Introduction

Patients with ulcerative colitis (UC) and their treating physicians are currently looking beyond symptom resolution to achieve mucosal healing for a better long-term outcome. The assessment of this target requires invasive tests at several occasions that has an impact on the quality of life.

Aims & Methods

To evaluate the role of serum, fecal and urine biomarkers for predicting endoscopic healing, histological improvement and long-term outcomes after medical treatment of UC.

Patients with newly diagnosed acute UC or relapse of UC between September 2018 and February 2020 were included and followed for three years for relapse of symptoms. Disease activity was measured using clinical, Mayo Endoscopic Subscore (MES), and histological scores (Geboes score and Robarts Histological index). Biomarkers such as ESR, CRP, Fecal Calprotectin, Serum NGAL and 24-hour urine potassium were done at baseline and at clinical remission. The utility of biomarkers to predict endoscopic healing (MES ≤ 1), histological improvement (Geboes ≤ 3), and disease flare on follow up were analysed.

Results

40 patients (43 episodes of UC) with a mean age of 35 ± 10 years were studied. Majority of patients had moderate to severe disease activity by clinical score (88%), MES (93%) and histology (82%). There was a significant reduction in baseline serum and fecal biomarkers and a significant increase in 24-hour urine potassium at clinical remission and those with endoscopic healing while those with histological improvement had significant reduction in fecal and serum markers only. Patients without endoscopic healing or histological improvement didn’t had significant changes in biomarkers.

Parameter	Achieved endoscopic healing(n=36)			Achieved histological improvement(n=18)
	Baseline	Clinical remission	P value	Baseline	Clinical remission	P value
Fecal calprotectin(µg/g)	612.57 (31.- 8249.2)	147.36 (10 – 4463)	0.01*	921.3(79.4 – 8249.2)	66.26(10.01 – 1345.2)	<0.001*
Serum NGAL(ng/ml)	35.4 (22.8 – 1077.8)	31.75 (19 – 682.6)	0.003*	36.04(25.6 – 1077.8)	28.49(19.08 – 682.6)	0.002*
24-Hour urine potassium(meq/day)	27(6.6 -200)	36.8(10-240)	0.002*	24.77 ± 12.05	47.47 ± 52.7	0.07#
	Endoscopic healing(n)			Histological improvement(n)
	Yes	No	P value	Yes	No	P value
Flare	14	4	0.25$	4	14	0.02$
No flare	13	1		9	5
*: Wilcoxon sign rank test, #: paired t test, $ : chisquare test

Among patients achieving clinical remission, 83.7% (n= 36) had endoscopic healing and 41.8% (n=18) had histological improvement. 14 patients (35 %) had worsening of fecal calprotectin despite a clinical remission. A reduction in the baseline fecal calprotectin levels by 33.89% (AUC: 0.802, sensitivity: 0.72, specificity: 0.86) and 67.8% (AUC: 0.869, sensitivity: 0.83, specificity: 0.68) predicted endoscopic healing and histological improvement respectively.

A total of 32 patients completed the three year follow up and 54.5% (n=18) had at least one disease flare. Fewer patients with histological improvement (n=4; 12.5%) after treatment experienced flares compared to those with endoscopic healing (n=14; 77.7%). Although two-third with worsening fecal calprotectin achieved endoscopic healing on follow up, none had histological improvement and everyone had symptom relapse on follow up.

Conclusion

Our study confirmed that one-third to two-third decline in fecal calprotectin with treatment predicted endoscopic healing and histological improvement in UC. As the disease flares during follow up was better predicted by an improvement in histology, a two-third fall in baseline calprotectin may be a useful marker for better long-term outcomes in UC.

Disclosure

None declared

Introduction

Crohn's disease (CD) is a chronic inflammatory bowel disease that is characterized by periods of active inflammation followed by periods of remission. Current Methods for defining Crohn's disease activity are limited by various factors including low specificity, bias, invasiveness, high costs, radiation exposure and patient preference. Therefore, an easy, noninvasive, inexpensive, user-friendly, and repeatable method for the assessment of disease activity is warranted. Abnormal body temperature is a natural indicator of illness. Infrared thermography (IRT) can map body surface temperature remotely. With the advent of modern infrared cameras, data acquisition, and processing techniques, it is now possible to have real-time high-resolution thermographic images. Inflamed bowel loops are hyper-vascular and hyperemic, as detected by high doppler signs of intestinal ultrasound and bowel wall contrast enhancement in MRE, and therefore can be detected using IRT.

Aims & Methods

Our aim was to examine thermal imaging using IRT as a noninvasive tool for detecting bowel wall inflammation and disease activity in Crohn's disease patients.
The design of the study was prospective non -interventional. Consecutive adult CD patients referred for an intestinal ultrasound (IUS) exam were included, and adult healthy volunteers were recruited from the general population. Thermal images were captured using a FLIR ONE thermal camera device (FLIR Systems, Inc. Wilsonville, OR, USA) that connects directly to smartphones and utilizes a frame rate frequency of 8.7 Hz, an object temperature range of -20°C to 120°C and thermal sensitivity of 100 mK . Disease activity was defined using IUS. Thermal images of the study population were processed and compared to the results of IUS in all participants. Our novel thermal image processing algorithms extracted texture and shape features of temperature distribution across the skin covering the region of interest (ROI).

Results

The study cohort included 147 CD patients and 14 healthy volunteers. Using IUS, disease activity was found in 100 CD patients (68%). All 14 healthy volunteers had a normal IUS. The average abdominal temperature measured in the Crohn's patients (both active and inactive) was significantly higher than that of the healthy volunteers (30.4⁰±2.9⁰ C vs. 28⁰±2.9⁰ C, p=0.0032). The average abdominal temperature measured in the Crohn's group with the active disease was also found to be significantly higher than that of the healthy volunteers (30.4±2.99 C vs. 28⁰±2.9⁰ C, p=0.0035). To differentiate between active CD and CD in remission, a new parameter was defined and extracted: the fractal dimension of gradient magnitude (FDGM). The mean FDGM was significantly higher in patients with active disease than in patients with normal IUS (1.66 vs 1.63, p=0.045).

Conclusion

We describe a novel easy-to-use tool for monitoring disease activity in CD. This new method can potentially be used by patients at home as well as an office-based exam that allows precise disease follow-up and disease activity monitoring.

Disclosure

Dan Carter: Consulting fees from Takeda, Abbvie, Taro, and Lapidot; speaker fees and/or research support from Takeda, Abbvie, Janssen, and Lapidot.

Introduction

Patients with inflammatory bowel disease (IBD) have increasedrisk to develop bacterial enteric infections (Clostridium difficile infection [CDI] and non-CDI). Thus, when hospitalized due to IBD flare, they often undergo assessment for enteric infection. Our study aimed to assess the impact of enteric infections on hospitalized patients with IBD on the disease course, morbidity, and mortality.

Aims & Methods

In our retrospective study, we included patients hospitalized due to IBD exacerbation who were further stratified in those with enteric infection (Clostridium difficile infection (CDI) and non-CDI) and those without infections. We collected demographic and clinical data including disease location and behavior, previous treatments and surgery, comorbidities, medications for IBD, symptoms at the time of admission at the emergency department (ED), number and type of blood and stool tests for enteric infections, CRP levels, therapies during hospitalization and after discharge, post discharge related hospitalization, post discharge surgery, post discharge mortality. Continuous variables are reported as median and IQR (interquartile range [25th percentile, 75th percentile]) while categorical ones as counts and percents. Similarity between distributions is tested using the Kolmogorov-Smirnov test. Pearson’s Chi Squared (with Yate’s continuity correction) and Fisher’s exact test are used for categorical variables, while Wilcoxon rank sum test (with continuity correction) it is used for continuous ones. Statistical analysis was performed using R (v. 4.2.2 - 2022).

Results

We included 267 patients hospitalized due to IBD exacerbation with a concomitant enteric infections and 89 IBD patients without. At baseline characteristics, IBD patients with enteric infections had longer median times of hospitalization than those without (10vs 6 days, p<0.001), and they presented higher CRP levels (36 vs 17, p<0.001). Post-discharge, 29/89 (32.6%) and 57/267 (21.3%) of patients with and without enteric infections, respectively, were readmitted to ED for a flare (p=0.04). Moreover, infected patients had higher steroid dependency after discharge (p=0.003) compared to those without enteric infection. Post-discharge, we did not find any difference in biological therapy optimization between the two groups (p=0.07). We then stratified IBD patients with infections in two sub-groups: patients with CDI (n=19) and patients with non-CDI (n=70). We found a statistically significant difference in IBD related re-hospitalization between the two groups (0% in CDI vs 22.9% in non-CDI, p=0.02).

Conclusion

Our findings suggest that enteric infections in IBD patients play an important role on complications like hospitalization and steroid dependency. Early detection, appropriate management, and prevention strategies are crucial to avoid their deleterious outcomes.

Disclosure

none

Introduction

Inflammatory bowel disease (IBD) management faces significant care gaps, particularly in areas such as diet and mental health support. Digital health applications provide remote support to patients with IBD to improve health, however few digital applications have published evidence of efficacy.

Aims & Methods

The purpose of this randomized controlled trial (RCT) was to identify if use of the LyfeMD digital health platform results in significant changes in health behaviours among patients in remission with Crohn’s Disease (CD) and Ulcerative Colitis (UC). LyfeMD is an integrated digital and human platform designed to improve physical and mental health. Patients over the age of 18 with UC or CD in remission were recruited in Calgary, Alberta. Participants were randomly assigned to the LyfeMD intervention (n=10) or the standard care control (n=10) group. The intervention group was given access to the LyfeMD mobile app for 8 weeks and assigned a health coach. Self-reported validated measures were collected at baseline and week 8 including demographics, leisure-time physical activity (LTPA), stress score (SS), depression and anxiety risk, sleep, screen-time outside of work, and sitting time. Diet intake was collected using 2 consecutive 24-hour recalls (ASA-24) at baseline and week 12. Intake data was used to calculate the healthy eating index (HEI). Independent and paired sample t-tests were used to identify significant differences between and within groups.

Results

Twenty people were recruited for this study (N=10 per group); 65% were female, with a mean age of 45.3 years (standard deviation) [SD] =9.9). Mean body mass index was 28.1kg/m2 (7.0) and 80% of the participants had CD. After 8 weeks the intervention group showed significant improvements in risk of anxiety (mean = -1.9/21 [2.3]) screen time (mean = -7.2/168 hours/week [11.3]), sitting hours (-10.6/168 hours/week, [12.9], and overall well-being (mean = +12.5/100 [21.2]) (p<0.05). At week 12 the intervention group also showed significant improvements in both overall diet quality (mean = +12.2/100 [16.6]) and moderation scores (mean= +5.6/50 [5.0]). Between the groups we see significant differences for both sitting time and for the moderation component of the HEI (p<0.05).

Conclusion

The LyfeMD digital health platform is a safe option for patients with IBD, providing accessible lifestyle therapy thus, reducing current gaps in the healthcare system. Future studies should focus on an increased sample size and targeting remote populations where this program may be even more valuable to healthcare providers and patients.

Disclosure

Lorian Taylor, Puneeta Tandon and Maitreyi Raman are cofounders of LyfeMD. Vidya Rajagopalan at the time of this study worked for the University of Calgary and presently works for LyfeMD.

Clinical Case Summary

A 72 years old caucasian women with no relevant medical history presented to the emergency department with two weeks history of abdominal pain in the upper quadrants associated with fullness, vomiting and a significant weight loss and nighttime hypersweating. On physical examination, abdomen was painful on epigastric and periumbilical region. Analytically, hemoglobin 11.1g/dL, leukocytes 9200/mm3, platelet count 315000/μL, CRP 8.22mg/dL. Tests for HIV and EBV were negative. Computed Tomography (CT) of the abdomen and pelvis revealed stomach with thickened walls, densification of adjacent fat and heterogeneous adenopathies. She was admitted to the department of Gastroenterology for investigation. The upper gastrointestinal endoscopy revealed extensive neoplasia of the body and gastric antrum. Biopsies revealed gastric mucosa with infiltration by atypical lymphoid proliferation with a "starry sky" pattern suggestive of high-grade B-cell non-Hodgkin's lymphoma (NHL). FISH analysis revealed t(8;14) c-myc positive. Once morphological and immunohistochemistry feature favors Burkitt’s lymphoma, she was transferred to the department of Hematology. Patient was treated with a full dose CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) and 3 cycles of dose adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab). Complete remission was documented on positron emission tomography (PET).
Sporadic Burkitt's lymphoma is rare (1-2% of all lymphomas in adults), being one of the most aggressive forms of B-cell NHL. Primary gastric involvement is extremely rare. With the advancement of medicine and greater survival, we must consider this diagnosis, even in the absence of risk factors, atypical location and age group. This case emphasizes the importance of clinicopathological correlation and the importance of early diagnosis for immediate and aggressive intervention, fundamental in reducing morbidity and mortality.

References

1. Zhimin Bai, Yong Zhou. A systematic review of primary gastric diffuse large B-cell lymphoma: Clinical diagnosis, staging, treatment and prognostic factors, Leukemia Research,
Volume 111, 2021, 106716, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2021.106716.
2. Čubranić A, Golčić M, Fučkar-Čupić D, Brozović B, Gajski D, Brumini I. BURKITT LYMPHOMA IN GASTROINTESTINAL TRACT: A REPORT OF TWO CASES. Acta Clin Croat. 2019 Jun;58(2):386-390. doi: 10.20471/acc.2019.58.02.25. PMID: 31819338; PMCID: PMC6884372.
3. Usman A. Pirzada, Kishore Kumar, Hassan Tariq, Masooma Niazi, Jasbir Makker; Case of Gastric Diffuse Large B-Cell Lymphoma. Case Rep Oncol 6 May 2019; 12 (1): 39–46. https://doi.org/10.1159/000496332
4. Khan A, Khan S, Arshad U. Primary Gastric Burkitt's lymphoma. Pak J Med Sci. 2017 Sep-Oct;33(5):1294-1297. doi: 10.12669/pjms.335.13002. PMID: 29142583; PMCID: PMC5673752.

Introduction

Children with inflammatory bowel diseases (IBD) are particularly vulnerable to Clostridioides difficile infections (CDI) and experience significantly worse health outcomes including increased hospitalisation and shorter time to their first bowel resection. Previous studies have correlated these outcomes to specific gastrointestinal microbiome features. However, data regarding features that may predispose PIBD patients to CDI is lacking. Furthermore, it is not known whether CDI has long-term impacts on the microbiome of PIBD patients in remission.

Aims & Methods

Our primary aims were to investigate whether PIBD-CDI patients had a distinct microbiota at baseline compared to PIBD controls, to examine whether PIBD-CDI patients had a distinct microbiome during remission than those without CDI, and whether there were changes in their stool short chain fatty acids (SCFA) composition. Finally, we aimed to assess whether PIBD patients with CDI had worse outcome.
Patients aged 2-17 years and newly diagnosed with IBD between November 2014 and March 2019 were invited to participate. Each patient was requested to submit 4 stool samples in an interval of six months between samples and follow up continued until June 2021. Patients were divided into those that developed CDI (IBD-CDI) and those who did not (IBD controls). DNA was extracted from stool samples and the microbiota of each was profiled using 16S rRNA amplicon sequencing on an Illumina MiSeq. SCFA were quantified from the stool samples. Data analysis was further divided into 2 cohorts: Cohort 1 represented microbiome data from samples of patients who developed CDI and were collected prior to the infection. Cohort 2 represented microbiome data from samples of patients in remission who had CDI. Microbial composition and SCFAs were compared to non-CDI controls within each cohort. Hazard ratio (HR) was calculated to progression to biologic treatment and surgeries in patients who had a CDI compares to those who did not. Random forest classification model was used to predict CDI using microbial composition.

Results

Patients who had CDI were more likely to progress to a biologic therapy (HR 1.85 P =0.06) and had significantly more hospitalisations (RR 2.20, P< 0.001) and surgery (HR 3.15, P= 0.019).
Cohort 1:
Patients who did not develop CDI had higher abundance of Bifidobacterium bifidum, Blautia hydrogenotrophica, Clostridium sensu stricto 2 cadaveris, Eubacterium, Ruminococcus torques group, and Lachnoclostridium.
The Eubacterium, Blautia hydrogenotrophica, Ruminococcus torques group and Lachnoclostridium were associated with high levels of stool SCFAs.
Random forest classification model was able to predict patient who did not develop CDI.
Cohort 2:
Patients post CDI had significantly lower beta diversity.
The Oscillospirales CAG 352, NK4A214 group and UCG 002 were all less abundant in post-CDI patients, and were associated with higher SCFA production. Specifically, propionic acid (CAG 352), isovaleric and isobutyric acid (NK4A214 and UCG 002). Additionally, alistipes was associated with higher levels of isovaleric and isobutyric acids.

Conclusion

We were able to predict paediatric IBD patients that were protected from CDI based on baseline microbial composition. Paediatric IBD patients who developed CDI during the course of the disease developed more severe outcome with more surgeries and hospitalisations. They had long term changes to their microbiome.

References

Pascarella F, Martinelli M, Miele E, Del Pezzo M, Roscetto E, Staiano A. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr. 2009 Jun;154(6):854–8.
Hellmann J, Andersen H, Fei L, Linn A, Bezold R, Lake K, et al. Microbial shifts and shorter time to bowel resection surgery associated with c. difficile in pediatric Crohn’s disease. Inflamm Bowel Dis. 2020;
Sokol H, Jegou S, McQuitty C, Straub M, Leducq V, Landman C, et al. Specificities of the intestinal microbiota in patients with inflammatory bowel disease and Clostridium difficile infection. Gut Microbes. 2018;

Disclosure

No conflict of interest