Peripheral Blood IL5RA Gene Expression as a Diagnostic Biomarker for Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus, often diagnosed late because of its challenging symptoms and costly and invasive diagnostic methods.1,2 To address the need for more accessible biomarkers in EoE,3 we aimed to investigate the potential of whole-blood RNA expression as a noninvasive biomarker for diagnosing and monitoring EoE, hypothesizing that genetic signatures in blood could distinguish EoE cases, correlate with disease activity, and predict treatment responses.

In Acute Severe Ulcerative Colitis Patients Who Receive Rescue Therapy, Prior Maintenance Therapy and Day 3 C-Reactive Protein After Rescue Therapy Are Associated With 12-Month Colectomy Risk.

In steroid-refractory patients with acute severe ulcerative colitis, the number of advanced therapies prior to admission and day 3 C-reactive protein post­rescue therapy is associated with a higher risk of colectomy within 12 months.

Diverticulosis Is Associated With Internal Hemorrhoids on Colonoscopy: Possible Clues to Etiology.

Hemorrhoids are a common but poorly understood gastrointestinal condition.1 Bowel habits and fiber consumption are frequently cited as risk factors for hemorrhoids, but research has been inconclusive.2 Recent genome-wide association studies (GWAS) have suggested an association between diverticular disease and hemorrhoids.3 We sought to investigate the association between colonic diverticulosis and internal hemorrhoids to validate the prediction from the GWAS.

Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.

Risk Factors for Colorectal Polyps and Cancer.

Colorectal cancer (CRC) is a common malignancy in the U.S. and worldwide. Most CRC cases arise from precancerous adenomatous and serrated polyps. Established risk factors for conventional adenomas and CRC include age, male sex, family history, obesity and physical inactivity, and red meat intake. White race and tobacco and alcohol use are important risk factors for serrated polyps, which have a distinct risk factor profile compared to conventional adenomas. A history of abdominopelvic radiation, acromegaly, hereditary hemochromatosis, or prior ureterosigmoidostomy also increases CRC risk. Understanding these risk factors allows for targeted screening of high-risk groups to reduce CRC incidence.

Urgency and Its Association With Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis.

INTRODUCTION: Urgency, the immediate need to defecate, is common in active ulcerative colitis (UC). We investigated the association of urgency in patients with UC with (i) quality of life (QoL) domains and (ii) future hospitalizations, corticosteroid use, and colectomy for UC. METHODS: We conducted a cross-sectional and subsequent longitudinal study within Inflammatory Bowel Disease Partners, a patient-powered research network. We described associations of levels of urgency in patients with UC with Patient-Reported Outcomes Measurement Information System QoL domains. We conducted a longitudinal cohort to determine associations between baseline urgency and subsequent hospitalization, corticosteroid use, or colectomy for UC within 12 months. We used bivariate statistics and logistic regression models to describe independent associations. RESULTS: A total of 632 patients with UC were included in the cross-sectional study. After adjusting for clinical variables, rectal bleeding, and stool frequency, urgency defined as "hurry," "immediately," and "incontinence" increased the odds of social impairment (odds ratio [OR] 2.05 95% confidence interval [CI] 1.24-3.4, OR 2.76 95% CI 1.1-6.74, and OR 7.7 95% CI 1.66-38.3, respectively) compared with "no hurry." Urgency also significantly increased the odds of depression, anxiety, and fatigue. Urgency was associated with a significant increase in risk of hospitalizations and corticosteroids, whereas "hurry," "immediately," and "incontinence" increased the odds of colectomy within 12 months by 1.42 (1.15-1.75), 1.90 (1.45-2.50), and 3.69 (2.35-5.80). DISCUSSION: We demonstrated that urgency is a patient-reported outcome independently associated with compromised QoL and future risk of hospitalizations, corticosteroids, and colectomy. Our findings support the consideration of urgency as a UC-specific patient-reported outcome and its use as an outcome in clinical trials to capture QoL and risk of clinical decompensation.

Loss to Follow-Up and Health Care Utilization After Initial Diagnosis of Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic disease, but the extent of patient loss to follow-up (LTFU) and health care utilization has not been fully investigated. AIM: To determine frequency and predictors of LTFU and health care utilization in EoE patients. METHODS: In this retrospective cohort study, we extracted data from patients with a new diagnosis of EoE. Follow-up time for each patient was calculated as the time from the first diagnostic endoscopy to the last GI-related contact date in the medical record. Patients with and without LTFU were compared, and the volume of EoE-related health care interactions was recorded. RESULTS: Of 944 EoE cases, 249 (26%) met the definition for LTFU. Major reasons for LTFU were never being scheduled (45%) and inability to contact patients (40%). Factors independently associated with regular follow-up were having insurance (aOR 2.89; 95% CI 1.85-4.50), white race (aOR 2.16; 95% CI 1.37-3.41), and longer symptom length (aOR 1.04 per year; 95% CI 1.01-1.08). At the time of last contact, patients with follow-up had better symptom response (55% vs. 12%; p < 0.001), improved esophageal caliber (14.3 vs. 12.4 mm; p = 0.005), and more histologic response (45% vs. 4% at 15 eos/hpf; p < 0.001). Health care utilization was high, with an average of 4.6 endoscopies and 4.0 clinic visits over the follow-up period. CONCLUSIONS: LTFU of newly diagnosed EoE cases was common and associated with lack of insurance, non-white race, and shorter symptom duration. Those who followed up had high health care utilization but improved response rates. Strategies are needed to help decrease LTFU in EoE.

Reg4 and its downstream transcriptional activator CD44ICD in stage II and III colorectal cancer.

Reg4 is highly expressed in gastrointestinal malignancies and acts as a mitogenic and pro-invasive factor. Our recent works suggest that Reg4 binds with CD44 and induces its proteolytic cleavage to release intra-cytoplasmic domain of CD44 (CD44ICD). The goal of this study is to demonstrate clinical significance of the Reg4-CD44/CD44ICD pathway in stage II/III colon cancer and its association with clinical parameters of aggression. We constructed a tissue microarray (TMA) of 93 stage II/III matched colon adenocarcinoma patients, 23 with recurrent disease. The TMA was immunohistochemically stained for Reg4, CD44, and CD44ICD proteins and analyzed to identify associations with tumor characteristics, recurrence and overall survival. The TMA data analysis showed a significant correlation between Reg4 and CD44 (r2 = 0.23, P = 0.028), CD44 and CD44ICD (r2 = 0.36, p = 0.0004), and Reg4 and CD44ICD (r2 = 0.45, p ≤ 0.0001). Reg4 expression was associated with larger tumor size (r2 = 0.23, p = 0.026). Although, no association was observed between Reg4, CD44, or CD44ICD expression and disease recurrence, Reg4-positive patients had a median survival of 4 years vs. 7 years for Reg4-negative patients (p = 0.04) in patients who recurred. Inhibition of the Reg4-CD44/CD44ICD pathway may be a future therapeutic target for colon cancer patients.