bluuebunny/crossref_metadata_2025 huggingface dataset:
P670 “What Matters To You?” – How do patient views compare with a patient experience framework and UK national standards of care?
Authors: Sheldon E , Roman S , Randall K , Rachel H , Winsor G , Wakeman R , Lobo A
Published: January 2023

Background

There is increasing focus on the organisation of services for people with IBD. Patient experience of care is an important consideration in service delivery. The United Kingdom NHS Long Term Plan indicates the importance of support that is more differentiated for individuals, with more personalised care when needed, which starts with the question ‘What matters to you?”. This is particularly important for people with inflammatory bowel disease (IBD).

Methods

The aim was to identify ‘What matters to you?’ for people attending a single UK teaching centre IBD service and to relate it to patient experience and national standards of care. Invitations to take part in the AWARE-IBD quality improvement programme were sent to 4082 patients receiving IBD care at a single UK teaching centre in 2 rounds (October 2021 and May 2022). Invitation letters included an anonymous open-ended questionnaire asking patients “what matters to you?”. Responses were extracted as qualitative data and coded using two frameworks: Patient experience domains (Bull et al) (Communication, Patient-centred Care, Quality, Integration, Involvement, Accessibility, Environment and Facilities, Discomfort) and national IBD UK Standards. Frequencies for each coding strategy were calculated to determine the most important patient experience domains and IBD UK standards.

Results

Responses were received from 408 and 205 patients from each recruitment round (n=613). Figure 1 displays frequencies for each patient experience domain. Accessibility (47.5% and 53.2% respectively), Communication (19.6% and 12.7%) and Patient-Centred Care (15.7% and 11.2%) were expressed most frequently. Sub-themes included access to and contact with IBD nurse specialists, timely and accessible appointments and regular contact with a specialist IBD health care professional (HCP). Responses were coded to IBD UK standards, where possible (Table 1). Responses most frequently coded to statements relating to shared decision making, having a personalised care plan, access to an IBD nurse specialist including helpline and regular clinical review. 77 responses could not be coded to an IBD UK standard.

Conclusion

Access to the IBD service when needed matters most to patients with good communication of information and personalised, patient-centred care. Service organisation should therefore reflect these facets of patient experience and defined standards. Patient views that are not currently represented in published standards should be considered in future iterations. This study also highlights personalised written care plans and improved access to the IBD Nurse Advice line.
P671 Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: Results from the UniStar study long-term extension
Authors: Turner D , Rosh J R , Cohen S A , Griffiths A , Hyams J S , Kierkuś J , Adedokun O J , Strauss R , Kim L , Volger S ,   UniStar Investigators
Published: January 2023

Background

Ustekinumab (UST) is an approved biologic for the treatment of adults with Crohn’s disease (CD). Through 16 weeks (wks), UST demonstrated high rates of efficacy, low rates of immunogenicity, and safety in paediatric patients (pts) similar to that observed in adults.1 Here, we evaluated UST in paediatric CD pts through 268 wks.

Methods

UniStar was a phase 1, multicentre, double-blind study in paediatric pts (2-18 years old; body weight ≥10kg) with moderately to severely active CD. Pts (n=45) were randomised 1:1 and stratified by body weight (<40kg or ≥40kg) to low (3 mg/kg [<40kg]; 130 mg [≥40kg]) or high (9 mg/kg [<40kg]; 390 mg [≥40kg]) dose intravenous UST. At wk 8, pts received 1 subcutaneous maintenance dose (2 mg/kg [<40kg]; 90 mg [≥40kg]). Pts responding to UST at wk 16 were eligible to enter the long-term extension (LTE) and continued UST maintenance dosing every 8 wks up to wk 268. This study reports efficacy, safety, pharmacokinetics (PK), and immunogenicity evaluated at wks 16, 24, 48, 224, and through 240 wks, as applicable. The primary visit was wk 48, representing outcomes after ~1 year of UST treatment.

Results

Of the 44 pts treated with UST, 34 (77%) responded and entered the LTE; the number of pts receiving treatment at wks 48, 104, 152, and 208 was 26 (77%), 16 (47%), 12 (35%), and 8 (24%), respectively. Among pts in the LTE (n=34), baseline median age (range) was 13.0 (6.0-17.0) years, 62% were female, 47% weighed <40kg, 18% weighed <30kg, and 94% previously failed anti-tumor necrosis factor therapy. At wk 48, 41% (14/34) of pts achieved clinical remission, and 59% (20/34) achieved clinical response. The proportion of pts with abnormal C-reactive protein (CRP) levels at baseline was 71% (24/34), and 59% (16/27) of pts achieved normalization of CRP (<3mg/L) at wk 48. By the final safety visit at wk 240, 91% of pts reported ≥1 adverse event (AE), and 15% discontinued due to AEs, with CD worsening as the most frequent reason. Infections occurred in 74% of pts, and 32% had serious AEs. The majority of serious AEs were gastrointestinal disorders associated with CD. No injection-site reactions, serious infections, malignancies, or deaths were reported. Median serum UST concentrations tended to be lower in pts weighing <40kg compared with pts weighing ≥40kg, but were generally consistent from wks 16 to 268 and remained detectable through wk 200 (Figure). Incidence of UST antibodies was low (1/34; 3%).

Conclusion

In the UniStar LTE, the efficacy, safety, PK, and immunogenicity of UST in paediatric pts with CD was generally consistent with adult pts for as long as 4 years of treatment.

Reference:

1. Rosh JR et al. J Crohns Colitis. 2021;15(11):1931.
P687 Durability of recaptured response to ozanimod during the True North open-label extension
Authors: Dignass A , Regueiro M , Colombel J F , Jain A , Canavan J B , Wu H , Lawlor G , Osterman M T , Vermeire S , Rubin D T
Published: January 2023

Background

Ozanimod is approved in the EU, US, and other countries for treatment of moderately to severely active ulcerative colitis (UC) in adults. In the phase 3 True North (TN) study, ozanimod 0.92 mg once daily demonstrated efficacy and safety for up to 52 weeks in patients (pts) with moderately to severely active UC. This open-label extension (OLE) analysis evaluated the long-term durability of ozanimod based on symptomatic and clinical endpoints in pts who experienced disease relapse while on placebo during the TN maintenance period (MP) and then recaptured response to ozanimod during the OLE.

Methods

Responders to ozanimod 10-week induction therapy were rerandomised 1:1 to ozanimod (n=230) or placebo (n=227); this OLE interim analysis (data cutoff: January 10, 2022, at which point the OLE Week 94 disposition was available for pts) included all pts who relapsed on placebo during the MP and reinitiated ozanimod in the OLE. Endpoints included symptomatic response and remission, clinical response and clinical remission (which include endoscopy subscores), and corticosteroid (CS)-free remission (clinical remission while off CS for ≥12 weeks) evaluated using observed case (OC) and nonresponder imputation (NRI) analyses, and mean total Mayo score over time.

Results

A total of 77/227 pts (34%) rerandomised to placebo during MP experienced a relapse after a median of 12.7 weeks and all entered the OLE. Symptomatic response was achieved by 46/73 (63%) pts 5 weeks after restarting ozanimod in the OLE (NRI analysis: 60% at OLE Week 5) and in 32/33 (97%) by OLE Week 94 in the OC analysis. Symptomatic remission was also achieved by OLE Week 5 by 24/73 (33%) pts. Sustained efficacy of ozanimod reinitiation was also demonstrated comparing OLE Weeks 46 and 94 across clinical endpoints by OC analysis (clinical response, 76% and 86%; clinical remission, 44% and 59%; CS-free remission, 37% and 52%) and NRI analysis (clinical response, 42% and 31%; clinical remission, 25% and 22%; CS-free remission, 21% and 20%) (Figure 1). In addition, 56.3%, 52.6%, and 50% of pts who experienced clinical response, clinical remission, and CS-free remission, respectively, at OLE Week 46 continued to sustain these endpoints at OLE Week 94. Reductions in mean total Mayo score at OLE Week 46 were also sustained through OLE Week 94 (Figure 2).

Conclusion

Response to ozanimod was regained after temporary therapy discontinuation for most pts, and this response was durable for up to 2 years as demonstrated by both symptomatic and clinical endpoints in this interim analysis from the TN OLE study. These results suggest that pts who experienced disease relapse after temporarily holding ozanimod in clinical practice may benefit from resumption of ozanimod.
P694 Long-term monitoring of post-surgical recurrence in Crohn’s disease using a strategy based on the periodic determination of fecal calprotectin in patients without early postoperative recurrence
Authors: Mañosa Ciria M , Oller B , Garcia-Planella E , Guardiola J , Cañete F , Gonzalez Muñoza C , Camps B , Calafat M , Domènech E
Published: January 2023

Background

Current guidelines recommend to perform an ileocolonoscopy 6-12 months after surgery in patients with Crohn’s disease (CD) and ileo-cecal resection with ileocolic anastomosis to assess the occurrence of endoscopic post-operative recurrence (PORe) and escalate therapy if necessary. However, it is not established whether and/or when endoscopic monitoring is advised in patients who do not present early PORe

Objective

To evaluate the usefulness of a strategy based on the periodic determination of faecal calprotectin (FC) to decide whether to carry out a new endoscopic control in patients without PORe (iR<2) in the last endoscopic assessment performed

Methods

Pilot, prospective, multicentre and open study. Inclusion criteria: 1) CD with intestinal resection and ileo-colic anastomosis; 2) last ileocolonoscopy after surgery with a Rutgeerts score i0 or i1; 3) No suspicion of clinical POR. Patients with an ostomy or chronic use of NSAIDs or omeprazole were excluded. Centralized FC determinations were performed every 4 months for 2 years and an ileocolonoscopy at the end of follow-up was performed. In the case of FC>250μg/g in 2 consecutive determinations, ileocolonoscopy was advanced and the patient was withdrawn from the study. The main variable of interest was the rate of advanced PORe (as defined by Rutgeerts score >i2) at the final ileocolonoscopy.

Results

55 patients were included, 13% perianal disease, 24% smokers and 27% surgery prior to the index surgery. 47% followed prevention with thiopurines and 14% with anti-TNF. During follow-up, 7 patients had FC>250μg/g in two consecutive determinations; advanced PORe was identified in 5 of these patients, PORe i2 in one and intestinal adenocarcinoma in another one. Among the patients who completed the 2-year follow-up, none had advanced PORe at the final ileocolonoscopy although intermediate PORe (i2) was found in 12. The rate of advanced PORe was 71% in those who finished the study before 2 years and 0% in those who were not advanced to endoscopy. The AUC for FC to detect advanced PORe was 0.98 (p=0.002). The cut-off point of FC>250μg/g obtained a sensitivity of 100% and specificity of 60% to detect advanced PORe.

Conclusion

The serial determination of FC is a suitable long-term monitoring tool to decide whether to perform ileocolonoscopy in patients without early PORe.
P707 Using urgent small bowel ultrasound (SBUS) as a tool for decision-making in patients with inflammatory bowel disease (IBD): retrospective analysis of United Kingdom (UK) patients' outcome.
Authors: Lehmann A , Nandra G , Power N , Lindsay J O ,   James Oliver Lindsay
Published: January 2023

Background

In the UK, magnetic resonance enterography (MRE) and colonoscopy are the gold standard assessment for mucosal disease activity in IBD. Both techniques require bowel preparation, may be poorly tolerated and are often subject to delay due to capacity issues. In several European centres, ultrasound is used as an alternative tool for disease activity monitoring and clinical decision-making. Recent studies confirm excellent sensitivity, specificity, correlation with MRE / colonoscopy and robust inter-observer agreement. In the UK, a lack of US training in IBD physicians has hindered development of accessible SBUS. In view of issues with MRI capacity during the covid pandemic, a dedicated small bowel ultrasound list with a gastroenterology fellow and a specialist radiology consultant for urgent IBD patients was initiated.

Methods

Records of IBD patients undergoing SBUS between June 2022 and November 2022 were reviewed. SBUS assessed disease activity (vascularity, bowel wall thickness, mesenteric fat and lymphnodes), length of disease, presence of obstruction or fistulating disease. Patients were then retrospectively asked to rate their SBUS experience compared to previous MREs.

Results

53 SBUS's (46 (86.7%) CD; 2 (3.7%) UC) were performed on a dedicated SBUS list by a gastroenterology fellow and specialist radiology consultant during the study. In 29 patients (54.7%), the area of interest was the terminal ileum. SBUS detected disease complications in 7 (2 (3.7%) patients with obstructive disease, and 5 (9.4%)) patients with penetrating disease. The average waiting time from the point of referral to SBUS was 4.7 weeks, compared to an average waiting time for MRE of 20 weeks. Treatment response was assessed in 18 patients (33.9%). We were able to make treatment decisions with 32 patients (60.3%) based on their SBUS results without further assessment. In 10 patients (18.8%), SBUS was used to confirm a diagnosis in addition to colonoscopy. 18/22 ( 81%) patients reported a preference for SBUS compared to MRE (preference score of 4.5 on scale of 1-5).

Conclusion

We developed an urgent SBUS service to aid timely clinical decision-making for IBD patients. In our practice, SBUS is an accurate tool to assess disease activity, significantly reduces patients waiting times and is the patient’s preferred investigation. There is a clear unmet need to train IBD doctors and radiologists in SBUS.
P730 Anti tumor necrosis factor treatment in Ulcerative Colitis: Real-world data and evaluation of current treatment targets (STRIDE II)
Authors: Lundekvam J A , Lie Høivik M , Anisdahl K , Cvancarova Småstuen M , Medhus A W ,   Inflammatory Bowel Disease Research Group - Oslo University Hospital
Published: January 2023

Background

In 2021, the Selection of Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative proposed updated recommendations for treatment targets for ulcerative colitis (UC) patients. The recommendations introduce clinical remission as a short/medium term target, normalisation of CRP and Fecal Calprotectin (FC) as an intermediate target, and advice that change of treatment should be considered if targets are not met. In this single-centre study, we report real-world experience with proactive therapeutic drug monitoring (TDM) strategy for UC patients with first-line anti tumor necrosis factor (TNFi) treatment, and reflect on how implementation of the STRIDE II recommendations might affect clinical practice.

Methods

Adult, biologically naïve UC patients starting TNFi between 2014 and 2021 at Oslo University Hospital were included in a medical chart review study, and data were recorded at three and twelve months. Clinical remission was defined as a patient-recorded outcome (PRO-2) ≤1. Biochemical remission was defined as CRP <5 mg/L and FC < 250 µg/g. Combined remission was defined as clinical and biochemical remission. Target serum drug levels were defined as ≥7.5 mg/L (adalimumab [ADA]) and ≥5 mg/L (infliximab [IFX]). Logistic regression was applied for association analyses.

Results

A total of 141 patients were included. Of these, 60% were male, median age was 25 years. In total, 67% received IFX and 32% received ADA. One third (n=39) patients discontinued TNFi or added a second biologic agent during follow-up and were considered in non-remission, resulting in 102 (72%) persistent patients. Percentages [95% CI] in remission at 3 and 12 months are summarized in Table 1, and for drug-persistent patients in Table 2. Target drug level at 3 months was associated with clinical remission at 12 months (OR 2.97, 95% CI [1.24 – 7.12]), biochemical remission at 12 months (OR 2.64, 95% CI [1.03 – 6.77]) but not with combined remission. In total, 125 dosage adjustments were recorded. Of these, 70 (56%) were classified as adjustments related only to serum drug levels.

Conclusion

Combined remission rates at 3 and 12 months for persistent patients suggest that 60% and 46% of our cohort should have been considered for a change of treatment according to the STRIDE II recommendations. A majority of dosage adjustments were made proactively, and as target drug levels at 3 months were associated with remission outcomes at 12 months, our data support the use of a proactive TDM strategy.
P798 Understanding anti-TNF treatment failure: mechanisms and management of loss of response to anti-TNF therapy, three-year data from the PANTS study
Authors: Chanchlani N , Lin S , Hamilton B , Bewshea C , Thomas A , Smith R , Roberts C , Nice R , McDonald T J , Goodhand J R , Ahmad T , Kennedy N A ,   PANTS Consortium
Published: January 2023

Background

PANTS (Personalised Anti-TNF Therapy in Crohn’s disease) is a prospective observational UK-wide study investigating the effectiveness of infliximab (IFX) and adalimumab (ADL) in active luminal Crohn’s disease. Here we report remission rates through three years of follow up; rates of and the factors that predicted loss of response (LOR); and the effect of dose intensification on drug persistence.

Methods

Remission was defined as CRP of ≤3 mg/L and HBI of ≤4 points (sPCDAI ≤15 in children), without corticosteroid therapy or exit for treatment failure.

LOR was defined in patients who initially responded to anti-TNF therapy at week 14 and continued in the PANTS extension, by symptomatic IBD activity that warranted an escalation of corticosteroids, immunomodulatory or anti-TNF therapy, resectional surgery, or exit due to adverse events.

The effect of dose intensification at the time of LOR on drug persistence was stratified by optimal anti-TNF drug level (IFX 7, ADL 12) (mg/L) and presence of antibodies (anti-IFX 9, anti-ADL 6) (AU/mL), measured using IDKmonitor® ELISA assays.

Results

Between March 2013 and July 2016, 1610 patients were included in PANTS: 358/955 (37%) treated with IFX (221/358 [62%] originator and 137/358 [38%] with biosimilar) and 187/655 (29%) treated with ADL, who had not exited for treatment failure at the end of year 1, opted to enrol in the extension.

Overall, 41.8%, 39.4%, and 41.3% of IFX- and 38.2%, 39.7%, and 39.2% of ADL-treated patients were in remission at year 1, 2 and 3, respectively. For both drugs, we observed a dose response association between week 14 drug concentration and remission status at the later timepoints (A).

34.3%, 54.0%, and 60.3% of IFX-, and 31.9%, 47.3%, and 69.0% of ADL-treated patients lost response at year 1, 2 and 3, respectively. Multivariable regression analyses showed that low drug concentration was the major independent risk factor associated with LOR for both drugs (B).

In patients who developed immunogenicity, factors associated with subsequent drug clearance were lower week 14 drug level (p<0.01), non-immunomodulator use (p=0.04), and obesity (p<0.01), but not carriage of HLA-DQA1*05 (p<0.34).

In the setting of LOR (n = 686 episodes), 42% patients had their anti-TNF dose intensified and 29% exited the study without further action (C). Compared to patients who experienced LOR with optimal drug levels, dose intensification was associated with lower rates of drug persistence in patients with immunogenic-pharmacokinetic and non-immunogenic pharmacokinetic treatment failure in patients treated with IFX, but not ADL (D).

Conclusion

Long term remission was observed in about 40% of patients treated with IFX and ADL. Loss of response and non-remission was predicted by low drug levels.
P820 Comparison of three nutritional screening tools with the new GLIM criteria for malnutrition among definitive and elective surgery Crohn’s patients in China
Authors: Zhao Z , Chen C , Li Y , Ye X , Zhu W ,   Research institute of General Surgery, Jinling Hospital, Medical School of Nanjing University
Published: January 2023

Background

The aim of this study was to evaluate and compare three nutritional screening tools with the new GLIM criteria for malnutrition among definitive and elective surgery Crohn’s patients in China.

Methods

Nutritional screening tools, including the nutritional screening tool for IBD (NS-IBD), the Nutritional Risk Screening 2002 (NRS 2002), the Prognostic Nutrition Index (PNI) were applied to 212 patients with definitive and elective surgery Crohn’s patients in China. We compared the diagnostic values of these tools for malnutrition, using the new GLIM criteria for malnutrition as the ‘gold standards’.

Results

According to the new GLIM criteria for malnutrition, 81(61.79%) of the patients were diagnosed as malnutrition. With the use of NRS-2002, 140(66.10%)of the patients were found to be at high risk of malnutrition; with the use of NS-IBD, 181(85.30% )of the patients were found to be at moderate/high risk of malnutrition; and according to PNI, 94(44.0%)of the patients were found to be at moderate/high nutritional risk. The comparison of each nutritional risk tool showed sensitivity of 83.26%,85.74%,79.83%, and specificity was 62.91%,54.62%,57.34% for NRS-2002, NS-IBD and PNI, respectively. NS-IBD was best correlated with the ESPEN diagnostic criteria (К=0.388, p<0.001) compared with PNI (К=0.208, p=0.007) and NRS-2002 (К=0.744, p<0.032).The receiver operating characteristic curve of PNI had the highest area under the curve (AUC) compared with NRS 2002 and NS-IBD.

Conclusion

In the future, the combined application of GLIM criteria and two nutritional screening tools can better reflect the nutritional status for definitive and elective surgery Crohn’s patients.
P858 Prevalence of sarcopenia in patients with inflammatory bowel disease and factors associated with it
Authors: Dharap V , Abraham P , Desai D , Gupta T , Dhoble P , Mehta N , Modhe J ,   Inflammatory bowel disease
Published: January 2023

Background

Sarcopenia is a progressive and generalized skeletal muscle disorder with significant reduction in skeletal muscle mass associated with low muscle strength and physical performance. Multiple factors contribute to sarcopenia in active as well as quiescent inflammatory bowel disease (IBD). It has been implicated in disease complications and surgical outcomes

Methods

Inclusion criteria: Consecutive consenting patients > 18 years old with IBD attending the division of Gastroenterology between June 2021 and June 2022

Exclusion criteria: Associated systemic diseases, patient with prior surgery for IBD, that could contribute to sarcopenia were excluded

All patients had anthropometric measurements, calculation of body mass index (BMI), and measurement of mid-arm muscle circumference. The muscle strength was measured by hand-grip strength by hand-held dynamometer. The physical performance was measured by gait speed by 4-meters walk test. The muscle mass was calculated by measuring skeletal muscle index (SMI) with single slice of CT scan at the level 3rd Lumbar vertebra.

Patients were categorized according to the European Working Group on Sarcopenia in Older People, 2018 definition, into probable sarcopenia (low muscle strength), sarcopenia (low muscle strength and low muscle mass), and severe sarcopenia (low muscle strength, low muscle mass, and low physical performance1. Factors evaluated for association with sarcopenia were age, gender, disease subtype (Crohn’s disease [CD], ulcerative colitis [UC] or IBD-U (unclassified), activity and nutrition. SMI value of <42 cm2/m2 for men and <38 cm2/m2 for women were taken as per a recent Indian study2.

Results

Of 117 patients, 73 had ulcerative colitis (UC), 42 Crohn’s disease (CD), and 2 IBD- unclassified (IBD-U). Forty (34.2%) patients had probable sarcopenia; 47 (40.2%) patients had sarcopenia (29 UC, 18 CD) including 10 with severe sarcopenia. Ten (21.3%) patients with sarcopenia were in disease remission. On univariate analysis BMI, disease activity, low hemoglobin, and biologic use were significantly associated with sarcopenia (Table1); on multivariate analysis, only BMI showed significant association with sarcopenia. (Table 2)

Conclusion

Sarcopenia was detected in over 40% of patients with IBD and a fifth had severe sarcopenia. One-fifth of them were in clinical remission. Low BMI significantly correlated with sarcopenia. Screening for sarcopenia should be considered in all patients with IBD.

1. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis.Age Ageing.2019;48:16-31

2. Sidhu S, Saggar K, Goyal O, Kishore H, Sidhu SS. Normative values of sarcopenia in the Indian population. Indian J Gastroenterol. 2018;37(suppl 1): A1–A137
P862 Dietary risk factors associated with onset of IBD: a systematic literature review and meta-analysis
Authors: Mallon K , McBride C , Doherty P G , Burns D R ,   The Health and Biomedical Research Centre (HEAL) Atlantic Technological University Sligo Ireland
Published: January 2023

Background

Several potential risk factors for Inflammatory Bowel Disease (IBD) have been highlighted, including dietary factors. Previous evidence has highlighted associations between high fibre, fruit, and vegetable intake and decreased risk of IBD. Conversely, low intake of dietary fibre, and low vitamin D levels are associated with incident IBD. One systematic review reported that high intake of total fats, PUFAs, and omega-6 fatty acids, were associated with an increased risk of Crohn’s Disease (CD) and Ulcerative Colitis (UC), whereas high fibre and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk. Despite this evidence, there remains a paucity of literature reporting on the various dietary risk factors for IBD systematically and quantitatively. Thus, the purpose of this systematic review is to determine whether dietary factors are associated with risk of developing IBD

Methods

We conducted searches in the following electronic databases: Ovid MEDLINE, Web of Science, and the Cochrane Library. Keywords and search terms related to ‘diet’ and ‘inflammatory bowel disease’ were applied. This review includes case-control, cohort studies, and RCTs investigating the association between dietary factors and onset of IBD.

Study protocol details have been published on the International prospective register of systematic reviews (PROSPERO). Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022290798Databases

Results

Our search identified 14,809 relevant articles to include, outlined in Figure 1. After title and abstract screening there were 119 articles that met the eligibility criteria. Overall, 24 articles were deemed suitable for study synthesis. When compared with those consuming the highest intake of carbohydrates, those consuming the lowest levels of carbohydrates had an overall reduced risk of IBD of 30% (RR 0.70, 95% CI 0.51-0.89) and a reduced risk of CD of 37% (RR 0.63, 95% CI 0.32-0.94). When compared with those consuming the lowest intake of vegetables, those consuming the highest levels of vegetables had an overall reduced risk of IBD of 42% (RR 0.58, 95% CI 0.53-0.63). When stratified by sub-group, those consuming the highest intake of vegetables compared with the lowest had a reduced risk of 87% of IBD (RR 0.13, 95% CI 0.04-0.22), 52% of UC (RR 0.48, 95% CI 0.24-0.71) and a reduced risk of CD of 18% (RR 0.82, 95% CI 0.76-0.88).

Conclusion

This systematic review provides a detailed summary of dietary factors associated with the onset of IBD. This evidence will inform on potential preventative strategies for IBD and will inform the academic community, patients, and policy makers about the role of dietary factors in the development of IBD.
P865 Anxiety and Depression is Associated with Poor Sleep Quality in patients with Inflammatory Bowel Disease (IBD)
Authors: Connaughton R , Kafienah Y , Ramkalawan K , Stacey W , Walker C , O'Donnell S , Ryan B , O'Connor A ,   Tallaght University Hospital Dublin Ireland
Published: January 2023

Background

Sleep disturbances affect 40-50% of patients with IBD and are associated with disease flares. Symptoms, treatment side effects and pro-inflammatory status have been shown to have an effect on sleep quality and duration. Anxiety and Depression disorders are also common with both conditions affecting approximately 20% of IBD patients. These disorders may also be associated with sleep disturbance

Aim

Our primary aim was to assess for a correlation between sleep quality and mood disorders in people with IBD. Our secondary aim was to assess the impact of these factors on quality of life.

Methods

87 patients with IBD were invited to complete an online survey. This survey included general demographic information, inflammatory bowel disease information, Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), disease activity scores (Harvey Bradshaw Index and partial MAYO score), and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). One-way ANOVA tests, Fisher’s test and unpaired t-tests were used to calculate the statistical significance.

Results

Mean age 43years. 46% male (n=40) and 54% female (n=47). Ulcerative Colitis 35.6% (n=31), Crohn’s Disease 62.1% (n=54), and indeterminate 2.3% (n=2).

The mean global PSQI score was 7.66, with 62% (n=54) of participants having a global PSQI score >5, indicating poor sleep quality.

Poor sleep quality was not associated with age or disease duration. However unsurprisingly, it was associated with increased disease activity; Remission 5.89, mild activity 7.53, and moderate activity 10.61 (p<0.001). See FIGURE 1

Participants with poor quality of sleep had significantly higher rates of anxiety (HADSA >8) with a mean HADS anxiety score of 10.78 with 79% (n=39/49) reporting anxiety, compared to those with good reported sleep with mean scores of 4.97 and 21% (n=7/33).reporting anxiety p<0.001. They also had higher rates of depression, 42%(n=21/49) versus 6%(n=2/33), p<0.001.

Conclusion

Poor sleep quality increases levels of anxiety and depression, which in turn impacts quality of life in patients with IBD. Physicians should enquire about sleep & mood when treating patients with IBD to improve sleep quality.
P879 Clinical significance of plasma interleukin-22 as a biomarker of inflammation in patients with Crohn’s disease and ulcerative colitis
Authors: Cabrera-Moksnes C , Fernandez-Llaneza D , Neisen J , Angermann B R , Gehrmann U , Olsson M , Cairns J , Powell N
Published: January 2023

Background

IL-22 is a key cytokine in the pathogenesis of inflammatory bowel disease (IBD). While evidence underpinning its central role as a biomarker of pathway activation, diagnosis, severity and activity for IBD has been accumulating, little is known about its application as a biomarker in IBD in real-world practice. Here, we characterize for the first time the relationship between IL-22 plasma concentrations and the clinical characteristics of a large, real-world population of patients with IBD.

Methods

This is a descriptive analysis of patients in the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus registry of the Crohn’s & Colitis Foundation in the United States. The SPARC registry includes patients with a diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). This study evaluated baseline data collected within ± 30 days from consent date. Assessments included demographics, clinical characteristics and IL-22 plasma concentrations. Disease severity was assessed using short CD Activity Index (sCDAI; scores <150 define remission, 150–219 mild activity, ≥220 moderate-severe activity) or 6-point UC Disease Activity Index (UCDAI; scores ≤1 define remission, 2–3 mild activity, ≥4 moderate-severe activity) disease severity categories.

Results

A total of 2667 patients with CD and 1326 patients with UC were eligible for inclusion in the study. For patients with CD, median age was 39 years, 57% were female and median disease duration was 13 years (Table 1). For patients with UC, median age was 40 years, 51% were female and median disease duration was 9 years (Table 1). In total, 1604 patients with CD and 836 patients with UC had valid IL-22 samples at baseline, of which 33% and 25%, respectively, were above the lower limit of quantification (LLOQ; 7.8 pg/mL). There was a trend toward fewer patients with IL-22 levels below the LLOQ among patients with high disease severity compared with those with lower disease severity both in patients with CD and those with UC (Figure 1). Additionally, there was an increase in the percentage of patients with IL-22 levels greater than the third quartile (overall Q3 = 10.8 pg/mL in CD, and = 7.9 pg/mL in UC) with increased disease severity (Figure 2). Comparison of subgroups of patients with low and medium/high IL-22 levels showed a consistent pattern with fewer patients in remission and more moderate-severe patients in the medium/high IL-22 group than in the low IL-22 group (Table 2).

Conclusion

Higher IL-22 levels tended to be associated with higher disease activity in this real-world population of IBD patients.
Time for Justice? Reflections on Narrative Absences and Presences in the Special Tribunal for Lebanon’s Ayyash Decision
Authors: Burgis-Kasthala Michelle
Published: January 2023

After a tumultuous inception and drawn-out in absentia trial, the Trial Chamber of the Special Tribunal for Lebanon finally handed down its key judgment in August 2020. This article offers a critical appraisal of the tribunal and the decision, first, by situating the finding within Lebanon’s political context and, second, by adopting a close narrative reading of the text itself. It argues that the judgment is structured around a series of presences and absences that build the Chamber’s narrative about post-civil war Lebanon and its need for justice. The article suggests that, while the Chamber succeeds in convicting one of the co-accused for his role in the terrorist conspiracy to assassinate Rafiq Hariri, it fails to produce a convincing narrative about the role of international criminal justice in the fractured polity of modern Lebanon.
Bromazolam Blood Concentrations in Postmortem Cases—A British Columbia Perspective
Authors: Mérette Sandrine A M , Thériault Sébastien , Piramide Lei E C , Davis Michael D , Shapiro Aaron M
Published: January 2023

Bromazolam is a designer benzodiazepine that was first detected in British Columbia in January 2021. Postmortem cases were analyzed using a comprehensive blood drug screening procedure by liquid chromatography–high-resolution mass spectrometry before being retrospectively analyzed using an in-house novel psychoactive substances data processing method. Bromazolam was detected in 41 postmortem cases in 2021 and quantitatively confirmed by standard addition, using liquid chromatography–tandem mass spectrometry. The mean bromazolam concentration observed was 11.4 ± 53.7 ng/mL (median concentration: 1.6 ng/mL), with a range from 0.5 to 319.3 ng/mL and the majority of cases co-occurring with fentanyl. These low concentrations may be indicative of a presumed enhancement of opioid effects, rather than being used as a stand-alone drug. Bromazolam was always detected with opioids (fentanyl and carfentanil), stimulants (methamphetamine) and/or other benzodiazepines (etizolam and flualprazolam). To our knowledge, this is the first report to provide concentrations of bromazolam in postmortem blood samples in Canada.
China National Intellectual Property Administration clarifies administrative adjudication measures for significant patent infringement disputes in pharmaceutical cases
Authors: Yu Qiang
Published: January 2023

The China National Intellectual Property Administration decided that the plaintiff’s administrative adjudication request met the conditions for acceptance according to the Measures for Administrative Adjudication of Significant Patent Infringement Disputes (2021), even if there was an ongoing judicial suit in the People’s Court concerning related patents. Although the defendant had filed an application for invalidation of the plaintiff’s patent, the defendants’ plea to suspend the ongoing patent infringement adjudication was dismissed based on considerations related to fairness and efficiency.
A specific technique of immunolabelling of urinary small extracellular vesicle biomarkers for the diagnostic of renal cancer
Authors: Mallouk Nora , Tan Sisareuth , Scepaniack Claire , Garcin Arnauld , Pradat Camille , Lambert Claude , Li Guorong
Published: January 2023

Small extracellular vesicles (EVs) are characterized by the membrane expression of CD63, CD81 and CD9 tetraspanins. Their size is inferior to 200 nm. They share the same characteristics as the native cells and are found in human fluids. Specific membrane protein biomarkers expressed on small EV are useful for the diagnosis of tumoural pathologies. Clear cell renal cell carcinoma (CCRCC) is diagnosed by imaging examinations and/or tissue biopsy. Carbonic anhydrase IX (CAIX) is a powerful biomarker of CCRCC. The detection of CAIX on small EV from the urine of patients could constitute a liquid biopsy for CCRCC. We have set up a specific protocol for the preparation, the immunostaining characterization and the transmission electron microscopy observation of small EVs isolated from the urine of CCRCC patients. The background labelling was significantly reduced. We successfully detected biomarkers on urinary small EVs from CCRCC patients. This technique could be extended with antibodies directed against other EV biomarkers for the detection and the monitoring of cancer diseases.
Anti-TIF1γ antibody-positive dermatomyositis associated with nivolumab administration in a patient with advanced oesophageal squamous cell carcinoma: A case report and literature review
Authors: Sakurai Takuya , Takahashi Junichiro , Komatsu Teppei , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: January 2023

We report a case of anti-transcriptional intermediary factor 1γ antibody-positive dermatomyositis following nivolumab treatment. The patient was successfully treated with pulse steroid therapy and high-dose intravenous immunoglobulin, followed by oral glucocorticoid treatment. Immune checkpoint inhibitors, such as nivolumab, may induce not only myositis as an immune-related adverse event but also dermatomyositides as a paraneoplastic syndrome by distracting immune tolerance. Differentiating between pathologies is warranted if patients develop myositis after immune checkpoint inhibitor administration.
Automatic detection and segmentation of postoperative cerebellar damage based on normalization
Authors: Zhang Silu , McAfee Samuel S , Patay Zoltan , Pinto Soniya , Scoggins Matthew A
Published: January 2023

Background

Surgical resection is the gold standard in the treatment of pediatric posterior fossa tumors. However, surgical damage is often unavoidable and its association with postoperative complications is not well understood. A reliable localization and measure of cerebellar damage is fundamental to study the relationship between the damaged cerebellar regions and postoperative neurological outcomes. Existing cerebellum normalization methods are likely to fail on postoperative scans, therefore current approaches to measure postoperative damage rely on manual labelling. In this work, we develop a robust algorithm to automatically detect and measure cerebellum damage in postoperative 3D T1 magnetic resonance imaging (MRI).

Methods

In our approach, normal brain tissues are first segmented using a Bayesian algorithm customized for postoperative scans. Next, the cerebellum is isolated by nonlinear registration of a whole-brain template to the native space. The isolated cerebellum is then normalized into the spatially unbiased atlas (SUIT) space using anatomical information derived from the previous step. Finally, the damage is detected in the atlas space by comparing the normalized cerebellum and the SUIT template.

Results

We evaluated our damage detection tool on postoperative scans of 153 patients with medulloblastoma based on inspection by human experts. We also designed a simulation to evaluate performance without human intervention and with an explicitly controlled and defined ground truth. Our results show that the approach performs adequately under various realistic conditions.

Conclusions

We develop an accurate, robust, and fully automatic localization and measurement of cerebellar damage in the atlas space using postoperative MRI.
CDKN2A/B co-deletion is associated with increased risk of local and distant intracranial recurrence after surgical resection of brain metastases
Authors: Morshed Ramin A , Nguyen Minh P , Cummins Daniel D , Saggi Satvir , Young Jacob S , Haddad Alexander F , Goldschmidt Ezequiel , Chang Edward F , McDermott Michael W , Berger Mitchel S , Theodosopoulos Philip V , Hervey-Jumper Shawn L , Daras Mariza , Aghi Manish K
Published: January 2023

Background

While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types.

Methods

A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence.

Results

A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status.

Conclusions

CDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.
Ending civil wars through fraudulent elections
Authors: Lehmann Michael Christian
Published: January 2023

Previous research finds a positive association between electoral fraud and post-election protests, violence, and civil conflict. This article contends that the effect of electoral fraud on peace can be heterogeneous. I investigate elections after civil wars that stalemated. My contribution is to present a theory and suggestive evidence that, in this context, electoral fraud by unpopular incumbents can be peace-promoting. An important policy implication is that international efforts to prevent electoral fraud (e.g. electoral observers), in this specific setting, may increase the odds that a civil war continues.
Brain Metastases from Biliary Tract Cancer: Case Series and Clinicogenomic Analysis
Authors: Dodoo Grace N , De Brian , Lee Sunyoung S , Abi Jaoude Joseph , Vauthey Jean-Nicolas , Tzeng Ching-Wei D , Tran Cao Hop S , Katlowitz Kalman A , Mandel Jacob J , Beckham Thomas H , Minsky Bruce D , Smith Grace L , Holliday Emma B , Koong Albert C , Das Prajnan , Taniguchi Cullen M , Javle Milind , Koay Eugene J , Ludmir Ethan B
Published: January 2023

Background

Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes.

Materials and Methods

A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected.

Results

Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 [range, 1.1-66.0] months. Median overall survival (OS) from primary diagnosis was 31.5 [2.9-99.8] months and median OS from BrM diagnosis was 4.2 [0.2-33.8] months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P = .060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P = .131).

Conclusion

This is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted.
Angular momentum inheritance from the Schwinger effect in (chromo)electromagnetic fields
Authors: Copinger Patrick , Hidaka Yoshimasa
Published: January 2023

The angular momentum of fermion pairs generated by the Schwinger effect is studied in homogeneous (chromo)electromagnetic fields, mimicking the early stages of a heavy-ion collision. It is demonstrated that the angular momentum density of produced pairs is proportional to that of the background fields. This is argued both heuristically in a virtual breaking condensate model by evaluating Wong’s equations, and out-of-equilibrium to one-loop using the in–in formalism.
FAM122A Is Required for Mesendodermal and Cardiac Differentiation of Embryonic Stem Cells
Authors: Yang Yun-Sheng , Liu Man-Hua , Yan Zhao-Wen , Chen Guo-Qiang , Huang Ying
Published: January 2023

Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved housekeeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multifaceted physiological and pathological processes. However, the in vivo function of FAM122A is largely unknown. In this study, we observed that Fam122 deletion resulted in embryonic lethality with severe defects of cardiovascular developments and significantly attenuated cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impaired mesendodermal specification and cardiac differentiation from mouse embryonic stem cells but showed no influence on pluripotent identity. Mechanical investigation revealed that the impaired differentiation potential was caused by the dysregulation of histone modification and Wnt and Hippo signaling pathways through modulation of PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This research not only significantly extends our understanding of the regulatory network of mesendodermal/cardiac differentiation but also proposes the potential significance of FAM122A in cardiac regeneration.