Publications

Corticosteroids are one of the most frequently prescribed medications for the management of inflammatory bowel disease. While corticosteroids have a critical role for select cases for induction of remission, there is a notable risk of over-use and miss-use of corticosteroids. This narrative review updates the evolving use of corticosteroids in the management of inflammatory bowel disease. The review focuses on the appropriate use, route of administration and duration for the use of corticosteroids. Additionally, this review summarizes the side effects, use of steroids in special populations (e.g. geriatrics, pregnancy, underrepresented minorities), and their use in the peri-operative setting.

Autoimmune hepatitis (AIH) is an organ-specific autoimmune disorder mainly affecting females and characterized by seropositivity for autoantibodies, hypergammaglobulinemia, and histological evidence of interface hepatitis. Liver damage in AIH is perpetrated by multiple immune cell subsets, including B, T lymphocytes, and macrophages. Dysfunction of regulatory T cells (Tregs), an immune subset central to immunotolerance, plays an important permissive role by enabling effector lymphocytes to act unopposed and perpetuate autoimmune liver injury. Corticosteroids and azathioprine are the mainstay of treatment, resulting in disease remission in 80-90% of cases. Second- and third-line treatment, including mycophenolate mofetil, calcineurin inhibitors, and anti-B lymphocyte strategies, are used in difficult-to-treat cases or intolerant patients. Although controlling inflammation, these immunosuppressants are associated with significant side effects that impact patients' quality of life and adherence to treatment and, importantly, do not enable immune tolerance reconstitution. Strategies based on adoptive transfer of or ex vivo expansion of Tregs would enable limiting effector cell immunity while reconstituting immune tolerance. Additional studies into the mechanisms resulting in Treg dysfunction at both systemic and tissue levels are warranted to engineer more potent, stable, and long-lasting Tregs to be used in immunotherapy. Restoring Treg pool would be a key step forward toward the cure of this autoimmune condition and other autoimmune diseases with similar pathogenesis.

BACKGROUND: Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients.

METHODS: Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy.

RESULTS: Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported.

CONCLUSION: Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

BACKGROUND AND AIMS: Endoscopic-related injuries (ERIs) for gastroenterologists are common and can impact longevity of an endoscopic career. This study examines sex differences in the prevalence of ERIs and ergonomic training during gastroenterology fellowship.

METHODS: A 56-item anonymous survey was sent to 709 general and advanced endoscopy gastroenterology fellows at 73 U.S. training programs between May and June 2022. Demographic information was collected along with questions related to endoscopic environment, ergonomic instruction, technique, equipment availability, and ergonomic knowledge. Responses of female and male gastroenterology fellows were compared using χ2 and Fisher exact tests.

RESULTS: Of the 236 respondents (response rate, 33.9%), 113 (44.5%) were women and 123 (52.1%) were men. Female fellows reported on average smaller hand sizes and shorter heights. More female fellows reported endoscopic equipment was not ergonomically optimized for their use. Additionally, more female fellows voiced preference for same-gender teachers and access to dial extenders and well-fitting lead aprons. High rates of postendoscopy pain were reported by both sexes, with significantly more women experiencing neck and shoulder pain. Trainees of both sexes demonstrated poor ergonomic awareness with an average score of 68% on a 5-point knowledge-based assessment.

CONCLUSIONS: Physical differences exist between male and female trainees, and current endoscopic equipment may not be optimized for smaller hand sizes. This study highlights the urgent need for formal ergonomic training for trainees and trainers with consideration of stature and hand size to enhance safety, comfort, and equity in the training and practice of endoscopy.

BACKGROUND: The relationship between subcutaneous infliximab [SC-IFX] concentrations and favourable therapeutic outcomes in patients with Crohn's disease [CD] and ulcerative colitis [UC] remains elusive.

PATIENTS AND METHODS: This cross-sectional study included consecutive adult patients with inflammatory bowel disease [IBD] treated with SC-IFX at a maintenance dose of 120 mg/2 weeks. Investigated therapeutic outcomes included sustained clinical remission; composite clinical and biomarker remission [clinical remission and C-reactive protein <5 mg/L]; biochemical remission [faecal calprotectin <250 µg/g]; and deep remission [clinical, biological, and biochemical remission].

RESULTS: Of 91 patients identified, 71 qualified for inclusion in the study [70% with CD; 27% with concomitant immunomodulators]. At the time of drug concentration measurement [median 13.5 months after switch], 55 [77%] patients had sustained clinical remission; n = 44 [62%] composite clinical and biomarker remission; n = 40 [56%] biochemical remission; and n = 31 [43%] deep remission. The mean SC-IFX concentrations were significantly higher in patients with sustained clinical remission [p = 0.014]; composite clinical and biomarker remission [p = 0.003]; biochemical remission [p < 0.001]; and deep remission [p < 0.001] compared to patients without having these outcomes. In multivariate analysis, SC-IFX concentration was the only factor independently associated with sustained clinical remission (odds ratio [OR]: 4.7, 95% confidence interval [CI]: 3.1-12.2, p = 0.005); clinical and biomarker remission [OR: 9.21, 95% CI: 6.09-18.7, p = 0.006]; biochemical remission [OR: 37, 95% CI: 14-39.3, p < 0.001]; and deep remission [OR: 29, 95% CI: 15.7-37.4, p < 0.001]. The optimal SC-IFX concentration cut-off associated with deep remission based on ROC analysis was 20 µg/mL [sensitivity: 0.91, specificity: 0.80, accuracy: 0.85]. Combination with an immunomodulator failed to improve SC-IFX pharmacokinetics.

CONCLUSION: Higher SC-IFX concentrations are associated with higher rates of favourable therapeutic outcomes in IBD patients. Serum SC-IFX concentrations >20 µg/mL were significantly associated with deep remission.

BACKGROUND/AIMS: Clinical guidelines should ideally be formulated from data representative of the population they are applicable to; however, historically, studies have disproportionally enrolled non-Hispanic White (NHW) patients, leading to potential inequities in care for minority groups. Our study aims to evaluate the extent to which racial minorities were represented in the United States Colorectal Cancer Surveillance Guidelines.

METHODS: We reviewed US guidelines between 1997 and 2020 and all identified studies cited by recommendations for surveillance after a baseline colonoscopy with no polyps, adenomas, sessile serrated polyps, and hyperplastic polyps. We analyzed the proportion of studies reporting race, and among these studies, we calculated the racial distribution of patients and compared the proportion of Non-NHW patients between each subtype.

RESULTS: For all guidelines, we reviewed 75 studies encompassing 9,309,955 patients. Race was reported in 24% of studies and 14% of total patients. Non-NHW comprised 43% of patients in studies for normal colonoscopies, compared with 9% for adenomas, 22% for sessile serrated polyps, and 15% for hyperplastic polyps. For the 2020 guidelines, we reviewed 33 studies encompassing 5,930,722 patients. Race was reported in 15% of studies and 21% of total patients. Non-NHW comprised 43% of patients in studies for normal colonoscopies, compared with 9% for tubular adenomas. Race was not cited for any other 2020 guideline.

CONCLUSION: Racial minorities are significantly underrepresented in US Colorectal Cancer Surveillance Guidelines, which may contribute to disparities in care. Future studies should prioritize enrolling a diverse patient population to provide data that accurately reflects their population.

BACKGROUND: Rectal bleeding is the most common presenting symptom of colorectal cancer, and guidelines recommend timely follow-up, usually with colonoscopy to ensure timely diagnoses of colorectal cancer.

OBJECTIVE: Identify loop closure rates and vulnerable process points for patients with rectal bleeding.

DESIGN: Retrospective cohort study, using medical record review of patients aged ≥ 40 with index diagnosis of rectal bleeding at 2 primary practices-an urban academic practice and affiliated community health center, between January 1, 2018, and December 31, 2020. Patients were classified as having completed recommended follow-up workup ("closed loop") vs. not ("open loop"). Open loop patient cases were categorized into six types of process failures.

PARTICIPANTS: A total of 837 patients had coded diagnoses of rectal bleeding within study window. Sixty-seven were excluded based on prior colectomy, clinical presentation more consistent with upper GI bleed, no rectal bleeding documented on chart review, or expired during the follow-up period, leaving 770 patients included.

MAIN MEASURES: Primary outcomes were percentages of patient cases classified as "open loops" and distribution of these cases into six categories of process failure that were identified.

KEY RESULTS: 22.3% of patients (N = 172) failed to undergo timely recommended workup for rectal bleeding. Largest failure categories were patients for whom no procedure was ordered (N = 62, 36%), followed by patients with procedures ordered but never scheduled (N = 44, 26%) or scheduled but subsequently cancelled or not kept (N = 31, 18%). While open loops increased after the onset of the COVID-19 pandemic, this difference was not significant within our study period.

CONCLUSIONS: Significant numbers of patients presenting to primary care with rectal bleeding fail to undergo recommended workup. The majority either have no procedure ordered, or procedure ordered but never scheduled or cancelled and not kept, suggesting these are important failure modes to target in future interventions. Ensuring reliable ordering and processes for timely scheduling and completion of procedures represent critical areas for improving the diagnostic process for patients with rectal bleeding in primary care.