Neurogenic stress cardiomyopathy (NSC) is a well-known syndrome complicating the early phase after an acute brain injury, potentially affecting outcomes. This article is a review of recent data on ...the putative role of localization and lateralization of brain lesions in NSC, cardiac innervation abnormalities, and new polymorphisms and other genetic causes of the sympathetic nervous system over-activity. Concerns regarding the management of stress-related cardiomyopathy syndromes during the perioperative period are also discussed. Future clinical research should explore whether specific factors explain different patient susceptibilities to the disease and should be directed towards early identification and stratification of patients at risk, so that such patients can be more carefully monitored and appropriately managed in critical care and during the perioperative period.
The autonomic nervous system (ANS) plays an important role in the human response to various internal and external stimuli, which can modify homeostasis, and exerts a tight control on essential ...functions such as circulation, respiration, thermoregulation and hormonal secretion. ANS dysfunction may complicate the perioperative course in the surgical patient undergoing anesthesia, increasing morbidity and mortality, and, therefore, it should be considered as an additional risk factor during pre‐operative evaluation. Furthermore, ANS dysfunction may complicate the clinical course of critically ill patients admitted to intensive care units, in the case of trauma, sepsis, neurologic disorders and cardiovascular diseases, and its occurrence adversely affects the outcome. In the care of these patients, the assessment of autonomic function may provide useful information concerning pathophysiology, risk stratification, early prognosis prediction and treatment strategies. Given the role of ANS in the maintenance of systemic homeostasis, anesthesiologists and intensivists should recognize as critical the evaluation of ANS function. Measurement of heart rate variability (HRV) is an easily accessible window into autonomic activity. It is a low‐cost, non‐invasive and simple to perform method reflecting the balance of the ANS regulation of the heart rate and offers the opportunity to detect the presence of autonomic neuropathy complicating several illnesses. The present review provides anesthesiologists and intensivists with a comprehensive summary of the possible clinical implications of HRV measurements, suggesting that autonomic dysfunction testing could potentially represent a diagnostic and prognostic tool in the care of patients both in the perioperative setting as well as in the critical care arena.
The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial ...intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology.
We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data.
A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data.
AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice.
Objective
Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly ...recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features.
Methods
In this cross‐sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient‐reported outcomes were analyzed using general linear models and Spearman correlation.
Results
The median age at the time of study visit was 47 years (interquartile range = 33–60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33‐item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4‐inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory‐10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls.
Significance
This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment‐related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies.
The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially ...in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.
This paper presents the observation of four-top-quark (
t
t
¯
t
t
¯
) production in proton-proton collisions at the LHC. The analysis is performed using an integrated luminosity of 140
fb
-
1
at a ...centre-of-mass energy of 13 TeV collected using the ATLAS detector. Events containing two leptons with the same electric charge or at least three leptons (electrons or muons) are selected. Event kinematics are used to separate signal from background through a multivariate discriminant, and dedicated control regions are used to constrain the dominant backgrounds. The observed (expected) significance of the measured
t
t
¯
t
t
¯
signal with respect to the standard model (SM) background-only hypothesis is 6.1 (4.3) standard deviations. The
t
t
¯
t
t
¯
production cross section is measured to be
22
.
5
-
5.5
+
6.6
fb, consistent with the SM prediction of
12.0
±
2.4
fb within 1.8 standard deviations. Data are also used to set limits on the three-top-quark production cross section, being an irreducible background not measured previously, and to constrain the top-Higgs Yukawa coupling and effective field theory operator coefficients that affect
t
t
¯
t
t
¯
production.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A search is made for potential cccover ¯cover ¯ tetraquarks decaying into a pair of charmonium states in the four muon final state using proton-proton collision data at sqrts=13 TeV, corresponding ...to an integrated luminosity of 140 fb^{-1} recorded by the ATLAS experiment at LHC. Two decay channels, J/ψ+J/ψ→4μ and J/ψ+ψ(2S)→4μ, are studied. Backgrounds are estimated based on a hybrid approach involving Monte Carlo simulations and data-driven methods. Statistically significant excesses with respect to backgrounds dominated by the single parton scattering are seen in the di-J/ψ channel consistent with a narrow resonance at 6.9 GeV and a broader structure at lower mass. A statistically significant excess is also seen in the J/ψ+ψ(2S) channel. The fitted masses and decay widths of the structures are reported.
This study tested the hypothesis that antioxidant supplementation would attenuate plasma cytokine (IL-6, tumor necrosis factor (TNF)- alpha ), and C-reactive protein (CRP) concentrations at rest and ...in response to exercise at 4300-m elevation. A total of 17 recreationally trained men were matched and assigned to an antioxidant (N = 9) or placebo (N = 8) group in a double-blinded fashion. At sea level (SL), energy expenditure was controlled and subjects were weight stable. Then, 3 wk before and throughout high altitude (HA), an antioxidant supplement (10,000 IU beta -carotene, 200 IU alpha -tocopherol acetate, 250 mg ascorbic acid, 50 mu g selenium, 15 mg zinc) or placebo was given twice daily. At HA, energy expenditure increased approximately 750 kcal times d super(-1) and energy intake decreased approximately 550 kcal times d super(-1), resulting in a caloric deficit of approximately 1200-1500 kcal times d super(-1). At SL and HA day 1 (HA1) and day HA13, subjects exercised at 55% of VO sub(2peak) until they expended approximately 1500 kcal. Blood samples were taken at rest, end of exercise, and 2, 4, and 20 h after exercise. No differences were seen between groups in plasma IL-6, CRP, or TNF- alpha at rest or in response to exercise. For both groups, plasma IL-6 concentration was significantly higher at the end of exercise, 2, 4, and 20 h after exercise at HA1 compared with SL and HA13. Plasma CRP concentration was significantly elevated 20 h postexercise for both groups on HA1 compared to SL and HA13. TNF- alpha did not differ at rest or in response to exercise. Plasma IL-6 and CRP concentrations were elevated following exercise at high altitude on day 1, and antioxidant supplementation did not attenuate the rise in plasma IL-6 and CRP concentrations associated with hypoxia, exercise, and caloric deficit.
PDF
