced psoriasis during therapy for Crohn's disease - Corrected Proof

2012-01-27

Abstract: Although therapy with tumor necrosis factor-alpha inhibitors (anti-TNF) provides beneficial effects in different immune inflammatory disorders, paradoxical cases of anti-TNF-induced psoriasis have increasingly been reported, mostly in the setting of rheumatologic diseases. To date, less than 50 cases of infliximab-induced psoriasis in inflammatory bowel disease patients have been described. The present report was aimed at describing two new cases of infliximab-induced psoriasis during therapy for Crohn's disease and at carrying out a review on this intriguing phenomenon.

Surgical management of gluteal metastatic cutaneous Crohn's disease - Corrected Proof

Niamh Hogan, Valerie Byrnes, Alan Hussey, Myles Joyce — 2012-01-27

Abstract: Metastatic cutaneous Crohn's disease is a rare entity first described by McCallum et al. in 1976. It is diagnosed when histologically characteristic granulomata are seen at a site not contiguous with inflammatory disease in the gastrointestinal tract. We herein report presentation, diagnosis and management of a 28year old lady with disabling, symptomatic cutaneous Crohn's of the buttocks and natal cleft refractory to Infliximab therapy. To the best of our knowledge only four other adult cases have been reported in the literature of metastatic cutaneous Crohn's disease of the buttock area distant from a flexure or area of skin apposition. The differential diagnosis in this case was Hidradenitis Suppurativa. A good cosmetic result and excellent symptom control were achieved with extensive debridement, wide local excision, vacuum assisted closure and delayed skin grafting.

On the zoonosis of M. avium subspecies paratuberculosis (MAP) - Corrected Proof

Robert J. Greenstein, D. William Cameron, Sheldon T. Brown — 2012-01-27

As investigators who hypothesize that MAP is zoonotic, we read with considerable interest Dr. van Kruiningen's review contending that supportive data are flawed. We would like to address three regions of major concern.

Much is still to be learned about pathogenic Mycobacteria - Corrected Proof

William M. Chamberlin — 2012-01-24

This letter is in response to the recent article by H. Van Kruiningen published in the JCC. In my opinion, Van Kruiningen's viewpoint is misleading. The association of Mycobacterium paratuberculosis (MAP) with Crohn's Disease (CD) is clearly established. The exact role (causal, secondary infection or unrelated) is controversial. Productive discussion of this controversy requires a working knowledge of MAP infection in animals and CD in humans, the behavior of pathogenic mycobacteria, and the host immune response to mycobacteria. Limited to 450 words, this rebuttal is sparse and selective. Readers are referred to an upcoming publication in Critical Reviews in Microbiology.

Exacerbation of Crohn's disease as paradoxical effect of infliximab - Corrected Proof

Antonio Tursi, Alfredo Papa — 2012-01-24

Dear Sir, It is recognized that anti-TNF-α antibodies have modified the therapeutic approach to severe inflammatory bowel disease.

Maternal imprinting and female predominance in familial Crohn's disease - Corrected Proof

2012-01-24

Abstract: Background and aim: Although the genetic risk factors for familial and sporadic inflammatory bowel disease (IBD) seem identical, the relative risk for contracting IBD in the familial setting is larger as that seen in the population at large, suggesting an important role of epi- and/or paragenetic factors in familial IBD. Epidemiological data indicate a female predominance in IBD, but how this relates to familial IBD has not been assessed.Methods: Familial IBD patients (N=608) were compared with a cohort of 415 sporadic IBD patients with regards to the patterns of sex and disease type distribution. The imprinting pattern in 87 families in which both a parent and a child had IBD was tested using Galton binominal statistics.Results: The percentage of females in familial IBD population was significantly higher (61%; female/male ratio 1.5) compared with sporadic IBD (54%; female/male ratio 1.2; p=0.011). The analysis of offspring sex distribution pattern revealed significantly higher female to female transmission compared with female to male transmission rate (36 vs. 18, respectively; p=0.02). A significantly higher number of mother to child transmissions (55 vs. 32 of father to child transmissions) was observed (p=0.018). The female imprinting was specifically related to Crohn's disease (31 vs. 14 mother vs. father to child transmissions, respectively; p=0.016).Conclusion: We propose that a female sex-specific epigenetic inheritance pattern for Crohn's disease is a major contributing factor in the family-specific risk in Crohn's disease. Sex-specific manifestation of familial Crohn's disease can partly explain the epidemiologically observed increased relative risk for females for contracting IBD.

Anaemia and iron deficiency in children with inflammatory bowel disease - Corrected Proof

Anthony E. Wiskin, Ben J. Fleming, Stephen A. Wootton, R. Mark Beattie — 2012-01-18

Abstract: Background and aims: Anaemia and iron deficiency are common in children with Inflammatory Bowel Disease (IBD) however it is not known if the prevalence of anaemia and iron deficiency alters following diagnosis.Methods: Laboratory results from diagnosis, and at follow up one and two years later were recorded retrospectively in children with IBD recruited from a tertiary centre. Anaemia was defined using WHO standards and iron deficiency defined using published guidelines.Results: 46 children (16 girls) with Crohn's disease and 34 children (18 girls) with UC were studied. 75% of children with IBD were anaemic at diagnosis, 30% were anaemic at follow up two years later. 90% of children with Crohn's and 95% of children with Ulcerative Colitis (UC) were iron deficient at diagnosis. At follow up two years later 70% of children with Crohn's and 65% of children with UC were iron deficient.Conclusions: Persistent anaemia and iron deficiency are common in childhood IBD, prevalence alters with duration of time from diagnosis.

Cyclosporine or infliximab as rescue therapy in severe refractory ulcerative colitis: Early and long-term data from a retrospective observational study - Corrected Proof

2012-01-16

Abstract: Introduction: About 30-40% of patients with acute severe ulcerative colitis (UC) fail to respond to intensive intravenous (iv) corticosteroid treatment. Iv cyclosporine and infliximab are an effective rescue therapy in steroid-refractory UC patients but up to now it is still unclear which is the best therapeutic choice.Methods: We reviewed our series of severe steroid-refractory colitis admitted consecutively since 1994 comparing two historical cohort treated with iv cyclosporine (2mg/kg) or iv infliximab (5mg/kg). The main outcome was the colectomy rate at 3 months, 12 months and at the end of the follow-up.Results: A total of 65 patients were included: 35 in the cyclosporine group and 30 in the infliximab one. At 3 months the colectomy rate was 28.5% in the cyclosporine group and 17% in the infliximab group (p=0.25), while 48% versus 17% at 12 months (p=0.007, OR 4.7; 95% CI: 1.47-15.16). The 1-2-3 year cumulative colectomy rates were 48%, 54%, 57% in the cyclosporine group, and 17%, 23%, 27% in the infliximab group. At the end of the follow-up the colectomy rate was 60% versus 30% (p=0.04, HR 2.2; 95% CI: 1.11-4.86). High level of C reactive protein (p=0.04), extensive disease (p=0.01) and no azathioprine treatment (p<0.001) were related to the risk of colectomy.Conclusion: This study, despite being retrospective, indicates that both cyclosporine and infliximab are effective in avoiding a colectomy in steroid-refractory UC patients. During the follow-up the risk of a colectomy is higher in patients treated with cyclosporine than with infliximab.

Lewis Score: A useful clinical tool for patients with suspected Crohn's Disease submitted to capsule endoscopy - Corrected Proof

Bruno Rosa, Maria João Moreira, Ana Rebelo, José Cotter — 2012-01-16

Abstract: Background/aims: The Lewis Score (LS) can assess inflammatory activity on small bowel capsule endoscopy (SBCE). We aimed to evaluate the LS usefulness in the setting of suspected Crohn's Disease (CD).Methods: Retrospective single-center study including 56 patients undergoing SBCE for suspected CD. Patients were divided into three groups, according to clinical presentation: Group 1 (28 patients): suspected CD not supported by the International Conference on Capsule Endoscopy (ICCE) criteria; Group 2 (19 patients): suspected CD based on two ICCE criteria; Group 3 (9 patients): patients fulfilling three or more criteria. Inflammatory activity was assessed with the LS. The diagnosis of CD required a minimum follow-up of 6months after SBCE, basing on clinical evaluation, endoscopic, histological, radiological, and/or biochemical investigations.Results: SBCE detected significant inflammatory activity (LS≥135) in 23 patients (41.1%), being 5 patients from Group 1 (17.8%), 11 from Group 2 (57.9%) and 7 from Group 3 (77.8%) (p<0.05). CD was diagnosed in 23 patients (41.1%): six patients from Group 1 (21.4%), 10 from Group 2 (52.6%) and 7 from Group 3 (77.8%) (p<0.05). CD was diagnosed in 82.6% of patients with significant inflammatory activity on CE (LS≥135), but in only 12.1% of those having a LS<135 (p<0.05). The LS Positive Predictive Value, Negative Predictive Value, Sensitivity and Specificity were 82.6%, 87.9%, 82.6% and 87.9%, respectively.Conclusions: The LS may be a valuable diagnostic tool in the setting of suspected CD. Patients not fulfilling the ICCE criteria have lower LS and fewer are diagnosed with CD during follow-up.

Low-dose smoking resumption in ex-smokers with refractory ulcerative colitis - Corrected Proof

Emma Calabrese, Henit Yanai, Dmitry Shuster, David T. Rubin, Stephen B. Hanauer — 2012-01-16

Abstract: Background and aim: Ulcerative colitis (UC) is primarily a disease of non-smokers. Ex-smokers may have a more refractory disease course and anecdotal evidence in non-controlled clinical trials have suggested that smoking resumption, or the administration of nicotine, may ameliorate signs and symptoms of UC in ex-smokers. We report outcomes of ex-smokers with refractory UC who resumed low-dose cigarette smoking.Methods: 17 ex-smokers with refractory UC were identified. Clinical remission was defined as a disease activity index score of 0.Results: Two out of 17 patients refused the recommendation to resume smoking. Of the 15 patients who resumed smoking, the mean daily number of cigarettes was 8.6. Fourteen out of those 15 patients who resumed smoking were able to maintain prolonged clinical remission off steroids. One out of the 15 patients failed to improve and required oral steroids. Another patient was compelled to quit smoking since he became addicted. His disease flared after maintaining a prolonged remission of 3years and he eventually underwent surgery. Three out of these 15 patients switched from cigarettes smoking to nicotine compounds and continued to maintain remission.Conclusion: Resumption of low dose smoking in a selected group of ex-smokers with refractory UC may ameliorate signs and symptoms. Quality of life, medication side effects, and smoking risk factors should all be considered and discussed with patients. Smokers should be meticulously followed for compliance with “low-dose” regimen and all associated smoking risks.

Long-term clinical impact of early introduction of granulocyte and monocyte adsorptive apheresis in new onset, moderately active, extensive ulcerative colitis - Corrected Proof

Takayuki Yamamoto, Satoru Umegae, Koichi Matsumoto — 2012-01-13

Abstract: Background and aims: The efficacy of granulocyte and monocyte adsorptive apheresis (GMA) for patients with a first episode of ulcerative colitis (UC) has been scarcely reported. This study was to see if the introduction of GMA at an early stage reduces corticosteroid administration and steroid dependency in the long term clinical course of UC.Methods: Forty consecutive patients with moderately active symptoms as the first attack of UC were included. Twenty patients were treated with GMA, with or without corticosteroids (GMA group), and the other 20 were given corticosteroids without GMA (steroid group). All patients were monitored for 5years. Relapses were treated in the same manner as the first attack in both groups. The total dose of steroid administered and the appearance of steroid-dependency were to be compared between the two groups.Results: All patients in both groups achieved clinical remission after the first attack. The mean number of relapses per patient was 2.8 in the GMA group and 2.9 in the steroid group (P=0.86). During this study, 5 patients in the GMA group did not require corticosteroids. The mean dose of steroid administered during the 5years was 2141mg in the GMA group vs 5443mg in the steroid group (P=0.002). One patient in the GMA group and 7 in the steroid group were steroid-dependent at the end of the study (P=0.048).Conclusions: In patients with the first UC episode, GMA therapy at an early stage significantly reduces steroid administration and steroid-dependency in the long-term clinical course.

Recommendations for the treatment of ulcerative colitis with infliximab: A gastroenterology expert group consensus - Corrected Proof

2012-01-12

Abstract: Background and aims: Infliximab is currently the only biologic approved for treatment of adults with moderate to severe, active ulcerative colitis (UC) unresponsive to conventional therapies. It rapidly controls symptoms, induces and sustains steroid-free remission, stimulates mucosal healing, and reduces serious complications. Although infliximab tends to be reserved for patients with severe disease, it may be even more beneficial for moderate disease earlier in the disease course. Therefore, it is important to identify which patients are candidates for infliximab therapy.Methods: A collaborative Delphi survey was used to obtain consensus on use of biologic therapy in patients with UC from an expert panel of 12 gastroenterologists with substantial experience using infliximab in clinical practice and clinical trials. The panel also addressed issues that influence the use of infliximab in UC, including its potential as an alternative to surgery.Results: The panel agreed that: (1) it is necessary to adopt additional treatment goals beyond symptom control, i.e., complete mucosal healing, steroid-free remission, improved QoL, and reduced long-term complications; (2) it may be possible to achieve these treatment goals with infliximab, especially if it is used earlier in the course of UC; and (3) infliximab should be offered as an alternative to surgery in patients being considered for colectomy. The panel also agreed on factors for identifying candidates for infliximab therapy (e.g., persistently active UC, steroid-dependent/refractory disease, and high C-reactive protein).Conclusions: This consensus statement provides useful and practical information on how to achieve evolving treatment goals with infliximab in moderate to severe UC.

Severity of primary sclerosing cholangitis and its impact on the clinical outcome of Crohn's disease - Corrected Proof

2012-01-12

Abstract: Background and aim: Crohn’s disease (CD) is associated with primary sclerosing cholangitis (PSC). The aim of the study was to study the association between the severity of PSC and clinical outcome of CD, comparing the course of CD in patients with PSC not needing orthotopic liver transplantation (OLT) and those requiring OLT.Methods: A total of 41 patients with PSC and CD seen at the Cleveland Clinic between 1985 and 2011 were included in this study. Clinical and demographic variables were obtained regarding the outcome of CD in patients with and without OLT.Results: Patients with PSC–CD were divided into two groups: 20 without OLT (non-OLT) and 21 with OLT. 18 (85.7%) of patients in the OLT group had pancolitis in contrast to 14 (70%) in the non-OLT group. (p=0.22). There were no significant differences regarding duration of CD, but the duration of PSC was longer in the OLT group [16.0±7.8 vs. 10.3±6.4, p=0.01]. The OLT and non-OLT groups did not differ in the number of CD flares [0 (0, 0) vs. 0 (0, 5), p=0.28) and need for surgery for CD [(6 (28.6%) vs. 9 (45%), p=0.27]. Colon carcinoma and dysplasia were similar in the non-OLT and OLT groups [(4 (20%) vs. 3 (13.2%), p=0.52]. On Cox regression analysis, OLT for PSC [Hazards ratio (HR) 1.2 (95% confidence interval (C.I.): 0.38–3.7, p=0.79] did not impact the risk of colectomy.Conclusions: In contrast to UC, severe PSC requiring OLT does not appear to impact the clinical outcome of CD.

Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy - Corrected Proof

2012-01-12

Abstract: Background and aims: Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is ≥235pmol/8×108 erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level.Methods: Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity.Results: Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263pmol/8×108 erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235pmol/8×108 erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04).Conclusions: Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response

Lean body mass, physical activity and quality of life in paediatric patients with inflammatory bowel disease and in healthy controls - Corrected Proof

2012-01-10

Abstract: Background and aims: Physical activity is important for muscle and bone strength in the growing child and may be impaired in paediatric patients with inflammatory bowel disease (IBD) even during quiescent disease. The SenseWearPro2 armband allows to measure physical activity under everyday life conditions.Methods: Thirty-nine IBD patients (27 Crohn's disease, 12 ulcerative colitis, 24 boys) in remission (n=26) or with only mild disease activity (n=13) were compared to 39 healthy age and sex-matched controls. Body weight, height, body mass index (BMI), lean body mass as phase angle α (determined by bioelectrical impedance analysis), and dynamometric grip force were expressed as age- and sex-related Z-scores. SenseWearPro2 armbands were applied for three consecutive days to record number of steps, duration of physical activity and sleeping time. Quality of life was assessed with the German KINDL and IMPACT III questionnaires, energy intake with prospective food protocols. Differences between patients and pair-matched controls were analysed by paired t-test.Results: Patients showed lower Z-scores for phase angle α (difference −0.72; 95% CI [−1.10; −0.34]) and lower grip strength (−1.02 [−1.58; −0.47]) than controls. They tended towards lesser number of steps per day (−1339 [−2760; 83]) and shorter duration of physical activity (−0.44h [−0.94; 0.06]), particularly in females and patients with mild disease. Quality of life and energy intake did not differ between patients and controls.Conclusion: In spite of quiescent disease lean body mass and physical activity were reduced. Interventions to encourage physical activity may be beneficial in this lifelong disease.

Prevalence and predictors of MRSA, ESBL, and VRE colonization in the ambulatory IBD population - Corrected Proof

2012-01-09

Abstract: Background and aims: Inflammatory bowel disease (IBD) patients may be at increased risk of acquiring antibiotic-resistant organisms (ARO). We sought to determine the prevalence of colonization of methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae containing extended spectrum beta-lactamases (ESBL), and vancomycin-resistant enterococi (VRE) among ambulatory IBD patients.Methods: We recruited consecutive IBD patients from clinics (n=306) and 3 groups of non-IBD controls from our colon cancer screening program (n=67), the family medicine clinic (n=190); and the emergency department (n=428) from the same medical center in Toronto. We obtained nasal and rectal swabs for MRSA, ESBL, and VRE and ascertained risk factors for colonization.Results: Compared to non-IBD controls, IBD patients had similar prevalence of colonization with MRSA (1.5% vs. 1.6%), VRE (0% vs. 0%), and ESBL (9.0 vs. 11.1%). Antibiotic use in the prior 3months was a risk factor for MRSA (OR, 3.07; 95% CI: 1.10–8.54), particularly metronidazole. Moreover, gastric acid suppression was associated with increased risk of MRSA colonization (adjusted OR, 7.12; 95% CI: 1.07–47.4). Predictive risk factors for ESBL included hospitalization in the past 12months (OR, 2.04, 95% CI: 1.05–3.95); treatment with antibiotics it the past 3months (OR, 2.66; 95% CI: 1.37–5.18), particularly prior treatment with vancomycin or cephalosporins.Conclusions: Ambulatory IBD patients have similar prevalence of MRSA, ESBL and VRE compared to non-IBD controls. This finding suggests that the increased MRSA and VRE prevalence observed in hospitalized IBD patients is acquired in-hospital rather than in the outpatient setting.

Prevention of postoperative recurrence of Crohn's disease - Corrected Proof

E.S. van Loo, G. Dijkstra, R.J. Ploeg, V.B. Nieuwenhuijs — 2012-01-09

Abstract: Background: Up to 75% of patients with Crohn's disease (CD) will have intestinal resection during their life. Most patients will, however, develop postoperative recurrence (endoscopic, clinical or surgical). Several medical and surgical strategies have been attempted to prevent postoperative recurrence. This review evaluates the efficacy of different drug regimens and surgical techniques in the prevention of clinical, endoscopic and surgical postoperative recurrence of CD.Methods: A literature search for randomized controlled trials on medical or surgical interventions was performed. The endpoints for efficacy were clinical, endoscopic and surgical recurrence. Meta-analyses were performed in case two or more RCTs evaluated the same drug or surgical technique.Results: Mesalamine is more effective in preventing clinical recurrence than placebo (P=0,012), as well as nitroimidazolic antibiotics at one year follow-up (P<0.001) and thiopurines (P=0.018). Nitroimidazolic antibiotics are also more effective than placebo in preventing endoscopic recurrence (P=0.037), as well as thiopurines (P=0.015) and infliximab (P=0.006). Budenoside, probiotics, Interleukin-10 nor any of the different surgical procedures showed any significant difference compared to placebo in postoperative recurrence rates of CD.Conclusion: Among the different drug regimens and surgical techniques, only thiopurines and nitroimidazolic antibiotics are able to reduce postoperative clinical as well as endoscopic recurrence of CD. Mesalamine and infliximab also seem to be superior to placebo in preventing clinical recurrence and endoscopic recurrence, respectively. There is a paucity of trials evaluating long-term follow-up and prevention of surgical recurrence of CD.

The image of mass destruction inevitably leads to intellectual mass distraction - Corrected Proof

R.J. Chiodini — 2012-01-09

We read with bewilderment the article by Van Kruiningen entitled “Where are the weapons of mass destruction — the Mycobacterium paratuberculosis in Crohn's disease?”. Although we have the utmost respect for Van Kruiningen's opinions and have followed his works over the years, we must take issue with his viewpoint from a scientific perspective.

Ectopıc spleen presentıng as an abdomınal mass ın a patıent wıth Crohn's dısease - Corrected Proof

Erdem Koçak, Bilal Ergül, Seyfettin Köklü, Erdem Akbal — 2012-01-09

Ectopic spleen is rare clinical condition with an incidence of less than 0.5%. Patients may have subacute to chronic abdominal complaints. In the course of Crohn's disease (CD), patients with palpable abdominal mass should evaluate to exclude abdominal abscesses and malignancies. Herein, we report a patient with CD presented with abdominal mass due to ectopic spleen.

The IBD passport: Bridging another gap in quality of care? - Corrected Proof

Raza Muhammad, Tina L. Law, Jimmy K. Limdi — 2012-01-03

Dear Sir, Despite unprecedented advances in our understanding of the pathogenesis of inflammatory bowel diseases and novel treatments there is abundant evidence that the quality of care delivered to IBD patients is both disparate and suboptimal. Scientific progress may have outpaced quality improvement measures. Quality of care research in IBD is fraught with challenges with the lack of established quality care measures being a significant limitation.

Long term safety and efficacy of H1N1 vaccine in a single-center cohort of IBD patients treated with immunomodulators and/or anti-TNFα biologics - Corrected Proof

2011-12-30

Long term efficacy and safety data on influenza A (H1N1) virus vaccination are lacking in patients with Crohn's disease (CD) and/or ulcerative colitis (UC) who are treated with immmunomodulators (IMM) and/or anti-TNFα biologics. This report summarizes our prospectively collected data on this topic in IBD patients who were in deep remission on IMM and/or anti-TNFα biologics who received the H1N1 vaccine (Focetria®) between November 2009 and April 2010 and were followed for one year. The activity of CD and UC were assessed by the Harvey-Bradshaw Index (HB-I) and the Partial Mayo Score (P-MS), respectively. Patients were scheduled to receive 2 doses of Focetria® with an interval of 4weeks.

Familial collagenous colitis involving a 6-year old child - Corrected Proof

Perminder S. Phull, Balasubramaniam Vijayan, William M. Bisset, Graeme I. Murray — 2011-12-26

Abstract: Collagenous colitis is a recognised cause of persistent, non-bloody, watery diarrhoea. There are few cases of collagenous colitis reported in children or occurring within families. To our knowledge, no familial cases under 14years of age have been reported previously; we describe a case of familial collagenous colitis affecting a 6-year old girl and her mother. The relevant published literature is reviewed and management is discussed. Colonic mucosal biopsies should be considered in both adults and children presenting with persistent watery diarrhoea even in the absence of any macroscopic abnormality at colonoscopy.

Molecular alterations in colitis-associated colorectal neoplasia: Study from a low prevalence area using magnifying chromo colonoscopy - Corrected Proof

2011-12-23

Abstract: Background and aim: Longstanding ulcerative colitis (UC) predisposes to colorectal cancer (CRC). To understand the molecular pathogenesis of colitis-associated colorectal neoplasia (UC-CRN), we studied the frequency of microsatellite instability (MSI) and mutations in p53, BRAF and KRAS genes in the tissues of patients with long standing UC with or without neoplasia and compared them with colitis patients without risk of neoplasia, and those with sporadic colorectal neoplasia (S-CRN) in an area with lower prevalence for either disease.Methods: Biopsies were obtained during magnifying chromo colonoscopy or routine colonoscopy in consecutive UC patients with high risk (UC-HR) and low risk (UC-LR) of neoplasia, and those with S-CRN. MSI (NCI-Bethesda panel) and mutations in p53, KRAS and BRAF genes were analysed.Results: Twenty-eight patients with UC-HR, 30 with UC-LR and 30 with S-CRN were included. Six (21.4%) of UC-HR had neoplasia (Progressors). MSI was not detected in the UC-CRN group as compared to 5 (16.7%) in the S-CRN group. p53 mutations occurred in 1 (3.3%) of UC-LR, increasing to 6 (27.3%, P<0.05) and 3 (50%, P<0.05) in the UC-HR subgroups without and with neoplasia respectively, as against 10 (33.3%) in sporadic neoplasia group. KRAS mutations were found only in the presence of neoplasia. None showed the BRAF mutation.Conclusions: In a population with a lower prevalence for UC and CRC, the molecular pathogenesis of colitis-associated colorectal neoplasia is comparable to that reported from areas with a higher prevalence of these diseases, MSI being an exception.

Sjögren's syndrome associated with Crohn's disease successfully treated with adalimumab - Corrected Proof

Antonio Tursi — 2011-12-23

Sjögren's syndrome (SS) is an autoimmune disease affecting predominantly the salivary, lacrimal and exocrine glands. The pathogenesis of SS remains unknown, but recruiting T-cells and clonal expansion with release of cytokines like tumor necrosis factor α (TNF-α) are believed to interfere with the neural signals, causing inhibition of glandular secretions. TNF-α is a key proinflammatory cytokine involved in the pathogenesis of Inflammatory Bowel Diseases. Although Crohn's disease (CD) has many autoimmune extraintestinal manifestations, and although TNF-alpha seems to be a key player in the development of both diseases, an association between CD and SS has rarely been reported.

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: A single-center cohort study - Corrected Proof

2011-12-22

Abstract: Background & Aims: The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use.Methods: In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments.Results: IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000pt/year vs 2.9/1000pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL,1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08–1.45; UC:HR 1.33;95%CI 1.15–1.55 for an increase by 5years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11–5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05–7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed).Conclusions: Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer.

A functional polymorphism in UGT1A1 related to hyperbilirubinemia is associated with a decreased risk for Crohn's disease - Corrected Proof

2011-12-19

Abstract: Background: An imbalance between the production of reactive oxygen species (ROS) and their capturing by antioxidants results in oxidative stress, this may play an important role in the pathogenesis of inflammatory bowel disease (IBD). Since bilirubin is an important endogenous antioxidant, increased levels of bilirubin may protect against IBD. UDP-glucuronosyltransferase 1A1 (UGT1A1) is the only enzyme involved in the conjugation of bilirubin and the common UGT1A1*28 allele in the UGT1A1 gene, which is strongly associated with Gilbert's syndrome in Caucasians, results in elevated plasma bilirubin levels.Aims: To test the hypothesis that the UGT1A1*28 allele is associated with lower disease susceptibility to, and disease behavior within, IBD. In addition, a possible altered risk for developing IBD-drug related side-effects was explored.Methodology: Genomic DNA of 751 patients with IBD (209 patients with ulcerative colitis and 542 patients with Crohn's disease) and 930 healthy controls was genotyped for the UGT1A1*28 promoter polymorphism, and genotype distribution was compared between patients and controls. Genotype phenotype interactions were also investigated.Results: Patients with Crohn's disease significantly less often bear the UGT1A1*28 homozygous genotype compared to the control group, with an odds ratio of 0.64, 95% CI: 0.42–0.98. The ulcerative colitis group showed no significant differences compared to controls.Conclusion: The homozygous state of the UGT1A1*28 polymorphism, associated with higher serum bilirubin levels, may be protective for the development of Crohn's disease, suggesting that the anti-oxidant capacity of bilirubin may play a part.

The usefulness of factor XIII levels in Crohn's disease - Corrected Proof

2011-12-19

Abstract: Background and Aims: The assessment of inflammatory activity in Crohn's disease (CD) is challenging, and no specific laboratory marker is currently available. Several studies have reported decreased serum factor XIII levels in CD patients as a function of disease activity. We aimed to determine whether the factor XIII level could be a marker for the evolution of CD.Methods: In this prospective, single-centre trial, 129 patients were included and categorised into two groups: functional bowel disorders (FBDs, n=42) and CD (n=86). The CD group was divided into two subgroups depending on disease activity, as defined by the Crohn's Disease Activity Index score: active disease (CDa, n=41) and disease remission (CDb, n=45). The factor XIII levels were evaluated for each patient. Serial factor XIII levels were evaluated in the patients within the CDa subgroup.Results: The factor XIII levels were significantly different between the FBD (117.69%) and CD (101.89%) groups (p=0.009) but there was no significant difference between the CDa and CDb subgroups (99.04% vs 104.65%, p>0.05), and the levels did not vary during follow-up for the patients in the CDa subgroup. By multivariate analysis, factor XIII levels did not correlate with the time course of disease evolution, CRP, serum fibrin levels, platelet count, disease distribution within the bowel, or the presence of a fistulising form of CD.Conclusions: Our results confirm that factor XIII levels are decreased in CD patients but cannot be recommended as a marker for the disease activity.

Adalimumab reversed a severe lymphopenia in a patient with Crohn's disease - Corrected Proof

2011-12-16

Abstract: Patients with Crohn's disease are frequently found to have low peripheral lymphocyte counts. Lymphopenia has been linked to disease activity, the effects of therapy and the presence of an abnormal T regulatory (Treg ) function. We present a patient with Crohn's disease and a severe total and CD4 lymphopenia that did not resolve after discontinuation of immunosuppressive treatment and resective surgery. Complete clinical remission and persistent normal levels of total and CD4 lymphocytes were observed after starting therapy with the anti-tumor necrosis factor monoclonal antibody adalimumab.

Genotyping should be considered the primary choice for pre-treatment evaluation of thiopurine methyltransferase function - Corrected Proof

Ulf Hindorf, Malin Lindqvist Appell — 2011-12-15

Abstract: Background and aims: A pre-treatment determination of the thiopurine S-methyltransferase (TPMT) genotype or phenotype can identify patients at risk of developing severe adverse reactions from thiopurine treatment. The risk of misclassifying a patient might be dependent on the method used. The aim of this study was to investigate the concordance between TPMT genotyping and phenotyping.Methods: The data consist of 7195 unselected and consecutive TPMT genotype and phenotype determinations sent to the division of Clinical Pharmacology, Linköping, Sweden. TPMT activity was measured in red blood cells (RBC) and the genotype determined by pyrosequencing for the three most common TPMT variants (TPMT *2, *3A, *3C).Results: TPMT genotyping identified 89% as TPMT wild type (*1/*1), 10% as TPMT heterozygous and 0.5% as TMPT defective. The overall concordance between genotyping and phenotyping was 95%, while it was 96% among IBD patients (n=4024). Genotyping would have misclassified 8% of the TPMT defectives as heterozygous as compared to 11% if only TPMT activity had been measured. 11% of the heterozygous patients had a normal TPMT activity (>8.9U/ml RBC) and 3% of the TPMT wild-type patients had an intermediate TPMT activity (2.5–8.9U/ml RBC).Conclusions: There is a risk for TPMT misclassification when only genotyping or phenotyping is used, but it is not reasonable to check both in all patients. Since TPMT genotyping is the more reliable test, especially in TPMT heterozygotes, we suggest that genotyping should be considered the primary choice for the pre-treatment evaluation of TPMT function before initiation of thiopurine therapy.

Neuroimmune interactions in patients with inflammatory bowel diseases: Disease activity and clinical behavior based on Substance P serum levels - Corrected Proof

2011-12-14

Abstract: Background and aim: The neuropeptide Substance P, plays a key role in modulating neuroimmune interactions in patients with inflammatory bowel diseases. We analyzed Substance P serum levels in patients with ulcerative colitis and Crohn's disease, to detail the involvement of the neuropeptide in the pathophysiology of these disorders.Methods: Serum samples were collected from 61 patients with ulcerative colitis (24 with active and 37 with inactive disease), 66 patients with Crohn's disease (29 with active and 37 with inactive disease) and 45 healthy subjects, enrolled into the study. Neuropetide serum levels were measured by means of an ELISA/EIA. Associations with disease activity and patients clinical features were also taken into account.Results: Compared to controls, Substance P serum levels were significantly increased in both patients with ulcerative colitis and Crohn's disease, (p<0.001). In patients with ulcerative colitis, levels paralleled disease activity (p=0.014), and the amount of the neuropeptide was considerably decreased during clinical and endoscopic remission of the disease, (p=0.025). Conversely, median Substance P levels did not differ between patients with active and inactive Crohn's disease. However, levels of the neuropeptide were more often elevated in patients with inactive and stricturing/fistulizing Crohn's disease, (p=0.002).Conclusions: Data underline that Substance P might exerts important immunomodulatory functions in inflammatory bowel disease. This study suggests a potential role for Substance P serum levels in monitoring intestinal inflammation in patients with inflammatory bowel disease.

Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitis - Corrected Proof

2011-12-12

Abstract: Aim: To evaluate the effect of infliximab induction therapy on calprotectin levels in patients with ulcerative colitis (UC).Patients and Methods: In this prospective study 53 patients with active UC from 17 centers were treated with infliximab therapy (5mg/kg) at baseline, week 2, and week 6. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10.Results: Median calprotectin levels decreased from 1260 (IQR 278.5- 3418 ) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p<0.001). After 10weeks, infliximab therapy induced endoscopic remission and a decrease in calprotectin to<50mg/kg or at least a 80% decrease from baseline level in 58% of patients.A significant and steep decrease of calprotectin levels was seen at week 2 for patients with an endoscopic remission at week 10 as compared to patients who did not show a remission. (p<0.001).At week 10 an excellent correlation was found between endoscopic remission and clinical Mayo score reflected by an AUC of ROC analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1)) : all patients with calprotectin levels <50mg/kg, and a normal clinical Mayo score (=0) were in endoscopic remission.Conclusions: Infliximab induces a fast and significant decrease of faecal calprotectin levels in anti-TNF naïve patients with ulcerative colitis predictive for remission of disease

Identification of areas of functioning and disability addressed in inflammatory bowel disease-specific patient reported outcome measures - Corrected Proof

2011-12-12

Abstract: Background and aims: Patient-reported outcome measures (PROMs) make it possible to assess health-status problems from the perspective of persons suffering from a disease. The objective of the paper is to examine and compare the contents of PROMs related to IBD based on the World Health Organization's International Classification of Functioning, Disability and Health (ICF) as the frame of reference.Methods: A systematic literature review (1999–2009) in the databases Medline, EMBASE, PsycINFO, CINAHL and CENTRAL was performed to select IBD-specific PROMs. Abstracts and full-text articles were checked applying predefined eligibility criteria; IBD-specific PROMs were identified. The contents of the identified PROMs were examined by linking the items to ICF categories. The linked ICF categories of the PROMs were then compared.Results: The review resulted in the selection of eight IBD-specific PROMs (e.g., Cleveland Global Quality of Life, Inflammatory Bowel Disease Quality of Life Questionnaire, Inflammatory Bowel Disease Questionnaire-32, Rating Form of IBD Patient Concerns, Short Inflammatory Bowel Disease Questionnaire). In total, 129 items were identified, the majority of which (n=90; 69.8%) could be linked to specific ICF categories. None of the linked categories were contained in all PROMs. The most frequently identified categories were ‘b1300 Energy level’, ‘b5254 Flatulence’, ‘d910 Community life’ and ‘d920 Recreation and leisure’.Conclusion: The present study provides an overview of IBD-specific PROMs and their items. The results of the content comparison provide valuable information to facilitate and account for the selection of appropriate PROMs for different purposes of data collection in clinical and research settings.

Internal fistula leakage due to a road traffic accident: A fortuitous diagnosis of Crohn's disease - Corrected Proof

2011-12-12

Abstract: Background and aim: Fistulae are one of the most frequent complications of Crohn's disease (CD) and occur in 30–40% of patients. Conversely, free perforation is a rare complication and is one of the indications for emergency surgery of CD because of secondary peritonitis. We report a case of a spontaneous fistula rupture secondary to a road traffic accident.Methods: Case report.Results: A 22year-old man, with no personal significant medical history, was admitted in the emergency room after a road traffic accident. He underwent abdominal CT, which revealed pelvis fractures, abnormal bowel wall of the terminal ileum (wall thickening and mucosal enhancement), peritoneal effusion within the pelvis, mesenteric nodes and extra-luminal gas within an area of mesenteric inflammation: these features were suggestive of ileum perforation associated with inflammatory bowel disease, most likely CD. Laparoscopic assessment was decided and an ileocaecal resection with ileocolonic anastomosis was performed. Histological analysis revealed terminal ileitis with ulcers, non caseating granulomas and submucosal fibrosis, a transparietal fistula and a caecoappendicular inflammation, confirming CD. Post surgical outcome was uneventful and the patient was discharged at day 9.Conclusion: Our patient presented this rare complication revealing CD. The involvement of the terminal ileum and fistulae were characteristics of CD. Rupture of the fistula was favored by the trauma and responsible for the peritonitis. A resection with primary anastomosis was possible. To our knowledge, it is the first case described for the rupture of an ileal fistula secondary to traumatism in a patient with CD.

Results of the 2nd Scientific Workshop of the ECCO (III): Basic mechanisms of intestinal healing - Corrected Proof

2011-12-12

Abstract: The second scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal healing for the disease course of inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms, markers for disease prediction, detection and monitoring of intestinal healing, impact of intestinal healing on the disease course of IBD as well as therapeutic strategies. The results of this workshop are presented in four separate manuscripts. This section describes basic mechanisms of intestinal healing, identifies open questions in the field and provides a framework for future studies.

Reply to Dr. Filik's letter - Corrected Proof

Dan Turner, Anne M. Griffiths — 2011-12-12

We would like to thank Dr. Filik for giving us the opportunity to clarify several points in our manuscript, in which we systematically evaluated the utility of CRP and ESR in pediatric ulcerative colitis (UC) using four large datasets. This has been the largest and most comprehensive pediatric study to date but still, it is a post-hoc analysis from existing datasets. Therefore, several biases and limitations are inherent to the study design, including the inability to look at experimental genetic alterations associated with CRP response and the availability of longitudinal data on only a subset of the patient. Nonetheless, we aimed to observe the association between CRP and ESR, and disease activity, and not to elucidate the reasons for the differing CRP and ESR response. It is true that clinical response may precede resolution of elevated biomarkers when effective treatments are given, resulting in persistently elevated CRP and ESR in the presence of clinically quiescent disease. However, we found the opposite, namely that despite active disease many of the patients have normal or near-normal CRP and ESR; these biomarkers were more accurate in the severe end of the spectrum. We certainly agree that clinical remission with increased CRP may represent lack of mucosal healing and thus increased risk for relapse. However, this notion is much more relevant to Crohn's disease than for UC, where clinical symptoms are associated more closely with endoscopic appearance. Indeed, looking at our data (Figure 1)we can see that of the 84 children in clinical remission and 79 with mild disease, very few outliers had excessive elevation of CRP or ESR. We agree that UC patients in remission with increased CRP values should be further evaluated, but this is apparently an uncommon situation in UC, at least in children. We thus believe that our conclusions still hold: 1) CRP and ESR are sensitive in the more severe patients but not in reflecting mild disease activity; 2) if either test performs well in a given individual, there is no need to test also the other; and 3) on average, CRP performs slightly better than ESR in reflecting disease activity in pediatric UC.

Thiopurine treatment in inflammatory bowel disease: Response predictors, safety, and withdrawal in follow-up - Corrected Proof

2011-12-09

Abstract: Background and aims: Thiopurines represent the mainstay of immunosuppressive therapy in inflammatory bowel diseases. Since it is likely that response to therapy and adverse events depends on the genetic background of patients our study aimed to evaluate retrospectively response to therapy and safety in a mixed IBD population in Southern Europe.Methods: We evaluated demographic and clinical data of our patients treated with thiopurines. after 6months in responders and non-responders to therapy. Moreover the likelihood to remain in thiopurine monotherapy was evaluated in responders, whereas adverse events were investigated in all patients.Results: Among disease- and patient-related parameters a shorter disease duration, female gender and ileal disease in Crohn's patients were associated with better response. By ROC analysis, the best predictors of response were decreasing values of C-reactive protein and erythrocyte sedimentation rate. In the long-term more than half of IBD patients who responded at 6months remained on monotherapy at 42months. Flu-like syndrome represented the most frequent adverse event followed by abnormalities of liver function tests and myelotoxicity. Adverse events did occur at any time and were frequently impredictable.Conclusions: In this retrospective study, thiopurines showed a good clinical efficacy, especially in patients with short duration of disease. Normalization of markers of systemic inflammation represents the most useful tool to assess response. Careful monitoring of patients is required during the whole duration of treatment although it may not prevent all severe complications.

CRP and pediatric ulcerative colitis - Corrected Proof

Levent Filik — 2011-12-09

I read with great interest the recent article by Turner et al. on the use of CRP and ESR in follow-up of pediatric patients with ulcerative colitis (UC). The article has very important data because CRP could be used as a non-invasive disease activity marker in those cases. Herein, there are some issues to be considered before some of the conclusions of the study could be drawn. The authors state that 104/288 children (36%) with moderate and severe disease activity had CRP of <5mg/L. The item of my concern is medications that could affect CRP levels for example corticosteroids or antibiotics in those patients. Could the authors eliminate confounding effects of those drugs? Similarly, genetic polymorphisms for example 308GG should have also been considered in those patients. Another issue of my concern is recurrence rates of patients in remission with relatively higher CRP in the follow-up. High CRP in patient with remission does not necessarily mean low specificity. In fact it might also indicate continuing inflammatory process of patients in remission and disease activity of those cases might increase in the follow-up.

Impact of budesonide on liver function tests and gut inflammation in patients with primary sclerosing cholangitis and ileal pouch anal anastomosis - Corrected Proof

2011-12-05

Abstract: Background and aim: Budesonide has been studied in patients with primary sclerosing cholangitis (PSC). This study was designed to evaluate the efficacy of oral budesonide on liver function tests in patients with PSC and pouchitis associated with ileal pouch-anal anastomosis (IPAA).Materials and methods: The study group consisted of 18 pouch patients with underlying ulcerative colitis (UC) and PSC who were treated with 9mg daily of budesonide for their underlying pre-pouch ileitis and pouchitis for 1-3months followed by 3-6mg maintenance for another 9months. Demographic and clinical variables were analyzed.Results: The mean age was 39.4±12.4years (range, 21–59years). There was no significant change in aspartate aminotransferase (AST) [median (interquartile range) (IQR) 32 (25, 43.8) vs. 35.5 (25.5, 53), p=0.35], alanine aminotransferase (ALT) [37.5 (25.5, 49.5) vs. 40 (30, 84.3), p=0.29], alkaline phosphatase [142.5 (98.5, 264.5) vs. 126 (94.3, 189.5), p=0.35], serum bilirubin [0.7 (0.4, 1.3) vs., 0.6 (0.4, 1.6), p=0.13] or albumin levels [4.3 (3.9, 4.4) vs. 4.2 (3.8, 4.4), p=0.22] at the end of the treatment period (1year). The revised Mayo Risk Score did not change significantly and three patients required evaluation for liver transplantation during treatment. There was a significant improvement in the endoscopy subscores in the afferent limb and pouch after a year of budesonide treatment (p=0.001).Conclusions: Oral budesonide appears to have no impact on liver function tests in pouch patients with PSC. However it significantly improved afferent limb and pouch inflammation in IPAA patients.

Personality and fatigue perception in a sample of IBD outpatients in remission: A preliminary study - Corrected Proof

Ingrid Banovic, Daniel Gilibert, Ahmed Jebrane, Jacques Cosnes — 2011-12-05

Abstract: Background and aims: Fatigue is considered as a feature of IBD. Nevertheless, medical variables would partly explain this complex phenomenon. Psychological variables would be especially connected to fatigue for patients in remission. Moreover, personality is known to be linked to the fatigue of patients with CFS. This preliminary study aimed to determine if personality dimensions are linked to the perception of fatigue in IBD.Methods: 81 IBD outpatients in remission completed the MFI (fatigue); ISI, EES (sleep disturbances); TCI-R (personality); HADS (depression and anxiety). Medical data were collected (ferritin, C-reactive protein, number of flare-ups, number of hospitalizations, duration of the disease and surgical sequelae).Results: With the exception of surgical sequelae, none of the medical variables was linked to fatigue perception. Anxiety and sleep disturbances were the most continuously connected to fatigue perception. Significant relationships were observed between personality categorization on Persistence, Self-Directness and the level of fatigue.Conclusion: In order to improve vitality in IBD patients in remission, identification and treatment of psychological aspects should become a dimension of disease management. Fatigue should not be considered only as a direct feature of IBD.

Use of small bowel MRI enteroclysis in the management of paediatric IBD - Corrected Proof

2011-12-02

Abstract: Introduction: Children with inflammatory bowel disease (IBD) frequently present with small bowel involvement at some stage of their disease. Hence, reliable assessment of the entire small bowel is required in order to adjust treatment accordingly. Recently, magnetic resonance imaging (MRI) of the small bowel in combination with luminal contrast agent delivered via a naso-jejunal tube (MR enteroclysis) is an emerging technique demonstrating good results in adult patients. However, data on its use and benefits in children is limited.Aims: In this study we report our experience on performing small bowel MR enteroclysis (MRE) in children with IBD. Specifically, we reviewed indications, MR findings, advantages and disadvantages of the technique in a tertiary unit.Methods: A total of 34 MRE studies (29 paediatric IBD patients) were retrospectively analysed. All patients underwent upper and lower endoscopy under general anaesthetic (GA) the day before MR imaging was performed. Nasojejunal (NJ)-tube was placed during endoscopy.Results: Frequently detected findings included small and large bowel wall thickening, small bowel strictures and intestinal lymph node enlargement. Importantly, in all our clinical cases, MRE results were key to making a clinical decision in the given scenario regardless of whether MRE findings were positive or negative.Conclusions: Within our setup, MR enteroclysis is a well-tolerated, sensitive technique for small bowel imaging, providing detailed information at crucial clinical decision points. Moreover, accurate information then allows appropriate clinical decisions to be made.

Clinical and radiographic presentation of superior mesenteric vein thrombosis in Crohn's disease: A single center experience - Corrected Proof

2011-11-28

Abstract: Background: Mesenteric vein thrombosis (MVT) is a rare and frequently underdiagnosed complicationof Crohn's disease (CD). This study describes the clinical and radiological characteristics of CD /patients with superior mesenteric vein thrombosis (MVT) diagnosed by CT/MRI.Patients and methods: The database of Crohn's disease patients treated in Sheba Medical Center between 2005-2010 was searched for MVT diagnosis. Imaging studies of identified patients were retrieved and reviewed by an experienced abdominal radiologist. MVT was defined by superior mesenteric vein obliteration and/or thrombus in the vessel lumen on abdominal imaging. The clinical and radiologic data of these patients were collected from the medical records.Results: MVT was demonstrated in 6/460 CD patients. Five patients had stricturing disease, and one patient had a combined fistulizing and stricturing disease phenotype. All patients had small bowel disease, but 3/6 also had colonic involvement. No patient had a prior thromboembolic history or demonstrable hypercoagulability. One patient had an acute SMV thrombus demonstrable on CT scanning, the remaining patients showed an obliteration of superior mesenteric vein. Two patients received anticoagulation upon diagnosis of thrombosis. No subsequent thromboembolic events were recorded.Conclusions: The incidence of mesenteric vein thrombosis is likely to be underestimated in patients with Crohn’s disease. Both CT and MRI imaging demonstrate the extent of enteric disease and coincident SMV thrombosis. In our cohort, thrombosis was associated with stricturing disease of the small bowel. The clinical impact of SMV thrombosis and whether anticoagulation is mandatory for all of these patients remains to be determined.

Management of inflammatory bowel disease with vitamin D: Beyond bone health - Corrected Proof

Neeraj Narula, John K. Marshall — 2011-11-28

Abstract: A relationship between vitamin D and several disorders, including Crohn's disease (CD), has recently been proposed. Vitamin D appears to have several important actions beyond the maintenance of bone health, including various effects on the immune system. Vitamin D deficiency has been implicated in the development of CD, and its analogues may have a role in the treatment of CD. Current research also suggests a role for vitamin D in counteracting some IBD-specific complications, including osteopenia, colorectal neoplasia, and depression. There remains a need for prospective studies to further delineate these relationships. Given current evidence and the apparent safety of vitamin D supplementation, it appears reasonable to screen for and treat vitamin D deficiency in patients with IBD.