In active UC, upadacitinib induced and maintained remission.

SOURCE CITATION: Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399:2113-28. 35644166.

"ASKing" the Right Questions About Screening for Celiac Disease.

ABSTRACT: Make a distinction between investigating symptoms and screening for disease. Understand the performance characteristics of a test for those with symptoms and for screening those without symptoms, whether at elevated risk or average risk of disease. Positive test results require patient education and follow-up. Importantly, screening should be advantageous to an individual, and disease treatment should be in their interest. The practical application of these principles in relation to population-based Celiac disease screening may be difficult, as a large Colorado study has found.

Opportunistic detection of anal intraepithelial neoplasia at colonoscopy.

BACKGROUND AND AIM: Human papilloma virus-associated anal intraepithelial neoplasia (AIN) precedes most anal cancers and can be detected at colonoscopy. We aimed to quantify AIN detection rates in a general population undergoing colonoscopy. METHODS: A retrospective review of a community-based practice for 2 years until December 2019 was conducted. RESULTS: A total of 2525 patients (1051 males and 1474 females; median age 59 years) had 2608 colonoscopies. Ten patients (two males and eight females; median age 57.5 years) had incidentally detected AIN (condyloma acuminatum or AIN1, n = 4; AIN2 or 3, n = 6). AIN was detected in 1 of 261 (95% CI 1/142-1/480) colonoscopies and 1 of 163 (95% CI 1/83-1/321) colonoscopies in women over 40 years old. CONCLUSIONS: Opportunistically detecting AIN, especially in women over 40 years old, should be an important adjunct to colonoscopy-based colorectal neoplasia detection.

Mesenchymal Stromal Cell Therapy in Crohn's Disease.

BACKGROUND: Mesenchymal stromal cells (MSC) are multipotent adult stem cells with immunomodulatory properties. They uniquely express HLA class I antigen at a low level, and do not express HLA class II. Hence, for allogeneic administration, donor to recipient matching is not required; yet a prolonged chimeric state does not occur. Contrary to haematopoietic stem cell transplantation, cytotoxic drug therapy is not required to harvest, or administer, cells. Key Messages: MSC are obtained from marrow, adipose tissue or placenta. In our centre, MSC are isolated from a 10 ml donor marrow aspirate, by virtue of their adherence to plastic. They are expanded in culture, cryopreserved, and subjected to strict quality controls before release for intravenous administration. These activities occur in a dedicated, nationally accredited, laboratory. Initial observations of allogeneic MSC efficacy were in graft-versus-host disease. Both autologous and allogeneic MSC have since been evaluated in biologic refractory luminal and fistulising Crohn's disease (CD). Data from early-phase studies have suggested efficacy for luminal disease when allogeneic MSC were given intravenously and also suggested efficacy for fistulising disease when either allogeneic or autologous MSC were administered into fistulas. MSC treatment is not reported to have caused serious adverse events. Although in vitro criteria for defining MSC exist, a major challenge lies in how to define MSC for clinical use. MSC function in vivo is likely to be dependent upon donor immunological characteristics, and widely varying manufacturing processes between laboratories. MSC dose, frequency of administration, stage of disease, and presence of concomitant immunosuppression also require to be defined. CONCLUSIONS: MSC therapy may have future utility in CD, but considerable work is first required to determine appropriate phenotypic and functional characteristics of administered cells.

A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn's disease refractory to biologic therapy.

BACKGROUND & AIMS: Transplantation of peripheral blood stem cells has been successful therapy for small numbers of patients with Crohn's disease (CD), but requires prior myeloconditioning. Mesenchymal stromal cells (MSCs) escape immune recognition, so myeloconditioning is not required before their administration. We investigated the efficacy of allogeneic MSCs in patients with luminal CD. METHODS: Our phase 2, open-label, multicenter study included 16 patients (21-55 y old; 6 men) with infliximab- or adalimumab-refractory, endoscopically confirmed, active luminal CD (CD activity index [CDAI], >250). Subjects were given intravenous infusions of allogeneic MSCs (2 × 10(6) cells/kg body weight) weekly for 4 weeks. The primary end point was clinical response (decrease in CDAI >100 points) 42 days after the first MSC administration; secondary end points were clinical remission (CDAI, <150), endoscopic improvement (a CD endoscopic index of severity [CDEIS] value, <3 or a decrease by >5), quality of life, level of C-reactive protein, and safety. RESULTS: Among the 15 patients who completed the study, the mean CDAI score was reduced from 370 (median, 327; range, 256-603) to 203 (median, 129) at day 42 (P < .0001). The mean CDAI scores decreased after each MSC infusion (370 before administration, 269 on day 7, 240 on day 14, 209 on day 21, 182 on day 28, and 203 on day 42). Twelve patients had a clinical response (80%; 95% confidence interval, 72%-88%; mean reduction in CDAI, 211; range 102-367), 8 had clinical remission (53%; range, 43%-64%; mean CDAI at day 42, 94; range, 44-130). Seven patients had endoscopic improvement (47%), for whom the mean CDEIS scores decreased from 21.5 (range, 3.3-33) to 11.0 (range, 0.3-18.5). One patient had a serious adverse event (2 dysplasia-associated lesions), but this probably was not caused by MSCs. CONCLUSIONS: In a phase 2 study, administration of allogeneic MSCs reduced CDAI and CDEIS scores in patients with luminal CD refractory to biologic therapy. ClinicalTrials.gov number, NCT01090817.

Diagnostic dilemmas in celiac disease.

Celiac disease (CD) is an immune-mediated systemic condition triggered by dietary gluten occurring in genetically susceptible individuals. Our understanding of its numerous and varied clinical presentations has evolved over time, which has contributed to the incidence of CD increasing. In most cases, the diagnosis is readily established and patients promptly improve after commencing a gluten-free diet (GFD). However, in some, the diagnosis is not straightforward and presents a challenge to clinicians. Potential dilemmas include those with positive serology but normal histology, negative serology but abnormal duodenal mucosal histology, failure to respond to a GFD or response to a GFD without evidence of CD. In recent years, development of new assays and modifications to existing diagnostic algorithms for CD has also challenged the traditional role of small-bowel histology as critical in CD diagnosis.

Acute gastrointestinal bleeding after percutaneous coronary intervention.

Bleeding from the GI tract is a commonly encountered clinical problem after percutaneous coronary intervention. The GI tract is likely to become the most commonly encountered site of bleeding as cardiologists adopt smaller access sheath sizes, percutaneous closure devices and a radial artery approach, further reducing access-site bleeding. To appropriately manage gastrointestinal bleeding in this setting, the clinician must strike a balance between arresting hemorrhage and preventing ischemic coronary complications. To do so, an appreciation of both cardiovascular and gastrointestinal issues is required. This review aims to provide the required knowledge, as well as a series of recommendations from our practice, to assist in the management of this potentially fatal complication.

Long-term health risks for children and young adults after infective gastroenteritis.

To quantify the risk and types of sequelae attributable to prior enteric infections, we undertook a population-based retrospective cohort study using linked administrative records. The risk for first-time hospitalization for sequelae was modeled by using Cox proportional regression analysis controlling for other health and sociodemographic factors. We identified a significant increase of 64% in the rate of first-time hospitalization for sequelae for persons with prior enteric infections: 52% for intragastrointestinal sequelae and 63% for extragastrointestinal sequelae compared with first-time hospitalization for those without prior infection. Extragastrointestinal sequelae occurred predominantly during the first 5 years after first-time enteric infection. In contrast, most intragastrointestinal sequelae occurred >10 years later. Infective gastroenteritis during childhood or adolescence increases the risk for first-time hospitalization for intragastrointestinal and extragastrointestinal disease over the 2 decades after first-time enteric infection, highlighting the importance of identifying ways of reducing the incidence of such infections.

Colorectal cancer screening tests: pros and cons, and for whom?

The past decade has seen major advances internationally in the implementation of colorectal cancer screening, influenced in differing ways by the profession, the public and by government. Relatively unique to colorectal cancer screening is the availability of so many test alternatives, which have substantial variation in methodology. While perhaps spoilt for choice, discerning the key advantages and disadvantages of each test is often difficult, depending on the perspective from which screening is viewed. Accordingly, this article provides an evaluation of screening tests as might be perceived by governments, the patient and the profession. Aligned issues such as choosing a screening test and provision of informed consent are discussed. Finally, the article identifies current problems with various screening tests that, if attended to, might change the perception of a test's value to a particular interest group.