Baseline Peripheral Blood Mononuclear Cell Transcriptomics Before Ustekinumab Treatment Is Linked With Crohn's Disease Clinical Response at 1 Year.

INTRODUCTION: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, is used for Crohn's disease (CD), and the documented clinical remission rate after 1 year was observed in approximately 50% of patients. We aimed to identify predictors for a clinical response using peripheral blood obtained from patients with CD just before ustekinumab treatment initiation. METHODS: RNA extraction from peripheral blood mononuclear cells was followed by mRNA paired-end sequencing. Differential gene expression was performed using DESeq2. RESULTS: We processed samples from 36 adults with CD (13 men, 36%) obtained at baseline before starting ustekinumab treatment. Twenty-two of 36 (61%) were defined as responders and 14/36 (39%) as nonresponders after 1 year based on Physician Global Assessment. Differential gene expression between responders (n = 22) and nonresponders (n = 14) did not show a gene expression signature that passed false discovery rate (FDR) correction. However, the analyses identified 68 genes, including CXCL1/2/3, which were induced in nonresponders vs responders with P < 0.05 and fold change above 1.5. Functional annotation enrichments of these 68 genes using ToppGene indicated enrichment for cytokine activity (FDR = 1.98E-05), CXCR chemokine receptor binding (FDR = 2.11E-05), IL-10 signaling (FDR = 5.03E-07), genes encoding secreted soluble factors (FDR = 1.73E-05), and myeloid dendritic cells (FDR = 1.80E-08). DISCUSSION: No substantial differences were found in peripheral blood mononuclear cell transcriptomics between responders and nonresponders. However, among the nonresponders, we noted an increased inflammatory response enriched for pathways linked with cytokine activity and chemokine receptor binding and innate myeloid signature. A larger cohort is required to validate and further explore these findings.

Patient activation and its association with health indices among patients with inflammatory bowel disease.

Background: Patient activation refers to patients' independence in daily activities, involvement in the therapeutic process, and ability to manage their health. This study examined the association between the activation of patients with inflammatory bowel disease (IBD) and its effect on health indices. Objectives: To evaluate the association between the activation of patients with IBD measured by patient activation measure (PAM-13) questionnaire with disease activity and quality of life in IBD. Design: A retrospective cross-sectional study. Methods: This study included patients with Crohn's Disease (CD) or ulcerative colitis (UC) followed at a large medical center in Israel, who were recruited during routine visits. They answered weekly questionnaires using a mobile smartphone application that included clinical and emotional disease parameters, including IBD control, quality of life [short IBD quality of life questionnaire (SIBDQ)], patient-reported outcomes measurement information system (PROMIS-10) and PAM-13. Additional clinical parameters were collected from electronic medical records. Results: Among 201 patients (113 females) who responded to the questionnaires, 152 (75.6%) had CD and 49 (24.4%) UC. For PAM-13, 158 (79%) patients were at PAM-13 levels 3-4 (mean score: 68.5, range: 60.0-73.1) and 43 (21%) were at levels 1-2 (mean score: 45.2, range: 40.9-49.9). PAM-13 levels were correlated with IBD control (r = 0.19, p = 0.023), SIBDQ (r = 0.20, p = 0.010), and PROMIS-10 score (r = 0.24, p = 0.017). Conclusions: Our findings demonstrate the importance of patient activation and engagement in IBD. Knowledge of patient activation may enable caregivers to predict levels of self-care and the likelihood of compliance with health behavior recommendations.

Keeping it simple: mental health assessment in the Gastroenterology Department - using the Hospital Anxiety and Depression Scale (HADS) for IBD patients in Israel.

BACKGROUND: Depression and anxiety are common among inflammatory bowel disease (IBD) patients. Not only do they worsen quality of life, but also worsen the prognosis of the IBD. Yet, there are no widely accepted guidelines for screening for depression or anxiety in this population. The Hospital Anxiety and Depression Scale (HADS) is a self-administered questionnaire designed to measure anxiety and depression in the physically ill. The purpose of this study was to establish the utility of the HADS as a screening tool in IBD patients. METHODS: Seventy-nine IBD patients (age 29.86 ± 8.36, 51.9% female, 77.2% Crohn's disease) were recruited consecutively at the day treatment unit, Gastroenterology Department, Sheba Medical Center. They were asked to complete the HADS, the Beck Depression Inventory (BDI), and the State-Trait Anxiety Inventory (STAI). The scores of the HADS depression and anxiety subscales were correlated with the BDI and STAI scores, and the rates of above-threshold scores were calculated and compared between the three questionnaires and findings from previous studies. RESULTS: The two HADS subscales significantly correlated with and the BDI (rs = .69, p < 0.001) and STAI state and trait anxiety (rs = .853, p < 0.001; r s = .744, p < 0.001, respectively). The usual HADS cut-off scores yielded adequate rate of anxiety but lower than expected depression rates. CONCLUSIONS: Our findings suggest the HADS as a valid screening tool for anxiety and depression in IBD patients. We recommend administering it routinely in gastrointestinal (GI) follow-ups using a lower cut-off score for depression than anxiety (greater than 7 vs greater than 11, respectively).

Barriers to international travel in inflammatory bowel disease patients.

BACKGROUND: Inflammatory bowel disease poses substantial challenges to travel. We aimed to investigate inflammatory bowel diseases (IBD)-associated challenges to travel, information-seeking behaviour and associated factors. METHODS: We collected data on patients' demographics, disease characteristics, travel barriers, information-seeking behaviour and travel outcomes in UK, Australia, New Zealand and Israel (2016-2018). Summary statistics were used to describe the sample, whereas multivariate binary and nominal logistic regression were used to model the outcome variables. RESULTS: Almost 75.4% (1878/2491) participants' data were analysed with 71.14%, 15.4%, 11.2% and 2.1% from UK, Australia, NZ and Israel, respectively (76.3% females, 48.2% 30-49 years old 58.8% Crohn's disease). About 7.7% of study participants sought medical advice/were hospitalised while overseas. About 43.8% cancelled/changed their plans due to IBD. The most common barriers were worry about toilet facilities (76.3%), cleanliness/sanitation (50.9%) and availability of medical care (41.1%). Only 60.5% sought travel advice; the most popular information source was IBD doctor/nurse (32.6%). Almost 32.6% of study participants did not get travel insurance that covered their IBD. Those who did not receive advice or found obtaining travel insurance difficult, were less likely to obtain travel insurance (P < 0.001). Participants who travelled for work were more likely to be hospitalised/seek medical advice overseas and not obtain travel insurance. CONCLUSIONS: We report a detailed investigation on the IBD-associated barriers while travelling abroad, common information-seeking behaviours and factors associated with worse outcomes. Importantly, patients from all the surveyed countries provided similar travel barrier and preparation habits, highlighting the consistent nature of the challenge.

Change in bowel habits during menstruation: are IBD patients different?

BACKGROUND AND AIM: Many female inflammatory bowel disease (IBD) patients report symptoms exacerbation before and during menses. Our aim was to characterize their symptoms and specific risk factors in comparison with healthy controls. METHODS: Female IBD patients aged 18-50 years were asked to fill out a questionnaire recording their demographic and disease characteristics, menstruation history and symptoms. Disease activity was defined by Harvey-Bradshaw index (HBI) for Crohn's disease (CD) patients and modified mayo score for ulcerative colitis (UC) patients. Healthcare providers answering an internet survey assessing bowel symptoms during menstruation served as healthy controls. RESULTS: A total of 139 IBD patients, of whom 100 were CD patients, filled the questionnaire. The mean age was 30.4 [±7.7 standard deviation (SD)], mean disease duration was 7.8 (±6 SD), mean HBI was 4.7 (±3.8 SD), and mean Mayo score was 2.1 (±2.5 SD). A change in bowel habits during menstruation was reported by 72% of CD patients compared with 56% of UC patients (p = 0.07). Out of 258 healthy controls, 93% reported a change in bowel habits during menstruation compared with 68% of IBD patients (p < 0.001). However, other abdominal and constitutional symptoms were significantly more prevalent among IBD patients compared with healthy controls (p < 0.01 for most parameters). Smoking status, biologic treatment, and previous abdominal operation were found to significantly aggravate symptoms during menses in IBD patients. CONCLUSION: IBD patients experience various symptoms during menses significantly more commonly than healthy women. Smoking, biologic treatment, and previous abdominal operations are risk factors for higher symptomatic burden. Following future validation and research, these results can help in patients' risk stratification and possibly in risk reduction.