Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:IL-17-mediated diseases have great global burden. Basic science research suggests that excessive sodium intake can trigger systemic IL-17-mediated inflammation, but population-based data on the association between sodium intake and IL-17-mediated diseases are limited. We aim to understand if increased estimated dietary sodium is associated with higher rates of IL-17-mediated disease. METHODS:We conducted a population-based cross-sectional study using UK Biobank data from 468,673 participants (aged 37-73 years) recruited between March 2006 and October 2010. The exposure, dietary sodium, was estimated using the International Study of Electrolyte Secretion and Blood Pressure equation. The main outcome, prevalence of any IL-17-mediated disease (psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis), was determined by diagnostic codes. RESULTS:After adjusting for age, sex, ethnicity, Townsend deprivation index, and education, a 1-gram higher estimated daily sodium intake was associated with higher odds of having an IL-17-mediated disease (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.06 to 1.10) as well as more IL-17-mediated diseases (adjusted rate ratio 1.08, 95% CI 1.06 to 1.10). Sub-analyses of individual diseases showed that higher estimated dietary sodium was associated with higher odds of psoriasis (aOR 1.17, 95% CI 1.13 to 1.22), psoriatic arthritis (aOR 1.22, 95% CI 1.13 to 1.32), hidradenitis suppurativa (aOR 2.07, 95% CI 1.73 to 2.47), and rheumatoid arthritis (aOR 1.19, 95% CI 1.14 to 1.24), and lower odds of having inflammatory bowel disease (aOR 0.84, 95% CI 0.80 to 0.88). There was no significant association with ankylosing spondylitis (aOR 1.00, 95% CI 0.93 to 1.08), systemic lupus erythematosus (aOR 0.93, 95% CI 0.69 to 1.26), or multiple sclerosis (aOR 0.95, 95% CI 0.81 to 1.12). CONCLUSION/CONCLUSIONS:In a large population-based cohort, higher estimated dietary sodium was associated with a small increase in the odds of IL-17-mediated disease, particularly those of the skin and joints. Future work should investigate whether a low-salt diet improves IL-17-mediated diseases.

BACKGROUND & AIMS/OBJECTIVE:We report 104-week placebo-controlled data and long-term open-label extension (OLE) data from the ongoing ELATIVE® phase III trial (NCT04526665) of elafibranor in primary biliary cholangitis (PBC). METHODS:161 patients were randomized 2:1 to elafibranor 80 mg or placebo. The double-blind period (DBP) consisted of 52-week common (Part 1) and variable (Part 2) periods. Patients completing Part 1 continued into Part 2 until all patients completed Part 1, or for a maximum of 104 weeks. All patients completing Part 1 could enter the OLE and receive elafibranor. RESULTS:At Week 104 in the DBP Part 2, 64.3% (18/28) and 10.7% (3/28) of elafibranor-treated patients achieved biochemical response and alkaline phosphatase (ALP) normalization, versus no placebo-treated patients. In patients with moderate-to-severe fatigue or pruritus at baseline, mean (SE) changes to Week 104 in PROMIS Fatigue Short Form 7a (PFSF 7a) and PBC Worst-Itch Numeric Rating Scale (PBC WI NRS) were -6.3 (2.2) versus -0.4 (1.2) and -4.1 (1.0) versus 0.3 (1.2) with elafibranor versus placebo. 138 patients entered the OLE (continuous elafibranor: n=93; crossover elafibranor: n=45). In continuous patients at Weeks 104 and 156, 58.8% (47/80) and 65.0% (13/20) achieved biochemical response, and 15.0% (12/80) and 25.0% (5/20) achieved ALP normalization. In crossover patients, 51.2% (21/41) and 22.0% (9/41) achieved biochemical response and ALP normalization after 52 weeks. In continuous patients with baseline moderate-to-severe symptoms, mean (SE) changes to Week 130 in PFSF 7a and PBC WI NRS were -4.8 (1.5) and -4.0 (0.7). There were no unexpected safety findings. CONCLUSIONS:Through three years of treatment, elafibranor led to sustained biochemical improvements and was generally well tolerated, with numerical improvements in fatigue and pruritus. TRIAL REGISTRATION/BACKGROUND:NCT04526665 (https://clinicaltrials.gov/study/NCT04526665); first registered 08/26/2020 IMPACT AND IMPLICATIONS: • Given the chronic, progressive nature of primary biliary cholangitis (PBC), the long-term efficacy and tolerability of treatments is important.• Here, we present two-year results from the double-blind period, and long-term data from the ongoing open-label extension of the phase III ELATIVE® trial, wherein elafibranor (a peroxisome proliferator-activated receptor-α/δ agonist) treatment led to sustained biochemical improvements, stable non-invasive tests of fibrosis, and numerical improvements in fatigue and pruritus, through three years.• Elafibranor demonstrated a favorable safety profile up to a maximum treatment exposure of 3.5 years, including in patients crossing over from placebo.• These findings support elafibranor's role as a durable long-term treatment for patients with PBC, and are particularly relevant for clinicians managing patients with inadequate response or intolerance to first-line treatments.

BACKGROUND:Colorectal cancer (CRC) outcomes vary by both race and ethnicity, and screening test use may contribute to this variation. We examined the association of race, ethnicity, and associated factors with CRC screening test use in a setting where financial barriers to screening are mitigated. METHODS:Survey information was gathered from US Veteran participants (N = 50,125) when enrolled into a randomized trial comparing screening colonoscopy to annual fecal immunochemical testing (FIT) in the prevention of CRC mortality. The primary exposures of interest were the participants' self-identified race and ethnicity, with adjustment for variables capturing access to care. Multivariable logistic regression, stratified by site and age, was used to assess the relationship between exposures of interest and prior use of any CRC screening test, prior colonoscopy, and prior fecal occult blood test (FOBT, including FIT) use. RESULTS:Screening test use was common (N = 28,330, 56.5%) with more Veterans reporting prior FOBT (N = 20,386, 40.7%) than prior colonoscopy (N = 12,671, 25.3%). In multivariable analysis, Black participants were more likely (odds ratio (OR), 1.06; 95% confidence interval (CI) 1.01-1.12) to have had any prior screening relative to White persons and this finding was driven by more frequent FOBT use relative to White persons (OR, 1.16; 95% CI 1.10-1.23). There was no association between Hispanic ethnicity (relative to White persons) on the primary outcomes. CONCLUSIONS:In this cohort, prior screening test use was common, with observed variation in overall test use by race, but not ethnicity. Further study of CRC screening test use in diverse populations are needed. CLINICALTRIALS.GOV ID/BACKGROUND:NCT#05612347.

Adequate bowel preparation is critical to the effectiveness of colonoscopy. Bowel preparations have evolved over the years and now there are many options available to patients. These options fall into three categories of regular volume, low-volume and ultra-low volume preparations. It is important to select a preparation that maximises patient adherence and improves patient experience.

BACKGROUND AND AIMS/OBJECTIVE:Incomplete resection of colorectal polyps can lead to polyp recurrence and post-colonoscopy colorectal cancer. At present, standardized methods for assessing resection completeness and calculating the incomplete resection rate (IRR) are lacking. This study aimed to establish expert consensus on optimal strategies and protocols for standardized evaluation of resection completeness for resections of polyps <20 mm in size. METHODS:An international modified Delphi consensus process consisting of three rounds of anonymized surveys was conducted. A total of 103 gastrointestinal endoscopy experts were invited. Agreement was defined as consensus among >80% of participants for each statement. Based on expert consensus, standardized assessment protocols were established for daily clinical practice, and for quality assurance and research. RESULTS:Sixty-seven experts from 18 countries participated, with 53 (51%) from 16 countries completing all three rounds. Consensus was achieved for 18 of 20 (90%) statements after three rounds. Key agreements included: (1) primary assessment of resection completeness using high-definition white-light inspection, supplemented by image-enhanced inspection for polyps 10-19 mm; (2) routine post-resection photo documentation for polyps 10-19 mm; (3) standard histopathological margin assessment for all non-fragmented and en bloc resected polyps; (4) preferential IRR measurement using extended margin resection; and (5) the need for endoscopists to know and monitor their personal IRR for polyps 10-19 mm. CONCLUSION/CONCLUSIONS:This study presents international expert consensus on evaluation of resection completeness for colorectal polyps <20 mm in size. Provided recommendations could guide more consistent and standardized evaluation of polyp resections and support establishment of the IRR as a valuable quality parameter for colonoscopy.

BACKGROUND AIMS/UNASSIGNED:AHB-137 is a novel ASO targeting a conserved region near the 3' end of all HBV mRNA. This first-in-human phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and antiviral efficacy in healthy subjects and chronic hepatitis B (CHB) patients. METHODS:Forty healthy subjects were randomized into four placebo-controlled single ascending dose (100-450 mg, 6:2 AHB-137:placebo) cohorts and one multiple-dose (MD; 300 mg, 6:2) cohort receiving four weekly subcutaneous doses with a Day 4 loading dose (5 doses). Twenty-four virally suppressed, HBeAg-negative CHB patients on stable nucleos(t)ide analogue therapy were enrolled: four in an open-label 300-mg MD cohort (5 doses) and 20 in two placebo-controlled 300-mg MD cohorts (4:1, stratified by baseline HBsAg), receiving an additional loading dose on Day 11 (6 doses). RESULTS:Treatment-related adverse events occurred in 73% of healthy subjects and 71% of CHB patients and were primarily mild or moderate injection-site reactions and headaches. No treatment-related serious adverse events, discontinuations, or deaths were observed. PK profiles showed rapid absorption (Tmax 2.96-5.50 h), dose-proportional exposure, no significant accumulation, long terminal half-life (150-220 h), and minimal renal excretion. In CHB patients, AHB-137 treatment led to a rapid HBsAg decline (mean 0.7-1.0 log10 IU/mL). HBsAg loss (<0.05 IU/mL) for at least one timepoint was observed in three patients, including two with baseline HBsAg <1 IU/mL and one with baseline HBsAg <1.5 IU/mL. CONCLUSIONS:In this Phase 1 study, AHB-137 demonstrated an acceptable safety profile, predictable PK, and rapid and prolonged HBsAg reductions, supporting further evaluation of dosing and treatment duration in CHB.

Colonoscopy is the most widely performed endoscopic procedures in the United States and considered as primary screening and surveillance modality for colorectal cancer (CRC) prevention. Effective screening and surveillance requires prompt recognition of colorectal polyps, optical diagnosis of predicted histology and safe and effective polypectomy. We aim to perform a comprehensive review of the current evidence on tools and techniques to improve polyp detection and best practices to optimize endoscopic removal. Utilization of water assisted colonoscopy, artificial intelligence (AI), image enhanced endoscopy (IEE) and distal attachment devices can improve polyp detection. Underwater endoscopic mucosal resection (EMR) has emerged as a popular technique with potentially better outcomes than conventional EMR. Modification of EMR techniques including tip-in EMR and pre-cutting EMR have also been summarized. Endoscopic full thickness resection (EFTR) is an emerging technique other than endoscopic submucosal dissection (ESD) for suitable lesions harboring early submucosal cancer. Further, we also outline the common adverse events associated with polypectomy including bleeding, perforation, post-polypectomy syndrome, and discuss preventative measures to mitigate these adverse events. Eventually, the goal of colonoscopy is to reduce interval CRC incidence and mortality, and the technology that reduces post colonoscopy CRC incidence and techniques that improve safety and recurrence would see earlier adoption in the real world practice.

BACKGROUND/UNASSIGNED:Complications such as intermittent pouchitis (IP) and chronic inflammatory disorders of the pouch (CP) are common after ileal pouch-anal anastomosis (IPAA), particularly among patients with both ulcerative colitis and primary sclerosing cholangitis (PSC). There are no standardized approaches for prophylaxis against these complications for patients with PSC undergoing IPAA. We compared outcomes among patients with PSC and IPAA who received antibiotic or immunosuppressive therapies to those who did not. METHODS/UNASSIGNED:We designed a retrospective cohort study that included patients with ulcerative colitis and PSC from 7 tertiary care centers that underwent IPAA between 1994 and 2023. Patients were categorized on whether they received medications following IPAA that may provide primary prophylactic benefit, such as antibiotics, probiotics, immunomodulators, or biologic medications; and the proportion of patients developing IP and CP was evaluated. RESULTS/UNASSIGNED: = 0.04; OR 0.24, 95% CI, 0.06-0.89). CONCLUSIONS/UNASSIGNED:In this retrospective cohort of patients with ulcerative colitis and PSC undergoing IPAA, usage of concomitant antibiotics or immunosuppression was low. However, use of concomitant antibiotics or immunosuppression may decrease the burden of inflammatory conditions of the pouch in these high-risk patients.