A Case of a Beta-Catenin-Activated Hepatic Adenoma in a Male Patient With Familial Adenomatous Polyposis.

Hepatocellular adenoma is a benign liver tumor often diagnosed incidentally in women of reproductive age who are taking oral contraceptives. In this study, we present a unique case of an 18-year-old man with known familial adenomatous polyposis who presented with sepsis in the setting of a recent total proctocolectomy and was incidentally found to have multiple large hepatic lesions. A biopsy of a liver lesion confirmed the diagnosis of a beta-catenin-activated hepatic adenoma. To the best of our knowledge, this is the first known case of beta-catenin-activated hepatic adenoma in a patient with a known familial adenomatous polyposis mutation. Beta-catenin is one of the many subtypes of hepatocellular adenomas, which carries a high risk of malignant transformation.

Hormone Replacement Therapy Is Associated with Disease Activity Improvement among Post-Menopausal Women with Inflammatory Bowel Disease.

(1) Background: There are limited data available to guide clinical decision-making regarding the effects of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize a population of post-menopausal women with IBD and to determine the effects of HRT on their disease activity. (2) Methods: A multicenter, retrospective, case-control cohort study of post-menopausal women with IBD was conducted. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. (3) Results: There was a significant reduction in the frequency of PGA scores ≥2 post HRT treatment (p < 0.01). HRT treatment was associated with a 5.6× increase in the odds of post-HRT PGA score improvement compared to controls (OR 5.6; 95% CL 1.6, 19.7) in our univariate logistic regression analysis. (4) Conclusion: Post-menopausal IBD women who underwent HRT therapy showed an improvement in their disease symptoms following HRT compared to post-menopausal women without HRT therapy, who showed no change.

Unusual case of amyloidosis presenting as a jejunal mass.

Amyloidosis constitutes a heterogeneous group of disorders of protein misfolding that can involve different organ systems. The disease can occur either in a systemic or localised manner that is well known to involve the gastrointestinal (GI) tract. GI amyloidosis can present with a wide range of symptoms including diarrhoea, bleeding and obstruction. This case illustrates a patient with localised jejunal amyloid light chain disease that was diagnosed serendipitously during a workup for haematuria. Our patient was otherwise asymptomatic, but this case underscores the importance of considering amyloidosis as a possible cause of isolated masses of the small intestine.

P041 Successful Reduction in Opioid Prescription for IBD Flare in the Emergency Department: A Retrospective Study and Quality Improvement Initiative.

BACKGROUND: Opioid use is associated with increased mortality, emergency department (ED) utilization, 30-day readmission rates and decreased quality-of-life in patients with inflammatory bowel disease (IBD). Opioid use in the ED for acute IBD presentations has not been well characterized in the literature. Safe, evidence-based, and effective pain management guidance for IBD flares is needed to promote opioid stewardship in the ED. METHODS: We performed a retrospective cohort study of adult patients who presented to an academic tertiary center ED with IBD flares from June 2019 through December 2019. Demographic and disease specific information and ED course, including analgesic use and numeric rating pain scores at ED presentation and discharge, were collected from the medical record. We designed and implemented a multimodal quality improvement intervention consisting of an evidenced-based IBD pain guideline, customized electronic health record order-set, Gastroenterology (GI) consult note smart-phrase and clinician education to promote opioid stewardship. The impact of our intervention was measured with a repeat retrospective analysis from December 2020 through April 2021. Run charts were generated to correlate the timing of interventions to changes in opioid exposure and prescription. RESULTS: Seventy-one patients were included in the pre-intervention cohort. A total of 78% of patients who presented to the ED with IBD flare were prescribed opioid(s) with an average of 29.3 morphine milligram equivalence (MME) per ED stay. Approximately half (49%) of patients did not receive any non-opioid analgesic and 13% patients received an opioid prescription at ED or hospital discharge. In the post-intervention cohort consisting of 49 patients, there was a significant reduction in the proportion of patients receiving opioids (45% vs. 78%; p < 0.001) and a significant reduction in the average total opioid administration (10.8 vs. 22.6 MME; p < 0.001). For each month during the post-intervention period, the proportion of patients who received an opioid in the ED and the average total opioid administered remained less than the median of the entire study period, which represents a nonrandom pattern. The use of a non-opioid analgesic, IV acetaminophen, was significantly increased (27% vs 3%; p < 0.001) and the risk of new or recurrent gastrointestinal bleeding was negligible in both cohorts (0% vs. 1%; p = 1.0). There was no significant difference between the average pain score (4.9 vs. 5.4 [10-point-scale]; p=0.440) and the difference between reported triage and final ED pain scores (-1.8 vs. -2.0; p=0.729). Furthermore, there was a significant reduction in GI consultation (35% vs. 58%; p <0.016) and a non-significant reduction in hospital admission (63% vs. 80%; p=0.058). CONCLUSION: Almost 80% of patients who present to ED with IBD flare are prescribed opioids, while only half of patients receive non-opioid analgesics. Also concerning was the high rate of opioid prescription at ED or hospital discharge. A multimodal intervention successfully reduced the proportion and amount of opioid prescribing in the ED without compromising pain control or increasing the risk of GI bleeding. This was also associated with a significant increase in a non-opioid analgesic administration and a significant decrease in GI service consultation. These findings support the role of implementing an evidence-based IBD pain management guideline with electronic prescribing support and education in the ED setting for acute IBD flares. Additional research is needed to determine long-term benefits of reduced opioid exposure in this population.

Microscopic Colitis Is Not an Independent Risk Factor for Low Bone Density.

BACKGROUND: Microscopic colitis (MC) is a subtype of inflammatory bowel disease (IBD) with overlapping risk factors for low bone density (LBD). While LBD is a known complication of IBD, its association with MC is not well-established. AIMS: Assess the prevalence of LBD in MC compared to control populations, and evaluate if MC predicts LBD when controlling for confounders. METHODS: Retrospective, observational case control study of adult patients with pathologically confirmed MC from 2005 to 2015. Bone density measurements were abstracted from dual-energy X-ray absorptiometry (DEXA) reports, and bone density was classified using T-score: normal (T ≥ - 1.0), osteopenia (- 1.0 > T > -2.5) or osteoporosis (T ≤ - 2.5). Demographics, disease, medication history and LBD risk factors were obtained from chart review. Prevalence of LBD was compared to national and local controls. A matched control cohort to MC patients without prior diagnosis of LBD was analyzed with logistic regression to assess the relationship of MC to LBD. RESULTS: One hundred and eighteen patients with MC were identified. Osteopenia in women with MC was more prevalent compared to national controls (67% vs. 49%, p = 0.0004), and LBD was more prevalent in MC patients compared to local controls (82% vs. 55%, p < 0.0001). In MC patients without prior diagnosis of LBD matched to controls, there was a higher prevalence of osteopenia (53.2% vs. 36.7%, p = 0.04). However, after controlling for confounders, MC was not associated with LBD (OR 0.83, 95% CI 0.22, 3.16, p = 0.8). CONCLUSIONS: While LBD was more prevalent in MC patients compared to control populations, with adjustment for key confounders (including BMI, steroids, smoking, vitamin D and calcium use), MC was not an independent predictor of LBD.

Vedolizumab Serum Trough Concentrations and Response to Dose Escalation in Inflammatory Bowel Disease.

Serum vedolizumab concentrations are associated with clinical response although, it is unknown if vedolizumab concentrations predict response to dose escalation. The aim of this study was to identify if vedolizumab trough concentrations predicted the response to vedolizumab dose escalation. We assessed a retrospective cohort of patients on maintenance vedolizumab dosing at five tertiary care centers with vedolizumab trough concentrations. Multivariate logistic regression was used to control for potential confounders of association of vedolizumab concentration and clinical status. Those who underwent a dose escalation were further examined to assess if vedolizumab trough concentration predicted the subsequent response. One hundred ninety-two patients were included. On multivariate analysis, vedolizumab trough concentration (p = 0.03) and the use of immunomodulator (p = 0.006) were associated with clinical remission. Receiver operator curve analysis identified a cut off of 7.4 µg/mL for clinical remission. Of the fifty-eight patients with dose escalated, 74% of those with a vedolizumab concentration <7.4 µg/mL responded versus 52% of those with a vedolizumab trough concentration ≥7.4 µg/mL (p = 0.08). After adjustment for relevant confounders, the odds ratio for response with vedolizumab concentration <7.4 µg/mL was 3.7 (95% CI, 1.1-13; p = 0.04). Vedolizumab trough concentration are associated with clinical status and can identify individuals likely to respond to dose escalation. However, a substantial portion of patients above the identified cut off still had a positive response. Vedolizumab trough concentration is a potentially helpful factor in determining the need for dose escalation in patients losing response.

Increased contrast enhancing lesion activity in relapsing-remitting multiple sclerosis migraine patients.

BACKGROUND AND OBJECTIVES: While the literature supports the idea that multiple sclerosis (MS) and migraine are related, the exact mechanism(s) of this association is not well understood. Observations of increased contrast enhancing (CE) lesion activity in individual MS patients suffering from migraine prompted us to determine a relationship between migraine and MRI outcomes in a large cohort of MS patients. METHODS: We included 509 MS and 64 clinically isolated syndrome (CIS) patients and 251 age- and sex-matched healthy individuals (HIs) who obtained 3 T MRI and were assessed for history of migraine. Number and volume of T2, T1 and CE lesions and brain volume measures were determined. The MRI findings were analyzed adjusting for key covariates and correcting for multiple comparisons. RESULTS: More MS (22.2%) and CIS (17.2%) patients had migraine, compared to HIs (14.6%, p = 0.067). More MS patients with migraine presented with CE lesions compared to those without (35.4% vs. 23.7%, p = 0.013). MS migraine patients had significantly increased number (p = 0.019) and volume (p = 0.022) of CE lesions compared to those without. In the regression analysis, MS migraine patients had an increased number of CE lesions (B = 1.242, p = 0.001), specifically those with relapsing-remitting disease course (B = 1.377, p = 0.001). No significant association of other MRI measures and migraine was found in MS and CIS patients or in HIs. CONCLUSIONS: Our findings suggest an increased inflammatory pathobiology in MS patients with migraine headaches requiring possibly more frequent MRIs and also more efficient anti-inflammatory treatment.

Increased seroreactivity to human T cell lymphoma/leukemia virus-related endogenous sequence-1 Gag peptides in patients with human T cell lymphoma/leukemia virus myelopathy.

Previously, we had shown that although only 8% of patients with large granular lymphocytic leukemia (LGLL) were infected with human T cell lymphoma/leukemia virus (HTLV)-2, almost half had antibodies to HTLV Gag and Env peptides. Herein, we investigated whether this could be due to cross-reactive antibodies to two homologous peptides in the Gag protein of the endogenous retrovirus HTLV-related endogenous sequence-1 (HRES-1). In addition, we had previously shown that patients with HTLV neurodegenerative diseases had increased seroreactivity to homologous HERV-K10 endogenous retrovirus peptides. Hence, in this study we also examined whether these patients had increased seroreactivity to the aforementioned HRES-1 Gag peptides. Sera from 100 volunteer blood donors (VBD), 53 patients with LGLL, 74 subjects with HTLV-1 or 2 infection (58 nonmyelopathy and 16 myelopathy), and 83 patients with multiple sclerosis (MS) were evaluated. The HTLV-positive myelopathy (HAM) patients had a statistically increased prevalence of antibodies to both HRES-1 Gag peptides (81%) vs. the VBD (0%), LGLL patients (13%), and MS patients (1%), and the HTLV-positive nonmyelopathy subjects (21%). The data suggest that cross-reactivity to HRES-1 peptides could be involved in the pathogenesis of HAM. The difference between the VBD and LGLL patients was also statistically significant, also suggesting a possible association in a minority of patients.

Increased seroreactivity to HERV-K10 peptides in patients with HTLV myelopathy.

BACKGROUND: Previously, we had shown that persons infected with human T-cell lymphoma leukemia virus 1 or 2 (HTLV-1 or 2) had an increased prevalence of antibodies to a peptide in the Pol protein of the retrovirus HERV-K10, homologous to a peptide in HTLV gp21 envelope protein. The prevalence rate was higher in those with myelopathy vs. non-myelopathy. We have now extended our observations to a cohort restricted to North America in whom the diagnosis of HTLV myelopathy was rigorously confirmed to also test for reactivity to another HERV-K10 peptide homologous to the HTLV p24 Gag protein. METHODS: Sera from 100 volunteer blood donors (VBD), 53 patients with large granular lymphocytic leukemia (LGLL), 74 subjects with HTLV-1 or 2 infection (58 non-myelopathy and 16 myelopathy) and 83 patients with multiple sclerosis (MS) were evaluated in ELISA assays using the above peptides. RESULTS: The HTLV myelopathy patients had a statistically significant increased prevalence of antibodies to both HERV-K10 peptides (87.5%) vs. the VBD (0%), LGLL patients (0%), MS patients (4.8%), and the HTLV positive non-myelopathy subjects (5.2%). CONCLUSION: The data suggest that immuno-cross-reactivity to HERV-K10 peptides and/or transactivation of HERV-K10 expression by the HTLV Tax protein may be involved in the pathogenesis of HTLV-associated myelopathy/tropical spastic paraparesis and spastic ataxia.