Diagnosis Of CD Research Articles

P0367 A Clustering approach to discriminate slow and rapid biologics switchers in difficult-to-treat Crohn’s Disease patients

Abstract Background CD patients exhibit highly variable responses to biologics. While some patients achieve sustained remission with only one biologic over the course of their disease, other will require the sequencing of multiple biologics (“difficult-to-treat” patients) for optimal disease control. The aim of this study was to delineate the profile of treatment regimen of the biological exposed CD patients with luminal disease. Methods Among CD patients diagnosed between 1999 and 2019 with B1 phenotype at diagnosis, 203 patients who maintained this phenotype at maximum follow-up (FU, median 11y [8–15]) were selected, based on inclusion criteria. All events were recorded from date of diagnosis to maximum FU, from disease characteristics to treatment adaptations. A temporal clustering approach using k-means was applied to determine biologics treatment regimen profiles. Patient profiles were compared using the Dynamic Time Warping (DTW) similarity measure, considering 3 successive cumulative biologic exposures (for primary/secondary non response only). Clusters number was chosen to balance maximizing silhouette score while ensuring sufficient individuals per cluster. Cumulative biologic exposures were summarized as cluster profiles, represented by their corresponding barycenters computed with soft-DTW distance. Clustering approach was performed using Python (tslearn). Results The 203 patients were clustered in 5 distinct profiles, based on their cumulative biologics exposure in the first 10 years after CD diagnosis (Figure 1). Patients in Cluster 1 were not exposed to biologics (n=55). Patients in Cluster 2 were treated late with one biologic (n=51) while patients in Cluster 3 were treated early with one biologic (n=53). Patients from Cluster 4 (n=23) and Cluster 5 (n=21) were both treated early with multiple biologics. Patients from Cluster 2 were exposed to biologics later after CD diagnosis than patients from Cluster 3 to 5 (Median 5.7y [3.6–6.9] vs 0.7y [0.2-1.8], p<0.0001), as also shown by their lower biological exposure compared to those of Cluster 3 to 5 (median 48% [37-58] vs 80% [60-89], p<0.0001). Most interestingly, patients from Cluster 5 required faster biologics changes compared to patients from Cluster 4 (Figure 2). In Cluster 5 (rapid switchers), patients were exposed earlier compared to patients in Cluster 4 (Slow Switchers) to the first (p<0.005), second (P<0.005) and third biologic (p=0.01), introducing the concept of rapid and slow biologic switchers among CD patients. Conclusion This clustering approach highlights the highly variable pattern of response to biologics in luminal CD patients. Furthermore, this study discriminatessingle and multiple biologics-exposed patients, in whom we identified slow and rapid biologic switchers.

P0915 Real-life experience with Upadacitinib in Crohn’s disease (UPARECOL-CD Induction): A Colombian cohort

Abstract Background In Latin America, clinical experience with Upadacitinib for CD in terms of effectiveness and safety is limited. In Colombia, CD is an orphan disease and in many cases is highly refractory to conventional treatments. The objective of this study is to describe the real-life experience in Colombian patients with CD treated with Upadacitinib. Methods Descriptive observational study, patients with CD treated with Upadacitinib in induction phase (45 mg orally once a day for 12 weeks) in different reference centers nationwide. The therapeutic response was evaluated in endoscopic and/or imaging, paraclinical and clinical terms (CDAI). Additionally, the frequency of adverse events (AE), steroid use and extraintestinal manifestations (EIM) were measured. Results 10 patients, 5/10 (50%) female, mean age 43.15 years (SD; 22.7 range 14.2-21.3). Mean age at diagnosis of CD 37.7 (SD 23.15) years (range 6.9-67.5). Mean time between disease onset and start of Upadacitinib 3.33 (SD 8.17) years (range 0.1-15.9). Most patients had moderate to severe CD; 7/10 (70%) patients with ileocolonic disease and 3 (30%) with ileal disease. 5 patients with stricturing disease and 3 patients with active penetrating disease. All patients had previously failed tumor necrosis factor inhibitors, 8/10 (80%) had failed integrin alpha4 beta7 inhibitors (Vedolizumab). Six patients had EIM. Six patients had a history of surgery for CD. Additionally, 4/10 (40%) patients were using a steroid before starting Upadacitinib and 6/10 (60%) patients were using an immunomodulator. During the induction phase, 7/10 (70%) achieved clinical response, 2/10 (20%) clinical remission, and 5/10 (50%) paraclinical remission. 4/6 (66.6%) patients achieved improvement in imaging findings. All patients with EIM showed improvement of EIM. 2/5 (40%) patients showed improvement of perianal disease. Only one patient required surgery for CD. 3/4 (75%) were able to discontinue corticosteroid and 1/4 (25%) achieved steroid dose reduction. One patient required discontinuation of Upadacitinib, due to lack of response and severe sepsis. One patient reported acne after induction. No other AEs were reported. Conclusion Upadacitinib is an effective option for patients with CD with inflammatory, stenosing and penetrating phenotypes refractory to multiple treatments, suggesting a reduced requirement for surgical procedures. Long-term real-life studies are needed to determine whether there is persistence of response in maintenance.

P0401 The IBD-disk accurately assesses disability and psychological burden at IBD diagnosis and predicts adverse outcomes in both UC and Crohn’s disease during the first year of treatment

Abstract Background Inflammatory bowel disease (IBD) is linked with increased prevalence of mental health diseases (MHD), particularly anxiety and depression. How this influences treatment outcomes is poorly studied at IBD diagnosis. The IBD disk is a patient-reported outcome measure that quantifies disease-associated disability. We aimed to determine if the disk can be used pre-diagnosis to screen for mental health symptoms and predict treatment outcomes. Methods Patients with suspected IBD were seen in a rapid-access clinic. An IBD disk was completed upon review, pre-diagnosis. A subgroup simultaneously completed the Hospital Anxiety and Depression scale (HADS). Repeat disks were completed after diagnosis, with 12-month outcomes collected prospectively. Results 188 patients completed a baseline disk (97 Crohn’s disease [CD], 91 Ulcerative colitis [UC]), 95 completed a simultaneous HADS and 82 completed a repeat disk. Both a pre-existing MHD diagnosis (CD 22%, UC 11%, X2 p=0.049) and an active anti-depressant prescription (CD 16%, UC 7%, X2 p=0.035) were more common at CD diagnosis than UC. The ‘Emotions’ domain correlated with HADS depression (rs=0.607 p<.001), anxiety (rs=0.586 p<.001) and reliably identified HADS defined moderate-severe depression (Area under the curve 0.873). A score ≥7 identified all patients meeting this HADS threshold (Sensitivity 100%, specificity 60.5%, Youden’s index 0.601). This is shown in Figure 1. Whilst the IBD Disk did not outperform traditional disease severity indices, elevated baseline disk scores in UC predicted the subsequent need for advanced therapies (p=0.019), persistent active disease at 12 months (p=0.023) and need for inpatient treatment (p<.001). In CD, elevated disk scores predicted need for advanced therapies (p=0.014), persistent active disease (p=0.015) and showed a weak association with the need for surgical resection within 12 months (p=0.064). These results are summarised in Table 1. After diagnosis and treatment, ongoing disability and psychological symptoms were driven by disease activity. In both UC and CD, the ‘Emotions’ domain fell significantly in those in remission at first follow-up (CD p<.001; UC p=0.008) but was unchanged when the disease remained active (CD p=0.71; UC p=0.72). Conclusion The IBD disk reliably screens for symptoms of depression and anxiety and identifies risk of adverse treatment outcomes at IBD presentation. Its use in the outpatient setting can support holistic disease assessment and identify those who are most likely to benefit from additional psychological support. Moreover, particularly in UC patients, elevated baseline IBD disk scores should prompt the consideration of treatment escalation early in the disease course.

P0511 Establishing a gastroenterologist-led intestinal ultrasound service in the United Kingdom: outcomes, correlation and patient satisfaction

Abstract Background Intestinal ultrasound (IUS) has been used a tool for assessing IBD in Europe over the preceding decades. Its use globally is increasing. Russells Hall Hospital has one of the first gastroenterologist-led services in the UK. IUS is a non-invasive tool for assessing IBD and potentially reduces the requirement for endoscopy and imaging. It reduces the requirement for multiple patient visits; giving a point-of-care assessment of IBD activity, gastroenterologist review and a management plan in one session. A study by a tertiary UK centre showed projected annual savings of almost £500,000 with the implementation of radiologist-led IUS in their centre. Methods To validate our accuracy of diagnosis at IUS, the first 50 patients assessed were offered IUS in addition to endoscopy and/or MRE. This data was collated and our accuracy assessed. We also provided patients with questionnaires, outlining their experience and satisfaction with IUS. Results 45 patients underwent assessment with IUS and either endoscopy or MRE. 28 (62.2%) were male, with an average age of 44 years. 17 patients had UC (37.8%) and 28 CD (62.2%). The median time to assessment with a second modality was 10 days (0-367 days). 86.7% of patients had IUS first. 18 patients had flexible sigmoidoscopy, 17 colonoscopy and 9 MRE. We showed a correlation of 86.7% between IUS and second modality. Notably, accuracy improved with time as the first 4 of 6 patients without correlation were within the first three months of IUS implementation. Notably, four patients with normal IUS had very mild disease activity at endoscopy with isolated ileal/neo-TI disease (Rutgeert’s i2a) or small aphthae in the left colon. Of patients with an abnormal IUS and normal subsequent assessment, one had a full course of prednisolone between IUS and MRE. From a patient satisfaction perspective, 40 patients completed surveys, with an equal gender split. 85.7% of patients had a CD diagnosis. 64.3% of patients were not aware of IUS prior to their visit. 92.9% found IUS “very easy”. 85.7%, 78.6%, 92.9% and 100% found it “very easy” compared to blood tests, stool tests, MRE and endoscopy, respectively. All patients would have a repeat IUS and 85.7% were extremely satisfied with having an IUS to assess their IBD. Conclusion Gastroenterologist-led IUS is a non-invasive and accurate modality for assessing IBD in the UK population. With increasing experience, we improved our accuracy, in keeping with published data and can offer patients IUS as a single modality for monitoring their IBD, potentially offering cost savings for our trust. Overall, patients were extremely satisfied with the service and found it much easier than routine methods of monitoring IBD.

P0286 Assessment of clinical predictive factors for the development of short bowel syndrome in a cohort of patients with Crohn’s disease

Abstract Background Short bowel syndrome(SBS)is a severe clinical condition occuring when,following multiple intestinal resections,the remaining small bowel in continuity is ≤200cm.SBS is associated with intestinal failure(IF)when the intestinal absorptive function is compromised,requiring intravenous nutritional or electrolyte supplementation.Crohn’s disease(CD)is one of adults’ most frequent causes of SBS.The aim of this study was to identify clinical predictive factors of SBS in CD pts Methods We performed a prospective study, enrolling consecutive CD outpatients (pts).Statistical univariate comparison for primary outcome was assessed for continuous variables by the Mann-Whitney U test and the Kruskal-Wallis ANOVA test.Categorical variables were compared using the chi-square test.We also assessed a multivariate logistic regression model to identify independent predictors of SBS Results We enrolled 169 CD pts(47.3% male,mean age 43.5 years[±14.1]).45.5% of them were smokers;extraintestinal manifestations(EIMs)were present in 45.5% of pts, and 67.5% of pts had bowel resections(26.6% of them with more than one surgical intervention).Median disease duration and median time between diagnosis and the first resection were 9y(IQR 4-17)and 6.5y(IQR 1-13),respectively.At baseline,101 pts were on anti-TNF therapy,and considering the course of the disease,overall,20.1% of the pts were exposed to ≥3 biologics.10% of pts had SBS and 5.3% IF.In univariate analysis,comparing patients with and without SBS,the following variables were statistically different:disease duration(p=0.000),upper gastrointestinal disease location(p=0.001),ileocolonic location(p=0.008),stenosing behavior(p=0.040),perianal disease(p=0.000)and time elapsing from CD diagnosis to start biological therapy(0.002).At multivariate analysis,disease duration(p=0.000),perianal disease(p=0.05)and time elapsing from CD diagnosis to start biological therapy(p=0.016)resulted independently associated with the development of SBS Conclusion Our data identify the clinical features that would allow the gastroenterologists to predict the risk of developing SBS in a cohort of CD pts.Further studies would be needed to confirm our findings.Funded by:2.1 “Rafforzamento e potenziamento della ricerca biomedica del SSN”,finanziato dall’Unione europea–NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project “Changing the future of intestinal failure in intestinal chronic inflammation:towards innovative predictive factors and therapeutic targets”code:PNRR-MAD-2022-12376791

Anthropometric Trajectories in Children Prior to Development of Inflammatory Bowel Disease

Poor nutrition and growth in childhood have short-term and long-term consequences, so understanding the timing of the onset of an impaired nutritional status is crucial for diagnosing and treating inflammatory bowel disease (IBD) at its earliest stage. To assess anthropometric trajectories before a pediatric diagnosis of IBD and growth recovery after diagnosis. This population-based cohort study included children born in Denmark from January 1, 1997, through December 31, 2015, with weight and length or height measurements at birth and at least 1 length or height and weight measurement at school age based on the Danish Medical Birth Register and the Danish National Child Health Register. Within this population, all individuals diagnosed with IBD at ages 5 to 17 years, according to the Danish National Patient Register, were identified. Data were analyzed from October 13, 2023, to April 17, 2024. A pediatric diagnosis of IBD compared with the corresponding population without the disease. The outcome measures were z scores for length or height, weight, and body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) before and after pediatric IBD diagnosis compared with reference and sibling populations. The final study population included 916 133 individuals (51.2% male) with a median of 3 pairs of length or height and weight measurements collected (IQR, 2-6 pairs). Of those, 1522 (median age, 14.3 years [IQR, 11.8-16.3 years]; 763 female [50.1%]) were diagnosed with IBD (851 [55.9%] with Crohn disease [CD] and 671 [44.1%] with ulcerative colitis [UC]). Compared with children without IBD, individuals with a later diagnosis of CD had declining anthropometric measures 3 years (weight: mean, -0.12 g [95% CI, -0.20 to -0.03 g]; BMI: mean, -0.13 [95% CI, -0.21 to -0.04]) and 1 year (length or height: mean, -0.20 cm [95% CI, -0.29 to -0.10 cm]) prior to diagnosis, whereas this was observed 1 year prior to a diagnosis of UC for weight (mean, -0.12 g [95% CI, -0.22 to -0.02 g]) and BMI (mean, -0.13 [95% CI, -0.23 to -0.03]). Deviating anthropometric patterns persisted after diagnosis, with the slowest recovery observed in children with CD. The findings of this large-scale population-based cohort study of anthropometrics in children suggest impaired nutritional status as assessed by weight up to 3 years and by length or height 1 year before a diagnosis of CD and by weight up to 1 year before a diagnosis of UC. These findings emphasize that the onset of pediatric IBD may occur years prior to diagnosis, that growth recovery may first occur after diagnosis and treatment, and that frequent nutritional screenings may help ensure a healthy transition to adulthood.

Cadmium availability in rhizosphere and non-rhizosphere soils in cacao farms in Santander, Colombia

Current research has highlighted the need to understand the factors influencing cadmium (Cd) availability in cacao-growing soils to elucidate its presence in cacao beans (the raw material for chocolate). Although literature about this topic is increasing, few report the importance of rhizosphere soils on Cd dynamics. This study aimed to understand the changes in available Cd and its association with soil properties (pH, pseudo-total Cd, available Cd (Cd-DTPA), Ca, Mg, K, Na, soil organic carbon, P, Zn, urease activity, exchangeable acidity, and cation exchange capacity) considering rhizosphere and non-rhizosphere soils. Both soil types (51 samples of each, 102 in total) were collected from two Colombian cacao farms. The medians of pseudo-total Cd (1.86 mg kg−1) and Cd-DTPA (0.76 mg kg−1) were, respectively, about threefold and fourfold higher in rhizosphere compared to non-rhizosphere soils. Principal component analysis showed a clear distinction between rhizosphere and non-rhizosphere soils based on differences in soil properties, which explained the observed changes in available Cd when comparing both soil types. Soil organic carbon and Zn were important drivers of available Cd in rhizosphere soils. Spatial distribution analysis revealed a tendency of available Cd to cluster in rhizosphere soils, and indicated hotspots within each farm. These findings highlight the importance of rhizosphere soils for Cd diagnosis and monitoring, and for improving knowledge about Cd dynamics in the soil-Theobroma cacao L. system.

Prevalence of celiac disease-specific antibodies and their association with clinical status and environmental factors

Background and aimsCeliac disease (CeD) affects 1–2% of the world's population. The aim of this study was to relate the incidence of CeD-related serological markers to symptoms, pathologies, and environmental exposure to wheat flour, given the number of flour mills present in the region. Materials & methodsSerum samples were collected from 537 inhabitants from a rural city. Levels of anti-transglutaminase (a-tTg), anti-gliadin, anti-DGP antibodies and total IgA levels were measured. Volunteers completed a questionnaire covering environmental factors, demographics, pregnancies, other diseases, symptoms, and CeD diagnosis. Geo-referencing of volunteers' homes and mills in the city was performed, and correlations between the different parameters assessed were analysed. ResultsA CeD incidence of 1.76 % was found. However, a-tTg and a-gliadin levels were elevated in the population without CeD diagnosis (9.6 % and 30.1 %). Subjects with CD diagnosis showed diarrhoea and colic pain. Women with CeD had fewer pregnancies. Positive a-tTg and number of CeD-associated symptoms appear to correlate with proximity to flour mills. ConclusionA high prevalence of CeD-related specific antibody positivity in a rural population was found, possibly due to environmental factors related to flour mills. Further research is needed to better understand CeD's pathogenesis and its health implications.

Point-of-care ultrasound of the inflammatory bowel disease

Background. The widespread use of portable ultrasound scanners has advanced the concept of ultrasound diagnosis (POCUS), namely «ultrasound examination (US) is performed at the bedside and is interpreted directly by a physician». Pocus is not a substitute for complex ultrasound, but rather allows the ultrasound doctor to quickly access clinical images for rapid diagnosis and effective examination and treatment of patients. Purpose – the work to identify ultrasound signs of inflammatory bowel disease (IBD) using POCUS. Materials and Methods. 70 patients aged 18 to 39 years (24 men and 46 women, mean age – 30.3 ± 13.7 years). The first group of patients included 32 people with a morphologically confirmed CD diagnosis, the second group included 38 people with a morphologically confirmed UC diagnosis. The control group consisted of 2 8 patients with no clinical and laboratory data on gastrointestinal lesions. Results. It was shown that the ultrasound can assess the thickness of the intestinal wall with sensitivity – 90.3% and specificity – 87.1% and ROC – 0.882, differentiation of the wall layers, surrounding structures (omentum, mesentery, lymph nodes), as well as the localization of the affected intestinal segment. Color Doppler Mapping (CDM) method with a sensitivity of 86.5% and specificity of 81.5% and ROC of 0.852 allows not only to assume the presence of active inflammation in the wall of the affected intestinal segment, but also to monitor the dynamics of the process during treatment. Conclusion. In this work, the capabilities of POCUS for the diagnosis of IBD were evaluated. Correct and accurate interpretation of POCUS findings is not only an important diagnostic step, but also a complement to other radiation and endoscopic imaging techniques. The main advantage of POCUS over CT and MRI is its fast availability, low cost, and high level of safety. An experienced ultrasound doctor is needed to examine the gastrointestinal tract, so training with ultrasound doctors and mastering practical skills is key to ensuring the effective use of POCUS.

Efficacy of Vaccination and Revaccination Against Hepatitis B Virus Using 2 Different Strategies in Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) exhibit an increased risk for acquiring hepatitis B virus (HBV), thus they should be vaccinated preferably, if not already infected or immunized. We assessed the efficacy of HBV vaccination in IBD patients and impact of different factors on the immune response. We also evaluated the success rate of 2 different revaccination strategies in the nonresponders. This was a retrospective observational cohort study carried out in 5 tertiary centers. All patients were tested for hepatitis B surface antigen, antibodies against hepatitis B surface antigen (anti-HBs), and antibodies against hepatitis B core antigen. Patients tested negative and underwent the standard schedule with 20 µg at 0, 1, and 6 months. Nonresponders (anti-HBs <10 IU/L) were offered a revaccination scheme with either 3 doses of 40 µg at 0, 1, and 6 months or an accelerated scheme with 20 µg at 0, 1, and 2 months. A total of 409 patients were included, and 273 (66.7%) of those (females: 49.5%; Crohn's disease [CD]: 56.7%) responded to baseline vaccination. A total of 189 (69.2%) of 273 (females: 48.1%; CD: 60.3%) developed anti-HBs >100 IU/L. Body mass index <30kg/m2 (P = .017) was positively associated, while diagnosis of CD (P = .013), extensive UC (P <.0001), extraintestinal manifestations (P = .001), and treatment with immunomodulators/anti-tumor necrosis factor (P < .00) negatively affected the response. Revaccination was offered to 103 patients, and 58.3% of them achieved anti-HBs >10 IU/L. Both revaccination strategies were equally effective. IBD patients demonstrate lower response to HBV vaccination compared with the general population. Age, body mass index, type, disease activity, and immunosuppression negatively affect the response. Half of nonresponders may benefit from an enhanced revaccination attempt.

Evaluation of chimeric recombinant antigens for the serodiagnosis of Trypanosoma cruzi in dogs: a promising tool for Chagas disease surveillance

BackgroundChagas disease (CD), a neglected parasitic disease caused by Trypanosoma cruzi, poses a significant health threat in Latin America and has emerged globally because of human migration. Trypanosoma cruzi infects humans and over 100 other mammalian species, including dogs, which are important sentinels for assessing the risk of human infection. Nonetheless, the serodiagnosis of T. cruzi in dogs is still impaired by the absence of commercial tests. In this study, we investigated the diagnostic accuracy of four chimeric recombinant T. cruzi IBMP antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) for detecting anti-T. cruzi antibodies in dogs, using latent class analysis (LCA).Methods We examined 663 canine serum samples, employing indirect ELISA with the chimeric antigens. LCA was utilized to establish a latent variable as a gold standard for T. cruzi infection, revealing distinct response patterns for each antigen.Results The IBMP (Portuguese acronym for the Molecular Biology Institute of Paraná) antigens achieved area under the ROC curve (AUC) values ranging from 90.9% to 97.3%. The highest sensitivity was attributed to IBMP-8.2 (89.8%), while IBMP-8.1, IBMP-8.3, and IBMP-8.4 achieved 73.5%, 79.6%, and 85.7%, respectively. The highest specificity was observed for IBMP-8.4 (98.6%), followed by IBMP-8.2, IBMP-8.3, and IBMP-8.1 with specificities of 98.3%, 94.4%, and 92.7%, respectively. Predictive values varied according to prevalence, indicating higher effectiveness in endemic settings.Conclusions Our findings underscore the remarkable diagnostic performance of IBMP-8.2 and IBMP-8.4 for the serodiagnosis of Trypanosoma cruzi in dogs, representing a promising tool for the diagnosis of CD in dogs. These chimeric recombinant antigens may not only enhance CD surveillance strategies but also hold broader implications for public health, contributing to the global fight against this neglected tropical disease.Graphical

Transmural cross-sectional findings and bowel damage assessment in preclinical Crohn’s disease: a case-control study

PurposeCrohn’s disease (CD) is a progressive disorder leading to cumulative bowel damage. The Lémann index is a validated tool that can help in monitoring the progression of the disease and evaluating the effectiveness of different therapies. Our aim was to describe the main radiological findings in incidentally diagnosed CD and to evaluate bowel damage in this subgroup compared to patients diagnosed at later stages.MethodsPatients with an incidental diagnosis of CD during the colorectal cancer screening program were compared to controls with a CD cohort diagnosed after symptomatic onset and matched 1:1 by disease extent. All cross-sectional examinations were centrally read, performing a descriptive analysis of the main findings and calculation of Lémann index.ResultsThirty-eight patients were included: 19 with preclinical CD (median age 55 years (IQR, 54–62), 53% male, 74% non-smokers; 74% B1 and 26% B2) and 19 matched-controls with symptomatic CD. In those with preclinical CD, the most frequent transmural findings on MRE were contrast enhancement (79%), wall thickening (79%), followed by lymphadenopathy (68%), edema (42%), and increased vascularity (42%). Among those with strictures, controls showed a higher rate of preestenotic dilation (100% vs. 0%, p = 0.01). Bowel damage assessment revealed no statistically significant differences in the Lémann index between preclinical CD and controls (p = 0.95). A statistically significant higher score in the colonic/rectum score was observed (p = 0.014).ConclusionPatients with preclinical CD demonstrate similar radiological findings and degree of bowel damage as new-onset symptomatic CD.

Increased Risk of Herpes Zoster Infection in Patients with Celiac Disease 50 Years Old and Older

BackgroundCeliac Disease (CD) is associated with increased susceptibility to certain bacterial and viral infections. Herpes zoster (HZ) is a viral infection that can be prevented by immunization. In the US, the vaccine is recommended for adults ≥ 50 or ≥ 19 with certain at-risk conditions, not including CD.AimsWe aimed to determine if adult patients aged < 50 or ≥ 50 years with CD had a higher risk of developing HZ.MethodsWe designed a retrospective cohort study. CD was defined as patients with the ICD-10 code for CD and positive Celiac serology. Patients with negative serology and lacking CD ICD-10 codes served as controls. Patients who had HZ before CD diagnosis were excluded. We formed two sub-cohorts, those aged < 50 (cohort 1) and aged ≥ 50 years (cohort 2), and evaluated HZ infection at 10-year follow-up. To account for confounding variables, we performed 1:1 propensity score matching (PSM).ResultsFollowing PSM, cohort 1 had 6,826 CD patients, and cohort 2 had 5,337 CD patients and respective matched controls. After ten years of follow-up, in cohort 1, 62 CD patients developed HZ versus 57 controls, RR: 1.09 (CI: 0.76–1.56, p-value = 0.64). In cohort 2, 200 CD patients developed HZ versus 159 controls, RR: 1.2 (CI: 1.02–1.54, p-value = 0.03).ConclusionThere was no significant difference in the likelihood of getting HZ in CD patients < 50, although CD patients ≥ 50 had a modestly increased risk. Our findings do not support routine early vaccination for HZ in CD, and the vaccine should be offered at age 50.

Efficacy of ferric carboxymaltose therapy in celiac patients

Aims: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA can be caused by reduced iron intake, impaired iron absorption or losses. Celiac disease can cause iron malabsorption by decreasing the surface absorption area in the duodenum and consequently can cause IDA. Oral or intravenous iron preparations are used in the treatment of IDA. In this study, we wanted to investigate the efficacy of ferric carboxymaltose (FCM) in celiac patients with RIA. Methods: Twenty-three patients who were followed up in the gastroenterology outpatient clinic of İnönü University Medical Faculty Hospital Turgut Özal Medical Center with the diagnosis of CD and who received FCM were included in the study. The hemogram, ferritin, iron and iron binding levels of the patients were retrospectively screened through the hospital medical record system. Results: Of the 23 patients included in the study, 3 (13.05%) were male and 20 (86.95%) were female. Hemoglobin concentration, iron and iron binding capacity before and after treatment showed a significant increase in all parameters after treatment. Ferritin value increased, although not significantly. Conclusion: In our study, we found that FCM is an effective and safe treatment modality in the treatment of IDA in celiac patients.

Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: a Mendelian randomization study.

The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated. Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren's syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn's disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships. There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings. There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.

Risk factors for surgery in stricturing small bowel Crohn's disease: A retrospective cohort study from the GETAID pédiatrique.

Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received before stricture diagnosis includedMODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection wereantibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.

Celiac Disease Review: Background and Emphasis on the Important Role of Health Education in the Prevention and Control of Symptom

Celiac disease is related to dietary gluten found in wheat, rye, and barley, CD is an immune-mediated enteropathy and it is one of the most prevalent lifelong food-related illnesses globally. In addition, CD is also thought to be a systemic ailment marked by a variety of gluten-related signs and symptoms as well as disease-specific antibodies. When gluten is consumed, it produces toxic gluten peptides that can trigger both innate and adaptive immune responses in people who are predisposed to them. The transglutaminase enzyme plays a role in the development of the situation by deaminating gluten to produce glutamic acid. Furthermore, the peptidase enzyme finds it difficult to break down the prolamin component of gluten, which is high in proline and glutamine. This leads to incomplete protein digestion and the creation of peptides that trigger the immunological response. Moreover, CD causes remarkable damage to the small intestinal mucosa in the jejunum, resulting in inflammation of the villi and villous atrophy, which hinders the absorption of nutrients. Combining small intestine mucosal histology under a gluten-containing diet with CD serology allows for the diagnosis of the condition. A stringent lifelong gluten-free diet is now the only effective treatment for CD; nevertheless, the diet is demanding, and avoiding gluten is challenging. Further research is needed to improve and develop the diagnosis and treatment of CD via healthcare professional education programs.

Development of diagnostic algorithm for Cushing’s syndrome: a tertiary centre experience

PurposeNo consensus exists as the gold standard for Cushing’s Syndrome (CS) screening. This study aimed to evaluate the diagnostic accuracy and utility of late-night salivary cortisol (LNSC) and cortisone (LNSE), overnight dexamethasone suppression test (ODST), and urinary free cortisol (UFC) in developing a screening algorithm for CS.MethodsA retrospective, single-centre analysis on 93 adult patients referred to the Oxford Centre for Diabetes, Endocrinology, and Metabolism for CS evaluation (2017–2022). Data were analysed using binomial logistic regression and area under the receiver-operating curve (AUROC).ResultsFifty-three patients were diagnosed with CS. LNSC (sensitivity 87.5%, specificity 64.9%, AUC 0.76), LNSE (sensitivity 72.4%, specificity 85.7%, AUC 0.79), and ODST (sensitivity 94.7%, specificity 52.1%; AUC 0.74) demonstrated comparable effectiveness for CS diagnosis. Their combined application increased diagnostic accuracy (AUC 0.91). UFC was not statistically significant. Pre-test clinical symptom inclusion improved screening test performance (AUC LNSC: 0.83; LNSE: 0.84; ODST: 0.82). For CD diagnosis, LNSE + LNSC (AUC 0.95) outperformed ODST. Combining these with ACTH levels < 12.6 pmol/L perfectly distinguished MACS (AUC 1.00). ODST (AUC 0.76) exhibited superior performance (sensitivity 100.0%, specificity 52.2%) in MACS detection.ConclusionsLNSC, LNSE, and ODST are robust tools for CS screening, with their combined use offering the highest diagnostic precision. LNSE, especially when used with LNSC, is highly effective for CD diagnosis, exceeding ODST accuracy. ODST is preferable for MACS identification. Integrating ACTH levels markedly improves differentiation between CD and MACS. Conversely, UFC shows limited diagnostic utility.

A28 A SERUM REDOX STATUS-RELATED INDICATOR IS ASSOCIATED WITH THE RISK OF ONSET OF CROHN'S DISEASE

Abstract Background Crohn's disease (CD) is a gastrointestinal disorder characterized by chronic inflammation. While increased oxidative stress is observed in established CD patients, it remains unknown whether a shift in redox status is present before the diagnosis of CD and whether it is correlated with changes in immune response and microbial composition. Our hypothesis is that oxidative stress plays a role in the development of CD, and it could be detected before the diagnosis of CD. Furthermore, it is likely to be correlated with systemic inflammation and alterations in gut microbiota composition. Aims We aimed to assess the relationship between the serum redox status-related indicators, specifically amino acids ratios, with risk of CD onset and if this is further association with systemic inflammation marker, and gut microbiota composition. Methods In the Genetic Environment Microbial Project (CCC-GEM), a cohort of first-degree relatives (FDRs) of CD patients was prospectively followed. Among them, we identified subjects who later developed CD, defined as pre-CD (n=69), and matched them at a 1:4 ratio with FDRs who remained disease-free (n=276). Serum levels at enrollment of cysteineglycine (reduced form) and cystineglycine (oxidized form) were quantified by mass spectrometry, and the cysteineglycine/cystineglycine ratio was used as an indicator of redox status. Conditional logistic regression assessed the association with CD, while partial Spearman regression evaluated its correlation with systemic inflammation, as indicated by c-reactive protein (CRP), and gut microbiota composition (determined by fecal 16S rRNA sequencing). Results A decrease in the ratio indicates a shift in redox status toward oxidative stress. The cysteineglycine/cystineglycine ratio was negatively associated with the likelihood of developing CD (coefficient = -0.6188; p =0.0146), and it was also negatively correlated with CRP levels (coefficient = -0.177; p =0.00095). A list of taxa belonging to the phyla Firmicutes and Actinobacteriota were positively correlated with cysteineglycine/cystineglycine ratio (p≤0.05). Conclusions This study is the first to report that when redox status shifts towards oxidative stress, as indicated by the cysteineglycine/cystineglycine ratio, the likelihood of CD increases. Furthermore, these markers also correlate with CRP levels and gut microbiota composition, indicating a loss of various taxa when the redox status shifts towards oxidative stress. Submitted on behalf of the CCC-GEM consortium. Funding Agencies CCC, CIHRHCT

A174 TESTING FOR AND INCIDENCE OF CELIAC DISEASE AUTOIMMUNITY SAW SIGNIFICANT BUT TEMPORARY DECLINES DURING COVID-19 PANDEMIC

Abstract Background Celiac disease (CD) is an autoimmune disorder with various complications and long-term health risks. The COVID-19 pandemic affected the entire healthcare system—including screening for and diagnosing non-infectious conditions. Aims Determine how the COVID-19 pandemic affected the testing for, and incidence of, CD autoimmunity. Methods Using the population-based Alberta Medical Laboratory database, all tissue transglutaminase antibody tests (tTG-IgA) were identified in Alberta (April 2012 to March 2023). Incident cases of CD autoimmunity comprised of individuals newly positive for tTG-IgA between April 2015 and March 2023. Prevalent cases of CD were excluded based on previous tTG-IgA positivity and/or CD diagnosis codes in outpatient or inpatient settings. Average monthly percent changes and inflection points for testing and incidence rates were estimated using Joinpoint regression. Autoregressive integrated moving average models were performed to forecast rates if the pandemic had not occurred. Incidence rate ratios (IRRs) were estimated to compare a pre-pandemic era (April 2017 to March 2020) and a pandemic era (April 2020 to March 2023) overall and across subgroups. Results In the pandemic era, 311,971 tTG-IgA tests were performed on 284,882 unique individuals (21.1 per 1000 person-years (Table 1)). Testing decreased by 23.4% per month from February 2020 until May 2020 (Figure 1A). From June 2020 to August 2020, testing rates increased by 22.3% per month and then remained stable until the end of the study period. There were 4907 new cases of CD autoimmunity in the pandemic era, with an incidence of 36.3 per 100,000 person-years (Table 1). Incidence rates decreased by 14.1% per month from January 2020 until April 2020 (Figure 1B). Subsequently, incidence continued to rise by 2.0% per month from May 2020 until the end of the study period. Conclusions The COVID-19 pandemic appears to have had a minor impact on identifying potential CD. Future surveillance is needed to determine if the pandemic affected the diagnostic pathway to biopsy-confirmed CD through upper endoscopy procedures and any adverse outcomes individuals may have had from delayed diagnosis. Table 1: Testing and incidence rates for CD autoimmunity in Alberta in pre-pandemic era (April 2017 to March 2020) and pandemic era (April 2020 to March 2023) IRR=incidence rate ratio; CI=confidence interval Figure 1: Testing (A) and incidence (B) rates for CD autoimmunity before and after the start of the COVID-19 pandemic Funding Agencies CAG, CIHRhttps://triangleprogram.org