Complication Of Crohn's Disease Research Articles

Management of inflammatory bowel disease in the emergency setting: the MIBODI international survey and evidence-based practices.

This study aimed to evaluate the impact of the WSES-AAST guidelines in clinical practice and to investigate the knowledge, attitudes, and practices of emergency surgeons in managing the complications of ulcerative colitis (UC) and Crohn's disease (CD). The MIBODI survey is a cross-sectional study among WSES members designed as an international web-based survey, according to the Checklist for Reporting Results of Internet E-Surveys, to collect data on emergency surgeons' knowledge, attitudes, and practices concerning the management of patients presenting with acute complications of CD and UC. The questionnaire was composed of 30 questions divided into five sections: (1) demographic data, (2) primary evaluation, (3) non-operative management, (4) operative management, and (5) perianal sepsis management. Two hundred and forty-two surgeons from 48 countries agreed to participate in the survey. The response rate was 24.2% (242/1000 members on WSES mail list). Emergency surgeons showed high adherence to recommendations for 6 of the 21 assessed items, with a "correct" response rate greater than or equal to 60%, according to WSES-AAST recommendations. Nine critical issues were highlighted, with correct answers at a rate of less than 50%. Inflammatory bowel disease is a complex disease that requires a multidisciplinary approach with close collaboration between gastroenterologists and surgeons. Emergency surgeons play a crucial role in managing complications related to IBD. One year after publication, the MIBODI study showed significant global implementation of the WSES-AAST guidelines in clinical practice, offering an imperative tool in the improved management of IBD in emergency and urgent settings.

Prevalence, incidence, and treatment patterns of fistulizing Crohn disease: A US population-based cohort study.

Population-based studies for patients with fistulizing Crohn disease (CD), a severe complication of CD, are limited. To report estimates of the prevalence and incidence rates of fistulizing CD in the United States and examine associated treatment patterns among incident cases. This retrospective, observational cohort study used a US administrative claims database from January 1, 2016, to December 31, 2019, with at least 365 days' continuous insurance enrollment. The prevalent patient population comprised patients with incident or existing cases of fistulizing CD. Crude, age, and sex-adjusted prevalence and incidence rates of fistulizing CD were estimated. Baseline characteristics, comorbidities, and CD-related medications and medical procedures were examined for patients with fistulizing CD. The overall crude prevalence (prevalent cases: n = 5,082) and incidence rates (incident cases: n = 2,399) between 2017 and 2019 were 25.2 (95% CI = 24.5-25.9) per 100,000 persons and 6.9 (95% CI = 6.6-7.1) per 100,000 person-years, respectively. Age- and sex-adjusted prevalence and incidence rates were 24.9 (95% CI = 24.2-25.6) per 100,000 persons and 7.0 (95% CI = 6.7-7.3) per 100,000 person-years, respectively. Approximately half of all patients with incident fistulizing CD were prescribed biologic therapies within 1 year of an incident fistula diagnosis, with anti-tumor necrosis factor therapies the most widely prescribed biologic class; antibiotic and corticosteroid use was also common. Among the incident cases, approximately one-third of patients required surgery during the follow-up period, most of which occurred within 3 months of the index date. This study reports age- and sex-adjusted prevalence and incidence rates for fistulizing CD of 24.9 per 100,000 persons and 7.0 per 100,000 person-years, respectively. As a concerning complication of CD, first-year treatment of fistulas in the United States commonly includes anti-tumor necrosis factor therapy, and there is a considerable surgical burden.

A new treatment option for complex perianal fistulas in Crohn's disease patients; development of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) in Japan

Crohn's disease (CD) is a chronic and relapsing inflammatory bowel disease affecting the entire gastrointestinal tract. The prevalence of CD among Japanese people is increasing. One of the most frequent complications of CD is perianal fistulas. People living with CD may experience complex perianal fistulas, which can cause intense pain, bleeding, swelling, infection, and anal discharge. Despite medical and surgical advancements, complex perianal fistulas in CD remain challenging for clinicians to treat. CD patients living with perianal fistulas reported a negative impact on many aspects of their quality of life. Darvadstrocel is a cell therapy product containing a suspension of allogeneic expanded adipose-derived mesenchymal stem cells. It has been approved in Europe and Japan for the treatment of complex perianal fistulas that have shown an inadequate response to at least one conventional or biologic therapy in adult patients with non-active/mildly active luminal CD. By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option for complex perianal fistulas in CD patients. In this manuscript, the characteristic of darvadstrocel, the summary of results from the pivotal phase 3 studies in Europe and Japan, and the development strategy in Japan were introduced.

Minimally Invasive Management of Complicated and Re-operative Crohn's Disease

AbstractMinimally invasive techniques for the surgical management of Crohn's disease have become the recommended approach for initial surgical intervention in noncomplicated patients as there is lower morbidity for patients without compromising treatment outcomes. There has been a push to expand minimally invasive approaches to complex and recurrent diseases, trying to benefit these difficult patients. However, until recently there have been little data to support the adoption of minimally invasive surgery (MIS) in these scenarios. This article aims to build on the 2019 Clinics in Colon and Rectal Surgery article on complex Crohn's and MIS by introducing new data in support of these approaches. Decisions for technique should be based on patient characteristics, but minimally invasive techniques have emerged as valid and possibly superior for complex and recurrent disease.

Predictive Factors of Non-Inflammatory Small Bowel Obstruction After Bowel Resection in Crohn's Patients.

The aim of the study was to investigate the risk factors associated with the development of small bowel obstruction (SBO) in Crohn's disease (CD) after small bowel resection (SBR) that are not due to active/recurrent inflammation. We conducted a retrospective cohort study of patients who had SBR for active or complicated CD. Abstracted data included demographics, phenotype, therapies for CD, endoscopic disease recurrence, and several surgical variables. The primary outcome was the development of non-inflammatory SBO (NI-SBO) within 5 years after SBR. A total of 335 patients were included. The cumulative rates of NI-SBO at 6 months, 1 year, and 5 years were 5 (1.5%), 8 (2.4%), and 29 (8.9%), respectively. Variables associated with the development of NI-SBO were active macroscopic or microscopic inflammation in the surgical margins (13 (56%) vs. 65 (27%), P = 0.004), open resection (vs. laparoscopic resection) (12 (41.4%) vs. 60 (19.5%), P = 0.0006) and a higher median number of previous resections (2 (interquartile range (IQR) 2 - 3) vs. 1 (IQR 1 - 2), P = 0.0002). Only 21% of patients who developed NI-SBO required surgical intervention. The incidence of NI-SBO after SBR in CD is low and associated with inflammation at the margins of the resected bowel, previous bowel resections, and an open laparotomy approach. Most NI-SBOs resolve with medical management.

Surgical management of complicated Crohn's disease

Surgical management of pediatric Crohn's disease is fundamentally palliative, aiming to treat the sequalae of complicated disease while preserving intestinal length. Multidisciplinary discussion of risk factors and quality of life should take place prior to operative intervention. Though the surgical management of pediatric Crohn's disease is largely based on the adult literature, there are considerations specific to the pediatric population – notably disease and treatment effects on growth and development. Intrabdominal abscess is approached with percutaneous drainage when feasible, reserving surgical intervention for the patient who is unstable or failing medical therapy. Pediatric patients with fibrostenotic disease should be considered for strictureplasty when possible, for maximum preservation of bowel length. Patients with medically refractory Crohn's proctocolitis should be treated initially with fecal diversion without proctocolectomy.

Spatial single cell profiling using imaging mass cytometry - inflammatory versus penetrating Crohn's disease.

Fistula formation is a major complication in Crohn's disease (CD) and the role of the immune cell compartment remains to be elucidated. Thus, we compared the immune-cell compartment of CD fistula to inflammatory CD colitis using imaging mass cytometry and immunofluorescence. A 36-marker panel including structural, functional and lineage markers for use in imaging mass cytometry (IMC) was established. This panel was applied to analyze paraffin-embedded CD fistula tract (n=11), CD colitis (n=10), and colon samples from non-inflamed controls (n=12). Computational methods for cell segmentation, dimensionality reduction and cell type clustering were used to define cell populations for cell frequency, marker distribution and spatial neighborhood analysis. Multiplex immunofluorescence was used for higher resolution spatial analysis. Analysis of cell frequencies in CD fistulas compared to CD colitis and control colonic samples revealed a significant increase in neutrophils, effector cytotoxic T cells and inflammatory macrophages in CD fistula samples, whereas regulatory T cells were decreased. Neutrophils in CD fistula expressed significantly more matrix metalloproteinase 9 (MMP9), correlating to extracellular matrix remodeling. Neighborhood analysis revealed a strong association between MMP9+ neutrophils and effector cytotoxic T cells in both CD fistulas and colitis. This study presents the first highly multiplexed single cell analysis of the immune-cell compartment of CD fistulas and their spatial context. It links immune cell dynamics, particularly MMP9+ neutrophils, to extracellular matrix remodeling in CD fistulas, offering insights into the complex network of cellular interactions and potential therapeutic targets for CD complications.

Multimodality imaging features of small bowel cancers complicating Crohn's disease: a pictorial review.

Patients with Crohn's disease (CD) are at increased risk of developing small bowel cancer, since chronic inflammation may trigger the histopathological sequence that begins from low-grade dysplasia of the intestinal epithelium and may eventually lead to malignant transformation. Owing to their location in a portion of the gastrointestinal tract which is not easily accessible to conventional endoscopic techniques, the detection of CD-related small bowel cancers is still a clinical challenge. The radiological features of CD-related small bowel adenocarcinoma (SBA) in patients with CD have been described in some previous studies, including its appearance in both CT and MRI examinations. Radiological signs of active or fibrostenotic CD may be intermixed with those suggesting the presence of CD-related SBA. In CT studies, the most relevant findings consistent with malignant transformation are the presence of a stricture with irregular asymmetric thickening of small bowel walls, loss of mural stratification, and moderate enhancement after intravenous administration of iodinated contrast media, in association with enlarged adjacent mesenteric lymph nodes. Many of the CD-related SBA features that can be observed on CT imaging are similar to those detectable by MRI. This latter modality provides the additional value of the functional characterization of small bowel strictures, thereby helping to distinguish between inflammatory, fibrotic, and malignant stenosis in the setting of active CD. Positron Emission Tomography (PET)/CT enables the metabolic assessment of enlarged mesenteric lymph nodes, and PET/MRI fusion imaging can incorporate morphological, functional and metabolic information into a single set of imaging data, thus overcoming the limitations of the separate assessment of each individual modality. Owing to the low incidence and prevalence of this long-term complication of CD, we believe that a detailed multimodality pictorial essay on this topic, also including the PET-CT and fusion imaging documentation of some cases, would be useful to the medical literature.

Predictors of Complicated Disease Course in Adults and Children With Crohn’s Disease: A Nationwide Study from the epi-IIRN

Abstract Background Since data on predictors of complicated Crohn’s disease (CD) from unselected populations are scarce, we aimed to utilize a large nationwide cohort, the epi-IIRN, to explore predictors of disease course in children and adults with CD. Methods Data of patients with CD were retrieved from Israel’s 4 health maintenance organizations, whose records cover 98% of the population (2005-2020). Time-to-event modeled a complicated disease course, defined as CD-related surgery, steroid-dependency, or the need for >1 class of biologics. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results. Results A total of 16 659 patients (2999 [18%] pediatric-onset) with 121 695 person-years of follow-up were included; 3761 (23%) had a complicated course (750 [4.5%] switched to a second biologic class, 1547 [9.3%] steroid-dependency, 1463 [8.8%] CD-related surgery). Complicated disease was more common in pediatric- than adult-onset disease (26% vs 22%, odds ratio, 1.3; 95% confidence interval [CI], 1.2-1.4). In a Cox multivariate model, complicated disease was predicted by induction therapy with biologics (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6) and severity of laboratory tests at diagnosis (HR, 1.7; 95% CI, 1.2-2.2), while high socioeconomic status was protective (HR, 0.94; 95% CI, 0.91-0.96). In children, laboratory tests predicted disease course (HR, 1.8; 95% CI, 1.2-2.5), as well as malnutrition (median BMI Z score −0.41; 95% CI, −1.42 to 0.43 in complicated disease vs −0.24; 95% CI, −1.23 to 0.63] in favorable disease; P < .001). Conclusions In this nationwide cohort, CD course was complicated in one-fourth of patients, predicted by laboratory tests, type of induction therapy, socioeconomic status, in addition to malnutrition in children.

Crohn's Disease-Associated Pathogenic Mutation in the Manganese Transporter ZIP8 Shifts the Ileal and Rectal Mucosal Microbiota Implicating Aberrant Bile Acid Metabolism.

A pathogenic mutation in the manganese transporter ZIP8 (A391T; rs13107325) increases the risk of Crohn's disease. ZIP8 regulates manganese homeostasis and given the shared need for metals between the host and resident microbes, there has been significant interest in alterations of the microbiome in carriers of ZIP8 A391T. Prior studies have not examined the ileal microbiome despite associations between ileal disease and ZIP8 A391T. Here, we used the Pediatric Risk Stratification Study (RISK) cohort to perform a secondary analysis of 16S ribosomal RNA gene sequencing data obtained from ileal and rectal mucosa to study associations between ZIP8 A391T carrier status and microbiota composition. We found sequence variants mapping to Veillonella were decreased in the ileal mucosa of ZIP8 A391T carriers. Prior human studies have demonstrated the sensitivity of Veillonella to bile acid abundance. We therefore hypothesized that bile acid homeostasis is differentially regulated in carriers of ZIP8 A391T. Using a mouse model of ZIP8 A391T, we demonstrate an increase in total bile acids in the liver and stool and decreased fibroblast growth factor 15 (Fgf15) signaling, consistent with our hypothesis. We confirmed dysregulation of FGF19 in the 1000IBD cohort, finding that plasma FGF19 levels are lower in ZIP8 A391T carriers with ileocolonic Crohn's disease. In the search for genotype-specific therapeutic paradigms for patients with Crohn's disease, these data suggest targeting the FGF19 pathway in ZIP8 A391T carriers. Aberrant bile acid metabolism may precede development of Crohn's disease and prioritize study of the interactions between manganese homeostasis, bile acid metabolism and signaling, and complicated ileal Crohn's disease.

P408 Complete endoscopic healing, the future therapeutic target in Crohn's disease? Results of a prospective multicenter study

Abstract Background The STRIDE II guidelines recognize endoscopic healing (EH), defined by an SES-CD score ≤2 or a CDEIS score <3, as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, complete endoscopic healing could reduce the risk of long-term complications in CD. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic healing achieved. Methods We conducted a prospective multicenter study that included all patients with CD undergoing colonoscopy for EH assessment or dysplasia screening between September 2019 and September 2022 in one university hospital, one general hospital and one private center. Two groups were compared: patients with complete EH (CDEIS = 0) and those with partial EH (CDEIS <4). The primary endpoint was CD relapse, defined as the need for drug intensification and/or initiation of corticosteroid and/or CD-related hospitalization and/or development of a fistula (luminal or perianal) or abscess, and/or the need for bowel resection. Patients were followed up every 6 months for two years. Based on previously published data, 138 patients were expected to demonstrate a 13% difference with a two-sided alpha risk of 5% and a power of 80%. Results A total of 133 patients were included. The majority of patients were female (55%), non-smokers (63%), with a median disease duration of 10 (IQR, 4-19) years. Fifty-seven (43%) patients had ileocolonic location and 81 (61%) an inflammatory (B1) behavior. Patients had been on treatment for a median of 18.0 months (IQR 8.6-52) prior to colonoscopy, with no difference between the two groups. There was no significant difference between the two groups apart from BMI. Eighty-four (63%) patients had complete EH. After adjustment for BMI, the risk of relapse was significantly higher in the CDEIS>0 group (23% vs. 41%, HR = 2.05; IC95% = [1.09 - 3.87]; p=0.027). After a median follow-up of 23.3 months, the number of drug intensification, hospitalizations, use of corticosteroids, occurrence of abscess, fistula, or bowel resection in the CDEIS 0 and CDEIS > 0 and <4 groups were 20% and 35% (p=0.065), 2.4 and 16% (p=0.005), 2.4% and 10% (p=0.10), 3.6% and 18% (p=0.009), 7.1% and 18% (p=0.048), 7.1% and 18% (p=0.048) respectively. Conclusion This prospective multicenter study confirms that complete endoscopic healing is associated with better long-term outcomes than partial endoscopic healing in patients with CD, as well as fewer surgeries and hospitalizations and an overall decreased risk of treatment failure.

P320 Impact of Enterography on the Outcomes of Endoscopic Balloon Dilation for Ileocolonic Anastomotic Strictures in Crohn's Disease

Abstract Background Ileocolonic anastomotic stricture (ICAS) is a common complication following surgery for complicated Crohn's Disease (CD). Endoscopic balloon dilation (EBD) has emerged as a non-invasive therapeutic modality for symptom relief and delaying surgical interventions. However, the impact of enterography, utilizing magnetic resonance imaging (MRI) or computed tomography (CT), in characterizing ICAS and its influence on short- and long-term EBD outcomes remain unclear. Methods This retrospective study included patients who underwent EBD for ICAS. Demographic and clinical data were collected, encompassing short-term outcomes (procedure complications and symptom improvement) and long-term outcomes (need for surgery, hospitalization, or repeat dilation). Results A total of 15 patients with ICAS were included in the study, with 46.7% being females, and a mean age of 41.2±15.6 years at the time of EBD. Six patients (40%) had undergone enterography six months prior to EBD. The median balloon diameter used for dilation was 15mm (range: 10mm to 17mm) and during the procedure, significant mucosal inflammation of the anastomosis (Rutgeerts Score ≥2) was observed in seven patients (46.7%). EBD was successful in 12 patients (80%) without any immediate complications. In the 12-month post-procedure period, one patient experienced hospital admission due to intestinal occlusion, one patient required abdominal surgery, and another patient underwent two additional EBD procedures. We did not observe a trend for an increased occurrence of complications in patients submitted to EBD without prior recent enterography, in the 12 months following the procedure or thereafter. Conclusion In this small but homogeneous cohort, our findings suggest that recent enterography does not significantly improve ICAS EBD outcomes. Therefore, our data suggest that performing enterography should not delay EBD in symptomatic CD patients with ICAS.

P832 Postoperative fever and CRP levels as predictive markers of postoperative recurrence of Crohn’s disease after ileocolic resection

Abstract Background Studies have shown that postoperative C-reactive protein (CRP) levels in patients with Crohn’s disease (CD) undergoing ileocolic resections (ICR) are higher than in control patients operated for cancer. This study aims to verify the association between postoperative fever and CRP levels with CD recurrence. Methods We performed a single-centre retrospective study of all CD patients undergoing an ICR between 2009 and 2019. CRP levels and fever (body temperature >38.5 °C) were measured preoperatively and during the first 7 postoperative days (POD). A colonoscopy was performed within 12 months after surgery. Endoscopic postoperative recurrence (POR) was defined as a modified Rutgeerts score ≥i2b. Surgical recurrence as the need for reoperation due to CD recurrence at the level of the ileocolic anastomosis. A multivariate regression model for longitudinal measures was used to obtain estimates of postoperative CRP levels. Association between fever and estimates of CRP levels with endoscopic and surgical POR was evaluated through a multivariate analysis including sex, age, Montreal classification, use of advanced therapies prior to surgery, associated surgical procedures, smoking habit, and continuation/initiation of medical therapy after surgery. Results We identified 372 patients, of which 299 (80.4%) had complicated CD (Montreal B2+B3) and 166 (44.7%) already received advanced therapies before surgery. 92 (24.7%) were active smokers at the time of surgery. In 26 patients (7.0%), one or more strictureplasties were performed simultaneously to the ICR. Prophylactic medical treatment was restarted/initiated immediately after surgery in only 9.7% of the patients. Estimates of CRP level at POD -1, +1, +3, and +5 were 9.23 mg/L (CI 7.85;10.86), 63.05 mg/L (CI 58.63;67.80), 82.55 mg/L (CI 75.09;90.76), and 56.79 mg/L (CI 49.76;64.81), respectively. Overall, 154/367 patients (42.0%) with available body temperature measures, experienced fever postoperatively. Endoscopic POR occurred in 144/332 patients (43.37%) with an available colonoscopy within 12 months postoperatively (Table 1). Surgical POR was 7.0% (CI 4.9%-11.1%) and 11.8% (CI 5.7%-8.8%) at 3 and 5 years follow-up, respectively (Figure 1). No association between postoperative fever and CRP levels estimates with either endoscopic (p=0.49; p=0.06) or surgical POR (p=0.52; p=0.07] was observed. Conclusion Despite previous evidence suggesting that CD patients develop an enhanced postoperative inflammatory response, CRP levels and fever after ICR do not seem predictive of early endoscopic (<12 months) or long-term surgical POR. Therefore, they should not be considered to stratify patients for postoperative medical prophylactic therapy.

P515 Exclusive enteral nutrition downstages complicated Crohn’s disease prior to surgical resection: A feasibility study

Abstract Background Exclusive enteral nutrition (EEN, oral or enteral liquid feeds only) is an established first-line therapy to induce remission in Crohn’s disease (CD) in children, but not in adults where low tolerance has been reported. Recently, smaller studies have suggested advantages of EEN in preoperative optimisation in adults. We hypothesise that in this setting, EEN is feasible and is associated with improved inflammatory and nutritional markers. Methods Consecutive patients with small bowel or ileocolic Crohns disease, who started preoperative EEN at two large IBD centres 2020-2023 were retrospectively studied. EEN was part of a 4-6week preoperative optimisation pathway. Outcomes were compliance and serum albumin, c-reactive protein and body weight, respectively. Medians (range) & Wilcoxon tests used. Results Thirty-two patients started EEN for stricturing (n=10) or penetrating disease (n=14). Six patients (19%) did not tolerate EEN and received parenteral nutrition (n=2) or reverted to normal diet (n=4), while 26 patients (81%) completed EEN until surgery. This group received EEN during 38 (17-70) days. C-reactive protein concentrations decreased from 8.5 (1-157) to 3 (1-96) mg/L (p = 0.0051), and albumin levels increased from 33.5 (27-44) to 38 (26-42) g/L (p< 0.001), while body weight did not change, from 67 (48.5-107) to 66.6 (48.5-105.7) kg (p = 0.25). 21 (81%) EEN patients underwent minimally invasive surgery, 22 (85%) had a primary anastomosis and 4 a stoma. Median postoperative length of stay was 4 (2-11) days. One patient with a severe complication, no one with an anastomotic leakage. Conclusion EEN was well tolerated in this cohort of patients undergoing surgery for complicated CD. EEN was associated with improved systemic inflammation, a maintained nutritional status, and favourable postoperative outcomes despite the complexity of disease in this group of patients. These results align with previous studies that have shown the effectiveness of EEN in reducing disease activity and promoting mucosal healing in CD patients.By reducing inflammation and uphold nutritional status, EEN might help to create a more favourable surgical environment, potentially leading to better outcomes and decreased postoperative complications.

DIAGNOSTIC ACCURACY OF INTESTINAL ULTRASOUND IN THE DETECTION OF INTRA-ABDOMINAL COMPLICATIONS IN CROHN'S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Crohn's disease (CD) is frequently associated with the development of strictures and penetrating complications. Intestinal ultrasound (IUS) is a non-invasive imaging modality ideal for point-of-care assessment. In this systematic review and meta-analysis we provide a current overview on the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, cross-sectional imaging, surgery and pathology. We conducted a literature search for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. Meta-analysis was performed for both conventional IUS (B-mode) and oral contrast IUS (SICUS). Of the 1498 studies we identified, 68 were included in this review and 23 studies (3863 patients) were used for the meta-analysis. Pooled sensitivities and specificities for strictures, inflammatory masses and fistulas by B-mode IUS were 0.81 and 0.90, 0.87 (sensitivities) and 0.95, and 0.67 and 0.97 (specificities), respectively. Pooled overall log diagnostic odds ratios were 3.56, 3.97 and 3.84 respectively. Pooled sensitivity and specificity of SICUS were 0.94 and 0.95, 0.91 and 0.97 (sensitivities), and 0.90 and 0.94 (specificities), respectively. Pooled overall log diagnostic odds ratio of SICUS were 4.51, 5.46 and 4.80, respectively. IUS is accurate for the diagnosis of intra-abdominal complications in CD. As a non-invasive, point-of-care modality, IUS is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.

MR Enterography in Ulcerative Colitis: Beyond Endoscopy.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) that progressively affects mucosa and submuccosa of the colon and rectum in a continual pattern. In comparison, Crohn disease (CD), the other type of IBD, is a chronic transmural inflammatory disorder that can involve any part of the gastrointestinal tract. MR enterography (MRE) has emerged as an important imaging modality for the diagnosis and detection of disease activity and complications in CD, with comparable results to those of endoscopy. But MRE has been underused for assessment of UC in recent years, and clinicians heavily rely on endoscopic findings for management of UC. Despite UC being considered an endoscopically assessable disease, MRE can provide useful information beyond that obtained with endoscopy about mural or extramural abnormalities, inaccessible parts of the colonic lumen, associated extraintestinal diseases, and superimposed pathologic conditions. Moreover, endoscopy might be contraindicated in some clinical settings due to the risk of colonic perforation. In addition to depicting the features of UC activity in different phases, MRE demonstrates findings of disease chronicity that cannot be achieved with endoscopy, particularly in a patient with colitis of unknown cause. The valuable diagnostic role of MRE to exclude undiagnosed CD in patients with UC who have refractory disease or those with postproctocolectomy complications is also emphasized. Radiologists can play a crucial role in the management of UC with MRE by addressing what is beyond endoscopy. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Impact of Treatment Response on Risk of Serious Infections in Patients With Crohn’s Disease: Secondary Analysis of the PYRAMID Registry

Traditional risk factors for serious infections with advanced therapies in patients with Crohn's disease (CD) have been assessed at baseline before starting therapy. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry (NCT00524537). We included patients with CD who initiated adalimumab and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs nonresponders (not in steroid-free clinical remission) at 6 months after treatment initiation (landmark). We compared the risk of serious infections between responders vs nonresponders between 6 and 36 months after treatment initiation through stabilized inverse probability of treatment weighting Cox proportional hazards model. Of 1515 adalimumab-treated patients, 763 (50.4%) were classified as responders at 6 months (37 ± 13 y; 56% female; disease duration, 9.5 ± 8.5 y). Compared with nonresponders, responders were less likely to have moderate to severe symptoms (55.6% vs 33%), or require steroids (45.5% vs 17.3%) or opiates (6.6% vs 1.3%) at baseline, without any differences in disease location, perianal disease, and prior CD complications. During follow-up evaluation, using stabilized inverse probability of treatment weighting, responders were 34% less likely to experience serious infections compared with nonresponders (hazard ratio, 0.66; 95% CI, 0.46-0.96). Risk of gastrointestinal and extraintestinal infections was lower in responders vs nonresponders. Patients with CD who respond to adalimumab have a lower risk of developing serious infections compared with nonresponders. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.

Validation of disease severity index for predicting complicated disease in Crohn's disease: A comparison study with Lémann index

BackgroundDisease Severity Index (DSI) provides comprehensive assessment of bowel damage (BD). AimsTo evaluate DSI in patients with Crohn's disease (CD) at high risk of disease progression, compared to Lémann Index (LI). MethodsPatients with CD in our center were reviewed consecutively between 2017 and 2019. DSI, LI, and complicated CD course were analyzed. ResultsThe median LI and DSI of included 300 patients were 1.63 (IQR 1.25–3.13) and 42 (IQR 32–51), respectively. 152 patients (50.7%) experienced a complicated disease course (median 5.1 months; IQR 1.1–20.2). DSI (AUC 0.66; 95% CI 0.60–0.72) better predicted a complicated course of CD over LI (AUC 0.56; 95% CI 0.50–0.63; P = 0.007). The cumulative probability of complicated CD course in severe patients was higher than those with ‘mild CD’ (P < 0.001). The Cox analysis identified DSI>43 (HR 2.18; 95% CI 1.54–3.09; P < 0.001), B2/3 vs. B1 (HR 2.80; 95% CI 1.99–3.94; P < 0.001), and a higher level of CRP (HR 1.01; 95% CI 1.00–1.02; P = 0.005) as independent prognostic factors for complicated CD. However, LI was not associated with complicated CD (P = 0.164). ConclusionsHigher DSI was associated with complicated disease outcomes. DSI might play a better role than LI in identifying patients at high risks of disease progression.

Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis

Background and aimsThe stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients. MethodsIleal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All samples underwent RNA sequencing. Human small intestinal fibroblasts were treated for 48 h with IL-1β, TFGβ1, PDGFB or TNF-α. Resistance to apoptosis was analysed by RT-PCR, western blot and immunohistochemistry in ileal tissue and by RT-PCR and FACS in cultured cells. ResultsGrowth factor-driven signaling pathways and increased RAS GTPase activity were up-regulated in affected ilea in which we found expression of both the antiapoptotic molecule MCL1 and the transcription factor ETS1 in submucosal fibroblasts, and a senescence-associated secretory phenotype. In cultured intestinal fibroblasts, PDGFB induced an ETS1-mediated resistance to apoptosis that was associated with the induction of both of TGFB1 and IL1B, a cytokine that replicated the expression of SASP detected in ileal tissue. ETS1 drove fibroblast polarization between inflammatory and fibrogenic phenotypes in IL1β-treated cells. ConclusionsOur data show resistance to apoptosis in complicated ileal CD, and demonstrate that PDGFB induce an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Results point to PDGFRB, IL1R1 or MCL1 as potential targets against ileal fibrosis.

Progression of Pediatric Crohn’s Disease Is Associated With Anti–Tumor Necrosis Factor Timing and Body Mass Index Z-Score Normalization

The evolution of complicated pediatric Crohn's disease (CD) in the era of anti-tumor necrosis factor (aTNF) therapy continues to be described. Because CD progresses from inflammatory to stricturing (B2) and penetrating (B3) disease behaviors in a subset of patients, we aimed to understand the risk of developing complicated disease behavior or undergoing surgery in relation to aTNF timing and body mass index z-score (BMIz) normalization. Multicenter, 5-year longitudinal data from 1075 newly diagnosed CD patients were analyzed. Descriptive statistics, univariate and stepwise multivariate Cox proportional hazard regression (CPHR), and log-rank analyses were performed for risk of surgery and complicated disease behaviors. Differential gene expression from ileal bulk RNA sequencing was correlated with outcomes. Stricturing complications had the largest increase: from 2.98% to 10.60% over 5 years. Multivariate CPHR showed aTNF exposure within 3 months from diagnosis (hazard ratio [HR], 0.33; 95% CI, 0.15-0.71) and baseline L2 disease (HR, 0.29; 95% CI, 0.09-0.92) to be associated with reduced B1 to B2 progression. For children with a low BMIz at diagnosis (n= 294), multivariate CPHR showed BMIz normalization within 6 months of diagnosis (HR, 0.47; 95% CI, 0.26-0.85) and 5-aminosalicyclic acid exposure (HR, 0.32; 95% CI, 0.13-0.81) were associated with a decreased risk for surgery while B2 (HR, 4.20; 95% CI, 1.66-10.65) and B2+B3 (HR, 8.24; 95% CI, 1.08-62.83) at diagnosis increased surgery risk. Patients without BMIz normalization were enriched for genes in cytokine production and inflammation. aTNF exposure up to 3 months from diagnosis may reduce B2 progression. In addition, lack of BMIz normalization within 6 months of diagnosis is associated with increased surgery risk and a proinflammatory transcriptomic profile.