Introduction

Ulcerative colitis (UC) is characterized by chronic immune mediated inflammation of the colon and rectum. Corticosteroid (CS) is a common treatment for patients with moderate to severe active UC, but its effect varies among patients, including resistance, response, and dependence. In addition, the longer CS therapy continues, the greater the concern regarding drug-related adverse effects. New immunomodulatory therapies are being developed for the treatment of UC drug showing promise in the treatment of patients with moderate UC refractory to aminosalicylic acid (5-ASA). Thus, the clinical benefit of being able to predict whether certain patients would benefit from CS therapy prior to administration cannot be overestimated.

Aims & Methods

We compared the clinical characteristics of patients with steroid-responder (SR) and steroid-non-responder (SNR) UC and retrospectively evaluated for biomarkers that could predict the efficacy of CS prior to administration in patients with moderate to severe active UC who failed to respond to 5-ASA.
We enrolled 100 UC patients presenting at Nippon Medical School Hospital with a history of CS administration prior to December 2023. The patients were divided into two groups, SR patients and SNR patients, and their clinical characteristics were determined according to medical records. Eosinophil counts were measured in the high-power field using Direct Fast Scarlet staining.

Results

Clinical characteristics of UC patients were as follows: the median age, 48±17 years; height 167±9.2 cm, and weight, 58±14 kg; including 61 males to 39 females. The most common disease extent type was the total colitis (63%), followed by left-sided colitis (32%), and proctitis (5%). Complete SNR was observed in 15 patients (15%), with remaining 85 patients (85%) classified as SR. There was no significant difference found in Mayo Endoscopic Score, first dose of CS, number of hospitalizations, number of relapses, propotion of patients with total-colitis type, or duration of CS treatment between the SR group and the SNR group. The non-remission rate, defined as failure to achieve mucosal healing, was significantly higher in the SNR group (66%) than in the SR group (36%) (P=0.03). The proportion of patients treated with azathioprine was significantly higher in the SR group (40%) than in the SNR group (39%). The proportion of patients treated with biologics or small molecular compounds was significantly higher in the SNR group (40%) than in the SR group (22%) (P=0.03).
We then compared hematological biomarkers in blood samples obtained prior to CS administration between the two groups. There was no significant difference in WBC counts, hemoglobin values, serum albumin concentrations, CRP values, and ESR between the two groups. However, eosinophil profiles (both total count numbers and ratio to white blood cell counts) were significantly higher in the SR group than in the SNR group (P=0.02). Neutrophil-lymphocyte ratio tended to be higher in the SR group than in the SNR group (P=0.06). The number of infiltrated eosinophils in the inflamed rectal mucosal tissue was not significantly different between the two groups. The number of infiltrated eosinophils in the rectal mucosa tended to decrease in the steroid-response groups (p = 0.07). However, there was no difference in the number of infiltrated eosinophils in the steroid-non-response groups.

Conclusion

Both eosinophil in the blood and in the rectal mucosa, and neutrophil-lymphocyte ratio in the blood could be potential biomarkers for steroid responsiveness prior to administration.

References

・British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019; 68: s1–s106
・Severe ulcerative colitis: at what point should we define resistance to steroids? WJG 2008 Sep 28;14(36):5504-7.
・A reproducible grading scale for histological assessment of inflammation in ulcerative colitis: Gut 47：404－409，2000
・Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease：J Clin Med Res,2022

Clinical Case Summary

A 39-year-old woman was admitted on June 20, 2024, with a right middle cerebral artery stroke, nine weeks after starting Upadacitinib for ulcerative colitis. She presented with dysarthria, dysphagia, and severe left-sided weakness. CT imaging revealed a wedge-shaped infarction without intracranial hemorrhage (CT head/ Brain MRI).
She was diagnosed with ulcerative colitis in November 2023, she initially responded to Mezavent and steroids but was hospitalized on March 31, 2024 for moderate UC flare, requiring infliximab rescue therapy. The patient presented with four bloody bowel movements and elevated inflammatory markers (CRP>100), confirmed by a Mayo score of 2 on flexible sigmoidoscopy and cytomegalovirus (CMV) infection was excluded. Clostridium difficile tests were negative twice and a CT scan revealed pancolitis. Despite minimal response to rescue therapy, she opted for medical treatment over colectomy.
On April 23, 2024, she began an eight-week induction of Upadacitinib 45 mg, which she tolerated well. However, on June 20, she developed sudden stroke symptoms while eating dinner, including difficulty swallowing, choking, left-sided weakness, and numbness. She had no vascular risk factors or family history of premature cardiovascular conditions. Lupus, and vasculitis work up were unremarkable and extensive thrombophilia screenings were all negative.
Discussion: Thrombosis in IBD patients can result from various potential causes. First of all, Inflammation and hypercoagulability, driven by elevated cytokines like TNF, interleukins, and CRP, activate the coagulation cascade, increasing thrombosis risk.
Conclusion: IBD is a known risk of thromboembolic disease, this risk increased during flare up will raise future research questions regarding extended anticoagulation prophylaxis during flare and uses of Jak stats inhibitor.

References

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2. Solitano V.Thrombosis in IBD in the Era of JAK Inhibition. Curr Drug Targets. 2021;22(1):126-136. doi: 10.2174/1389450121666200902164240.

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Introduction

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, characterized by a relapsing-remitting course, primarily comprising Ulcerative Colitis (UC) and Crohn’s Disease (CD). These conditions, which lack a clearly defined cause, pose significant interest to the medical community for identifying reliable predictors of disease progression and treatment response.
The specific profile of extrachromosomal circular DNA fragments (eccDNA) has emerged as a promising diagnostic and prognostic biomarker for various types of cancer. However, their role in IBD patients, including the specific gene fragments they carry, has not been thoroughly investigated so far.

Aims & Methods

This monocentric, observational, case-controlled study enrolled consecutive patients diagnosed with IBD and non-IBD healthy controls undergoing colonoscopy for colorectal cancer screening at Fondazione Policlinico Universitario “A: Gemelli”. Disease activity in IBD patients was assessed using different scoring systems: the Partial Mayo Score (PMS) and Mayo Endoscopic Subscore (MES) for UC, and the Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) for CD. Colonic biopsies were obtained from both inflamed and healthy mucosa of IBD patients and from non-IBD controls. Purification of human eccDNA was optimized according to the Circle-Seq method, including eccDNA enrichment, removal of linear and mitochondrial DNA, rolling-circle amplification and sequencing; subsequently, eccDNAs were identified using Circle Finder software. The study compared the relative abundances of genes within eccDNAs between IBD patients and non-IBD controls, focusing on those that were differentially abundant, defined as Differentially Produced per Gene eccDNAs (DPpGCs).

Results

133 patients with IBD (69 with CD, 64 with UC) and 17 healthy controls (HC) were included in the study. Colonic mucosal samples from IBD patients revealed a higher average abundance of eccDNAs compared to samples from HC. This increase was consistent across all chromosomes, suggesting a global upregulation of eccDNA production throughout the human genome. Furthermore, there was a slight yet statistically significant trend towards larger eccDNAs sizes in IBD patients compared to HC. Even when considering only eccDNA derived from genic elements ("genic eccDNAs"), IBD patients exhibited a significantly higher abundance of eccDNA in the gut compared to non-IBD controls.
Further analysis focused on DPpGCs with a fold change >1 log2 between IBD patients and HC, with a significance threshold of p < 0.01. Forty-nine genes were found to be enriched in IBD patients, including GRID2 and NRG3. Similarly, in CD patients, 176 genes, such as FGF14, SOX5, and ZBTB20, were significantly enriched compared to HC. In UC patients, 31 genes, including NRG1, SPOCK3, and ATP13A4, showed enrichment compared to HC. Moreover, IBD patients in endoscopic remission (SES-CD < 3, EMS of 0-1) tended to have fewer eccDNAs in their intestines compared to those with active disease, although this difference did not reach statistical significance. Five DPpGCs, including FARS2, HERC3, and PNK2, were identified when applying the aforementioned criteria.

Conclusion

In conclusion, our study unveils a distinct pattern of eccDNA production specific to IBD. We showed that circles harboring specific genes can distinguish UC and CD from healthy controls with statistical significance (p < 0.01). We suggest that eccDNA identification may serve as a novel diagnostic biomarker for IBD patients.

Introduction

Adequacy of bowel preparation (ABP) directly affects colonoscopy performance and adenoma detection rate. Studies attributed a role to the dosing regimen of the bowel cleansing agent, social and economic factors and comorbidities. However, data on the impact of kidney failure and renal replacement therapy (RRT) are lacking.

Aims & Methods

This study investigated how ABP compares between patients on RRT and age-matched subjects with normal kidney function.
All patients on RRT undergoing an elective colonoscopy between January 2016 and December 2021 were identified from the medical records of a university hospital, and matched to 2 closest age controls undergoing colonoscopy at the same date ± 7 days. Study subjects and controls were compared for demographics, comorbidities including history of abdominal surgery, use of bowel transit-influencing drugs, residential care stay and colonoscopy-related data (bowel preparation regimen, sedation type, colonoscopy findings, ABP defined as a cumulative Bristol Bowel Preparation Score >= 6 and a score of >= 2 for each colon segment). Statistical significant contributors to ABP were assessed by logistic regression.

Results

Ninety-one patients on RRT (76 on haemodialysis and 15 on peritoneal dialysis) and 182 controls were identified. Patients on RRT were older (69±12 vs. 64±14y, p=.008) and less frequently women (34% vs. 50%, p=.013). They had more diabetes (40% vs. 24%, p=.008), more history of abdominal surgery (32% vs. 21%, p=.047) and took more bowel transit-influencing drugs (50% vs. 28%, p<.0001). Bowel preparation regimens were equally distributed between both groups. There was no difference in the rate of ABP between groups (87% vs. 81%, p=NS). Logistic regression analysis did not reveal an association between RRT and ABP. ABP was negatively influenced by residency in residential care, overnight stay in the hospital before colonoscopy, history of central nervous system disease, and positively by split-dose regimen (Nagelkerke R square 0.329, p=<.001).

Conclusion

Despite less favourable associated conditions, ABP in RRT patients remains comparable to controls. Split-dose regimen, neurological conditions and in-hospital stay are significant predictors of adequate bowel preparation.

References

Clark BT, Rustagi T, Laine L. What level of bowel prep quality requires early repeat colonoscopy: systematic review and meta-analysis of the impact of preparation quality on adenoma detection rate. Am J Gastroenterol. 2014;109(11):1714-23; quiz 24.
Hassan C, East J, Radaelli F, Spada C, Benamouzig R, Bisschops R, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy. 2019;51(8):775-94.
Saumoy M, Jesudian AB, Aden B, Serur D, Sundararajan S, Sivananthan G, et al. High prevalence of colon adenomas in end-stage kidney disease patients on hemodialysis undergoing renal transplant evaluation. Clin Transplant. 2016;30(3):256-62.
24. Calderwood AH, Schroy PC, 3rd, Lieberman DA, Logan JR, Zurfluh M, Jacobson BC. Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness. Gastrointest Endosc. 2014;80(2):269-76.
25. Clark BT, Protiva P, Nagar A, Imaeda A, Ciarleglio MM, Deng Y, et al. Quantification of Adequate Bowel Preparation for Screening or Surveillance Colonoscopy in Men. Gastroenterology. 2016;150(2):396-405; quiz e14-5.
artel M, Barkun AN, Menard C, Restellini S, Kherad O, Vanasse A. Split-Dose Preparations Are Superior to Day-Before Bowel Cleansing Regimens: A Meta-analysis. Gastroenterology. 2015;149(1):79-88

Introduction

Motorized Spiral Enteroscopy (MSE) reduces procedure time and increases insertion depth into the small bowel. MSE has shown to be safe and effective for deep enteroscopy in studies performed at expert centers in patients with and without prior abdominal surgery.
Here we present data on our first 250 MSE procedures, focusing on the safety profile using the MSE for various diagnostic and therapeutic small bowel examinations.

Aims & Methods

Data on safety were collected retrospectively on patients who underwent MSE with an indication for deep small bowel enteroscopy.
Adverse events (AEs) were recorded during and after the procedure within a 30-day follow-up period. AEs were classified as minor or serious AEs (SAEs). Minor events included: mucosal abrasions or superficial lacerations in the small bowel, stomach, esophagus, or colon; a sore throat of less than 72 hours duration; abdominal discomfort lasting less than 48 hours, and mild nausea or vomiting not requiring hospital admission. SAEs included perforation, significant bleeding requiring blood products, pancreatitis, or unplanned hospital admission related to the procedure.

Results

A total of 240 patients (150 M/90 F; median age 66 years, range 23–91) were included. Between March 2020 and March 2023, these patients underwent a total of 250 procedures in a single center. 20% of patients had previous abdominal operations or surgically-altered GI anatomy. The American Society of Anesthesiologists score (ASA score) was: ASA 1 [33 (14%)], ASA 2 [159 (66%)], ASA 3 [48 (20%)]. All procedures were performed under propofol sedation without endotracheal intubation.
Enteroscopy procedures were either antegrade only (80), retrograde only (20), or bidirectional in one session (150). In other words, a total of 230 and 170 procedures via antegrade and retrograde routes were performed, respectively.
Total (pan)-enteroscopy in one session was achieved in 70% of intended procedures, either exclusively antegrade or bi-directional.
The following interventions were performed: hemostasis using APC and/or hemoclips (90; 36%), balloon dilatation of strictures (13; 5%), EMR polypectomies (4; 1.6%), and VCE retrieval (3; 1.2%).
A total of 44 (17.6%) adverse events were documented; 40 (16%) were minor, while SAEs occurred in 3 (1.2%) patients. No significant hemodynamic changes were observed. Except for those 3 SAE, no other patient required hospital admission, a blood transfusion, or other interventions. No special care was needed for the mucosal damages observed during MSE. Previous operations or altered GI anatomy did not increase the risk of complications. An overview of the adverse events is given in the table.

Conclusion

This retrospective data show that MSE is a safe procedure in a large cohort of patients. Previous abdominal operations and an altered GI anatomy did not increase the risk of complications. Although progress of the enteroscope may be slower in postoperative situations, this did not translate into an increased risk of adverse events.
Meticulous adherence to procedural safety instructions and careful patient selection are necessary to achieve optimal results and decrease the incidence of serious adverse events.