Interleukins are considered to be potential therapeutic targets that can alter the prognosis and disease progression of IBD. IL-21 has proven to be involved in effector Th1, Th2 and Th17 responses. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of the colonic Tregs in animal models of colitis and patients with IBD. In this retrospective study, we have studied the expression of these interleukins, using immunohistochemistry, in 121 patients with moderate to severe IBD before and after treatment with biologics. The results were statistically processed using SPSSTM. Increased IL-21 expression was found in the UC and CD groups versus the controls. The IL-33 expression was found to be increased in the post-treatment UC and CD groups, suggesting a protective role of this interleukin against bowel inflammation. The IL-33 expression post-treatment was reversely correlated with the activity index score in CD patients, suggesting a better response to treatment in patients with higher IL-33 mucosa levels. This is the first immunohistochemical study of the expression of those interleukins in bowel mucosa before and after treatment with biologics. These data support a possibly promising future use of these interleukins as biomarkers of severe disease and response to treatment and as potential therapeutic targets for novel monoclonal antibodies.

Survey studies have found an increased prevalence of migraine in patients with inflammatory bowel disease (IBD). However, the clinical characteristics of migraines in this population are unknown. We conducted a retrospective medical record review study to characterize migraines in the IBD population.
Six hundred seventy-five migraine patients (280 with IBD, 395 without IBD) who were evaluated at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida between July 2009 and March 2021 were included. Patients with ICD codes for migraine and either Crohn\'s disease (CD) or ulcerative colitis (UC) were selected. Electronic health care records were reviewed. Patients confirmed to have IBD and migraine were included. Demographic, IBD, and migraine characteristics were collected. Statistical analysis was completed using SAS.
Patients with IBD were less often male (8.6% vs 21.3%, P < .001) and had a higher Charlson Comorbidity Index (>2: 24.6% vs 15.7%, P = .003); 54.6% had CD and 39.3% had UC. Patients with IBD had migraine with aura and without aura more frequently ( OR 2.20, P < .001 and OR 2.79, P < .001, respectively) than non-IBD patients. Additionally, those with IBD less commonly had chronic migraine (OR 0.23, P < .001) and less commonly had chronic migraine or treatment for migraine (ORs 0.23-0.55, P ≤ .002).
Migraine with and without aura have increased prevalence in IBD patients. Further study of this topic will be helpful to clarify the prevalence of migraine, establish this population\'s response to treatment, and better understand the reason(s) for a low rate of treatment.

Although colorectal cancer (CRC) surveillance is embedded in clinical inflammatory bowel disease (IBD) practice, a subset of patients still develops advanced neoplasia (AN) (high-grade dysplasia [HGD] and/or CRC). We aimed to assess the impact of surveillance quality on AN risk in IBD.
In this multicenter case-control study, we searched the Dutch nationwide pathology databank to identify IBD cases with AN and controls with indefinite or low-grade dysplasia. The surveillance colonoscopy preceding the index lesion (first indefinite for dysplasia [IND]/low-grade dysplasia [LGD] or AN) was used to assess the impact of surveillance quality. We assessed intervals, bowel preparation, cecal intubation, and absence of inflammation as primary quality indicators. In addition, we assessed chromoendoscopy, endoscopist expertise, hospital setting, and biopsy strategy. Associations of quality indicators with AN risk were determined with multivariable logistic regression analyses with Firth\'s correction.
We included 137 cases and 138 controls. Delayed intervals (58.2% vs 39.6%) and active inflammation (65.3% vs 41.8%) were frequently present in cases and controls and were associated with AN (delayed interval: adjusted odds ratio [aOR], 2.00; 95% confidence interval [CI], 1.07-3.81; P = .03; active inflammation: aOR, 2.46; 95% CI, 1.33-4.61; P < .01). Surveillance compliant with primary quality indicators was associated with a reduced AN risk (aOR, 0.43; 95% CI, 0.22-0.91; P = .03), similar to chromoendoscopy (OR, 0.11; 95% CI, 0.01-0.89; P = .01). Other indicators were not significantly associated with AN.
Surveillance compliant with primary quality indicators is associated with a reduced colitis-associated AN risk. Delayed surveillance intervals and active inflammation were associated with an increased AN risk. This underlines the importance of procedural quality, including endoscopic remission to optimize the effectiveness of endoscopic surveillance.

In the inflammatory bowel disease literature, emergency surgery for Crohn\'s disease (CD) is associated with worse postoperative outcomes as compared to elective surgery. Previous studies have compared heterogeneous groups only. We hypothesized that this association would be lost after matched analysis. We aimed to compare matched CD patients undergoing elective vs emergency surgery.
The National Surgical Quality Improvement database (01/2005-12/2019) was utilized to identify adult CD surgical patients. Univariate and conditional logistic regression models were used to analyze unmatched and matched cohorts. Propensity-score matching was performed to match emergency to non-emergency patients 1:1. Our primary outcome was a composite of any complication. Our secondary endpoints were hospital readmission, unplanned reoperation and 30-day morbidity and mortality.
In the unmatched analyses (n = 12,181/95.28% elective and n = 603/4.72% emergency) of Crohn\'s patients undergoing colectomy, 20% of elective and 42% of emergency patients experienced a complication (p < 0.001). Over 20 outcomes measured including length of stay (LOS), readmission, infections and respiratory, cardiovascular and renal complications, were worse in the emergency cohort. In the matched analyses (n = 400 emergency/400 elective patients) only the categories of any complication (OR 1.44, 1.06-1.96 95% CI, p = 0.02), any surgical site infection (SSI, OR 1.53, 1.07-2.19 95% CI, p = 0.02), superficial SSI (OR 2.25, 1.14-4.44 95% CI, p = 0.02), organ space SSI (1.58 OR 1.04-2.4 95% CI, p = 0.03), unplanned intubation (OR 5.0, 1.45-17.27 95% CI, p = 0.01), ventilation > 48 h (OR 9.0, 1.4-38.79 95% CI, p = 0.003) and septic shock (OR 4.5, 1.86-10.9 95% CI, p < 0.001) were higher in the emergency cohort.
Matching CD patients resulted in a loss of the observed increase in cardiovascular and renal complications, reoperation and LOS following emergency surgery; however, SSIs and respiratory complications remained increased despite matching.

UNASSIGNED: Inflammatory bowel disease (IBD) negatively affects fertility and fecundity. We aimed to determine longitudinal trends in and factors that affect pregnancy rates in women with ulcerative colitis (UC) and Crohn\'s disease (CD).
UNASSIGNED: Women in the University of Manitoba IBD Epidemiology Database aged 15 to 45 were identified between 1992 and 2018 and matched up to 10 non-IBD controls. Pregnancy and live birth rates were compared between women with and without UC or CD stratified by time-period, disease duration and maternal age at conception. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were calculated. Poisson regression was used to adjust these rates for year of pregnancy, disease duration, maternal age, severity of IBD, and prior IBD-related surgery.
UNASSIGNED: Compared to controls, women with UC had lower rates of pregnancies (IRR 0.91, 95% CI: 0.82-0.99) and women with CD had lower rates of pregnancies (IRR 0.85, 95% CI: 0.79-0.93) and live births (IRR 0.83, 95% CI: 0.75-0.92). Although rates of pregnancies and live births were significantly lower in women with UC and CD compared to controls prior to 2010, there appeared to be no differences between the two groups after 2010. Prior intestinal surgery and active disease at conception appeared to lower pregnancy rates in women with UC and CD, respectively.
UNASSIGNED: This study demonstrates that women with IBD have lower pregnancy rates compared to those without IBD, though these differences are no longer evident after 2010. Factors that continue to reduce these rates include prior colectomy and underlying disease activity.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral disease characterized by progressive neurodegeneration with variable involvement of multisystemic abnormalities. Crohn\'s disease (CD) is an inflammatory bowel disease (IBD) with a multifactorial etiology influenced by variants in NOD2. Here, we investigated a patient with plausible multisystemic overlapping manifestations of both NPC and CD. Her initial hospitalization was due to a prolonged fever and non-bloody diarrhea. A few months later, she presented with recurrent skin tags and anal fissures. Later, her neurological and pulmonary systems progressively deteriorated, leading to her death at the age of three and a half years. Differential diagnosis of her disease encompassed a battery of clinical testing and genetic investigations. The patient\'s clinical diagnosis was inconclusive. Specifically, the histopathological findings were directed towards an IBD disease. Nevertheless, the diagnosis of IBD was not consistent with the patient\'s subsequent neurological and pulmonary deterioration. Consequently, we utilized a genetic analysis approach to guide the diagnosis of this vague condition. Our phenotype-genotype association attempts led to the identification of candidate disease-causing variants in both NOD2 and NPC1. In this study, we propose a potential composite digenic impact of these two genes as the underlying molecular etiology. This work lays the foundation for future functional and mechanistic studies to unravel the digenic role of NOD2 and NPC1.

Traditional cigarette use adversely impacts disease outcomes in Crohn\'s disease (CD). There has been a worldwide increase in the use of e-cigarettes over the past decade. The impact of use of nicotine containing e-cigarettes on disease outcomes in CD or ulcerative colitis (UC) has not been well defined.
This was a retrospective case-control study of patients with CD or UC who were current users of nicotine containing e-cigarettes (cases). Each case was matched to two non-vaping controls. Our primary study outcome was a composite of new biologic initiation, switch of existing biologic therapy, or IBD-related hospitalization or surgery over 2 years. Multivariable models adjusting for relevant covariates were construction.
The study consisted of 127 patients with IBD who were current e-cigarette users compared to 251 controls. Current e-cigarette users were younger than non-users and were more likely to have had an IBD-related surgery previously. On multivariable analysis among those with CD, current e-cigarette use was not associated with higher risk of study outcome (OR 0.82, 95% CI 0.36-1.87). No difference was observed separately among those who were current or former smokers. Similarly, in those with UC, current e-cigarette use was not associated with the primary outcome (OR 1.05, 95% CI 0.33-3.39).
Current e-cigarette use was not associated with worse outcomes among patients with IBD. However, larger studies particularly of patients de novo initiating vaping are needed to draw robust conclusions. Patients should be discouraged from initiating vaping recognizing overall adverse health effects.

OBJECTIVE: This study prompted by growing evidence of the relationship between the yeast Candida albicans and Crohn\'s disease (CD) was intended to assess the effect of a 6-month course of the antifungal fluconazole (FCZ) on post-operative recurrence of CD.
METHODS: Mycological samples (mouth swabs and stools) and serum samples were collected from 28 CD patients randomized to receive either FCZ (n = 14) or placebo (n = 14) before surgical resection. Serological analysis focused on levels of calprotectin, anti-glycan antibodies, and antibody markers of C. albicans pathogenic transition. Levels of galectin-3 and mannose binding lectin (MBL) involved in C. albicans sensing and inflammation were also measured.
RESULTS: 1, 2, 3, and 6 months after surgery, endoscopy revealed recurrence in 5/12 (41.7%) patients in the FCZ group and 5/9 (55.6%) in the placebo group, the small cohort preventing any clinical conclusions. In both groups, surgery was followed by a marked decrease in C. albicans colonization and biomarkers of C. albicans pathogenic transition decreased to non-significant levels. Anti-glycan antibodies also decreased but remained significant for CD. Galectin-3 and calprotectin also decreased. Conversely, MBL levels, which inversely correlated with anti-C. albicans antibodies before surgery, remained stable. Building biostatistical multivariate models to analyze he changes in antibody and lectin levels revealed a significant relationship between C. albicans and CD.
CONCLUSIONS: Several combinations of biomarkers of adaptive and innate immunity targeting C. albicans were predictive of CD recurrence after surgery, with area under the curves (AUCs) as high as 0.86. FCZ had a positive effect on biomarkers evolution. ClinicalTrials.gov ID: NCT02997059, 19 December 2016. University Hospital Lille, Ministry of Health, France. Effect of Fluconazole on the Levels of Anti-Saccharomyces cerevisiae Antibodies (ASCA) After Surgical Resection for Crohn\'s Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo.

Children with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS).
This prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response.
A total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3-16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination. All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn\'s disease the day after vaccination. The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078).
VZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).

Poor global sleep quality is commonly reported in people with inflammatory bowel disease (IBD) and is linked to poorer health-related quality of life (HRQoL). However, understanding is currently limited by a lack of: (1) longitudinal research and (2) research investigating the impact of specific types of problems sleeping on IBD-related outcomes, particularly on HRQoL.
Observational longitudinal cohort study.
N = 276 participants with IBD completed measures at baseline (T1) and 4 weeks later at T2. Four specific sleep disturbances associated with IBD including sleep apnoea, insomnia, restless legs, and nightmares were measured alongside depression, anxiety and stress, and HRQoL.
After controlling for participant demographics and clinical characteristics, T1 depression, anxiety, stress, and T1 HRQoL, more severe symptom severity of sleep apnoea (B = -0.30, p < .05) and insomnia symptoms (B = -0.23, p < .05) at T1 significantly predicted poorer HRQoL at T2. However, the experience of restless legs (B = -0.03, p > .87) and nightmares (B = -0.14, p > .11) at T1 did not predict HRQoL.
Symptoms synonymous with sleep apnoea and insomnia might represent modifiable risk factors that provide independent contributions to HRQoL over time in those with IBD. These findings suggest that interventions designed to improve sleep apnoea and insomnia could confer benefits to HRQoL in those with IBD. However, more longitudinal research is needed to understand the contribution of sleep disturbances over the longer term, as well as more randomized controlled trials testing the effect of improving sleep on IBD-related outcomes.