bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of a prehabilitation program before major abdominal surgery
Authors: Martin D , Besson C , Pache B , Michel A , Geinoz S , Gremeaux-Bader V , Larcinese A , Benaim C , Kayser B , Demartines N , Hübner M
Published: May 2021

Objective

Prehabilitation programs claim to improve exercise capacity and postoperative outcomes. The study aim was to assess the feasibility of a prehabilitation program and its effects on fitness and clinical outcomes after major abdominal surgery.

Methods

In this prospective pilot study, patients were assigned to high-intensity physical exercise training with 3 training sessions per week for 3 weeks preoperatively. Feasibility of this intervention was assessed based on recruitment and adherence to the training program. Impact on fitness (VO2 AT) was evaluated and correlated with complications and length of stay (LOS).

Results

Of 980 eligible patients, 87 patients (8.9%) were approached for inclusion. Main obstacles to not approach patients were insufficient time (< 3 weeks) prior to scheduled surgery (n = 276, 28.2%) or screening failure (n = 312, 31.8%). Out of these 87 patients, 24 (28%) declined to participate, 43 (49%) met exclusion criteria and 20 (23%) were included. Six patients (30%) could not complete the prehabilitation program due to contra-indication for exercise training evidenced during the test (n = 3), lack of motivation (n = 2) and modification of the planned operating date (n = 1). VO2 AT increased from 9.8 to 11.5 ml/min/kg (p = 0.050). There were no correlations between the change in VO2 AT and postoperative complications (r = -0.133, p = 0.649) and LOS (r = -0.94, p = 0.750).

Conclusion

Prehabilitation programs are difficult to implement and many patients are either not eligible or not motivated. Future efforts should concentrate on those patients who are most likely to benefit from these time- and cost-intensive interventions.
Cerebrospinal fluid catecholamines in delirium and dementia
Authors: Henjum Kristi , Godang Kristin , Quist-Paulsen Else , Idland Ane-Victoria , Neerland Bjørn Erik , Sandvig Heidi , Brugård Anniken , Raeder Johan , Frihagen Frede , Wyller Torgeir Bruun , Hassel Bjørnar , Bollerslev Jens , Watne Leiv Otto
Published: May 2021

Dopamine and noradrenaline are functionally connected to delirium and have been targets for pharmacological interventions but the biochemical evidence to support this notion is limited. To study the CSF levels of dopamine, noradrenaline and the third catecholamine adrenaline in delirium and dementia, these were quantified in three patient cohorts: (i) cognitively normal elderly patients (n = 122); (ii) hip fracture patients with or without delirium and dementia (n = 118); and (iii) patients with delirium precipitated by another medical condition (medical delirium, n = 26). Delirium was assessed by the Confusion Assessment Method. The hip fracture cohort had higher CSF levels of noradrenaline and adrenaline than the two other cohorts (both P < 0.001). Within the hip fracture cohort those with delirium (n = 65) had lower CSF adrenaline and dopamine levels than those without delirium (n = 52, P = 0.03, P = 0.002). Similarly, the medical delirium patients had lower CSF dopamine levels than the cognitively normal elderly (P < 0.001). Age did not correlate with the CSF catecholamine levels. These findings with lower CSF dopamine levels in hip fracture- and medical delirium patients challenge the theory of dopamine excess in delirium and question use of antipsychotics in delirium. The use of alpha-2 agonists with the potential to reduce noradrenaline release needs further examination.
Taste and Smell Function in Head and Neck Cancer Survivors
Authors: Alfaro Raul , Crowder Sylvia , Sarma Kalika P , Arthur Anna E , Pepino Marta Yanina
Published: May 2021

Survivors of head and neck squamous cell cancers (HNSCC) frequently complain of taste dysfunction long after radiation therapy is completed, which contradicts findings from most sensory evaluation studies that predict dysfunction should resolve few months after treatment. Therefore, it remains unclear whether taste and smell function fully recovers in HNSCC survivors. We evaluated HNSCC survivors (n = 40; age 63 ± 12 years, mean ± standard deviation) who received radiation therapy between 6 months and 10 years before recruitment and compared their responses to those of a healthy control group (n = 20) equivalent in age, sex, race, smoking history, and body mass index. We assessed regional (tongue tip) and whole-mouth taste intensity perception using the general Labeled Magnitude Scale and smell function using the University of Pennsylvania Smell Identification Test (UPSIT). To determine possible differences between groups in retronasal smell perception, we used solutions of sucrose with strawberry extract, citric acid with lemon extract, sodium chloride in vegetable broth, and caffeine in coffee and asked participants to rate perceived smell and taste intensities with and without nose clips. We found groups had similar UPSIT and taste intensity scores when solutions were experienced in the whole mouth. However, HNSCC survivors were less likely to identify low concentrations of bitter, sweet, or salty stimuli in the tongue tip relative to healthy controls. Our findings suggest persistent and subtle localized damage to the chorda tympani or to the taste buds in the fungiform papillae of HNSCC survivors, which could explain their sensory complaints long after completion of radiotherapy.
Rapid Determination of 6-Methyl-5-hepten-2-one in Fruit with LLE-GC-MS
Authors: Zhou Zhen , Wang Xiuqing , Cui Xia , Wang Haijing
Published: May 2021

The volatile compound 6-methyl-5-hepten-2-one (MHO) is an important chemical intermediate and flavor component derived from carotenoid during fruit metabolism, which is important factor impacting consumer-liking. Fruit has complex matrix and is difficult to be purified during MHO analysis. A rapid liquid–liquid extraction-gas chromatography–mass spectrometry (LLE-GC–MS) method was developed for effective determination of MHO in fruit in this study. The calibration curves for MHO showed high linearity in the range of 100–2000 ng/ml with internal standard method. The limit of detection (LOD), limit of quantification (LOQ) were both <100 ng/ml. Real samples of tomato cultivar fruit were analyzed and RSD of biological replicates varied in the range of 2.01% to 12.59%. MHO showed varied content in different tomato fruit tissues of the selected cultivars, in addition to the variation between cultivars. Furthermore, the possible fragmentation patterns were proposed for the main characteristic ions of MHO and internal standard, based on isolation of the fragment ions after the precursor ion underwent splitting at the electron impact ion source. Compared with reported solid-phase microextraction (SPME)-GC–MS method, the validated method was more rapid, precise, accurate and low cost for MHO quantitation.
A Hybrid Intelligent Text Watermarking and Natural Language Processing Approach for Transferring and Receiving an Authentic English Text Via Internet
Authors: Hilal Anwer Mustafa , Al-Wesabi Fahd N , Abdelmaboud Abdelzahir , Hamza Manar Ahmed , Mahzari Mohammad , Hassan Abdulkhaleq Q A
Published: May 2021

Due to the rapid increase in the exchange of text information via internet networks, the security and the reliability of digital content have become a major research issue. The main challenges faced by researchers are authentication, integrity verification, and tampering detection of the digital contents. In this paper, a Robust English Text Watermarking and Natural Language Processing Approach (RETWNLPA) is proposed based on word mechanism and first level order of Markov model to improve the accuracy of tampering detection of sensitive English text. The RETWNLPA approach embeds and detects the watermark logically without altering the original text document. Based on the hidden Markov model (HMM), the first-level order of word mechanism is used to analyze the interrelationship between English text. The extracted features are used as watermark information and integrated with text zero-watermarking techniques. To detect eventual tampering, RETWNLPA has been implemented and validated with attacked English text. Experiments were performed on four datasets of varying sizes under random locations of common tampering attacks. The simulation results prove the tampering detection accuracy of our method against all kinds of tampering attacks. Comparison results show that RETWNLPA outperforms baseline approaches HNLPZWA (an intelligent hybrid of natural language processing and zero-watermarking approach) and ZWAFWMMM (Zero-Watermarking Approach based on Fourth level order of Word Mechanism of Markov Model) in terms of tampering detection accuracy.
The Reliability of Patient Self-reported Utilization in an Inflammatory Bowel Diseases Learning Health System
Authors: van Deen Welmoed K , Freundlich Noah , Kwon Michelle H , Patel Devin B , Crate Damara J , Oberai Ridhima , Shah Samir A , Hwang Caroline , Weaver S Alandra , Siegel Corey A , Melmed Gil Y
Published: May 2021

Background

Inflammatory bowel disease (IBD) care is beset with substantial practice variation. Learning health systems (LHSs) aim to learn from this variation and improve quality of care by sharing feedback and improvement strategies within the LHS. Obtaining accurate information on outcomes and quality of care is a priority for LHS, which often includes patients’ self-reported data. While prior work has shown that patients can accurately report their diagnosis and surgical history, little is known about their ability to self-report recent healthcare utilization, medication use, and vaccination status.

Methods

We compared patient self-reported data within the IBD Qorus LHS regarding recent IBD-related emergency department (ED) visits, hospitalizations, computerized tomography (CT) scans, corticosteroid use, opioid use, influenza vaccinations, and pneumococcal vaccinations with electronic health record (EHR) data.

Results

We compared 328 patient self-reports to data extracted from the EHR. Sensitivity was moderate-to-high for ED visits, hospitalizations, and CT scans (76%, 87%, and 87%, respectively), sensitivity was lower for medication use with 71% sensitivity for corticosteroid use and only 50% sensitivity for self-reported use of opioids. Vaccinations were reported with high sensitivity, but overall agreement was low as many patients reported vaccinations that were not registered in the EHR.

Conclusions

Self-reported IBD-related ED visits, hospitalizations, and CT scans are reported with high sensitivity and accuracy. Medication use, and in particular opioid use, is less reliably reported. Vaccination self-report is likely more accurate than EHR data as many vaccinations are not accurately registered.
Serum Ustekinumab Concentrations Are Associated With Remission in Crohn’s Disease Defined by a Serum-Based Endoscopic Healing Index
Authors: Walshe Margaret , Borowski Krzysztof , Battat Robert , Hudesman David , Wolf Douglas C , Okada Lauren , Jain Anjali , Silverberg Mark S
Published: May 2021

Background

Optimal ustekinumab levels (UST) in Crohn disease (CD) treatment have not been defined. We set out to define the optimal UST to differentiate between remission and active CD, as defined using the serum-based endoscopic healing index (EHI).

Methods

Paired serum UST and EHI tests were analyzed. Remission was defined as EHI <20. Active disease was defined as EHI ≥50. The proportion of patients in remission was compared across UST quartiles. UST in subjects with EHI <20 and EHI ≥50 were compared. An area under receiver operating characteristic curve was generated to identify an optimal UST to differentiate between active disease and remission.

Results

A total of 337 unique patients were identified; median UST and EHI were 5.0 µg/mL [interquartile range (IQR) 2.7–9.1] and 37 (IQR 26–53), respectively. EHI <20 (remission) was found in 57 (16.9%) patients. EHI ≥50 (active disease) was found in 97 (28.8%) patients. Higher proportions of subjects were in remission for increasing UST quartiles, P = 0.01. Median UST in patients with EHI <20 and EHI ≥50 were 7.5 µg/mL (IQR 4.6–10.9) and 3.1 µg/mL (IQR 1.8–6.6), respectively, P < 0.001. An UST threshold of 3.75 µg/mL optimally differentiated between active disease and remission (area under the curve 0.725). UST levels >3.75 µg/mL were associated with a lower proportion of subjects with active disease (EHI ≥50; 18.9%) compared with UST levels ≤3.75 µg/mL (45.6%, P < 0.001).

Conclusions

Using the EHI, we identified a threshold UST level of 3.75 µg/mL to optimally differentiate between active and quiescent CD. These data suggest that UST serum concentrations of >3.75 µg/mL are optimally associated with endoscopic remission in CD.
DOP06 Histologic activity in Ulcerative Colitis patients achieving endoscopic healing is associated with higher rate of relapse and a distinct mucosal microbial and transcriptional profile
Authors: Hernandez-Rocha C , Turpin W , Nayeri S , Borowski K , Stempak J , Conner J , Silverberg M S
Published: May 2021

Background

Histologic remission (HR) in ulcerative colitis (UC) has been associated with better clinical outcomes. However, this therapeutic target is hard to achieve with the available medications. We aim to assess the relapse-free survival (RFS) of patients with persistent histologic activity (HA) upon achieving endoscopic healing (EH) and the microbial and molecular signatures associated with this condition.

Methods

Left-sided and extensive UC patients and healthy controls (HC) were recruited at colonoscopy and sigmoid colon (SC) biopsy samples were obtained for HA evaluation, 16S rRNA sequencing and host RNA-seq. EH was defined as Mayo endoscopic subscore (MES) 0–1, and HA and histologic remission (HR) as the presence and absence of neutrophil infiltration, respectively. UC relapse was retrospectively evaluated and defined as symptomatic and endoscopic worsening. Cumulative RFS was assessed by log-rank test. Principal component analysis (PCA) was used for capturing cluster structure. For differential expressed genes (DEG) and enrichment pathway analyses, glmQLFTest in EdgeR and enrichKEGG in clusterProfiler were applied, respectively. Genes with log fold change > 2 and a log count per million > 1 were considered DEG. Dada2 algorithm in QIIME2 for amplicon sequence variant generation and ANCOM-BC package for differential abundance (DA) taxa analysis were applied. P-values of omics data were corrected by false discovery rate (FDR) method.

Results

Sixty-five UC patients had EH (37 MES 0 and 28 MES 1). Nine (20.9%) MES 0 and 17 (40.5%) MES 1 showed HA. Over a median follow-up of 4.2 years (IQR 2.6–6.1), UC patients with HA showed a significant lower RFS compared to HR (p < 0.05; Figure 1). This difference was not observed between MES 0 and MES 1 (p = 0.2). Transcriptomics data was available for 27 samples with HR and 9 samples with HA, as well as 43 HC and 13 MES 2–3 samples. PCA showed that HR and HA samples cluster with HC and MES 2–3 samples, respectively (Figure 2). Compared to HR, 163 DEG (118 up and 45 downregulated) were found in HA. Enrichment analysis showed significant upregulation of cytokine-cytokine interaction, Th17 and chemokine signaling pathways (Figure 3). Microbiome data was available for 43 and 19 samples with HR and HA, respectively. Three genera had significant DA in HA compared to HR (Figure 4).

Conclusion

HA in UC is better than MES at distinguishing a higher risk of relapse and has a transcriptomics profile closer to active endoscopic disease despite EH with significant upregulation of chemokine, cytokine and Th17 pathways. A different microbial signature is also observed in HA. These particular signatures could help to define strategies to reduce the risk of UC relapse in patients achieving EH.
P183 Risk of eating disorders in italian children and adolescents with Inflammatory Bowel Disease: results of a multicenter nationwide study
Authors: Gatti S , Vallorani M , Zoppi E , Palego G , Aloi M , Bramuzzo M , Felici E , Zuin G , Borali E , Catassi G , Grazian F , Quagliarella A , Catassi C
Published: May 2021

Background

The prevalence and risk of Eating Disorders (ED) in IBD, despite the potential overlap of these two conditions, have been rarely reported. ED diagnosis should be considered in patients with IBD and multidisciplinary approach would be recommended in these complex cases to provide an adequate therapeutic intervention. Screening tools to evaluate eating attitudes and behaviours in patients with IBD could be used in daily practice, as for example the Eating Attitude Test – 26

Methods

Children and adolescents (8–18 years) with IBD and age and gender matched healthy controls were prospectively enrolled in 5 italian pediatric IBD units between June 2019 and August 2020. Subjects with an existing diagnosis of ED were excluded. The risk of ED was assessed using a 26 points Likert scale screening tool (CH-EAT-26 and EAT-26 for children < and > 14 years respectively), with a total score of 20 or above indicating a risk for ED. Correlations between clinical and disease’s parameters and the CH-EAT-26/EAT-26 score were calculated

Results

110 patients with IBD and 110 age and matched healthy controls were screened with the CH-EAT26/EAT-26 questionnaire. The total EAT26 scores and the prevalence of an at-risk score (score>20) did not differ in IBD subjects compared to controls. IBD patients were more frequently on an exclusion diet with lactose free-diet being the most common regimen. Furthermore, 8.1% of IBD children was on a partial enteral nutrition (PEN). In IBD subjects elevated scores on the Ch-EAT26/EAT-26 were associated with being younger (r=-0,2226, p=0.002), following an exclusion diet (r=0.25, p=0.009) and a partial enteral nutrition (PEN: r=0,2507, p=0.009). Type, duration and activity of disease, gender, weight, height and BMI z-scores were not significantly correlated to the CHEAT26/EAT-26 score. Being on a PEN and following an exclusion diet were the only independents factors influencing the EAT26 score at the multiple regression analysis (p= 0,004; p= 0,034; R2 = 0,25)

Conclusion

Our results indicate that 5.45% of IBD children have a behavior at risk for developing an ED, a percentage that is not statistically different compared to healthy controls. A particular follow-up should be reserved to patients on restricted diets and on partial enteral nutrition, that can develop maladaptive attitudes toward eating. The development of a disease specific tool or a validation of pre-existing questionnaires would help to identify a robust screening instrument and ultimately to correctly classify the risk of patients. Once the risk is correctly assessed it is mandatory to address the patient to a specific multidisciplinary follow-up.
P203 Sexual Dysfunction in Chronic Inflammatory Bowel Disease: Myth or Reality?
Authors: Hassine A , Hammami A , Ben Ameur W , Dahmani W , Elleuch N , Jaziri H , Ben Slama A , Braham A , Ksiaa M , Bannour R , Jmaa A
Published: May 2021

Background

Sexual dysfunction is often associated with impaired body image and quality of life in patients. However, little data exists on sexual dysfunction (SD) in patients with Chronic Inflammatory Bowel Disease (IBD). The aim of this study was to assess the prevalence and risk factors for sexual dysfunction in patients with IBD.

Methods

This is a cross-sectional study of all patients followed for IBD. Sexual function was assessed by the Female Sexual Index Function (FSIF) for women and the International Index of Erectile Function (IIEF) for men. Sexual dysfunction was confirmed when the total FSIF score was less than 26, or the IIEF score less than 26. Crohn’s disease (CD) activity was assessed by the Harvey-Bradshaw index (HBI), and that of ulcerative colitis (UC), by the clinical Mayo scores.

Results

We collected 100 patients, with a mean age of 42.18 ± 15.71 and a sex ratio (M / F) = 1.5. Sixty eight patients had CD and 32 patients had UC. Ano-perineal manifestations were present in 38.2% of cases. Severe disease activity was noted in 14 patients (20.6%) with CD and 10 patients (31.3%) with UC. Twelve patients had proctitis. 38% of patients had surgical treatment: 18.75% for patients with UC and 47.05% for those with CD. Total colectomy was performed in 12% of cases. At the time of the study, 20% of patients were on systemic corticosteroid therapy, 22% on Azathioprine, 4% on Salazopyrine, 8% on 5-ASA and 46% on Anti-TNFα. Sexual dysfunction was reported by 42.9% of women: 57.14% (UC) vs 38.46% (CD) (p = 0.042). On the other hand, sexual dysfunction was reported by 27.6% of men: 22.2% of men with UC and 28.57% with CD, with no statistically significant difference (p = 0.78). A significant association was found between sexual dysfunction and the degree of disease activity (p <0.001 for CD, p = 0.003 for UC), as well as pancolitic involvement in women with UC (p = 0.002). However, the presence of anoperineal manifestations, rectal involvement and history of surgery were not significantly associated with the frequency of sexual disturbances.

Conclusion

Our study showed a high prevalence of sexual dysfunction in patients with IBD. Training gastroenterologists in the management of sexual dysfunction would make it possible to satisfy patient expectations.
P319 Impact of biological agents on postoperative complications in inflammatory bowel disease: a multicentre study of GETECCU
Authors: García García M J , Rivero M , Miranda-Bautista J , Bastón-Rey I , Mesonero F , Leo-Carnerero E , Casas-Deza D , Cagigas Fernández C , Martin-Cardona A , El Hajra I , Hernández-Aretxabaleta N , Pérez-Martínez I , Fuentes-Valenzuela E , Jiménez N , Rubín de Célix C , Gutiérrez A , Suárez Ferrer C , Huguet J M , Fernández-Clotet A , González-Vivó M , Del Val B , Castro-Poceiro J , Melcarne L , Dueñas C , Izquierdo M , Monfort D , Bouhmidi A , Ramírez De la Piscina P , Romero E , Molina G , Zorrilla J , Calvino-Suárez C , Sánchez E , Nuñez A , Sierra O , Castro B , Zabana Y , González-Partida I , Chaparro M , Gisbert J P
Published: May 2021

Background

It has been suggested that biologic therapy may increase the risk of postoperative complications in inflammatory bowel disease (IBD), but the evidence is scarce. Our aim was to evaluate whether the treatment with anti-TNF agents, ustekinumab or vedolizumab increase the risk of complications after surgery.

Methods

IBD patients undergoing intra-abdominal surgery between 1st January 2009 and 31st December of 2019 were retrospectively selected. Data collection included clinical characteristic of IBD, biochemical parameters and surgical aspects. Postoperative complications (PC) were defined as those occurring within 30 days after surgery. Exposed cohort (EC): Patients who received the last dose of the biologic within 3 months before surgery. Non-exposed cohort (NEC): Patients who did not receive biologic treatment within 3 moths prior to surgery. Predictive factors for PC and for infections were identified by logistic regression analyses. A genetic matching score was performed to balance the clinical characteristics of both groups.

Results

A total of 1,535 surgeries performed in 37 centres were included: 81% in Crohn’s disease, 18% in ulcerative colitis and 1% in unclassified-IBD patients. A total of 711 surgeries (46.3%) had been exposed to biologics (583 under anti-TNF therapy, 58 under vedolizumab and 69 under ustekinumab) and 824 surgeries (53.7%) the NEC. PC were reported in 38% (n=267) of patients in the exposed cohort and in 34% (n=280) of patients in the non-exposed one (p=0.15), including dehiscence, infection, obstruction, ileus, bleeding, thrombosis, fistula and evisceration. The most frequent complications were infections (48% of all the cases). A 30-day hospital readmission was needed in 7% (n=110) of the patients, and 2% (n=29) required a new surgery with no differences (p>0.05). Multivariate analysis for PC and infections is presented in table 1. The frequencies of PC for each biologic in the univariate analysis are represented in figure 1. No specific treatment was associated to PC or infections in multivariate analysis.

Conclusion

Preoperative administration of biological therapy does not seem to be a risk factor for overall PC, although it may be for postoperative infections.
P364 Patient reported outcomes, partial MAYO score and SCCAI are equally accurate in predicting mucosal healing in UC: final results form a prospective study
Authors: Golovics P , Gonczi L , Reinglass J , Verdon C , Pundir S , Afif W , Wild G , Bitton A , Bessissow T , Lakatos PhD P L
Published: May 2021

Background

Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine how strong patient reported outcomes, clinical scores and symptoms correlate with endoscopy for assessment of disease activity in UC patients.

Methods

171 patients were included prospectively and consecutively (age: 49 (IQR: 38-61) years, duration 12 (4-19)years, 79 females (46.2%), 57.3% extensive disease, 42.7% on biologicals) at the time of the colonoscopy. The 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES), Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 83 and 45.6% of patients. 17.0% had clinical flare, treatment was escalated in 14.6% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed.

Results

Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission were similarly associated to mucosal healing defined by MES (0 or ≤1) or Baron (0 or ≤1) scores (Table 1).

PRO2 (AUCMES0/Baron0: 0.770/0.740, AUCMES0-1/Baron0-1: 0.868/0.858), SF (AUCMES0/Baron0:0.751/0.724, AUCMES0-1/Baron0-1:0842/0.820), RBS (AUCMES0/Baron0: 0.718/0.698, AUCMES0-1/Baron0-1: 0.814/0.845) partial Mayo (AUCMES0/Baron0: 0.823/0.788, AUCMES0-1/Baron0-1: 0.927/0.902) and SCCAI (AUCMES0/Baron0: 0.767/0.752, AUCMES0-1/Baron0-1:0.888/0.867) were similarly associated with mucosal healing in a ROC analysis.

There was a strict association between MES 0 and Baron 0 (k=0.917) and UCEIS <4 and MES 0-1 (k=0.813), while moderate to fair agreement between UCEIS <4 and MES 0 (K=0.471) or Baron 0 (K=0.414)/Baron 0-1 (K=0.353), and between MES 0-1 and Baron 0-1 (K= 0.350) scores.

Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K~0.2), while agreement between FCAL (>100 or >250) and RBS-PRO2 remission (K>100 or >250: 0.44-0.60) or pMAYO (K>100 or >250: 0.41-0.59) or MES/Baron 0 was moderate to good (K>100:0.53-0.52 and K>250:0.57-0.53).

Conclusion

We found no difference across accuracy of RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing. A strong association was found with high PPV for MES/Baron ≤1 and high NPV for MES/Baron 0. FCAL, but not CRP was associated to clinical and endoscopic remission.
P369 High prevalence of abdominal pain in Crohn’s Disease patients of the TRUST study cohort- Is there a connection to inflammatory activity?
Authors: Kugel T , Maaser C , Kucharzik T , Fischer I , Kolterer S , Hammer L , Rath S , Sturm A
Published: May 2021

Background

Pain is a debilitating symptom in many patients with Crohn’s disease (CD) both in flare and in remission [1]. However, pain is insufficiently understood and therefore often underrepresented in disease management [2]. Thus, it is of paramount importance to raise awareness for this common but insufficiently managed IBD symptom. With this analysis, we aimed to investigate (1) the prevalence of abdominal pain (AP) and (2) the correlation of AP with further parameters including inflammatory activity assessed by intestinal ultrasound (IUS), lab parameters and patient-well-being in CD patients of the TRUST study cohort.

Methods

We evaluated the prevalence of pain in 230 of 234 CD patients of the prospective, non-interventional, multi-centre TRUST study. At baseline, all patients were in clinical flare (Harvey-Bradshaw index (HBI) of≥7) and received treatment intensification. IUS parameters such as bowel wall thickness (BWT) and clinical data were assessed at baseline and after 3, 6, and 12 months. AP was analysed using the HBI subscore 2. To investigate the connection between AP and inflammation, AP was correlated with BWT and C-reactive protein (CRP).

Results

Based on the TRUST study, we found that 95.2% of patients in clinical flare experienced AP. AP was significantly reduced within 12 weeks after treatment intensification (p < 0.001) but 30% (n=69) to 48.3% (n=111) of patients still experienced AP at the subsequent visits (p(T1-T2) = 0.668; p(T2-T3) = 1.000) (figure 1). Of note, 35.6%-42.5% of patients with clinical response had a lasting pain experience (figure 2). AP positively correlated with poor well-being which is in line with previously published results [3]. We found a weak positive correlation between AP and inflammatory activity, represented by BWT (not shown), and between AP and CRP (table 1).

Figure 1: Percentage of patients with mild, moderate or severe abdominal pain during the study. *Friedman test with post-hoc Wilcoxon tests.

Figure 2: Percentage of patients with abdominal pain and clinical response (reduction of total HBI≥3 points) at the indicated visit

Table 1: Spearmann rank correlations for abdominal pain vs. poor general well-being (as measured by the HBI subscore 1) and vs. CRP at baseline

Conclusion

Our results clearly demonstrate that more than 1/3 of CD patients suffers from AP despite treatment intensification and clinical improvement. We found a weak correlation between AP and markers of inflammatory activity suggesting the existence of a subgroup of patients with persistent pain experience even with IBD treatment. Our data emphasize the importance of adjuvant pain management in IBD.

References
P371 Using digital monitoring during the COVID pandemic to streamline outpatient appointments
Authors: Walsh A J , Matini L , Wilson J , Lyden S , Al-Hillawi L , Kantschuster R , Kormilitzin A , Smith T , Slater J , Payton S , White L , Woodley H , Brain O , Palmer R , Ambrose T , Satsangi J , Travis S P L
Published: May 2021

Background

Demand for outpatient appointments (OPAs) for IBD often exceeds capacity, partly due to scheduled follow up of patients who are well. The TrueColours-IBD (TC-IBD) platform and Escalation of Therapy or Intervention (ETI) calculator was trialed as a tool to triage appointments during the pandemic

Methods

TC-IBD is a web-based programme of email prompts linked to validated disease-specific indices. The ETI calculator was created after logistic regression showed that patient-reported symptoms and quality of life could calculate the probability of therapy escalation or intervention during an OPA (Fig 1). A score ≤20 equates to ≤10% chance of escalation

The ETI calculator was developed for UC, but it was also applied to CD during the pandemic, replacing the SCCAI score with HBI. From Mar-Oct 2020 the ETI calculator was used to extend 145 OPAs (87 UC, 58 CD) from 1034 ETI assessments. TC-IBD data was assessed 2-6 weeks before a scheduled OPA. Patients were eligible for OPA extension if >2 symptom (SCCAI/HBI) and 1 QoL responses (IBD Control) within 4 weeks and ETI score ≤20. Patients with extended OPAs were monitored for 3 & 6-monthly ICHOM outcomes (www.ichom.org), collected through the TC-IBD platform

Results

ICHOM outcomes available for 113/145 patients at 3 mo and 125/145 patients at 6 mo. There were no emergency department visits, no hospitalisations, no surgery, colon cancer or death at either time point in patients whose appointment was extended. 1 patient with UC required prednisolone (Table 1)

Conclusion

Routine digital monitoring of symptoms, quality of life and PROMs can safely streamline outpatient care in IBD
P375 A simulation study to evaluate the performance of a multiple imputation method to address missing data in an analysis of clinical effectiveness using the ImproveCareNow Registry of pediatric patients with Crohn’s disease
Authors: Zhang N , Liu C , King E , Chen S , Olano K , Steiner S , Colletti R , Saeed S , Strauss R , Volger S , Lo K H , Wang Y
Published: May 2021

Background

Patient registries are a source of real-world data (RWD) that are increasingly used to generate real-world evidence (RWE) for the safety and effectiveness of medical therapies. However, in registries, outcome data typically collected in clinical trials may be missing in some patients, creating a major challenge in evaluating RWD reliably. Clinical remission in pediatric Crohn’s disease (PCD), defined by the Short Pediatric Crohn’s disease Activity Index (sPCDAI) <10, is routinely collected in the ImproveCareNow (ICN) Registry, the world’s largest registry of pediatric patients with inflammatory bowel disease (IBD). A feasibility analysis of ICN as a RWD source to estimate the efficacy of therapies in PCD found about one-third of patients were missing at least 1 of the 6 components needed to calculate the sPCDAI scores at Week 52. We conducted a simulation study to evaluate the performance of the multiple imputation (MI) method in addressing the missing data issue.

Methods

A Starting Dataset from the ICN registry included CD patients age 2 to <18 yr when beginning treatment with a biologic agent other than ustekinumab during 2014 to 2019, who had a baseline visit and a “Week 52” visit. A Complete Dataset included only patients in the Starting Dataset who had all components required to calculate a sPCDAI score at the Week 52 visit. The true remission rate was calculated for the Complete Dataset. For the simulation, missing data patterns for individual sPCDAI components that were observed in the Starting Dataset were randomly imposed in the Complete Dataset. Variables that were predictive of sPCDAI scores, its components, and sPCDAI missingness were included. Ten thousand datasets were simulated for each of three scenarios: base case of the observed missingness in the Starting Dataset, 1.5 times the base case and 2 times the base case. The MI method was applied to the simulated datasets to estimate the remission rate. MI performance was measured by bias and coverage of the true remission rate from the Complete Dataset.

Results

The Starting and Complete Datasets included 1,458 and 1,212 patients, respectively. The true clinical remission rate in the Complete Dataset was 75.1% (95% CI: 72.6%-77.5%). Analysis without MI for the missing sPCDAI data resulted in underestimation of clinical remission rate, with bias about -2% to -5% (Table 1). The MI method eliminated the bias and had 100% coverage in all simulation scenarios by using a large number of independent predictors.

Conclusion

The MI method improved the validity, reliability, and efficiency of using RWD for estimating clinical remission in pediatric patients with CD and could be valuable in other registry studies.
P387 Depression in biologic-treated patients with inflammatory bowel disease during the COVID19 pandemic
Authors: Lin S , Bewshea C , Chanchlani N , Chee D , Pollok R C , Kennedy N A , Ahmad T , Goodhand J R
Published: May 2021

Background

Given the existential threat from COVID-19 and the consequent restrictive public health measures it is perhaps unsurprising that SARS-CoV-2 infection has been linked to increases in rates of depression in the general population. Few studies, however have addressed anxiety and depression in patients with inflammatory bowel disease (IBD) during the COVID19 pandemic. We aimed to define, in patients with IBD treated with infliximab or vedolizumab and/or an immunomodulator, the prevalence, demographic and disease-related factors associated with depression and the effect of restrictive public health measures on rates of depression.

Methods

CLARITY IBD is a United Kingdom (UK) wide, multicentre, prospective observational cohort study investigating the impact of infliximab and vedolizumab and/or concomitant immunomodulators (thiopurines or methotrexate) on SARS-CoV-2 acquisition, illness, and immunity in patients with IBD. Patients were recruited between 22nd September and 23rd December 2020 and then assessed every 8 weeks. We measured depression using the 8-item Patient Health Questionnaire (PHQ-8). Secondary outcomes were anxiety and IBD-related quality of life assessed using the General Anxiety Disorder Assessment (GAD-7) and IBD-Control questionnaires, respectively. Multivariable logistic regression models were used to identify factors independently associated with depression at entry to the study. Baseline and paired responses during the third UK government’s stay-at-home lockdown order which commenced on the 4th January 2021 were compared using the Wilcoxon signed-rank test.

Results

The prevalence of depression at entry to the CLARITY study was 26% (1794/6933): 14% patients satisfied criteria for mild, 6% moderate and 5% severe depression. Depression scores were associated with anxiety (Spearman’s rho= 0.78, p<0.0001) and poorer IBD-Control-8 quality of life scores (Spearman’s rho=-0.67, p<0.0001). Multivariable analysis showed that vedolizumab (vs infliximab), steroid use, female sex, younger age, remaining at home, ulcerative colitis, comorbidity and higher income deprivation were associated with depression at entry to the study (Figure 1). Paired depression scores were unchanged between study entry and when assessed during the lockdown period (p=0.91).

Conclusion

Depression was negatively associated with infliximab therapy and was unchanged during the third UK stay-at-home lockdown. Longitudinal follow up in this cohort will allow us to determine whether COVID-19 vaccination influences depression and whether depression is linked to vaccine hesitancy or impaired serological responses to SARS-CoV-2 vaccination.
P412 Effectiveness of ustekinumab in fistulising perianal Crohn′s disease refractory or intolerant to anti-TNF
Authors: Carpio D , Calviño-Suarez C , Martínez-Cadilla J , Molina G , Vázquez-Rey M T , Martí E , Fernández-Salgado E , Barreiro-de Acosta M , Hernández V , Echarri A , Diz-Lois M T , Baz A
Published: May 2021

Background

The management of fistulising perianal Crohn′s disease (pCD) is a challenging problem for patients and physicians. New therapeutic alternatives are needed, particularly in anti-TNF refractory patients. Data regarding ustekinumab (UST) effectiveness in pCD are scarce. Our aim was to evaluate the clinical and radiologic effectiveness of UST in pCD patients refractory or intolerant to anti-TNF.

Methods

We conducted a multi-center retrospective observational study. All patients with anti-TNF refractory pCD treated with UST were evaluated. Demographic and clinical variables including concomitant drugs were registered. Clinical response was evaluated at 16 weeks and 12 months and was defined as a reduction of 50% of draining fistulas or a marked reduction in fistula drainage. In patients with a magnetic resonance imaging (MRI) before and after treatment initiation, radiologic response was defined according to Ng Score (healed, partial response, unchanged, deterioration).

Results

Thirty-two patients were included, 68.8% female, median age 44,11 (IQR 36.28-48.56). Median time from diagnosis to UST initiation was 12.94 years (IQR 7.52-19.52), 90.6% had received previously 2 anti-TNF (37.5% also vedolizumab) and 46.9% had more than 2 fistulas. In 22 patients (68.8%) pCD was the main indication for UST treatment while in the remaining 31.2% the main indication was luminal disease. Fifteen patients (46.9%) received antibiotics at the initiation of UST, 8 (25%) combo therapy with thiopurines and 21 (65.6%) had setons. Patients received a 6mg/kg IV dose and 87.5% received 90mg/8 week SQ for maintenance. Dose intensification was needed in 20 patients (62.5%) at a median of 13 months (IQR 8.00-19.5). Fifteen patients (46,9%) achieved clinical response at week 16, while 18/30 (60%) had clinical response at 12 months (three of them were in clinical remission). Nineteen patients (59,4%) had an MRI performed pre and post-treatment at a median of 15 months (IQR 10-19). 10/19 patients (52.6%) achieved a radiological response although no patient had all fistulas healed. In the multivariate analysis the only factor associated with clinical response at 12 months was the presence of setons at UST initiation (OR 7.0; IC95% 1.3-37.9). There were no factors significantly associated with radiological response or clinical response at week 16. Four patients experienced adverse effects (three perianal abscesses and one transient skin rash).

Conclusion

Ustekinumab was effective in achieving clinical and radiological response in anti-TNF-refractory fistulising pCD patients, although clinical and radiological remission was rare. Most patients needed UST dose intensification in this highly refractory cohort. Adverse effects were infrequent, mainly perianal abscesses.
P414 Obesity is associated with a higher risk of immunogenicity to adalimumab, but not to infliximab in patients with Inflammatory Bowel Disease
Authors: Mahmoud R , Schultheiss J , Louwers J , van der Kaaij M , van Hellemondt B , Mahmmod N , van Boeckel P , Jharap B , Fidder H , Oldenburg B
Published: May 2021

Background

Globally, the prevalences of both inflammatory bowel diseases (IBD) and obesity have increased over the past decades. Recently, obesity has been linked to treatment failure in anti-TNF-treated patients with inflammatory bowel disease (IBD). We assessed whether obesity was associated with an increased risk of treatment failure and immunogenicity (i.e. anti-drug antibodies) among IBD patients treated with adalimumab (ADA) or infliximab (IFX).

Methods

This was a multicenter, retrospective cohort study of adult patients with IBD, treated with ADA or IFX for at least four months between 2011-2019 at a general hospital or a tertiary referral center. Obesity was defined as body mass index (BMI) >30kg/m2. Adjusted hazard rates (aHR) were calculated by mixed-effects Cox regression analysis, accounting for multiple treatment episodes in individual patients and adjusted for sex, prior anti-TNF exposure, immunomodulator use, IBD phenotype (ulcerative colitis versus Crohn’s disease), age, disease duration, smoking and rheumatological comorbidity. Multiple imputation was used to replace missing values (5% for BMI).

Results

We included 728 patients, providing 2339 patient-years of follow-up and 868 treatment episodes with anti-TNF; 130 (17.9%) patients were obese. Obesity was associated with female sex (67% vs 54%), smoking (36% vs 22%), older age (median 42 vs 36 years) and prior exposure to methotrexate (25% vs 15%). In patients receiving ADA, obesity was significantly and independently associated with a higher risk of immunogenicity (Figure 1a, aHR: 2.15, 95%CI: 1.10 – 4.19) and treatment failure (Figure 2a), although significance of the latter association was lost after correcting for relevant confounders (aHR: 1.33, 95%CI: 0.87 – 2.03). In patients treated with IFX, obesity was not associated with immunogenicity (Figure 1b, aHR: 1.05, 95%CI: 0.54 – 2.03) or treatment failure (Figure 2b, aHR: 0.98, 95%CI: 0.70 – 1.39). Trough levels were significantly lower in obese patients treated with ADA, but not IFX.

Conclusion

In patients treated with ADA, but not IFX, obesity is associated with immunogenicity and possibly a higher risk of treatment failure. Proactive therapeutic drug monitoring may be warranted in obese patients treated with ADA.
P415 Paradoxical onset of Takayasu’s arteritis in patients with inflammatory bowel disease treated with anti-tumour necrosis factor-α agents
Authors: Matsune Y , Kouyama J , Tsuru Y , Shimizu K , Asami S , Matsuyama S , Katsuki S , Ishihara H , Onizawa R , Shonai S , Tatsuno M , Nishikawa Y , Takeuchi K , Watanabe M , Nakamori Y , Hirayama A , Toyoda J , Ikeda A , Madarame A , Nishio M , Ogashiwa T , Matsubayashi M , Fujii A , Kimura H , Kunisaki R
Published: May 2021

Background

Takayasu’s arteritis (TA) is a rare complication associated with inflammatory bowel disease (IBD). TA is a granulomatous systemic vasculitis of uncertain aetiology affecting large arteries, predominantly the aorta and its main branches, leading to stenotic and expansible lesions. The estimated prevalence of coexisting of TA in patients with ulcerative colitis (UC) is 0.3%, and that in patients with Crohn’s disease (CD) is 0.1%. Anti-tumour necrosis factor-α (TNF-α) agents are used to treat both TA and IBD, although some patients with IBD paradoxically develop TA during treatment with anti-TNF-α agents. However, data regarding the incidence and clinical features of TA in such cases are lacking. This study was performed to clarify the prevalence, risk factors, and clinical features of TA that develops paradoxically during treatment with anti-TNF-α agents in patients with IBD.

Methods

Consecutive patients with IBD who were regularly seen at our centre, a tertiary IBD centre in Japan, from 2000 to 2019 were included in this retrospective single-centre study. We evaluated the prevalence of TA according to the presence or absence of treatment with anti-TNF-α agents and the patients’ clinical manifestations.

Results

Of 1846 patients with UC and 1249 patients with CD, 7 (0.23%) patients with UC developed TA. The prevalence of TA in patients treated with anti-TNF-α agents was significantly higher (4/254, 1.6%) than that in patients without anti-TNF-α agent treatment (3/1592, 0.19%) (p=0.0087, Fisher’s exact test). Among four patients with UC who paradoxically developed TA during treatment with anti-TNF-α agents, three (75%) received infliximab, one (25%) received adalimumab, and one (25%) received golimumab. One was male and three (75%) were female. The median interval from starting treatment with anti-TNF-α agents to diagnosis of TA was 49.0 (34–63) months. All patients had pancolitis as well as persistent active colitis resistant to anti-TNF-α antibody treatment. The treatments for TA administered after anti-TNF-α therapy were as follows: Two (50%) patients discontinued anti-TNF-α agent therapy, three (75%) were treated with prednisolone, and one (25%) received tocilizumab. No patient required an operation for TA.

Conclusion

To our knowledge, this is the first study to show the prevalence and clinical features of TA in patients with IBD following administration of anti-TNF-α agent therapy. Although TA is a rare complication, our results suggest that it can develop as paradoxical reaction following administration of anti-TNF-α agents.