Administration of Free Amino Acids Improves Exogenous Amino Acid Availability when Compared with Intact Protein in Critically Ill Patients: A Randomized Controlled Study.

Background: Protein digestion and amino acid absorption appear compromised in critical illness. The provision of enteral feeds with free amino acids rather than intact protein may improve postprandial amino acid availability.

Objective: Our objective was to quantify the uptake of diet-derived phenylalanine after the enteral administration of intact protein compared with an equivalent amount of free amino acids in critically ill patients.

Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis.

Microcirculatory alterations play an important role in the early phase of sepsis. Shedding of the endothelial glycocalyx is regarded as a central pathophysiological mechanism causing microvascular dysfunction, contributing to multiple organ failure and death in sepsis. The objective of this study was to investigate whether endothelial glycocalyx thickness at an early stage in septic patients relates to clinical outcome.

Intrathoracic stomach in hiatal hernia: the role of laparoscopic repair.

Introduction: For decades, intrathoracic stomach has been an indication for surgical repair and over time laparoscopy has become standard treatment. However, there are still many aspects in the treatment of intrathoracic stomach that are subject of debate. We performed a literature review to discuss the role of laparoscopy in intrathoracic stomach repair.

Increased Dicarbonyl Stress as a Novel Mechanism of Multi-Organ Failure in Critical Illness.

Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated.

Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients.

Background: Pancreatic cancer is often accompanied by cachexia, a syndrome of severe weight loss and muscle wasting. A suboptimal response to nutritional support may further aggravate cachexia, yet the influence of nutrition on protein kinetics in cachectic patients is poorly understood.

Methods: Eight cachectic pancreatic cancer patients and seven control patients received a primed continuous intravenous infusion of l-[ring-(2)H5]phenylalanine and l-[3,3-(2)H2]tyrosine for 8 h and ingested sips of water with l-[1-(13)C]phenylalanine every 30 min.

Steroid use is associated with clinically irrelevant biopsies in patients with suspected giant cell arteritis.

Temporal artery biopsy (TAB) is the diagnostic gold standard for giant cell arteritis (GCA). GCA is treated by high-dose corticosteroids. In cases of high clinical suspicion, steroids may be administrated despite negative TAB, making TAB clinically irrelevant.

[13-Year old boy with abdominal pain].

A 13-year old boy presents with pain in the lower right abdomen, showing clinical signs of appendicitis. During McBurney' incision an appendix sana was seen. Histologic examination showed penetrating enterobiasis.

Hemolysis compromises nitric oxide-dependent vasodilatory responses in patients undergoing major cardiovascular surgery.

Background: The hemolytic products cell-free oxyhemoglobin (FHb) and arginase-1 reduce nitric oxide (NO) bioavailability by scavenging NO and by degrading the NO precursor arginine to ornithine, respectively. In this study we evaluated the relevance of hemolysis to NO-dependent blood flow in patients undergoing cardiovascular surgery.

Methods: Plasma FHb, arginase-1, and amino acid concentrations were measured perioperatively.

Urinary ammonia excretion increases acutely during living donor liver transplantation.

Introduction: Arterial ammonia concentrations increase acutely during the anhepatic phase of a liver transplantation (LTx) and return to baseline within 1 h after reperfusion of a functioning liver graft. So far, this return to baseline has solely been attributed to hepatic ammonia clearance. No data exist on the potential contribution of altered renal ammonia handling to peritransplantation ammonia homoeostasis.

Accurate perioperative flow measurement of the portal vein and hepatic and renal artery: a role for preoperative MRI?

Background: Quantification of abdominal blood flow is essential for a variety of gastrointestinal and hepatic topics such as liver transplantation or metabolic flux measurement, but those need to be performed during surgery. It is not clear whether Duplex Doppler Ultrasound during surgery or MRI before surgery is the tool to choose.

Objective: To examine whether preoperative evaluation of abdominal blood flow using MRI could prove to be a useful and reliable alternative for the perioperative sonographic approach.

To pee or not to pee: ammonia hypothesis of hepatic encephalopathy revisited.

Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver failure. Its aetiology has been debated for the past 100 years. Nevertheless, elevated ammonia levels are still believed to play a central role in its pathogenesis.

Gut and liver handling of interleukin-6 during liver resection in man.

Background: Plasma interleukin-6 (IL-6) levels increase during liver resection. The source of this IL-6 is hitherto unclear. It has been demonstrated that the hepatosplanchnic area takes up IL-6 but the role of the gut and liver is unknown.

C-reactive protein concentration is associated with prognosis in patients suffering from peritoneal carcinomatosis of colorectal origin.

Purpose: Only a limited number of patients with peritoneal carcinomatosis (PC) of colorectal origin benefit from palliative chemotherapy. Identification of prognostic factors may aid in patient selection. The plasma concentration of C-reactive protein (CRP) is increasingly recognized as prognostic factor in a variety of malignancies.

Randomized controlled trial analyzing the effect of 15 or 30 min intermittent Pringle maneuver on hepatocellular damage during liver surgery.

Background & Aims: Aminotransferases are commonly used to determine the optimal duration of ischemic intervals during intermittent Pringle maneuver (IPM). However, they might not be responsive enough to detect small differences in hepatocellular damage. Liver fatty acid-binding protein (L-FABP) has been suggested as a more sensitive marker.

A toxicogenomics-based parallelogram approach to evaluate the relevance of coumarin-induced responses in primary human hepatocytes in vitro for humans in vivo.

A compound for which marked species differences have been reported in laboratory animals and humans is coumarin. In rats, metabolites of coumarin are highly toxic, whereas in humans, the compound is mainly metabolized to non-toxic metabolites. In the present study, a toxicogenomics-based parallelogram approach was used to compare effects of coumarin on gene expression in human hepatocytes relevant for the situation in vivo.

Short chain fatty acids exchange across the gut and liver in humans measured at surgery.

Background & Aims: Short chain fatty acids (SCFAs; acetate, propionate and butyrate) are important energy sources for colonocytes and are assumed to play a key role in gut health. Local effects of SCFAs have been investigated, but less is known about whole body metabolism of these SCFAs. The aim of the present study was to quantify the role of the gut and liver in interorgan exchange of SCFAs in humans in vivo.

Enteral administration of alanyl-[2-(15)N]glutamine contributes more to the de novo synthesis of arginine than does intravenous infusion of the dipeptide in humans.

Background: We previously confirmed in humans the existence of a pathway of glutamine into citrulline and arginine, which is preferentially stimulated by luminally provided glutamine. However, because glutamine is unstable, we tested this pathway with a stable dipeptide of glutamine.

Objectives: The objectives were to explore whether alanyl-glutamine contributes to the synthesis of arginine in humans and whether this depends on the route of administration.

Parallelogram approach using rat-human in vitro and rat in vivo toxicogenomics predicts acetaminophen-induced hepatotoxicity in humans.

The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct comparison of toxicant-induced gene expression profiles and infers mechanisms between several systems. In the present study, acetaminophen (APAP) was used as a model compound to compare gene expression responses between rat and human using in vitro cellular models, hepatocytes, and between rat in vitro and in vivo.

The gut does not contribute to systemic ammonia release in humans without portosystemic shunting.

The gut is classically seen as the main source of circulating ammonia. However, the contribution of the intestines to systemic ammonia production may be limited by hepatic extraction of portal-derived ammonia. Recent data suggest that the kidney may be more important than the gut for systemic ammonia production.

Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production.

The amino acid arginine is the sole precursor for nitric oxide (NO) synthesis. We recently demonstrated that an acute reduction of circulating arginine does not compromise basal or LPS-inducible NO production in mice. In the present study, we investigated the importance of citrulline availability in ornithine transcarbamoylase-deficient spf(ash) (OTCD) mice on NO production, using stable isotope techniques and C57BL6/J (wild-type) mice controls.

Glutamine is an important precursor for de novo synthesis of arginine in humans.

Background: A metabolic relation exists between glutamine and arginine, 2 amino acids with properties that enhance the recovery of seriously ill patients. It is possible that glutamine exerts part of its beneficial effects by enhancing the availability of arginine.

Objectives: We aimed to quantify under postabsorptive conditions the metabolic pathway of plasma glutamine into arginine via the intermediate citrulline and to establish the contribution of the kidneys to the synthesis of arginine.

Decreased hepatosplanchnic antioxidant uptake during hepatic ischaemia/reperfusion in patients undergoing liver resection.

Oxidative stress mediates cell injury during ischaemia/reperfusion. On the other hand, experimental findings suggest that ROS (reactive oxygen species) induce processes leading to ischaemic preconditioning. The extent and source of oxidative stress and its effect on antioxidant status in the human liver during intermittent ischaemia and reperfusion remains ill-defined.

Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator?

Objective: Glutamine and arginine are both used as nutritional supplements in critically ill patients. Although glutamine has been shown to be beneficial for the metabolically stressed patient, considerations about arginine supplementation are not unanimously determined. Our aim is to review the current knowledge on the possible interplay between glutamine and arginine generation in the stressed patient and to elaborate on whether these amino acids may function as a common denominator.

Liver volumetry plug and play: do it yourself with ImageJ.

Background: A small remnant liver volume is an important risk factor for posthepatectomy liver failure and can be predicted accurately by computed tomography (CT) volumetry using radiologic image analysis software. Unfortunately, this software is expensive and usually requires support by a radiologist. ImageJ is a freely downloadable image analysis software package developed by the National Institute of Health (NIH) and brings liver volumetry to the surgeon's desktop.

Effect of major liver resection on hepatic ureagenesis in humans.

Changes in hepatic ureagenesis following major hepatectomy are not well characterized. We studied the relation between urea synthesis and liver mass before and after major hepatectomy in humans. Fifteen patients scheduled for resection of malignancies in otherwise healthy livers were studied.