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Background and Aim Contemporary techniques to assess disease activity or bowel damage in patients with inflammatory bowel disease [IBD], such as endoscopy and imaging, are either invasive or lack accuracy. Non-invasive biomarkers for this purpose remain an unmet medical need. Herein, we provide a comprehensive systematic review of studies evaluating blood extracellular matrix [ECM] biomarkers and their relevance in IBD. Methods We conducted a systematic review of PubMed, EMBASE, Web of Science, and Scopus to identify citations pertaining to ECM biomarkers of IBD up to March 1, 2024. Studies were categorized based on marker subtype and clinical use. Results Thirty-one ECM markers were identified, 28 of which demonstrated the ability to differentiate IBD disease activity. Collagen III emerged as the most extensively investigated [1212 IBD patients], with the degradation marker C3M and deposition marker PRO-C3 being associated with IBD and subtypes. Collagen V markers C5M and PRO-C5 emerged as the most accurate single markers for diagnosis of IBD, with an area under the curve of 0.91 and 0.93, respectively. Overall, studies were characterized by variable endpoints. None of the studies included histological grading of intestinal damage, repair, or fibrosis formation as the primary outcome in relation to the ECM blood markers. Conclusions Multiple ECM markers are linked with IBD and its phenotypes. However, more rigorous study designs and clearly defined endpoints are needed to ensure reproducibility and develop reliable and accurate biomarkers. ECM markers hold promise as they provide a 'window' into transmural tissue remodelling and fibrosis burden, warranting further investigation. [ABSTRACT FROM AUTHOR]

Background and Aims Non-invasive cross-sectional imaging via magnetic resonance enterography [MRE] offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease [CD] but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathological inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. Methods This single-centre, cross-sectional study included 51 CD patients [ n  = 34 for discovery; n  = 17 for validation] with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both were evaluated against histopathology. Results Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both the discovery (area under the curve [AUC = 0.69, 0.83] and validation [AUC = 0.67, 0.78] cohorts. Radiologist visual scoring had an AUC = 0.67 for identifying severe inflammation and AUC = 0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation [AUC = 0.79] and modestly improved assessment of severe fibrosis [AUC = 0.79 for severe fibrosis] over individual approaches. Conclusions Radiomic features of CD strictures on MRE can accurately identify severe histopathological inflammation and severe histopathological fibrosis, as well as augment performance of the radiologist visual scoring in stricture characterization. [ABSTRACT FROM AUTHOR]

Background Herein, we present a proof-of-concept study of three-dimensional [3D] pouchography using virtual and printed 3D models of ileal pouch-anal anastomosis [IPAA] in patients with normal pouches and in cases of mechanical pouch complications. Methods We performed a retrospective, descriptive case series of a convenience sample of 10 pouch patients with or without pouch dysfunction, who had CT scans appropriate for segmentation who were identified from our pouch registry. The steps involved in clinician-driven automated 3D reconstruction are presented. Results We included three normal patients who underwent CT imaging and were found to have no primary pouch pathology, and seven patients with known pouch pathology identifiable with 3D reconstruction [including pouch strictures, megapouch, pouch volvulus, and twisted pouches], underwent 3D virtual modelling; one normal and one twisted pouch were 3D-printed. We discovered that 3D pouchography reliably identified staple lines [pouch body, anorectal circular and transverse, and tip of J], the relationship between staple lines, and variations in pouch morphology and pouch pathology. Conclusion Three-dimensional reconstruction of IPAA morphology is highly feasible using readily available technology. In our practice, we have found 3D pouchography to be an extremely useful adjunct to diagnose various mechanical pouch complications and improve planning for pouch salvage strategies. Given its ease of use and helpfulness in understanding the pouch structure and function, we have started to routinely integrate 3D pouchography into our clinical pouch referral practice. Further study is needed to formally assess the value of this technique to aid in the diagnosis of pouch pathology. [ABSTRACT FROM AUTHOR]

Background and Aims Crohn's disease [CD] symptoms are a main driver for impaired quality of life, and fast relief is important for patient care. Stool frequency [SF] and abdominal pain score [APS] are patient-reported outcomes [PROs] measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab [RZB], a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints. Methods Individual and combined measures of SF and AP at Weeks 1, 2, and 3 were assessed in patients with moderate to severe CD who received 600 mg intravenous RZB or placebo [PBO] in the ADVANCE or MOTIVATE induction studies. Multivariate logistic regression was used to examine the predictiveness of early symptom improvement for clinical and endoscopic outcomes following RZB induction and maintenance. Results Higher rates of SF/APS clinical remission and enhanced clinical response were observed as early as Week 1 with RZB vs PBO. A larger proportion of patients achieved clinical endpoints with RZB vs PBO, irrespective of prior bio-failure status. Early PRO improvement was associated with a greater likelihood of achieving clinical and endoscopic improvement following 12-week induction and 52-week maintenance RZB dosing. Conclusions After the first intravenous RZB induction dose, significantly greater rates of symptom improvement vs PBO were achieved. Improvements could be observed as early as Week 1 and were predictive of Weeks 12 and 52 clinical and endoscopic improvement. [ABSTRACT FROM AUTHOR]

Background and Aims NX-13 activation of NLRX1 reduces intracellular reactive oxygen species and decreases inflammation in animal models of colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic profile with good tolerability. This phase Ib study aimed to evaluate the safety, tolerability, and pharmacokinetics of NX-13 in patients with active ulcerative colitis [UC]. Methods We conducted a multicentre, randomized, double-blind, placebo-controlled trial of NX-13 in patients with active UC. Patients with a Mayo Clinic Score of 4–10 were randomly assigned [3:3:3:1 ratio] to three NX-13 oral dose groups (250 mg immediate release [IR], 500 mg IR, or 500 mg delayed release [DR], or placebo) once daily for 4 weeks. Safety and pharmacokinetics were the primary and secondary objectives, respectively. Results Thirty-eight patients [11 females] were recruited and randomized to placebo [five], NX-13 250 mg IR [11], NX-13 500 mg IR [11], or NX-13 500 mg DR [11] and received at least one dose. There were no serious adverse events or deaths during the trial. One patient [500 mg DR, 1/11] withdrew due to worsening of UC and a second [500 mg IR, 1/11] on the last day of treatment after a panic attack associated with atrial fibrillation. In the efficacy population [36 patients], clinical improvement in rectal bleeding and stool frequency scores relative to placebo were seen as early as week 2 and endoscopic response was seen at week 4. Conclusions NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741. [ABSTRACT FROM AUTHOR]

Background and Aims To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC]. Methods Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N  = 1162, induction] and W40 [LUCENT-2: N  = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR. Results Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [ p  <0.001], irrespective of prior biologic/tofacitinib failure [ p  <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [ p  <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [ p  <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [ p  <0.05]; ER at W12 was associated with clinical remission [CR] [ p  <0.05] and corticosteroid-free remission [CSFR] at W40 [ p  = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [ p  <0.05]. Conclusions Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092. [ABSTRACT FROM AUTHOR]

Background The Lémann Index [LI] and the recently updated LI are tools for measuring structural bowel damage in adults with Crohn's disease [CD] but have not been evaluated in children. We aimed to validate the updated LI in the prospective multicentre ImageKids study of paediatric CD. Methods We included children with CD undergoing magnetic resonance enterography [MRE], pelvic magnetic resonance imaging [MRI] and ileocolonoscopy. Half were followed for 18 months, when MRE was repeated. Serum was collected for fibrosis-related proteomic markers. The LI was calculated by central readers from the MRE, ileocolonoscopy, physical examination and surgical data. Reliability and construct validity were assessed at baseline, while responsiveness and test–retest reliability were explored longitudinally. Results In total, 240 children were included (mean age, 14.2 ± 2.5 years; median disease duration, 2.2 years [interquartile range, IQR 0.25–4.42]; median baseline LI, 4.23 [IQR 2.0–8.8]). The updated LI had excellent inter-observer reliability (interclass correlation coefficient [ICC] = 0.94, 95% confidence interval [CI] 0.92–0.95) but poor, although statistically significant, correlation with radiologist and gastroenterologist global assessments of damage and with serum proteomic levels of fibrotic markers [ rho = 0.15–0.30, most p < 0.05]. The updated LI had low discriminative validity for detecting damage (area under the receiver operating characteristic curve [AUC-ROC] 0.69, 95% CI 0.62–0.75). In 116 repeated MREs, responsiveness was suboptimal for differentiating improved from unchanged disease [AUC-ROC 0.58, 95% CI 0.45–0.71]. Test–retest reliability was high among stable patients [ICC = 0.84, 95% CI 0.72–0.91]. Conclusion Overall, the updated LI had insufficient psychometric performance for recommending its use in children. An age-specific index may be needed for children with shorter disease duration than typical adult cohorts. [ABSTRACT FROM AUTHOR]

Despite the significant advances in the medical armamentarium for inflammatory bowel diseases [IBD], current treatment options have notable limitations. Durable remission rates remain low, loss of response is common, administration routes are largely parenteral for novel biologics, and medication safety remains a concern. This explains an ongoing unmet need for safe medications with novel mechanisms of action that are administered orally. In line with these criteria, hypoxia-inducible factor [HIF]-1α stabilizers, acting via inhibition of prolyl hydroxylase enzymes, are emerging as an innovative therapeutic strategy. We herein review the mechanism of action and available clinical data for HIF-1α stabilizers and their potential place in the future IBD treatment algorithm. [ABSTRACT FROM AUTHOR]

Background Postoperative recurrence [POR] of Crohn's disease following ileocolonic resection is common. The impact of immediate postoperative intra-abdominal septic complications [IASC] on endoscopic and surgical recurrence has not been elucidated. Aims To evaluate if IASC is associated with an increased risk for endoscopic and surgical POR. Methods This was a retrospective study of adult Crohn's disease patients undergoing ileocolonic resection with primary anastomosis between 2009 and 2020. IASC was defined as anastomotic leak or intra-abdominal abscess within 90 days of the date of surgery. Multivariable logistic and Cox proportional hazard modelling were performed to assess the impact of IASC on endoscopic POR [modified Rutgeerts' score ≥ i2b] at index postoperative ileocolonoscopy and long-term surgical recurrence. Results In 535 Crohn's disease patients [median age 35 years, 22.1% active smokers, 35.7% one or more prior resection] had an ileocolonic resection with primary anastomosis. A minority of patients [ N  = 47; 8.8%] developed postoperative IASC. In total, 422 [78.9%] patients had one or more postoperative ileocolonoscopies, of whom 163 [38.6%] developed endoscopic POR. After adjusting for other risk factors for postoperative recurrence, postoperative IASC was associated with significantly greater odds (adjusted odds ratio [aOR]: 2.45 [1.23–4.97]; p  = 0.01) and decreased time (adjusted hazards ratio [aHR]: 1.60 [1.04–2.45]; p  = 0.03] to endoscopic POR. Furthermore, IASC was associated with increased risk (aOR: 2.3 [1.04–4.87] p  = 0.03) and decreased survival-free time [aHR: 2.53 [1.31–4.87]; p  = 0.006] for surgical recurrence. Conclusion IASC is associated with an increased risk for endoscopic and surgical POR of Crohn's disease. Preoperative optimization to prevent IASC, in addition to postoperative biological prophylaxis, may help reduce the risk for endoscopic and surgical POR. [ABSTRACT FROM AUTHOR]

Background and Aims Intestinal fibrosis has recently been characterised in adult ulcerative colitis and may affect motility, diarrhoea, and the symptom of urgency. We aimed to charactersze the presence of fibrosis in paediatric patients with ulcerative colitis, and its link to severity and chronicity of mucosal inflammation, as well as clinical factors of severity. Methods We performed a single-centre cross-sectional study in children ages 1–18 years with ulcerative colitis, undergoing colectomy or proctocolectomy. Tissue cross-sections were derived from proximal, mid, and distal colon and rectum, and inflammation and fibrosis were graded based on previously developed scores. Clinical data were collected prospectively. Results From 62 patients, 205 intestinal sections were evaluated. Median age at diagnosis was 13 years, 100% had extensive colitis, and all resections were done for refractory disease. The presence, chronicity, and degree of inflammation were linked with the presence of fibrosis. Thickness of the muscularis mucosa was also linked with presence and chronicity of inflammation. The overall submucosal fibrosis burden was associated with prior anti-tumour necrosis factor use. Conclusions Paediatric patients with ulcerative colitis exhibit colorectal submucosal fibrosis and muscularis mucosa thickening, which correlate with the presence, chronicity, and degree of mucosal inflammation. Fibrosis should be recognised as a complication of paediatric ulcerative colitis, and ulcerative colitis should be considered a progressive disease. [ABSTRACT FROM AUTHOR]

Artificial intelligence [AI] techniques are quickly spreading across medicine as an analytical method to tackle challenging clinical questions. What were previously thought of as highly complex data sources, such as images or free text, are now becoming manageable. Novel analytical methods merge the latest developments in information technology infrastructure with advances in computer science. Once primarily associated with Silicon Valley, AI techniques are now making their way into medicine, including in the field of inflammatory bowel diseases [IBD]. Understanding potential applications and limitations of these techniques can be difficult, in particular for busy clinicians. In this article, we explain the basic terminologies and provide a particular focus on the foundations behind state-of-the-art AI methodologies in both imaging and text. We explore the growing applications of AI in medicine, with a specific focus on IBD to inform the practising gastroenterologist and IBD specialist. Finally, we outline possible future uses of these technologies in daily clinical practice. [ABSTRACT FROM AUTHOR]

Background and Aims Sweet syndrome [SS] is a dermatological condition associated with both inflammatory bowel disease [IBD] and azathioprine use. We performed a systematic review to better delineate clinical characteristics and outcomes of SS in IBD patients. Methods Peer-reviewed, full-text journal publications from inception to April 2020 in English language and adult subjects with IBD were included. Skin biopsy was required as SS gold-standard diagnosis. Azathioprine-associated SS required recent azathioprine introduction or recurrence of SS after azathioprine re-challenge. Results We included 89 publications with 95 patients [mean age of SS diagnosis: 44 years; 59% female; 20 with azathioprine-associated SS and 75 without]. SS was diagnosed prior to IBD in 5.3%, at time of IBD diagnosis in 29.5% and after diagnosis in 64.2%. In total, 91% of patients with SS had known colonic involvement and the majority [76%] had active IBD at diagnosis; 22% had additional extra-intestinal manifestations. Successful therapies for SS included corticosteroids [90.5%], anti-tumour necrosis factor [TNF]-α inhibitor therapy [14.8%] and azathioprine [11.6%]. Azathioprine-associated SS was distinct, with 85% male patients, mean age of SS diagnosis of 50 years and a lower likelihood to be prescribed corticosteroids for treatment [75% vs 94.7% of non-azathioprine-associated SS, p = 0.008]. All patients with azathioprine-associated SS improved with medication cessation and developed recurrence after re-challenge. Conclusions SS may precede or occur with IBD diagnosis in almost one-third of cases. Azathioprine and IBD-associated SS present and behave distinctly, especially with regard to gender, age at diagnosis and recurrence risk. Corticosteroids and TNF-α inhibitors have demonstrated efficacy in treating SS in IBD. [ABSTRACT FROM AUTHOR]

Background and Aims Intestinal fibrosis is a common complication of Crohn's disease [CD]. It is characterised by an accumulation of fibroblasts differentiating into myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods We performed a pilot proteomic study comparing the proteome of surface epithelium, isolated by laser-capture microdissection, in normal and fibrotic zones of resected ileal CD strictures [13 zones collected in five patients]. Proteins of interests were validated by immunohistochemistry [IHC] in ileal and colonic samples of stricturing CD [ n = 44], pure inflammatory CD [ n = 29], and control [ n = 40] subjects. The pro-fibrotic role of one selected epithelial protein was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. Results Proteomic study revealed an endoplasmic reticulum [ER] stress proteins increase in the epithelium of CD ileal fibrotic strictures, including anterior gradient protein 2 homologue [AGR2] and binding-immunoglobulin protein [BiP]. This was confirmed by IHC. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2 intracellular expression and its secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin, led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. By using recombinant protein and blocking agent for AGR2, we demonstrated that the secretion of this protein by epithelial cells can play a role in the myofibroblastic differentiation. Conclusions The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2. [ABSTRACT FROM AUTHOR]

Background and Aims Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. Methods MCFI was developed based on vascular findings on CT in a retrospective cohort [ n  = 91] and validated in a prospective cohort [ n  = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. Results In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate–severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p  = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p  = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [ r  = 0.840, p  = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. Conclusions MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis. [ABSTRACT FROM AUTHOR]

Background There are limited data on the postoperative outcomes in Crohn's disease patients exposed to preoperative ustekinumab or vedolizumab. We hypothesised that preoperative biologic use in Crohn's disease is not associated with postoperative complications after ileocolic resection. Methods Crohn's disease patients who underwent ileocolic resection over 2009–2019 were identified at a large regional health system. Preoperative biologic use within 12 weeks of surgery was categorised as no biologic, anti-tumour necrosis factor, vedolizumab, or ustekinumab. The primary endpoint was 90-day intra-abdominal septic complication. Risk factors included preoperative medical therapies, demographics, disease characteristics, laboratory values, and surgical approach. Regression models assessed the association of biologic use with intra-abdominal septic complication. Results A total of 815 Crohn's disease patients who underwent an ileocolic resection were included [62% no biologic, 31.4% anti-tumour necrosis factor, 3.9% vedolizumab, 2.6% ustekinumab]. Primary anastomosis was performed in 85.9% of patients [side-to-side 48.8%, end-to-side 26%, end-to-end 25%] in primarily a stapled [77.2%] manner. Minimally invasive approach was used in 41.4%. The 90-day postoperative intra-abdominal sepsis rate of 810 patients was 12%, abscess rate was 9.6%, and anastomotic leak rate was 3.2%. Multivariable regression modelling controlling for confounding variables demonstrated that preoperative biologic use with anti-tumour necrosis factor [ p  = 0.21], vedolizumab [ p  = 0.17], or ustekinumab [ p  = 0.52] was not significantly associated with intra-abdominal septic complication. Preoperative albumin < 3.5 g/dl was independently associated with intra-abdominal septic complication (odds ratio [OR] 1.76 [1.03, 3.01]). Conclusions In Crohn's disease patients undergoing ileocolic resection, preoperative biologics are not associated with 90-day postoperative intra-abdominal septic complication. Preoperative biologic exposure should not delay necessary surgery. [ABSTRACT FROM AUTHOR]

Background and Aim Penetrating disease is a common condition complicating Crohn's disease [CD]. Establishing the presence of a fistula and the anatomical definition of the fistulous tracts are essential for deciding on appropriate treatment strategies. We aimed to assess the diagnostic accuracy of intra-cavitary contrast-enhanced ultrasound [IC-CEUS] for the detection of a fistulous tract associated with abscesses in CD patients. Methods In this prospective cohort study, consecutive CD patients suspected of having an intra-abdominal abscess, who were referred for US-guided aspiration were recruited. IC-CEUS was performed by injecting diluted contrast agent [SonoVue] into the abscess cavity immediately following the ultrasound-guided needle abscess aspiration and drainage. The diagnostic accuracy of IC-CEUS in demonstrating the presence of fistulous tracts was compared with that of computed tomography enterography/magnetic resonance enterography [CTE/MRE], using surgical and gross pathological findings as the reference standard. Results Thirty-one patients who underwent IC-CEUS and subsequent surgery were included in the final analysis. IC-CEUS demonstrated fistulous/sinus tracts in 26 of 31 participants with a sensitivity and specificity of 86.7 % (95% confidence interval [CI], 68.4–95.6%) and 100% [95% CI, 5.5–100.0%], respectively. Moreover, IC-CEUS correctly demonstrated fistulous/sinus tracts in 13 participants without delineation of fistulous/sinus tracts on CTE/MRE. Combining IC-CEUS and CTE/MRE, the fistula/sinus tract was clearly demonstrated in 29 patients [93.5%, 29/31]. The mean duration of the IC-CEUS procedure was 8.6 min [range 5.0–12.0]. No severe adverse events occurred during the IC-CEUS procedure. Conclusion In this pilot study, IC-CEUS accurately delineated the anatomical definition of fistulous/sinus tracts associated with intra-abdominal abscesses in CD patients. As a radiation-free and safe technique, IC-CEUS may be used as an alternative/adjunctive method to CTE/MRE for detecting penetrating disease in patients with CD. [ABSTRACT FROM AUTHOR]

Background: Gastric and duodenal Crohn's disease [CD]-associated strictures are rare. Evidence on endoscopic balloon dilation [EBD] of upper gastrointestinal [GI] CD strictures is limited, in particular in respect to serial dilations. Methods: Prospective short- and long-term outcome data as well as complication rates on a cohort of upper GI CD-associated stricture dilations [stomach and duodenum] were collected from 1999 to 2015. Factors linked with clinical and technical success, long-term efficacy and complication rates were investigated. Results: A total of 35 CD patients with symptomatic CD-associated upper GI strictures [20% gastric, 67% duodenal, 11% both; mean age at diagnosis 25 years; mean CD duration to stricture 79.9 months; median post-dilation follow-up 22.1 months] underwent a total of 96 pneumatic dilations [33 gastric and 63 duodenal]. The median maximal dilation diameter was 15 mm. Technical success was achieved in 93% and clinical success in 87%, with a complication rate of 4% per procedure. The mean time to re-dilation was 2.2 months and mean time to stricture-related surgery after first dilation was 2.8 months. There was no difference in short-term efficacy, safety, or long-term outcome between the first and any later dilation procedure in the same patient. Conclusions: Pneumatic dilation of upper GI CD-associated strictures has a high rate of short-term technical and clinical success, with moderate long-term efficacy and acceptable complication rates. Serial dilations do not change the efficacy and could be a feasible option to delay or prevent surgical intervention. [ABSTRACT FROM AUTHOR]

This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classiication, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016]. [ABSTRACT FROM AUTHOR]

This ECCO topical review of the European Crohn's and Colitis Organisation [ECCO] focused on prediction, diagnosis, and management of fibrostenosing Crohn's disease [CD]. The objective was to achieve evidence-supported, expert consensus that provides guidance for clinical practice. [ABSTRACT FROM AUTHOR]

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on intestinal fibrosis in inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms and markers of intestinal fibrosis as well as to suggest new therapeutic targets to prevent or treat fibrosis. The results of this workshop are presented in three separate manuscripts. This section describes markers of fibrosis in IBD, identifies unanswered questions in the field and provides a framework for future studies addressing the unmet needs in the field of intestinal fibrosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Literature on endoscopic dilation of Crohn's disease (CD) strictures, especially for primary (non-anastomotic) strictures is limited. Methods: A historical cohort study was performed on patients who underwent endoscopic stricture dilations for CD in our IBD center. Primary endpoint was the efficacy of first endoscopic dilation in preventing the need for surgery in primary strictures compared to anastomotic strictures. Cox proportional hazards models using robust sandwich covariance matrix estimate were used to evaluate the need for surgery and any further endoscopic intervention. Results: In our study cohort (mean age 42.2±13.1years, 57% females, 16.4% current smokers, and median follow-up 1.8years), 128 patients underwent a total of 430 endoscopic stricture dilations for 169 strictures (88 primary, 81 secondary). Forty-two patients (32.8%) required surgery in the follow-up period, with a mean interval period between first dilation and surgery of 33months. There was no difference between primary or anastomotic strictures with respect to the need for surgery (34.1% vs. 29.6%, p =0.53), redilation (59.1% vs. 58%, p =0.89) or total interventions (surgery+redilations, 71.6% vs. 72.8%, p =0.86). Multivariable analysis did not show any significant difference between patients who received and did not receive intralesional steroid injections, biologics or immunomodulators with respect to the need for repeat intervention or surgery. Conclusion: Efficacy and safety of endoscopic dilation are similar between primary and anastomotic CD strictures. Intralesional steroid injection or use of biologics did not decrease the need for re-intervention or surgery for either primary or anastomotic strictures. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: Background and aims: Intestinal fibrosis is a common complication of IBD that can become seriously symptomatic and may require surgical intervention if stricture formation ensues. This review discusses existing and developing knowledge of intestinal fibrosis and its implications for therapy. Methods: Review of the literature, personal communications, unpublished observations. Results: Known mechanisms of intestinal fibrosis include fibroblast proliferation and migration, activation of stellate cells, and extraintestinal fibroblast recruitment. However, novel mechanisms are being uncovered, including epithelial-to-mesenchymal transition, endothelial-to-mesenchymal transition, pericyte differentiation, and fibrocyte recruitment. Most of the traditional and novel mechanisms underlying intestinal fibrosis are associated to the presence of chronic inflammation, but is also possible that fibrosis develops independently of persistent immune activation in the gut. At the moment, the development of preventive, non-interventional, and more effective management of intestinal fibrosis is hampered by the lack of a greater knowledge of its basic pathophysiology and predisposing factors. Conclusions: It is reasonable to expect that therapy of IBD-associated fibrosis will radically improve once the underlying mechanisms are better understood, and therapeutic modalities will emerge that prevent or reverse this complication of IBD. [Copyright &y& Elsevier]