Abstract Background Ulcerative colitis (UC) is thought to arise from dysregulated immune responses due to intestinal dysbiosis and altered epithelial barrier function. Dietary components may affect the gut microbiome and contribute to either inflammation or its resolution. The relationship between diet and disease activity in UC warrants further investigation. Aims This prospective cohort study explored the relationship between dietary components, and markers of disease activity: fecal calprotectin (FCP) and partial Mayo score (PMS) in patients with UC. Methods 40 participants were recruited from University of Calgary IBD clinics. Study staff obtained two 24-hour diet recalls using the validated automated self administered (ASA)-24 and captured PMS at baseline (T1) and follow-up at week 12 (T2). FCP samples were collected at T1 and T2. Diet variables included adjusted macro/micronutrients (n=44), food groups (n=36) and the validated Canadian healthy eating index-2009 (CHEI) where higher scores reflect healthier intake. CHEI captures intake of dark green and orange foods (DGO) and moderation scoring (MOD) of saturated fats (SF), sodium and added sugars. Higher CHEI scores result from increased intake of DGO and lower intake of SF, sodium and added sugars (higher MOD score). Associations with outcome variables were examined at T1 and T2 individually and across both timepoints (BT). Mixed effect logistic regression models identified relationships between dietary variables, FCP and PMS. Models were adjusted for age, sex, BMI, medications, probiotics, and for repeated measures in both timepoint analyses. Results A positive association was identified between FCP as a continuous variable and SF (T1:Coef=0.22, p_adj=0.02) and a negative association identified between FCP with citrus/melon/berries (BT:Coef=-1.01, p_adj =0.04), total sugars (BT:Coef=-0.06, p_adj=0.025) and HEI (BT:Coef=-0.13, p_adj =0.06 and T1 coef=-0.18, p_adj =7.0 e-5). FCP increased as SF (-0.30,p_adj=0.01), DGO (-0.60, p_adj=0.02), and MOD (-0.21, p_adj=0.02) scores decreased. The presence of inflammation (as a binary variable, FCP >250) was negatively associated with higher fiber intake (BT: Odds Ratio (OR)= 0.016, CI(0.001,0.40) p_adj=0.08). For PMS as a continuous variable, HEI had a negative association with PMS (T2: -0.05, p_adj=0.06). With PMS as a discrete score (remission=PMS<2) there was no significant association with any diet components. Conclusions This study suggests that a healthier diet, both in overall pattern and specific dietary components, was associated with lower FCP and PMS. Our findings related to SF, citrus/melons/berries, and DGO parallel the IOIBD dietary guidelines. Future research should explore through controlled intervention studies whether modifying dietary patterns and components independently reduces disease activity. Funding Agencies Crohn’s and Colitis Foundation

Malnutrition is highly prevalent in inflammatory bowel disease (IBD) patients and disproportionately affects those admitted to hospital. Malnutrition is a risk factor for many complications in IBD, including prolonged hospitalization, infection, greater need for surgery, development of venous thromboembolism, post-operative complications, and mortality. Early screening for malnutrition and prompt nutrition intervention if indicated has been shown to prevent or mitigate many of these outlined risk factors. There are many causes of malnutrition in IBD including reduced oral food intake, medications, active inflammation, and prior surgical resections. Hospitalization can further compound pre-existing malnutrition through inappropriate diet restrictions, nil per os (NPO) for endoscopy and imaging, or partial bowel obstruction, resulting in “post-hospital syndrome” after discharge and readmission. The aim of this article is to inform clinicians of the prevalence and consequences of malnutrition in IBD, as well as available screening and assessment tools for diagnosis, and to offer an organized approach to the nutritional care of hospitalized adult IBD patients.

There is a high prevalence of malnutrition amongst hospitalized patients in Canada which is associated with poor outcomes including increased length of stay, readmission rates and mortality. Despite its ubiquity, malnutrition is often underdiagnosed and undertreated which is of concern because intervention has been shown to improve many of these outcomes, including mortality. In Canada, an interdisciplinary group called the Canadian Malnutrition Task Force has developed a framework for the screening of, diagnosis and treatment of malnutrition which has been successfully implemented at multiple sites across the country. Despite advancements in the field, many clinicians report feeling unknowledgeable about nutrition management as there is minimal training provided in most medical school and residency curriculums. This is a short review article highlighting the essentials of what we believe internists should know about malnutrition in hospitalized patients. RésuméParmi les patients hospitalisés au Canada, on constate une forte prévalence de malnutrition qui est associée à de mauvais résultats, notamment une augmentation de la durée d’hospitalisation, du taux de réhospitalisation et de la mortalité. Malgré son omniprésence, la malnutrition est souvent sousdiagnostiquée et partiellement traitée, ce qui est préoccupant, car il a été démontré qu’une intervention pouvait améliorer bon nombre de ces résultats, y compris la mortalité. Au Canada, un groupe interdisciplinaire appelé le Groupe de travail canadien sur la malnutrition a élaboré un cadre pour le dépistage, le diagnostic et le traitement de la malnutrition qui a été mis en œuvre avec succès à plusieurs endroits un peu partout au pays. Malgré les progrès réalisés dans ce domaine, beaucoup de cliniciens estiment manquer de connaissances sur la gestion de la nutrition, car la plupart des curriculums des écoles de médecine et des programmes de résidence ne prévoient qu’une formation minimale dans ce domaine. Ce court article de synthèse met en lumière l’essentiel de ce que nous pensons que les internistes devraient savoir à propos de la malnutrition chez les patients hospitalisés.

Abstract Background Patients with Crohn’s disease (CD) often seek advice on optimizing their diet to reduce gut inflammation. The relationship between dietary patterns, major food groups and individual nutrients, with disease activity in Crohn’s disease (CD) is incompletely understood and warrants further investigation. Aims 1.To determine whether a diversified (DD) or nondiversified (NDD) dietary pattern is related to biological activity in CD (BACD) in long-term follow up. 2.To determine if specific foods or nutrients are associated with increased BACD. Methods In this retrospective cohort study, forty-six CD patients (52% male) in remission completed 3-day food records between 2015–2017 for a 3-month intervention study and were classified as DD or NDD. Remission was defined by a Harvey Bradshaw Index <5 and no endoscopic ulcerations within 6 months of baseline data collection. Patients were classified as NDD if dietary fibre was ≤15 g/day or total fruit/vegetable servings ≤3/week, and if they consumed ≥3 servings/week of red and processed meat. Patients were otherwise defined as DD. A retrospective chart review captured BACD data. BACD was defined as one of either fecal calprotectin (FCP) ≥250 ug/g, hospitalization for CD flare, bowel resection for active CD, biologic dose escalation/switch due to non-response (not therapeutic drug monitoring), corticosteroid use, endoscopic evidence of apthous or large ulcers, or active disease on contrast enhanced ultrasound or magnetic resonance enterography. Machine learning methods with random forest prediction models assessed if diet composition was associated with BACD followed by univariate Mann-Whitney tests to compare differences between high and low disease activity. Results Sixteen patients (35%) had BACD during the mean 42 month follow up (31–54 months,SD ± 6.6). See Table 1 for additional demographics. Based on the random forest prediction model, both vitamins and minerals, food groups and Mediterranean diet cut-points could predict disease activity responses (ROC-AUC = 0.68 and 0.75, respectively). For these models, baseline intake of vitamins E, D, B1, and C and leafy greens, and fruit intake were the most important predictors of BACD. For the univariate analysis, the high disease group had lower intakes of fiber, vitamin E, and C (p = 0.047, 0.066, and 0.09, respectively). A higher proportion of patients consumed a NDD with BACD compared to those without BACD (50% vs. 23.3%, p=0.07). Conclusions To our knowledge, this is the first study to assess if dietary patterns, foods and nutrients are able to predict disease activity over a mean 42 month follow up. Further research into the dietary determinants of BACD in CD is warranted. With higher baseline FCP observed in the BACD, multivariate analyses to assess the independent effect of diet to predict BACD is required. Funding Agencies Litwin IBD Pioneers Foundation, Alberta’s Collaboration of Excellence for Nutrition in Digestive Diseases (Ascend)

Background: This study aimed to explore longitudinal relationships between bedside nutrition assessment tools (NAT): hand grip strength (HGS), mid upper arm circumference (MAC), and subjective global assessment (SGA), and clinical outcomes including: liver related hospitalizations, and liver transplant-free survival (LTFS) in patients undergoing liver transplantation assessment. Methods: Cirrhosis patients, referred to a cirrhosis focused malnutrition clinic, (N=41) completed NAT during the baseline visit and received one follow-up visit with NAT reassessment and were then followed up 24-months post assessment (median 23.0 months (IQR: 10.5 -29.1)). Log rank Kaplan-Meier and Cox proportional-hazard regression models were used to assess associations between demographic, clinical characteristics and NAT with outcomes. Results: Neither baseline NAT assessment or improvements affected the risk of hospitalizations in our cohort. In univariate analyses, improvement of SGA status (Hazard ratio [HR]: 0.28, 95% confidence interval [CI] 0.09-0.88, p=0.03) HGS (HR: 0.91, 95%CI 0.83-1.00, p=0.05) and MAC (HR 0.85, 95% 0.72.1.00, p=0.05) were associated with LTFS. However, NAT did not independently predict LTFS in adjusted multivariate analyses. Conclusions: Prospective larger cohorts are needed to further evaluate the impact of temporal improvement of NAT on LTFS and hospitalizations.]

Introduction: In cirrhosis patients, identifying significant associations between malnutrition, diseaseseverity and health-related quality of life (HRQoL) may help identify important targets for clinical assessment. Methods: The primary aim of this prospective study from 2014-2017 was to explore the influence of (1) nourishment state measured by subjective global assessment (SGA [Figure 1]), mid-arm circumference (MAC) and hand-grip strength (HGS), and; (2) disease-severity using Model of End-Stage Liver Disease score (MELD-Na) on HRQoL. HRQoL was measured with the validated Short-Form (SF) 36 subscales: vitality (V), physical function (PF), bodily pain (BP), general health (GH), physical role (PR), emotional role (ER), social function (SF) and mental health (MH). After identifying correlations ≥ 2, variables were entered into regression analyses controlled for age and gender. If a curvilinear relationship was present the Kruskal-Wallis test was used.823_A Figure 1. Subjective Global Assessment criteria to assess nutritional statusResults: This study included 81 patients with SGA breakdown outlined in Figure 2. After evaluation of correlation matrices, MELD-Na had correlation ≥ 2 with GH; MAC did not have any correlations ≥ 2 with any HRQoL subscale; HGS had correlations ≥ 2 with all subscales excluding SF, and; SGA had correlations ≥ 2 with all subscales. For SGA, PR demonstrated a significant relationship between SGA levels A and B compared to C (chi-squared=0.63, p=0.04); PF worsened as SGA did (Adjusted R2=19%; β=-0.24, p=0.03); V and SF worsened as SGA did (Adjusted R2=8% for both; β=-0.28, p=0.02 and β=-0.32, p<0.01), and; SGA had a borderline nonsignificant relationship with GH (β=-0.23, p=0.08). HGS was only significantly associated with PF (β=0.36, p<0.01). MELD-Na and MAC did not demonstrate any significant relationships with HRQoL. Neither BP nor MH demonstrated any significant relationships with assessment tools.823_B Figure 2. Breakdown of SGA of 81 patientsConclusion: Malnutrition was present in 70% of the study patients and was significantly related to decreased HRQoL for 4 subscales including physical role, physical function, vitality, and social function. Malnutrition measured by SGA was the only significant relationship with HRQoL in most analyses; HGS was significantly related to physical function only. This study identifies SGA as an important clinical tool to measure in cirrhosis patients and moderate to severe malnutrition (SGA B or C) is associated with reduced HRQoL. Future studies should explore if improvements in SGA relate to improved HRQoL.

Malnutrition is highly prevalent in cirrhosis and an independent predictor of negative clinical outcomes such as hospitalizations, infections, hepatic encephalopathy (HE), GI bleeding and mortality. Ambulatory nutrition interventions in cirrhosis and their effects on clinical outcomes have been under-explored. The study aim was to identify if a personalized nutrition intervention in malnourished pre-transplant patients with cirrhosis impacted clinical outcomes at 6–12 months. A prospective cohort study was conducted from 2014–2017 at the University of Calgary malnutrition clinic. Participants were assessed by a registered dietitian and a physician nutrition specialist and completed measurement of subjective global assessment (SGA), handgrip strength (HGS) and mid arm circumference (MAC). Patients identified as malnourished received tailored nutrition intervention. Clinical outcomes on frequency of hospitalizations, infections, HE and mortality were collected 6–12 months following intervention. T-tests, chi-squared analyses and analysis of covariance (ANCOVA) were used to examine relationships between nutrition assessment measures and outcomes. This study included 43 patients and 53.1%(n=25) were male. Compared to baseline, at 6–12 months there was a significant increase in BMI, improvements in HGS and MAC category, and more patients in a lower MELD-Na category, reflecting less severe disease (Table 1). Clinically, SGA classification improved, but this did not reach statistical significance. Patients whose SGA improved had a greater improvement in MELD-Na compared to those whose SGA worsened or was maintained (F(2)=6.95, p<0.05). Worsening SGA at follow up was associated with increased infections and HE (Chi2(1) =7.93, p<0.01; Chi2(2) =5.82, p=0.05, respectively). Fewer hospitalizations were potentially observed in patients with improved SGA status (p=0.11) and MAC (p=0.13), but this was not statistically significant. No other associations were found between HGS or MAC changes and clinical outcomes at follow-up compared to baseline. Improvement in SGA status appears to be associated with fewer infections and lower frequency of HE at 6–12 months. Nutrition assessment and intervention may benefit clinical outcomes in patients with cirrhosis. Table 1. Characteristics at baseline and 6–12 month follow up Table 1. Characteristics at baseline and 6–12 month follow up None

suppress death from CRC by ~25% (Ruiz-Casado et al., Trends Cancer 2017).However, since patients are frequently non-compliant, finding pharmacological modalities to mimic exercise is critical.While the benefit for exercise is undoubtedly pleiotropic, emerging evidence implicates the role of cytokines secreted by contracting the muscle (Roy et al Future Onc, 2018).We hypothesized that myokines may prevent CRC through targeting COX-2.Methods: We developed a cell culture exercise system where myotubules were subjected to electrically pulses (Roy et al, Future On 2018).The conditioned media containing myokines was concentrated with an Amicon tube (10kDa) and applied to human CRC cells, HT29.Controls were from unstimulated myotubules.Human Phospho-RTK Array Kit and Human Phospho-kinase Array Kit were used to determining the phosphorylation level.Results: Lipidomics analysis and found a 6.4 fold (p=0.004)increase in arachidonic acid level in HT29 CRC cells treated with stimulated myokine consonant with COX-2 blocks.In this regard, the downstream product of COX-2, prostaglandin E2 was decreased by ~90% (p= 0.01).COX-2 message was decreased by >75%.To identify the active fractions, we used a COX-2 promotor luciferase assay transfected into HT29s and noted that the 10kDa fraction was optimal reducing promotor activity by 92% loss (p<0.0001) in COX-2 promoter.Since myokines are presumed to act on the cell surface and EGFR is known to regulate COX-2 (Coffey et al., PNAS 1997).Treatment of 10KD fraction on HT29 cells results in decreased phosphorylation of several kinases including EGFR (37%), indicating inactivation of multiple kinases by 10KD fraction.Using EGFR kinase activity assay, we have validated that 10KD fraction reduces the EGFR kinase activity.Finally, to demonstrate the importance of EGFR-COX-2 axis in the anti-neoplastic area we used gefitinib, an EGFR inhibitor and celecoxib, a COX-2 inhibitor and combination treatment of these inhibitors with 10KD fraction blunted the anti-neoplastic effects of stimulated 10Kd fraction (Stim; Fig. 1) indicating the possibility that these myokines are working predominantly through these pathways.Conclusion: We demonstrate, for the first time, that exercise myokines provides a novel modality for suppressing COX-2 and having anti-neoplastic effects through an anti-EGFR activity.While the 10 KD myokinome is complex but future proteomic studies will identify specific myokines to serve as a novel cancer preventive and therapeutic agents.

BACKGROUNDTo explore the influence of nourishment state measured by various nutrition assessment tools (NATs) on health-related quality of life (HRQoL) in a pretransplant population with cirrhosis.METHODSWe collected demographic, nutrition assessment, and disease specific data on 81 patients. HRQoL was measured with the Short-Form 36 and divided into 8 subscales. Significant relationships between NATs and HRQoL were examined using independent sample t-tests, χ2 analyses, correlations, and multiple and logistic regression adjusted for age and gender.RESULTSStudy mean age was 54.2 years (SD 10.4 years), and 57% were male. Subjective Global Assessment (SGA) was significantly related to all HRQoL subscales, except bodily pain and mental health. In the adjusted regression models, general health, vitality, and social functioning were all significantly lower in patients with poorer nutrition status measured using SGA (adjusted R2 = 11%, β = -0.34, p < 0.01; adjusted R2 = 8%, β = -0.27, P < 0.05; and adjusted R2 = 12%, β = -0.38, P < 0.01, Q4 respectively). Physical functioning improved as hand grip strength increased (adjusted R2 = 20%, β = 0.36, P < 0.01). MELDNa demonstrated a significant negative relationship with role-emotional (adjusted R2 = 3%, β = 0.25, P < 0.05), and mid-arm circumference did not demonstrate any significant relationships with HRQoL.CONCLUSIONSMalnutrition assessed by SGA is associated with lower HRQoL in patients with cirrhosis. Future research should identify if nutrition interventions can effectively improve HRQoL in cirrhosis patients.

Malnutrition is highly prevalent in cirrhosis and is an independent predictor of negative clinical outcomes. Nutrition assessment (NA) is often not performed in patients with cirrhosis and this may result from a lack of clarity surrounding valid bedside tools. The study aimed to identify relationships between baseline NA measurements and adverse clinical outcomes in patients with cirrhosis. A prospective cohort study was conducted between 2014–2018 at the University of Calgary. Ambulatory pre-liver transplant patients with cirrhosis were co-assessed by a registered dietitian and a physician nutrition specialist in a specialized malnutrition clinic, and completed measurements of subjective global assessment (SGA), handgrip strength (HGS) and mid upper arm circumference (MUAC). Clinical outcomes including frequency of hospitalizations, length of stay, infections, and hepatic encephalopathy were collected in the 6–12 months following nutrition assessment. Mortality was examined from baseline to 3 years. T-tests and chi-squared analyses were used to examine relationships between NA tools and clinical outcomes. This study included 66 patients, mean age 54 (±10.1) years, and 56% (n=37) male. Baseline demographic characteristics are summarized in Table 1. Malnourished SGA status (9.5% (n=2) SGA A vs. 90.5% (n=19) who were SGA B and C) and lower HGS category (23.8% (n=5) who had a higher HGS vs. 76.2% (n=16) with a lower HGS) both had significantly higher proportions of mortality (SGA: (χ2(2)=6.6, p<0.05); HGS: (χ2(1)= 15.9, p<0.001), while MUAC was not significantly related to mortality (χ2(1) =1.9, p=0.17). The probability of a mortality event was 3.2 times more likely when they were in a lower HGS category. Higher MELD category was also associated with increased mortality (χ2(1) =4.1, p=0.04). SGA, HGS and MUAC were not significantly related to the other clinical outcomes. In our study, malnutrition diagnosed by both SGA and HGS is predictive of mortality in cirrhosis. Incorporating SGA and HGS into routine clinical practice for pre-liver transplant patients with cirrhosis to identify patients who may benefit form nutrition therapy should be considered. Demographic and Health Characteristics Demographic and Health Characteristics Baxter Canada