Quantitative magnetization transfer imaging as a biomarker for effects of systemic inflammation on the brain

BACKGROUND Systemic inflammation impairs brain function and is increasingly implicated in the etiology of common mental illnesses, particularly depression and Alzheimer's disease. Immunotherapies selectively targeting proinflammatory cytokines demonstrate efficacy in a subset of patients with depression. However, efforts to identify patients most vulnerable to the central effects of inflammation are hindered by insensitivity of conventional structural magnetic resonance imaging. METHODS We used quantitative magnetization transfer (qMT) imaging, a magnetic resonance imaging technique that enables quantification of changes in brain macromolecular density, together with experimentally induced inflammation to investigate effects of systemic inflammatory challenge on human brain microstructure. Imaging with qMT was performed in 20 healthy participants after typhoid vaccination and saline control injection. An additional 20 participants underwent fluorodeoxyglucose positron emission tomography following the same inflammatory challenge. RESULTS The qMT data demonstrated that inflammation induced a rapid change in brain microstructure, reflected in increased magnetization exchange from free (water) to macromolecular-bound protons, within a discrete region of insular cortex implicated in representing internal physiologic states including inflammation. The functional significance of this change in insular microstructure was demonstrated by correlation with inflammation-induced fatigue and fluorodeoxyglucose positron emission tomography imaging, which revealed increased resting glucose metabolism within this region following the same inflammatory challenge. CONCLUSIONS Together these observations highlight a novel structural biomarker of the central physiologic and behavioral effects of mild systemic inflammation. The widespread clinical availability of magnetic resonance imaging supports the viability of qMT imaging as a clinical biomarker in trials of immunotherapeutics, both to identify patients vulnerable to the effects of systemic inflammation and to monitor neurobiological responses

The heart failure specialists of tomorrow: a network for young cardiovascular scientists and clinicians

The "Heart failure specialists of Tomorrow" (HoT) group gathers young researchers, physicians, basic scientists, nurses and many other professions under the auspices of the Heart Failure Association of the European Society of Cardiology. After its foundation in 2014, it has quickly grown to a large group of currently 925 members. Membership in this growing community offers many advantages during, before, and after the 'Heart Failure and World Congress on Acute Heart Failure'. These include: eligibility to receive travel grants, participation in moderated poster sessions and young researcher and clinical case sessions, the HoT walk, the career cafe, access to the networking opportunities, and interaction with a large and cohesive international community that constantly seeks multinational collaborations.Peer reviewe

Effect of blood glucose level on standardized uptake value (SUV) in F-18- FDG PET-scan : a systematic review and meta-analysis of 20,807 individual SUV measurements

Objectives To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in F-18-FDG-PET scan. Methods A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, F-18-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (200 mg/dl). Results Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p <0.001, p <0.001,) and muscle (p <0.001, p <0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p=0.008, p200 mg/dl had significantly lower SUVmax. Conclusion If BGL is lower than 200mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.Peer reviewe

Cardiovascular toxicities of immune therapies for cancer&nbsp;–&nbsp;a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio‐Oncology

ABSTRACT: The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell‐based immune therapies including chimeric antigen receptor T lymphocyte (CAR‐T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune‐related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune‐related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI‐related myocarditis with cardiogenic shock to more common complications including less severe ICI‐related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non‐inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR‐T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Hydrogen production via aqueous - Phase glucose reforming: A thermodynamic approach

In the present work the thermodynamic analysis of aqueous - phase glucose reforming reaction has been studied. For the investigation purposes the temperature range of 0 - 100°C and atmospheric total pressure have been considered. The equilibrium constant as a temperature function and the conversion of glucose to hydrogen and carbon dioxide were estimated. It was found that at almost 45°C the reaction's conversion approaches 100%. It has been reported that except for hydrogen and carbon oxides, possible products of the reaction are mostly alkanes. According to thermodynamics, glucose can be totally converted to alkanes even at very low temperature values. However, the reforming of the alkanes under the same conditions has a negligible conversion (∼0%) to hydrogen. The effect of water/carbon ratio was also examined. Results showed that as the above ratio increases conversion to hydrogen increases intensely. The effect of pressure on glucose reforming reaction was considered as well. The thermodynamic analysis showed, as expected, that total pressure affects negatively the conversion of the reaction

The FIREDASS (Fire Detection and Suppression Simulation) Model

The FIREDASS (FIRE Detection And Suppression Simulation) project is concerned with the development of fine water mist systems as a possible replacement for the halon fire suppression system currently used in aircraft cargo holds. The project is funded by the European Commission, under the BRITE EURAM programme. The FIREDASS consortium is made up of a combination of Industrial, Academic, Research and Regulatory partners. As part of this programme of work, a computational model has been developed to help engineers optimise the design of the water mist suppression system. This computational model is based on Computational Fluid Dynamics (CFD) and is composed of the following components: fire model; mist model; two-phase radiation model; suppression model and detector/activation model. The fire model - developed by the University of Greenwich - uses prescribed release rates for heat and gaseous combustion products to represent the fire load. Typical release rates have been determined through experimentation conducted by SINTEF. The mist model - developed by the University of Greenwich - is a Lagrangian particle tracking procedure that is fully coupled to both the gas phase and the radiation field. The radiation model - developed by the National Technical University of Athens - is described using a six-flux radiation model. The suppression model - developed by SINTEF and the University of Greenwich - is based on an extinguishment crietrion that relies on oxygen concentration and temperature. The detector/ activation model - developed by Cerberus - allows the configuration of many different detector and mist configurations to be tested within the computational model. These sub-models have been integrated by the University of Greenwich into the FIREDASS software package. The model has been validated using data from the SINTEF/GEC test campaigns and it has been found that the computational model gives good agreement with these experimental results. The best agreement is obtained at the ceiling which is where the detectors and misting nozzles would be located in a real system. In this paper the model is briefly described and some results from the validation of the fire and mist model are presented

Cognitive deficits in myopathies

Myopathies represent a wide spectrum of heterogeneous diseases mainly characterized by the abnormal structure or functioning of skeletal muscle. The current paper provides a comprehensive overview of cognitive deficits observed in various myopathies by consulting the main libraries (Pubmed, Scopus and Google Scholar). This review focuses on the causal classification of myopathies and concomitant cognitive deficits. In most studies, cognitive deficits have been found after clinical observations while lesions were also present in brain imaging. Most studies refer to hereditary myopathies, mainly Duchenne muscular dystrophy (DMD), and myotonic dystrophies (MDs); therefore, most of the overview will focus on these subtypes of myopathies. Most recent bibliographical sources have been preferred. © 2020 by the authors. Licensee MDPI, Basel, Switzerland