Mutual changes of thioredoxin and nitrosothiols during biliary cirrhosis: results from humans and cholestatic rats

Cholestasis is associated with changes in NO metabolism and thiol oxidation. Thioredoxin contributes to regulate vascular tone and intracellular redox status by cleaving nitrosothiols and maintaining -SH groups. This study investigated the changes in circulating thioredoxin and nitrosothiols and the relationship with protein sulfhydryls (PSH), hepatic concentrations, hyaluronate, and histology in patients with primary biliary cirrhosis (PBC) and in rats with bile duct ligation (BDL). PSH in erythrocytes were significantly decreased in stage III and IV PBC and at day 10 after BDL. Compared with controls, erythrocyte thioredoxin levels were higher in stage I through III PBC and lower in stage IV patients. Serum thioredoxin levels were significantly higher in PBC stages I and II and lower in stages III and IV. Serum nitrosothiols were higher in all PBC patients and inversely related to thioredoxin and hyaluronate. In rats, serum, hepatic, and mitochondrial thioredoxin had initially increased after BDL (day 1-3) and then decreased. After day 7 BDL, nitrosothiols were 10-fold increased in serum and liver, and even higher in mitochondria. In the liver, thioredoxin was inversely related to both nitrosothiols and PSH. In rats, the difference in time average changes from baseline among serum, hepatic, and erythrocyte thioredoxin suggests that most of circulating thioredoxin originates from the liver. Conclusion: Our findings indicate that cholestasis is associated with significant mutual and interrelated changes between circulating and hepatic thioredoxin and nitrosothiols. The increase of hepatic, mitochondrial, and circulating nitrosothiols with ongoing cholestasis suggests an active participation of NO in both liver injury and extrahepatic change

Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry

Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and predictors are still elusive. To investigate this issue, the Italian Society of Internal Medicine undertook the “Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry” (PRO-LIVER). This prospective multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven hundred and fifty-three (68 % men; 64 ± 12 years) patients were included in the present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral (44 %) etiology was predominant. Around half of the patients had a mild-severity disease according to the Child–Pugh score; hepatocellular carcinoma was present in 20 %. The prevalence of ultrasound-detected portal vein thrombosis was 17 % (n = 126); it was asymptomatic in 43 % of the cases. Notably, more than half of the portal vein thrombosis patients (n = 81) were not treated with anticoagulant therapy. Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis (p < 0.001), Child–Pugh Class B + C (p < 0.001), hepatocellular carcinoma (p = 0.01), previous upper gastrointestinal bleeding (p = 0.030) and older age (p = 0.012) were independently associated with portal vein thrombosis. Portal vein thrombosis is a frequent complication of cirrhosis, particularly in patients with moderate–severe liver failure. The apparent undertreatment of patients with portal vein thrombosis is a matter of concern and debate, which should be addressed by planning interventional trials especially with newer oral anticoagulants. Clinicaltrials.gov identifier NCT01470547

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors