Prognostic association supports indexing size measures in echocardiography by body surface area.

Body surface area (BSA) is the most commonly used metric for body size indexation of echocardiographic measures, but its use in patients who are underweight or obese is questioned (body mass index (BMI) < 18.5 kg/m2 or ≥ 30 kg/m2, respectively). We aim to use survival analysis to identify an optimal body size indexation metric for echocardiographic measures that would be a better predictor of survival than BSA regardless of BMI. Adult patients with no prior valve replacement were selected from the National Echocardiography Database Australia. Survival analysis was performed for echocardiographic measures both unindexed and indexed to different body size metrics, with 5-year cardiovascular mortality as the primary endpoint. Indexation of echocardiographic measures (left ventricular end-diastolic diameter [n = 230,109] and mass [n = 224,244], left atrial volume [n = 150,540], aortic sinus diameter [n = 90,805], right atrial area [n = 59,516]) by BSA had better prognostic performance vs unindexed measures (underweight: C-statistic 0.655 vs 0.647; normal weight/overweight: average C-statistic 0.666 vs 0.625; obese: C-statistic 0.627 vs 0.613). Indexation by other body size metrics (lean body mass, height, and/or weight raised to different powers) did not improve prognostic performance versus BSA by a clinically relevant magnitude (average C-statistic increase ≤ 0.02), with smaller differences in other BMI subgroups. Indexing measures of cardiac and aortic size by BSA improves prognostic performance regardless of BMI, and no other body size metric has a clinically meaningful better performance.

Decreased diastolic hydraulic forces incrementally associate with survival beyond conventional measures of diastolic dysfunction.

Decreased hydraulic forces during diastole contribute to reduced left ventricular (LV) filling and heart failure with preserved ejection fraction. However, their association with diastolic function and patient outcomes are unknown. The aim of this retrospective, cross-sectional study was to determine the mechanistic association between diastolic hydraulic forces, estimated by echocardiography as the atrioventricular area difference (AVAD), and both diastolic function and survival. Patients (n = 5176, median [interquartile range] 5.5 [5.0-6.1] years follow-up, 1213 events) were selected from the National Echo Database Australia (NEDA) based on the presence of relevant transthoracic echocardiographic measures, LV ejection fraction (LVEF) ≥ 50%, heart rate 50-100 beats/minute, the absence of moderate or severe valvular disease, and no prior prosthetic valve surgery. NEDA contains echocardiographic and linked national death index mortality outcome data from 1985 to 2019. AVAD was calculated as the cross-sectional area difference between the LV and left atrium. LV diastolic dysfunction was graded according to 2016 guidelines. AVAD was weakly associated with E/e', left atrial volume index, and LVEF (multivariable global R2 = 0.15, p < 0.001), and not associated with e' and peak tricuspid regurgitation velocity. Decreased AVAD was independently associated with poorer survival, and demonstrated improved model discrimination after adjustment for diastolic function grading (C-statistic [95% confidence interval] 0.644 [0.629-0.660] vs 0.606 [0.592-0.621], p < 0.001) and E/e' (0.649 [0.635-0.664] vs 0.634 [0.618-0.649], p < 0.001), respectively. Therefore, decreased hydraulic forces, estimated by AVAD, are weakly associated with diastolic dysfunction and demonstrate an incremental prognostic association with survival beyond conventional measures used to grade diastolic dysfunction.

Anti-fibrinolytic agent tranexamic acid suppresses the endotoxin-induced expression of Tnfα and Il1α genes in a plasmin-independent manner.

INTRODUCTION: Tranexamic acid (TXA) is widely used as an antifibrinolytic agent in hemorrhagic trauma patients. The beneficial effects of TXA exceed the suppression of blood loss and include the ability to decrease inflammation and edema. We found that TXA suppresses the release of mitochondrial DNA and enhances mitochondrial respiration. These results allude that TXA could operate through plasmin-independent mechanisms. To address this hypothesis, we compared the effects of TXA on lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines in plasminogen (Plg) null and Plg heterozygous mice. METHODS: Plg null and Plg heterozygous mice were injected with LPS and TXA or LPS only. Four hours later, mice were sacrificed and total RNA was prepared from livers and hearts. Real time quantitative polymerase chain reaction with specific primers was used to assess the effects of LPS and TXA on the expression of pro-inflammatory cytokines. RESULTS: LPS enhanced the expression of Tnfα in the livers and hearts of recipient mice. The co-injection of TXA significantly decreased the effect of LPS both in Plg null and heterozygous mice. A similar trend was observed with LPS-induced Il1α expression in hearts and livers. CONCLUSIONS: The effects of TXA on the endotoxin-stimulated expression of Tnfα and Il1α in mice do not depend on the inhibition of plasmin generation. These results indicate that TXA has other biologically important target(s) besides plasminogen/plasmin. Fully understanding the molecular mechanisms behind the extensive beneficial effects of TXA and future identification of its targets may lead to improvement in the use of TXA in trauma, cardiac, and orthopedic surgical patients.

A Multirobot Person Search System for Finding Multiple Dynamic Users in Human-Centered Environments.

Multirobot coordination for finding multiple users in an environment can be used in numerous robotic applications, including search and rescue, surveillance/monitoring, and activities of daily living assistance. Existing approaches have limited coordination between robots when generating team plans or do not consider user location probability within these plans. This results in long searches and robots potentially revisiting the same locations in succession. In this article, we present a novel multirobot person search system to generate search plans for multirobot teams to find multiple dynamic users before a deadline. Our approach is unique in that it simultaneously considers the search actions of all robots and user location probabilities when generating team plans, where user location probabilities are represented as conditional spatial-temporal probability density functions. We model this multirobot person search problem as a two-stage optimization problem to maximize the expected number of users found before the deadline. Stage 1 solves the action selection problem to determine a set of team actions, and the second stage solves the action allocation problem to distribute these actions amongst the robots. Namely, in stage 1, a novel conditional multiperiod multiknapsack problem is modeled as a min-flow graph solved sequentially by the Bellman-Ford shortest path algorithm. Stage 2 is a variant of the min-max multitraveling salesperson problem which models the environment topology as a search region network and search times selected by the previous stage. This stage is solved by a novel fuzzy clustering method. Numerous experiments comparing our proposed method to other existing approaches with varying environment sizes, search durations, and the number of users showed that our approach was able to find more target users before a defined deadline.

Non-reversible tissue fixation retains extracellular vesicles for in situ imaging.

Extracellular vesicles (EVs) are secreted nanosized particles with many biological functions and pathological associations. The inability to image EVs in fixed tissues has been a major limitation to understanding their role in healthy and diseased tissue microenvironments. Here, we show that crosslinking mammalian tissues with formaldehyde results in significant EV loss, which can be prevented by additional fixation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) for visualization of EVs in a range of normal and cancer tissues.