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Background & aimsMore than half of Crohn's disease patients develop intestinal fibrosis-induced intestinal strictures. Elafin is a human protease inhibitor that is down-regulated in the stricturing intestine of Crohn's disease patients. We investigated the efficacy of elafin in reversing intestinal fibrosis and elucidated its mechanism of action.MethodsWe developed a new method to mimic a stricturing Crohn's disease environment and induce fibrogenesis using stricturing Crohn's disease patient-derived serum exosomes to condition fresh human intestinal tissues and primary stricturing Crohn's disease patient-derived intestinal fibroblasts. Three mouse models of intestinal fibrosis, including SAMP1/YitFc mice, Salmonella-infected mice, and trinitrobenzene sulfonic acid-treated mice, were also studied. Elafin-Eudragit FS30D formulation and elafin-overexpressing construct and lentivirus were used.ResultsElafin reversed collagen synthesis in human intestinal tissues and fibroblasts pretreated with Crohn's disease patient-derived serum exosomes. Proteome arrays identified cathepsin S as a novel fibroblast-derived pro-fibrogenic protease. Elafin directly suppressed cathepsin S activity to inhibit protease-activated receptor 2 activity and Zinc finger E-box-binding homeobox 1 expression, leading to reduced collagen expression in intestinal fibroblasts. Elafin overexpression reversed ileal fibrosis in SAMP1/YitFc mice, cecal fibrosis in Salmonella-infected mice, and colonic fibrosis in trinitrobenzene sulfonic acid-treated mice. Cathepsin S, protease-activated receptor 2 agonist, and zinc finger E-box-binding homeobox 1 overexpression abolished the anti-fibrogenic effect of elafin in fibroblasts and all 3 mouse models of intestinal fibrosis. Oral elafin-Eudragit FS30D treatment abolished colonic fibrosis in trinitrobenzene sulfonic acid-treated mice.ConclusionsElafin suppresses collagen synthesis in intestinal fibroblasts via cathepsin S-dependent protease-activated receptor 2 inhibition and decreases zinc finger E-box-binding homeobox 1 expression. The reduced collagen synthesis leads to the reversal of intestinal fibrosis. Thus, modified elafin may be a therapeutic approach for intestinal fibrosis.

Intestinal strictures are a frequent complication in patients with Crohn’s Disease (CD) and the presence of fibrosis within strictures impacts the therapeutic treatment approach. Here, we evaluate quantitative phase imaging (QPI) using digital holographic microscopy (DHM) for the evaluation of fibrosis within CD strictures. 30 full thickness resection specimens were obtained from non-stenotic and stenotic tissue areas of 15 CD patients. Cryostat sections were analyzed by DHM to measure the spatial distribution of the refractive index (RI) to quantify tissue density. Complementary, histopathological evaluation of H&E staining and immunofluorescence (IF) targeting fibrosis markers served as the gold standard. Moreover, tissue stiffness was evaluated by elastography. RI values assessed by DHM were significantly higher in stenotic compared to non-stenotic tissue areas (p

Supplementary files for a submission to Physiological Reviews

Background Despite the knee extensor weakness, less attention has been paid to the evaluation of patellar tendon after total knee arthroplasty (TKA). We previously observed patellar tendon hypertrophy after TKA. The purpose of this study is to reanalyze these ultrasound data to detect whether brightness mode ultrasound imaging reflects pathological changes of the patellar tendon after TKA. Methods Twenty-eight participants with post unilateral TKA were assigned to an intervention group or control group. The intervention group underwent a 12-week skiing program. Patellar tendon mechanical properties were obtained by combining isometric dynamometry, ultrasound imaging, and electromyography in operated knee and nonoperated knee. Luminosity ratio (LR) was measured using echo intensity in a relaxed and maximally loaded phase. Results Baseline comparisons revealed significant effects of the surgical side (P < .001) and loading phase (P = .017), but no interaction between leg and phase (P < .149). LR of the operated knee was significantly lower than LR of the nonoperated knee in relaxed (P < .001) and maximally loaded phases (P = .003). In addition, there was a significant correlation between LR of maximum phase and isometric knee extension torque (r2 = 0.156, P = .038). However, LR was not related to patellar tendon stiffness, Youngs modulus, or strain. There was a significant time effect in knee extension torque, but no time effects on LR and tendon force. Conclusion Patellar tendon LR is decreased along with degenerative change after TKA. Ultrasound imaging provides a promising metric to acquire in vivo patellar tendon pathological assessment after TKA. (VLID)5531341

Introduction: The effect of chronic patellar tendinopathy on tissue function and integrity is currently unclear and underinvestigated. The aim of this cohort comparison was to examine morphological, material, and mechanical properties of the patellar tendon and to extend earlier findings by measuring the ability to store and return elastic energy in symptomatic tendons. Methods: Seventeen patients with chronic (>3 months, VISA-P < 80), inferior pole patellar tendinopathy (24 4 years; male = 12, female = 5) were carefully matched to controls (25 3 years) for training status, pattern, and history of loading of the patellar tendon. Individual knee extension force, patellar tendon stiffness, stress, strain, Youngs modulus, hysteresis, and energy storage capacity, were obtained with combined dynamometry, ultrasonography, magnetic resonance imaging, and electromyography. Results: Anthropometric parameters did not differ between groups. VISA-P scores ranged from 28 to 78 points, and symptoms had lasted from 10 to 120 months before testing. Tendon proximal cross-sectional area was 61% larger in the patellar tendinopathy group than in the control group. There were no differences between groups in maximal voluntary isometric knee extension torque (p = 0.216; d < 0.31) nor in tensile tendon force produced during isometric ramp contractions (p = 0.185; d < 0.34). Similarly, tendon strain (p = 0.634; d < 0.12), hysteresis (p = 0.461; d < 0.18), and strain energy storage (p = 0.656; d < 0.36) did not differ between groups. However, patellar tendon stiffness (19%; p = 0.007; d < 0.74), stress (27%; p< 0.002; d < 0.90) and Youngs modulus (32%; p = 0.001; d < 0.94) were significantly lower in tendinopathic patients compared to healthy controls. Discussion: In this study, we observed lower stiffness in affected tendons. However, despite the substantial structural and histological changes occurring with tendinopathy, the tendon capacity to store and dissipate energy did not differ significantly. (VLID)5346698

BackgroundPatients with Crohn’s disease (CD) may develop fibrostenotic strictures. No currently available therapies prevent or treat fibrostenotic CD (FCD), making this a critical unmet need.AimTo compare health outcomes and resource utilisation between CD patients with and without fibrostenotic disease.MethodsPatients aged ≥18 years with FCD and non-FCD between 30 October 2015 and 30 September 2018 were identified in the Truven MarketScan Commercial Claims and Encounters Database. We conducted 1:3 nearest neighbour propensity score matching on age, sex, malnutrition, payer type, anti-tumour necrosis factor use, and Charlson Comorbidity Index score. Primary outcomes up to 1 year from the index claim were ≥1 hospitalisation, ≥1 procedure, ≥1 surgery, and steroid dependency (>100 day supply). Associations between FCD diagnosis and outcomes were estimated with a multivariable logistic regression model. This study was exempt from institutional review board approval.ResultsPropensity score matching yielded 11 022 patients. Compared with non-FCD, patients with FCD had increased likelihood of hospitalisations (17.1% vs 52.4%; pConclusionsFCD was associated with higher risk for hospitalisation, procedures, abdominal surgery, and steroid dependency. Patients with FCD had a greater mean annual cost per patient. FCD represents an ongoing unmet medical need.

Background Although ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice of many patients with ulcerative colitis and other conditions, some patients may require pouch excision (PE). We aimed to describe our experience with pouch excisions and associated outcomes with an emphasis on late medical, endoscopic, and surgical interventions for IBD. Methods We performed a retrospective review of a prospective colorectal surgery database. All PEs performed at our quaternary pouch center from 2006 – 2019 were included; pelvic exenteration, PE with neo-IPAA or Kock-pouch were excluded. Early complications occurred 30 days. Medications taken prior to PE were included if taken within 12 weeks of pouch excision. Data are reported in frequency (proportion) or median (interquartile range). Results A total of 197 cases met inclusion criteria, and were performed by 23 surgeons, median 6 excision (IQR 2 - 14) cases over a 14-year period: of these, 105 had their index pouch created at our quaternary pouch referral center (overall PE rate 2.7%). Indications for PE are shown in Table 1. Median time to PE was 7 years and 94 (48%) patients had re-diversion prior to PE. Medications prior to PE: 34 (17%) steroids, 27 (14%) biologics, and 22 (11%) immune-modulators. The median duration of surgery was 4 hours (3.2–5). The median estimated blood loss was 263 ml (150–500) with 24 patients (12%) requiring at least one unit of packed red blood cells intra-operatively. Most pouch excisions were done through laparotomy; 2 cases (1%) were started robotically and 11 cases (10%) laparoscopically with a 26% conversion rate. Intersphincteric dissection was used in 172 cases (87%) while 26 cases (13%) required abdomino-perineal resection, of which 58% had a neoplastic indication. Intra-operative, early and late complications are shown in Table 2; 40 patients (20%) had perineal wound complications in less than 30 days, while 26 patients (13%) had long-term perineal wound complications, of which 15 patients required return to the operating room. After PE, 23 patients (12%) required continuation of IBD medications, 6 patients (3.1%) required surgery, and 4 patients (2%) required endoscopic intervention for their IBD. Conclusions In this large series of ileoanal pouch excisions, we found that perineal wound complications are common, but infrequently require operative intervention. For most IBD patients in this series, pouch excision did appear to be a destination therapy for IBD with a small minority requiring ongoing medical therapy for IBD.

Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.

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 classification, 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].

Introduction: During running and jumping activities, elastic energy is utilized to enhance muscle mechanical output and efficiency. However, training-induced variations in tendon spring-like properties remain under-investigated. The present work extends earlier findings on sport-specific profiles of tendon stiffness and cross-sectional area to examine whether years of distinct loading patterns are reflected by tendons' ability to store and return energy. Methods:Ultrasound scans were performed to examine the morphological features of knee extensor and plantar flexor muscle-tendon units in elite ski jumpers, distance runners, water polo players, and sedentary controls. Tendon strain energy and hysteresis were measured with combined motion capture, ultrasonography, and dynamometry. Results: Apart from the fractional muscle-to-tendon cross-sectional area ratio being lower in the knee extensors of ski jumpers (−31%) and runners (−33%) than in water polo players, no difference in the considered muscle-tendon unit morphological features was observed between groups. Similarly, no significant difference in tendon energy storage or energy return was detected between groups. In contrast, hysteresis was lower in the patellar tendon of ski jumpers (−33%) and runners (−30%) compared to controls, with a similar trend for the Achilles tendon (significant interaction effect and large effect sizes η2 = 0.2). Normalized to body mass, the recovered strain energy of the patellar tendon was ~50% higher in ski jumpers than in water polo players and controls. For the Achilles tendon, recovered strain energy was ~40% higher in ski jumpers and runners than in controls. Discussion: Advantageous mechanical properties related to tendon spring-like function are observed in elite athletes whose sport require effective utilization of elastic energy. However, the mechanisms underpinning the better tendon capacity of some athletes to retain elastic energy could not be ascribed to intrinsic or morphological features of the lower limb muscle-tendon unit.

Introduction: During running and jumping activities, elastic energy is utilized to enhance muscle mechanical output and efficiency. However, training-induced variations in tendon spring-like properties remain under-investigated. The present work extends earlier findings on sport-specific profiles of tendon stiffness and cross-sectional area to examine whether years of distinct loading patterns are reflected by tendons' ability to store and return energy. Methods: Ultrasound scans were performed to examine the morphological features of knee extensor and plantar flexor muscle-tendon units in elite ski jumpers, distance runners, water polo players, and sedentary controls. Tendon strain energy and hysteresis were measured with combined motion capture, ultrasonography, and dynamometry. Results: Apart from the fractional muscle-to-tendon cross-sectional area ratio being lower in the knee extensors of ski jumpers (31%) and runners (33%) than in water polo players, no difference in the considered muscle-tendon unit morphological features was observed between groups. Similarly, no significant difference in tendon energy storage or energy return was detected between groups. In contrast, hysteresis was lower in the patellar tendon of ski jumpers (33%) and runners (30%) compared to controls, with a similar trend for the Achilles tendon (significant interaction effect and large effect sizes 2 = 0.2). Normalized to body mass, the recovered strain energy of the patellar tendon was 50% higher in ski jumpers than in water polo players and controls. For the Achilles tendon, recovered strain energy was 40% higher in ski jumpers and runners than in controls. Discussion: Advantageous mechanical properties related to tendon spring-like function are observed in elite athletes whose sport require effective utilization of elastic energy. However, the mechanisms underpinning the better tendon capacity of some athletes to retain elastic energy could not be ascribed to intrinsic or morphological features of the lower limb muscle-tendon unit. (VLID)1773031

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 classification, 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].

The present study aimed to determine whether distinct sets of tendon properties are seen in athletes engaged in sports with contrasting requirements for tendon function and structural integrity. Patellar and Achilles tendon morphology and force-deformation relation were measured by combining ultrasonography, electromyography and dynamometry in elite ski jumpers, distance runners, water polo players and sedentary individuals. Tendon cross-sectional area normalized to body mass2/3 was smaller in water polo players than in other athletes (patellar and Achilles tendon; -28 to -24%) or controls (patellar tendon only; -9%). In contrast, the normalized cross-sectional area was larger in runners (patellar tendon only; +26%) and ski jumpers (patellar and Achilles tendon; +21% and +13%, respectively) than in controls. Tendon stiffness normalized to body mass2/3 only differed in ski jumpers, compared to controls (patellar and Achilles tendon; +11% and +27%, respectively) and to water polo players (Achilles tendon only; +23%). Tendon size appears as an adjusting variable to changes in loading volume and/or intensity, possibly to preserve ultimate strength or fatigue resistance. However, uncoupled morphological and mechanical properties indicate that functional requirements may also influence tendon adaptations. Hans-Peter Wiesinger, Florian Rieder, Alexander Kösters, Erich Müller

The aim of this study was to investigate the effect of alpine skiing on patellar tendon properties in patients with total knee arthroplasty (TKA). Thirty-one adults (70.4 ± 4.7 years) with unilateral TKA were recruited 2.7 ± 0.9 years after surgery and assigned to an intervention (IG) or a control group (CG). The IG underwent a 12-week guided skiing program. Tendon stiffness, Young's modulus, and cross-sectional area (CSA) were measured before and after the intervention. In both groups, mean tendon CSA was 28% (P

This study investigated the effectiveness of recreational skiing as an intervention to improve quadriceps muscle architecture, strength, and antagonistic co-activation in patients with unilateral total knee arthroplasty (TKA). Hence, patients with TKA were assigned to either an intervention group (IG) or control group (CG). The IG completed a 12-week guided skiing program whereas the CG was instructed not to change their daily routines for the same period and was not allowed to ski. Before, after the intervention/after an 8-week retention period m. rectus femoris (RF) cross-sectional area (CSA), m. vastus lateralis muscle thickness, fascicle length, and pennation angle were measured with ultrasonography, while isometric (90° knee angle) knee extension, flexion torque and m. biceps femoris co-activation were assessed on an isokinetic dynamometer in 26 patients. There were significant and stable increases in RF CSA for the operated (10%; P 0.05). There were no significant effects for other parameters (all P > 0.05). Overall, the skiing intervention was successful in increasing muscle mass in TKA older patients.

Animal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque–angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque–angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.

eingereicht von Florian Rieder Salzburg, Univ., Dipl.-Arb., 2015 Zsfassung / Abstract in dt. und engl. Sprache

eingereicht von Florian Rieder Salzburg, Univ., Dipl.-Arb., 2010

Die Suppression von Tumor-Nekrose-Faktor-a durch die spezifische Hemmung der Phosphodiesterase konnte bisher sowohl in vitro als auch in verschiedenen Tiermodellen für chronisch entzündliche Erkrankungen gezeigt werden (Torphy 1998; Schudt et al. 1999; Bundschuh et. al. 2001; Hatzelmann und Schudt 2001). In der vorliegenden Arbeit wurde die Wirkung des spezifischen Phosphodiesterase Typ 4-Inhibitors Roflumilast und des dualselektiven Phosphodiesterase Typ 3/4-Inhibitors Pumafentrine im Mausmodell der Dextran-Sodium-Sulfat induzierten Kolitis getestet. Hierbei handelt es sich nach unserer Kenntnis um die erste Prüfung dieser Substanzen in diesem Tiermodell und um die erste Untersuchung eines Phosphodiesterase Typ 3/4-Inhibitors in einem Kolitismodell überhaupt. Die Kolitis wurde durch orale Gabe von Dextran-Sodium-Sulfat im Trinkwasser über 11 Tage induziert. Die Entzündung des Kolons war mit geringer Variation gut reproduzierbar. Die Phosphodiesterase-Inhibitoren wurden mit Beginn der Dextran-Sodium-Sulfat-Gabe einmal täglich p. o. über den gesamten Versuchs-verlauf appliziert. 109 weibliche Balb/c Mäuse wurden in den Versuchsreihen eingesetzt. Roflumilast zeigte eine dosisabhängige Wirksamkeit. Die 5 mg/kg KG Dosis zeigte einen deutlichen therapeutischen Effekt auf den klinischen Verlauf, die Kolonlänge, die Produktion von Tumor-Nekrose-Faktor-a im Kolon sowie das Milzgewicht. Diese Verbesserung korrelierte mit einer geringeren Ausprägung der histopathologischen Veränderungen im Kolon. Bei der 1 mg/kg KG Dosis wurden nur der klinische Score, die Kolonlänge und das Milzgewicht signifikant verbessert. Pumafentrine bewirkte in der mittleren eingesetzten Dosierung (5 mg/kg KG) eine Besserung des klinischen Scores, der Kolonlänge und der Tumor-Nekrose-Faktor-a-Produktion im Kolongewebe. Es konnte keine Beeinflussung der systemischen Entzündungsreaktion anhand einer Verringerung des Milzgewichtes beobachtet werden, jedoch zeigte sich bei ex vivo stimulierten Splenozyten eine signifikant geringere Aktivierbarkeit und Zytokinsynthese. Die 20 mg/kg KG Dosis verbesserte als einzigen Endpunkt die Tumor-Nekrose-Faktor-a-Produktion im Kolon, während die 1,5 mg/kg KG Dosis in keinem der untersuchten Parameter zu einer signifikanten Wirksamkeit führte. Die Ergebnisse dieser Arbeit zeigen, dass die Phosphodiesterase-Inhibitoren Roflumilast und Pumafentrine dosisabhängig zu einer Verbesserung der Dextran-Sodium-Sulfat-induzierten Kolitis - als einem Modell für chronisch entzündliche Darmerkrankungen - führen. Die spezifische Hemmung der Phosphodiesterase Typ 4 und die duale Hemmung der Phosphodiesterase Typ 3/4 stellen deshalb viel versprechende Ansätze in der Therapie chronisch entzündlicher Darmerkrankungen dar. Beide Substanzen befinden sich in fortgeschrittenen klinischen Studien für die chronisch obstruktive Lungenerkrankung und für Asthma bronchiale. Deshalb sollten diese Präparate in anderen Tiermodellen für chronisch entzündliche Darmerkrankungen oder klinischen Studien weiter untersucht werden.

ObjectiveSeveral advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA.MethodsWe updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.ResultsThe number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab.ConclusionWe have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

ispartof: JOURNAL OF CROHNS & COLITIS vol:13 issue:2 pages:144-+ ispartof: location:England status: published

BACKGROUND The presentation of Crohn's disease (CD) is heterogeneous and often leads to serious complications and need for surgery. We tested serum anti-zymogen granule glycoprotein 2 (GP2) antibodies, including its novel isoform alpha, for association with genetic variants, diagnosis, disease stratification, and prediction of CD courses in a combined cross-sectional and cohort study. METHODS Serum samples of 303 CD, 108 ulcerative colitis, 72 other inflammatory gastrointestinal diseases, and 206 controls without predominant gastrointestinal diseases controls (HC) were tested for the presence of Anti-GP2 and Anti-Saccharomyces cervisiae (ASCA) by enzyme-linked immunosorbent assay. Genetic analysis was performed using the Illumina Immunochip. RESULTS GP2 IgA and IgG had the highest discriminatory capability for CD versus ulcerative colitis and CD versus inflammatory gastrointestinal diseases. We identified an association of GP2 IgA and IgG each with 5 distinct single-nucleotide polymorphisms. Levels of anti-GP2 IgG were moderately associated with ileal disease location. Interestingly, both, anti-GP2 IgA and IgG were exclusively associated with the occurrence of stenosis and need for surgery, independently of disease location, but not with fistulizing CD, early disease onset or disease activity. ASCA IgG and IgA were qualitatively and quantitatively linked to CD, CD complications, and need for surgery. Increased levels of ASCA IgG and IgA and positivity for ASCA IgG, but neither levels nor positivity for GP2 IgG or IgA were predictive of the earlier occurrence of complications or surgery. CONCLUSIONS Anti-GP2 antibodies may aid as a tool for diagnosis and differentiation of CD and could indicate a more complicated CD course.

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.

In the last 10 years, we have learned much about the pathogenesis, diagnosis, and management of intestinal fibrosis in patients with inflammatory bowel diseases. Just a decade ago, intestinal strictures were considered to be an inevitable consequence of long-term inflammation in patients who did not respond to anti-inflammatory therapies. Inflammatory bowel diseases−associated fibrosis was seen as an irreversible process that frequently led to intestinal obstructions requiring surgical intervention. This paradigm has changed rapidly, due to the antifibrotic approaches that may become available. We review the mechanisms and diagnosis of this serious complication of inflammatory bowel diseases, as well as factors that predict its progression and management strategies.

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.