bluuebunny/crossref_metadata_2025_split huggingface dataset:
P181 infliximab exposure during induction associate with time to remission and disease control of inflammatory bowel disease
Authors: Laharie D , Rabizadeh S , D’Haens G , Dubinsky M , Panetta J C , Everts-van der Wind A , Dreesen E , Spencer E , Vermeire S , Dervieux T 
Published: January 2023

Abstract

Background
Infliximab (IFX) exposure is established predictive factor of pharmacokinetic (PK) origin in inflammatory bowel disease, and expert consensus is to achieve adequate exposure during induction (1). We evaluated the performance of a Bayesian PK tool in IBD patients starting IFX.

Methods
Trough IFX collected immediately before the third and fourth infusion (corresponding to week 6 and 14 on a standard dosing schedule, respectively) were evaluated from 307 IBD patients starting IFX and enrolled in three cohorts of IBD. The first cohort patients was adult CD enrolled in the TAILORIX trial (n=101, mean age [SEM]: 35.0±1.4 years, 60% female) (2), a second cohort was from the PRECISION trial (n=158, mean age 15.8±0.5, 75% CD, 46% female) (3) and a third cohort consisted of pediatric patients (n=45, mean age 13.2±0.5, 71% CD, 40% female). Forecasted IFX concentration at the 4th infusion were estimated using serum IFX, antibodies to IFX and albumin determined at the third infusion using population PK calculator with Bayesian prior. The outcome variable was a CRP-based clinical remission during follow-up with CRP levels below 3 mg/L in the absence of symptoms (corresponding to remission). Sustained CRP-based clinical remission status over the maintenance period was also calculated. Statistics consisted of Kaplan Meier analysis with calculation of Hazard ratio (HR), and logistic regression.

Results
IFX concentration above 15 µg/mL before the third infusion had shorter time to CRP-based clinical remission as compared to IBD with IFX concentration below 15 µg/mL (mean followup: 182±11 days). Measured IFX concentrations above 10 µg/mL before the 4th infusion were also associated with a higher rate and shorter time to remission (p&lt;0.01). Similar results were observed with forecasted concentration above 10 µg/mL at the 4th infusion (p&lt;0.01). In the presence of IFX concentration above 15 µg/mL there was a 2.5-fold higher likelihood of sustained CRP based clinical remission status during maintenance as compared to IFX concentrations below 15 µg/mL (p&lt;0.01). Forecasted IFX level above 10 µg/mL at 4th infusion associated with 3.9-fold higher likelihood of CRP-based clinical remission. (p&lt;0.01).

Conclusion
These data further support that IFX concentrations above recommended cutoffs are best to predict enhanced disease control. Patients presenting with low forecasted exposure may benefit from dose intensification sooner than the scheduled standard infusion.
References:
(1) Cheifetz AS et al. Am J Gastroenterol. 2021 116:2014-2025. (2) D’Haens G et al., Gastroenterology. 2018 154:1343-1351. (3) Dubinsky M et al. Inflamm Bowel Dis. 2022 28:1375-1385
P186 Impact of tofacitinib maintenance therapy on key Ulcerative Colitis patient-reported outcomes of fatigue, urgency, abdominal pain and sexual dysfunction using IBDQ and SF-36 individual items as proxies
Authors: Dubinsky M C , Gardiner S , Hur P , Guo X , Paulissen J , Cappelleri J C , Bushmakin A G , Panés J 
Published: January 2023

Abstract

Background
Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This novel analysis evaluated tofacitinib outcomes using items from the Inflammatory Bowel Disease Questionnaire-32 (IBDQ) and Short Form-36 Health Survey (SF-36) as proxies for key UC patient-reported outcomes (PROs) of fatigue, urgency, abdominal pain and sexual dysfunction over 52 weeks of maintenance treatment.

Methods
Data from 593 patients with UC in OCTAVE Sustain (NCT01458574) were included.1 PROs were assessed via self-reported proxy items for each UC symptom/dysfunction of interest in the IBDQ and SF-36. A longitudinal mixed-effects model compared tofacitinib 5 and 10 mg twice daily (BID) vs placebo up to 52 weeks for change from baseline (CFB) in each predefined IBDQ and SF-36 item. Least squares (LS) mean differences and standardised effect sizes (ES; LS mean difference divided by the standard deviation [SD] of baseline item scores) were calculated for tofacitinib vs placebo; ES of 0.1, 0.2, 0.5 and 0.8 were trivial, small, medium and large, respectively, with ES categorisation intervals defined as the midpoints between these absolute values.2 LS means and ES (LS mean/SD of baseline item scores) for both tofacitinib doses and placebo at Week 52 vs baseline were calculated. p&lt;0.05 denoted statistical significance.

Results
At Week 52, all IBDQ proxies were improved with tofacitinib 5 and 10 mg BID vs placebo, with significant LS mean differences. Large ES were reported for fatigue and urgency proxies; abdominal pain and sexual dysfunction proxies had medium ES (Figure 1). For SF-36 proxy items, LS mean differences vs placebo were significant at Week 52, except for the SF-36 fatigue proxies, ‘Did you feel worn out?’ and ‘Did you feel tired?’ (both 5 and 10 mg BID). Small to large ES were reported for fatigue proxies; the abdominal pain proxy had medium to large ES (Figure 2). Regarding CFB, tofacitinib 5 and 10 mg BID maintained responses in IBDQ and SF-36 proxies at Week 52. LS mean changes from baseline in IBDQ items were generally not significant with tofacitinib; this was not as evident for SF-36 items. Trivial to small ES were reported for tofacitinib 5 and 10 mg BID, and medium to large ES for placebo. Significant worsening was observed with placebo for all items of interest.

Conclusion
Compared with placebo, tofacitinib 5 and 10 mg BID had better IBDQ and SF-36 proxy item responses at Week 52, as reflected through ES. Responses were maintained over 52 weeks with tofacitinib therapy but worsened with placebo. Proxy items have not been validated to measure the symptom PROs of interest.
1. Sandborn WJ et al. N Engl J Med 2017;376:1723–1736.
2. Dubinsky MC et al. Inflamm Bowel Dis 2021;27:983–993.
P188 Middle small-bowel segment Lewis score may predict long-term outcomes among patients with quiescent Crohn’s disease
Authors: Ukashi O , Yablecovitch D , Lahat A , Selinger L , Neuman S , Eliakim R , Ben-Horin S , Kopylov U 
Published: January 2023

Abstract

Background
Video capsule endoscopy (VCE) has been proven to accurately diagnose small-bowel inflammation and predict flares among patients with quiescent Crohn’s disease (CD). In this study we aimed to predict worse clinical outcomes over an extended follow-up.

Methods
This was a post-hoc analysis of adult patients with quiescent small-bowel CD who were followed with VCE, inflammatory biomarkers and magnetic resonance enterography (MRE) in a prospective study (between 2013-2018). We extracted extended clinical data from our hospital electronic health records to include the most recent follow-up (until Apr 2022). The primary composite outcome was clinical exacerbation defined as either intestinal-surgery, endoscopic dilation, CD-related admission, need for corticosteroids or biological/immunomodulator treatment change during the follow-up.

Results
Out of the 61 patients who were included in the study (median age of 29 [24-37] years, male–57.4%, current biologic treatment–46.7%), 18 patients met the composite outcome during an extended long-term follow-up (median of 58 [interquartile range 35-93] months). On univariable analysis, complicated (Hazard ratio [HR] 7.348, p=0.002) and stricturing disease-phenotype (HR 5.305, p=0.001) were associated with higher risk for clinical exacerbation during follow-up. A baseline VCE middle small-bowel segment Lewis score (midLS) of≥135 identified patients with future exacerbation (AUC of 0.767, 95% CI 0.633-0.902, p=0.001, HR 6.317, negative predictive value [NPV] of 93%), while the conventional Lewis score had an AUC of 0.734 (CI 0.589-0.879, p=0.004). Performing sensitivity analysis restricted to patients with either complicated (n=34) or stricturing disease-phenotype (n=26), we revealed that midLS still predicted disease exacerbation during the extended follow-up (AUC of 0.747 and 0.753, respectively) in these patients.

Conclusion
MidLS predicts treatment failure in quiescent Crohn's disease patients (median follow-up 5 years) independently of disease-phenotype.
P190 Delayed IBD diagnosis leads to worse outcomes over years, with multiple implications on service delivery
Authors: Rao A , Bazarova A , Mitra P , Majumder S , Parigi T , Ghosh S , Iacucci M , Shivaji U 
Published: January 2023

Abstract

Background
Delays in diagnosis can be patient and health-system related. Such delays have been reported to increase overall complications in Inflammatory Bowel Diseases (IBD). The aim of our study was to report on the impact of delays on IBD-related adverse outcomes (AOs), as hospitals currently face challenges with long waiting lists in the post-COVID-19 era.

Methods
New patients referred for suspected IBD to a single tertiary care centre between Jan 2013 to Dec 2017 were identified using EMR. A cut-off time was set for each delay-type based on best average hospital waiting times. Reasons for delays until start of treatment and data on pre-defined AOs (steroid & other rescue therapies, hospitalisations, surgery) were recorded for each patient until end of June 2021. Data was analysed using multiple Pearson correlations and Cox proportional Hazard model to determine if there was a difference in survival without AOs between patients with and without delay.

Results
105 patients were identified using strict criteria (M=58; median age=32y) with a median follow-up of 55 months. The most frequent presenting complaints were abdominal pain (44, 41.9%), loose stools (40, 38.1%), bloody diarrhoea (37, 35.2%) and bleeding per-rectum (33, 31.4%). 65, 27 and 13 patients had a final diagnosis of Ulcerative colitis, Crohn’s disease and Unclassified colitis respectively, and were analysed jointly.
The longest delay-types noted: patients seeking medical attention (median=4 months; range 1 to 84 months); arranging gastroenterology clinic review after GP referral (median=5 weeks; 1 to 30 weeks); and waiting for index endoscopy (median=3 weeks; 1 to 36 weeks).
Patient stratification based on delay-type, using specific cut-off times for each showed a statistically significant difference in survival without AOs for all (when comparing delay vs no delay).
- delay in seeking medical attention (cut-off=1m; p=0.004) (Fig 1A)
- delay in GP referral to specialty review (cut-off=1w; p=0.048)
- delay in index endoscopy (cut-off=4w; p=0.01) (Fig 1B)
- delay in starting treatment (cut-off=4w; p=0.03)
Fig 1A-Time to seek medical attention (survival without AOs; p=0.004)

Fig 1B-Time from clinic review to index endoscopy (survival without AOs; p=0.01)

Conclusion
Several bottlenecks of delays increase AOs in IBD over the follow-up period. A delay as short as a week, between GP referral to specialty review, is significant in determining AOs, relevant for specialist IBD centres particularly in the post-Covid period. Endoscopy units should prioritise suspected IBD patients to reduce AOs, which is likely to have implications on service delivery and planning. Long delays observed in patients seeking medical attention highlights the need for better patient education in the community.
P191 Robotic Surgery shows significant promise in delivering superior outcomes for patients with Inflammatory Bowel Disease
Authors: Karri R , Grewal C , Yassin N 
Published: January 2023

Abstract

Background
Robotic surgery is a relatively novel surgical advancement in minimally invasive surgery for patients with Inflammatory Bowel Disease (IBD). The pathophysiology of the disease inherently makes these surgeries more complex with high complication rates. This study aimed to the evaluate the efficacy of robotic procedures for such patients and compare the short-term outcomes with laparoscopic surgery in patients with IBD.

Methods
A retrospective review was conducted of all patients who underwent robotic and laparoscopic surgery for IBD between November 2018 and April 2022 at a single institution. Demographics, peri-operative, intra-operative and post-operative data were analysed.

Results
24 robotic cases were performed in the time period (75% Crohn’s) whilst 18 cases were performed laparoscopically (39% Crohn’s). Majority of the robotic patients had a Right Hemicolectomy (63%) with stoma formations in 38% of the procedures. 44% of the laparoscopic patients had a Total Colectomy and 39% had a Right Hemicolectomy with 78% of them having stomas. There was no significant difference in the patients age or BMI with a median age of 30 and BMI of 24.1 in the laparoscopic surgeries and a median age of 36 and BMI of 24.8 in the robotic group. The median operative time for the laparoscopic procedures was longer with 250 minutes versus 220 minutes in the robotic patients. The length of hospital stay for the patients was also greater for laparoscopic patients with a median of 9 compared to 6 days for robotic patients. 3 patients necessitated return to the ward within 30 days after laparoscopic surgery (17%) compared to only one robotic case (4%). However, 2 patients had a Clavin Dindo Grade 3 complication after robotic surgery compared to one in the laparoscopic set. In both sets of patients, one patient required surgery within 30 days: the robotic patient requiring laparotomy for adhesion-lysis and the laparoscopic patient for wound closure post wound dehiscence. Zero cases across all the patients necessitated conversion to open surgery and the mortality rate was 0%.

Conclusion
The results of this single centre study provide further support to studies demonstrating the feasibility and efficacy of robotic surgery in IBD patients. Patients operated robotically had a comparable safety profile with a similar complication rate whilst having whilst having shorter operating times and shorter length of hospital stay. Length of stay in hospital is a surrogate marker for early recovery post-surgery and carries significant benefit in the modern-day demand for hospital bed spaces. Therefore, robotic surgery offers a potentially superior alternative in minimally invasive surgery.
P199 Clonal patterns between pouch neoplasia and prior colorectal neoplasia in Inflammatory Bowel Disease patients: an exploratory cohort study
Authors: Van Lierop L , te Groen M , Derikx L , Ylstra B , Hoentjen F , Nagtegaal I , Simmer F 
Published: January 2023

Abstract

Background
Inflammatory Bowel Disease (IBD) patients with an ileo-anal pouch anastomosis (IPAA) bear an increased risk of pouch neoplasia, with prior colorectal neoplasia as the strongest predictor. It is unknown if pouch neoplasia develops independently or is derived from prior colorectal neoplasia. Therefore, we aimed to elucidate the pathogenesis of pouch neoplasia by assessment of clonality between prior colorectal neoplasia and pouch neoplasia in IPAA patients with IBD.

Methods
In this explorative study we used the Dutch Nationwide Pathology Databank to identify IBD patients with both pouch neoplasia and prior colorectal neoplasia. Clonality was assessed on tissue with shallow whole genome sequencing based copy number aberration (CNA) analysis and validated with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

Results
Three out of 13 included patients showed clonally matching CNA profiles between colorectal neoplasia and pouch neoplasia, validated with matching IHC and FISH for p16 and HER2. Patients with clonal samples corresponded with concordant histology pre- and post IPAA, positive resection margins, metastasized disease or a short interval (&lt;2 years) between colorectal and pouch neoplasia diagnoses.

Conclusion
CNA provides a feasible method for clonality assessment in patients with colorectal neoplasia and subsequent pouch neoplasia. Most pouch neoplasia in our cohort were molecularly different from their prior colorectal neoplasia. This may indicate a multifactorial pathogenesis of pouch neoplasia.
P201 Assessment of factors associated with cumulative bowel damage in surgically naïve patients using Lemann index and global MaRIA index in Crohn’s disease
Authors: Domislović V , Hrabric Sonje K , Brinar M , Cukovic-Cavka S , Turk N , Grgic D , Barisic A , Jelakovic M , Prutki M , Krznaric Z 
Published: January 2023

Abstract

Background
The Lémann index (LI) is a unique tool that measures cumulative bowel damage in Crohn’s disease (CD) and is composed of surgical procedures and severity and extent of bowel lesions according to endoscopy and MR enterography (MRE). Since there is a significant contribution of previous surgery in LI calculation, our aim of this study is to investigate factors associated with cumulative bowel damage using LI in both total population and surgically naïve patients.

Methods
In this cross-sectional study, LI was calculated evaluating 20 small bowel, 7 large bowel and 3 upper GI segments. For each segment bowel resections, inflammatory, stricturing or penetrating lesions were considered using MRE and upper and lower endoscopy. Global MaRIA (gMaRIA) index was calculated using following parameters on 6 bowel segments on MRE: bowel wall thickness, ulcers, edema, and relative contrast enhancement. Longstanding disease was ≥10-year duration. Disease activity was defined as CRP&gt;5 or HBI≥5. Extent and disease behavior were assessed using Montreal classification. Multivariate logistic regression adjusted for confounders was performed (age, gender, BMI, smoking status, CRP, disease behavior and extension, biological therapy, gMaRIA score, and HBI).

Results
This study included 320 CD patients [age 36 (24-46), 54.6% males, disease duration 7.2 (1-14) years, BMI 21.3 (17.4-24.8) kg/m2]. There were 142 (44.4%) surgically naïve and 128 (40%) patients with longstanding disease. In total population, higher LI values were observed among those with longstanding disease (10.31 vs 5.35 years, p&lt;0.001), patients treated with biological therapy (9.7 vs. 6.4, p=0.005) and prior surgery (11.81 vs. 1.62, p&lt;0.005). There was no difference in LI according to activity (p=0.921) and smoking status (p=0.336). Multivariate analysis on total population revealed independent predictors of elevated LI which were BMI (β=-0.268, p&lt;0.02), disease duration (β=0.120, p=0.041) and prior surgery (β=5.42, p&lt;0.001). Hence, separate multivariate analysis was performed on surgically naïve which revealed following predictors of LI (other than surgery): current smoking (β=1.14, p=0.010), perianal disease (β=1.39, p=0.02) and gMaRIA score (β=0.093, p&lt;0.001).

Conclusion
Positive predictors of cumulative bowel damage in surgically naïve patients were smoking, perianal disease, and radiological activity (gMaRIA), while in total population longer disease duration, BMI and prior surgery. There are several important contributing variables on cumulative bowel damage which were revealed after removing previously operated patients, which would otherwise remain unrecognized. This risk factors in CD could stratify patients at high risk for complicated course of disease.
P211 Factors associated with estimated cardiorespiratory fitness in patients with Inflammatory Bowel Disease: an exploratory analysis of real-world data
Authors: Demers K , Rezazadeh Ardabili A , Bongers B C , Romberg-Camps M J L , van Bodegraven A A , Jonkers D M A E , Pierik M J , Stassen L P S 
Published: January 2023

Abstract

Background
Cardiorespiratory fitness (CRF) as a potential predictor of disease outcome in Inflammatory Bowel Disease (IBD) is understudied, as are risk factors for impaired CRF. Lifestyle interventions focusing on improving CRF may aid in enhancing subjective health, decreasing disability, or even controlling inflammation. The aim of this exploratory study was to investigate risk factors for low estimated CRF (eCRF), as well as the association between eCRF and patient-reported outcomes of IBD in a real-world cohort.

Methods
A cross-sectional multicenter study was performed between 26 Oct 2021 and 19 Oct 2022, enrolling IBD patients using the remote monitor platform myIBDcoach. Patients reported on disease activity, lifestyle factors, and psychosocial functioning. The four-question Modified Duke Activity Status Index (M-DASI-4Q) was used to assess eCRF, which is a simple screening tool for detecting the risk of impaired CRF as objectively measured with physical exercise tests. The number of positive responses to each of the four questions determines the final score, ranging from 0 to 4. To date, no accepted cut-off for (e)CRF has been identified for patients with IBD. Therefore, an M-DASI-4Q score below the 25th percentile of the study population was exploratively used to define low eCRF. Multivariable logistic regression analysis was performed to identify factors associated with eCRF.

Results
In total, 410 patients were included, of which 91 (22.2%) had low eCRF. The median M-DASI-4Q score was 3 (IQR 2-4). Low eCRF was characterized by higher age, female sex, higher BMI, and more comorbidities compared to patients with adequate eCRF (Table 1). Patients with low eCRF reported statistically significant higher levels of fatigue and stress, lower subjective disease control, and, remarkably, higher physical activity levels (Table 2). Multivariable logistic regression showed that female sex (adjusted Odds Ratio [aOR] 3.09), higher BMI (aOR 1.06), more comorbidities (aOR 3.77, aOR 8.52), fatigue (aOR 2.26), lower subjective disease control (aOR 0.90), and higher physical activity levels (aOR 2.29) were associated with low eCRF (Table 3).

Conclusion
In this exploratory study, we described an association between eCRF and patient- and clinical characteristics (sex, BMI, and comorbidities), as well as patient-reported outcomes of IBD (fatigue, and subjective disease control). Future research should investigate the validity of the M-DASI-4Q and determine thresholds for referral for further objective assessment for patients that might benefit from personalized interventions. Furthermore, future studies should further elucidate the interaction between physical activity and (e)CRF in patients with IBD to define recommendations.