Prophylactic versus endoscopy-driven treatment of Crohn's postoperative recurrence: A retrospective, multicentric European study (PORCSE study).

BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence (POR) after ileocecal resection (ICR) for Crohn's disease (CD).We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD-patients undergoing first ICR were assigned to cohort1 if a biologic or immunomodulator was (re)started prophylactically after ICR, or to cohort2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR (Rutgeerts>i1). Secondary endpoints were severe endoscopic POR (Rutgeerts i3/i4), clinical POR, surgical POR and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment (proactive/cohort1) and 52.6% did not (reactive/cohort2).Endoscopic POR (Rutgeerts>i1) rate was significantly higher in cohort2 (41.5% vs 53.8%, OR1.81, P=0.039) at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found (OR1.29, P=0.517). Cohort2 had significantly higher clinical POR rates (17.7% vs 35.7%, OR3.05, P=0.002) and numerically higher surgical recurrence rates (6.7% vs 13.2%, OR2.59, P=0.051). Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach (HR2.50, P=0.057). Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in cohort2 (mean ratio 0.53, P=0.002), but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared to expectant management after first ileocecal resection for Crohn's disease.

Safety and Effectiveness of Vedolizumab and Ustekinumab in Elderly Patients with Inflammatory Bowel Disease: A Real-Life Multicentric Cohort Study.

BACKGROUND: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. METHODS: A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. RESULTS: A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. CONCLUSIONS: Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.

IL-22-Activated MUC13 Impacts on Colonic Barrier Function through JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK Signaling.

Overexpression of the transmembrane mucin MUC13, as seen in inflammatory bowel diseases (IBD), could potentially impact barrier function. This study aimed to explore how inflammation-induced MUC13 disrupts epithelial barrier integrity by affecting junctional protein expression in IBD, thereby also considering the involvement of MUC1. RNA sequencing and permeability assays were performed using LS513 cells transfected with MUC1 and MUC13 siRNA and subsequently stimulated with IL-22. In vivo intestinal permeability and MUC13-related signaling pathways affecting barrier function were investigated in acute and chronic DSS-induced colitis wildtype and Muc13-/- mice. Finally, the expression of MUC13, its regulators and other barrier mediators were studied in IBD and control patients. Mucin knockdown in intestinal epithelial cells affected gene expression of several barrier mediators in the presence/absence of inflammation. IL-22-induced MUC13 expression impacted barrier function by modulating the JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK signaling pathways, with a cooperating role for MUC1. In response to DSS, MUC13 was protective during the acute phase whereas it caused more harm upon chronic colitis. The pathways accounting for the MUC13-mediated barrier dysfunction were also altered upon inflammation in IBD patients. These novel findings indicate an active role for aberrant MUC13 signaling inducing intestinal barrier dysfunction upon inflammation with MUC1 as collaborating partner.

Position statement on the management of the immune checkpoint inhibitor-induced colitis via multidisciplinary modified Delphi consensus.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) in cancer immunotherapy has shown increased overall survival in a wide range of cancer types with the associated risk of developing severe immune-mediated adverse events, commonly involving the gastrointestinal tract. AIM: The aim of this position statement is to provide an updated practice advice to the gastroenterologists and oncologists on the diagnosis and management of ICI-induced gastrointestinal toxicity. METHODOLOGY: The evidence reviewed in this paper includes a comprehensive search strategy of English language publications. Consensus was reached using a three-round modified Delphi methodology and approved by the members of the Belgian Inflammatory Bowel Disease Research and Development Group (BIRD), Belgian Society of Medical Oncology (BSMO), Belgian group of Digestive Oncology (BGDO), and Belgian Respiratory Society (BeRS). CONCLUSIONS: The management of ICI-induced colitis requires an early multidisciplinary approach. A broad initial assessment is necessary (clinical presentation, laboratory markers, endoscopic and histologic examination) to confirm the diagnosis. Criteria for hospitalisation, management of ICIs, and initial endoscopic assessment are proposed. Even if corticosteroids are still considered the first-line therapy, biologics are recommended as an escalation therapy and as early treatment in patients with high-risk endoscopic findings.

Role of Intestinal Ultrasound in the Management of Patients with Inflammatory Bowel Disease.

Intestinal ultrasound (IUS) has gained popularity as a first line technique for the diagnosis and monitoring of patients with inflammatory bowel diseases (IBD) due to its many advantages. It is a non-invasive imaging technique with non-ionizing radiation exposure. It can be easily performed not only by radiologists but also by trained gastroenterologists at outpatient clinics. In addition, the cost of IUS equipment is low when compared with other imaging techniques. IUS is an accurate technique to detect inflammatory lesions and complications in the bowel in patients with suspected or already known Crohn's disease (CD). Recent evidence indicates that IUS is a convenient and accurate technique to assess extension and activity in the colon in patients with ulcerative colitis (UC), and can be a non-invasive alternative to endoscopy. In patients with IBD, several non-specific pathological ultrasonographic signs can be identified: bowel wall thickening, alteration of the bowel wall echo-pattern, loss of bowel stratification, increased vascularization, decreased bowel peristalsis, fibro-fatty proliferation, enlarged lymph nodes, and/or abdominal free fluid. Considering the transmural CD inflammation, CD complications such as presence of strictures, fistulae, or abscesses can be detected. In patients with UC, where inflammation is limited to mucosa, luminal inflammatory ultrasonographic changes are similar to those of CD. As the technique is related to the operator's experience, adequate IUS training, performance in daily practice, and a generalized use of standardized parameters will help to increase its reproducibility.

In-Depth Study of Transmembrane Mucins in Association with Intestinal Barrier Dysfunction During the Course of T Cell Transfer and DSS-Induced Colitis.

BACKGROUND AND AIMS: There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases [IBD] but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin expression is reported in the colon of IBD patients, we studied the association between mucin expression, inflammation and intestinal permeability in experimental colitis. METHODS: We quantified 4-kDa FITC-dextran intestinal permeability and the expression of cytokines, mucins, junctional and polarity proteins at dedicated time points in the adoptive T cell transfer and dextran sodium sulfate [DSS]-induced colitis models. Mucin expression was also validated in biopsies from IBD patients. RESULTS: In both animal models, the course of colitis was associated with increased interleukin-1ß [IL-1ß] and tumour necrosis factor-α [TNF-α] expression and increased Muc1 and Muc13 expression. In the T cell transfer model, a gradually increasing Muc1 expression coincided with gradually increasing 4-kDa FITC-dextran intestinal permeability and correlated with enhanced IL-1ß expression. In the DSS model, Muc13 expression coincided with rapidly increased 4-kDa FITC-dextran intestinal permeability and correlated with TNF-α and Muc1 overexpression. Moreover, a significant association was observed between Muc1, Cldn1, Ocln, Par3 and aPKCζ expression in the T cell transfer model and between Muc13, Cldn1, Jam2, Tjp2, aPkcζ, Crb3 and Scrib expression in the DSS model. Additionally, MUC1 and MUC13 expression was upregulated in inflamed mucosa of IBD patients. CONCLUSIONS: Aberrantly expressed MUC1 and MUC13 might be involved in intestinal barrier dysfunction upon inflammation by affecting junctional and cell polarity proteins, indicating their potential as therapeutic targets in IBD.

Next generation of biologics for the treatment of Crohn's disease: an evidence-based review on ustekinumab.

The limited efficacy of the currently available medical therapies in a proportion of patients with Crohn's disease has led to the research and development of molecules that can block new inflammatory pathways. Ustekinumab is a fully human IgG1 monoclonal antibody which targets the common p40 subunit of the cytokines interleukin-12 as well as interleukin-23. Consequently, the Th1 and Th17 inflammatory responses are inhibited. Ustekinumab has been recently approved for its use in patients with Crohn's disease. Its efficacy and safety was initially proved in patients with psoriasis and psoriatic arthritis. More recently, three Phase III trials have confirmed its efficacy in patients with Crohn's disease refractory to anti-tumor necrosis factor therapy. This biologic agent appears safe, with no increased risk of infectious or malignant complications, and a low immunogenic profile.

Autologous Haematopoietic Stem Cell Transplantation for Refractory Crohn's Disease: Efficacy in a Single-Centre Cohort.

BACKGROUND: Haematopoietic stem cell transplantation [HSCT] is considered a therapeutic option for patients with severe Crohn's disease [CD] unresponsive to currently available therapies. METHODS: Autologous HSCT was considered for CD patients with active disease, unresponsive or intolerant to approved medications and unsuitable for surgery. After HSCT, patients were closely followed up every 6 weeks during the first 2 years and every 6 months thereafter up to 5 years. Colonoscopy and/or magnetic resonance imaging were performed at Months 6, 12, 24, and 48 after HSCT. RESULTS: From December 1, 2007 to December 31, 2015, 37 CD patients were assessed for HSCT. Of these, 35 patients [13 within the ASTIC trial] underwent mobilisation. Six patients did not complete the transplant for various reasons and 29 patients were finally transplanted. Patients were followed up during a median of 12 months [6-60]. At 6 months, 70% of patients achieved drug-free clinical remission (Crohn's Disease Index of Severity [CDAI] < 150). The proportion of patients in drug-free remission (CDAI < 150, Simple Endoscopic activity Score [SES]-CD < 7] was 61% at 1 year, 52% at 2 years, 47% at 3 years, 39% at 4 years, and 15% at 5 years. Patients who relapsed were re-treated and 80% regained clinical remission. Six out of the 29 [21%] required surgery. One patient died due to systemic cytomegalovirus infection 2 months after transplant. CONCLUSIONS: HSCT is a salvage therapy for patients with extensive and refractory CD. Although relapse occurs in a majority of patients within 5 years after transplant, drug responsiveness is regained and clinical remission achieved in 80% of cases.

A Simplified Geboes Score for Ulcerative Colitis.

BACKGROUND AND AIMS: The original Geboes Score [OGS] is the most commonly used histological score in ulcerative colitis [UC], but rather complicated to use in daily clinical practice. The aim of this study was to develop a Simplified Geboes Score [SGS] and to compare it with the OGS in patients newly diagnosed with UC. METHODS: All patients diagnosed with UC at a tertiary referral centre between 2005 and 2010, who had serial colonoscopies with biopsies, were retrospectively included. The 5-year endoscopic/histological evolution after diagnosis was recorded. Histological activity was scored by an experienced inflammatory bowel disease pathologist and three trained readers using the OGS and also the new SGS that only includes variables linked to active inflammatory disease. The correlation between endoscopic and histological activity and the histological inter-observer agreement were measured. RESULTS: A total of 528 slides from 339 colonoscopies of 103 UC patients were reviewed. Forty [12%] colonoscopies presented Mayo 0, 74 [22%] Mayo 1, 107 [31%] Mayo 2 and 118 [35%] Mayo 3. Active microscopic disease [≥ 3.1 in both scores] was described in 10/40 [25%] patients who were in complete endoscopic remission [Mayo 0], and 62/74 [84%] with mild endoscopic lesions [Mayo 1]. The correlation analysis between endoscopy and OGS/SGS did not show significant differences between the histological scores. The inter-observer agreement was moderate for all the grades of the SGS. CONCLUSIONS: The assessments of histological activity based on the OGS and the SGS were comparable in newly diagnosed active UC patients. Further prospective validation should now be done to replace the OGS with the SGS.

Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer.

Patients with inflammatory bowel disease have an additional risk of developing cancer compared with the general population. This is due to local chronic inflammation that leads to the development of gastrointestinal cancers and the use of thiopurines, associated with a higher risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. Similar to the general population, a previous history of cancer in inflammatory bowel disease patients increases the risk of developing a secondary cancer. Large studies have not shown an increased risk of cancer in patients treated with biologics. In this review we discuss the prevention and treatment of cancer in patients with inflammatory bowel disease.

Long-lasting Remission Induced by Syngeneic Haematopoietic Stem Cell Transplantation in a Patient with Refractory Crohn's Disease.

BACKGROUND AND AIMS: Autologous haematopoietic stem cell transplantation (HSCT) is considered a salvage therapy for patients with refractory immune-mediated diseases. Syngeneic HSCT may be an alternative to autologous HSCT, with potential advantages in terms of safety and efficacy. METHODS: A patient with severe Crohn's disease refractory to available medical therapies underwent a syngeneic HSCT from her identical twin sister. Cyclophosphamide and rabbit anti-thymocyte globulin were administered for conditioning. RESULTS: After transplant, the patient presented successful engraftment, complete haematological and immunological reconstitution, and no severe complications. The patient achieved complete remission after transplant which is sustained 4 years after transplantation without any active treatment for Crohn's disease. CONCLUSIONS: Patients with refractory immune-mediated diseases who have an identical disease-free twin may benefit from a syngeneic HSCT.

Improving safety of autologous haematopoietic stem cell transplantation in patients with Crohn's disease.

OBJECTIVE: To evaluate the feasibility and toxicity of autologous haematopoietic stem cell transplantation (HSCT) for the treatment of refractory Crohn's disease (CD). DESIGN: In this prospective study, patients with refractory CD suffering an aggressive disease course despite medical treatment, impaired quality of life and in whom surgery was not an acceptable option underwent HSCT. Toxicity and complications during the procedure and within the first year following transplantation were evaluated, along with the impact of the introduction of supportive measures on safety outcomes. RESULTS: 26 patients were enrolled. During mobilisation, 16 patients (62%) presented febrile neutropaenia, including one bacteraemia and two septic shocks. Neutropaenia median time after mobilisation was 5 days. 5 patients withdrew from the study after mobilisation and 21 patients entered the conditioning phase. Haematopoietic recovery median time for neutrophils (>0.5×10(9)/L) was 11 days and for platelets (>20×10(9)/L) 4 days. Twenty patients (95%) suffered febrile neutropaenia and three patients (27%) presented worsening of the perianal CD activity during conditioning. Among non-infectious complications, 6 patients (28.5%) presented antithymocyte globulin reaction, 12 patients (57%) developed mucositis and 2 patients (9.5%) had haemorrhagic complications. Changes in supportive measures over the study, particularly antibiotic prophylaxis regimes during mobilisation and conditioning, markedly diminished the incidence of severe complications. During the first 12-month follow-up, viral infections were the most commonly observed complications, and one patient died due to systemic cytomegalovirus infection. CONCLUSIONS: Autologous HSCT for patients with refractory CD is feasible, but extraordinary supportive measures need to be implemented. We suggest that this procedure should only be performed in highly experienced centres.

Contemporary methods for the diagnosis and treatment of microscopic colitis.

Microscopic colitis is a common cause of chronic diarrhea. It is characterized by non-bloody watery diarrhea with macroscopically normal colonic mucosa. Its specific histological characteristics confirm the diagnosis. Two distinct histological forms can be identified, namely, collagenous colitis and lymphocytic colitis. In collagenous colitis, a thick colonic subepithelial collagenous deposit can be observed, whereas in lymphocytic colitis, a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band can be identified. Microscopic colitis occurs more frequently in elderly females and its etiology is believed to be multifactorial, although smoking and consumption of several drugs have been identified as risks factors for the development of the disease. The treatment is based on avoiding the risks factors and administration of oral budesonide.

Intraperitoneal Administration of Autologous Tolerogenic Dendritic Cells for Refractory Crohn's Disease: A Phase I Study.

BACKGROUND AND AIMS: Ex vivo-generated autologous tolerogenic dendritic cells [tolDCs] can restore immune tolerance in experimental colitis. The aim of this study was to determine the safety and tolerability of administration of autologous tolDCs in refractory Crohn's disease [CD] patients. METHODS: A phase-I, single-centre, sequential-cohorts, dose-range study was designed. Stable tolDCs were generated ex vivo from monocytes following a previously developed protocol, and administered by sonography-guided intraperitoneal injection. Six sequential refractory-CD cohorts were established: the first three cohorts received a single intraperitoneal injection of tolDCs at escalating doses [2 x 10(6)/5 x 10(6)/10 x 10(6)]; and the last three cohorts received three biweekly intraperitoneal injections at same escalating doses. Safety was sequentially evaluated. Patients were assessed from week 0 to 12 and followed up for 1-year period for safety. RESULTS: Nine patients were included. No adverse effects were detected during tolDC injection or follow-up. Three patients withdrew from the study due to CD worsening. Crohn's Disease Activity Index [CDAI] decreased from 274 [60] {mean (standard deviation [SD])} to 222 [113] [p = 0.3]; one [11%] patient reached clinical remission [CDAI < 150] and two [22%] clinical response [CDAI decrease ≥ 100]. Crohn's Disease Endoscopic Index of Severity [CDEIS] decreased from 18 [5] to 13 [8] [p = 0.4]; lesions improved markedly in three patients [33%]. Quality of life (inflammatory bowel disease questionnaire [IBDQ]) changed from 125 [27] to 131 [38] [p = 0.7]; remission [IBDQ at Week 12 ≥ 170] was reached in one [11%] case and response [IBDQ score increase ≥ 16] in two [22%]. CONCLUSIONS: Intraperitoneal administration of autologous tolDCs appears safe and feasible in refractory CD patients. Further studies should be developed to test clinical benefit, determine the optimal administration route and dose, and monitor the immune responses; See [www.eudract.ema.europa.eu, EudraCT number 2007-003469-42; www.aemps.gob.es number PEI 08-049].

Characterization of inflammation and fibrosis in Crohn's disease lesions by magnetic resonance imaging.

OBJECTIVES: Measurement of the component of fibrosis in Crohn's disease (CD) may have important therapeutic implications. The aim of this study was to characterize the Magnetic Resonance Imaging (MRI) findings that are differentially associated with the presence of fibrosis and those associated with inflammatory activity, using the pathological analysis of surgically resected intestinal lesions as reference standard. METHODS: MRI studies with identical imaging protocol of 41 CD patients who underwent elective bowel resection within 4 months before surgery were reviewed. MRI evaluated wall thickening, edema, ulcers, signal intensity at submucosa at 70 s and 7 min after gadolinium injection, stenosis, and pattern of enhancement in each phase of the dynamic study and changes on this pattern over time. Pathological inflammatory and fibrosis scores were classified into three grades of severity. RESULTS: In all, 44 segments from 41 patients were analyzed. The pathological intensity of inflammation was associated with the following MRI parameters: hypersignal on T2 (P=0.02), mucosal enhancement (P=0.03), ulcerations (P=0.01), and blurred margins (P=0.05). The degree of fibrosis correlated with the percentage of enhancement gain (P<0.01), the pattern of enhancement at 7 min (P<0.01), and the presence of stenosis (P=0.05). Using percentage of enhancement gain, MRI is able to discriminate between mild-moderate and severe fibrosis deposition with a sensitivity of 0.94 and a specificity of 0.89. CONCLUSIONS: MRI is accurate for detecting the presence of severe fibrosis in CD lesions on the basis of the enhancement pattern.

Accuracy of advanced endoscopy and fecal calprotectin for prediction of relapse in ulcerative colitis: a prospective study.

BACKGROUND: The aim of this study was to determine the accuracy of advanced endoscopy for prediction of relapse in ulcerative colitis, in comparison with serum and fecal biomarkers. METHODS: Patients with ulcerative colitis with sustained clinical remission defined as absence of blood in stool for a minimum of 3 months and Mayo endoscopic subscore of 0 were included. High-resolution rectosigmoidoscopy was performed at baseline and at the end of study (week 52 or relapse), assessing mucosal pit pattern by chromoendoscopy and narrow band imaging as well as vascular pattern by narrow band imaging. Histology was evaluated at baseline and at the end of the study. Follow-up for 1 year or until relapse with clinical evaluations and serum and fecal biomarkers every 3 months was established. Relapse was defined as presence of blood in stool and a Mayo endoscopic subscore ≥1 with histologic confirmation. RESULTS: Seventeen out of 64 patients (27%) relapsed during the follow-up period. Baseline clinical characteristics in patients who relapsed and those who did not were similar. Neither pit or vascular pattern nor histology was significantly different between relapsers and nonrelapsers. Among serum biomarkers, high platelet count was significantly associated with higher relapse rates. Fecal calprotectin was predictor of relapse within 3- and 12-month period with high specificity but low sensitivity. CONCLUSIONS: Advanced endoscopy and histology do not predict relapse over 1-year period in patients with ulcerative colitis. Fecal calprotectin can predict relapse in 3- and 12-month period with low accuracy.

Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease.

BACKGROUND & AIMS: We assessed the accuracy of magnetic resonance enterography (MRE) in monitoring response to therapy in patients with Crohn's disease (CD) using ileocolonoscopy as a reference standard. METHODS: We performed a prospective multicenter study of 48 patients with active CD and ulcers in at least one ileocolonic segment. All patients underwent ileocolonoscopy and MRE at baseline and 12 weeks after completing treatment with corticosteroids (CS) or anti-tumor necrosis factor agents. Disease activity was quantified using Crohn's Disease Endoscopic Index of Severity (CDEIS) and Magnetic Resonance Index of Activity (MaRIA). The primary analysis was to determine the accuracy of MRE in identification of healing, defined as the disappearance of ulcers in endoscopy examination. Additional analyses established the accuracy of MRE in determining endoscopic remission (a CDEIS score <3.5) and change in severity based on consideration of all segments. RESULTS: MRE determined ulcer healing with 90% accuracy and endoscopic remission with 83% accuracy. The mean CDEIS and MaRIA scores significantly changed at week 12 in segments with ulcer healing, based on endoscopic examination (CDEIS: 21.28 ± 9.10 at baseline vs 2.73 ± 4.12 at 12 weeks; P < .001 and MaRIA: 18.86 ± 9.50 at baseline vs 8.73 ± 5.88 at 12 weeks; P < .001). The MaRIA score accurately detected changes in lesion severity (Guyatt score: 1.2 and standardized effect size: 1.07). MRE was as reliable as endoscopy in assessing healing; no significant changes in CDEIS or MaRIA scores were observed in segments with persistent ulcers, based on endoscopic examination (CDEIS: 26.43 ± 9.06 at baseline vs 20.77 ± 9.13 at 12 weeks; P = .18 and MaRIA: 22.13 ± 8.42 at baseline vs 20.77 ± 9.17 at 12 weeks; P = .42). The magnitude of change in CDEIS scores correlated with those in MaRIA scores (r = 0.51; P < .001). CONCLUSIONS: MRE evaluates ulcer healing with a high level of accuracy when ileocolonoscopy is used as the reference standard. The MaRIA is a valid, responsive, and reliable index assessing response to therapy in patients with CD.

Cell therapies for IBD: what works?

The inflammatory response in patients with inflammatory bowel disease is a complex self-amplifying process with multiple cellular and molecular pathways controlling activation and shut-off of the process. Available therapeutic interventions with drugs that have a very selective action, such as anti-tumor necrosis factor antibodies, or broader effects such as corticosteroids still leave a significant proportion of patients with Crohn's disease and ulcerative colitis insufficiently treated. Cellular therapies are emerging as promising new approaches to treat inflammatory bowel diseases and in particular Crohn's disease. Experimental and clinical data are the origin of the increasing utilization of cell therapies for severe immune-mediated diseases including inflammatory bowel disease. The types of cell therapies for these diseases can be divided into two different areas: hematopoietic stem cell therapies, and selected/conditioned immune cell therapy, the latter including mesenchymal stem cells and T-regulatory cells-based therapies.

Risk of developing tuberculosis under anti-TNF treatment despite latent infection screening.

BACKGROUND: In patients treated with TNF-antagonists, incident cases of tuberculosis (TB) after a negative screening have been reported, leading to the suggestion that improved TB testing is necessary. AIM: The aim of the current study is to establish the incidence of TB and its characteristics in patients with inflammatory bowel disease (IBD) under TNF antagonists to design improved prevention strategies. METHODS: IBD patients from a single center treated with anti-TNF therapy between January 2000 and September 2011 were identified through a database that prospectively records clinical data, treatments and adverse events. RESULTS: During the study period 423 patients received anti-TNF therapy. Screening for latent TB infection (LTBI) previous to anti-TNF treatment was positive in 30 patients (6.96%). Seven patients (1.65%) developed TB while under anti-TNF treatment. Six patients (five under immunosuppressant treatment) had a negative LTBI screening. TST was positive in one patient not receiving immunosuppressants, and was treated with isoniazid before starting anti-TNF therapy. In 4 patients TB was diagnosed within the first 16 weeks after starting anti-TNF therapy. Three cases had pulmonary TB and 4 extrapulmonary disease. CONCLUSIONS: In the IBD population under study, incidence of TB infection associated with anti-TNF therapy is higher than that reported in controlled trials and occurs early after treatment initiation. False negative results of LTBI despite appropriate measures may occur, suggesting that more effective screening strategies are needed.