bluuebunny/crossref_metadata_2025_split huggingface dataset:
P642 Crossroads of vitamin B6 deficiency and inflammation in inflammatory bowel disease: Preliminary results of a cross-sectional study
Authors: Farrag K , Woldeab J , Stein J M , Aksan A 
Published: January 2022

Abstract

Background
The robust relationship between vitamin B6 and inflammation has become apparent over the last decade. However, the mechanistic nature of this relationship remains unclear. Evidence suggests an inverse relationship between blood levels of B6 and inflammation, but also a potential two-way relationship between the two. Thus, whereas inflammation can deplete serum vitamin B6, vitamin B6 insufficiency can attenuate inflammation. This study aimed to assess vitamin B status in patients with IBD in routine clinical practice and identify possible relationships between vitamin B6 status and clinical disease characteristics.

Methods
In a comparative, retrospective cross-sectional study, serum samples of patients with IBD were studied. CBC, albumin and hsCRP were determined and samples assessed for presence/absence of inflammation (serum hsCRP, cut-off &lt;5mg/L). Vitamin B6 status was determined via direct measurement of pyridoxal 5′-phosphate (PLP) by enzymatic assay.

Results
149 patients with IBD (64f/85m; 82CD/67UC; 39.9±14.6y) were included. Of these, 44/149 had inflammation (19f/25m; 22CD/22UC; 41.2±14.9y) and 105/149 no inflammation (45f/60m; 60CD/45UC; 39.3±14.4y). In patients with inflammation, mean serum PLP levels were significantly lower (7.2[1.9–46.0] µg/L) vs. patients without inflammation (9.8[0.1–88.0] µg/L) (p&lt;0.05). Accordingly, vitamin B6 deficiency occurred significantly more frequently in patients with vs. without inflammation (34.1% vs. 19.0%, p&lt;0.05). A higher incidence of vitamin B6 deficiency was seen in patients with CD vs. UC, though without statistical significance (26.8% vs. 19.4%, p&gt;0.05). The frequency of vitamin B6 deficiency did not differ according to disease localisation (p&gt;0.05). Serum PLP levels inversely correlated with the inflammatory markers hsCRP and ESR (r=-0.306, p&lt;0.001 and r=-0.203, p&lt;0.001, respectively). Furthermore, there was a significant positive correlation between blood PLP levels and other selected acute-phase reactants, e.g., TSAT% (r= 0.207, p&lt;0.05). However, no significant correlation was found with ferritin (r=-0.152, p=0.064).

Conclusion
Low serum total vitamin B6 levels were associated with inflammation but not disease type or localisation in patients with IBD. In line with preclinical findings and previous observational studies, vitamin B6 deficiency was more pronounced in patients with inflammation. Our findings suggest vitamin B6 may have a bigger role than thought in IBD; besides its relationship with inflammation, a possible involvement of vitamin B6 deficiency as cause or effect in IBD pathogenesis warrants investigation. Routine assessment and correction of vitamin B6 status may ameliorate IBD and help maintain intestinal integrity.
P657 Persistence in smoking cessation in inflammatory bowel disease (IBD)
Authors: González Muñoza C , Gely C , Teller M , Mombiela A , Roig C , Lopez-Faba A , Bertoletti F , Gordillo J , Garcia-Planella E 
Published: January 2022

Abstract

Background
Smoking Habit (SH) is a relevant epidemiological factor in IBD, so it is recommended to quit. We have no data on the persistence of its long-term abandonment.

Methods
All patients of our hospital registred in the ENEIDA registry (spanish national IBD registry) with active SH at time of diagnosis were identified. Ex-smokers (&gt; 6 months of abstinence) were invited to participate by telephone contact and epidemiological and SH data were recorded using medical records and telephone survey. The Fargeström Test for Nicotine Dependence (FTND) was used to grade the degree of addiction.

Results
122 ex-smokers [88 Crohn Disease (CD), 33 Ulcerative Colitis (UC)] were included, the mean age of SH abandonment (SHA) was 41 years (33–48), lower in CD (38 years) compared to UC (46) (p-value 0.002). The mean time from diagnosis to SHA was 72 months in CD and 98 in UC. Patients had a 2-point degree of FTND addiction, higher in CD (p-value 0.063), with 80% of them working. In CD, the main motivation was medical indication as a specific treatment (28%) and for general health advice (23%); in UC were general health advice (45%) followed by associated comorbidities (15%). 90% of the cohort managed to quit smoking on their own and only 11% needed pharmacological help. 60% explained a relapse, on average at 12 months (3–36), with a higher rate in CD (46%) compared with UC (24%) (p-value 0.029) despite a longer mean follow-up of patients with UC (114 VS 168, p-value 0.035). 39% of them referred to be living with a smoker at the time of relapse. The only factor of those assessed that directly impacted the risk of relapse was a higher score on the FTND (p-value 0.027).

Conclusion
- The overall risk of relapse is 60%, half of which during the first year. Patients with CD have a higher risk, possibly due to a higher degree of addiction.
- The only factor associated with relapse in (SH) was a higher FTND score.
- SHA is delayed in relation to the diagnosis of IBD.
P662 Colorectal Cancer in Patients with Ulcerative Colitis: A National Cohort Study between 1991–2020
Authors: Heuthorst L , Harbech H , Snijder A , Mookhoek A , D’Haens G , Vermeire S , D’Hoore A , Bemelman W , Buskens C 
Published: January 2022

Abstract

Background
Studies on the colorectal cancer (CRC) risk in patients with ulcerative colitis (UC) show conflicting results. The aim of the current study was to assess if there is an indication shift for surgery in patients with UC from refractory disease to malignant degeneration over the last 3 decades.

Methods
From the nationwide Dutch Pathology Registry (PALGA), pathology excerpts from all patients with histologically confirmed UC who underwent a colorectal resection for all indications between January 1st, 1991 and November 12th, 2020 were included. The primary outcome was the CRC rate in the colon specimens. Outcomes were compared between 3 time periods (P1: 1991–2000, P2: 2001–2010, P3: 2011–2020).

Results
Overall, 6,094 UC patients were included of which 5,026 underwent a (procto)colectomy and 1,068 a segmental resection. In 1,031 (16.9%) patients, pathological examination demonstrated CRC after a median disease duration of 11 years [IQR 3.0–19.0]. The CRC rate in the colectomy specimen increased from 11.3% in P1, to 16.1% in P2, to 22.8% in P3 (p-trend &lt;0.001). Compared to patients in P1, patients in P2 and P3 had a longer disease duration before resection (4 years [IQR 0.0–9.0] vs. 10 years [IQR 3.0–16.0] vs. 17 years [IQR 7.0–23.0], p&lt;0.001). The proportion of patients diagnosed with advanced disease (pT3/T4) (P1: 61.2% vs. P2: 65.2% vs. P3: 62.4%, respectively, p=0.633) and lymph node metastasis (P1: 33.0% vs. P2: 41.9% vs. P3: 38.2%, respectively, p=0.113) did not decrease over time.

Conclusion
This nationwide pathology study demonstrated an increased surgical indication rate for CRC in UC patients over the last 3 decades. We hypothesize that the expanding therapeutic armamentarium for UC likely leads to exhausting medical options and hence postponed colectomy. This however, might be at the expense of increased risk of CRC in the long term. Despite the introduction of surveillance programs, the incidence of advanced colon carcinoma remains high.
P671 Occurrence and clinical impact of eosinophilic esophagitis in a large cohort of children with Inflammatory Bowel Disease
Authors: Aloi M , Rossetti D , Bucherini S , Felici E , Romano C , Martinelli M , Di Pasquale V , Lionetti P , Oliva S 
Published: January 2022

Abstract

Background
Scarce data have investigated the association between pediatric Inflammatory bowel disease (IBD) and Eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and a possible peculiar phenotype and natural history of such association.

Methods
Case-control study based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a concomitant diagnosis of IBD and EoE were included. Overall prevalence and incidence in 2 periods, 2009–2015 and 2016–2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups.

Results
Eleven patient (age 11,27 ± 2,83, Male 91%) with EoE-IBD out of 3090 patients with IBD only were identified, resulting in a prevalence of 0,35% and an incidence of 0,18% for the period 2009–2015 and 0,45% for the period 2016–2021. Treatment escalation rates were significantly higher in patients with IBD compared to EoE-IBD at 12 and 24-month follow-up (0 vs 30%, p = 0.04 and 9% Vs 45,5%, p = 0.03, respectively). Patients with IBD only were at a significantly higher risk of hospitalization than both EoE-IBD and EoE only patients (Log Rank p &lt; 0.001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared to EoE patients.

Conclusion
Overall, the incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in the six years. Having an EoE appears to be associated with a milder IBD disease course while having an IBD doesn’t seem to affect the natural history of EoE. More data are needed to better define the phenotype of such condition.
P684 Increased risk of cardiovascular disease and high risk profiles compatible with metabolic syndrome in patients with Inflammatory Bowel Disease: a cross-sectional analysis of matched cohorts
Authors: Sleutjes J , Roeters van Lennep J E , Kavousi M , Aribas E , van der Woude C J , de Vries A C 
Published: January 2022

Abstract

Background
Patients with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease (CVD). This probably results from a cumulative effect of chronic inflammation and traditional CVD risk factors. We assessed the CVD risk profile of IBD patients as compared to the general population.

Methods
In this cross-sectional study, consecutive IBD patients aged ≥45 years were included at the Gastroenterology and Hepatology outpatient clinic. CVD risk profiles wese assessed by anthropometrics (blood pressure, length, weight, waist and hip circumference), serum analyses (nonfasting glucose and lipid spectrum) and self-administered questionnaires (history of CVD events, traditional CVD risk factors, medication use). One to four controls from the Rotterdam Study were matched to each IBD case by sex and age (scope +-5 years). Stratification was applied to asses differences between sex, IBD diagnosis and clinical disease activity (HBI or SCCAI&gt;5).

Results
235 IBD patients were included (44% male; median age 59 years (IQR 51–66)) and matched to 829 controls (44% male; median age 62 years (IQR 57–68)). IBD patients were more frequently diagnosed with CVD (OR 2.01, 95%CI 1.23–3.27). IBD patients showed lower odds of overweight defined as BMI ≥25 kg/m2 (OR 0.48, 95%CI 0.35–0.66) and hypercholesterolemia defined as total cholesterol ≥6.2 mmol/L, self-reported diagnosis or use of lipid lowering drugs (OR 0.45, 95%CI 0.31–0.65). The following markers of metabolic syndrome were increased in IBD patients: hypertension defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, self-reported diagnosis or use of antihypertensive drugs (OR 1.67, 95%CI 1.19–2.32), waist circumference (92 cm (SE±10) vs 88 cm (SE±8), p=.006) and triglyceride level (2.7 mmol/L (SE±0.8) vs 2.1 (SE±0.8), p&lt;.001). (Table 1) Male patients had higher waist circumference, less favorable lipid profiles and were more frequently diagnosed with hypertension (OR 1.72, 95%CI 0.99–2.94) as compared to female patients. Patients with ulcerative colitis were more frequently smokers (OR 4.34, 95%CI 1.27–16.66) and showed higher odds of hypercholesterolemia (OR 1.85, 95%CI 1.06–3.33) as compared to patients with Crohn’s disease.

Conclusion
Patients with IBD are more frequently diagnosed with CVD as compared to age-sex matched controls. The CVD risk profile in IBD patients is characterized by components of the metabolic syndrome, i.e. hypertension, truncal obesity and hypertriglyceridemia, particularly among male IBD patients. The prevalence of other traditional CVD risk factors was comparable or even lower in IBD patients as compared to controls. The exploration of targeted preventive management strategies is required.
P685 Strong Response to SARS-CoV-2 Vaccine Additional Doses among Patients with Inflammatory Bowel Diseases
Authors: Kappelman M , Weaver K , Zhang X , Chun K , Long M 
Published: January 2022

Abstract

Background
Current recommendations in many countries support additional COVID-19 vaccine doses in patients with inflammatory bowel disease (IBD) who are treated with immunosuppressants, yet real-world data on the effectiveness and safety of additional vaccine doses is lacking. We sought to quantify the humoral immune response to an additional vaccine dose in patients with IBD.

Methods
We performed a direct-to-patient, internet-based cohort study of patients with IBD in the United States who have received any SARS-CoV-2 vaccine granted EUA. Participants completed baseline and follow-up surveys and had blood work obtained approximately 8 weeks following completion of the initial vaccination series and 6 weeks following administration of an additional vaccine dose. We performed quantitative measurement of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 using the LabCorp Cov2Quant IgG™ assay.

Results
A total of 659 participants were included [415 participants (63%) initially received BNT162b2, 243 participants (37%) initially received mRNA-1273, and 5 participants (1%) initially received Ad26.COV2.S]. Demographic, clinical, and treatment characteristics of the study population are provided in Table 1. Over 98% of those receiving an initial mRNA vaccine received the same type additional dose. Whereas 93% had detectable antibody after the initial vaccination series, 99.5% had detectable antibodies following an additional dose. Mean (SD) increase in antibody level was 61 ug/mL (103) in those receiving BNT162b2 and 78 ug/mL (143) for those receiving mRNA-1273 (Figure 1). Importantly, of 47 of patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose. Additional vaccination was generally well tolerated in this population, with 44%, 24%, 25%, and 6% reporting no, mild, moderate, and severe side effects respectively.

Conclusion
These findings demonstrate robust immunogenicity to additional doses of SARS-CoV-2 vaccine, even amongst patients with undetectable antibody following the initial series. Adverse event rates were low. These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression.
P691 Influence of ethnicity on the phenotype and clinical outcomes in Inflammatory Bowel Disease; comparison of a South American with a North American population
Authors: Pérez T , Pizarro B , Ascui G , Tobar F , Cerda-Villablanca M , Alvares D , Orellana M , De la Vega A , Canistra M , Cornejo B , Baez P , Silva V , Arriagada E , Estela R , Hernandez-Rocha C , Alvarez-Lobos M , Rivera-Nieves J 
Published: January 2022

Abstract

Background
Inflammatory Bowel Diseases (IBD) are chronic systemic inflammatory disorders, which affect the gastrointestinal tract. An increased incidence of IBD has been vastly reported in Europe, and North America, however, IBD has now emerged as a global disease affecting people of different genetic backgrounds and geographic locations, with increasing incidence in developing and newly industrialized regions such as South America, offering the opportunity to explore differences and similarities in disease presentation and outcomes across these variables.

Methods
Our study includes 265 patients with a diagnosis of Ulcerative Colitis (UC) (n=173) or Crohn′s Disease (CD) (n=92). We carried out an exploratory analysis of databases of Chilean and North American IBD patients to compare the clinical phenotype between both cohorts. We used an unsupervised machine learning approach using Principal Component Analysis (PCA), t- Stochastic Neighbor Embedding (t-SNE), among others, for each disease (CD and UC). Finally, we predicted the center (North American versus Chilean) using random forest, among other supervised machine learning methods to confirm these results.

Results
Several unsupervised machine learning methods separated two main groups supporting differences between North American and Chilean patients in each disease. The variables that explained the loadings of the clinical metadata on the principal components were related to therapies and disease extension/location at diagnose. Our Random Forest (RF) models were trained for cohort classification (Chilean or North American) based on clinical characteristics, obtaining a high accuracy of 0.86 (UC) and 0.89 (CD). Similarly, variables related to therapies and disease extension/location had a higher Gini index. In the same line, univariate analysis showed a later CD age at diagnoses in Chilean IBD patients (37 vs 24; p=0.005)

Conclusion
Our study suggests a clinical difference between North American and Chilean IBD patients; later CD age at diagnoses with a predominate less aggressive phenotype (39% vs. 54% B1), a more localized disease despite less biological therapies used in Chile for both diseases. The next research steps to confirm these results with more patients and explore more factors between different populations that could determine a less aggressive phenotype. Understanding the causes of these differences could unravel new pathways or protective factors, which could improve treatments.
P692 Clinical, therapeutic and evolutionary profile of fistulizing ano-perineal lesions in Crohn’s disease
Authors: Hassine H , Kahlaoui F , Mtir M , Cherif D , Tlili R , Kchir H , Maamouri N 
Published: January 2022

Abstract

Background
Ano-perineal lesions (APLs) during Crohn’s disease (CD) are frequent and varied. Ano-perineal fistulas (APF) are the most common and severe manifestations. They are associated with increased morbidity and considerable impairment of quality of life. Their management is not always easy despite therapeutic advances, particularly anti-TNFα.The aim of our work was to describe the epidemiological profile, the therapeutic modalities and the evolutionary aspects of APF during CD.

Methods
This was a retrospective, descriptive, single-center study collecting records of patients followed for CD with APF between January 2010 and December 2020. The patients had a proctological examination and a perineal MRI. We recorded clinical, endoscopic, radiological data, therapeutic management and clinical response to the initial therapeutic regimen. Complete remission was defined as closure of all initially productive fistulas, partial response was defined as closure of more than 50% of fistulas. Therapeutic failure was defined as closure of less than 50% of the initially productive fistulas.

Results
83 patients followed up for CD with APLs were collated of which 38 had APF (45.7%). The mean age was 42 years [26 - 73] with a sex ratio of 0.4. Active smoking was noted in six patients (15.8%). In 55.3% of cases, PAF was present at the time of diagnosis of CD (n=21).17 patients had developed one or more PAFs during the course of their disease with a mean delay of seven years [1 - 29]. APFs were associated with luminal involvement in 94.7% of cases, with ileal location in 10 patients (26.3%), colonic location in 13 patients (34.2%) and ileocolic location in 13 patients. The APFs were perianal in 34cases, vulvovaginal in five cases and gluteal in one case. There were complex fistulas in 92.1% of cases. The number of external orifices at the time of diagnosis was respectively: 1 orifice in 63.2% of cases, 2orifices in 26.3% of cases and more than two orifices in 10.5% of cases. A perineal abscess was associated in 44.7% of cases and anorectal stricture was observed in 7.9% of patients. Seton drainage was performed in 86.6% of patients. All patients with complex APF had received anti-TNFα after disappearance of collections if initially present (infliximab (92.1%), adalimumab (7.9%)) combined with thiopurines in 97.4% of cases. After a mean follow-up of 40 months, a complete remission was observed in 14 patients (36.8%), a partial response was noted in 13 patients (34.2%). 11 patients (28.9%) were in therapeutic failure.

Conclusion
In our study, APFs during CD account for almost half of all APLs.Thus, the development of local therapeutic means proves to be of necessity in order to increase the efficacy of biotherapies and to accelerate the healing of APFs.
P696 Genetic predisposition to infliximab immunogenicity in patients with immune-mediated inflammatory diseases – secondary analyses from a randomised clinical trial
Authors: Bjørlykke K , Brun M K , Viken M K , Stenvik G E , Klaasen R A , Gehin J E , Warren D J , Sexton J , Haavardsholm E A , Jahnsen J , Lie B A , Goll G L , Bolstad N , Syversen S W , Jørgensen K K 
Published: January 2022

Abstract

Background
Immunogenicity is a leading cause of treatment failure to TNF inhibitors. Genetic variations in HLA class II genes have been suggested to predispose to anti-drug antibody formation, but studies using high-resolution HLA typing as well as characterisation of biologically relevant haplotypes are currently lacking. The aim of this study was to assess associations between HLA loci and immunogenicity to infliximab.

Methods
Patients with immune-mediated inflammatory diseases (IMID) treated with infliximab (N=612) (120 rheumatoid arthritis, 181 spondyloarthritis, 72 psoriatic arthritis, 114 ulcerative colitis, 80 Crohn disease, and 45 psoriasis) were included in the randomised, Norwegian Drug Monitoring (NOR-DRUM) trial. Neutralising anti-drug antibodies were detected with an automated fluorescence assay. Next generation HLA sequencing at G group resolution were performed and trimmed to 2nd field. Haplotype analyses including the most significant HLA loci were performed, and epitope predictions for the infliximab light- and heavy-chain were assessed.

Results
Anti-drug antibodies to infliximab were detected in 147 (24 %) of patients. The most significant associations with immunogenicity were with the genes HLA-DQB1 (P=1.4x10-6), -DRB1 (P= 2.7x10-5), -DQA1 (P=0.00017) and -B (P=0.0009). Conditional analyses indicated that HLA-DQB1 represents the primary association(Table 1). Haplotype analyses showed that there was significantly increased risk of immnogenicity in patients carrying the HLA-DQ2 haplotypes DQB1*02:01~DQA1*05:01 (P=1.1x10-6) and DQB1*02:02~DQA1*02:01 (P=0.008), while one protective haplotype DQB1*05:01~DQA1*01:01 (P=0.0005) was identified (Figure 1a-c). Presence of HLA-DQ2 more than doubled the risk of anti-drug antibody formation (HR 2.54, 95%CI 1.82–3.56) (Figure 1d), in a model including the covariates age, sex, diagnosis, and concomitant immunosuppressive therapy. Association tests of each level of HLA analyses showed that HLA-DQ2 represents the strongest association(Figure 2). Epitope predictions revealed that the HLA-DQ2 haplotypes DQB1*02:01-DQA1*05:01 and DQB1*02:02-DQA1*02:01 share nine strong binder peptides, originating from the infliximab light chain, encompassing the amino acid core-peptide sequences INTVESEDI and VYACEVTHQ.

Conclusion
Using high-resolution HLA sequencing, we here demonstrate a genetic association between HLA-DQ2 and infliximab immunogenicity in IMID patients. The presence of either HLA-DQ2 risk haplotypes more than doubled the risk of anti-drug antibody formation across all diagnoses. Testing for HLA-DQ2 could be of clinical value in identifying patients at risk for immunogenicity and facilitate treatment decisions. Whether these findings apply to other TNF inhibitors should be further explored.