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Background: Postprandial rise of plasma essential amino acids (EAAs) determines the anabolic effect of dietary protein. Disturbed gastrointestinal function could impair the anabolic response in critically ill patients. Aim was to investigate the postprandial EAA response in critically ill patients and its relation to small-intestinal function., Methods: Twenty-one mechanically ventilated patients and 9 healthy controls received a bolus containing 100 ml of a formula feed (Ensure) and 2 g of 3-O-Methyl-d-glucose (3-OMG) via postpyloric feeding tube. Fasting and postprandial plasma concentrations of EAAs, 3-OMG, total bile salts, and the gut-released hormone fibroblast growth factor 19 (FGF19) were measured over a 4-hour period. Changes over time and between groups were assessed with linear mixed-effects analysis. Early (0-60 minutes) and total postprandial responses are summarized as the incremental area under the curve (iAUC)., Results: At baseline, fasting EAA levels were similar in both groups: 1181 (1055-1276) vs 1150 (1065-1334) μmol·L-1, P = .87. The early postprandial rise in EAA was not apparent in critically ill patients compared with healthy controls (iAUC 60 , -4858 [-6859 to 2886] vs 5406 [3099-16,853] µmol·L -1 ·60 minutes; P = .039). Impaired EAA response did not correlate with impaired 3-OMG response (Spearman ρ 0.32, P = .09). There was a limited increase in total bile salts but no relevant FGF19 response in either group., Conclusion: Postprandial rise of EAA is blunted in critically ill patients and unrelated to glucose absorption measured with 3-OMG. Future studies should aim to delineate governing mechanisms of macronutrient malabsorption., (© 2021 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: The early diagnosis of biliary tract cancer (BTC) remains challenging, and there are few effective therapies. This study investigated whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a role in the diagnosis and therapy of BTC., Methods: Plasma and bile M2-PK concentrations were measured by enzyme-linked immunosorbent assay in 88 patients with BTC, 79 with benign biliary diseases, and 17 healthy controls. M2-PK expression was assayed in a BTC tissue array by immunohistochemistry. The role of M2-PK in tumor growth, invasion, and angiogenesis was evaluated in BTC cell lines by retrovirus-mediated M2-PK transfection and short hairpin RNA silencing techniques., Results: Sensitivity (90.3%) and specificity (84.3%) of bile M2-PK for malignancy were significantly higher than those for plasma M2-PK and serum carbohydrate antigen 19-9. M2-PK expression was specific for cancer cells and correlated with microvessel density. M2-PK positivity was a significant independent prognostic factor by multivariable analysis. Transfection of M2-PK in a negatively expressed cell line (HuCCT-1 cells) increased cell invasion, whereas silencing in an M2-PK-positive cell line (TFK cells) decreased tumor nodule formation and cellular invasion. A significant increase in endothelial tube formation was noted when supernatants from M2-PK-transfected cells were added to an in vitro angiogenesis assay, whereas supernatants from silenced cells negated endothelial tube formation., Conclusions: Bile M2-PK is a novel tumor marker for BTC and correlates with tumor aggressiveness and poor outcome. Short hairpin RNA-mediated inhibition of M2-PK indicates the potential of M2-PK as a therapeutic target., (Copyright © 2012 American Cancer Society.)

Background: This study aims to evaluate whether withdrawal of a soy oil-based lipid emulsion from the parenteral nutrition (PN) regimen in humans is associated with improved triglyceride and liver enzyme concentrations., Methods: In this retrospective study, patients with hypertriglyceridemia (>4.50 mmol/L) while receiving PN were retrieved from a prospective complication registration database. Patients received Intralipid 20% as part of an all-in-one system containing all necessary macro- and micronutrients, electrolytes, trace elements, and vitamins., Results: Forty patients with hypertriglyceridemia were included. Lipid emulsions were withdrawn from the all-in-one mixture for a median of 5 (range, 1-23) days, after which triglyceride concentrations decreased significantly (mean difference -2.5 ± 0.30 mmol/L, P < .001). Aspartate aminotransaminase and leukocyte count decreased significantly (mean difference -35 ± 17 U/L, P = .049 and -3.8 ± 1.7*10E9/L, P = .028, respectively), whereas albumin level increased significantly (mean difference 2.1 ± 0.9 g/L, P = .027). Alanine aminotransaminase showed a nonsignificant reduction (mean difference -30 ± 22 U/L, P = .194). In 11 patients, the lipid emulsion was reintroduced, after which triglyceride levels showed a significant increase (mean difference 1.5 ± 0.30 mmol/L, P = .001)., Conclusions: Short-term withdrawal of the lipid fraction in the PN mixture is associated with a significant reduction of plasma triglyceride concentration. Reintroduction was related to an increase of triglyceride concentration. In addition, liver enzyme abnormalities and leukocyte count reduced, whereas albumin levels increased, suggesting that even short withdrawal of the lipid emulsion diminished hepatocellular damage and systemic inflammation.