Branched Chain Amino Acids Are Associated with Physical Performance in Patients with End-Stage Liver Disease.

Decreased circulating branched chain amino acids (BCAA) represent a prominent change in amino acid profiles in patients with end-stage liver disease (ESLD). These alterations are considered to contribute to sarcopenia and hepatic encephalopathy and may relate to poor prognosis. Here, we cross-sectionally analyzed the association between plasma BCAA levels and the severity of ESLD and muscle function in participants of the liver transplant subgroup of TransplantLines, enrolled between January 2017 and January 2020. Plasma BCAA levels were measured by nuclear magnetic resonance spectroscopy. Physical performance was analyzed with a hand grip strength test, 4 m walking test, sit-to-stand test, timed up and go test, standing balance test and clinical frailty scale. We included 92 patients (65% men). The Child Pugh Turcotte classification was significantly higher in the lowest sex-stratified BCAA tertile compared to the highest tertile (p = 0.015). The times for the sit-to-stand (r = -0.352, p < 0.05) and timed up and go tests (r = -0.472, p < 0.01) were inversely correlated with total BCAA levels. In conclusion, lower circulating BCAA are associated with the severity of liver disease and impaired muscle function. This suggests that BCAA may represent a useful prognostic marker in the staging of liver disease severity.

Brachial and Axillary Artery Vascular Access for Endovascular Interventions.

BACKGROUND: Endovascular access is usually achieved through the common femoral artery due to its large size and accessibility. Access through the upper extremity can however be necessary due to anatomic reasons, obesity, or peripheral arterial disease. The 2 main methods of access are surgical cutdown and percutaneous puncture. In this single-centre retrospective cohort study we compared complication risks for both surgical cutdown and percutaneous puncture of an upper arm approach. MATERIALS AND METHODS: Data was obtained from patients receiving endovascular access through the brachial or axillary artery between 2005 and 2018. A total of 109 patients were included. Patient demographics including age, sex, medical history, smoking status, and actual medication were registered, as well as postoperative complications including hematoma, thrombosis, dissection, infection, pseudoaneurysm, nerve injury, reoperation, and readmission. RESULTS: Access was achieved through surgical cutdown in 53% (n = 58) and through percutaneous puncture in 47% (n = 51) of patients. Fifty-eight percent (n = 63) received access via the brachial artery (BA) and 42% (n = 46) via the axillary artery. Complication rate was 25.0% (3 of 12) for surgical cutdown via the BA, 29.4% (15 of 51) for percutaneous puncture via the BA, and 10.9% (5 of 46) for surgical cutdown via the axillary artery. Major complication rate was 8.3% (1 of 12) for surgical cutdown via the BA, 13.7% (7 of 51) for percutaneous puncture via the BA, and 4.3% (2 of 46) for surgical cutdown via the axillary artery. There was no association between baseline patient characteristics and complication rate. CONCLUSIONS: In this nonrandomized retrospective study, surgical cutdown via the axillary artery was the safest option with fewest complications, but selection of patients may have blurred the results. Surgical cutdown and percutaneous puncture seem equally safe in terms of complication rate in the BA.

Glycogen storage disease type 1a is associated with disturbed vitamin A metabolism and elevated serum retinol levels.

Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by mutations in the G6PC gene, encoding the catalytic subunit of glucose-6-phosphatase. Early symptoms include severe fasting intolerance, failure to thrive and hepatomegaly, biochemically associated with nonketotic hypoglycemia, fasting hyperlactidemia, hyperuricemia and hyperlipidemia. Dietary management is the cornerstone of treatment aiming at maintaining euglycemia, prevention of secondary metabolic perturbations and long-term complications, including liver (hepatocellular adenomas and carcinomas), kidney and bone disease (hypovitaminosis D and osteoporosis). As impaired vitamin A homeostasis also associates with similar symptoms and is coordinated by the liver, we here analysed whether vitamin A metabolism is affected in GSD Ia patients and liver-specific G6pc-/- knock-out mice. Serum levels of retinol and retinol binding protein 4 (RBP4) were significantly increased in both GSD Ia patients and L-G6pc-/- mice. In contrast, hepatic retinol levels were significantly reduced in L-G6pc-/- mice, while hepatic retinyl palmitate (vitamin A storage form) and RBP4 levels were not altered. Transcript and protein analyses indicate an enhanced production of retinol and reduced conversion the retinoic acids (unchanged LRAT, Pnpla2/ATGL and Pnpla3 up, Cyp26a1 down) in L-G6pc-/- mice. Aberrant expression of genes involved in vitamin A metabolism was associated with reduced basal messenger RNA levels of markers of inflammation (Cd68, Tnfα, Nos2, Il-6) and fibrosis (Col1a1, Acta2, Tgfß, Timp1) in livers of L-G6pc-/- mice. In conclusion, GSD Ia is associated with elevated serum retinol and RBP4 levels, which may contribute to disease symptoms, including osteoporosis and hepatic steatosis.

Plasma Levels of Retinol Binding Protein 4 Relate to Large VLDL and Small LDL Particles in Subjects with and without Type 2 Diabetes.

BACKGROUND: Retinol binding protein 4 (RBP4) carries retinol in plasma, but is also considered an adipokine, as it is implicated in insulin resistance in mice. Plasma RBP4 correlates with total cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides, and may confer increased cardiovascular risk. However, controversy exists about circulating RPB4 levels in type 2 diabetes mellitus (T2DM) and obesity. Here, we analyzed the relationships of RBP4 and retinol with lipoprotein subfractions in subjects with and without T2DM. METHODS: Fasting plasma RBP4 (enzyme-linked immunosorbent assay) and retinol (high performance liquid chromatography) were assayed in 41 T2DM subjects and 37 non-diabetic subjects. Lipoprotein subfractions (NMR spectroscopy) were measured in 36 T2DM subjects and 27 non-diabetic subjects. Physical interaction of RBP4 with lipoproteins was assessed by fast protein liquid chromatography (FPLC). RESULTS: Plasma RBP4 and retinol were strongly correlated (r = 0.881, p < 0.001). RBP4, retinol and the RBP4/retinol ratio were not different between T2DM and non-diabetic subjects (all p > 0.12), and were unrelated to body mass index. Notably, RBP4 and retinol were elevated in subjects with metabolic syndrome (p < 0.05), which was attributable to an association with elevated triglycerides (p = 0.013). Large VLDL, total LDL and small LDL were increased in T2DM subjects (p = 0.035 to 0.003). Taking all subjects together, RBP4 correlated with total cholesterol, non-HDL cholesterol, LDL cholesterol, triglycerides and apolipoprotein B in univariate analysis (p < 0.001 for each). Age-, sex- and diabetes status-adjusted multivariable linear regression analysis revealed that RBP4 was independently associated with large VLDL (ß = 0.444, p = 0.005) and small LDL particles (ß = 0.539, p < 0.001). Its relationship with large VLDL remained after further adjustment for retinol. RBP4 did not co-elute with VLDL nor LDL particles in FPLC analyses. CONCLUSIONS: Plasma RBP4 levels are related to but do not physically interact with large VLDL and small LDL particles. Elevated RBP4 may contribute to a proatherogenic plasma lipoprotein profile.