Faculty Bibliography

Pregnancy is a vital period affecting both maternal and fetal health, with impacts on maternal metabolism, fetal growth, and long-term development. While the maternal metabolome undergoes significant changes during pregnancy, longitudinal shifts in maternal urine have been largely unexplored. In this study, we applied liquid chromatography-mass spectrometry-based untargeted metabolomics to analyze 346 maternal urine samples collected throughout pregnancy from 36 women with diverse backgrounds and clinical profiles. Key metabolite changes included glucocorticoids, lipids, and amino acid derivatives, indicating systematic pathway alterations. We also developed a machine learning model to accurately predict gestational age using urine metabolites, offering a non-invasive pregnancy dating method. Additionally, we demonstrated the ability of the urine metabolome to predict time-to-delivery, providing a complementary tool for prenatal care and delivery planning. This study highlights the clinical potential of urine untargeted metabolomics in obstetric care.

BACKGROUND:The alcohol-induced facial flushing phenotype (flushing) is common among East Asians. Despite a small intake of alcohol, they experience heightened levels of acetaldehyde, a group-1 carcinogen, which, in turn, causes unpleasant symptoms such as redness, acting as a robust protective mechanism against consuming alcohol. However, some individuals with this genetic trait exhibit weakened alcohol restraint, which increases the risk of developing alcohol-related cancers, such as esophageal and head or neck cancer, by several times. Although this flushing phenomenon is crucial for public health, there is a paucity of studies that have comprehensively investigated the effect of flushing or its genotype on alcohol consumption in a large group of East Asians while controlling for various sociodemographic and health-related variables at a country level. OBJECTIVE:This 2-year cross-sectional study aims to explore the effect of flushing on drinking behavior in Koreans and to examine whether the effect varies across sociodemographic and health-related factors. METHODS:test, 2-tailed t test, and multinomial logistic regression analysis. RESULTS:The suppressive effect of flushing was significant (P<.001) across all pronounced categories of alcohol consumption in 2019. The ranges of standardized regression slopes and odds ratios (ORs) were -6.70≥β≥-11.25 and 0.78≥OR≥0.50 for frequency and -5.37≥β≥-17.64 and 0.73≥OR≥0.36 for amount, respectively. The effect became somewhat stronger when adjusted for confounders. The effect also exhibited an overall stronger trend as the severity of alcohol consumption increased. The β values and ORs were consistently smaller in 2020 compared to the previous year. A simple effect analysis revealed a diminished alcohol-suppressive effect of flushing on alcohol consumption for specific groups (eg, those with low levels of education, limited family support, physical labor, or health-related issues). CONCLUSIONS:Our findings suggest that flushing suppresses drinking in Koreans overall but has little or no effect in certain susceptible populations. Therefore, health authorities should conduct targeted epidemiological studies to assess drinking patterns and disease profiles, particularly regarding alcohol-related cancers, and establish effective preventive measures tailored to this population.

INTRODUCTION/BACKGROUND:A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS:Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS:Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION/CONCLUSIONS:Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract that might lead to progressive bowel damage and disability. The exact cause of Crohn's disease is unknown, but evidence points towards multifactorial events causing dysregulation of the innate immune system in genetically susceptible people. Commonly affecting the terminal ileum and proximal colon, Crohn's disease inflammation is often discontinuous and patchy, segmental, and transmural. Identification of characteristic findings on ileocolonoscopy and histology remains the diagnostic gold standard, but complete assessment involves laboratory abnormalities, including micronutrient deficiencies, cross-sectional imaging to identify transmural disease extent, severity and complications, and a psychosocial assessment. Treatment strategies for patients with Crohn's disease now go beyond achieving clinical remission to include deeper targets of endoscopic healing and consideration of adjunctive histological and transmural targets to alter disease progression potentially further. The use of early effective advanced therapies and development of therapies targeting alternative novel pathways with improved safety profiles have resulted in a new era of healing in Crohn's disease management. Future combination of advanced therapies with diet or other biological drugs and small molecules, together with improvements in tight control monitoring tools and predictive biomarkers might continue to improve outcomes for patients with Crohn's disease.

Novel technology is one of the five focus areas of the Challenges in Inflammatory Bowel Disease (IBD) Research 2024 document. Building off the Challenges in IBD Research 2019 document, the Foundation aims to provide a comprehensive overview of current gaps in IBD research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of a multidisciplinary collaboration from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. Specifically, the Novel Technologies section focuses on addressing key research gaps to enable interception and improve remission rates in IBD. This includes testing predictions of disease onset and progression, developing novel technologies tailored to specific phenotypes, and facilitating collaborative translation of science into diagnostics, devices, and therapeutics. Proposed priority actions outlined in the document include real-time measurement of biological changes preceding disease onset, more effective quantification of fibrosis, exploration of technologies for local treatment of fistulas, and the development of drug delivery platforms for precise, location-restricted therapies. Additionally, there is a strong emphasis on fostering collaboration between various stakeholders to accelerate progress in IBD research and treatment. Addressing these research gaps necessitates the exploration and implementation of bio-engineered novel technologies spanning a spectrum from materials to systems. By harnessing innovative ideas and technologies, there's a collective effort to enhance patient care and outcomes for individuals affected by IBD.

BACKGROUND:Data are limited on the safety and efficacy of combining advanced therapies for refractory patients with IBD. AIM/OBJECTIVE:To evaluate the real-world efficacy and safety of dual advanced therapy (DAT), combining 2 biologics or a biologic with a small molecule, in children and young adults with refractory IBD. METHODS:Primary outcome of this single IBD center cohort was DAT remission (clinical and biomarker remission) at first assessment (T1). Secondary outcomes included remission at T2, if DAT de-intensification (De-I) occurred and T3, if T2 DAT re-intensification (Re-I) occurred. Efficacy and safety outcomes were described. RESULTS:Of the 30 patients [43% female, 30% CD, median age of 18.3 [15.1-19.8] years], all 11 UST + TOFA achieved T1 remission; 6/10 De-I failed at T2; and 4/4 Re-I achieved T3 remission. Of 9 VDZ + TOFA, 6 achieved T1 remission; 5/6 De-I failed at T2; and 1/1 failed T3 Re-I. Of 4 UST + VDZ, 3 achieved T1 remission; 2/3 De-I failed at T2; and 0 had Re-I. Of 5 UST + UPA, 4 achieved T1 remission; 1/5 De-I failed at T2 but recaptured T3 remission post-Re-I. One VDZ + OZA achieved T1 remission and maintained T2 remission post-De-I to OZA monotherapy. At last follow-up, 43% were on original DAT, 17% on one of original DAT, and 40% neither. One UST + TOFA patient developed mild leukopenia and another developed septic arthritis and venous thromboembolism on VDZ + TOFA and prednisone. CONCLUSION/CONCLUSIONS:Most children and young adults treated with DAT achieved remission with minimal safety events; however, de-intensification had limited success.

DESCRIPTION/METHODS:In the past 3 years, the use of intestinal ultrasound (IUS) for monitoring inflammatory bowel disease in clinical practice has grown substantially in the United States. This American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) aims to review the available evidence and guidance regarding the role of intestinal ultrasound in inflammatory bowel disease care. METHODS:This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important and recently published studies in this field, and it reflects the experiences of the multidisciplinary group of authors composed of adult and pediatric gastroenterologists.