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

Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis

Background Kawasaki disease (KD) is a systemic inflammatory condition occurring predominantly in children. Coronary artery bypass grafting (CABG) is performed in the presence of inflammation and aneurysms of the coronary arteries. The objectives of our study were to assess which CABG strategy provides better graft patency and early and long-term outcomes. Methods A systematic review using Medline, Cochrane, and Scopus databases was performed in February 2020, incorporating a network meta-analysis, performed by random-effect model within a Bayesian framework, and pooled prevalence of adverse outcomes. Hazard ratios (HR) and corresponding 95% credible intervals (CI) were calculated by Markov chain Monte Carlo methods. Results Among 581 published reports, 32 studies were selected, including 1,191 patients undergoing CABG for KD. Graft patency of internal thoracic arteries (ITAs), saphenous veins (SV), and other arteries (gastroepiploic artery and radial artery) was compared. ITAs demonstrated the best patency rates at long-term follow-up (HR 0.33, 95% CI: 0.17\u20130.66). Pooled prevalence of early mortality after CABG was 0.28% (95% CI: 0.00\u20130.73%, I2 = 0%, tau2 = 0), with 63/1,108 and 56/1,108 patients, undergoing interventional procedures and surgical re-interventions during follow-up, respectively. Pooled prevalence was 3.97% (95% CI: 1.91\u20136.02%, I2 = 60%, tau2 = 0.0008) for interventional procedures and 3.47% (95% CI: 2.26\u20134.68%, I2 = 5%, tau2 <0.0001) for surgical re-interventions. Patients treated with arterial, venous, and mixed (arterial plus second venous graft) CABG were compared to assess long-term mortality. Mixed CABG (HR 0.03, 95% CI: 0.00\u20130.30) and arterial CABG (HR 0.13, 95% CI: 0.00\u20131.78) showed reduced long-term mortality compared with venous CABG. Conclusions CABG in KD is a safe procedure. The use of arterial conduits provides better patency rates and lower mortality at long-term follow-up

Methods to diagnose acute anterior cruciate ligament rupture: a meta-analysis of instrumented knee laxity tests

The aims of this meta-analysis were to determine the sensitivity and specificity of the KT 1000 Arthrometer, Stryker Knee Laxity Tester and Genucom Knee Analysis System for ACL rupture. It was hypothesized that the KT 1000 test is the most sensitive and specific. Secondly, it was hypothesized that the sensitivity and specificity of the KT 1000 arthrometer increase when the amount of Newton force is increased. An electronic database search was performed using MEDLINE and EMBASE. All cross-sectional and cohort studies comparing one or more instrumented examination tests for diagnosing acute complete ACL rupture in living human subjects to an accepted reference standard such as arthroscopy, arthrotomy and MRI were included. The sensitivity of the KT 1000 Arthrometer with 69 N was 0.54. With 89 N, the sensitivity was 0.78 and the specificity 0.92, and with maximum manual force, the sensitivity was 0.93 and the specificity 0.93. For the Stryker Knee Laxity Tester, the sensitivity was 0.82 and the specificity 0.90. And for the Genucom Knee Analysis System, the sensitivity was 0.74 and the specificity 0.82. The KT Arthrometer performed with maximum manual force has the highest sensitivity, specificity, accuracy and positive predictive value for diagnosing ACL rupture. Meta-analysis, Level

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