Citations

ABSTRACT Objective This study aimed to evaluate relationships between delayed gastric emptying and appetite suppression during treatment with liraglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA). Methods We conducted a secondary data analysis from a 16‐week randomized, placebo‐controlled liraglutide trial in patients with obesity. We examined correlations between solid food gastric emptying and measurements of satiation and energy intake in the entire cohorts at baseline and end of treatment and separately in placebo‐ and liraglutide‐treated patients who completed the trial. We also compared appetitive measures among liraglutide‐treated participants who displayed either normal, persistently delayed, or transiently delayed emptying during treatment. Results In the entire cohorts at baseline and completion, gastric emptying correlated significantly with energy intake and, at baseline, with one parameter of satiation. Gastric emptying accounted for only 4%–6% of the variance in these appetitive measures. No such correlations were found in the placebo‐ or liraglutide‐treated groups alone. There were no differences in appetitive measures among the subgroups that displayed different gastric emptying patterns during liraglutide treatment. Conclusions Delayed gastric emptying appears to play little direct role in appetite suppression induced by liraglutide. Further research should explore whether delayed emptying or other gastrointestinal effects of other GLP‐1RAs affect appetite directly or indirectly. Trial Registration: ClinicalTrials.gov identifier: NCT02647944

Abstract Introduction The aim of this case–control study was to determine if exposure to tumor necrosis factor alpha inhibitors (TNFIs) or immunomodulators (thiopurines or methotrexate) was associated with development of primary gastrointestinal lymphoma (PGIL) in patients with chronic inflammatory conditions. Methods Patients with PGIL and controls evaluated at a tertiary care center over 20 years were matched 1:3 using a medical record informatics search engine based on their chronic inflammatory condition (Crohn’s disease [CD], ulcerative colitis [UC], rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) and duration of follow-up. Patients who started on TNFI within 3 months of PGIL diagnosis were excluded. We extracted demographics, medical history, and medications used. Univariate models using conditional logistic regression were used due to the small number of matched pairs. Results Twenty PGIL cases matched with 60 controls were followed for a mean 9.9 ± 6.9 and 9.7 ± 8.6 years, respectively. Mean age at time of PGIL diagnosis was 47.5 ± 22.0 (standard deviation) years and the majority (75%) were males. The most common inflammatory diagnosis was inflammatory bowel disease (80% of cases; 45% with UC and 35% with CD). Development of PGIL was not associated with TNFI (odds ratio [OR] = 2.6; 95% confidence interval [CI] 0.69–11.01; P = .18), but with use of TNFI in combination with thiopurines (OR = 8.93; 95% CI 1.43–80.25; P = .014). Risk of PGIL increased with every additional TNFI (2.277 (1.002–5.713); P = .0494). All cases exposed to multiple TNFI were also exposed to thiopurines. Use of thiopurines (alone or in combination) was the greatest risk factor (OR = 6.32; 95% CI 1.55–37.05; P = 0.006) to develop PGIL. Conclusions TNFI therapy was not associated with increased risk for PGIL unless used in combination with thiopurines and with every switch to a different TNFI.

Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient’s quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. Conclusions: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.

Background: Obesity is on the rise within the inflammatory bowel disease population. The impact obesity has on the natural history of Crohn’s disease (CD) is not well-understood. We aimed to describe the prevalence of obesity in a population-based cohort of newly diagnosed patients with CD, and the impact obesity had on disease phenotype and outcomes of corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease. Materials and Methods: A chart review was performed on Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2010. Data were collected on demographics, body mass index, CD location and behavior, CD-related hospitalizations, corticosteroid use, and intestinal resection. The proportion of individuals considered obese at the time of CD diagnosis was evaluated over time, and CD-associated complications were assessed with Kaplan-Meier survival analysis. Results: We identified 334 individuals diagnosed with CD between 1970 and 2010, of whom 156 (46.7%) were either overweight (27.8%) or obese (18.9%) at the time of diagnosis. The proportion of patients considered obese at the time of their diagnosis of CD increased 2-3 fold over the course of the study period. However, obesity did not have a significant impact on the future risk of corticosteroid use, hospitalization, intestinal resection, or development of penetrating and stricturing complications. Conclusions: Obesity is on the rise in patients with CD, although in this cohort, there did not appear to be any negative association with future CD-related outcomes. Further prospective studies, ideally including obesity measures such as visceral adipose tissue assessment, are warranted to understand the implications of the rising prevalence of obesity on CD outcomes.

Background A gap remains in the role of neoadjuvant therapy for patients with ILC. Method Single-institution retrospective review of patients with ILC who received neoadjuvant therapy between 2008 and 2019. Results 141 patients met inclusion criteria: 71 neoadjuvant chemotherapy (NACT) and 70 neoadjuvant endocrine therapy (NET). 7/71 (9.9%) patients had a pCR following NACT compared to 1/70 (1.4%) with NET ( P = .063). pCR was observed in 5/18 (27.8%) patients with Her2Neu-positive disease following NACT, compared to 2/53 (3.8%) with Her2Neu-negative disease ( P = .01). For luminal B tumors, median Ki-67 decrease was similar following NACT and NET (18.3 vs 16.3, P = .26). T category decreased in 59 (42.1%) patients following neoadjuvant therapy, increased in 9 (6.4%), and was unchanged in 72 (51.4%). More patients had an increase (28.6%) than decrease (12.1%) in their N category, including 13/60 (21.7%) who were clinically node-negative at diagnosis and identified to have node-positive disease following neoadjuvant therapy, at definitive surgery. Conclusion In Her2Neu-negative ILC, the potential of a pCR with NACT or NET is low. Most patients’ nodal status and tumor size remain unchanged. There is a potential for pathologic stage to be higher at surgery compared to the clinical stage prior to neoadjuvant therapy.

INTRODUCTION: Outcomes and safety of budesonide maintenance therapy in microscopic colitis (MC) are not well known. METHODS: Adult residents of Olmsted County, Minnesota, diagnosed with MC (2002–2019) and treated with budesonide were identified using the Rochester Epidemiology Project. Response was assessed at 12 ± 4 weeks after initiation of therapy and defined as complete (resolution of diarrhea), partial (≥50% improvement in the number of bowel movements), nonresponse (<50% improvement), and intolerance (discontinued because of side effects). For safety outcomes, cases (budesonide maintenance) and MC controls (no budesonide therapy) were matched by sex and age at diagnosis (±2 years). RESULTS: A total of 450 patients were identified, of whom 162 (36.0%) were treated with budesonide for induction of clinical remission (median age 67 [23–91] years and 126 women [77.8%] ). Clinical outcomes for induction were as follows: 130 (80.2%) complete response, 22 (13.6%) partial response, 8 (4.9%) no response, and 2 (1.2%) intolerance. After induction, 96 (63.2%) had recurrence after discontinuation, of whom 27 (28.1%) required further budesonide induction treatment without maintenance, 56 (58.3%) required long-term budesonide maintenance, and 13 (13.5%) were treated with other therapies. Of those receiving budesonide maintenance, all responded (55 [98.2%] complete and 1 [1.8%] partial). No patient stopped maintenance from adverse events. The median duration of follow-up was 5.6 years (0.3–18.9). There was no significant difference between cases and controls in the incidence of osteopenia/osteoporosis, diabetes mellitus, hypertension, glaucoma, or cataracts. DISCUSSION: The long-term use of budesonide in MC seems to be effective and generally well tolerated with limited adverse effects.

Background. Early-onset gastric cancer (EOGC,age≤60years at diagnosis) now comprises >30% of new gastric cancers in the United States. It is hypothesized that chronic acid suppression with proton-pump inhibitors (PPIs) may promote tumorigenesis, while other medications including statins, nonsteroidal anti-inflammatory drugs (NSAIDs), metformin, and cyclooxygenase-2 (COX-2) inhibitors have been proposed as protective. We aimed to assess for an association between use of the aforementioned commonly prescribed medications and EOGC development. Methods. We used a population-based medical record linkage system, to identify cases of EOGC in Olmsted County, Minnesota, between January 1, 1995, and December 31, 2020. Patients were matched 1 : 1 with controls based on age at diagnosis, sex, smoking status, and body mass index (BMI). Conditional logistic regression was used to examine associations with the odds of EOGC development. Results. Ninety-six cases of EOGC were identified during the study period. On both univariate and multivariate regression analysis, there was no significant association between use of PPIs, statins, NSAIDs, or metformin and EOGC development. In a final multivariable model, there was a significant reduction in odds of EOGC with COX-2 inhibitor use for six months or more prior to cancer diagnosis (OR=0.39, 95% CI 0.16-0.94). Conclusion. In this retrospective, population-based study of individuals in Olmsted County, MN, we found significantly reduced odds of EOGC development associated with COX-2 inhibitor use for six months or more prior to diagnosis, but no association between EOGC development and use of PPIs and other commonly prescribed medications.

ABSTRACTObjectives:Excessive fecal bile acids in adults have been associated with diarrhea‐predominant irritable bowel syndrome (IBS‐D), but their role in pediatric IBS‐D is unknown. Serum markers including 7α‐hydroxy‐4‐cholesten‐3‐one (C4) and fibroblast growth factor‐19 (FGF‐19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48‐hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF–19 and 48FBA in a pediatric population, to compare measurements in IBS‐D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS‐D.Methods:Using a cross‐sectional design, 26 patients with IBS‐D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF‐19 and 48FBA were obtained. Participants completed a 7‐day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations.Results:Mean age was 14.7 ± 2.5 years (42.3% female) in IBS‐D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF‐19 (r = –0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF‐19 (P = 0.1), or 48FBA (P = 0.5) between IBS‐D and HC groups; however, 20% of IBS‐D patients had elevated C4 and 28% had low FGF‐19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002).Conclusions:Correlations of C4 with 48FBA and FGF‐19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS‐D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS‐D.

Abstract Background We sought to estimate the incidence of home parenteral nutrition (HPN) use in a population-based cohort of patients with Crohn disease (CD), and to assess clinical outcomes and complications associated with HPN. Methods We used the Rochester Epidemiology Project (REP) to identify residents of Olmsted County, who were diagnosed with CD between 1970 and 2011, and required HPN. Results Fourteen out of 429 patients (3.3%) with CD received HPN (86% female). Eleven patients (79%) had moderate–severe CD and 12 patients (86%) had fistulizing disease. Thirteen patients (93%) underwent surgery, primarily due to obstruction. Among CD incidence cases, the cumulative incidence of HPN from the date of CD diagnosis was 0% at 1 year, 0.5% at 5 years, 0.8% at 10 years, and 2.4% at 20 years. Indications for HPN included short bowel syndrome in 64%, malnutrition in 29%, and bowel rest in 21%. The median duration of HPN was 2.5 years. There was an average weight gain of 1.2 kg at 6 months, an average weight loss of 1.4 kg at 1 year, and a further weight loss of 2.2 kg at 2 years from the start of HPN. Patients were hospitalized a mean of 5 times after the start of HPN, mainly due to catheter-related bloodstream infections and thrombosis. Conclusions Less than 4% of patients with CD need HPN. Most have moderate to severe disease with short bowel syndrome or malnutrition. Possible reasons for the patients’ weight loss could be noncompliance, and increased metabolic needs because of active disease.