Diagnosis Of Crohn's Disease Research Articles

P1118 High Crohn’s Disease burden but disproportionally low use of biologics in Crohn’s Disease patients with Intestinal Failure: a longitudinal comparative study from 1973-2018

Abstract Background Patients with Crohn’s Disease (CD) complicated by Intestinal Failure (CDIF) are considered to be among those with the most severe form of CD. Their clinical course before IF onset has not been well characterised. We aimed to describe and compare CD-specific natural history, disease burden and treatment between CDIF patients and CD patients without IF over a 40-year period. Methods CDIF patients from Copenhagen Intestinal Failure Database (1973-2018) and a Danish nationwide CD cohort without IF (1977-2018) were followed from onset of CD until IF, death, or 31/12/2018. Hospital contacts, surgeries, prescription dispensation, employment and mortality data were extracted from multiple population-based registries. Groups were compared using logistic regression for proportions and Poisson regression for rates. Standard mortality ratio (SMR) was calculated against age, gender and year-matched Danish population references, and an adjusted mortality rate ratio between CDIF and CD patients was obtained from Cox models. Results 182 CDIF and 22845 CD patients were followed for 3035.7 and 293536.5 patient-years, respectively. At CD diagnosis, CDIF patients were younger (median age 24 years vs 35 years, p<0.0001), from earlier decades (71.5% vs 16.5% before 1991, p<0.0001), and had fewer comorbidities (6.9% vs 20.4%, p<0.0001). The 10-year cumulative incidence of IF declined from 2.7% in patients diagnosed with CD prior to 1980 to 0.2% in patients diagnosed after 2000, but the number of new CDIF patients has not declined over the decades (Table). A greater proportion CDIF patients received at least 1 course of steroids (70.8% versus 59.8%, p=0.02) and immunomodulators (59.3% vs 48.7%, p=0.03), had IBD-related hospital contacts (98.2% vs 55.2%, p<0.0001) and abdominal surgeries (94.9% vs 47.6%, p<0.0001), and stopped working for >6 months (65.8% vs 57.8% of working-age patients, p=0.05). However, in the biologics era (after 2000), CDIF patients were not treated with biologics more often (20.4% vs 21% had any biologics, p=ns). In those who were treated, CDIF patients had less cumulative time on biologics (3.9 years vs 11.2 years per 100 patient-years, p=0.001). CDIF and CD patients had a SMR of 3.7 (97.5% CI 2.79,4.72) and 1.7 (97.5% CI 1.61, 1.72), respectively. After adjusting for age, sex and co-morbidity, CDIF patients were at 3.42 times risk of dying compared to CD patients. Conclusion The incidence of CDIF has reduced in newly diagnosed CD patients, however the number of new CDIF patients has not yet declined due to increasing CD prevalence. Despite CDIF patients experiencing a significantly higher burden of CD before the onset of IF, they were not more likely to receive biologics. They also appear more refractory to biologics.

N12 The Experience of Post-traumatic Growth Process in Newly Diagnosed Chinese Patients with Crohn’s Disease: A Longitudinal Qualitative Study

Abstract Background The impact of Crohn’s disease (CD) is not purely negative, it may become an opportunity for patients to undergo positive psychological adjustments and achieve personal growth. To date there has been limited in-depth research to understand the patients’ experiences of post-traumatic growth (PTG) process following an CD diagnosis using a qualitative study with a longitudinal perspective. Methods A longitudinal qualitative design was adopted. Sixteen newly diagnosed Chinese patients with CD were recruited through purposive sampling. Semi-structured interviews were conducted on three occasions: 3, 6 and 12 months post-diagnosis. Data were collected between November 2021 and December 2022. Data analysis of each time point was based on conventional content analysis. Afterwards, all data were combined for a comprehensive re-analysis to capture change. Results Four themes and fifteen sub-themes were formed through analysis (table 1). The process of PTG was shown in Figure 1. Within the first year post-diagnosis, patients with CD experienced considerable physical discomforts and psychological distress. Their personal development was also limited. With increased disease knowledge, and driven by a strong sense of responsibility and external support, the patients’ disease acceptance transformed from "difficult to accept" to "have to accept" to "should accept" then to "be able to accept". Living with CD, they actively engaged in monitoring disease condition, cooperating with treatment, exploring patterns of flare-ups, relieving stress and focusing on problem solving to eliminate negative emotions, and regaining hope and positively planning for future. Over time, the impact of CD on the patients’ lives became smaller, they integrated their disease as a part of themselves, and achieved personal growth. This growth was manifested by "developing closer relationships with others", "increasing personal strength", "changing in life philosophy" and "emerging new possibilities". Overall, as disease duration increased, the disease related sufferings diminished, and CD patients’ disease acceptance improved. In addition, as time goes by, the patients’ ability to self-manage disease enhanced, and their experience of personal growth increased. Conclusion The process of PTG in patients with CD within the first year of diagnosis primarily consists of four stages: "enduring hardships", "accepting illness", "living with illness", and "achieving personal growth". This growth was not linear, but rather cyclical. Nurses could provide targeted guidance to patients based on the trajectory identified in this study, helping them unearth inner resources and create conditions for PTG.

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<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.

P365 Incidental terminal ileitis in asymptomatic patients. Is it Crohn’s disease?

Abstract Background Inflammation of the terminal ileum is a common finding during colonoscopy, even in patients without symptoms as an accidental finding. Nevertheless, there are no guidelines or wide consensus about the indications for treatment or follow-up, since the clinical importance and natural history of this entity has not yet been fully investigated. Methods This was a retrospective cohort study, where the electronic database of the Gastroenterology Department of University Hospital of Heraklion, Greece was searched through using the term "inflammation of terminal ileum" and "ulcers of terminal ileum", through the years 2012-2023. All cases with terminal ileitis as an accidental finding in asymptomatic patients, where colonoscopies performed for miscellaneous reasons (e.g. screening colonoscopy, follow-up colonoscopy after polypectomy) were identified. Patients with symptoms, or known Crohn’s Disease (CD) were excluded. Patients’ demographics, endoscopic and clinical follow-up data, as well as treatment and final diagnosis of CD were registered. Possible risk factors for terminal ileitis [smoking, use non-steroidal anti-inflammatory drugs (NSAIDs)] were also recorded. Univariate and multivariate analysis of the data was performed with SpSS v22 software. Results In a total of 465 cases with terminal ileitis 205 had known CD, 153 underwent colonoscopy for symptoms whereas 107 patients (62 females) underwent colonoscopy with no associated symptoms and constituted the study population. Among these 107 patients [median age 50, interquartile range (IQR) 39-64years, median BMI 25kg/m2, IQR 23.2-27.1kg/m2, median follow-up 4years) 27 (25%) patients were current smokers, 32 (30%) ex-smokers and 22 (20%) reported recent use of NSAIDS (Table 1). During follow-up, 88 (82%) patients had a new colonoscopy with persistence of terminal ileitis in 66 (62%) of them, 68 (64%) developed symptoms, 37 (35%) were diagnosed with CD,39 (36%) received treatment, and 18 (17%) required hospitalization. In the group of the patients that required treatment, only 8 (7.4% of the study population) eventually required systemic immunosuppression (corticosteroids, thiopurines, biologic agents. In multivariate analysis, there was no statistically significant correlation between the persistent terminal ileitis on follow-up colonoscopy and BMI, the use of NSAIDs, or ex-smoking. Nevertheless, there was a significant correlation between active smoking and the persistence of terminal ileitis (p=.005). Conclusion Most of the patients with incidental, asymptomatic terminal ileitis remain asymptomatic and don’t require treatment. Close monitoring is required since diagnosis of Crohn’s disease is established in one third of them.

P411 Is transmural healing better than mucosal healing in pediatric Crohn’s disease?

Abstract Background While the long-term benefit of achieving mucosal healing (MH) in Crohn’s disease (CD) has been demonstrated, data on transmural healing (TH), assessed by non-invasive imaging modalities (i.e. magnetic resonance enterography, MRE) are scarce, particularly in the pediatric setting. Nonetheless it has been deemed as an adjunctive target for CD by the STRIDEII consensus. We aimed to investigate the outcomes of pediatric CD patients with TH comparing them to those with MH and with “no healing”. Methods Prospective, single-center, observational study conducted at the Pediatric Gastroenterology and Liver Unit of the Umberto I Hospital, Sapienza University of Rome. Children with an established diagnosis of CD and under biological therapy undergoing an MRE and an ileocolonoscopy performed within a 3-month interval were consecutively enrolled. Transmural healing was defined as the complete healing of both the mucosa at endoscopy (absence of ulceration) and of the bowel layers at the MRE. In the presence of a normal colonoscopy but an active MRE children were deemed as MH. The group “no healing” (NH) included children with an active endoscopy, regardless of the MRE classification. At 6, 12, and 24 months, the following outcomes were evaluated and compared in the three groups: disease flares, CD-related hospitalization, CD-related surgery, need for step-up treatment, and occurrence of complications. Results 93 children were included (30% female, mean age 11,2±3,8). Twenty-three (25%) were classified as TH, 27 (29%) as MH and 43 (46%) as NH. Overall, at the Kaplan Meier analysis, the risk of any unfavorable outcome was significantly lower in both TH and MH patients compared to NH (Log Rank p<0.0001 and p=0.002, respectively). Specifically, children with TH were at lower risk of hospitalization (p=0.02), and complications (p=0.007) compared to those with NH. No difference was found between MH and NH children for the same outcomes. Both TH and MH children were at lower risk of step-up treatment (p<0.0001 and p=0.0.0002, respectively) compared to NH. No difference was found between TH and MH patients for all the outcomes evaluated. Conclusion Achieving transmural healing in pediatric CD is associated with better long-term outcomes, although the additional benefit compared to reaching MH alone does not appear significant. However, the persistence of inflammation is associated with worse outcomes in all patients.

P659 Prognostic markers in Treat-to-Target for Crohn’s Disease- an Asian institution’s experience

Abstract Background Endoscopic healing (EH) is a long-term treatment target in the Treat-to-Target approach for Crohn’s Disease (CD). However, not all patients with CD will achieve this treatment target due to a combination of factors. This study aims to evaluate the proportions of patients with CD who achieve EH at 24 months from diagnosis. Secondary aims include proportion of patients who achieve corticosteroid free clinical remission (CSFR), biomarker (BM) normalization and predictors of failure to achieve EH. Methods This is a retrospective study of all patients with Crohn’s disease seen at a tertiary hospital in Singapore from January 2010 to December 2021. Patients with a confirmed diagnosis of CD based on endoscopic, clinical and histological findings were identified from existing IBD registry. Those with a follow-up period of less than 12 months, no repeat endoscopy and missing data were excluded from analysis. We collected data on baseline demographics, disease characteristics and treatment received. Treatment targets were assessed in terms of CSFR, biomarkers normalization, EH and transmural healing (when available). We defined these targets as outlined in the selecting therapeutic Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) II initiative. Statistical analysis was performed in Python using statsmodels 0.14.0. Results We identified a total of 86 CD patients. After excluding 29 patients, 59 patients were included in the final analysis.Mean age at diagnosis was 33 years old, and 69.5% were males. Table 1 demonstrates the baseline demographics and disease characteristics of all patients. The median follow-up period was 101 months. Out of 59 patients, 88% (n=52) and 80% (n=47) achieved CSFR and biomarker normalization respectively at 12 months. At 24 months of follow up, EH was achieved in 54% (n =32) of all patients. Of those who achieved EH, 22 had repeat imaging and transmural healing was documented in 14 patients. On multivariate logistic regression, Montreal B3 (penetrating type) disease was predictive of failure to achieve EH (OR 9.8, p= 0.036). Use of biologics also showed a trend for failing to achieve EH though this was not statistically significant (OR 3.5, p = 0.075). Conclusion A vast majority of CD patients were able to achieve corticosteroid free clinical remission and biomarker normalization. Penetrating disease was predictive of failure to achieve EH at 24 months. This study provides additional evidence in determining treatment targets for CD patients based on their disease phenotypes. These findings could be further validated in larger cohort, prospective studies.

P827 Has opioid use increased among adults with Crohn’s disease? A Swedish Nationwide cohort Study 2008-2020

Abstract Background Chronic opioid use has turned into a global health challenge. Crohn’s disease (CD) patients may experience severe pain requiring opioids which could exacerbate CD symptoms and pose a risk of chronic use. The use of opioids among CD patients has not been explored on a national level. We compared the secular trends of opioid use among prevalent CD patients and matched reference individuals in Sweden. Methods This nationwide cohort study included adults with a prevalent CD diagnosis who lived in Sweden for at least 12 consecutive months at some point between 1 January 2008 and 31 December 2020. For each patient, up to 10 reference individuals from the general population were matched on birth year, sex, calendar year, and place of residence. We retrieved the data on dispensed opioid prescriptions (opioid use) from the National Prescribed Drug Register. We defined opioid use as ≥1 filled prescription per calendar year. We also estimated the annual prevalence of ≥1 dispensation of weak (codeine combinations, tramadol, and Dextropropoxifen) and/or strong opioids (Oxycodone, Morphine, Hydromorphone, Fentanyl, Buprenorphine, Tapentadol, and Petidin). Results We identified 43,155 adult CD patients and 418,218 reference individuals (Table 1). The prevalence of opioid use was stable from 2008-2016. However, between 2017 and 2020 it decreased from 19.7% (95% CI: 19.2, 20.2) to 16.9% (95% CI: 16.2, 17.7) and from 8.5% (95% CI: 8.4, 8.7) to 6.9% (95% CI: 6.7, 7.1) among CD patients and reference individuals, respectively (Figure 1a). However, between 2008 and 2020, the prescription of strong opioids more than doubled among both CD patients (increasing from 4.3% [95% CI: 4.1, 4.6] to 11.5% [95% CI: 11.1, 11.8]), and reference individuals (increasing from 1.3% [95% CI: 1.3, 1.4] to 5.4% [95% CI: 5.3, 5.5]) (Figure 1b). In 2020, the last year of the observation, compared with males, both female CD patients (20.3% [19.7, 20.8] vs 9.3% [9.2, 9.5]) and their matched reference individuals (15.3% [14.8, 15.9] vs 7.1% [6.9, 7.2]) had a higher prevalence of annual opioid use. The secular trends of overall opioid use and increasing use of strong opioids were similar for males and females (data not shown). Conclusion Annual opioid use among prevalent CD patients in Sweden, a country with publicly-funded healthcare and access to modern CD treatment, was two-fold higher than in the general population in the last 13 years. The annual opioid use remained stable from 2008-2016 and slightly decreased from 2017-2020 for CD patients and reference individuals. During the same period, the use of strong opioids more than doubled for CD patients and the general population.

P302 Diagnostic Delayed is Associated with a Poor Prognosis in Patients with Crohn's Disease

Abstract Background The studies show that diagnostic delay, especially in Crohn’s disease (CD), is associated with a higher risk of complications and major surgery. We aimed to investigate timing of the diagnostic delay (DD) and its impact on the CD outcomes. Methods We retrospectively evaluated demographic and clinical features of CD patients between June 1993 and October 2023. Diagnostic delay was defined as the time interval from the onset of the first symptoms to the making of the CD diagnosis. The first CD related symptoms were evaluated by a review of the physician’s notes and medical record. Specific symptoms of CD included chronic or recurrent bloody or non-bloody diarrhea, and/or abdominal pain accompanied by noticeable weight loss, general weakness, and fever. Results 514 patients with CD were included in the study. The median age of disease onset was 34.14 years (16–84 years). Male sex was 299 (58.2%). DD was detected median 13 months (5-47) (14 months in male and 12 months in female). DD was 12 months for diseases with onsets before the age of 40 and 15 months for diseases with onsets after the age of 40. DD was 25 months in isolated ileal involvement, in terminal ileal involvement was 21.5 months, ileo-colonic involvement was 20 months, and colonic location was 10 months. Ileal involvement was found to have a longer duration for DD than colonic involvement. Compared to stenosing behavior (20 months) and penetrating behavior (17 months), DD was shorter in non-stenosing non-penetrating behavior (12 months). DD was longer in perianal disease (18 months) than in those without (12 months). Current smokers had a longer duration of the DD (20 months) compared to non-smokers (11.5 months) and ex-smokers (10 months). The duration of DD (18 months) was longer in CD patients with extraintestinal manifestations than in those without (12 months). Regarding the biological treatment, CD patients who experienced multiple biologics and resistance had longer DD (24 months) than those who experienced biologic monotherapy and responded (12 months). Compared to patients who had not had surgery (12 months), DD was longer in CD patients who had undergone surgery (15 months). Conclusion Our study showed that ileal involvement, stenosing-penetrating behavior, perianal disease, current smoking and existing extraintestinal manifestations were connected with DD. DD was also associated with multiple biologic needed and surgery. DD may have a role a significantly increased risk of bowel damage.

P307 Novel proteomic analysis of 11,000 serum proteins distinguishes between Crohn’s disease and ulcerative colitis in pediatric patients

Abstract Background While the two main inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), share various clinical features, they differ in clinical, endoscopic and histological features, and may have different underlying etiopathological mechanisms, resulting in different treatment options. Consequently, the development of reliable, highly accurate, non-invasive biomarkers that differentiate CD and UC in pediatric IBD are an unmet need of paramount importance in terms of medical care, surgical intervention, and prognosis. The most advanced proteomics technology, the aptamer-based SomaScan, enables measurement of 11,000 biologically relevant proteins, including very low abundant proteins, and was tested to discover serum protein biomarkers capable of differentiating between pediatric CD and UC. Methods SomaScan (SomaLogic; Boulder, CO) quantitative serum protein profiles were generated from pediatric subjects diagnosed with CD (n=56) and UC (n=25) using standard diagnostic criteria. The disease location for patients with CD was 18 L1 (ileal), 9 L2 (colonic), 27 L3 (ileo-colonic) and 2 L4 (small bowel); Inflammatory phenotype (B1) occurred in 40, stricturing (B2) in 8, penetrating (B3) in 6, and B2B3 in 2. To develop highaccuracy predictors with the lowest number of proteins for discriminating CD from UC, we used machine learning and conditional logistic regression to calculate odds ratios(OR) and 95% confidence intervals(CI) per one standard deviation increase in protein levels. Area under the curve (AUC) was calculated to determine the performance of the multi-protein model in discriminating CD cases from UC cases. Ingenuity pathway analysis was conducted to identify pathophysiological pathway differences between CD and UC. Results There were 256 proteins that were discriminating between CD and UC with fold change >1.3 and an unadjusted p-value <0.05. Of these, 38 proteins were associated with increased odds and 218 proteins were associated with decreased odds of CD diagnosis. Compared to UC, CD cases had decreased neutrophil movement and degranulation, inflammatory response, and metabolism of reactive oxygen species but enhanced apoptosis. When we developed a multi-protein model and assessed its performance to discriminate CDs cases from UC cases, a 4-protein model showed an AUC=0.97. Conclusion Using the most comprehensive proteomics platform, we identified serum proteins and developed a high accuracy multi-protein model discriminating between pediatric CD and UC. The utility of SomaScan demonstrates not only the value of these diagnostic biomarkers, but also the potential to discover immune and metabolic pathways that distinguish CD from UC.

P670 Intestinal Motility Changes in Patients Undergoing Removable Stent Treatment for Focal Crohn’s Disease Strictures

Abstract Background Management and assessment of fibrostenotic Crohn’s disease(CD) is a research priority. Deep phenotyping is key for effective therapeutic development. In this study, we explore MRI assessed bowel motility before and after endoscopic stent treatment of focal fibrotic strictures in patients with CD. Methods Patients (n = 12, median age = 51 y) undergoing removable stent treatment were recruited as part of an approved study. Average CD diagnosis was 31y (range 16-57 y). All strictures were fibrotic in nature- three were de novo, while the remaining were anastomotic (ileocolonic). All patients had symptoms attributable to focal stricturing. Each patient had an MR – Enterography (MRE) scan (median 21 weeks) before and after (median 17 weeks) stent dilation. MR – Enterography (MRE) protocol included oral preparation, anatomical and cine ‘motility’ sequences across the abdomen in 20s breath hold (1 image/second). Motility sequences were processed with CE/FDA cleared GIQuant (Motilent, UK) to produce a quantitative map from which, objective data could be generated across the bowel. Stricture assessment was performed by a consultant radiologist. Non parametric statistics were used to investigate the following questions: 1. Was the baseline regional motility (mean, range) at stricture, dilation and morphologically normal bowel different across patients (Kruskal-Wallis)? 2. What were the changes in stricture motility pre and post stent placement (Wilcoxin Rank)? 3. Was stricture motility associated with stricture morphology (Spearman’s Rho)? Results 1. Motility at the stricture (126, range 62 to 139), pre-stenotic terminal ileum (252, range 80 to 478) and the global small bowel (269, range 166 to 339) was varied across the cohort (P < 0.001). 2. All patients had improvement in symptom scores & reporting, without change in stricture motility (P = 0.94). 3. A positive change in stricture motility was associated with reduced length of pre stricture dilatation (R = 0.64, P = 0.02) Conclusion Strictured intestine displayed reduced motility compared with adjacent bowel segments. While reduced, peristalsis was still present although paired analysis suggested no change pre and post stent stricture management. This implies that symptomatic relief was not related to altered peristalsis across the study. Finally, the length of dilation did appear to be associated with dynamic changes in stricture motility. In summary, as noted in stent-treated CD strictures, a dynamic physiological environment exists which can be captured with Cine MRI. These motility assessments, which have been studied as a proxy indicator of active CD, represent the first reported dynamic motility outcomes following stricture intervention.

P362 Mesenteric fat proliferation and fat edema in magnetic resonance enterography as predictor of long-term disease complications in Crohn’s disease

Abstract Background Fibrofatty proliferation of the mesenteric fat is a common finding in magnetic resonance enterography (MRE) in patients with Crohn’s disease (CD). Mesenteric fat is thought to play an active role in inflammation, fibrosis and stricture formation in CD. However, it is unclear whether these findings have a prognostic value in prediction of bowel damage and complications. We aimed to examine the association between mesenteric fat proliferation and inflammation on MRE and risk for hospital admissions and bowel surgery. Methods Patients with established CD diagnosis with at least 1 available MRE imaging data were followed for hospital admissions for CD exacerbation or abdominal surgery. MRE were reviewed by an expert radiologist for various characteristics (intestinal wall thickening and enhancement, stricture, or abscess formation, fibrofatty proliferation and fat edema reflecting fat inflammation). The association between mesenteric fat and outcomes was assessed using the Kaplan Meier method and log rank test. Crude and adjusted Hazard ratios (HR) with 95% confidence interval (CI) adjusting for baseline MRE characteristics (wall thickness and stricture and pre-stenotic dilatation) were estimated from the Cox proportional hazards regression model (R version 4.2.1). Results 159 CD patient charts and MRE imaging data were analyzed. Patients’ characteristics and medication exposure at described in table 1. On initial MRE the frequency of mesenteric fat proliferation was noted in 43 (27.0%) and fat edema in 79 (49.7%). Other MRE features noted were: mild, moderate and severe wall thickening in 72 (45.5%), 47 (29.9%) and 11 (7.0%) patients, respectively. Contrast intestinal wall enhancement was present in 122 (76.7%) patients. Intestinal stricture with pre-stenotic dilatation was noted in 17 (10.7%) patients and abscess and fistula formation was seen in 10 (6.3%) and 11 (6.9%) patients, respectively. During a mean (SD) follow up of 95.7 (39.5) months, 100 (62.9%) and 40 (25.2%) patients underwent hospitalization or surgery, respectively. On survival analysis, fat proliferation was associated with hospitalizations (Fig 1A, p=0.0005) and surgery (fig 1B, p<0.0001), while fat edema was associated with abdominal surgery (Fig 1D p=0.0003) but not with hospitalization (Fig 1C p=0.28). On multivariable analysis of the associations between fat proliferation and surgery and hospitalization remained highly significant (adjusted HR (95%CI) =3.15 (1.57-6.33) and adjusted HR (95%CI) =1.77 (1.06-2.97), respectively. Conclusion in this analysis of baseline MRE features, mesenteric fat proliferation was independently associated with increased risk for abdominal surgery and hospital admission for disease flares.

Upadacitinib (Rinvoq)


 CADTH recommends that public drug plans reimburse Rinvoq for the treatment of moderately to severely active Crohn disease (CD) if certain conditions are met.
 Rinvoq should only be covered to treat adult patients with moderately to severely active CD who do not respond to, stop responding to, or who cannot tolerate conventional or biologic therapies, provided that Rinvoq is covered for a similar patient population and in a similar way to biologic therapies currently reimbursed by public drug plans for the treatment of adult patients with moderately to severely active CD.
 Rinvoq should only be reimbursed if prescribed by a physician experienced in the diagnosis and management of CD, if it is not used in combination with biologics for CD, and if the cost of Rinvoq is reduced so that it does not cost the drug programs more than the least costly biologic therapy reimbursed for the treatment of moderately to severely active CD. Patients must respond to treatment in the first 12 weeks of starting Rinvoq to continue receiving the drug.

Prevalence and Clinical Relevance of Anti-FcεRI Autoantibody in Crohn's Disease.

Mast cells can be activated in various ways and were shown to be involved in the development of Crohn's disease (CD). The diagnosis of CD is still challenging, and seeking novel biomarkers is a worthwhile endeavor. An indirect enzyme-linked immunosorbent assay (ELISA) was successfully established for semi-quantitative detection of IgG anti-FcεRI in serum using human FcεRIα coated microplates and an enzyme-labeled anti-human IgG as secondary antibodies. The optimal working conditions were explored, followed by conducting the method evaluation. The serum samples and clinical data of 117 CD patients and 75 healthy controls were collected. IgE was measured by the rate turbidity turbidimetry; IgG anti-IgE and IgG anti-FcεRI were detected by ELISA. IgG anti-pancreatic antibody (PAB) and anti-Saccharomyces cerevisiae antibody (ASCA) were determined by indirect immunofluorescence assay. Data were analyzed concerning the clinical characteristics. IgG anti-FcεRI was an effective marker for CD (P < 0.001), but IgE and IgG anti-IgE (P = 0.089, 0.219, respectively) were not. There was a positive correlation between anti-IgE and anti-FcεRI (R = 0.380, P < 0.001). Anti-FcεRI positive patients behaved with higher disease activity [OR: 1.478 (1.200~1.821), P < 0.001], but were less likely to be located in L4 among Montreal classification [OR: 0.253 (0.077~0.837), P = 0.024]. Existing indicators, PAB and ASCA, behaved with high specificity (both > 95%) with low sensitivity (both < 30%). The combination of anti-FcεRI with existing markers significantly improved the diagnostic efficiency [AUC: 0.879 (0.831~0.928)]. An ELISA for the detection of anti-FcεRI was established and validated, which may contribute to facilitating research on Crohn's diseases. Anti-FcεRI positive CD patients were associated with higher disease activity indices, suggesting its potential value in the diagnosis and management of CD.

A Machine Learning Method for Differentiation Crohn's Disease and Intestinal Tuberculosis.

Whether machine learning (ML) can assist in the diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB) remains to be explored. We collected clinical data from 241 patients, and 51 parameters were included. SixML methods were tested, including logistic regression, decision tree, k-nearest neighbor, multinomial NB, multilayer perceptron, and XGBoost. SHAP and LIME were subsequently introduced as interpretability methods. The ML model was tested in a real-world clinical practice and compared with a multidisciplinary team (MDT) meeting. XGBoost displays the best performance among the six ML models. The diagnostic AUROC and the accuracy of XGBoost were 0.946 and 0.884, respectively. The top three clinical features affecting our ML model's result prediction were T-spot, pulmonarytuberculosis, and onset age. The ML model's accuracy, sensitivity, and specificity in clinical practice were 0.860, 0.833, and 0.871, respectively. The agreement rate and kappa coefficient of the ML and MDT methods were 90.7% and 0.780, respectively (P<0.001). We developed an ML model based on XGBoost. The ML model could provideeffective and efficient differential diagnoses of ITB and CD with diagnosticbases. The ML model performs well in real-world clinical practice, and the agreement between the ML model and MDT is strong.

Isolated nonspecific terminal ileitis: prevalence, clinical evolution and correlation with metachronous diagnosis of Crohn's disease: a retrospective study and review of the literature.

The existing literature does not provide adequate guidance on the diagnosis and management of patients with nonspecific terminal ileitis, while data regarding the percentage of patients who ultimately develop Crohn's disease (CD) are scarce. We evaluated the prevalence and natural course of nonspecific terminal ileitis in patients who underwent colonoscopy during a 11-year period. All patients with endoscopic findings of terminal ileitis and nonspecific histological findings were included. Exclusion criteria were a clinical history of CD or any other disease that can cause terminal ileitis, or a recent history of using drugs implicated in lesions of the terminal ileum. From 5353 colonoscopies, 92 patients with nonspecific terminal ileitis were identified (prevalence: 1.7%). Among these patients, 56 (61%) had available follow up for ≥6 months after the initial endoscopy. Main indications for endoscopy were chronic diarrhea (37.5%), screening endoscopy (23%), and abdominal pain (20%). Sixteen (29%) patients received medical treatment, while recession of symptoms was recorded in 19 of 43 symptomatic patients (44.1%). Twenty-three (41%) of the 56 patients underwent a second endoscopy and 15 (65.2%) cases had persistent endoscopic findings. Eleven (19.6%) of the 56 patients were eventually diagnosed with CD. The probability of CD diagnosis was significantly higher in patients with persistent symptoms (P=0.002) and endoscopic findings at follow up (P=0.038). Nonspecific terminal ileitis generally has a benign clinical course. However, patients with persistent symptoms and endoscopic lesions are at increased risk for subsequent development of CD.

Pediatrik İnflamatuar Bağırsak Hastalıklarının Tanısında ve Ayrımında Manyetik Rezonans Enterografinin Rolü

Background/Aims: Inflammatory bowel diseases (IBD) are of two types: Crohn’s disease (CD) and ulcerative colitis (UC). The differential diagnosis of these two diseases is important because their treatment strategies are different. The present study aimed to evaluate the Magnetic Resonance Enterography (MRE) findings of pediatric patients who were clinically diagnosed with CD or UC. Material and Method: The patients under the age of 18, who underwent MRE examination, were retrospectively screened. Fifty five of those patients, who were clinically diagnosed with CD or UC, were included in the study. Bowel wall thickening, mesenteric fat tissue changes and complications were evaluated, and the findings were recorded. The sensitivity and specificity of MRE in the diagnosis of CD and UC in IBD patients were calculated. Results: Three of the patients clinically diagnosed with CD (7.3%) and six patients who had UC (42.9%) had involvement from the rectum to the proximal colonic segments (continuous lesions). Of those diagnosed with CD, 11 (26.8%) had skip lesions. In patients with IBD, the sensitivity of MRE for the diagnosis of CD was 56.1% and the specifity was 100%. The sensitivity of MRE for the diagnosis of UC was 42.9% and the specificity was 90.2%. Conclusion: MRE is helpful to identify the signs and complications of inflammatory bowel diseases. Although MRE has low sensitivity to differentiate between CD or UC in pediatric patients, it may help with its high specificity rates.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

The long-term effect on surgery-free survival of biological compared to conventional therapy in Crohn’s disease in real world-data: a retrospective study

BackgroundThe introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term.This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn’s disease (CD) who were never with the surgical option.MethodsThis is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L’Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population.ResultsTwo hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01–8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69–6.44).ConclusionThis study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

Identifying risk factors of anti-TNF induced skin lesions and other adverse events in paediatric patients with inflammatory bowel disease.

While higher infliximab (IFX) trough concentrations (TCs) are associated with better outcomes in patients with inflammatory bowel disease (IBD), they could pose a risk for adverse events (AEs), including IFX-induced skin lesions. Therefore, we studied correlations between IFX TCs and occurrence of AEs in paediatric IBD patients. In this single-centre study, all children with Crohn's disease (CD) and ulcerative colitis (UC) receiving IFX maintenance therapy who underwent proactive drug monitoring between March 2015 and August 2022 were included. IFX doses/intervals/TCs and patient characteristics were systematically registered, as well as AEs and skin lesions appearance. A total of 109 patients (72 CD and 37 UC) contributed 2913 IFX TCs. During a median follow-up of 3.0 [1.5-4.5] years, we observed 684 AEs in 101 patients and 49 skin lesions in 35 patients. There was no significant difference (p = .467) in median TCs between patients with and without skin lesions. However, higher median IFX doses were associated with an increased hazard rate of skin lesions [HR 1.084 (1.024-1.148), p = .005], in addition to female sex [2.210 (1.187-5.310), p = .016] and diagnosis of CD [1.695 (1.241-1.877), p = .011]. Considering IFX therapeutic TC cut-offs of 5.0 and 9.0 µg/mL, there was no significant difference in AE rate (p = .749 and p = .833, respectively). Also, no significant association between IFX doses and AE rate (p = .159). Increasing the IFX dose to achieve therapeutic TCs may not increase the overall risk of AEs in paediatric IBD patients. However, concerns arise regarding the risk of skin lesions, especially in female CD patients.

COMPARATIVE CHARACTERISTICS OF DIFFERENT TYPES OF INFLAMMATORY BOWEL DISEASE IN CHILDREN

Background. Inflammatory bowel disease (IBD) is a group of idiopathic, chronic, relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC), Crohn's disease (CD), and unspecified colitis (UnC). Objective. To provide a comparative characteristic of clinical and laboratory features of various IBD types in children according to the morphology, and to identify clinical and laboratory markers of unspecified colitis in children. Material and methods. 118 pediatric patients diagnosed with chronic inflammatory bowel disease were observed. Statistical processing of clinical and laboratory data was carried out using the statistical package R, version 4.1. Results. A comprehensive examination revealed 36 patients with Crohn's disease (CD), 54 those with ulcerative colitis (UC), and 28 with UnC. It was found out that in patients diagnosed with unspecified colitis, clinical manifestations were statistically more often observed at an earlier age (28,5 months [8; 50]) in contrast to children with UC (31 months [14; 122]) and CD patients (96 months [34,5;132]) (p=0,004). All patients with IBD had significant changes in stool frequency (from 3 to 9 or more times per day), 45 (83.3%) patients with UC having blood in stool (p &lt;0.001). Pain syndrome was less common in patients diagnosed with UnC – 22 (78,6%) (p=0,048). The two clinical and laboratory symptoms were significantly more often observed in the group of patients with UC: protein-energy malnutrition (PEM) – 24 (44,4%)(p=0.008) and anemia – 39 (72,2%) (p&lt;0.001). Patients diagnosed with UnC had a lower platelet count (292±68) (p=0.005). CD patients had a lower mean relative lymphocyte count (30,8%) (p=0.005). The level of C-reactive protein (CRP) was significantly more often elevated in patients with UC – 30 (55,6%) (p=0,005). Conclusions. Though standard methods used for examining patients with IBD allow us to establish the diagnoses of UC and CD, such examination is not sufficient for children with UnC. It is necessary to include new molecular genetic criteria in the examination protocol for patients with IBD, which will make it possible to offer appropriate treatment at an early stage of the disease.