Surgical Correction of Carcinoid Heart Disease Improves Liver Function and 5-Hydroxyindoleacetic Acid Levels.

Introduction: Carcinoid heart disease (CHD) is a consequence of neuroendocrine tumors releasing 5-hydroxytryptamine (5-HT) into the systemic circulation, affecting right heart valves, causing fibrosis, and eventually right heart failure. The aim of this study was to determine the effect of valve-replacement on kidney function, liver function, and 5-hydroxyindoleacetic acid (5-HIAA) levels. Methods: A Retrospective study of 17 patients with CHD who had undergone heart-valve replacement surgery between 2010 and 2019, from the Queen Elizabeth Hospital Birmingham. 5-HIAA levels, liver, and kidney function were measured in addition to hepatic inferior vena cava (IVC) diameter and its relationship to carcinoid symptoms. Results: Eleven patients were male and six were female. At time of surgery, average age was 66.6 ± 8.1 years and average BMI was 25.8 ± 5.5 Kg/cm2. Three out of 17 patients had one valve replaced, 13/17 had two replaced (tricuspid and pulmonary), and 1/17 had three replaced (tricuspid, pulmonary and aortic). There was a 31% average decline in 5-HIAA [799.8 (343.6-1078.0) to 555.3 (275.8-817.9), p = 0.011], a 35% decline in bilirubin [20 (16-29) to 13 (10-19), p = < 0.001], and a 15% reduction in the short and long axes of the IVC after valve-replacement surgery [20.0 (18.0-25.0) and 36.5 (29.0-39.8) to 17.0 (14.5-19.3) and 31.0 (26.5-34.3) respectively, p = < 0.001 and 0.002 respectively]. Conclusion: Valve replacement surgery improves 5-HIAA levels alongside improved liver function and hepatic IVC diameter. These findings are consistent with resolution of congestive hepatopathy, and therefore enhanced clearance of 5-HIAA. This suggests that valve-replacement surgery can indirectly have beneficial outcomes on hepatic function and is also associated with a drop in the circulating levels of tumor derived serotonin.

When two actors perform different tasks: Still no evidence for shared task-sets in joint task switching.

Two different variations of joint task switching led to different conclusions as to whether co-acting individuals share the same task-sets. The present study aimed at bridging this gap by replicating the version in which two actors performed two different tasks. Experiment 1 showed switch costs across two actors in a joint condition, which agreed with previous studies, but also yielded even larger switch costs in a solo condition, which contradicted the claim that actors represent an alternative task as their own when it is carried out by the co-actor but not when no one carries it out. Experiments 2 and 3 further examined switch costs in the solo condition with the aim to rule out possible influences of task instructions for and experiences with the other task that was not assigned to the actor. Before participants were instructed on the second of the two tasks, switch costs were still obtained without a co-actor when explicit task names ("COLOUR" and "SHAPE") served as go/nogo signals (Experiment 2), but not when arbitrary symbols ("XXXX" and "++++") served as go/nogo signals (Experiment 3). The results thus imply that switch costs depend on participants' knowledge of task cues being assigned to two different tasks, but not on whether the other task is performed by a co-actor. These findings undermine the assumption that switch costs in the joint conditions reflect shared task-sets between co-actors in this procedure.

Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response.

BACKGROUND & AIMS: Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events. METHODS: We evaluated a cohort of PBC patients (n=386) attending the Liver Unit in Birmingham (derivation cohort), seeking to identify risk-variables associated with transplant-free survival independent of UDCA-response. A validation cohort was provided through well-characterised patients attending the Toronto Center for Liver Diseases (n=479) and Jena University Hospital (n=150). RESULTS: On multivariate analysis, factors at diagnosis associated with liver transplant (LT)/death were patient age (HR:1.06; p<0.001), elevated bilirubin (HR:1.27; p<0.001), early-onset cirrhosis (HR:2.40; p<0.001) and baseline AST/platelet ratio index (APRI) (HR:1.95; p<0.001). At 1-year, UDCA biochemical non-response predicted poorer transplant-free survival, and additional factors (multivariate) associated with adverse outcome were age (HR:1.02; p<0.05) and 1-year APRI (HR:1.15; p<0.001). Obtaining a cut-point from our derivation cohort, APRI >0.54 at baseline was predictive of LT/death (adjusted HR: 2.40; p<0.001), and retained statistical significance when applied at 1-year (APRI-r1, adjusted HR:2.75; p<0.001) despite controlling for UDCA-response. Across both cohorts, transplant-free survival was poorer for biochemical-responders with an APRI-r1 >0.54 vs. biochemical-responders with a lower APRI-r1 (p<0.01 and p<0.001, respectively); non-responders with high APRI-r1 had the poorest outcomes (p<0.001 and p<0.001). CONCLUSION: In PBC, elevated APRI is associated with future risk of adverse events, independently and additively of UDCA-response. This cross-centre, robustly validated observation will contribute to ongoing efforts to refine existing risk-stratification tools, as well as direct focus for new therapies in patients with PBC.