bluuebunny/crossref_metadata_2025_split huggingface dataset:
P279 Excessive accumulation of neutrophils in the epithelium, but not lamina propria, predicts resistance to ustekinumab in ulcerative colitis
Authors: Saifuddin A , Powell N 
Published: January 2024

Abstract

Background
Many patients experience primary treatment resistance when treated with ustekinumab for ulcerative colitis (UC). Predictive clinical parameters would allow such individuals to be identified pre-treatment so alternative strategies could be initiated. We explored the utility of the different histological features present in baseline samples to predict ustekinumab resistance.

Methods
We assessed the total Geboes score (TG) (0–22, least to most severe), and the epithelial and lamina propria neutrophil subscores (EpiN and LpN, respectively) (both 0–3) in a subset of patients with moderate-to-severely active UC (n = 448) enrolled in the phase 3 UNIFI study that evaluated the efficacy of ustekinumab therapy. We explored the relationships between histological parameters and clinical indices of activity, including faecal calprotectin (FCP), CRP, Mayo score, and treatment outcomes (clinical remission, endoscopic healing and mucosal healing at week 8, and disease clearance, which combines these all) using Spearman rank correlation. Area under the receiver operating characteristic curve (AUC) analyses were performed (presented with 95% confidence interval, CI). Analyses were performed using R 4.2.3 (Vienna, Austria) and GraphPad Prism (v 9.5.1).

Results
TG correlated highly with EpiN (ρ = 0.804, p &lt; 0.0001) but did not correlate with LpN (ρ = 0.082, p = 0.07). Neither EpiN (ρ = 0.081, p = 0.09) nor LpN (ρ = -0.011, P = 0.82) correlated with FCP, though EpiN correlated weakly with log10FCP (ρ = 0.113, p = 0.017). Full Mayo score correlated with EpiN (ρ = 0.23, p &lt; 0.0001) and TG (ρ = 0.23, &lt; 0.0001).
Of the patients with pre-treatment EpiN of 0, 23.1%, 26.9%, 23.1% and 19.2% experienced clinical remission, endoscopic healing, mucosal healing and disease clearance, respectively. Response rates incrementally reduced as EpiN increased, such that 4.2%, 12.5%, 8.3% and 4.2% of patients with EpiN of 3 achieved these outcomes, respectively. Similar trends were seen with tertiles of TG, though not with LpN. EpiN and TG predict mucosal healing with AUC 0.59 (CI: 0.50 - 0.68; p = 0.044) and 0.61 (CI: 0.52 - 0.70; p = 0.016), respectively. The addition of other clinical variables did not improve performance of the models.

Conclusion
There is weak or insignificant correlation between Geboes score parameters and other clinical indices of UC activity. EpiN and TG, but not LpN, stratify patients’ response to ustekinumab, with almost 6-fold difference in clinical remission between high and low EpiN. TG and EpiN predict resistance to ustekinumab, suggesting that the epithelial inflammatory milieu may be key to driving resistance to ustekinumab and possibly other therapies. This supports recent evidence highlighting the role of neutrophils in resistant UC.
P325 Post-COVID general health symptoms in patients with Immune Mediated Inflammatory Diseases
Authors: Van De Pol N , van der Woude C J , Vis M , van Doorn M , Schrauwen S L , Cetinözman-Teunissen F , West R L , Pan Q , de Vries A C 
Published: January 2024

Abstract

Background
Post-COVID entails persistent symptoms following a presumed or confirmed SARS-CoV-2 infection and has a prevalence of 12.5% in the general population in The Netherlands. The aim of this study is to evaluate post-COVID general health symptoms reported by patients with Immune Mediated Inflammatory Diseases (IMIDs), given the unclear prevalence.

Methods
An online questionnaire was distributed to IMID patients at dermatology, rheumatology and gastroenterology departments in an academic and teaching hospital in Rotterdam, the Netherlands. Only patients on systemic therapy were included. General health symptoms were compared between patients with and without prior SARS-CoV-2 infection. Multivariable logistic regression, adjusted for disease-related factors and known post-COVID risk factors, was performed to assess the association between SARS-CoV-2 infection and symptom occurrence. Additionally, the self-reported prevalence of post-COVID symptoms was assessed by asking patients if they linked their symptoms to the previous SARS-CoV-2 infection.

Results
The final study population comprised 1,518 patients, of whom 58% (n=877) reported ≥ 1 SARS-CoV-2 infections (table 1). More patients with a prior SARS-CoV-2 infection reported general health symptoms compared to those without (56% vs 44%; P&lt;0.001) (figure 1). After adjusting for potential risk factors, including age, sex, smoking, diagnosis, SARS-CoV-2 vaccination status, and immunosuppressive therapy, a consistent significant association was found between SARS-CoV-2 infection and symptoms (OR 1.53; 95%CI 1.23-1.91; P&lt;0.001). Sub-analysis showed a significant association between self-reported COVID-19 severity and symptoms, while presumed SARS-CoV-2 variant (based on date of reported infection) and number of infections were not associated. Fatigue was the most common symptom in both patients with and without a previous SARS-CoV-2 infection, with significantly higher prevalence among patients with previous SARS-CoV-2 infection (42% vs 32%; P&lt;0.001). After adjusting for the potential risk factors, a previous SARS-CoV-2 infection remained significantly associated with fatigue (OR 1.31; 95%CI 1.04-1.64; P=0.021). Of the patients with a prior SARS-CoV-2 infection, 14% (122 out of 877) reported post-COVID symptoms, with fatigue as the most common complaint (78%).

Conclusion
The self-reported prevalence of post-COVID general health symptoms among IMID patients on systemic therapy (14%) aligns with that of the general population. The prevalence of symptoms, particularly fatigue, is elevated in patients with a history of a SARS-CoV-2 infection. Our findings emphasize the importance of incorporating SARS-CoV-2 infection history when evaluating fatigue in IMID patients during outpatient visits.
P326 Impact of disease flares on resource use, health-related quality of life and productivity in untreated Crohn’s Disease patients in US: an analysis of national health and wellness survey data
Authors: Dubon-Garcia A , Naessens D , Pollack P , Sikirica M , Sanon M 
Published: January 2024

Abstract

Background
Patients with Crohn’s Disease (CD) alternate periods of exacerbation, flares, and periods of remission. The periods of flares can be debilitating to patients causing significant discomfort impacting the patient’s health-related quality of life (HRQoL). Despite symptoms, many patients do not receive treatments for their condition thus our objective was to describe the burden related to healthcare resource utilization (HRU), HRQoL and work productivity among a real-world cohort of patients who are not receiving any prescribed medications for CD.

Methods
The 2019 National Health and Wellness US Survey (NHWS) data was analyzed. NHWS is a self-administered Institutional review board (IRB) approved, internet-based annual survey that assesses numerous health conditions, demographic characteristics, medical history, healthcare utilization, attitudes, and outcomes. Respondents currently not taking prescription treatment for CD were categorized by flare frequency as infrequent (0-2 flares/year), intermediate (3-6/year), and frequent (&gt;1/month to &lt;7/week). HRU included HCP visits, gastroenterologist visits, emergency room (ER) visits and hospitalizations. HRQoL was assessed using the 5-dimension EuroQoL questionnaire (EQ5D), and work activity impairment using the Work Productivity and Activity Impairment questionnaire.

Results
A total of 74,994 respondents participated in the survey, of whom 577 reported being diagnosed with CD and 231 (40.0%) of whom were not taking prescription treatment for CD. Fifty-six percent of the untreated sample reported having mild disease. Among the untreated patients, 37% reported infrequent, 21% intermediate and 42% frequent flares. The mean age of patients with frequent flares was lower than those with infrequent or intermediate flares (infrequent: 51 years; intermediate: 45 years; frequent: 41 years). The mean EQ5D summary score decreased as the frequency of flares increased (infrequent: 0.77, intermediate: 0.66 and frequent: 0.63). Patients with frequent flares had higher gastroenterologists, ER and hospitalization rates compared to patient with infrequent of intermediate flares (Table 1). Overall work impairment was reported by 40%, 52% and 63% of patients with infrequent, intermediate, and frequent flares respectively (Figure 1).

Conclusion
This real-world analysis shows up to two-thirds of untreated CD patients present intermediate or frequent flares. In addition, those with frequent flares experienced poorer HRQoL, lower work productivity, and had higher healthcare resource use. This study reveals a high level of disease burden in patients who are not receiving treatment, the majority of whom reported to have ‘mild’ disease.
P340 The association between colon pseudopolyps presence and clinical adverse events in UC patients treated with biologics
Authors: Tomasic V , Biscanin A , Cacic P , Babic F , Burcul I , Siranovic Pongrac I , Kralj D , Dorosulic Z , Ogresta Kordej D , Hrabar D 
Published: January 2024

Abstract

Background
Colon pseudopolyps (aka post-inflammatory polyps) are potential marks of previous severe ulcerative colitis (UC) activity. The association between outcomes of patients treated for UC with biologics and presence (or lack of presence) of pseudopolyps, are unclear.

Methods
A single center, noninterventional retrospective cohort review study was performed on real-life data of adult patients with moderate-to-severe UC who were treated with biologics (infliximab, vedolizumab, ustekinumab) for a minimum of 6 months. The difference in first occurence of treatment failure defined as a negative composite outcome (need for steroid rescue therapy, biologic switch, IBD-related hospitalization and/or surgery) between two groups (with or without pseudopolyps) was investigated. Participants’ characteristics were assessed using descriptive statistics. Normal distribution was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Categorical variables were analyzed using Chi-square test and continuous variables using Mann-Whitney test. Kaplan-Meier analysis and log-rank test were used in order to assess difference in therapy duration between two groups.

Results
Total of 92 patients (51% females; smokers 17%; 24% with pseudopolyps) were included. There were no differences in key baseline characteristics such as age, sex, smoking status, extraintestinal manifestations, serum albumin and CRP as well as fecal calprotectin levels between groups of patients with or without pseudopolyps. Median duration of follow up was 18.5 months (IQR 8-37). Presence of pseudopolyps was not associated with a higher risk for treatment failure; there was no statisticaly significant difference in the occurrence (χ2(1, N =91)=1.38, p=0.31) of negative composite outcomes or time to develop negative composite factor (χ2(1, N =91)=1.57, p=0.21).

Conclusion
In our cohort we have failed to detect any association between presence of colon pseudopolyps and rates of first occurence of treatment failure in UC patients treated with biologics.
P362 Mesenteric fat proliferation and fat edema in magnetic resonance enterography as predictor of long-term disease complications in Crohn’s disease
Authors: Spector Cohen I , Lopez-Alonso R , Ben Hur D , Ron S , Ilivitzki A , Waterman M 
Published: January 2024

Abstract

Background
Fibrofatty proliferation of the mesenteric fat is a common finding in magnetic resonance enterography (MRE) in patients with Crohn’s disease (CD). Mesenteric fat is thought to play an active role in inflammation, fibrosis and stricture formation in CD. However, it is unclear whether these findings have a prognostic value in prediction of bowel damage and complications. We aimed to examine the association between mesenteric fat proliferation and inflammation on MRE and risk for hospital admissions and bowel surgery.

Methods
Patients with established CD diagnosis with at least 1 available MRE imaging data were followed for hospital admissions for CD exacerbation or abdominal surgery. MRE were reviewed by an expert radiologist for various characteristics (intestinal wall thickening and enhancement, stricture, or abscess formation, fibrofatty proliferation and fat edema reflecting fat inflammation).
The association between mesenteric fat and outcomes was assessed using the Kaplan Meier method and log rank test. Crude and adjusted Hazard ratios (HR) with 95% confidence interval (CI) adjusting for baseline MRE characteristics (wall thickness and stricture and pre-stenotic dilatation) were estimated from the Cox proportional hazards regression model (R version 4.2.1).

Results
159 CD patient charts and MRE imaging data were analyzed. Patients’ characteristics and medication exposure at described in table 1. On initial MRE the frequency of mesenteric fat proliferation was noted in 43 (27.0%) and fat edema in 79 (49.7%). Other MRE features noted were: mild, moderate and severe wall thickening in 72 (45.5%), 47 (29.9%) and 11 (7.0%) patients, respectively. Contrast intestinal wall enhancement was present in 122 (76.7%) patients. Intestinal stricture with pre-stenotic dilatation was noted in 17 (10.7%) patients and abscess and fistula formation was seen in 10 (6.3%) and 11 (6.9%) patients, respectively. During a mean (SD) follow up of 95.7 (39.5) months, 100 (62.9%) and 40 (25.2%) patients underwent hospitalization or surgery, respectively. On survival analysis, fat proliferation was associated with hospitalizations (Fig 1A, p=0.0005) and surgery (fig 1B, p&lt;0.0001), while fat edema was associated with abdominal surgery (Fig 1D p=0.0003) but not with hospitalization (Fig 1C p=0.28). On multivariable analysis of the associations between fat proliferation and surgery and hospitalization remained highly significant (adjusted HR (95%CI) =3.15 (1.57-6.33) and adjusted HR (95%CI) =1.77 (1.06-2.97), respectively.

Conclusion
in this analysis of baseline MRE features, mesenteric fat proliferation was independently associated with increased risk for abdominal surgery and hospital admission for disease flares.
P376 A prospective multi-model study on diagnostic performance of 18F-FAPI PET/CT in comparison with 18F-FDG PET/CT or magnetization transfer MR imaging to detect intestinal fibrosis in Crohn’s disease
Authors: Li Z , Wang Y , Zhang R , Huang S , Feng S T , Li X 
Published: January 2024

Abstract

Background
Accurate and early detection of Crohn's disease (CD) induced intestinal fibrosis is crucial for effective clinical management, yet it remains an unmet requirement. The magnetization transfer MR Imaging (MTI) was reported to offer high accurancy for detection of intestinal fibrosis. Recently, the utilization of fibroblast activating protein inhibitor (FAPI) PET/CT has emerged as a promising tool for assessing fibrosis. The diagnostic efficacy of 18F-FAPI PET/CT in detecting intestinal fibrosis was compared with that of 18F-FDG PET/CT and MTI.

Methods
Twenty-two rats were treated with TNBS for 2-4 weeks to simulate fibrosis development, and multi-model quantitative imaging was performed during a week. The mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated on 18F-FAPI and 18F-FDG PET/CT, as well as the normalized magnetization transfer ratio on MTI (normalized MTR). Pathological evaluation of intestinal fibrosis was performed, and MTI was used as the imaging standard for fibrotic analysis. Imaging and pathological criteria were used to compare the diagnostic effects of fibrosis imaging parameters. Ten patients with 34 cases of intestinal stenosis were prospectively recruited to validate their diagnostic performance using the same imaging protocol.

Results
In patients, the accuracy of MTI (AUCs=0.90-0.91, P≤0.05) was comparable to FAPI uptake (AUCs=0.80-0.87, both P≤0.01) but higher than that of FDG uptake in distinguishing between non-to-mild and moderate-to-severe fibrosis (AUCs=0.53-0.82, P=0.01-0.36). In rats, FAPI uptake showed a rapid response to intestinal fibrosis at an early disease phase (week 0-2) and demonstrated a significant increasing trend with prolonged treatment duration (week 0-4;). In contrast, normalized MTR and FDG uptake presented only a minimal response at week 2 and did not correlate so clearly with treatment duration. Consistently, in early disease phase (rats treated till week 2), the correlations of FAPI uptake (SUVmean: R=0.69) with fibrotic scores were stronger than those of FDG uptake (SUVmean: R=0.17) and normalized MTR (R=0.52). In late disease phase (rats treated till week 3 or 4), normalized MTR (R=0.93) showed stronger correlations with fibrotic scores than FAPI uptake (SUVmean: R=0.55) or FDG uptake (SUVmean: R=0.19).

Conclusion
In accurately identifying early-stage intestinal fibrosis, 18F-FAPI PET/CT demonstrates vast potential and outperforms the performance of the other two imaging modalities, warranting further research. However, 18F-FAPI PET/CT offer an equal performance for characterization of intestinal fibrosis with MTI and has significant advantages compared to 18F-FDG PET/CT in the whole disease course from Crohn's disease.
P378 The link between periodontitis and disease activity in inflammatory bowel disease
Authors: Madsen G R , Bertl K , Pandis N , Stavropoulos A , Burisch J 
Published: January 2024

Abstract

Background
Periodontitis and inflammatory bowel disease (IBD) share similarities in their aetiopathogenesis and patients with IBD are reported to have more often severe periodontitis. Conversely, recent studies have suggested that periodontitis also impacts IBD activity. In this study we used two distinct IBD-populations to assess whether the presence of periodontitis is associated with increased IBD activity, disability, and severity.

Methods
Identical questionnaire-based surveys were conducted in Sweden and Denmark, distributed by the respective patient-organisations. The survey included self-reported oral health as well as IBD-related characteristics. Oral health was assessed by the Periodontal Screening Score (PESS), which is a validated instrument to screen for severe periodontitis (indicated by a score ≥5), and by the number of remaining teeth, as tooth loss is the ultimate outcome of untreated periodontitis. Disease activity in patients with ulcerative colitis (UC) was assessed by the Simple Clinical Colitis Index (SCCAI), and in Crohn’s disease (CD) by the Harvey & Bradshaw’s Activity Index (HBI). Disease related disability was assessed by the Inflammatory bowel disease disability index (IBD-DI).

Results
In total, 1,879 IBD patients, encompassing 898 patients (47.8%) with UC and 981 patients with CD (52.2%), completed the questionnaire. In both UC and CD, severe periodontitis was significantly associated with a higher level of current disease activity [OR 1.51 (1.18;1.93); p=0.001] based on SCCAI/HBI, increased IBD disability score [Coef. 3.62 (1.46;5.79); p=0.001], and increased disease activity in the last 12 months (defined as number of episodes of disease activity in the last 12 months) [OR 1.50 (1.20;1.87); p=&lt;0.001]. Tooth loss (&lt;20 remaining teeth) was associated with both an increased disease activity in the last 12 months [OR 1.36 (1.05;1.76); p=0.018] as well as IBD disability score [Coef. 4.15 (1.66; 6.65); p=0.001]. Tooth loss also showed a tendency to be associated with current disease activity (SCCAI/HBI), although this was not significant [OR 1.31 (0.99;1.75); p=0.062]. IBD severity (a composite parameter of history of IBD-related surgery and/or treatment with biological therapy) was neither associated with severe periodontitis [OR 1.17 (0.90;1.54); p=0.241], nor tooth loss [OR 1.30 (0.95;1.78); p=0.100].

Conclusion
In this questionnaire-based study with responses from 1,879 IBD patients from two countries, we found the presence of periodontitis and tooth loss to be closely associated with both increased disease activity and disability in IBD patients. These findings emphasize the need for an increased focus on the oral health of patients with IBD.
P388 Eliakim score performance among patients with active Crohn’s disease
Authors: Ukashi O , Lahat A , Ungar B , Levy H , Eidler P , Ben-Horin S , Eliakim R , Kopylov U 
Published: January 2024

Abstract

Background
Pan-enteric capsule endoscopy [PEC] (PillCam Crohn’s, Medtronic, USA) is a useful tool for disease assessment and monitoring in Crohn’s disease (CD). We have previously demonstrated the reliability and accuracy of Eliakim score (ES) in the assessment of CD-activity among patients with quiescent disease. We aimed to examine the performance of ES among patients who experienced clinical flare, as well as its responsiveness and sensitivity to change during follow-up (≤52weeks).

Methods
Patients with CD who have been started on biologics were included. They were prospectively followed with clinical visits, biomarkers and PEC at baseline, and after 14 and 52 weeks. At each time-point Crohn’s disease activity index (CDAI), C-reactive protein (CRP) and fecal-calprotectin (FC) levels were collected, and Lewis score (LS) and ES were calculated (independently reviewed by two experienced readers). Inter-class classification (ICC) was used to asses for agreement between readers. Baseline correlations were obtained using the Spearman's correlation. Repeated-measures correlation (RMC) was calculated using the rmcorr package in R (version 3.3-1). William's test was used to assess difference between correlations.

Results
Seventy-four patients were included (median age of 31.0 [22.5-46.5] years, male–50%). 142 PEC procedures were performed (Baseline– 62, week 14– 58, week 52– 22). Inter-rater agreement between both readers was high for both the LS and ES (ICC of 0.872 [p&lt;0.001] and 0.925 [&lt;0.001], respectively). At baseline, the correlations between FC and ES (r=0.509 [p&lt;0.001]) and FC and LS (r=0.467 [p&lt;0.001]) were comparable (p=0.68). RMC between biomarkers and ES were higher than between biomarkers and LS (CRP: r=0.376 [p=0.005] vs. r=0.204 [p=0.138], FC: r=0.549 [p&lt;0.001] vs. r=0.412 [p=0.003], for ES and LS, [p=0.034/0.021], respectively), while no difference was observed (p=0.77) with regard to CDAI score (r=0.381 [p=0.007] vs. r=0.346 [p=0.015]). Performing sub-group analysis restricted to procedures which were confined to the small bowel (n=88), RMC was numerically higher (p=0.12) between FC and ES (r=0.590 [p=0.001]) than between FC and LS (r=0.470 [p=0.010]).

Conclusion
ES is a reliable and accurate scoring system in assessing mucosal inflammation in patients with active CD, and might have a higher sensitivity to clinical/inflammatory biomarker changes over time compared to LS.