Intestinal Crohn's Disease Research Articles

Microbial assimilatory sulfate reduction-mediated H2S: an overlooked role in Crohn’s disease development

BackgroundH2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota.ResultsOur analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives.ConclusionsOur study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD.Dka3P5uGJeBhH66pkNJcogVideo

Pediatric cutaneous Crohn disease: A case series of 89 patients and review.

Cutaneous (or "Metastatic") Crohn disease (CCD) is a rare and underrecognized disease characterized by cutaneous granulomatous inflammation. We describe patient demographics, clinical characteristics, histology, and treatment of 89 pediatric cases of CCD, including 78 previously reported and 11 new cases seen at four academic institutions. We emphasize the efficacy of biologic mono- and dual therapy. PubMed identified cases using keywords including "metastatic Crohn disease" and "cutaneous Crohn disease". Patients were identified by retrospective review of the electronic health record including histopathologic diagnosis consistent with CCD. Chart review collected demographic, clinical, and histologic data. Most pediatric patients with CCD are male 55% (49/89), present with edema (73/89, 82%) and erythema (47/89, 53%) of the genitals (33/49, 67%), and have intestinal Crohn disease (69/89, 78%). Oral corticosteroids (53/75, 71%) and metronidazole (29/75, 39%) are the most frequently prescribed medications. Of the 17 patients treated with tumor necrosis factor (TNF)-blockade, 94% (16/17) had partial or total clearance. Ustekinumab resulted in clearance of cutaneous disease in two patients (2/3, 67%) and partial clearance in one patient (1/3, 33%). Two cases achieved total clearance with the use of dual biologic therapy defined as the use of two biologic therapies with differing mechanisms of action or the use of a biologic therapy and small molecule inhibitor. TNF blockade is an effective treatment for pediatric CCD, and interleukin-12/23 inhibitors may be similarly effective. Consideration of dual biologic therapy may be useful in pediatric patients requiring discordant therapies for their intestinal and cutaneous CD.

Computed tomography-based radiomics combined with machine learning allows differentiation between primary intestinal lymphoma and Crohn's disease.

Due to similar clinical manifestations and imaging signs, differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical practice. To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD. We collected contrast-enhanced computed tomography (CECT) and clinical data from 120 patients form center 1. A total of 944 features were extracted single-phase images of CECT scans. Using the last absolute shrinkage and selection operator model, the best predictive radiographic features and clinical indications were screened. Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model. The area under the receiver operating characteristic curve, accuracy, sensitivity and specificity were used for evaluation. A total of five machine learning models were built to distinguish PIL from CD. Based on the results from the test group, most models performed well with a large area under the curve (AUC) (> 0.850) and high accuracy (> 0.900). The combined clinical and radiomics model (AUC = 1.000, accuracy = 1.000) was the best model among all models. Based on machine learning, a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.

Targeted surgery combined with postoperative medical therapy for residual disease for severe and multifocal Crohn disease

BackgroundIn patients with multifocal intestinal Crohn disease requiring surgery for complication or uncontrolled disease, resection of all the lesions may lead to diarrhea and malnutrition. MethodsThis is a single-center retrospective review of all patients undergoing targeted surgery for multifocal Crohn disease with at least one residual Crohn disease location left behind. The primary endpoint was the rate of insufficient control of residual Crohn disease lesions requiring redo-surgery targeting these lesions. The rate of clinical remission defined by Harvey–Bradshaw index <4 was studied over time. ResultsFrom January 2012 to August 2022, among 320 patients undergoing surgery for intestinal Crohn disease, 30 met all criteria. Before surgery, patients had received a mean of 3 medical treatment lines; 83% (n = 25) had a clinically active Crohn disease (Harvey–Bradshaw index ≥4). Surgery consisted in ileocolonic (n = 14;47%), small bowel (n = 5;17%) or colonic resection (n = 12;40%) and strictureplasty (n = 4;13%). Operative mortality was nil. Overall postoperative and severe morbidity rates were 15 of 30 (50%) and 3 of 30. Residual lesions were in the small bowel (n = 15;50%), the colon (n = 16;53%), and/or the rectum (n = 16;53%). Twenty-five patients (83%) had postoperative medical therapy. Median follow-up was 65. Six patients (20%) required reoperation for insufficient control of residual lesions at index surgery after a mean of 98 ± 8 months. The clinical remission rate increased from 17% before surgery to 59% at 6–12 months and 71% at 24 months. ConclusionIn patients with multifocal Crohn disease, surgery targeted to severe and complicated lesions combined with postoperative medical treatment is a safe and effective strategy.

Long-term outcomes of intestinal penetrating Crohn's disease following successful nonoperative management.

There is a paucity of data on the surgical or medical treatment for abscess/fistula complicating Crohn's disease after successful nonsurgical management. We conducted a cohort study to investigate the long-term outcomes and the risk factors for the requirement of subsequent surgical intervention in Crohn's disease patients with complicating fistulas/abscess following successful nonsurgical management. Data were collected on penetrating Crohn's disease experiencing successful nonsurgical treatment between December 2012 and December 2021. Long-term outcomes and risk factors of surgery were assessed by univariate and multivariate analysis, and subgroup analysis was performed based on penetrating phenotype including abscess, fistula, and phlegmon. A total of 523 penetrating Crohn's disease patients; there were 390, 125, and 60 patients complicated with fistulas, abscess, and phlegmon, respectively. Long-term outcomes showed that BMI < 18.5 (kg/m 2 ), the recurrent abscess, and stricture were independent risk factors of surgery. Biologics and resolution of abscess were independent protective factors of surgery. Furthermore, in 399 patients undergoing early surgery, stricture and BMI < 18.5 (kg/m 2 ) were independent risk factors, and biologics and abscess resolution were protective of the early surgery. Subgroup analysis based on fistula, abscess, and phlegmon phenotype also demonstrated that concomitant stricture was an independent risk factor and the use of biologics was protective of surgical resection. Our data indicate that biologics can delay the requirement of surgery and may be given to patients with penetrating complicating Crohn's disease who have been successfully treated nonoperatively, but surgical resection should be considered in the setting of malnutrition and stenosis formation.

Few-shot learning for the classification of intestinal tuberculosis and Crohn's disease on endoscopic images: A novel learn-to-learn framework

Background and aimStandard deep learning methods have been found inadequate in distinguishing between intestinal tuberculosis (ITB) and Crohn's disease (CD), a shortcoming largely attributed to the scarcity of available samples. In light of this limitation, our objective is to develop an innovative few-shot learning (FSL) system, specifically tailored for the efficient categorization and differential diagnosis of CD and ITB, using endoscopic image data with minimal sample requirements. MethodsA total of 122 white-light endoscopic images (99 CD images and 23 ITB images) were collected (one ileum image from each patient). A 2-way, 3-shot FSL model that integrated dual transfer learning and metric learning strategies was devised. Xception architecture was selected as the foundation and then underwent a dual transfer process utilizing oesophagitis images sourced from HyperKvasir. Subsequently, the eigenvectors derived from the Xception for each query image were converted into predictive scores, which were calculated using the Euclidean distances to six reference images from the support sets. ResultsThe FSL model, which leverages dual transfer learning, exhibited enhanced performance metrics (AUC 0.81) compared to a model relying on single transfer learning (AUC 0.56) across three evaluation rounds. Additionally, its performance surpassed that of a less experienced endoscopist (AUC 0.56) and even a more seasoned specialist (AUC 0.61). ConclusionsThe FSL model we have developed demonstrates efficacy in distinguishing between CD and ITB using a limited dataset of endoscopic imagery. FSL holds value for enhancing the diagnostic capabilities of rare conditions.

P461 Deep learning model for endoscopic differential diagnosis between intestinal lymphoma and Crohn's disease: a multicenter study

Abstract Background Primary and secondary intestinal lymphoma (IL) are a relatively rare cancer, while easily misdiagnosed due to the unclear aetiology and unspecific clinical symptoms. Moreover, the endoscopic features of IL vary depending on pathological types, making it difficult to distinguish from Crohn's disease (CD). This study aims to develop deep learning models based on endoscopic images, facilitating the differential diagnosis of IL and CD. Methods We retrospectively recruited 271 patients with IL and 232 patients with CD from 6 tertiary centres in China. With out-of-focus or poor-bowel-prepared images excluded, we used 1739 IL and 1649 CD images for internal and external validation to build deep learning models. For internal validation, we used five-fold cross-validation with 1517 IL images and 1428 CD images from 5 centres randomly assigned without any patient overlap. 222 IL and 221 CD images from the 6th centre were used for independent external validation to measure the generalization ability of models. Further, we compared the performance of models with that of clinical physicians consisting of 2 junior physicians and 2 endoscopy specialists with more than ten years of clinical experience. We evaluated models using metrics such as accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) and used the kappa statistic to measure the inter-rater reliability between models and clinical physicians. Results We developed multiple convolutional neural network models, including ResNet18, ResNet34, ResNet50, VGG16, VGG19, DenseNet121, Inception v3, and Xception. The top 3 models in the internal validation were Inception v3, Xception, and DenseNet121. Inception v3 showed the best performance (accuracy: 83.1%; AUC: 0.910), while Xception performed better on average (average accuracy: 76.8%; average AUC: 0.834). In the external validation, the top 3 models were Inception v3, DenseNet121, and VGG19. Inception v3 achieved the highest accuracy of 81.9%, while DenseNet121 had the best AUC of 0.903. Compared with clinical physicians, Inception v3 performed better than junior physicians (average accuracy: 67.2%) and showed good agreement with the best endoscopy specialist (kappa: 0.604, p&amp;lt;0.05). Conclusion Convolutional neural network models using endoscopic images were able to differentiate PIL from CD, with better-diagnosing performance than junior physicians, good agreement with specialists, and good generation ability, which were expected to assist clinical physicians lacking experience to differentiate PIL and CD more precisely under endoscope.

P750 Endoscopic balloon dilation associated with biological therapy in Crohn's Disease strictures: a single center experience

Abstract Background Symptomatic luminal stricture in Crohn’s Disease (CD) occurs in up to 20% of patients at the diagnosis and in more than 50% during their lifetime. A considerable percentage of patients often require further surgery for post-operative CD recurrence, with a consequent increased burden of short bowel syndrome. In this scenario, combining biological therapy with endoscopic balloon dilation (EBD) could potentially reduce this risk. Our study aimed to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD patients. Methods We conducted a retrospective study including consecutive CD patients who underwent EBD for low gastrointestinal strictures from December 2015 until November 2022 at our tertiary IBD Center. Subsequent subocclusive/occlusive episodes, the need for steroids, and surgery due to CD stenosis were evaluated during a follow-up period of 6 and 12 months. Results A total of 52 patients treated with EBD with an overall number of 55 strictures were included. The mean age was 46,8 (18-77) years. The median of disease duration was 9 (0-42) years. Among the total of 55 studied strictures: 14 (25%) in patients with active smoking, 21 (38%) with increased CRP values at the time of dilation, 43 (78%) had evidence of moderate or severe endoscopic disease activity with ulcerative lesions at stricture site. Anastomotic strictures accounted for 26 (47%) of all 55 strictures. The remaining 29 (53%) were de novo stricture: 8 (15%) ileal, 11 (20%) at ileocecal valve, 4 (7%) colonic, and 6 (11%) anal . Forty-two patients (76%) were under biologic therapy at the time of EBD and 2 (4%) started after EBD. EBD technical success was reported in 60% of the procedures, and no adverse events were recorded. After 6 months from EBD, at univariate analysis, increased CRP at the time of dilation resulted in a risk factor for the need for steroids (OR 14,63, IC 2,690 to 71,50; p-value = 0,0006, Table 2). Concomitant biological therapy, active smoke, and the presence of ulcerative lesions did not show a significant correlation with considered outcomes. After 12 months from EBD, concomitant biological therapy resulted in being a protective factor for surgery (OR 0,06; IC 0,005 to 0,502; p-value=0,0047), while subocclusive and occlusive events were less frequent in anastomotic strictures than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p-value=0,0152). Conclusion In patients with CD undergoing EBD for intestinal CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.

Clinical Significance of Prognostic Nutrition Index in Patients with Crohn's Disease after Primary Bowel Resection.

Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn's disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140-6.649, p=0.024; OR=2.986, 95% CI=1.451-6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064-4.617, p=0.034). Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD.

Ileocecal involvement in intestinal Behçet's disease and Crohn's disease: comparison of clinicopathological and immunophenotypic features.

Intestinal Behçet's disease (BD) predominantly affects the ileocecal region and is currently diagnosed based on endoscopic features and clinical manifestations. It is difficult to distinguish between intestinal BD and Crohn's disease (CD) due to similar patient populations, gastrointestinal involvement, extraintestinal manifestations, and long-term recurrent course. In this study we aimed to compare the clinicopathological and immunophenotypic features of intestinal BD to CD. The medical and pathological records of 29 cases of intestinal BD and 120 cases of CD diagnosed at Sir Run Run Shaw Hospital were retrospectively analyzed. Immunohistochemistry for CD3, CD20, FOXP3, myeloperoxidase, and quantitative analysis of the infiltrating inflammatory cells was conducted. Intestinal BD with ileocecal ulcer had a higher incidence of abdominal pain and a higher erythrocyte sedimentation rate than CD, while chronic diarrhea was more common in CD. Excessive neutrophils in the mucosal lamina propria, neutrophilic exudate on the ulcer surface, and prominent lymphocytic infiltration in ulcer tissues were statistically more frequent in intestinal BD than in CD. The numbers of FOXP3+ T cells, CD3+ T cells, and CD20+ B cells in biopsy tissue from intestinal BD were significantly higher than CD, but the ratio of FOXP3+ T cells to CD3+ T cells was not statistically different. Besides the typical clinical and endoscopic findings, diagnostic biopsies from the ileocecal region in intestinal BD show some histological and immunophenotypic features that are different from CD, which may be useful in distinguishing these two entities.

Enhancing the Differentiation between Intestinal Behçet's Disease and Crohn's Disease through Quantitative Computed Tomography Analysis.

Behçet's disease (BD) behaves similarly to Crohn's disease (CD) when the bowel is involved. Computed tomography enterography (CTE) can accurately show intestinal involvement and obtain body composition data. The objective of this study was to evaluate whether CTE could improve the ability to distinguish between intestinal BD and CD. This study evaluated clinical, laboratory, endoscopic, and CTE features on first admission. Body composition analysis was based on the CTE arterial phase. The middle layers of the L1-L5 vertebral body were selected. The indicators assessed included: the area ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) (VSR) in each layer, the total volume ratio of VAT/SAT, the quartile of VAT attenuation in each layer and the coefficient of variation (CV) of the VAT area for each patient was also calculated. Two models were developed based on the above indicators: one was a traditional model (age, gender, ulcer distribution) and the other was a comprehensive model (age, gender, ulcer distribution, proximal ileum involvement, asymmetrical thickening of bowel wall, intestinal stenosis, VSRL4, and CV). The areas under the receiver operating characteristic (ROC) curve of the traditional (sensitivity: 80.0%, specificity: 81.0%) and comprehensive (sensitivity: 95.0%, specificity: 87.2%) models were 0.862 and 0.941, respectively (p = 0.005).

Nomogram based on computed tomography images and clinical data for distinguishing between primary intestinal lymphoma and Crohn's disease: a retrospective multicenter study.

Differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical diagnosis. To investigate the validity of the nomogram based on clinical and computed tomography (CT) features to identify PIL and CD. This study retrospectively analyzed laboratory parameters, demographic characteristics, clinical manifestations, and CT imaging features of PIL and CD patients from two centers. Univariate logistic analysis was performed for each variable, and laboratory parameter model, clinical model and imaging features model were developed separately. Finally, a nomogram was established. All models were evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, and decision curve analysis (DCA). This study collected data from 121 patients (PIL = 69, CD = 52) from Center 1. Data from 43 patients (PIL = 24, CD = 19) were collected at Center 2 as an external validation cohort to validate the robustness of the model. Three models and a nomogram were developed to distinguish PIL from CD. Most models performed well from the external validation cohort. The nomogram showed the best performance with an AUC of 0.921 (95% CI: 0.838-1.000) and sensitivities, specificities, and accuracies of 0.945, 0.792, and 0.860, respectively. A nomogram combining clinical data and imaging features was constructed, which can effectively distinguish PIL from CD.

Mucosal Healing and Clinical Efficacy of Adalimumab in Small Intestinal Crohn's Disease (SIMCHA Study): Final Results From a Prospective, Open-Label, Single-Arm Study.

Endoscopic healing is a key treatment target in inflammatory bowel disease; few data are available on the clinical and endoscopic efficacy of biological therapy in upper gastrointestinal Crohn's disease. This study aimed to investigate small bowel mucosal healing and clinical efficacy of adalimumab therapy by video capsule endoscopy in patients with endoscopically active upper gastrointestinal Crohn's disease. This prospective, open-label, single-arm study included Crohn's disease patients with moderate-severe endoscopic proximal small bowel involvement, defined by a Lewis score >790. Patients were treated with adalimumab monotherapy for 24 weeks. Co-primary outcomes were endoscopic healing, defined as Lewis score <350, and endoscopic response, defined as >50% decrease in Lewis score. Secondary outcomes included clinical (Harvey-Bradshaw index <4) and biomarker remission (fecal calprotectin <250 μg/g, and C-reactive protein <5 mg/L). A total of 59 Crohn's disease patients were screened; 17 patients have met eligibility criteria and were enrolled. Endoscopic healing was observed in 8 patients (47.1%) and endoscopic response in additional 5 patients (29.4%) at 24 weeks. Median Lewis score was significantly decreased compared to baseline (1912 vs. 337, P = .0005). Eleven of 13 patients (84.6%) with clinical activity achieved clinical remission (baseline: 13/17 vs. week 24: 2/17, P < .0001). Nine of 10 patients with elevated C-reactive protein achieved normal C-reactive protein after treatment and the median C-reactive protein significantly decreased from 7.4 to 1.6 mg/L, P = .032. In contrast, no change was observed in fecal calprotectin pre- and posttreatment. Adalimumab induced endoscopic healing and clinical remission in patients with active small bowel Crohn's disease, with approximately half of the patients achieving endoscopic healing.

Immediate Results of Small Bowel Crohn’s Disease Surgery

Introduction: Despite the progress made in the medical management of Crohn's disease (CD), a vast number of patients are operated on at least once in their lifetime. Although this is a mild disease that occurs mainly in young patients with little comorbidity, CD surgery is accompanied by significant postoperative morbidity (PO). This study aims to analyse the PO complications of the small intestine's CD and look for the risk factors for its occurrence. Patients and methods: this is a single-centre prospective study that collected 83 files of patients operated on for CD of the small intestine for 28 months (May 2017 - September 2019). All patients had histologic confirmation of CD. Isolated anoperineal and colorectal forms were excluded from this work. PO morbidity is defined by all complications occurring during the first 30 days of PO. A statistical analysis of PO morbidity was performed as a function of 12 parameters: age; sex; comorbidity; history of abdominal surgery; history of surgery for CD; haemoglobin level (Hb &lt;or&gt; at 10 mg/dl); albumin level (&lt;or&gt; at 34g / l); BMI (&lt;or&gt; at 19); ASA score; mode of surgery (cold vs emergency); intra-abdominal abscess; operative procedure (resection-anastomosis vs resection-stoma). Statistical analysis was performed first univariate and then multivariate (SPSS 16 software). Results: These were 56 women and 27 men, with a sex ratio of 2. The mean age of the patients was 35 years (13-65). The overall PO morbidity rate was 26%; this morbidity was surgical in 86%, septic in 89.5% and intra-abdominal septic in 50% of cases. Complications were major (CMPO) in 39.5% of cases. The mode of emergency surgery was an independent risk factor for the occurrence of complications (p = 0.005). Conclusion: Small intestine CD surgery is associated with very high PO morbidity. The mode of emergency surgery is an independent risk factor for the onset of PO complications. Patients who require surgery should be operated on as elective or scheduled surgery. The indications for emergency surgery for CD are sporadic.

Perfusion Computed Tomography May Help in Discriminating Gastrointestinal Tuberculosis and Crohn’s Disease

Gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) are close mimics. This prospective study aimed to evaluate the diagnostic performance of perfusion computed tomography (CT) in differentiating GITB from CD. Consecutive patients with ileocaecal thickening underwent perfusion CT of the ileocaecal region between January 2019 and July 2020. Two radiologists (blinded to the final diagnosis) independently assessed blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability at perfusion CT. These parameters were compared among the patients with GITB as well as active and inactive CD. Receiver operating characteristic curves were utilized for determining the diagnostic performance of perfusion CT. Interclass correlation coefficient and Bland-Altman analysis were performed to compare the observations of the two radiologists. During the study period, 34 patients underwent perfusion CT. Eight patients had diagnoses other than intestinal tuberculosis or CD. Thus, 26 patients (mean age 36 ± 14 years, 18 males) with GITB (n = 11), active CD (n = 6), and inactive CD (n = 9) were evaluated. BF, MTT, and permeability showed significant differences among the groups, while BV did not differ significantly among the groups. BF and permeability had 100% sensitivity and 100% specificity, while MTT had 61.5-100% sensitivity and 70-100% specificity for differentiating GITB from active CD and active from inactive CD. The interclass correlation coefficient for perfusion CT parameters was 0.88-1. Perfusion CT is a novel imaging technique that can improve the diagnostic performance of differentiating tuberculosis from CD.

P709 Endoscopic healing and clinical remission after administration of adalimumab to patients with Crohn’s disease of the small intestine

Abstract Background In patients with Crohn’s disease (CD) localized in the small intestine, endoscopic healing can be assessed by small bowel capsule endoscopy (SBCE). We aimed to investigate the rate of achieving deep remission, i.e. endoscopic healing and clinical remission in patients with CD of the small intestine, after treatment with adalimumab. Methods Retrospective analysis of prospectively collected data from all patients who were subjected to SBCE in our department from 1/3/2003 to 30/9/2022. Out of the patients who were subjected to the test for the investigation of suspected or confirmed CD of the small intestine we sought those who were treated with adalimumab (originator or biosimilar) and underwent repetitive SBCE at least 24 weeks after the start of treatment. Endoscopic healing was defined as a Lewis score &amp;lt; 350, while clinical remission was defined as Harvey Bradshaw index ≤ 4. Results During the study period, 102 patients (men/women: 54/48, mean age ± SD: 31.2±14.1 years) were subjected to SBCE before and after administration of adalimumab for the treatment of small intestinal CD. Of these patients, 11 (10.7%) also had extra-intestinal manifestations (arthritis: n=9, erythema nodosum: n=1, uveitis: n=1). After a mean period of 104 weeks (range 24-416 weeks), endoscopic healing was observed in 49 patients (48.0%). All patients who experienced endoscopic healing were also in clinical remission. There was no statistically significant difference in patients with endoscopic healing between those receiving adalimumab originator or biosimilar (36 out of 73, 49.3% vs 13 out of 29, 44.8%, p=NS). Conclusion Small bowel capsule endoscopy can help us to identify endoscopic healing, which is observed in about half of patients with CD of the small intestine treated with adalimumab.

Manejo actual del fracaso intestinal por enfermedad de Crohn en nuestro medio: resultados de una encuesta GETECCU

IntroductionIntestinal failure is a rare pathology which requires knowledge and highly specialized multidisciplinary management. Crohn's disease (CD) being one of the most frequent causes in adults. Material and methodsSurvey format study carried out within the GETECCU group, included closed format questions about the diagnosis, management and current knowledge of intestinal failure in CD. ResultsForty-nine doctors participated, belonging to different Spanish centers (19 cities).It was considered that a patient suffered from intestinal failure, in 67.3% (33/49 surveyed) when there was a disorder malabsorptive associated regardless of the intestinal length resected, with surgeries resective ileal repeated (40.8%, 20/49), the most frequent cause.It highlights frequent ignorance about the pathology (24.5%) did not know if there were patients in their center and also 40% did not know the pharmacological treatment.A total of 228 patients were registered for follow-up due to intestinal failure of any aetiology, 89 patients (39.5%) were identified with CD.Regarding the therapeutic management of patients with CD and intestinal failure (72.5%) were receiving total parenteral nutrition (NTP) and 24 patients (27%) with teduglutide. Regarding the response to the drug: 37.5% had no response to teduglutide, 37.5% partial response (reduce NTP) and 25% good response (withdrawal of home NTP).In questions related to knowledge about intestinal failure, it was considered limited (53.1%) or very limited (12.2%) by the surveyed. ConclusionIt is necessary to carry out a combined management of intestinal failure and CD in the context of a multidisciplinary approach.

A BET Protein Inhibitor Targeting Mononuclear Myeloid Cells Affects Specific Inflammatory Mediators and Pathways in Crohn's Disease.

Background: Myeloid cells are critical determinants of the sustained inflammation in Crohn’s Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess wide-ranging toxicities. In the current study, we make use of a BET inhibitor containing an esterase sensitive motif (ESM-iBET), which is cleaved by carboxylesterase-1 (CES1), a highly expressed esterase in mononuclear myeloid cells. Methods: We profiled CES1 protein expression in the intestinal biopsies, peripheral blood, and CD fistula tract (fCD) cells of CD patients using mass cytometry. The anti-inflammatory effect of ESM-iBET or its control (iBET) were evaluated in healthy donor CD14+ monocytes and fCD cells, using cytometric beads assay or RNA-sequencing. Results: CES1 was specifically expressed in monocyte, macrophage, and dendritic cell populations in the intestinal tissue, peripheral blood, and fCD cells of CD patients. ESM-iBET inhibited IL1β, IL6, and TNFα secretion from healthy donor CD14+ monocytes and fCD immune cells, with 10- to 26-fold more potency over iBET in isolated CD14+ monocytes. Transcriptomic analysis revealed that ESM-iBET inhibited multiple inflammatory pathways, including TNF, JAK-STAT, NF-kB, NOD2, and AKT signaling, with superior potency over iBET. Conclusions: We demonstrate specific CES1 expression in mononuclear myeloid cell subsets in peripheral blood and inflamed tissues of CD patients. We report that low dose ESM-iBET accumulates in CES1-expressing cells and exerts robust anti-inflammatory effects, which could be beneficial in refractory CD patients.

Surgical strategies for intestinal Crohn's disease.

As a type of inflammatory bowel disease, Crohn's disease (CD) is characterized by jumping lesions and transmural inflammation. The treatment goal is to control the development of inflammation with drugs such as 5-Amino Salicylic Acid, azathioprine and hormones, but most patients still need surgical treatment eventually. The surgical treatment of CD requires exquisite surgical design and solid surgical procedures to minimize the progression of intestinal lesions and preserve the normal bowel segment as much as possible. This study aims to summarize and discuss the surgical treatments for intestinal CD, and to provide references for the surgical treatment of intestinal CD. Clinical data of 122 patients with CD were analyzed retrospectively. They all received surgical treatments in the Second Xiangya Hospital of Central South University between Jan. 1, 2015 and Jan. 1, 2021. The data included general information, clinical manifestations, preoperative examination, preoperative preparation, surgical methods, pathological examination, complications, and follow-up data. Except 1 case of emergency surgery, all the other patients met the surgical indications of intestinal CD after multi-disciplinary discussion (MDT) and they were transferred to surgery for elective surgery, and received high-quality intestinal preparation before surgery. Among them, 99 cases underwent one-stage abdominal operation and 23 cases underwent the second abdominal operation. All patients underwent successful surgery with good surgical results, with significantly alleviated clinical symptoms and the BMI significantly increased compared with those before surgery. There were 14 cases (11.5%) of postoperative complications. One case of delayed anastomotic fistula and one case of small intestinal cutaneous fistula which were successfully treated by conservative treatment, the other 12 cases were successfully treated by reoperation, and there were no complications with follow-up operation. The postoperative pathological diagnosis for all patients was clear. All patients received regular follow-up with 5-70 (median 36) months and no clinical recurrence was found. As the surgical treatment of intestinal CD, surgeons should strictly grasp the surgical indications based on the MDT. During the operation of small intestinal CD, it is advisable to preserve bowel segment as much as possible. For patients with short remaining normal bowel segment, the intestinal canal should be preserved as far as possible, even for the mildly diseased bowel, so as to avoid the occurrence of short bowel syndrome and leave room for possible reoperation. In the treatment of secondary duodenal CD, it is necessary to carefully identify the nature of the local lesions. Different surgical treatments should be performed according to whether there is an internal fistula and the size of this fistula. Meanwhile, duodenectomy or pancreaticoduodenectomy should be considered as the final surgical method in the treatment of primary duodenal CD.

Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn's disease in tuberculosis endemic areas.

Intestinal tuberculosis (ITB) and Crohn's disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL. Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55-0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.