A Novel FibroScan Examination Dedicated to Spleen Stiffness Measurement.

Esophageal varices (EVs) are among the most severe complications of cirrhosis, with a prevalence of 50% to 60% among cirrhotic patients. International guidelines therefore recommend that cirrhotic patients should be screened for the presence of EVs. The main objective of this study was to introduce a new spleen-dedicated FibroScan (Echosens, Paris, France) examination and to assess its performance in detecting large EVs (grade 2 and 3). This novel examination has been validated in simulation and phantom studies and has been used in a population of patients with chronic liver disease. The study described here suggests that the novel spleen-dedicated FibroScan examination performs better than the standard FibroScan for the detection of large EVs (area under the curve = 0.70 for the standard examination and 0.79 [p <0.01] for the spleen examination), but further clinical studies are needed to investigate the role of spleen stiffness in the management of cirrhotic patients

FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study

BACKGROUND The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]). METHODS This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009. FINDINGS Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76–0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74–0·95, 0·85; 95% CI 0·83–0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0. INTERPRETATION The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease

Improvements of Liver MR Imaging Clinical Protocols to Simultaneously Quantify Steatosis and Iron Overload

International audiencePurpose : Fat accumulation and iron overload are important cofactors in chronic liver disease. Clinical quantifications of fat fraction and iron are currently assessed using MRI protocols. The purpose is to improve these measurements to simultaneously provide iron and fat maps from a single acquisition. Methods: Ten healthy volunteers and ten patients with steatosis underwent MRI for fat fraction (FF: IDEAL-IQ ®), iron overload concentration (IOC: Gandon, Starmap ®) and viscoelastic characterization (MR-Touch ®). IDEAL-IQ ® data, the clinical FF reference, were compared to the advanced Gandon protocol, post-treated with a 3pt Dixon method. The originality was to use IDEAL-IQ ® fat sequence to quantify iron volu-metrically using the Wood equation. To validate the iron data, the reference Gandon protocol was applied and improved to provide map of IOC. Then, IOC data were also compared to another clinical sequence (Starmap ®) which was also improved (scale, number of ROI). The estimated error associated with each method was evaluated with the coefficient of variation. Results: IDEAL-IQ ® and Gandon protocols were modified to provide simultaneously FF and IOC maps (2D, volume). Healthy FF were in the same range with all protocols (≈3%). For patients with steatosis, Gandon protocols underestimated the FF value (≈7%) compared to IDEAL-IQ ®. Healthy and fibrosis patients were correctly diagnosed (no hemochromatosis) with all the protocols and viscoelastic properties were in the same range. Conclusion: Manufacturer's tools were improved to simultaneously quantify liver markers saving time for the patient and the clinical setting. These parameters are of great value for clinical diagnostics and novel therapeutics to treat liver diseases

MEDINFO 2013 : proceedings of the 14th world congress and medical and health informatics : part 1 and 2

Non-alcoholic fatty liver disease (NAFLD) is a hepatic dis-ease associated with metabolic syndrome. NAFLD covers a spectrum of liver disease from steatosis to non-alcoholic stea-tohepatitis (NASH) and cirrhosis. NASH is a disease evolving under the influence of various stimuli still poorly understood. In this paper we present new clinical decision support system (CDSS) for the diagnosis of NASH and the comparison of this system with machine learn-ing algorithms

Risk factors for candidemia after open heart surgery: Results from a multicenter case-control study

30nononeBackground. Candida species are among the most frequent causative agents of health care-associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. Methods. This retrospective, matched case-control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. Results. Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14-36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73-98.95; P <.001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57-30.67; P =.001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61-20.41; P =.007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91-16.63; P =.002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study. Conclusions. Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.openGiacobbe D.R.; Salsano A.; Del Puente F.; Miette A.; Vena A.; Corcione S.; Bartoletti M.; Mularoni A.; Maraolo A.E.; Peghin M.; Carnelutti A.; Losito A.R.; Raffaelli F.; Gentile I.; Maccari B.; Frisone S.; Pascale R.; Mikus E.; Medaglia A.A.; Conoscenti E.; Ricci D.; Lupia T.; Comaschi M.; Giannella M.; Tumbarello M.; de Rosa F.G.; Bono V.D.; Mikulska M.; Santini F.; Bassetti M.Giacobbe, D. R.; Salsano, A.; Del Puente, F.; Miette, A.; Vena, A.; Corcione, S.; Bartoletti, M.; Mularoni, A.; Maraolo, A. E.; Peghin, M.; Carnelutti, A.; Losito, A. R.; Raffaelli, F.; Gentile, I.; Maccari, B.; Frisone, S.; Pascale, R.; Mikus, E.; Medaglia, A. A.; Conoscenti, E.; Ricci, D.; Lupia, T.; Comaschi, M.; Giannella, M.; Tumbarello, M.; de Rosa, F. G.; Bono, V. D.; Mikulska, M.; Santini, F.; Bassetti, M

Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF). a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study

Background: Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. Methods: In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. Findings: Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14–1·68) for asundexian 20 mg (three events), 0·16 (0·01–0·99) for asundexian 50 mg (one event), and 0·33 (0·09–0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. Interpretation: The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. Funding: Bayer