Hidradenocarcinoma in a Crohn's patient on ustekinumab: A case report.

Hidradenocarcinoma is a locally aggressive malignancy of the sweat glands, most commonly found on the head, neck, and upper body. Although rare, it has been seen in patients with hidradenitis supparativa, who have an increased risk of non-melanoma skin cancers. Ustekinumab, a biologic agent used to treat inflammatory bowel disease, has been associated with development of cancer in some patients. We present a case of a 36-year-old female with hidradenitis supparativa and Crohn's disease who developed hidradenocarcinoma in setting of ustekinumab use, demonstrating the need for further study of the relationship between biologic therapy and malignancy.

Inflammatory Bowel Disease-Associated Arthritis Is Associated with Concomitant Autoimmune and Inflammatory Disorders.

BACKGROUND: Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. METHODS: Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. RESULTS: The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. CONCLUSION: This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA.

Cholinergic Mechanisms in Gastrointestinal Neoplasia.

Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia. Herein, after briefly reviewing the classification of acetylcholine-activated receptors and the role that nicotinic and muscarinic cholinergic signaling plays in normal digestive function, we consider the mechanics of acetylcholine synthesis and release by neuronal and non-neuronal cells in the gastrointestinal microenvironment, and current methodology and challenges in measuring serum and tissue acetylcholine levels accurately. Then, we critically evaluate the evidence that constitutive and ligand-induced activation of acetylcholine-activated receptors plays a role in promoting gastrointestinal neoplasia. We focus primarily on adenocarcinomas of the stomach, pancreas, and colon, because these cancers are particularly common worldwide and, when diagnosed at an advanced stage, are associated with very high rates of morbidity and mortality. Throughout this comprehensive review, we concentrate on identifying novel ways to leverage these observations for prognostic and therapeutic purposes.

Correlation Between Serum and Fecal Biomarkers and Patient-Reported Outcomes in Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Patient-reported outcomes (PROs), such as the short CD activity index (sCDAI) and partial Mayo Score (PMS), are used to define clinical remission in IBD, but may not represent the true degree of inflammation and endoscopy is invasive. Non-invasive testing options include c-reactive protein (CRP) and fecal calprotectin (FCP). AIM: The aim of this study was to assess the degree of correlation of non-invasive biomarkers with PROs and the impact other clinical variables can have on their levels. METHODS: We reviewed data collected from the prospective cohort, Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD), comprised of over 3000 patients from 17 tertiary referral centers. Demographic and clinical variables were analyzed by disease type, disease severity was based on PROs, and baseline CRP and FCP were measured. For comparative analysis, we performed Fisher's exact test and Welch's t test, where p < 0.05 was significant. RESULTS: 1547 patients were included; 63% had CD, 56% were female, with an average disease duration of 13.6 years. CRP and FCP were associated with symptom severity in inflammatory CD. CRP was useful to differentiate symptoms across different disease locations in CD, whereas FCP was associated with symptom severity in Crohn's colitis only. For UC, FCP was able to distinguish symptom severity better in distal UC, whereas in extensive or pancolitis, it was useful only to distinguish severe symptoms from other categories of symptom severity. CONCLUSION: PROs correlate with CRP and FCP; however, disease location and phenotype impact their ability to distinguish symptom severity.

Low-dose pulsed vs standard pulsed fluoroscopy during ERCP to reduce radiation without change in image quality: Prospective randomized study.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) poses the risk of radiation exposure (RE) to patients and staff and increases the risk of adverse biological effects such as cataracts, sterility, and cancer. Newer fluoroscopy equipment (C-Arm) provides options to limit radiation in the form of lower radiation dose and frame rate or time-limited "pulsed" settings. However, the impact of lower settings on image quality has not been assessed, and no standard protocol exists for fluoroscopy settings used during ERCP. Patients and methods This was a single-center, double-blind, prospective randomized study of consecutive adult patients undergoing standard-of-care ERCP at a tertiary academic medical center. Patients were randomized into two groups: 1) standard-dose pulsed and 2) low-dose pulsed. Pulsed mode (8 fps) was defined as x-ray exposure either in the manufacturer standard-dose or low-dose settings limited to 3 seconds each time the foot-operated switch was depressed. Results Seventy-eight patients undergoing ERCP were enrolled and randomized. No difference in age, gender, or body mass index was found between the two groups. No significant difference in image quality was found between standard-dose and low-dose fluoroscopy P = 0.925). The low-dose group was exposed to significantly less radiation when compared with standard-dose P < 0.05). Fluoroscopy time (minutes) was similar in both groups (2.0 vs 1.9), further suggesting that group assignment had no impact on image quality or procedure time. Conclusions Low-dose pulsed fluoroscopy is a reliable method that substantially reduces radiation without compromising image quality or affecting procedure or fluoroscopy times. This underscores the need for standardization in ERCP fluoroscopy settings to limit radiation exposure.

ExpLOring the role of the intestinal MiCrobiome in InflammATory bowel disease-AssocIated SpONdylarthritis (LOCATION-IBD).

Background: Inflammatory Bowel Disease (IBD)-associated arthritis is a frequent and potentially debilitating complication of IBD, that can affect those with or without active intestinal disease, and is often difficult to treat. The microbiome is known to play a role in IBD development and has been shown to be associated with inflammatory arthritis without concomitant IBD, but its role in IBD-associated arthritis is still unexplored. Further, disease localization is associated with development of IBD-associated arthritis, and stool compositional profiles are predictive of disease localization, yet mucosal location-specific microbiomes have not been well characterized. To address this gap in understanding, we designed a study (LOCATION-IBD) to characterize the mucosa-associated intestinal microbiome and metabolome in IBD-associated arthritis. Methods: Adults with an established diagnosis of IBD undergoing clinical colonoscopy between May of 2021 and February of 2023 were invited to participate in this study; those interested in participation who met inclusion criteria were enrolled. Prior to enrollment, participants were stratified into those with or without IBD-associated arthritis. All participants were interviewed and had clinical and demographic data collected, and 97.8% completed clinical colonoscopy with biopsy collection. Results and conclusion: A total of 182 participants, 53 with confirmed IBD-associated arthritis, were enrolled in this study, resulting in 1151 biopsies obtained for microbiome and metabolome analysis (median 6, mean 6.3 per participant). Clinical and demographic data obtained from the study population will be analyzed with microbiome and metabolome data obtained from biopsies, with the goal of better understanding the mechanisms underpinning the host-microbiome relationship associated the development of IBD-associated arthritis.

Gastroenterology Fellowship and Postdoctoral Training in Omics and Statistics-Part I: Why Is It Needed?

A multitude of federally and industry-funded efforts are underway to generate and collect human, animal, microbial, and other sources of data on an unprecedented scale; the results are commonly referred to as "big data." Often vaguely defined, big data refers to large and complex datasets consisting of myriad datatypes that can be integrated to address complex questions. Big data offers a wealth of information that can be accessed only by those who pose the right questions and have sufficient technical knowhow and analytical skills. The intersection comprised of the gut-brain axis, the intestinal microbiome and multi-ome, and several other interconnected organ systems poses particular challenges and opportunities for those engaged in gastrointestinal and liver research. Unfortunately, there is currently a shortage of clinicians, scientists, and physician-scientists with the training needed to use and analyze big data at the scale necessary for widespread implementation of precision medicine. Here, we review the importance of training in the use of big data, the perils of insufficient training, and potential solutions that exist or can be developed to address the dearth of individuals in GI and hepatology research with the necessary level of big data expertise.

Gastroenterology Fellowship and Postdoctoral Training in Omics and Statistics-Part II: How Can It Be Achieved?

Data are being generated, collected, and aggregated in massive quantities at exponentially increasing rates. This "big data," discussed in depth in the first section of this two-part series, is increasingly important to understand the nuances of the gastrointestinal tract and its complex interactions and networks involving a host of other organ systems and microbes. Creating and using these datasets correctly requires comprehensive training; however, current instruction in the integration, analysis, and interpretation of big data appears to lag far behind data acquisition. While opportunities exist for those interested in acquiring the requisite training, these appear to be underutilized, in part due to widespread ignorance of their existence. Here, to address these gaps in knowledge, we highlight existing big data learning opportunities and propose innovative approaches to attain such training. We offer suggestions at both the undergraduate and graduate medical education levels for prospective clinical and basic investigators. Lastly, we categorize training opportunities that can be selected to fit specific needs and timeframes.