Inflammatory Bowel Disease (IBD) is a chronic, idiopathic autoimmune disease characterized by the inflammation of the GI tract. The main subcategories of IBD include Crohn Disease (CD), ulcerative colitis (UC), and Indeterminate Colitis (IC). Currently, IBD is diagnosed and evaluated using clinical, endoscopic, biochemical, and histologic measures - which can be invasive and costly. Previous studies have shown that measurement of serum and fecal inflammatory biomarkers might be effective both for the assessment of intestinal infectious or inflammatory processes, as well as for gauging IBD disease activity. Inflammatory biomarkers investigated in this study include serum and fecal Anti-Saccharomyces-Cerevisiae Antibody (ASCA), serum and fecal lactoferrin, fecal calprotectin, fecal hemoglobin, IL1-𝛼, IL1-β, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). IMPACT-III questionnaires are utilized to measure the quality of life in enrolled subjects. Data collected in this study investigated the relationship between changes in serum and fecal biomarker levels, clinical disease activity, and the mental wellbeing of patients. The primary objective was to measure changes in inflammatory biomarker levels in patients with CD, UC, and IC after being treated with the anti-TNF therapy Infliximab (Remicade). The second objective is to study the relationship between changes in these biomarker levels and the clinical, biochemical, and endoscopic outcome parameters of IBD in patients. This is a multicenter, longitudinal, cohort study following 50 pediatric patients with IBD over the course of six Remicade infusion appointments. The project was conducted in partnership with Riley’s Children Hospital in Indianapolis. Patients with CD, UC, and IC were recruited for the study and stratified with respect to the temporal phase of their Remicade infusions, including: • Induction • Past induction, but less than 6 months • Those who have been receiving Remicade for over one year. A total of 58 eligible IBD patients are currently enrolled. 13 patients have withdrawn from the study, leaving 45 active patients: 27 CD, 17 UC, and 1 IC remaining in the prospective cohort. Patients provided serum and fecal samples and completed IMPACT-III questionnaires at the time of each Remicade infusion. Baseline serum ASCA levels were 0.014 ±0.029 OD from (n=15) patients with CD, 0.0083 ±0.022 OD in (n=12) patients with UC, and 0.002 OD in one patient with IC. Baseline fecal ASCA levels were 0.068 ±0.186 OD in (n=10) patients with CD, 0.0018 ±0.0013 OD in (n=9) patients with UC, and 0.001 OD in one patient with IC. At both baseline and at the time of the first infusion, CRP levels were significantly higher in patients with CD (p<0.05). At the time of the first infusion, the ESR in patients with CD was significantly higher than that in patients with UC (p<0.10). Serum lactoferrin was significantly higher in patients with UC at infusion 2 (p<0.05). ESR was significantly higher in patients with UC (p<0.10) at their fourth infusion. Our data support the hypothesis that serum and fecal biomarkers are useful in evaluating the response of intestinal inflammation to Remicade therapy. This study is ongoing, and further sample collection and data analysis are needed to more conclusively determine the accuracy of inflammatory biomarkers as a diagnostic tool for use in the diagnosis and interval assessment of patients with IBD.

INTRODUCTION Rheumatoid arthritis (RA) is a disease of chronic inflammation in the joints and organs. RA patients exhibit 4-fold increased incidence of CVD, increased prevalence of insulin resistance (IR) and increased mortality. Aerobic and resistance training (RT) programs have been suggested for the management of RA symptoms and reduction of comorbidities, including insulin resistance. Exercise has been shown by recent evidence to be safe and beneficial in RA patients. RT has been documented to improve inflammation and insulin sensitivity. The present study was undertaken to examine the impact of a sixteen week intensive training regimen on disease status, body composition, markers of inflammation and indicators of insulin resistance in RA patients undergoing infliximab therapy, a potent RA treatment.METHODS30 RA patients were randomized into exercise (EX) or control (C) groups. EX patients underwent a 16-week supervised, intensive, progressive and individualized resistance training regimen. Participants were monitored by professional fitness trainers during all exercise sessions. Subjects were assessed prior to and after intervention. Assessments included disease status, strength and functional testing, anthropometrical and body composition analysis, analysis of markers of inflammation and assessment of insulin sensitivity.RESULTS EX subjects significantly increased in strength and functional ability without worsening of disease state, and increased lean mass from baseline. Fat mass was significantly reduced in EX. Glucose and resistin levels increased significantly following EX intervention. Mean IR was unchanged, but EX subjects with elevated IR did show improvement following training. Regression analysis indicates duration of infliximab therapy to be correlated with improved insulin sensitivity.CONCLUSIONS RA patients taking infliximab tolerated an intensive resistance training program. Participants increased strength and lean mass while decreasing fat mass and displayed improved functional capacity. Disease status was not worsened by the regimen. Though the mean measure of IR did not improve, those patients with the most adverse scores did show improvement following the intervention. Furthermore, regression analysis indicates that infliximab treatment duration was linked to reduced IR. In conclusion, resistance training improved strength and functional ability in RA patients taking infliximab without disease degradation, and may help reduce IR in those patients with elevated resistance.

BACKGROUND: Patients who have been diagnosed with Inflammatory Bowel Disease (IBD) present with increased risk of deficient vitamin D levels. Previous studies have demonstrated that these IBD patients who live in areas with lack of sun exposure are especially susceptible to becoming vitamin D deficient. Studies have also shown that the standard vitamin D dosing protocols have not proven effective in consistently improving vitamin D status. This failure is likely related to a combination of under-dosing and patient noncompliance. Vitamin D sufficiency is essential in the maintenance of both skeletal health and the immune system in children and adolescents. OBJECTIVES: The primary aim of this study is to investigate the safety and efficacy of administering an interval, high dose oral vitamin D supplementation in pediatric patients with IBD treated with Remicade. A secondary aim is to study the association between changes in serum 25OHD (25-hydroxyvitamin D3) levels and clinical and biochemical markers of IBD. The findings from this study will provide preliminary data for future studies using serial measurements of serum 25OHD levels to better articulate the optimal dosage for interval vitamin D supplementation in pediatric patients with IBD. METHODS: We identified and screened pediatric patients with IBD at Boston Children’s Hospital (BCH) with vitamin D deficiency (serum 25OHD level < 30 ng/mL). Vitamin D dosing was determined by a patient’s Remicade interval. Patients received either 50,000 international units (IU) of vitamin D3 (every 4-5 weeks) or 100,000 IU of vitamin D3 (every 6-8 weeks), concurrent with their Remicade infusion interval. Longitudinal data, including anthropomorphic measurements, serum chemistry labs, spot urine calcium to creatinine ratios, quality of life metrics, and surveys gauging dietary vitamin D intake and sunlight exposure, were collected throughout the study. RESULTS: Baseline vitamin D status in the 60 enrolled patients did not differ by gender, dosing group, diet, or diagnosis (Crohn disease, ulcerative colitis, or indeterminate colitis). Of the 57 patients for whom baseline and final serum 25OHD levels were available, there was a significant increase in total serum 25OHD levels from 22.53 ± 4.65 ng/mL to 29.91 ± 6.60 ng/mL, respectively. Similarly, increases in mean serum 25OHD levels were noted in both dosing formats and disease groups. Interestingly, there was no significant parallel impact of increased 25OHD levels on either disease activity or quality of life. There were no significant changes in serum calcium, phosphorous, and creatinine levels in response to changes in 25OHD levels. There were no reports of significant adverse events related to vitamin D supplementation. CONCLUSION: High dose, interval vitamin D supplementation improved vitamin D status from baseline in a majority of studied pediatric patients with IBD. The data suggest that this type of interval, high dose format is likely more effective than more traditionally once-daily dosing. Further studies are necessary to determine the optimal dosage regimens optimal in further increasing vitamin D status and to assess for its impact on clinical management.