bluuebunny/crossref_metadata_2025_split huggingface dataset:
P237 Proteomic analyses do not reveal subclinical inflammation in fatigued patients with quiescent Inflammatory Bowel Disease
Authors: Bourgonje A R , Wichers S J , Hu S , van Dullemen H M , Visschedijk M C , Faber K N , Festen E A M , Dijkstra G , Samsom J N , Weersma R K , Spekhorst L M 
Published: January 2022

Abstract

Background
Fatigue is a common and clinically challenging symptom in patients with inflammatory bowel diseases (IBD). While fatigue occurs most often in patients with active disease, up to 50% of patients with quiescent disease still report significant fatigue of unknown aetiology. Here, we aimed to investigate whether fatigue in patients with quiescent IBD is reflected by circulating inflammatory proteins, that in turn might reflect ongoing subclinical inflammation.

Methods
Ninety-two (92) different inflammation-related proteins were measured in plasma of 350 patients with quiescent IBD (188 Crohn’s disease [CD]; 162 ulcerative colitis [UC]). Quiescent IBD was defined as clinical (Harvey-Bradshaw Index [HBI] &lt;5 or Simple Clinical Colitis Activity Index [SCCAI] &lt;2.5) and biochemical remission (C-reactive protein [CRP] &lt;5 mg/L) at time of sampling. Fatigue severity was assessed on a visual analogue scale (VAS).

Results
None of the analysed plasma proteins were differentially abundant between mildly (1st quartile, Q1) or severely (4th quartile, Q4) fatigued patients under a false discovery rate of 10%. Considering nominal significance (P&lt;0.05), however, leukemia inhibitory factor receptor (LIF-R) concentrations were inversely associated with severe fatigue, also after adjustment for confounding factors (P &lt;0.05) (Figure 1). Although solely LIF-R showed weak ability to discriminate between mild (Q1) and severe (Q4) fatigue (area under the curve [AUC]=0.61, 95% CI: 0.53–0.69, P&lt;0.05), a combined set of the top seven (7) fatigue-associated proteins (LIF-R, vascular endothelial growth factor-A [VEGF-A], glial-derived neurotrophic factor [GDNF], interleukin-20 receptor subunit alpha [IL-20RA], Delta and Notch-like epidermal growth factor-related receptor [DNER], T-cell surface glycoprotein CD5 [CD5], and extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE], also known as protein S100-A12, all P&lt;0.10) was observed to have reasonable discriminative performance (AUC=0.82 [95% CI: 0.74–0.91], P&lt;0.01).

Conclusion
Fatigue in patients with IBD is not clearly reflected by distinct circulating inflammatory protein signatures, which suggests that subclinical immune activation as defined by the studied panel of inflammatory proteins could not be detected. Reduced shedding of the LIF-R protein could be related to fatigue in IBD through modification of the oncostatin-M (OSM) signaling pathway, or through induction of pro-inflammatory phenotypes of T-cells, macrophages, or neural cells. Future studies are warranted to investigate other proteomic or metabolic markers that may accurately reflect fatigue in quiescent IBD, which might represent alternative pathophysiological pathways.
P250 Clinical validation of a point of care test for fecal calprotectin in distinguishing irritable bowel syndrome from Inflammatory Bowel Disease
Authors: Bray K , Bahur B , Yadav M , Skinner M , Wong M , Chon K , Huang R , Day V , Mimms L , Hale M 
Published: January 2022

Abstract

Background
Calprotectin is a small calcium-binding protein that when measured in human stool has shown utility in assessing the degree of bowel inflammation in inflammatory bowel disease (IBD) and in distinguishing IBD from irritable bowel syndrome (IBS). However, most fecal calprotectin (FCP) assays are slow and inconvenient. This study examined the analytical agreement and clinical utility of a point of care (POC) assay for FCP.

Methods
A fast (~5 min.), time-resolved fluorescence resonance energy transfer based immunoassay (Procise FCP™) was developed for the POC measurement of FCP using 15 mg of fecal specimen eluted in collection fluid from the Procise Stool Collection Device™. The analytical agreement between the Procise FCP assay and a commercial ELISA assay: Inova Quanta Lite Calprotectin Extended Range was assessed using 46 leftover deidentified fecal specimens.
Clinical performance of the assay was assessed using stored frozen stool specimens from a nested cohort derived from a prospective study of chronic diarrhea patients. Chronic diarrhea was defined as unexplained diarrhea of at least 4 weeks duration. Study subjects were males and females of ages 2 – 70 with no chronic liver disease and were consecutively enrolled. Diagnoses were made by attending physicians, and IBD patients did not necessarily have active disease beyond diarrhea at the time of specimen collection. Primary endpoint: Proportion of patients diagnosed with either IBS or IBD testing positive for FCP.

Statistical analysis
Method comparison analysis was performed by Deming linear regression. A post hoc analysis of patients from the diarrhea study diagnosed with either IBS or IBD was performed. The significance of the proportion of patients diagnosed with either IBS or IBD testing positive for FCP was calculated using Fisher’s Exact Probability Test. The assay was assessed at cut-offs of 50 µg/g and 120 µg/g.

Results
Figure 1.

Table 1.

Table 2.

Conclusion
The Procise FCP assay shows excellent analytical agreement to another commercial FCP assay and can clinically significantly distinguish between IBD and IBS in chronic diarrhea patients. Thus, the assay can aid in the differentiation of IBD from IBS. Distinguishing IBS from IBD with a convenient POC format test enhances the clinical utility of FCP by enabling faster treatment response
P255 Mirikizumab modulates genes associated with the symptom of bowel urgency
Authors: Krishnan G , Steere B , Higgs R , Wang Y C , Harris C J , Milch C , Escobar R , Reinisch W , Dubinsky M 
Published: January 2022

Abstract

Background
Bowel urgency (BU) is one of the most common and distressing symptoms experienced by patients (pts) with ulcerative colitis (UC). Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and an acceptable safety profile in a phase 2 randomized clinical trial in pts with moderately to severely active UC. We have previously shown that miri significantly downregulates transcripts associated with disease activity defined by modified Mayo score and Robart‘s Histopathology Index, and upregulates genes expressing transporter proteins associated with healthy mucosa in pts with UC. Here we investigate associations between colon tissue transcripts and patient-reported BU at Baseline (BL) and Week (W)12. We assess the effect of miri induction treatment on genes associated with BU.

Methods
Pts were randomized 1:1:1:1 to receive intravenous placebo (N=63), miri 50mg (N=63) or 200mg (N=62) with possibility of exposure-based dose increases, or fixed miri 600mg (N=61) every 4 weeks for 12 weeks. Patient colonic biopsies were collected at BL and W12 (placebo N=58, miri 50mg N=52, 200mg N=51, 600mg N=54). Gene expression was measured using an Affymetrix HTA2.0 microarray workflow. Differential gene expression was determined by paired T-test comparing expression values at W12 and BL. BU was reported daily by pts as yes/no. Proportion of days of BU at BL and at W12 was calculated for the 3 days prior to visit on a 4-point ordinal scale (0: absence of urgency on all 3 days; 3: presence of urgency all 3 days). BL and W12 gene expression and BU values were pooled and associations identified based on non-parametric Kendall’s tau. Pathway analysis of correlated genes were performed using over-representation analysis on Hallmark and Reactome gene sets from MSigDB. p values of enrichment were determined by hypergeometric distribution test and adjusted for multi-testing with Benjamini-Hochberg (BH) procedure.

Results
A total of 249 pts reported BU scores at BL and W12. The presence of BU was associated with 320 genes (|tau|&gt; 0.225 and qval &lt;0.001). Pathway analysis identified pathways significantly associated with BU (Table). Among the 320 correlated transcripts, 296 were positively correlated (higher gene expression) and 24 were negatively correlated (lower gene expression) with the frequency of BU. Treatment with miri (200mg) resulted in a statistically significant decrease in the 296 transcripts positively correlated with BU, and an increase in the 24 transcripts negatively correlated with BU.

Conclusion
This is the first study to identify colon-based transcripts pertinent to mucosal inflammation and healing that correlate with bowel urgency and that are consistently modulated by miri.
P262 Decreased infliximab trough levels (TLI) is a moderate predictor of loss of response to IFX in IBD patients
Authors: Roblin X , Berger A E , Bastide L , Tournier Q , Veyrard P , Paul S 
Published: January 2022

Abstract

Background
If the use of anti-TNF trough levels (TDM) are proposed in case of loss of response (reactive attitude), a proactive strategy has not shown in most randomized trials its interest. The aim of this study was to analyze the predictive value of a decrease of TLI in IBD patients in terms of loss of response over time.

Methods
This was a retrospective study that included all IBD patient followed in our university hospital. Eligible patients had to have IBD treated with IFX as maintenance therapy (5mg/kg/8weeks). Patients had to be in clinical remission of the disease at inclusion with calprotectin levels &lt; 100 µg/g stool and therapeutic levels of IFX concentration (TLI &gt; 5 µg/ml) on IFX mono- or combination therapy. IFX levels were analyzed by ELISA (Theradiag, France). Every two months, patients were reviewed in the day hospital with fecal calprotectin, TLI and a measure of the clinical activity score (CDAI for CD and Mayo clinical score for UC). Loss of response was defined for CD as a CDAI &gt; 220 with fecal calprotectin &gt; 250µg/g stool and for UC as a full Mayo score &gt; 5 with an endoscopic Mayo score &gt; 1. Low TLI during follow-up was defined as a level below 3 µg/mL. Patients who had dose optimization based on calprotectin or TLI alone were excluded from the study.

Results
145 patients (65% CD, mean age 34 years, disease duration 4.5 years) were included. The mean follow-up was 66 months. 79 patients (55%) showed a loss of response. A decrease of TLI was found in 65% of patients who relapsed within 6 months versus 33% in patients in long-term clinical remission (p=0.14). The predictive value of loss of response within 6 months was moderate in the presence of low IFX levels (sensitivity: 71%, specificity: 73%; PPV: 73%, NPV: 68%). Conversely, fecal calprotectin (&gt; 250 µg/g stools) increase was strongly predictive of loss of response within 6 months (sensitivity: 85%, specificity: 85%). The association of the two markers (decrease of TLI and/or increase of fecal calprotectin) improved the predictivity of relapse in the follow-up (sensitivity: 90%, Specificity: 89%). For the 79 patients who relapsed, for 35% (28 patients) of the cases, the rise of fecal calprotectin preceded the fall of TLI but for 25% of the cases (25 patients), apparition of low TLI preceded the rise of fecal calprotectin.

Conclusion
The decrease of TLI is n moderately predictive of a loss of clinical response in the short or medium term under IFX for IBD. These results may explain the negative results of a proactive attitude based on TDM alone. A proactive strategy based on TDM and fecal calprotectin could be very interesting but needs to be confirmed.
P265 Open approach for ileocolic resection in Crohn’s disease in the era of minimally invasive surgery: indications and perioperative outcomes in a referral centre
Authors: Calini G , Abdalla S , Abd El Aziz M A , Benammi S , Merchea A , Behm K T , Mathis K L , Larson D W 
Published: January 2022

Abstract

Background
Minimally invasive surgery (MIS) is the first-line approach for ileocolic resection in patients with Crohn’s disease (CD) and it is safe and feasible even in complex cases. However, an open approach is still required, but indications to open ileocolic resection for CD are not well described.

Methods
All consecutive adult patients with CD who underwent elective ileocolic resection in the Departments of Colon and Rectal Surgery at Mayo Clinic Rochester, Minnesota and Jacksonville, Florida between September 2014 and March 2021 were included and divided into “open” and “MIS” groups. Open approach was defined as upfront laparotomy, MIS included laparoscopic and robotic approaches, and conversion was defined as incision made earlier than planned. Indications to open approach were retrospectively reviewed by two authors, and any incongruity was resolved. Analogous indications were also assessed in the MIS group, as appropriate. Indications, baseline, perioperative characteristics, and short-term postoperative outcomes were compared between open and MIS.

Results
Among 319 ileocolic resections for CD, 45 (14.1%) were open and 274 (85.9%) MIS. Indications for open approach were severe disease, adhesions at previous surgery, history of abdominal sepsis, multifocal and extensive disease, abdominal wall involvement, concomitant open procedures, small bowel dilatation, and anaesthesiologic contraindications (Table 1). In addition, two or more of the above indications were present in 40 patients (89%) in the open group, while only in 6 patients (2%) in the MIS group (p&lt;0.001). Compared to MIS patients, patients undergoing open ileocolic resection were older, with longer CD duration, more previous surgery and preoperative intra-abdominal abscess drainage (Table 2). Nine patients were converted in the MIS group (3.3%). Intraoperatively, open group had more adhesiolysis ≥45 min, more intraoperative complications, more blood loss, more primary stoma, less anastomosis, and longer operative time (Table 3). Postoperatively, they had more overall postoperative complications, ileus, surgical site infections, dehydration, vascular thromboembolism, higher severity by Clavien-Dindo classification, and longer length of stay (Table 4).

Conclusion
Overall rate of open approach ileocolic resection for CD was 14 % during a 7-years period in a referral centre. Open approach was the only operation performed in cases of abdominal wall involvement, concomitant open procedures, and anaesthesiologic contraindication. In addition, the presence of at least two indications,predicting high technical complexity, may be considered as a no-go for the MIS approach in ileocolic resections for CD.
P267 Milan Ultrasound Criteria are accurate in assessing endoscopic remission and treatment response in patients with ulcerative colitis
Authors: Allocca M , Dell’Avalle C , Radice S , Furfaro F , Zilli A , D’Amico F , Peyrin-Biroulet L , Fiorino G , Danese S 
Published: January 2022

Abstract

Background
We assessed the accuracy and the responsiveness to change of Milan Ultrasound Criteria (MUC) in patients with ulcerative colitis (UC), using colonoscopy as the reference standard.

Methods
We performed a prospective observational study of 49 patients with active UC. All patients underwent bowel ultrasound and colonoscopy at baseline and at reassessment, at week 48, after treatment with biologics (29 patients were treated with infliximab, 14 with vedolizumab, four with adalimumab, two with ustekinumab). Furthermore, patients underwent bowel US also at week 12 and 24. Disease activity was quantified using Mayo endoscopic subscore and MUC. The primary analysis was to determine the accuracy of MUC in identification of endoscopic remission defined as a Mayo endoscopic subscore &lt; 2. Additional analyses established the accuracy of MUC in determining change in lesion severity. Logistic regression was used to examine the relationship between the absence or presence (0/1) of endoscopic remission at reassessment as the dependent variable and possible predictors at week 12 as the independent variables. The model was performed using the stepwise backward method.

Results
Eighteen patients (37%) got endoscopic remission at reassessment. In Table 1 are summarized endoscopic and ultrasound outcomes achieved at reassessment according to the different treatments. MUC &lt; 6.2 determined endoscopic remission with 83% sensitivity, 84% specificity, 84% accuracy, 75% PVP and 90% PVN (Table 2). MUC was sensitive to change in ulcerative colitis [Guyatt’s responsiveness index: 1.73; standardised effect size ratio: 2.0]. MUC changed significantly from baseline to reassessment [8.72 (7.78−9.14) vs 7.60 (4.71−8.53), p &lt; 0.0001], with the largest drop at week 12 [8.72 (7.82−9.19) vs 7.46 (5.80−7.98), p &lt; 0.0001] (Figure 1). A change of -2 in MUC overtime predicted endoscopic remission at reassessment (AUC 0.806, 95% CI 0.667–0.904; sensitivity 89%, specificity 77%). At multivariable analysis only MUC &lt; 6.2 at week 12 was statistically significantly associated with endoscopic remission at reassessment (Table 3).

Conclusion
MUC accurately detects endoscopic remission. MUC is a highly responsive, reliable tool for assessing treatment response in patients with ulcerative colitis.
P271 Fecal calprotectin at diagnosis is associated with oral steroid use first year of Inflammatory Bowel Disease
Authors: Strande V , Småstuen M C , Huppertz-Hauss G , Perminow G , Henriksen M , Bengtson M B , Høie O , Ricanek P , Opheim R , Cetinkaya R B , Torp R , Vatn S , Aabrekk T B , Detlie T E , Hovde Ø , Høivik M L , Kristensen V A 
Published: January 2022

Abstract

Background
Fecal (f-) calprotectin is demonstrated to predict forthcoming flares in Inflammatory Bowel Disease (IBD). Predictive value in newly diagnosed IBD is scarcely studied. The aim of this study was to investigate if high or low f-calprotectin at time of diagnosis of IBD was associated with need of steroids during first year of disease in a population-based inception cohort study (IBSEN III).

Methods
Newly diagnosed IBD patients &gt;18 years, enrolled from the South-Eastern Health Region of Norway in the period of 2017–2019, were studied. Age, gender, smoking status, CRP and level of f-calprotectin were registered at diagnosis. At one-year follow-up, oral and intravenous (IV) steroid use during first year of disease were registered. Associations between high levels of f-calprotectin (≥ 500 mg/kg) at diagnosis and steroid use were tested using logistic regression analyses. A p-value of 0.05 was considered statistically significant.

Results
At baseline, 352 adult patients with Crohn’s disease (CD) and 702 patients with ulcerative colitis (UC) provided samples for f-calpotectin and were included in this study. Steroid use (both IV and oral) was associated with higher levels of f-calprotectin. When adjusted for CRP, age, gender and smoking status, the association remained statistically significant for oral steroid use (CD: OR=2.21, 95%CI [1.25; 3.93], p=0.007. UC: OR=1.87, 95%CI [1.26;2.78], p=0.002), however not for IV steroid use.

Conclusion
High level of f-calprotectin at time of diagnosis is associated with oral steroid use during the first year of disease for patients with IBD.
P277 Assessment of fatigue as a patient-reported outcome: Correlation with baseline disease activity and therapy response in Inflammatory Bowel Disease
Authors: Tran F , Schrinner F , Nikolaus S , Kümpers J , Sievers L K , Lessing A , Lintner J , Lessing M , Rosenstiel P , Aden K , Franke A , Schreiber S 
Published: January 2022

Abstract

Background
Currently available disease activity indices for IBD (e.g., CDAI and Mayo score) focus on symptoms directly related to intestinal function, while other relevant health consequences of disease activity including quality of life, neuropsychiatric symptoms like depression, and social functionality, are not captured. With better therapies more stringent definitions of patient health have come into focus. One of the most common patient reported outcomes (PROs) in IBD is fatigue, which can be unrelated to endoscopic disease activity. We have shown earlier a strong degradation of tryptophan in active IBD (Nikolaus et al, 2017, Gastroenterology) and low tryptophan levels have been linked in various chronic disease to high fatigue levels. Here, we aim to study the relationship of fatigue with disease activity in the context of therapy response to a biological treatment.

Methods
Patients with Crohn’s disease and ulcerative colitis with high disease activity (Mayo score ≥ 6, CDAI ≥ 220) and planned new therapy with a biologic agent were included into a prospective observational protocol. After informed consent, clinical disease activity, inflammatory biomarkers, tryptophan levels in serum and fatigue levels were assessed longitudinally at week 0, 2, 6 and 14 after start of induction therapy. Complete assessments including week 14 were available for 38 patients for this interim analysis of the ingoing study. For fatigue assessment we used the validated German version of the fatigue subscale of the FACIT-F questionnaire. Patients were stratified into therapy responder (clinical remission (CR), reduction of partal Mayo score (pMayo) &gt; 50%, CDAI &lt; 150), non-responders (reduction of Mayo &lt;30%, CDAI reduction &lt;70) and partial responders at week 14.

Results
In the cross-sectional analysis of all patients (n = 76), the fatigue score strongly (inversely) correlated with pMayo and CDAI and correlated positively with tryptophan levels in serum. In receiver operating characteristic (ROC) analysis, FACIT-F score were able distinguish active vs. non-active disease (p &lt; 0.0001, AUC = 0.7619) with specificity of 0.7103 and sensitivity of 0.7160. We did not observe significant differences in fatigue scores between males and females. In the longitudinal analysis, fatigue score only improved in the CR group (n = 25, median FACIT score 30 at baseline vs. 44 at week 14, p = 0.0221), and was significantly higher in CR vs. non-responder (n = 16, median FACIT score 44 vs. 31.5, p = 0.007).

Conclusion
Fatigue is strongly related but not completely overlapping with disease activity. Fatigue will be evaluated as a a patient-oriented indicator for therapeutic response. This observation will be extended by increasing the cohort size and independent validation.