Hepatocellular carcinoma (HCC) is a metabolically heterogeneous cancer and the use of glucose by HCC cells could impact their tumorigenicity. Dt81Hepa1-6 cells display enhanced tumorigenicity compared to parental Hepa1-6 cells. This increased tumorigenicity could be explained by a metabolic adaptation to more restrictive microenvironments. When cultured at high glucose concentrations, Dt81Hepa1-6 displayed an increased ability to uptake glucose (P<0.001), increased expression of 9 glycolytic genes, greater GTP and ATP (P<0.001), increased expression of 7 fatty acid synthesis-related genes (P<0.01) and higher levels of Acetyl-CoA, Citrate and Malonyl-CoA (P<0.05). Under glucose-restricted conditions, Dt81Hepa1-6 used their stored fatty acids with increased expression of fatty acid oxidation-related genes (P<0.01), decreased triglyceride content (P<0.05) and higher levels of GTP and ATP (P<0.01) leading to improved proliferation (P<0.05). Inhibition of lactate dehydrogenase and aerobic glycolysis with sodium oxamate led to decreased expression of glycolytic genes, reduced lactate, GTP and ATP levels (P<0.01), increased cell doubling time (P<0.001) and reduced fatty acid synthesis. When combined with cisplatin, this inhibition led to lower cell viability and proliferation (P<0.05). This metabolic-induced tumorigenicity was also reflected in human Huh7 cells by a higher glucose uptake and proliferative capacity compared to HepG2 cells (P<0.05). In HCC patients, increased tumoral expression of Glut-1, Hexokinase II and Lactate dehydrogenase correlated with poor survival (P = 2.47E, P = 0.016 and P = 6.58E). In conclusion, HCC tumorigenicity can stem from a metabolic plasticity allowing them to thrive in a broader range of glucose concentrations. In HCC, combining glycolytic inhibitors with conventional chemotherapy could lead to improved treatment efficacy.

Background An average daily moderate-to-vigorous physical activity (MVPA) of at least 60 minutes was recommended by the Canadian Guidelines for children. Because of lockdown restrictions during the COVID-19 pandemic, maintaining physical activity levels (PAL) has been a challenge for youth. Aims The primary aim of this study was to compare MVPA levels in children with inflammatory bowel diseases (IBD) before and after this period. The secondary aims were to assess clinical factors that might influence any changes in MVPA patterns. Methods Patients with IBD, age ≥5 years, were enrolled in a prospective study on PAL starting June 2018 (self-reported questionnaires during outpatient visits). They were then surveyed online at the end of the second lockdown in July-August 2021. PAL were assessed with the Canadian Health Measure Survey Children-Physical Activity Questionnaire. The responses were converted into metabolic equivalents of tasks by using validated tables. Influence of clinical factors of IBD on changes in MVPA was assessed. A multivariate logistic regression was performed to investigate the association between several risk factors and PAL. Results We included 72 patients (38 males; mean (SD) age 17.0 (2.89) years, 48 (66.7%) diagnosed with Crohn’s disease, 19 (26.4%) with ulcerative colitis, and 5 (6.9%) with indeterminate colitis). At last follow-up, 90.3% were in clinical remission according to validated disease activity score. During summer 2021, 16.7% of patients reached the Canadian PAL target, compared to 38.9% before the pandemic. The median daily duration of MVPA in summer 2021 decreased from 37 (Interquartile range (IQR) = 3–82) to 21 (IQR=3–40) minutes. The proportion of sedentary patients increased by 1.4% (37.5% to 38.9%). The proportion of extremely active patients decreased by 16.7% (27.8% to 11.1%), while moderately active patients increased by 20.9% (8.3% to 29.2%). Age, gender, disease type and activity were not significantly associated with the PAL at baseline or at follow-up. Conclusions This study found a significant decrease in PAL and time spent doing MVPA in children with IBD in Quebec following the COVID-19 pandemic lockdown. While the recommended target was far from being met before the pandemic, the gap has widened further during the pandemic. We found no clinical factors associated with the PAL. The impact of low PAL on well-being, weight, disease activity and quality of life will be assessed during the follow-up of this cohort. Funding Agencies None

No abstract

Background Foreign Body Ingestions (FBI), sometimes associated with severe complications, are a common reason for emergency unit visits in children. In Quebec, since March 2020, the restrictions in response to the COVID-19 pandemic have increased the time children spend at home. We hypothesized that this could contribute to a rise in FBI incidence and severity. Aims The primary objective of our study was to evaluate the incidence as well as the clinical presentation of FBI cases seen at CHU Sainte-Justine Children’s Hospital in Montreal (CHUSJ) during the COVID-19 pandemic as compared to the two previous years. Our secondary objectives were to estimate the rate of severe FBI (involving hospitalisations and/or complications) and to evaluate the nature of the foreign bodies that were ingested. Methods All children referred to or who presented at CHUSJ for FBI between March 2018 and February 2020 (pre-pandemic) as well as between March 2020 and February 2021 (pandemic) were included (n=690). Cases of food impaction were excluded (n=78). Incidence of FBI was calculated by dividing the number of FBI cases by the total number of emergency department visits per period. Differences between the two groups were analyzed by Student T test or Chi-square test. Results Between March 2018 and February 2021, 612 patients (median age 3.5 years (1.6–5.9); 54% male) were eligible. The mean monthly number of FBI cases (min-max) in 2020–2021 was 18.6 (9–28), significantly higher than the year 2018 [16.6 (8–22)] and the year 2019 [15.5 (9–24)]; p=0.04. The incidence rate of FBI doubled during the pandemic as compared to the prepandemic group: respectively 57.5/10,000 emergency department visits and 23.2/10,000 visits (p=0.002). Almost one fourth of the cohort was hospitalized. The hospitalization rate (&gt;1 day) was similar between the 2 periods: 8.8% before the pandemic and 7.1% during the pandemic. Digestive endoscopy was performed in 21.5% of cases, a rate similar before and during the pandemic. A total of 3.3% of the children developed complications related to FBI. This rate remained stable between the two periods. The most frequently ingested objects were coins (25.0%), toys (10.8%), button batteries (10.6%), magnets (6.2%), and jewellery (6.2%). There was no significant difference in the nature of FB ingested between the 2 periods although the number of magnet ingestions increased during the pandemic (18 per year vs 10 per year). Conclusions The incidence of FBI increased significantly during the pandemic in comparison with the two previous years. The high hospitalization and complications rates, although stable during the pandemic, underline the significant impact of pediatric FBI. Funding Agencies None