Modeling Brain–Heart Crosstalk Information in Patients with Traumatic Brain Injury

Publisher Copyright: © 2021, The Author(s).Background: Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality. Methods: In our previous work, we introduced a novel measure of brain–heart interaction termed brain–heart crosstalks (ctnp), as well as two additional brain–heart crosstalks indicators [mutual information (mict) and average edge overlap (ωct)] obtained through a complex network modeling of the brain–heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package. Results: A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain–heart crosstalks varied (mean 58, standard deviation 57). The Kruskal–Wallis test comparing brain–heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for mict, 0.005 for ctnp and 0.006 for ωct). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: − 0.13 for ctnp (p value 0.04), − 0.19 for ωct (p value 0.002969) and − 0.09 for mict (p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16–29, 30–49, 50–65, and 65–85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16–29, 50–65, and 65–85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain–heart crosstalks and mortality was also confirmed. Conclusions: The presence of a negative relationship between mortality and brain–heart crosstalks indicators suggests that a healthy brain–cardiovascular interaction plays a role in TBI.Peer reviewe

Political & Quasi-Adjudicative Dispute Settlement Models in European Union Free Trade Agreements - Is the Quasi-Adjudicative Model a Trend or is it Just Another Model?

In this paper, interpretation and application dispute settlement provisions of European Union (EU) Free Trade Agreements (FTAs) signed between 1963 and 2006 are analysed. This will be through the two models of Dispute Settlement in International Law: the political and adjudicative. Political elements of dispute settlement mechanisms in Public International Law and General Agreement of Tariffs and Trade (GATT) served to establish those of the EU FTAs. Adjudicative and quasi-adjudicative elements of dispute settlement mechanisms of Public International Law and World Trade Organization (WTO) Law were used as parameters to set up those of the EU FTAs. These parameters also helped to define a new and unique hybrid model. The features of this model were found in Agreements with trade issues other than FTAs. It is possible, however, for future FTAs to incorporate them. The hybrid model is based on an adjudicative framework and includes both political and adjudicative elements. In conclusion, it was found that even though WTO Members incorporated adjudicative elements in the Dispute Settlement Understanding (DSU), the EU did not incorporate them bilaterally for a further five years. Furthermore, since the creation of the DSU in 1995, the EU has established more FTAs based on a political model than on a quasi-adjudicative. Consequently, the quasi-adjudicative dispute settlement model has not represented a clear trend in EU FTAs

Diffuse Intracranial Injury Patterns Are Associated with Impaired Cerebrovascular Reactivity in Adult Traumatic Brain Injury: A CENTER-TBI Validation Study.

Recent single-center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intracranial injury and worse cerebrovascular reactivity. The goal of this study was to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high-resolution intensive care unit (HR ICU) data set. Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher) and the presence of a digital admission CT scan. Physiological signals were processed for pressure reactivity index (PRx) and both the percent (%) time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH), and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere-Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased percent (%) time and hourly dose above PRx threshold of 0, +0.25, and +0.35 (p < 0.02 for all). Logistic regression analysis displayed an association between deep peri-contusional edema and mean PRx above a threshold of +0.25. These results suggest that diffuse injury patterns, consistent with acceleration/deceleration forces, are associated with impaired cerebrovascular reactivity. Diffuse admission intracranial injury patterns appear to be consistently associated with impaired cerebrovascular reactivity, as measured through PRx. This is in keeping with the previous single-center retrospective literature on the topic. This study provides multi-center validation for those results, and provides preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern