Does proteolysis explain glutamine release from the septic brain?

Berg and colleagues report on amino acid exchange across the human brain during endotoxin infusion. Lipopolysaccharide infusion induced a decrease in the ratio between branched chain amino acids and aromatic amino acids, increased unidirectional phenylalanine uptake, and increased net brain glutamine release. Cerebral proteolysis is suggested to play a role, but the question is whether this is the case and why this would happen

Surrogate endpoints in liver surgery related trials: a systematic review of the literature

AbstractBackgroundAlthough the safety of liver surgery has improved enormously, hepatic surgery continues to face challenging complications. Therefore, improvements supported by evidence‐based guidelines are still required. The conduct of randomized controlled trials in liver surgery using dichotomous outcomes requires a large sample size. The use of surrogate endpoints (SEPs) reduces sample size but SEPs should be validated before use.AimThe aim of this review was to summarize the SEPs used in hepatic surgery related trials, their definitions and recapitulating the evidence validating their use.MethodA systematic computerized literature search in the biomedical database PubMed using the MeSH terms ‘hepatectomy’ or ‘liver resection’ or ‘liver transection’ was conducted. Search was limited to papers written in the English language and published between 1 January 2000 and 1 January 2010.ResultsA total of 593 articles met the search terms and 49 articles were included in the final selection. Standard biochemical liver functions tests were the most frequently used SEP (32 of 49 the studies). The used definitions of SEPs varied greatly among the studies. Most studies referred to earlier published material to justify their choice of SEP. However, no validating studies were found.ConclusionMany SEPs are used in liver surgery trials however there is little evidence validating them

Nodular Regenerative Hyperplasia Secondary to Neoadjuvant Chemotherapy for Colorectal Liver Metastases

Liver resection is the only curative treatment for patients with colorectal liver metastases (CLMs). Neoadjuvant chemotherapy can improve resectability but has a potential harmful effect on the nontumorous liver. Patients with chemotherapy-induced hepatic injury undergoing liver surgery have higher risks of post-resectional morbidity. We present two cases of patients without pre-existent liver disease treated with oxaliplatin-based chemotherapy followed by surgical resection of their CLMs. Their intra-operative liver specimen showed morphologic abnormalities characteristic of nodular regenerative hyperplasia (NRH). NRH led to portal hypertension in both patients that resulted in deleterious post-resectional complications and death of one patient. Interestingly, the other patient underwent two repeat nonanatomic liver resections because of recurrent CLMs. The intra-operative liver specimen still showed signs of NRH and sinusoidal congestion, but the post-resectional courses were uneventful. Nevertheless, caution is recommended in patients with suspected NRH. Careful volumetric analysis should guide the operative strategy. When future remnant liver volume is regarded insufficient, portal vein embolization or restrictive surgery should be considered

Visceral obesity measured using computed tomography scans:No significant association with mortality in critically ill patients

Introduction: The association between obesity and outcome in critical illness is unclear. Since the amount of visceral adipose tissue(VAT) rather than BMI mediates the health effects of obesity we aimed to investigate the association between visceral obesity, BMI and 90-day mortality in critically ill patients. Method: In 555 critically ill patients (68% male), the VAT Index(VATI) was measured using Computed Tomography scans on the level of vertebra L3. The association between visceral obesity, BMI and 90-day mortality was investigated using univariable and multivariable analyses, correcting for age, sex, APACHE II score, sarcopenia and muscle quality. Results: Visceral obesity was present in 48.1% of the patients and its prevalence was similar in males and females. Mortality was similar amongst patients with and without visceral obesity (27.7% vs 24.0%, p = 0.31). The corrected odds ratio of 90-day mortality for visceral obesity was 0.667 (95%CI 0.424–1.049, p = 0.080). Using normal BMI as reference, the corrected odds ratio for overweight was 0.721 (95%CI 0.447–1.164 p = 0.181) and for obesity 0.462 (95%CI 0.208–1.027, p = 0.058). Conclusion: No significant association of visceral obesity and BMI with 90-day mortality was observed in critically ill patients, although obesity and visceral obesity tended to be associated with improved 90-day mortality.</p

Visceral obesity measured using computed tomography scans:No significant association with mortality in critically ill patients

Introduction: The association between obesity and outcome in critical illness is unclear. Since the amount of visceral adipose tissue(VAT) rather than BMI mediates the health effects of obesity we aimed to investigate the association between visceral obesity, BMI and 90-day mortality in critically ill patients. Method: In 555 critically ill patients (68% male), the VAT Index(VATI) was measured using Computed Tomography scans on the level of vertebra L3. The association between visceral obesity, BMI and 90-day mortality was investigated using univariable and multivariable analyses, correcting for age, sex, APACHE II score, sarcopenia and muscle quality. Results: Visceral obesity was present in 48.1% of the patients and its prevalence was similar in males and females. Mortality was similar amongst patients with and without visceral obesity (27.7% vs 24.0%, p = 0.31). The corrected odds ratio of 90-day mortality for visceral obesity was 0.667 (95%CI 0.424–1.049, p = 0.080). Using normal BMI as reference, the corrected odds ratio for overweight was 0.721 (95%CI 0.447–1.164 p = 0.181) and for obesity 0.462 (95%CI 0.208–1.027, p = 0.058). Conclusion: No significant association of visceral obesity and BMI with 90-day mortality was observed in critically ill patients, although obesity and visceral obesity tended to be associated with improved 90-day mortality.</p

Intestinal Fatty Acid Binding Protein as a Predictor of Early Mesenteric Injury Preceding Clinical Presentation:A Case Report

Introduction: Diagnosing non-occlusive mesenteric ischaemia (NOMI) in patients is complicated, due to poor signs and symptoms and non-specific laboratory tests, leading to a high mortality rate. This case study presents the rare case of a patient who developed mesenteric ischaemia after an emergency thoracic endovascular aneurysm repair (TEVAR) for a type B aortic dissection (TBAD) and peri-operative cardiogenic shock. Study outcomes revealed that intestinal fatty acid binding protein (I-FABP) identified early mucosal damage two days before the clinical presentation. Report: A 43 year old male patient was admitted to the emergency department with an acute TBAD and a dissection of the superior mesenteric artery (SMA), for which TEVAR was performed with additional stent placement in the SMA. Peri-operatively, the patient went into cardiogenic shock with a sustained period of hypotension. Post-operatively, the plasma I-FABP levels were measured prospectively, revealing an initial increase on post-operative day five (551.1 pg/mL), which continued beyond day six (610.3 pg/mL). On post-operative day seven, the patient developed a fever and demonstrated signs of peritonitis and bowel perforation. He underwent an emergency laparotomy, followed by an ileocaecal resection (&lt;100 cm) with a transverse ileostomy. Pathological analysis confirmed the diagnosis of mesenteric ischaemia. Discussion: The diagnosis of NOMI in critically ill patients is often complicated, and the currently available diagnostic markers lack the specificity and sensitivity to detect early intestinal injury. This case report highlights that elevated I-FABP in plasma levels may indicate the presence of early mesenteric injury. Further research needs to be conducted before I-FABP can be applied in daily practice.</p

Myosteatosis predicts survival after surgery for periampullary cancer::a novel method using MRI

Background: Myosteatosis, characterized by inter-and intramyocellular fat deposition, is strongly related to poor overall survival after surgery for periampullary cancer. It is commonly assessed by calculating the muscle radiation attenuation on computed tomography (CT) scans. However, since magnetic resonance imaging (MRI) is replacing CT in routine diagnostic work-up, developing methods based on MRI is important. We developed a new method using MRI-muscle signal intensity to assess myosteatosis and compared it with CT-muscle radiation attenuation.Methods: Patients were selected from a prospective cohort of 236 surgical patients with periampullary cancer. The MRI-muscle signal intensity and CT-muscle radiation attenuation were assessed at the level of the third lumbar vertebra and related to survival.Results: Forty-seven patients were included in the study. Inter-observer variability for MRI assessment was low (R-2 = 0.94). MRI-muscle signal intensity was associated with short survival: median survival 9.8 (95%-CI: 1.5-18.1) vs. 18.2 (95%-CI: 10.7-25.8) months for high vs. low intensity, respectively (p = 0.038). Similar results were found for CT-muscle radiation attenuation (low vs. high radiation attenuation: 10.8 (95%-CI: 8.5-13.1) vs. 15.9 (95%-CI: 10.2-21.7) months, respectively; p = 0.046). MRI-signal intensity correlated negatively with CT-radiation attenuation (r=-0.614, p &lt;0.001).Conclusions: Myosteatosis may be adequately assessed using either MRI-muscle signal intensity or CT-muscle radiation attenuation.</p

Effect of wheat bran derived prebiotic supplementation on gastrointestinal transit, gut microbiota, and metabolic health: a randomized controlled trial in healthy adults with a slow gut transit

Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125.</p

Impaired brain glymphatic flow in experimental hepatic encephalopathy

Background & Aims: Neuronal function is exquisitely sensitive to alterations in the extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain is thought to result from liver disease and may contribute to neuronal dysfunction and cognitive impairment. This study was designed to test the hypothesis that the accumulation of these substances, such as bile acids, may result from reduced clearance from the brain. Methods: In a rat model of chronic liver disease with minimal HE (the bile duct ligation [BDL] model), we used emerging dynamic contrast-enhanced MRI and mass-spectroscopy techniques to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from the brain. Immunofluorescence of aquaporin-4 (AQP4) and behavioural experiments were also performed. Results: We identified discrete brain regions (olfactory bulb, prefrontal cortex and hippocampus) of altered glymphatic clearance in BDL rats, which aligned with cognitive/behavioural deficits. Reduced AQP4 expression was observed in the olfactory bulb and prefrontal cortex in HE, which could contribute to the pathophysiological mechanisms underlying the impairment in glymphatic function in BDL rats. Conclusions: This study provides the first experimental evidence of impaired glymphatic flow in HE, potentially mediated by decreased AQP4 expression in the affected regions. Lay summary: The 'glymphatic system' is a newly discovered brain-wide pathway that facilitates clearance of various sub-stances that accumulate in the brain due to its activity. This study evaluated whether the function of this system is altered in a model of brain dysfunction that occurs in cirrhosis. For the first time, we identified that the clearance of substances from the brain in cirrhosis is reduced because this clearance system is defective. This study proposes a new mechanism of brain dysfunction in patients with cirrhosis and provides new targets for therapy