Computed tomography enterography, magnetic resonance enterography, and bowel ultrasound are complementary tools central to diagnosing and monitoring Crohn disease. These modalities can identify active inflammation, penetrating, and stricturing disease. Crohn disease must be monitored frequently to guide therapy, and resolution of inflammation on imaging correlates directly with steroid-free clinical remission. While disease activity assessment is qualitative, newer quantitative techniques to assess active inflammation are emerging. These as well as other techniques, such as contrast-enhanced ultrasound (US) and US elastography, will offer new tools for future radiologists.

Healing in Crohn's disease is complex and difficult to measure due to incongruencies between clinical symptoms and disease states. Mucosal healing (MH) and transmural healing (TH) are increasingly used to measure clinical improvement in Crohn's disease, but definitions of MH and TH can vary across studies, and their relationship to long-term outcomes is not clear. To address this knowledge gap, we performed a systematic literature review (SLR) to examine studies measuring MH and TH in Crohn's disease.

Database records from 2012 to 2022 were searched for real-world evidence and interventional studies that reported the association of MH or TH with clinical, economic, or quality of life outcomes of adult patients with Crohn's disease.

A total of 46 studies were identified in the systematic literature review, representing a combined patient population of 5530. Outcomes of patients with MH were reported by 39 studies; of these, 14 used validated scales for endoscopic assessment. Thirteen studies reported outcomes of patients with TH. Among studies that examined the outcomes of patients with and without MH or TH, patients with healing generally experienced improved clinical outcomes and reduced healthcare resource utilization, including fewer hospitalizations and surgeries and improved rates of clinical remission. This was especially true for patients with TH.

Mucosal and transmural healing are associated with positive long-term outcomes for adult patients with Crohn's disease. The adoption of standardized measures and less invasive assessment tools will maximize the benefits of patient monitoring.

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation, progressive bowel damage and gastrointestinal lesions. Although treatment strategies for CD have traditionally focused on a stepwise pharmacological approach to achieve clinical remission or symptom resolution, these treatment goals correlate poorly with disease activity. Thus, achieving full clinical remission and full endoscopic healing alone may be insufficient, as patients may remain at risk of inflammatory complications. Individualised 'treat-to-target' (T2T) pharmacological and treatment approaches represent a promising strategy for improving endoscopic remission and symptom resolution among patients with CD. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II guidelines, launched in 2013 and later renewed, identified individualised targets for a T2T therapeutic approach for patients with IBD. These guidelines facilitate the individualisation of target treatment goals through evidence-based, long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article aims to summarise the STRIDE-II guidelines and provide intellectual guidance for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the United Kingdom (UK). Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice.

Assessing the cumulative degree of bowel injury in ileal Crohn's disease (CD) is difficult. We aimed to develop machine learning (ML) methodologies for automated estimation of cumulative ileal injury on computed tomography-enterography (CTE) to help predict future bowel surgery.

Adults with ileal CD using biologic therapy at a tertiary care center underwent ML analysis of CTE scans. Two fellowship-trained radiologists graded bowel injury severity at granular spatial increments along the ileum (1 cm), called mini-segments. ML segmentation methods were trained on radiologist grading with predicted severity and then spatially mapped to the ileum. Cumulative injury was calculated as the sum (S-CIDSS) and mean of severity grades along the ileum. Multivariate models of future small bowel resection were compared with cumulative ileum injury metrics and traditional bowel measures, adjusting for laboratory values, medications, and prior surgery at the time of CTE.

In 229 CTE scans, 8,424 mini-segments underwent analysis. Agreement between ML and radiologists injury grading was strong (κ = 0.80, 95% confidence interval 0.79-0.81) and similar to inter-radiologist agreement (κ = 0.87, 95% confidence interval 0.85-0.88). S-CIDSS (46.6 vs 30.4, P = 0.0007) and mean cumulative injury grade scores (1.80 vs 1.42, P < 0.0001) were greater in CD biologic users that went to future surgery. Models using cumulative spatial metrics (area under the curve = 0.76) outperformed models using conventional bowel measures, laboratory values, and medical history (area under the curve = 0.62) for predicting future surgery in biologic users.

Automated cumulative ileal injury scores show promise for improving prediction of outcomes in small bowel CD. Beyond replicating expert judgment, spatial enterography analysis can augment the personalization of bowel assessment in CD.

To demonstrate the clinical advantages of a deep-learning image reconstruction (DLIR) in low-dose dual-energy computed tomography enterography (DECTE) by comparing images with standard-dose adaptive iterative reconstruction-Veo (ASIR-V) images.

In this Institutional review board approved prospective study, 86 participants who underwent DECTE were enrolled. The early-enteric phase scan was performed using standard-dose (noise index: 8) and images were reconstructed at 5 mm and 1.25 mm slice thickness with ASIR-V at a level of 40% (ASIR-V40%). The late-enteric phase scan used low-dose (noise index: 12) and images were reconstructed at 1.25 mm slice thickness with ASIR-V40%, and DLIR at medium (DLIR-M) and high (DLIR-H). The 70 keV monochromatic images were used for image comparison and analysis. For objective assessment, image noise, artifact index, SNR and CNR were measured. For subjective assessment, subjective noise, image contrast, bowel wall sharpness, mesenteric vessel clarity, and small structure visibility were scored by two radiologists blindly. Radiation dose was compared between the early- and late-enteric phases.

Radiation dose was reduced by 50% in the late-enteric phase [(6.31 ± 1.67) mSv] compared with the early-enteric phase [(3.01 ± 1.09) mSv]. For the 1.25 mm images, DLIR-M and DLIR-H significantly improved both objective and subjective image quality compared to those with ASIR-V40%. The low-dose 1.25 mm DLIR-H images had similar image noise, SNR, CNR values as the standard-dose 5 mm ASIR-V40% images, but significantly higher scores in image contrast [5(5-5), P < 0.05], bowel wall sharpness [5(5-5), P < 0.05], mesenteric vessel clarity [5(5-5), P < 0.05] and small structure visibility [5(5-5), P < 0.05].

DLIR significantly reduces image noise at the same slice thickness, but significantly improves spatial resolution and lesion conspicuity with thinner slice thickness in DECTE, compared to conventional ASIR-V40% 5 mm images, all while providing 50% radiation dose reduction.

Transmural healing (TH) is emerging as a potential Crohn's disease (CD) treatment target. Early biological treatment seems to be associated with improved disease outcomes, but its impact on TH remains unclear. We aimed to assess the impact of early biological treatment initiation on TH and its influence on CD prognosis.

This multicenter retrospective study included adult patients with CD starting biological therapy. TH was assessed using magnetic resonance enterography (MRE) at 12 ± 6 months post-therapy initiation, with radiological examinations reviewed by blinded expert radiologists. TH was defined as complete normalization of all MRE parameters. Timing of biological therapy initiation was analyzed as a continuous variable, with optimal cutoff determined using the Youden index and clinical relevance. Logistic regression with propensity score-adjusted analysis was used to assess the association between early biological therapy initiation and TH. Long-term outcomes (bowel damage progression, CD-related surgery, CD-flare hospitalization, and therapy escalation) were evaluated.

Among 154 patients with CD, early biological therapy initiation within 12 months of diagnosis was associated with significantly higher TH rates (adjusted odds ratio [aOR], 3.23; 95% confidence interval [CI], 1.36-7.70; P < .01), which persisted after adjusting for previous biological therapy use (aOR, 2.82; 95% CI, 1.13-7.06; P = .03). Time-to-event analysis demonstrated that TH was significantly associated with reduced risk of bowel damage progression (adjusted hazard ratio [aHR], 0.28; 95% CI, 0.10-0.79; P = .02), CD-related surgery (aHR, 0.21; 95% CI, 0.05-0.88; P = .03) and therapy escalation (aHR, 0.35; 95% CI, 0.14-0.88; P = .02), independently of early biological therapy.

Early initiation of biological therapy within 12 months of diagnosis significantly increases TH rates, leading to improved long-term outcomes in patients with CD.

Transmural healing (TH) has emerged as a potential treatment goal for Crohn's disease (CD). However, further research is needed to confirm its benefits and risk factors associated with TH remain unclear.

We aimed to assess the value of TH based on magnetic resonance enterography (MRE) in Chinese CD patients regarding the long-term outcomes and its associated factors.

Retrospective, observational cohort study.

Patients with CD diagnosed by colonoscopy and MRE examination between 2015 and 2022 were included. All patients were evaluated with endoscopy together with MRE within 6-12 months after baseline and followed up for at least 6 months after evaluation. The primary endpoint was the occurrence of major outcomes during the follow-up, including drug escalation, hospitalization, and surgery. The cumulative probabilities of major outcomes were calculated using Kaplan-Meier survival curves. Logistic regression analyses were used to predict TH within 6-12 months after baseline.

A total of 175 patients were included in the study. Of these, 69 (39.4%) patients achieved mucosal healing (MH), but only 34 (19.4%) of them achieved TH. The median follow-up duration was 17.4 months (interquartile range, 11.6-25.5), and major outcomes occurred in 58.3% of patients. A lower occurrence rate of major outcomes was noted in patients who achieved TH than in those who achieved MH only (p = 0.012). The baseline lymphocyte/C-reactive protein ratio (LCR) [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.50; p = 0.039] and bowel wall thickness (BWT) (OR, 0.72; 95% CI, 0.59-0.90; p = 0.003) were independent predictors associated with TH. According to multivariate Cox regression analysis, low LCR [hazard ratio (HR), 2.34; 95% CI, 1.51-3.64; p < 0.001], and no healing (HR, 5.45; 95% CI, 2.28-13.00; p < 0.001) were associated with an increased risk of major outcomes.

Patients with CD who achieved TH showed improved prognosis compared to those who achieved MH only. Baseline LCR and BWT might predict TH.

Background/Objectives: Inflammatory bowel diseases (IBDs) are chronic disorders that require close monitoring with imaging techniques such as magnetic resonance enterography (MRE). Standardization of radiological reports is crucial for the optimal management of IBD. We surveyed Italian radiologists regarding their experiences with MRE examinations and reporting for IBD. Methods: All members of the Italian Society of Medical and Interventional Radiology (SIRM) were invited to complete an anonymous questionnaire in April 2023. Comparison tests between variables were assessed using the χ2 test or Fisher exact test according to the least frequency group. Significance level was set for p-value < 0.05. Results: A total of 253 radiologists responded to the survey. Around 70% of the respondents declared personal clinical experience with IBD. Great agreement with the items included and described for both disease activity (i.e., intestinal wall thickness, presence of mucosal ulcers, presence of edema, mucous enhancement) and complications was reported. One-third of the respondents regularly used a structured MRE report. Centers with a high number of IBD patients per year (>1000) mostly used 3 T scanners or both 1.5 T and 3 T scanners (p < 0.001). The incorporation of scores of disease activity was associated with university and high-volume hospitals (p < 0.001). Conclusions: This survey highlighted the current routine practice and experience of MRE reports of IBD patients among Italian radiologists. We found deficiencies in the use of radiological scores in MRE reports and attendance at IBD multidisciplinary meetings.

Disease Severity Index (DSI) provides comprehensive assessment of bowel damage (BD).

To evaluate DSI in patients with Crohn's disease (CD) at high risk of disease progression, compared to Lémann Index (LI).

Patients with CD in our center were reviewed consecutively between 2017 and 2019. DSI, LI, and complicated CD course were analyzed.

The 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).

Higher DSI was associated with complicated disease outcomes. DSI might play a better role than LI in identifying patients at high risks of disease progression.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract that might lead to progressive bowel damage and disability. The exact cause of Crohn's disease is unknown, but evidence points towards multifactorial events causing dysregulation of the innate immune system in genetically susceptible people. Commonly affecting the terminal ileum and proximal colon, Crohn's disease inflammation is often discontinuous and patchy, segmental, and transmural. Identification of characteristic findings on ileocolonoscopy and histology remains the diagnostic gold standard, but complete assessment involves laboratory abnormalities, including micronutrient deficiencies, cross-sectional imaging to identify transmural disease extent, severity and complications, and a psychosocial assessment. Treatment strategies for patients with Crohn's disease now go beyond achieving clinical remission to include deeper targets of endoscopic healing and consideration of adjunctive histological and transmural targets to alter disease progression potentially further. The use of early effective advanced therapies and development of therapies targeting alternative novel pathways with improved safety profiles have resulted in a new era of healing in Crohn's disease management. Future combination of advanced therapies with diet or other biological drugs and small molecules, together with improvements in tight control monitoring tools and predictive biomarkers might continue to improve outcomes for patients with Crohn's disease.

Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. CLINICAL RELEVANCE STATEMENT: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. KEY POINTS: • Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. • Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. • Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease.

Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn's disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.

The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison to balloon-assisted enteroscopy (BAE) for patients with small bowel Crohn's disease (CD). We studied the correlation of MARIAs with simple endoscopic scores for CD (SES-CD) of the ileum based on magnetic resonance enterography (MRE) and BAE in patients with small bowel CD.

Fifty patients with small bowel CD who underwent BAE and MRE concurrently within 3 months from September 2020 to June 2021 were enrolled in the study. The primary outcome was the correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE. The cutoff value for MARIAs identifying endoscopically active/severe disease, defined as ileal SES-CDa/ileal SES-CD of 5/7 or more, was analyzed.

Ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p<0.001; R=0.78, p<0.001). The area under the receiver operating characteristic curve of MARIAs for ileal SES-CDa ≥5 and ileal SES-CD ≥7 was 0.92 (95% confidence interval, 0.88 to 0.97) and 0.92 (95% confidence interval, 0.87 to 0.97). The cutoff value of MARIAs for detecting active/severe disease was 3. A MARIAs index value of ≥3 identified ileal SES-CDa ≥5 with a sensitivity of 85% and specificity of 87% and detected ileal SES-CD ≥7 with a sensitivity of 87% and specificity of 86%.

This study validated the applicability of MARIAs compared to BAE-based ileal SES-CDa/SES-CD.

The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD).

Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH.

Ileal/ileocolonic CD patients scheduled for biological therapy were prospectively evaluated, at baseline (T0) and after 1 year of treatment (T1), with Harvey Bradshaw Index score, blood tests, ileocolonscopy, and MRE. Clinical activity was assessed after 2 years of treatment (T2). Wall thickness ratio (WTR) was calculated in the same affected ileal segment, as the ratio between the ileum wall thickness value at T1 and the ileum wall thickness value at T0.

A total of 103 patients were included. Mean WTR at T1 in nonresponders was significantly higher than in responders. At receiver operating characteristic analysis, WTR values were significantly associated to biological therapy responsiveness. A WTR cutoff value of 0.77 mm was identified to discriminate responders from nonresponders (sensitivity: 79%; specificity: 67%). In responders, the proportion of patients with a WTR<0.77 was significantly higher than the proportion of patients achieving TH at T1. Among patients achieving endoscopic remission, 11/29 (37.9%) presented TH, while 20/29 (68.9%) presented WTR<0.77 ( P : 0.035). At multivariate logistic regression analysis, WTR<0.77 was significantly associated to biological therapy response.

WTR index represents an easy-to-calculate MRE parameter and seems to be a promising tool for monitoring therapeutic response in CD patients during biological therapy.

The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn´s disease.

We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to 'treat to target.' The relevant publications in Pubmed were identified in a literature review with the key word 'Crohn´s disease.'

All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.

MR-enterography/enteroclysis (MRE) is increasingly used for primary diagnosis, detection of complications, and monitoring of patients with inflammatory bowel disease (IBD). Standardization of reporting is relevant to ensure quality of the methodology and to improve communication between different faculties. The current manuscript describes the features that are required for optimized reporting of MRE in IBD.

An expert consensus panel of radiologists and gastroenterologists conducted a systematic search of the literature. In a Delphi process, members of the German Radiological Society (DRG) and members of the Competence Network for Inflammatory Bowel Diseases voted on relevant criteria for the reporting of findings in MRE. Based on the voting results, statements were developed by the expert consensus panel.

Clinically relevant aspects of MRE findings have been defined to optimize reporting and to standardize terminology. Minimal requirements for standardized reporting are suggested. The statements focus on the description of disease activity as well as on complications of IBD. Attributes of intestinal inflammation are described and illustrated by exemplary images.

The current manuscript provides standardized parameters and gives practical recommendations on how to report and how to characterize MRE findings in patients with IBD.

· Systematic overview provides practice-oriented recommendations and names and evaluates the decisive criteria for reporting and interpretation of MRI in inflammatory bowel disease.. · Standardized terminology and reporting criteria for MRI in IBD improves interdisciplinary communication.. · Standardized collection and documentation of MRI findings in IBD helps to further establish the method and to improve care for IBD patients..

· Wessling J, Kucharzik T, Bettenworth D et al. Intestinal MRI in Inflammatory Bowel Disease - Literature and Survey-Based Recommendations regarding Reporting by the German Radiological Society (DRG) and the German Competence Network for Inflammatory Bowel Diseases. Fortschr Röntgenstr 2023; 195: 675 - 690.

It is well known that infliximab (IFX) trough levels (TLs) are associated with endoscopic healing (EH) in Crohn's disease (CD). We investigated whether IFX TLs are associated with transmural healing (TH) in pediatric patients with CD following 1-year treatment.

Pediatric patients with CD treated with IFX were included in this single-center prospective study. IFX TL tests, magnetic resonance enterography (MRE), and colonoscopies were simultaneously conducted after 1-year IFX treatment. TH was defined as a wall thickness of ≤3 mm without inflammatory signs evaluated using MRE. EH was defined as a Simple Endoscopic Score for Crohn's disease of <3 points on colonoscopy.

Fifty-six patients were included. EH and TH were observed in 60.7% (34/56) and 23.2% (13/56) of patients, respectively. IFX TLs were higher in patients with EH (median, 5.6 vs. 3.4 µg/mL, P = 0.002), whereas IFX TLs showed no significant difference in patients with and without TH (median, 5.4 vs. 4.7 µg/mL, P = 0.574). No significant difference was observed in EH and TH between patients whose intervals were shortened or not. Multivariate logistic regression analysis showed that IFX TLs and disease duration to IFX initiation were associated with EH (odds ratio [OR] = 1.82, P = 0.001, and OR = 0.43, P = 0.02, respectively).

In pediatric patients with CD, IFX TLs were associated with EH but not with TH. Further studies investigating long-term TH and proactive dosing based on therapeutic drug monitoring may clarify whether an association between IFX TLs and TH exists.

Mesenchymal stem cells (MSCs) are novel therapeutics for treatment of Crohn's disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc, a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effect and mechanism of human bone marrow-derived MSCs (hMSC).

hMSC immunosuppressive potential was evaluated through in vitro mixed lymphocyte reaction, ELISA, macrophage co-culture, and RT-qPCR. Therapeutic efficacy and mechanism in SAMP were studied by stereomicroscopy, histopathology, MRI radiomics, flow cytometry, RT-qPCR, small animal imaging, and single-cell RNA sequencing (Sc-RNAseq).

hMSC dose-dependently inhibited naïve T lymphocyte proliferation in MLR via PGE 2 secretion and reprogrammed macrophages to an anti-inflammatory phenotype. hMSC promoted mucosal healing and immunologic response early after administration in SAMP model of chronic small intestinal inflammation when live hMSCs are present (until day 9) and resulted in complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSC mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism of action that explains their long-term efficacy.

hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation. Despite being short-lived, exert long-term effects via macrophage reprogramming to an anti-inflammatory phenotype.

Single-cell RNA transcriptome datasets are deposited in an online open access repository 'Figshare' (DOI: https://doi.org/10.6084/m9.figshare.21453936.v1 ).

Crohn's disease is an inflammatory bowel disease that can affect any segment of the gastrointestinal tract. It has a variable clinical course, with alternating periods of disease activity and remission. Because the incidence and prevalence of Crohn's disease have been increasing, evaluation by imaging methods has become more important. The most widely used methods are computed tomography enterography, magnetic resonance enterography (as an elective examination), and contrast-enhanced computed tomography (in the context of emergency). Computed tomography enterography and magnetic resonance enterography are useful for diagnosis, follow-up, evaluation of complications, and prognosis. Both can be used in order to evaluate the small bowel loops and the associated mesenteric findings, as well as to evaluate other abdominal organs. They both also can detect signs of disease activity, fibrosis, penetrating disease, and complications. The interpretation of such changes is essential to the multidisciplinary approach, as is the standardization of the nomenclature employed in the reports. In this paper, we review and illustrate the imaging findings of Crohn's disease, using the standardized nomenclature proposed in the multidisciplinary consensus statement issued by the Society of Abdominal Radiology, the Society of Pediatric Radiology, and the American Gastroenterology Association, with recommendations for descriptions, interpretations, and impressions related to those findings.

In their original report of regional ileitis, Crohn, Ginzburg and Oppenheimer already described that inflammation involved not only the ileal mucosa: "the submucosal and, to a much lesser extent, the muscular layers of the bowel are the seat of marked inflammatory hyperplastic and exudative changes", they wrote 1. Ninety years later it is well established that the inflammatory process that characterizes Crohn´s disease (CD) involves all the layers of the intestinal wall; this fact is directly related with the development of progressive digestive tract damage related to disabling complications such as strictures, fistulae, perforation, and perianal or abdominal abscesses.

Leucine-rich alpha-2 glycoprotein (LRG) is a newly studied biomarker for inflammatory diseases. This study aimed to investigate whether LRG can be used for evaluating transmural activity in patients with Crohn's disease (CD).

We performed magnetic resonance enterography (MRE) in 227 consecutive CD patients from June 2020 to August 2021. We prospectively compared MRE findings with clinical and laboratory data including LRG. MRE was evaluated using 2 validated scoring systems, and transmural inflammation was defined as having a maximum simplified magnetic resonance index of activity (sMaRIA) score of ≥4 and a 5-point classification score of ≥9, respectively.

The correlation between LRG and the total MRE score showed a positive correlation ( r = 0.576 for sMaRIA score, P < 0.01 and r = 0.633 for 5-point score, P < 0.01). Serum concentrations of LRG significantly increased as MRE scores increased ( P < 0.01). The area under the curve of LRG for sMaRIA score of ≥4 and 5-point score of ≥9 was 0.845 and 0.869, respectively, which was significantly higher than that of CDAI ( P < 0.01) or C-reactive protein ( P < 0.01). LRG levels of ≥14 μg/mL had a 67% sensitivity and a 90% specificity for sMaRIA score of ≥4, and 73% sensitivity and 89% specificity for 5-point score of ≥9. Patients with high LRG levels were also strongly associated with CD-related hospitalization, surgery, and clinical relapse compared to those with low LRG levels ( P < 0.01 for all).

LRG is a highly accurate serum biomarker for detecting transmural activity in CD patients. Results need to be validated in further multicenter studies.

Endoscopy remains the reference standard for the diagnosis and assessment of patients with inflammatory bowel disease (IBD), but it has several important limitations. Cross-sectional imaging techniques such as magnetic resonance enterography (MRE) and intestinal ultrasound (IUS) are better tolerated and safer. Moreover, they can examine the entire bowel, even in patients with stenoses and/or severe inflammation. A variety of cross-sectional imaging activity scores strongly correlate with endoscopic measures of mucosal inflammation in the colon and terminal ileum. Unlike endoscopy, cross-sectional techniques allow complete visualisation of the small-bowel and assess for extraintestinal disease, which occurs in nearly half of patients with IBD. Extramural findings may predict outcomes better than endoscopic mucosal assessment, so cross-sectional techniques might help identify more relevant therapeutic targets. Coupled with their high sensitivity, these advantages have made MRE and IUS the primary non-invasive options for diagnosing and monitoring Crohn's disease; they are appropriate first-line investigations, and have become viable alternatives to colonoscopy. This review discusses cross-sectional imaging in IBD in current clinical practice as well as research lines that will define the future role of these techniques.

Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and under evaluation for the management of Crohn's disease in phase 3 clinical trials.

Our goal is to describe our real-world experience with upadacitinib in Crohn's disease.

This is a two-center retrospective cohort study of adult patients with moderate to severe Crohn's disease on upadacitinib. The primary outcome was clinical response and remission as determined by stool frequency and abdominal pain scores. Secondary endpoints included endoscopic response and remission as determined by change in simple endoscopic score for Crohn's. Outcomes were assessed at three months after starting upadacitinib and at patients' most recent follow-up. We further evaluated adverse events and dose-related response.

A total of 45 Crohn's disease patients received upadacitinib and were included in the safety analysis. Thirty-six patients received upadacitinib for Crohn's disease, whereas 9 received it for inflammatory arthritis (n=8) or pyoderma (n=1). Thirty-three patients received upadacitinib for 3 months or longer and were included in the efficacy analysis. At 3-month follow up, 21 patients achieved clinical response (63.6%) and 9 achieved clinical remission (27.2%). At time of last follow-up, 23 patients had clinical response (69.7%), 10 achieved clinical remission (30.3%), and 4 (28.6%) achieved endoscopic remission. Adverse events occurred in 12 patients (26.7%). Two patients had a serious adverse event (4.5%) without associated mortality.

In this real-world cohort of highly refractory Crohn's disease patients, upadacitinib was effective in inducing remission and had an acceptable safety profile.

Objective Transmural healing (TH) has been attracting attention as a new therapeutic target for Crohn's disease, but there are few clinical data on TH in Japan. We introduced low-dose computed tomography enterography (CTE) as a monitoring method for Crohn's disease and retrospectively investigated the accuracy of evaluating TH by CTE. Methods Among Crohn's disease patients who underwent low-dose CTE at our hospital from January 2009 to March 2021, 122 patients who underwent colonoscopy or balloon endoscopy within 2 weeks were included. Results of radiological and endoscopic examinations were reviewed independently by radiologists and gastrointestinal endoscopists, respectively. The concordance rate of the diagnosis between CTE and endoscopy was evaluated. Results Twenty-six patients (21.3%) achieved TH, and the kappa index was 0.743. On comparing the TH and non-TH groups, the Crohn's disease activity index (p=0.02), endoscopic healing rate (p<0.001), serum albumin (p=0.043), and serum C-reactive protein level (p=0.018) showed significant differences. Among the 122 patients, 69 (56.5%) showed concordance between the diagnosis of CTE and endoscopy, and 22 (18.0%) achieved both TH and endoscopic healing. Conclusion This study provides real-world data on Crohn's disease evaluated with low-dose CTE in Japan. The TH criterion used in this study has a high kappa coefficient and can be used reproducibly in many institutions.

The optimal treatment goal in Crohn's disease (CD) is endoscopic healing (EH). However, transmural healing (TH) facilitated by the development and increasing performance of magnetic resonance enterography (MRE) is emerging as a potential treatment goal.

To assess TH rates after 1 year of treatment by MRE and its relationship with EH in paediatric patients with CD receiving anti-tumour necrosis factor (TNF) agents, and to investigate factors associated with TH after 1 year of treatment.

This multi-centre, prospective, observational study included Korean paediatric patients with luminal CD diagnosed at age < 19 years who were naïve to anti-TNF treatment. They simultaneously underwent ileocolonoscopy and MRE at baseline and after 1 year of treatment with biologics.

We included 116 patients. At 1 year, EH and TH were achieved in 59.5% (69/116) and 38.8% (45/116) of the patients, respectively. Both EH and TH was observed in 35.3% (41/116), EH without TH in 24.1% (28/116), TH without EH in 3.4% (4/116), and neither EH nor TH in 37.1% (43/116). Moreover, 59.4% (41/69) of patients who achieved EH at 1 year exhibited TH, and 91.1% (41/45) of patients who achieved TH exhibited EH. Baseline MaRIA score was associated with TH according to a multivariate analysis (OR 0.97, 95% CI 0.95-0.99, p = 0.023).

TH is a more stringent goal than EH. Regular follow-up evaluation of transmural status, and efforts to achieve TH, may alter the natural course of CD in the era of treat-to-target.

Numerous tools have emerged over recent decades to aid in the increasingly complex management of patients with Crohn's disease (CD) beyond endoscopy, including video capsule endoscopy, magnetic resonance enterography, computed tomography enterography, a variety of biomarkers, and even wearable biosensors and smartphone applications. These tools have allowed for a more sophisticated and less invasive complementary approach to the evaluation of disease activity and treatment response in patients with CD. This article details the characteristics, practical application, and limitations of these various modalities and discusses how updated guidelines are now incorporating many of them into a treat-to-target strategy.

The association between radiological remission and natural history of disease in children with inflammatory bowel diseases (IBD) is poorly known.

(i) To assess the correlation between cross-sectional imaging (CSI) (ultrasound and magnetic resonance imaging) and clinical, biomarker and endoscopic disease activity; (ii) to evaluate the impact of radiological activity on the occurrence of complications in pediatric patients with IBD.

A retrospective study including pediatric patients with IBD and radiological follow-up of at least one year was conducted between 2003 and 2019 at the Nancy University Hospital.

In total, 118 patients (66 Crohn's disease (CD) and 52 ulcerative colitis (UC)) were included. Median follow-up duration was 5.2 years (range: 1.1-15.4). Seventeen (25.8%) patients with CD and 7 (13.5%) patients with UC achieved and maintained radiological remission until last follow-up. No IBD patient achieving radiological remission experienced complications or relapse. In patients not achieving radiologic remission, complications and surgery occurred in 13/49 (26.5%) and 8/49 (16.3%) patients with CD and in 5/45 (11.1%) and 5 (11.1%) subjects with UC. Among patients with CD, the association for remission status between radiological and endoscopic assessment was excellent (Cramer's V test (V) = 0.50), and moderate between radiological and either clinical (V = 0.30) or biochemical (V = 0.33) assessments. In UC, the association for remission status between radiological and either endoscopic or clinical assessments were weak (V = 0.19 and V = 0.20 respectively), and moderate (V = 0.23) between radiological and biochemical assessments.

CSI may replace endoscopic monitoring in pediatric CD. Radiological remission status predicts long-term disease outcomes.

Intestinal ultrasound (IUS) is an increasingly used non-invasive tool to evaluate Crohn's disease (CD) activity. Recently, two IUS scores that evaluate inflammatory activity have emerged: the Simple Ultrasound Activity Score for CD (SUS-CD) and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS). We aimed to compare the accuracy of SUS-CD, IBUS-SAS and contrast-enhanced ultrasound (CEUS) in predicting inflammatory activity in the terminal ileum in ileocolonoscopy in CD patients.

Retrospective study including all consecutive CD patients submitted to IUS with CEUS directed to the terminal ileum performed by a single operator between April 2016 and March 2020. Segmental SUS-CD and IBUS-SAS were calculated. A time-intensity curve of the contrast bowel wall enhancement was created with measurement of peak intensity using CEUS. The CD endoscopic activity in ileocolonoscopy was graded by Simple Endoscopic Score for CD (SES-CD) as inactive (SES-CD < 7) or active (SES-CD ≥ 7).

Fifty patients were included, 54.0% were female, with mean age of 34 ± 12 years, and most had isolated ileal disease (60.0%), and a nonstricturing, nonpenetrating behaviour (44.0%). Most of the patients (60.0%) had active endoscopic disease (SES-CD ≥ 7). SUS-CD and IBUS-SAS were not different between patients with active or inactive endoscopic disease (p = 0.15; 0.57, respectively), having a poor accuracy to correlate endoscopic activity (area under de curve (AUC) 0.62; 0.55, respectively). Peak intensity in CEUS was significantly different in patients with active or inactive endoscopic disease (p = 0.004), having a good accuracy to correlate endoscopic activity (AUC 0.80).

Unlike CEUS, SUS-CD and IBUS-SAS were not able to accurately correlate endoscopic activity in terminal ileum in CD. Therefore, CEUS is a non-invasive emerging method that should be increasingly integrated in the ultrasonographic evaluation of CD patients.

The diagnosis and follow up of patients with inflammatory bowel disease [IBD] requires cross-sectional imaging modalities, such as intestinal ultrasound [IUS], magnetic resonance imaging [MRI] and computed tomography [CT]. The quality and homogeneity of medical reporting are crucial to ensure effective communication between specialists and to improve patient care. The current topical review addresses optimized reporting requirements for cross-sectional imaging in IBD.

An expert consensus panel consisting of gastroenterologists, radiologists and surgeons convened by the ECCO in collaboration with ESGAR performed a systematic literature review covering the reporting aspects of MRI, CT, IUS, endoanal ultrasonography and transperineal ultrasonography in IBD. Practice position statements were developed utilizing a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥80% of the participants agreed on a recommendation.

Twenty-five practice positions were developed, establishing standard terminology for optimal reporting in cross-sectional imaging. Assessment of inflammation, complications and imaging of perianal CD are outlined. The minimum requirements of a standardized report, including a list of essential reporting items, have been defined.

This topical review offers practice recommendations to optimize and homogenize reporting in cross-sectional imaging in IBD.

This paper reviews different imaging options for small bowel (SB) Crohn's disease (CD) patients.

In total, 80% of patients suffering from CD have SB involvement, being the exclusive manifestation in 30% of cases. As the proximal disease is related to poor response to treatment, a higher rate of stenosis and a greater need for surgical treatment, a SB assessment should be performed. This evaluation should be done not only once the disease has been diagnosed but periodically. The former to determine the extent of the disease, and the latter according to a treat-to-target strategy. Available techniques such as magnetic resonance imaging, intestinal ultrasound and capsule endoscopy (CE) have shown good accuracy parameters in CD patients. Cross-sectional studies are superior for penetrating and stricturing disease, whereas CE is excellent for proximal involvement and mucosal healing. Local expertise and availability may lead the election between techniques, nevertheless, they should not be considered as competitors but as complementary tools.

SB involvement in CD patients is frequent and related to poorer outcomes. Hence, SB evaluation should be screened after diagnosis and routinely during the follow-up.

Ileocolonoscopy (IC) detects mucosal inflammation and magnetic resonance enterography (MRE) detects transmural inflammation in Crohn disease (CD). We aimed to evaluate the relationship between the simplified magnetic resonance index of activity (MARIAs) and measures of inflammation by IC in children with newly diagnosed CD.

Retrospective review of 140 patients 6-18 years of age with CD who had baseline IC and MRE within 5 weeks of diagnosis. MARIAs was calculated for each intestinal segment (terminal ileum [TI], ascending colon, transverse colon, descending colon, sigmoid colon, rectum), defined as (1 × thickness > 3 mm) + (1 × edema) + (1 × fat stranding) + (2 × ulcers). Sensitivity and specificity were derived using receiver operating characteristic (ROC) curves to compare MARIAs to IC findings.

Using IC as the reference standard, the cutoff MARIAs ≥1 identified TI segments with active inflammation with 84% sensitivity, 73% specificity, 85% positive predictive value (PPV), 70% negative predictive value (NPV), and area under the curve (AUC) 0.782 (95% confidence interval [CI] 0.689-0.876). The cutoff MARIAs ≥2 identified TI segments with severe lesions with 87% sensitivity, 76% specificity, 87% PPV, 76% NPV, and AUC 0.814 (95% CI 0.712-0.916). There was poor sensitivity for all colonic segments.

The MARIAs is feasible and accurate in reflecting disease activity in the TI, but not in the colon, in children with newly diagnosed CD. Although the MARIAs may be useful for monitoring TI disease activity over time, full assessment continues to require both IC and MRE.

To describe response to therapy of small bowel (SB) Crohn's disease (CD) at CT or MR enterography (CTE/MRE) in patients on vedolizumab.

Patients with SB CD who underwent CTE/MRE exams greater than 12 months apart on vedolizumab therapy were included. Length (in cm) and inflammation severity (EMBARK score) of inflamed SB segments were assessed. Changes in inflammation length of 3.4 cm or greater or inflammation severity of 2 EMBARK points or greater was categorized as response or progression, as appropriate, with development of newly inflamed segments, strictures, or penetrating complications also indicating progression. Patients not meeting the criteria for response or progression were categorized as having stable disease.

Of 36 SB CD patients, the large majority had prior surgery (86%; 31), anti-TNF use (92%; 33), and internal penetrating (78%; 28) disease. Thirty-two patients had paired baseline and follow-up CTE/MRE exams without interval surgery, with clinical response observed in 24/32 (75%). Based on imaging response criteria, 22% (7/32; 95% CI: 9%-40%) had response, 50% (16/32; 95% CI: 32%-68%) were stable, and 28% (9/32; 95% CI: 14%-47%) had disease progression. Fifty-six percent of (18/32; 95% CI: 38%-74%) patients had clinical improvement with response or stable disease by imaging. Patients with stable disease had shorter median baseline lengths of SB inflammation (P = .012). Proportion of patients with colonic inflammation, perianal disease, or penetrating complications did not change.

Most patients on vedolizumab for over 12 months demonstrated response or stable SB disease when using objective cross-sectional radiologic imaging criteria using CTE/MRE.

Although endoscopic healing (EH) is recommended as the therapeutic goal in patients with Crohn's disease (CD), combined EH and radiologic healing (RH) could be a more ideal therapeutic goal considering the transmural nature of CD. We compared the prognosis of patients with CD who achieved EH, RH, both EH and RH (deep healing; DH), or no healing under treatment with anti-tumor necrosis factor (TNF) agents.

We analyzed 392 patients with CD who received anti-TNF treatment for more than 1 year and evaluated with CT enterography or magnetic resonance enterography together with colonoscopy within 3 months between July 2017 and December 2018. Major outcomes (anti-TNF dose intensification, switch to other biologics, CD-related bowel resection, and hospitalization) were compared according to the EH and RH status.

During the follow-up (median 18 months; interquartile range, 15-21), the DH group showed a better rate of major outcome-free survival compared with other groups (P < 0.001). In multivariable analysis, elevated C-reactive protein (adjusted hazard ratio [aHR], 2.166; 95% confidence interval [CI], 1.508-3.110; P < 0.001), EH-only (aHR, 3.903; 95% CI, 1.635-9.315; P = 0.002), RH-only (aHR, 3.843; 95% CI, 1.545-9.558; P = 0.004), and no healing (aHR, 8.844; 95% CI, 4.268-18.323; P < 0.001) were associated with increased risks of major outcomes.

Patients with CD who achieved DH under anti-TNF therapy showed a better prognosis compared with those who only achieved EH. The possibility of DH being used as a new therapeutic target for patients with CD should be investigated in further studies.

We aimed to determine if patient symptoms and computed tomography enterography (CTE) and magnetic resonance enterography (MRE) imaging findings can be used to predict near-term risk of surgery in patients with small bowel Crohn's disease (CD).

CD patients with small bowel strictures undergoing serial CTE or MRE were retrospectively identified. Strictures were defined by luminal narrowing, bowel wall thickening, and unequivocal proximal small bowel dilation. Harvey-Bradshaw index (HBI) was recorded. Stricture observations and measurements were performed on baseline CTE or MRE and compared to with prior and subsequent scans. Patients were divided into those who underwent surgery within 2 years and those who did not. LASSO (least absolute shrinkage and selection operator) regression models were trained and validated using 5-fold cross-validation.

Eighty-five patients (43.7 ± 15.3 years of age at baseline scan, majority male [57.6%]) had 137 small bowel strictures. Surgery was performed in 26 patients within 2 years from baseline CTE or MRE. In univariate analysis of patients with prior exams, development of stricture on the baseline exam was associated with near-term surgery (P = .006). A mathematical model using baseline features predicting surgery within 2 years included an HBI of 5 to 7 (odds ratio [OR], 1.7 × 105; P = .057), an HBI of 8 to 16 (OR, 3.1 × 105; P = .054), anastomotic stricture (OR, 0.002; P = .091), bowel wall thickness (OR, 4.7; P = .064), penetrating behavior (OR, 3.1 × 103; P = .096), and newly developed stricture (OR: 7.2 × 107; P = .062). This model demonstrated sensitivity of 67% and specificity of 73% (area under the curve, 0.62).

CTE or MRE imaging findings in combination with HBI can potentially predict which patients will require surgery within 2 years.

To assess inter-reader agreement of key features from the SAR-AGA recommendations for the interpretation and reporting of MRE in adult patients with CD, focusing on the impact of radiologist experience on inter-reader agreement of CD phenotypes.

Two experienced and two less-experienced radiologists retrospectively evaluated 99 MRE in CD patients (50 initial MRE, 49 follow-up MRE) performed from 1/1/2019 to 3/20/2020 for the presence of active bowel inflammation (stomach, proximal small bowel, ileum, colon), stricture, probable stricture, penetrating disease, and perianal disease. The MRE protocol did not include dedicated perianal sequences. Inter-rater agreement was determined for each imaging feature using prevalence-adjusted bias-adjusted kappa and compared by experience level.

All readers had almost-perfect inter-reader agreement (κ > 0.90) for penetrating disease, abscess, and perianal abscess in all 99 CD patients. All readers had strong inter-reader agreement (κ: 0.80-0.90) in 99 CD patients for active ileum inflammation, proximal small bowel inflammation, and stricture. Less-experienced readers had significantly lower inter-reader agreement for active ileum inflammation on initial than follow-up MRE (κ 0.68 versus 0.96, p = 0.018) and for strictures on follow-up than initial MRE (κ 0.76 versus 1.0, p = 0.027). Experienced readers had significantly lower agreement for perianal fistula on follow-up than initial MRE (κ: 0.55 versus 0.92, p = 0.008).

There was strong to almost-perfect inter-reader agreement for key CD phenotypes described in the SAR-AGA consensus recommendations including active ileum and proximal small bowel inflammation, stricture, penetrating disease, abscess, and perianal abscess. Areas of lower inter-reader agreement could be targeted for future education efforts to further standardize CD MRE reporting. Dedicated perianal sequences should be included on follow-up MRE.

The purpose of this article is to describe clinical and imaging characteristics of confirmed cases of cryptogenic multifocal ulcerous stenosing enteritis (CMUSE).

Retrospective review of electronic medical records identified patients considered for a diagnosis CMUSE over 20-years in a single large tertiary center. Clinical data were abstracted and diagnosis was confirmed based on published criteria. Two GI radiologists reviewed CT and MR enterography (CTE/MRE) exams in consensus of confirmed patients to characterize the imaging features of CMUSE.

Eight patients with confirmed CMUSE diagnosis were included for image review, and 9 CTEs and 1 MRE were analyzed. Most patients were males (75%) with a median age at diagnosis of 59.5 years (25-71) presenting with iron deficiency anemia (75%). Patients were commonly refractory (87.5%) to their first therapy, including steroids, with half being refractory to surgical intervention. Major imaging features included multiple (≥ 5; 88%; 7/8), short (< 2 cm; 100%; 8/8), circumferential (100%; 8/8) strictures with moderate wall thickening (6-9 cm), and stratified hyper enhancement (100%; 8/8) located in the ileum (100%; 8/8). Median proximal small bowel dilation was 2.95 cm (2.5-4.1 cm). No CMUSE cases demonstrated penetrating disease (e.g., abscess, fistula).

CT and MR enterography are invaluable tools in the multidisciplinary diagnostic evaluation of CMUSE, a rare cause of small bowel strictures with overlapping clinical and imaging features of Crohn's disease and NSAID enteropathy.

Crohn's disease (CD) is a major concern due to relatively high incidence and major complications like stricture or fistulas, often requiring surgical treatment. In recent years, magnetic resonance enterography (MRE) became a popular method of diagnosis and disease surveillance. The purpose of this review is to summarize and discuss the major and most recent advances in various aspects of MRE usage in diagnosong Crohn's disease, and to discuss advances in technique, disease activity monitoring and response to treatment.

A literature search was performed and relevant publications were included, with emphasis on articles from the past decade.

In this review we have presented articles with major advances in the field of MRE of CD patients such as proper sequence selection, recent advances in scoring of disease activity, differentiation between inflammation and fibrosis, response to treatment and technological advances such as the use of AI.

The main goal in improving MRE performance will be sequence selection aimed at differenting between inflammation and stricture while shortening the study length adjusted to patient compliance, and developing a standardized scoring system for MRE reporting assisted by artificial intelligence.

Single-shot diffusion-weighted imaging (ssDWI) has been shown useful for detecting active bowel inflammation in Crohn's disease (CD) without MRI contrast. However, ssDWI suffers from geometric distortion and low spatial resolution.

To compare conventional ssDWI with higher-resolution ssDWI (HR-ssDWI) and multi-shot DWI based on multiplexed sensitivity encoding (MUSE-DWI) for evaluating bowel inflammation in CD, using contrast-enhanced MR imaging (CE-MRI) as the reference standard.

Prospective.

Eighty nine patients with histological diagnosis of CD from previous endoscopy (55 male/34 female, age: 17-69 years). FIELD STRENGTH/SEQUENCES: ssDWI (2.7 mm × 2.7 mm), HR-ssDWI (1.8 mm × 1.8 mm), MUSE-DWI (1.8 mm × 1.8 mm) based on echo-planar imaging, T2-weighted imaging, and CE-MRI sequences, all at 1.5 T.

Five raters independently evaluated the tissue texture conspicuity, geometry accuracy, minimization of artifacts, diagnostic confidence, and overall image quality using 5-point Likert scales. The diagnostic performance (sensitivity, specificity and accuracy) of each DWI sequences was assessed on per-bowel-segment basis.

Inter-rater agreement for qualitative evaluation of each parameter was measured by the intra-class correlation coefficient (ICC). Paired Wilcoxon signed-rank tests were performed to evaluate the statistical significance of differences in qualitative scoring between DWI sequences. A P value <0.05 was considered to be statistically significant.

Tissue texture conspicuity, geometric distortions, and overall image quality were significantly better for MUSE-DWI than for ssDWI and HR-ssDWI with good agreement among five raters (ICC: 0.70-0.89). HR-ssDWI showed significantly poorer performance to ssDWI and MUSE-DWI for all qualitative scores and had the worst diagnostic performance (sensitivity of 57.0% and accuracy of 87.3%, with 36 undiagnosable cases due to severe artifacts). MUSE-DWI showed significantly higher sensitivity (97.5% vs. 86.1%) and accuracy (98.9% vs. 95.1%) than ssDWI for detecting bowel inflammation.

MUSE-DWI was advantageous in assessing bowel inflammation in CD, resulting in improved spatial resolution and image quality.

2 TECHNICAL EFFICACY STAGE: 2.

Transmural healing (TH) is being increasingly recognized for reflecting deep remission in Crohn's disease (CD). The long-term clinical significance of achieving TH is still not fully known. We aimed to evaluate TH as a predictor of long-term positive outcomes using intestinal ultrasonography (US), with comparison with the established endpoint mucosal healing (MH).

CD patients were consecutively recruited from September 2015 to August 2018 at a single tertiary hospital. All patients were evaluated at baseline and followed up at 6 months prospectively with a guideline-based treatment regimen. Achieving TH/MH or not was evaluated by US/colonoscopy at the first follow-up. Long-term outcomes including steroid-free clinical remission (CR), drug escalation, hospitalization, and surgery, were recorded after at least another 12 months.

We identified 77 patients with a median age of 30 years (range, 12-73 years). Twenty-five (32%) patients achieved TH, and 31 (40%) patients achieved MH. TH and MH were poorly correlated (Cohen's κ = 0.387; p < 0.05). Univariate analysis showed that both MH and TH were associated with better long-term outcomes. In multivariate analysis, TH was an independent predictor of steroid-free CR [odds ratio (OR), 52.6; p < 0.001], drug escalation (OR, 0.1; p = 0.002), and hospitalization (OR, 0.05; p = 0.005), while MH was an independent predictor of drug escalation (OR, 0.3; p = 0.05). Smoking habit was the only predictor of surgery (OR, 6.6; p = 0.02).

TH is an independent predictor of more favorable long-term outcomes than MH, suggesting that TH could become the potential treatment endpoint in CD.Plain language summary: Transmural healing predicts good prognosis in Crohn's disease The therapeutic endpoints of Crohn's disease keep evolving. The long-term clinical significance of achieving transmural healing is not fully discovered.Transmural healing is an independent predictor of more favorable long-term outcomes than mucosal healing.Transmural healing could become the potential treatment endpoint in Crohn's disease.

Transmural healing is associated with substantial improvements in disease-related outcomes for patients with Crohn's disease, but there is no single validated definition of transmural healing to date. We did a systematic review to summarise the available definitions and to evaluate the effect of transmural healing on disease-related outcomes for patients with Crohn's disease by searching PubMed, Cochrane Library, and Web of Science for interventional and non-interventional studies. Seventeen studies were included, reporting rates of transmural healing in between 14·0% and 42·4% of patients. Transmural healing was assessed with magnetic resonance enterography, bowel sonography, or CT enterography. Most studies used bowel wall thickness, with 3 mm or less as the most frequent cutoff, to define transmural healing. Vascularisation assessed by doppler ultrasound and absence of complications or contrast enhancement were also used for this definition. Transmural healing was significantly associated with improvements in disease-related outcomes. In addition, there was a good correlation between transmural healing, mucosal healing, and selected biomarkers. We conclude that bowel wall thickness is the most frequently used item to evaluate transmural healing, which is associated with improvements in long-term outcomes of Crohn's disease and should be considered as a new treatment target.

Certolizumab pegol (CZP) has been successfully used for the treatment of Crohn disease (CD); however, real-world data regarding the utility of CZP trough levels (CTLs) are lacking. We aimed to correlate CTL with CD outcomes and to determine frequency of CZP antibodies.

Retrospective evaluation of all CD patients on maintenance CZP with CTL obtained between 2016 and 2019. Outcomes included: median CTL, presence of anti-CZP antibodies, biochemical response (BR), clinical response (CR), radiologic response (RR), radiologic healing (RH), and mucosal healing (MH).

Seventy-seven CD patients were included. Median CTL was 18.9 µg/mL (interquartile range, 7.6-35.4). Twenty-three patients (27.3%) had positive antibody levels, with lower median CTL compared to patients with no antibodies (0.0 vs 29.8; P < 0.0001). Median CTL levels were higher in patients with vs without CR (30.4 vs 10.3 µg/mL; P = 0.0015) and RR (29.6 vs 5.8 µg/mL; P = 0.006). CZP dosing at least every 2 weeks was associated with higher odds of achieving MH (odds ratio, 3.2; 95% confidence interval, 1.03-9.97). CTL resulted in change in clinical management in 62.7% of cases and presence of CMZ antibodies was associated with an odds ratio of 5.83 (95% confidence interval, 1.57-21.73) of change in management. Receiver operating characteristic curve and quartile analysis suggested that CTL >19 µg/mL is associated with increased rates of CR and RR.

Higher CTL was significantly associated with CR and RR. The rate of CZP antibodies was 27.3%. Our data suggest maintenance CTL of ≥19 µg/mL should be achieved in order to optimize outcomes in clinical practice.