Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease.

Background: Serum protein reflects albumin and globulin levels, both of which can be altered in inflammatory bowel disease (IBD). The implications of a high globulin fraction in IBD are unknown. We hypothesized that a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period. Methods: This was an observational study from a prospective IBD registry of a tertiary care center. High globulin fraction was defined as an elevated globulin level >4 g/dL. Data collected included patient demographics, medication exposures, quality-of-life scores, disease activity, emergency department visits, telephone calls, hospitalizations, and IBD-related surgeries over a 4-year period. Comparisons between patients with a high globulin fraction and those without were performed using Pearson's chi-squared, Student's and Mann-Whitney tests. Multivariate analyses were used to assess the relationship between high globulin fraction and healthcare utilization. Results: A total of 1767 IBD patients with a 4-year follow up were included: 53.5% female, mean age 48.4±15.1 years, and 65.4% with Crohn's disease. Of these patients, 446 (25.2%) presented with elevated globulin fraction. Patients with a high globulin fraction were more likely to be hospitalized during the study period. This result remained significant after multivariate analysis for both Crohn's disease patients and those with ulcerative colitis. Conclusion: A high globulin fraction is independently associated with greater disease severity and healthcare utilization in IBD patients, and may function as a routinely available biomarker of a more severe future disease trajectory.

A self-training teacher-student model with an automatic label grader for abdominal skeletal muscle segmentation.

Deep learning on a limited number of labels/annotations is a challenging task for medical imaging analysis. In this paper, we propose a novel self-training segmentation pipeline (Self-Seg in short) for segmenting skeletal muscle in CT images. Self-Seg starts with a small set of annotated images and then iteratively learns from unlabeled datasets to gradually improve the segmentation performance. Self-Seg follows a semi-supervised teacher-student learning scheme and there are two contributions: 1) we construct a self-attention UNet to improve segmentation over the classical UNet model, and 2) we implement an automatic label grader to implicitly incorporate medical knowledge for quality assurance of pseudo labels, from which good quality pseudo labels are identified to enhance learning of the segmentation model. We perform extensive experiments on three CT image datasets and show promising results on five evaluation settings, and we also compared our method to several baseline and related methods and achieved superior performance.

High Sugar-Sweetened Beverage Consumption Is Associated with Increased Health Care Utilization in Patients with Inflammatory Bowel Disease: A Multiyear, Prospective Analysis.

BACKGROUND: Dietary factors like sugar-sweetened beverage (SSB) consumption are known to influence disease course in a variety of illnesses; however, long-term outcomes are not well documented for inflammatory bowel disease. OBJECTIVE: Does high consumption of SSBs lead to high healthcare utilization (ie, hospitalizations and emergency department visits), inflammation, and disease severity in patients with inflammatory bowel disease? DESIGN: A prospective cohort study was conducted from 2015 to 2019. Patients enrolled in the discovery study cohort were followed for 3 years, whereas patients in the validation cohort were followed for 2 years. They underwent nutrition assessment and received routine care. Dietary intakes of SSBs and fiber were quantified by a validated, self-reported questionnaire. PARTICIPANTS/SETTING: For the discovery study cohort, 1133 adult patients were recruited from the University of Pittsburgh Medical Center Digestive Disease Clinic in Pittsburgh, PA. Eligible patients had a preexisting diagnosis of Crohn's disease or ulcerative colitis and had at least annual follow-up at this tertiary referral center. High SSB consumption was defined as 7 or more SSBs per week. Moderate was defined as > 2 but < 7 SSBs per week. Low SSB consumption was defined as 2 or fewer SSBs per week. MAIN OUTCOME MEASURES: Primary outcome was time to hospitalization and emergency department visits. Secondary outcomes assessed laboratory markers of disease severity and inflammation. Tertiary outcomes assessed time to hospitalization and emergency department visits in a subsequent independent cohort of patients. STATISTICAL ANALYSIS PERFORMED: Multivariable logistic regression, Kaplan-Meier, and Cox proportional hazards modeling RESULTS: The discovery cohort included of 1,133 adult patients with inflammatory bowel disease (58% women, 70% with Chron's disease, 30% with ulcerative colitis, median age 46 years). Low SSB consumption, moderate SSB consumption, and high SSB consumption occurred in 57%, 17%, and 26% in the discovery cohort, respectively. Among patients without active disease at enrollment, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption (hazard ratio 1.55, 95% CI 1.06 to 2.27; and hazard ratio 1.53, 95% CI 1.10 to 2.13). In terms of disease severity and inflammatory biomarkers, high SSB consumption was associated with increase odds of elevated erythrocyte sedimentation rate (odds ratio 2.04, 95% CI 1.31 to 3.18), elevated C-reactive protein level (odds ratio 1.60, 95% CI, 1.07-2.37), eosinophilia (odds ratio 1.88, 95% CI 1.06 to 3.335), and monocytosis (odds ratio 1.81, 95% CI 1.18 to 2.79) when compared with low SSB consumption after adjusting for baseline differences. Lastly, the validation cohort produced similar results to our primary outcome (ie, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption). CONCLUSIONS: High SSB consumption was associated with decreased time to hospitalization and emergency department visits. Furthermore, high SSB consumption is associated with disease severity biomarkers and inflammation. Prospective studies assessing the therapeutic influence of nutrition counseling and decreased SSB consumption on long-term inflammatory bowel disease clinical course are warranted.

The Impact of Cholecystectomy on Long-Term Disease Outcomes and Quality of Life in Patients with Crohn's Disease.

BACKGROUND: Cholecystectomy (CCY) is one of the most frequently performed abdominal surgeries. However, the impact of CCY in clinical settings with altered gastrointestinal physiology and anatomy, such as Crohn's disease (CD), has not been fully characterized. We sought to investigate clinical outcomes, disease severity, and quality of life of CD patients after CCY. METHODS: We utilized a prospective, longitudinal registry of consented CD patients followed at a tertiary center. Crohn's disease patients that had or had not undergone CCY formed the 2 study groups. The absence or presence of gallbladder was confirmed with abdominal CT scans obtained during routine care. Multiyear clinical, biochemical, and histologic data were collected and analyzed. RESULTS: Among 834 CD patients, 151 (18%) had undergone CCY. History of CCY was associated with higher disease activity (median Harvey-Bradshaw index; P < 0.001), more years with anemia (P = 0.048), lower albumin (P = 0.001), worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P < 0.001), chronic abdominal pain (P < 0.001), higher risk for incident colonic dysplasia (P = 0.011), higher rates of annual hospital admissions (P = 0.004), and opioid use (P < 0.001). In multivariate analysis, CCY remained associated with higher disease activity (P < 0.001), lower albumin (P = 0.008), lower quality of life (P < 0.001), and more hospital admissions (P = 0.008), whereas CD patients with diseased ileum had higher risk for colonic dysplasia (P = 0.031). CONCLUSIONS: CCY in CD patients was associated with multiple markers of disease activity and worse quality of life during multiyear follow up. This data suggests that CCY in CD patients may adversely impact the long-term clinical course.

Serum IgG4 Subclass Deficiency Defines a Distinct, Commonly Encountered, Severe Inflammatory Bowel Disease Subtype.

BACKGROUND: Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. METHODS: We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels. RESULTS: We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals. CONCLUSIONS: An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.