Introduction

Volatile organic compounds (VOC) in stool samples may reflect functional activity of gut microbiome. Previous studies showed that gut flora may influence transient relaxations of lower esophageal sphincter through short-chain fatty acids production and thus - participate in pathogenesis of gastroesophageal reflux disease (GERD). However, the role of VOC in pathogenesis of GERD is poorly studied yet.

Aims & Methods

The aim of this study (FGMF-2025-0003) was to perform correlation analysis between concentrations of VOC in stool samples and GERD-Q score.
We enrolled willing to participate patients referred to perform multichannel 24-h pH-impedance recording (Ohmega, Laborie). According to the Lyon 2.0 criteria patients were allocated to the GERD or the control group. GERD-Q questionnaire was filled in by the participants on the same day as stool samples were collected. Thermo TSQ 8000 triple quadrupole mass-spectrometer (GC/MS) was used for the measurement of VOCs in stool samples were analyzed with. Correlation analysis (Spearman rank R) was performed between values of 80 VOCs in stool samples and the results of GERD-Q questionnaire.

Results

Data of 76 patients were eligible: 42 with GERD and 34 - of the control group. Participants in the GERD group were older (54.7±12.2 y.o. vs 46±14.9 y.o., P<0.05) and their BMI was greater (30.9±5.2 vs 27.2±6.5 kg/m², P<0.05). GERD-Q score was logically greater in GERD group (11.0±2.5 vs 5.2±1.2, p<0.01). Correlation analysis revealed significant correlations between GERD-Q score and concentrations of 2-methylbutyric acid (Spearman R =-0.31), caproic acid (0.34) and enantiic acid (0.396) in stool samples.

Conclusion

GERD-Q score positively correlates with concentrations of Caproic acid (0.34) and Enantiic acid (0.396) in stool samples and negatively – with 2-Methylbutyric acid. The data of this pilot study may serve as a basis for further research on the role of functional activity of gut microbiome in pathogenesis of GERD.

Introduction

Postoperative recurrence (POR) after ileocecal resection for Crohn's disease (CD) represents a significant clinical challenge

Aims & Methods

This study aimed to identify clinical risk factors for surgical recurrence in patients undergoing ileocecal resection for CD. This multicenter retrospective cohort study included 1,066 patients with CD who underwent ileocecal resection across 13 Italian centers. Univariate and multivariate logistic regression analyses were performed to identify clinical risk factors associated with surgical recurrence.

Results

The cohort comprised 59.0% males with a median age at diagnosis of 29 years [IQR: 22-40]. Most patients presented with stricturing disease (55.2%) or penetrating disease (40.9%), with ileal (49.6%) and ileocolonic (47.6%) locations predominating. Over a median follow-up of 70 months [IQR: 31-131], 101 patients (9.5%) required recurrent surgery. The median time to recurrent surgery was 78.5 months [IQR: 19.0-138.0]. Most patients (72.3%) had at least one clinical risk factor for POR, with penetrating phenotype (40.4%), previous intestinal resections (27.2%), and perianal disease (21.4%) being most common.
Univariate analysis identified significant risk factors for surgical recurrence including prior intestinal resection (OR 5.56, 95% CI 3.62-8.56, p<0.001), perianal disease (OR 3.50, 95% CI 2.28-5.35, p<0.001), large intestinal resection ≥50 cm (OR 4.80, 95% CI 3.04-7.58, p<0.001), and continued smoking after surgery (OR 1.84, 95% CI 1.16-2.94, p=0.010). Disease duration >10 years (OR 2.20, 95% CI 1.44-3.36, p<0.001) and colonic involvement (L2: OR 3.00, 95% CI 1.18-7.65, p=0.021) increased risk, while ileal localization (L1) was protective (OR 0.35, 95% CI 0.22-0.54, p<0.001). Bowel perforation as surgical indication significantly increased recurrence risk (OR 2.58, 95% CI 1.29-5.16, p=0.007). Multivariate analysis confirmed perianal disease (aOR 2.58, 95% CI 1.56-4.26, p<0.001), previous intestinal resection (aOR 5.70, 95% CI 3.52-9.23, p<0.001), and large resection (aOR 4.04, 95% CI 2.43-6.72, p<0.001) as independent predictors of recurrence. Unlike previous studies, penetrating behavior was not associated with increased risk, while disease duration >10 years and colonic involvement emerged as significant factors. Additionally, this study uniquely identified bowel perforation as a surgical indication distinct from other penetrating complications in predicting recurrence.

Table 1: Independent Risk Factors for Surgical Recurrence After Ileocecal Resection in Crohn's Disease

Risk Factor	Odds Ratio (95% CI)	p-value
Previous intestinal resection	5.70 (3.52-9.23)	<0.001
Large intestinal resection (≥50 cm)	4.04 (2.43-6.72)	<0.001
Perianal disease	2.58 (1.56-4.26)	<0.001
Continued smoking after surgery	2.23 (1.30-3.83)	0.004
Bowel perforation as surgical indication	2.58 (1.29-5.16)	0.007
Disease duration >10 years	2.20 (1.44-3.36)	<0.001
Ileal localization (L1)	0.35 (0.22-0.54)	<0.001

Conclusion

This large cohort study identified several robust predictors of surgical recurrence after ileocecal resection for CD, with some notable differences from prior research. Previous intestinal resection, perianal disease, large intestinal resection, colonic involvement, and continued smoking emerged as particularly strong risk factors, while penetrating disease behavior was not confirmed as a predictor. These findings challenge some aspects of current risk stratification guidelines and can help inform personalized postoperative management strategies.

Introduction

Patients with ulcerative colitis (UC) and concurrent cytomegalovirus (CMV) colitis are at higher risk of poorer outcomes, including developing steroid refractoriness or toxic megacolon. Given its relevance, the European Crohn's and Colitis Organization recommends, in case of flare-ups, to search for CMV by endoscopic biopsy, preferably with tissue polymerase chain reaction (PCR) or alternatively with immunohistochemistry (IHC).

Aims & Methods

The aims of our study were to compare the diagnostic yield of tissue and plasma CMVDNA PCR to IHC and to explore the different level of tissue viral load in both steroid-refractory and steroid-sensitive UC patients. This prospective study included consecutive patients undergoing colonoscopy or proctosigmoidoscopy for UC, independent of disease activity, in a single tertiary center betwen July 2024 and January 2025. Patients underwent the same day endoscopy with multiple biopsies (3 from sigmoid colon and 4 from rectum) and plasma sampling for CMVDNA analysis using real-time quantitative PCR assay; histological presence of CMV was evaluated using IHC and hematoxylin-eosin staining. Concordance among CMV detection techniques was calculated using K cohen concordance index. Continuous variables were compared using Mann-Whithney test. ROC analysis allowed to identify an ideal cut-off of viral load value of CMV infection.

Results

Twenty-one consecutive patients were enrolled. Twelve (57,1%) patients were male and 9 (42,9%) female, (range 19-79 years). Nine (42,8%) patients had a diagnosis of pancolitis, three (14,3%) of left-sided UC, seven (33,4%) of procto-sigmoiditis and two (9,5%) of proctitis. Six (28,6%) patients were subclassified as steroid-refractory, the remaining fifteen (71,4%) as steroid-responsive.
IHC positivity was observed in tissue samples from 3 (14,3%) patients, while CMVDNA was detected in tissue samples from 5 (23,8%) patients and in 3 (14,3%) plasma samples. Comparing IHC to plasma CMVDNA, the k index was only fair consistent (0.277 CI -0.327 to 0.758), while IHC versus tissue DNA showed a higher consistency, with a k index of 0.500 (CI 0.048 to 0.952).
Interestingly, the mean value of tissue CMVDNA in the steroid-refractory group was higher, although not significant, than the steroid-responsive group (respectively 140.00 copies/mg ±260.00 vs 98.00 copies/mg ±360.00, p value= 0.14). In order to identify a possible tissue CMVDNA level able to distinguish between the two groups, a receiver operating characteristic (ROC) curve analysis was performed: a cut-off value of 102.56 was associated with a sensitivity of 92.86% and a specificity of 33.3%, resulting in a likelihood ratio of 1.39. The area under the ROC curve (AUC) was 0.6667 ± 0.1415, indicating a modest discriminative ability.

Conclusion

This study showed a good concordance between immunohistochemistry and tissue PCR for the detection of CMV in UC patients. Steroid-refractory UC patients showed a higher tissue viral load compared to steroid-responsive patients.

Disclosure

No conflict of interest to declare

Introduction

Vedolizumab (VDZ), a monoclonal antibody therapy approved for moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) in China in 2020¹ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.² However, there is limited data on VDZ's real-world effectiveness and safety in Chinese IBD patients.³ Interim results from the VALUE study that enrolled patients with UC have been published ^3,4 and final results are reported here.

Aims & Methods

VALUE (NCT04872491), a multicenter, single-arm, prospective, observational study evaluated the safety and effectiveness of VDZ in adult Chinese patients with IBD (N = 500) over 72 weeks. Clinical response, clinical remission, and endoscopic remission were assessed at Weeks 14, 30, and 54. Partial Mayo and Mayo endoscopic subscores at baseline and Weeks 14, 30, and 54 were calculated. Clinical response was defined as ≥2-point reduction in Partial Mayo Clinic score and ≥25% decrease from baseline score accompanied with ≥1-point decrease in the rectal bleeding or absolute rectal bleeding subscore ≤1. Clinical remission was defined as Partial Mayo Clinic score ≤2 with no subscore >1, endoscopic remission as Mayo endoscopic subscore ≤1, and complete endoscopic remission as Mayo endoscopic subscore 0. Safety results and CD patients’ data are presented in separate VALUE abstracts (IDs: AS-UEG-2025-01329 and AS-UEG-2025-01324).

Results

Among 409 UC patients enrolled in the final analysis, 91.9% (376/409) were included in the effectiveness analysis set. Mean age (±standard deviation [SD]) of patients was 46.3 (±15.1) years, and 59.4% (n=243) were male. At baseline, 30.8% (126/409) of patients had moderate UC, and 29.8% (122/409) had severe UC. The median duration of UC was 2.5 years, concomitant steroids were prescribed in 18.9% (71/376). Mean (±SD) partial Mayo score was 5.1 (2.1) at baseline, which declined to 1.7 (1.7), 1.5 (1.7) and 1.3 (1.5) by Weeks 14, 30 and 54, respectively, post-VDZ treatment. Patients achieving clinical response, clinical remission, endoscopic remission, and complete endoscopic remission were 76.9% (220/286), 71.1% (207/291), 63.6% (35/55), and 21.8% (12/55) at Week 14; 78.1% (193/247), 76.3% (190/249), 63.6% (28/44), and 27.3% (12/44) at Week 30; and 80.3% (155/193), 83.3% (165/198), 71.4% (20/28), and 50.0% (14/28) at Week 54, respectively. Patients with moderate and severe UC; biologic naïve patients and patients with prior exposure to biologics at baseline also achieved clinical response, clinical remission, and endoscopic remission (Table). Compared with baseline, mean (±SD) reduction of C-reactive protein (mg/L) at Weeks 14, 30, and 54 were 7.8 (20.2), 6.5 (22.2), and 3.4 (24.8), respectively; mean (±SD) reduction of fecal calprotectin (mu g/g) was 42.7 (150.7) at Week 14 and 212.6 (480.1) at Week 30. The proportion of patients achieving clinical remission without steroid use by Week 14 was 37.7% (23/61), which increased to 60.6% (20/33) by Week 54.

Data are presented as % (n/N). N, number of patients having clinical response/remission/endoscopic remission data. n, number of patients achieving clinical response/remission and endoscopic remission data.
	Moderate UC			Severe UC
	Clinical response	Clinical remission	Endoscopic remission	Clinical response	Clinical remission	Endoscopic remission
Week 14	89.8 (79/88)	65.9 (58/88)	57.1 (12/21)	90.0 (72/80)	63.8 (51/80)	56.3 (9/16)
Week 30	87.7 (64/73)	69.9 (51/73)	30.8 (4/13)	91.2 (62/68)	66.2 (45/68)	90.9 (10/11)
Week 54	92.2 (59/64)	81.3 (52/64)	62.5 (5/8)	88.5 (46/52)	73.1 (38/52)	60.0 (3/5)
	Biologic-exposed UC: 10.9% (41/376)			Biologic-naïve UC: 89.1% (335/376)
Week 14	69.0 (20/29)	66.7 (20/30)	16.7 (1/6)	77.8 (200/257)	71.7 (187/261)	69.4 (34/49)
Week 30	74.2 (23/31)	71.0 (22/31)	83.3 (5/6)	78.7 (170/216)	77.1 (168/218)	60.5 (23/38)
Week 54	60.0 (15/25)	81.5 (22/27)	83.3 (5/6)	83.3 (140/168)	83.6 (143/171)	68.2 (15/22)

Conclusion

This study indicated that VDZ demonstrated a good effectiveness profile in Chinese UC patients in the real-world setting.

References

1. Yan J et al., Medicine (Baltimore). 2024; 103: e38759.
2. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
3. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.
4. Yan C et al. Am J Gastroenterol. 2023; 119: S894-S895.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Xiuli Zuo, Ye Chen, and Yingchao Li have no conflicts of interest. Lifei Gu and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.

Introduction

Patients with inflammatory bowel disease (IBD) experiencing severe flares are at increased risk of opportunistic infections, particularly cytomegalovirus (CMV), due to immunosuppressive therapy.

Aims & Methods

This study aimed to assess the prevalence and risk factors associated with CMV infection during severe acute colitis.
We conducted a retrospective analytical study on hospitalized patients with severe acute colitis. CMV infection was confirmed by positive anti-CMV IgM serology, positive colonic biopsy PCR for CMV DNA, or histological evidence of CMV cytopathic effect. Patients were divided into two groups: Group 1 (CMV-positive) and Group 2 (CMV-negative). Clinical, biological, and therapeutic data were compared (SPSS, p<0.05).

Results

Among 41 patients (mean age 39.8 years, 14 men), 17 (41.5%) had confirmed CMV infection. CMV was diagnosed by PCR (n=13), serology (n=3), or histology (n=1). Most received antiviral therapy (Ganciclovir or Valganciclovir). One patient required emergency colectomy; three experienced relapse, with two receiving Foscarnet and one undergoing colectomy for bleeding. No significant association was found between CMV infection and age, sex, disease duration, corticosteroid or immunosuppressant use, anemia, hypoalbuminemia, or CRP >45 mg/L. However, CMV infection was significantly associated with steroid resistance (p=0.003).

Conclusion

CMV infection is frequent during severe IBD flares and is strongly associated with corticosteroid resistance. Early recognition of this risk factor is essential for timely diagnosis and management to avoid complications.

Introduction

Mirikizumab (MIRI), a p19-directed antibody against interleukin-23, demonstrated improvements in fatigue, abdominal pain (AP) and stool frequency (SF) at Week (W) 12 and W52 in the VIVID-1 clinical trial.¹

Aims & Methods

The aim of this analysis is to show the effect of MIRI on fatigue, AP, SF and achievement of clinical remission by Patient-Reported Outcome (PRO; SF ≤3 and AP ≤1 and neither worse than baseline) in the VIVID-2 open-label extension study through W104. This analysis includes data from primary analysis set in patients with Crohn’s disease (CD) randomised to the MIRI treatment arm in VIVID-1 who achieved endoscopic response (≥50% reduction from baseline in Simple endoscopic score for CD) at W52 and continued the MIRI subcutaneous dosing (300 mg) in VIVID-2. Change from VIVID-1 baseline was measured for continuous endpoints. Endpoints included fatigue measured using FACIT-Fatigue (measured as change from baseline, and clinically-meaningful improvement of ≥6-points among patients with baseline ≤46), AP improvement (measured as change from baseline, and achievement of ≤1 among patients with baseline >1), SF improvement (measured as change from baseline, and achievement of ≤3 among patients with baseline >3) and clinical remission by PRO, assessed at W64 and 104. Missing data were handled using observed case (OC) and modified non-responder imputation (mNRI) for response rates, while using modified baseline observation carried forward (mBOCF) for change from baseline. Response rates were presented as unadjusted proportions with 2-sided 95% confidence intervals using the Rubin's Rules (mNRI). ANCOVA models were used for continuous variables, adjusting for baseline values and intervention group.

Results

Fatigue mean (standard error [SE]) change from baseline was 10.7 (0.56) at W64; 9.4 (0.59) at W104, (observed response, n [%]: 152 [67.6%] at W64; 136 [64.8%] at W104; Table). AP improved (mean [SE] change: −1.5 [0.04] at W64; −1.6 [0.05] at W104), with response rates increasing from 174 (77.3%) to 161 (84.7%). SF showed sustained improvement (mean [SE] change: −4.3 [0.14] at W64; −4.3 [0.16] at W104), with response rates reaching 155 (89.6%) at W104 (Table). Similar rates of achievement of clinical remission by PRO were observed (178 [73.6%] at W64; 165 [80.1%] at W104) (Table).

Table: Improvement in fatigue, abdominal pain, stool frequency and achievement of clinical remission by PRO up to Week 104

	FACIT-Fatigue (N=251)		Abdominal pain (N=251)		Stool frequency (N=251)		Clinical remission by PRO (N=251)
	Week 64	Week 104	Week 64	Week 104	Week 64	Week 104	Week 64	Week 104
Change from baselinea (mBOCF), LSM (SE)	10.7 (0.56)	9.4 (0.59)	−1.5 (0.04)	−1.6 (0.05)	−4.3 (0.14)	−4.3 (0.16)	NA	NA
Response (observed)b, n (%) (95% CI)	152 (67.6) (61.2–73.3)	136 (64.8) (58.1–70.9)	174 (77.3) (71.4–82.3)	161 (84.7) (78.9–89.2)	175 (86.6) (81.3–90.6)	155 (89.6) (84.2–93.3)	178 (73.6) (67.7–78.7)	165 (80.1) (74.1–85.0)
Responseb (mNRI), % (95% CI)	67.1 (61.0–73.3)	60.8 (54.4–67.2)	76.7 (71.2–82.2)	79.2 (73.7–84.7)	85.8 (80.9–90.6)	84.0 (78.8–89.2)	72.6 (66.9–78.2)	75.0 (69.4–80.7)

CI, confidence interval; LSM, least squares mean; mBOCF, modified baseline observation carried forward; mNRI, modified non-responder imputation; n, no of patients; NA, not applicable; PRO, Patient-Reported Outcome; SE, standard error
^aBaseline of VIVID-1 study
^bFACIT-Fatigue: ≥6-point improvement for baseline score ≤46; Abdominal pain: achievement of ≤1 for baseline score >1; Stool frequency: achievement of ≤3 for baseline score >3; Clinical remission by PRO: SF ≤3 and AP ≤1 and neither worse than baseline

Conclusion

MIRI sustained improvement in fatigue, AP, SF and clinical remission by PRO through 104 weeks of continuous treatment. These consistent findings support the long-term treatment with MIRI to address key symptoms of CD.

References

1. Ferrante, MarcTron, Emiliano, et al. The Lancet. 404 (10470):2423-2436.

Disclosure

PB: Received financial support for research from AbbVie, EG; lecture fees from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media; served on an advisory board for AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, Tetrameros. AA: Consultant for Geneoscopy; received research support from Takeda. AV, GY and JW: Employee and shareholder of Eli Lilly and Company. NL: Consultant for Eli Lilly and Company. JRA: Consultant for Janssen, Pfizer, Abbvie, Vedanta, Geneteche, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myer Squibb, Roivant, Celltrion, and TRXBio, Xencor, Shattuck Labs; Speaker for Abbvie, Janssen. MC: Provided educational activities for AbbVie, China Medical System, IPSEN, Janssen, and Takeda; served on an advisory board for Boehringer Ingelheim and Janssen; and has support for clinical research from Janssen and Takeda.