Comparison of automated ASPECTS, large vessel occlusion detection and CTP analysis provided by Brainomix and RapidAI in patients with suspected ischaemic stroke.

OBJECTIVES: The ischaemic core and penumbra volumes derived from CTP aid the selection of patients with an arterial occlusion for mechanical thrombectomy. Different post-processing software packages may give different CTP outputs, potentially causing variable patient selection for mechanical thrombectomy. The study aims were, firstly, to assess the correlation in CTP outputs from software packages provided by Brainomix and RapidAI. Secondly, the correlation between automated ASPECTS and neuroradiologist-derived ASPECTS and accuracy in detecting large vessel occlusion was assessed. MATERIALS AND METHODS: This retrospective study included patients undergoing CTP for suspected anterior circulation large vessel occlusion. Pearson's correlation coefficient was used for testing the correlation in CTP outputs, ASPECTS/automated ASPECTS, and-in those with complete or near complete occlusion-final infarct volume. Diagnostic statistics were calculated for large vessel occlusion detection. RESULTS: Correlation was high for ischaemic core and penumbra volumes (0.862 and 0.832, respectively) but lower for the mismatch ratio (0.477). Agreement in mechanical thrombectomy eligibility was achieved in 85% of cases (46/54). Correlation between ischaemic core and final infarct volume was higher for Brainomix (0.757) than for RapidAI (0.595). The correlation between ASPECTS and automated ASPECTS (0.738 and 0.659) and the accuracy of detecting large vessel occlusion (77% and 71%) was higher for Brainomix than for RapidAI. CONCLUSION: There was high correlation between the CTP output from Brainomix and RapidAI. However, there was a difference in MT eligibility in 15% of cases, which highlights that the decision regarding MT should not be based on imaging parameters alone.

Fibrosis progression rate in a systematic review of placebo-treated nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Liver fibrosis is the critical determinant of liver-related outcomes in persons with nonalcoholic fatty liver disease. The rate that fibrosis develops determines the time taken to reach cirrhosis and consequent clinical outcomes. Estimates of the fibrosis progression rate (FPR) are uncertain having been defined in small observational series that rely largely on nonstandardised repeat biopsy in selected patients. The aim of this study was to evaluate the FPR in placebo-treated participants with nonalcoholic steatohepatitis (NASH) in randomised controlled trials (RCTs). METHODS: Systematic review and meta-analysis of RCTs in NASH with data on fibrosis change extracted. Calculated fibrosis progression rates were pooled in meta-analysis. The pooled estimate was then used to model the proportion of hypothetical cohorts starting with no fibrosis at the age of 30 who develop cirrhosis. RESULTS: A total of 35 trials including 1419 placebo-treated participants who underwent repeat liver biopsy were evaluated. Considering all trials, the overall FPR was 0.00 stages per year, increasing to 0.03 stages per year in both trials at low risk of bias and trials including >50 placebo-treated participants. This estimate was markedly lower than the value derived from previously pooled analyses of observational data. Using a FPR of 0.03 resulted in a substantial reduction in the proportion of patients developing cirrhosis compared with the FPR derived from observational studies (13% vs 28%). CONCLUSIONS: The FPR in placebo-treated participants in RCTs is lower than that described from observational data. Slower fibrosis progression predicts fewer persons with NASH will progress to cirrhosis than previously estimated.

Modeling the benefits and harms of surveillance for hepatocellular carcinoma: Information to support informed choices.

Surveillance by ultrasonography for hepatocellular carcinoma (HCC) for individuals with cirrhosis is recommended. There is debate regarding the effectiveness of surveillance in reducing mortality, and there is little information on the harms available to patients considering surveillance. The aim of this study was to provide estimates of both the benefit and harms of surveillance. A Markov model was built to simulate outcomes of individuals aged 50 years with well-compensated cirrhosis entering surveillance. Following identification of a focal lesion by ultrasound surveillance, further investigations were defined by the European Association for the Study of the Liver/European Organization for Research and Treatment of Cancer recall policy. Benefit and harm outcomes are expressed per 1,000 patients over 5 years. For every 1,000 patients in surveillance over 5 years, there are 13 fewer deaths (95% confidence interval [CI], 12-14) compared with no surveillance, equating to a number needed to screen to prevent one death from HCC of 77. In comparison, many more individuals experienced harm through surveillance. For every 1,000 patients, 150 (95% CI, 146-154) had one or more false-positive tests equating to a number needed to harm from surveillance of 7. As a consequence of a false-positive test, 65 individuals required at least one additional unnecessary computed tomography scan or magnetic resonance imaging and 39 required an unnecessary liver biopsy according to the recall policy. Surveillance benefits were sensitive to the incidence of HCC and the mortality benefit achieved by treatment. Harms were sensitive to the rates of false-positive testing and the frequency of liver biopsy. CONCLUSION: There is a balance between the small absolute mortality benefit to surveillance for HCC and the numerically more frequent harms resulting from false-positive testing. Implementation of the recently revised American Association for the Study of Liver Diseases recommendations is predicted to reduce harms from unnecessary liver biopsy. (Hepatology 2017;66:1546-1555).

Fusel alcohols regulate translation initiation by inhibiting eIF2B to reduce ternary complex in a mechanism that may involve altering the integrity and dynamics of the eIF2B body.

Recycling of eIF2-GDP to the GTP-bound form constitutes a core essential, regulated step in eukaryotic translation. This reaction is mediated by eIF2B, a heteropentameric factor with important links to human disease. eIF2 in the GTP-bound form binds to methionyl initiator tRNA to form a ternary complex, and the levels of this ternary complex can be a critical determinant of the rate of protein synthesis. Here we show that eIF2B serves as the target for translation inhibition by various fusel alcohols in yeast. Fusel alcohols are endpoint metabolites from amino acid catabolism, which signal nitrogen scarcity. We show that the inhibition of eIF2B leads to reduced ternary complex levels and that different eIF2B subunit mutants alter fusel alcohol sensitivity. A DNA tiling array strategy was developed that overcame difficulties in the identification of these mutants where the phenotypic distinctions were too subtle for classical complementation cloning. Fusel alcohols also lead to eIF2alpha dephosphorylation in a Sit4p-dependent manner. In yeast, eIF2B occupies a large cytoplasmic body where guanine nucleotide exchange on eIF2 can occur and be regulated. Fusel alcohols impact on both the movement and dynamics of this 2B body. Overall, these results confirm that the guanine nucleotide exchange factor, eIF2B, is targeted by fusel alcohols. Moreover, they highlight a potential connection between the movement or integrity of the 2B body and eIF2B regulation.