bluuebunny/crossref_metadata_2025_split huggingface dataset:
P276 Reactivation of Epstein–Barr virus and cytomegalovirus behaves differently in pathophysiology of ulcerative colitis
Authors: Yamada S , Yamamoto S , Honzawa Y , Hayashi Y , Kitamoto H , Okabe M , Seno H 
Published: January 2020

Abstract

Background
Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) are members of the herpesvirus family. CMV reactivation is often complicated with ulcerative colitis (UC) and is known as one of exacerbation factors. However, the association between EBV reactivation and pathophysiology of UC is still unclear.

Methods
This study enrolled 116 active UC patients who received colonoscopy between January 2005 and January 2019 in Kyoto University Hospital. 244 biopsy specimens were obtained from inflamed colonic mucosa to assess EVB and CMV reactivation. Viral loads of EBV and CMV in inflamed mucosa were measured by real-time PCR assay. The reactivation of those viruses was defined as DNA quantity more than 10 copies/μg DNA. Clinical severity was assessed by Lichtiger index and defined as follow: 4–8 as mild, 9–12 as moderate, and more than 12 as severe. Endoscopic severity was assessed by Mayo endoscopic score. We examined the correlation between the positivity of each viral reactivation and patients’ characteristics or prognosis of UC.

Results
(1) Median age, Lichtiger score and Mayo endoscopic score at the time to assess the viral reactivations were 36 years-old, 8, and 3, respectively. (2) EBV and CMV reactivation were observed in 127 samples (52.0%) and 73 samples (29.9%), respectively. There was no correlation between EBV and CMV viral load (correlation coefficient 0.19), although a significant correlation between those viral reactivations was observed in active colonic mucosa of UC patients (p = 0.002). (3) The proportion of EBV reactivation was higher in both clinically and endoscopically severe UC patients compared with those with mild activity. On the other hands, there was no association between CMV reactivation and clinical or endoscopic severity. (4) Multivariate analysis indicated risk factors for EBV reactivation as receiving anti-TNF-α antibodies (odds ratio [OR] 4.2) or calcineurin inhibitors (OR 3.5), and CMV reactivation (OR 2.1), respectively. (5) Multivariate analysis also indicated risks for CMV reactivation as steroid-refractory (OR 4.7) and EBV reactivation (OR 2.0). (6) EBV and CMV reactivation did not affect clinical outcomes including the requirement of colectomy or intensification of immunosuppressive treatments and the incidence of colitis-associated cancer, dysplasia and lymphoproliferative disease.

Conclusion
Reactivation of EBV or CMV may behave differently in pathophysiology of UC. Further studies are required to clarify the role of EBV reactivation on colonic inflammation in UC patients.
P283 Patient-reported symptoms over a period of 14 days reliably predict endoscopic and histological disease activity in ulcerative colitis (UC)
Authors: Kormilitzin A , Walsh A J , Matini L , Kantschuster R , Lepetyukh M , Wilson J , Brain O , Palmer R , Ambrose T , Satsangi J , Travis S P L 
Published: January 2020

Abstract

Background
Disease activity assessment in UC is most accurately evaluated by endoscopy and biopsy, which often correlates poorly with current symptoms. We investigated whether a machine learning classification algorithm using patient-reported Simple Clinical Colitis Activity Index (SCCAI) over 14 days and signature features could reliably distinguish endoscopic and histopathologic activity from remission.

Methods
The TrueColours ulcerative colitis (UC) monitoring platform was used to collect symptoms (SCCAI, daily) and endoscopic/histopathological activity, as per the UCEIS and Nancy indices (twice in 6 months) in 233 patients. The longitudinal data may be seen as a trajectory. The signature is a collection of statistics which efficiently summarises the trajectory and serves as a non-parametric hierarchical method for longitudinal data representation. Signature features were used as input to the extreme gradient boosting classification algorithm to categorise subjects into remission or active disease groups. Remission: UCEIS ≤1 AND Nancy ≤1; Active disease: UCEIS ≥4 AND Nancy ≥2. The advanced signature-based approach was compared with a baseline model with manually constructed features (mean SCCAI score over 14 days preceding endoscopy). Cross-validation was used to report metrics, Table 1.

Results
Disease activity classification with signature features significantly outperformed mean-SCCAI based approach (AUC 0.87 vs. AUC 0.79 correspondingly, p = 0.011, Figure 1). All other statistical metrics (including sensitivity (0.89), specificity (0.78), PPV (0.82) and NPV) demonstrated the same trend, favouring the signature method. The decision-tree-based ensemble gradient boosting classification algorithm (XGBoost) has the intrinsic ability to rank feature importance. The signature feature of the fourth item within the SCCAI (blood in stool) dominated, followed by cross-correlation between the first (daily bowel frequency) and fourth item.

Conclusion
Gradient boosting classification algorithm with signature features extracted from the longitudinal six-item symptoms of the SCCAI, reliably identified subjects with endoscopic and histopathological disease activity. The developed algorithm may be used with the TrueColours platform as a decision support tool.
P286 Rate of colectomy in ulcerative colitis: Results from a Spanish cohort with 15 years of follow-up
Authors: Rodriguez Gutiérrez C , Elosua Gonzalez A , Prieto Martínez C , Rubio Iturria S , Vicuña M A , Nantes Castillejo Ó 
Published: January 2020

Abstract

Background
Knowing the natural history of ulcerative colitis (UC) is essential to understand the evolution of the disease, assess the impact of different therapeutic strategies, identify poor prognostic factors and provide patients with understandable information who help them in decision making. It has been suggested that biological drugs could modify natural history of UC and therefore decrease the rates of colectomy. In Spain, infliximab is approved for CU since 2005.

Methods
We performed a retrospective study that includes all patients with a definitive diagnosis (DD) of UC or Unclassifiable Colitis (UC) in the Navarra Incident Cohort (which includes all patients diagnosed between 2001 and 2003 in Navarra, Spain). Our objectives were to analyse the Colectomy Incidence Rate (CIR) from diagnosis to the end of follow-up (12-31-2017) and identify predictive factors of colectomy.

Results
We included 174 patients with DD of UC (42.5% E2 - 26.8% E3) and 5 of IC: 44.1 women, median age 39.2 years (7–88), median follow-up of 15.7 years. At the end of the follow-up, 8 patients underwent colectomy (CIR 3 surgeries per 100000patients-year). Timing of colectomy was: 3 at the initial diagnosis (&lt;1 month), 2 in the first 2 years, 2 at 5 years and 1 at 12 years from diagnosis. All had previously received steroids, 5 immunomodulators and 2 biological agents. In 7 (87%) the surgery was urgent and the indication, megacolon in 3 (37.5%), severe outbreak in 3 (37.5%) and failure to medical treatment in 2 (25%). In 5 cases (62.5%), an ileoanal reservoir was made and in 3 definitive ileostomy.

Conclusion
In our cohort, global colectomy rates are lower than those reported in other series and occur mostly in the first 5 years of evolution.
P295 VALIDation of the IBD-Disk instrument for assessing disability in inflammatory bowel diseases in a population-based cohort: The VALIDate study
Authors: Le Berre C , Bourreille A , Flamant M , Bouguen G , Siproudhis L , Dewitte M , Dib N , Cesbron-Metivier E , Goronflot T , Gourraud P A , Kerdreux E , Poinas A , Trang-Poisson C 
Published: January 2020

Abstract

Background
Inflammatory bowel diseases (IBD) are disabling disorders. The IBD-Disability Index (IBD-DI) was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a shortened and visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk in a large cohort of IBD patients and to assess its variability over time.

Methods
From March 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3–12 months intervals (NCT03590639). Validation included concurrent validity, reproducibility, internal consistency, and evaluation of IBD-Disk correlation with IBD activity. Variability was assessed by comparing scores between baseline and follow-up visits.

Results
A total of 559 patients (73% Crohn’s disease, 27% ulcerative colitis) were included and 389 were followed up (Table 1). There was a good correlation between IBD-Disk and IBD-DI scores (r = 0.75, p &lt; 0.001) (Figure 1). The IBD-Disk was significantly higher in patients with active disease according to Physician/Patient Global Assessment (Figure 2), clinical scores (Figure 3), and biomarkers levels, compared with patients with inactive disease. Reproducibility was excellent (intra-class correlation coefficient = 0.90), as well as internal consistency (Cronbach’s α = 0.89). The IBD-Disk score significantly decreased in patients becoming inactive over time.

Conclusion
This is the first study to validate the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability in clinical practice. Further studies are warranted to assess its correlation with endoscopic activity, to explore its responsiveness to change, and to evaluate the factors associated with disability.
P308 The need for psychological and psychotherapeutic interventions in Austrian patients with inflammatory bowel disease
Authors: Kutschera M , Waldhör T , Gröchenig H P , Haas T , Wenzl H , Steiner P , Koch R , Feichtenschlager T , Eckhardt G , Mayer A , Kirchgatterer A , Ludwiczek O , Platzer R , Papay P , Gartner J , Fuchssteiner H , Peters P G , Reicht G , Moser G , Dejaco C , Primas C , Novacek G , Miehsler W 
Published: January 2020

Abstract

Background
inflammatory bowel diseases (IBD) are lifelong conditions challenging the patient not only with respect to somatic complaints but also affecting psychosocial issues. This may lead to the need for additional psychological care. The present study investigated the patients’ subjective need for additional psychological care and indicators for such a need.

Methods
We performed a cross-sectional multicentre study on Austrian IBD patients who were in routine care at one of the 18 participating IBD centres. The patients were asked to fill in a questionnaire booklet including the ADAPT, a validated questionnaire on the need for psychological care which gives two separate scores (‘ADAPT-IPC’ -need for integrated psychosomatic care, ‘ADAPT-PT’- need for psychotherapy), a validated questionnaire on the use of complementary and alternative medicine (CAM), the SIBDQ, and questions on clinical and sociodemographic data. The primary endpoint was the need for integrated psychosomatic care, psychotherapy or both.

Results
1286 patients returned the questionnaire. In total, 29.7% of all patients expressed a need for additional psychological care, 18.6% expressed a need for ADAPT-IPC and 20.2% expressed a need for ADAPT-PT. The multivariable regression analysis revealed the two dominating factors associated with the need for both types of psychological care were the use of CAM and a low SIBDQ-score ≤ 50 (see Table for details).

Conclusion
About 30% of the Austrian IBD patients expressed a need for integrated psychosomatic therapy a/o psychotherapy. This need was especially associated with reduced quality of life and the use of CAM which may indicate the desire for emphathetic and dedicated care. Further studies will be necessary to clarify if these results can be reproduced in other countries.
P322 Impact of the presence of Epstein–Barr virus in intestinal mucosa of inflammatory bowel disease patients
Authors: NUÑEZ ORTIZ A , Trigo Salado C , De la Cruz Ramírez M D , Márquez Galán J L , Herrera Justiniano J M , Leo Carnerero E 
Published: January 2020

Abstract

Background
To evaluate the importance of positive Epstein–Barr virus (EBV) status in intestinal biopsy in patients with inflammatory bowel disease (IBD), its association with active disease and immunosuppressive (IM) therapy and its influence on the clinical evolution of IBD.

Methods
We retrospectively analysed patients with IBD who were tested for EBV in intestinal mucosa between November 2009 and June 2017. Pathologists decided EBV testing based on the presence of severe histologic activity with/without prominent lymphoplasmacytic infiltrate or refractory disease to various treatments. We analysed phenotypic characteristics, previous treatments, active therapies at the time of EBV testing, EBV status by immunohistochemistry, presence of lymphoma, treatment decision making after EBV testing and subsequent clinical evolution based on hospital admissions and treatment escalation requirement.

Results
We included 56 patients, 28 with Crohn’s disease (CD) and 28 with ulcerative colitis (UC). The predominant phenotype of patients with CD was A2L3C1. Regarding patients with UC, 14 patient had left-sided and 14 extensive colitis.
EBV was positive (EBV+) in 26 cases (46%), one of them associated with a lymphoproliferative disorder. EBV+ status was associated with clinically active disease (53.3% vs. 25%, p = 0.08); severe endoscopic (54.5% vs. 37.5%, p = 0.02) and severe histological activity (72.2% vs. 33.3%, p = 0.007) and the presence of a prominent lymphoplasmacytic infiltrate (68.8% vs. 16.7%, p &lt; 0.0005). In addition, active steroid treatment, but not IM and/or biological therapy, at the time of EBV testing was associated with EBV+ status (61.5% vs. 33.3%, p = 0.03). Only the presence of a prominent lymphoplasmacytic infiltrate showed significant association with EBV+ in the multivariate analysis (p = 0001). IM therapy was de-escalated in 6/26 EBV-positive patients. In EBV- patients, IM treatment was escalated in 10/30. After a mean follow-up of 53.3 months, 17 patients required hospital admission and 26 escalation of therapy. Both risk of admissions and escalation of treatment during follow-up were higher in EBV+ patients (38.5% vs. 23.3%, p = 0.2; and 65.4% vs. 30%, p = 0.008, respectively). Only female sex was associated with a greater possibility of hospital admission and EBV+ with the need for treatment escalation (p = 0.03) in the multivariate analysis. None of the patients developed lymphoma during follow-up.

Conclusion
EBV+ status in intestinal mucosa is associated with histological activity. Prominent lymphoplasmacytic infiltrate is the only factor associated with EBV+ status independently of immunosuppression status. EBV+ is associated with subsequent poor clinical evolution and a greater need for escalation of IM therapy.
P329 ECCO grant recipient: preliminary results of the HOT-TOPIC trial (Hyperbaric Oxygen Therapy for the Treatment Of Perianal fistulas In Crohn’s disease)
Authors: Lansdorp C , Gecse K , Buskens C , Löwenberg M , Stoker J , Bemelman W , D’Haens G , van Hulst R 
Published: January 2020

Abstract

Background
Beneficial effects of hyperbaric oxygen (HBO) therapy for perianal fistulising Crohn’s disease (pCD) have been suggested in previous publications. The HOT-TOPIC study was designed to further investigate its feasibility and therapeutic effect in 20 therapy-refractory patients with pCD. Here we present the preliminary results.

Methods
17 patients with pCD refractory to conventional-therapy &gt; 6 months (medical and/or surgical, no patients with deviating stoma) were treated with 40 sessions of HBO therapy (243–253 kPa, 110 min per session throughout 8 weeks). Medical treatment remained stable from screening, seton drain(s) were removed after 30 treatment. Co-primary outcomes were clinical response as measured by the perianal disease activity index (PDAI) and MRI improvement measured by the modified van Assche index. Secondary outcomes were clinical response as assessed by fistula drainage assessment (FDA), biochemical response and patient-reported outcomes. All outcomes were assessed at baseline and 2 months after HBO.

Results
17 patients (6 female, median age 34 years, median duration of disease 13 years) were treated. Median PDAI scores decreased from 8 to 4 (p &lt; 0.001) and MRI scores from 9.4 to 7.3 (p = 0.001). Defined as PDAI of 4 or less, 11 out of 17 patients had inactive perianal disease after treatment, with 3 patients also having a predominantly fibrotic tract on MRI. Of the 45 external openings draining at baseline, 22 were clinically closed after treatment (49%, assessed by FDA). Four patients, three with one external opening and one with five openings at baseline, had no remaining openings after treatment. Median C-Reactive Protein and faecal calprotectin levels decreased from 5.0 and 416 to 2.3 and 31 (p = 0.002 and p = 0.003), respectively. Median scores of the inflammatory bowel disease questionnaire (IBDQ) increased from 169 to 185 (p = 0.001) and VAS scores from the Euroqol-5-dimensions questionnaire increased from 65 to 75 (p = 0.07), higher scores reflecting better quality of life. When asked on a validated decision regret scale if patients regretted their decision to undergo HBO, the mean score was 12.5 (0–100, higher scores indicating higher regret). During follow-up, none of the patients needed new (experimental) medication, re-interventions or stoma. Seven out of 17 patients experienced trouble equalising middle ear pressure during HBO, with four patients showing signs of barotrauma after otoscopy. Three patients needed tympanostomy tubes. No other clinically relevant adverse events occurred, and no adverse events led to discontinuation of the treatment.

Conclusion
Based on preliminary data, HBO treatment is associated with significant improvement in pCD, as measured by clinical and MRI endpoints.
P332 Mindfulness-based stress reduction and cognitive intervention improve the health-related quality-of-life and ability to work in Crohn’s disease patients: A randomised controlled trial
Authors: Schwartz D , Sergienko R , Goren G , Reggev S , Friger M , Nemirovsky A , Monsonego A , Greenberg D , Sarid O , Slonim-Nevo V , Odes S 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) patients have reduced quality-of-life (QoL) in physical, emotional and social domains, and diminished work and leisure activities. We examined whether Mindfulness-Based Stress Reduction and Cognitive Intervention (‘Intervention’) can improve QoL and ability to work.

Methods
Patients (≥18 years), Harvey–Bradshaw Index (HBI) &gt;4 and &lt;16, were randomised to Intervention or Control groups. Intervention was taught in 8 weekly sessions by social workers via SKYPETM with twice-daily practice and back-report required. Medications were not controlled. HBI was completed at entry (T1) and 12 weeks (T2), and these questionnaires: (1) Short inflammatory bowel disease questionnaire (SIBDQ), disease-specific HRQoL measure. (2) Short-Form 12 (SF-12) questionnaire, generic HRQoL measure of physical health (PH) and mental health (MH). (3) EQ-5D-3L HRQoL questionnaire. (4) Work Productivity and Activity Impairment (WPAI) questionnaire, measuring absenteeism, presenteeism (reduced productivity), work impairment (composite of absenteeism and presenteeism), and leisure activity impairment. Statistics: Pearson Chi-squared, Wilcoxon signed-rank test.

Results
There were 39 Intervention and 43 Control patients. Demographic and medical characteristics (median, %) were: age 30 y; women 65%, married/partner 48%; higher education 83%; BMI 22; non- or past-smokers 92%; disease duration 5 y; HBI 8 (range 5–15); past surgery 17%; Montreal A2 89%, L2+L3 89%, B1+B2 89%, perianal disease 18%; drugs: corticosteroids 4%, 5-ASA 5%, immunomodulators 21%, biologics 43%; (p = ns between groups). Socio-economic status was higher in Intervention (87% = good/very good) than Control (58%, p = 0.016). HBI, SIBDQ and SF PH improved in both groups, but SF MH, EQ-5D-3L and all WPAI measures improved only in Intervention group (Table). Non-significance of WPAI indices between groups resulted from small sample size.

Conclusion
Mindfulness-Based Stress Reduction and Cognitive Intervention led to increased QoL and less work and activity impairment. If confirmed in a large cohort the intervention may be offered to all CD patients.
P334 Impact of disease duration on tofacitinib efficacy in patients with ulcerative colitis
Authors: Travis S , Dotan I , Danese S , Chiorean M , Yamamoto-Furusho J , Ponce de Leon D , Su C , Paulissen J , Maller E , Modesto I , Colombel J F 
Published: January 2020

Abstract

Background
Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib in patients with UC were evaluated in two Phase 3 induction studies (OCTAVE Induction 1 and 2; NCT01465763, NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574) [1], and an ongoing, open-label, long-term extension study (NCT01470612) [2]. We evaluated the impact of disease duration on tofacitinib efficacy in the OCTAVE trials.

Methods
Patients received tofacitinib 10 mg twice daily (BID) or placebo in OCTAVE Induction 1 and 2, and responders at Week 8 were eligible to receive tofacitinib 5 or 10 mg BID or placebo during OCTAVE Sustain (final efficacy assessment at Week 52). Non-responders from OCTAVE Induction 1 and 2 and completers/treatment failures from OCTAVE Sustain could enter the OLE study. In the OLE study, patients who did not show clinical response to 8 weeks of tofacitinib 10 mg BID in OCTAVE Induction 1 and 2 (induction non-responders [IndNR]) received an additional 8 weeks of tofacitinib 10 mg BID; all patients underwent endoscopy at Month 2 (data as of Sep 2018). Patients were stratified by UC disease duration (&lt;3, 3–6 and &gt;6 years) at OCTAVE Induction 1 and 2 baseline (ie prior to study treatment). Associations between disease duration category and efficacy endpoints were assessed using the Cochran-Mantel–Haenszel Chi-square test.

Results
Among patients who received tofacitinib 10 mg BID in OCTAVE Induction 1 and 2, remission and mucosal healing rates at Week 8 were numerically higher in those with shorter disease duration than those with longer disease duration, but associations were not statistically significant (Table). Clinical response rates were similar across disease duration categories. At Week 52 of OCTAVE sustain, remission and mucosal healing rates were highest in patients with the shortest disease duration (&lt;3 years; Table). Among IndNR, the proportions of patients achieving efficacy endpoints at Month 2 of the OLE study were lowest in those with disease duration &lt;3 years, but associations were not statistically significant (Table).

Conclusion
In general, disease duration did not impact tofacitinib efficacy. Patients diagnosed with UC &lt;3 years prior to starting tofacitinib treatment were numerically more likely to achieve remission and mucosal healing in induction and maintenance trials than those with longer disease duration, but the associations were not statistically significant. These analyses are post hoc and limited by the small sample size, and further data are needed to understand whether disease duration may have an impact on the response to tofacitinib treatment.

References