Impact of propofol on mid-latency auditory-evoked potentials in children†

Background Propofol is increasingly used in paediatric anaesthesia, but can be challenging to titrate accurately in this group. Mid-latency auditory-evoked potentials (MLAEPs) can be used to help titrate propofol. However, the effects of propofol on MLAEP in children are unclear. Therefore, we investigated the relationship between propofol and MLAEP in children undergoing anaesthesia. Methods Fourteen healthy children aged 4-16 yr received anaesthesia for elective surgery. Before surgery, propofol was administered in three concentrations (3, 6, 9 µg ml−1) through a target-controlled infusion pump using Kataria and colleagues' model. MLAEPs were recorded 5 min after having reached each target propofol concentration at each respective concentration. Additionally, venous propofol blood concentrations were assayed at each measuring time point. Results Propofol increased all four MLAEP peak latencies (peaks Na, Pa, Nb, P1) in a dose-dependent manner. In addition, the differences in amplitudes were significantly smaller with increasing propofol target concentrations. The measured propofol plasma concentrations correlated positively with the latencies of the peaks Na, Pa, and Nb. Conclusions Propofol affects MLAEP latencies and amplitudes in children in a dose-dependent manner. MLAEP measurement might therefore be a useful tool for monitoring depth of propofol anaesthesia in childre

Cells' Flow and Immune Cell Priming under alternating g-forces in Parabolic Flight

Gravitational stress in general and microgravity (mu g) in particular are regarded as major stress factors responsible for immune system dysfunction in space. To assess the effects of alternating mu g and hypergravity (hyper-g) on immune cells, the attachment of peripheral blood mononuclear cells (PBMCs) to adhesion molecules under flow conditions and the antigen-induced immune activation in whole blood were investigated in parabolic flight (PF). In contrast to hyper-g (1.8 g) and control conditions (1 g), flow and rolling speed of PBMCs were moderately accelerated during mu g-periods which were accompanied by a clear reduction in rolling rate. Whole blood analyses revealed a "primed" state of monocytes after PF with potentiated antigen-induced pro-inflammatory cytokine responses. At the same time, concentrations of anti-inflammatory cytokines were increased and monocytes displayed a surface molecule pattern that indicated immunosuppression. The results suggest an immunologic counterbalance to avoid disproportionate immune responses. Understanding the interrelation of immune system impairing and enhancing effects under different gravitational conditions may support the design of countermeasures to mitigate immune deficiencies in space

NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation?

This poster paper reviews the use of 14 day undersea missions as a possible analog for short duration spaceflight for the study of immune system dysregulation. Sixteen subjects from the the NASA Extreme Enviro nment Mission Operations (NEEMO) 12, 13 and 14 missions were studied for immune system dysregulation. The assays that are presented in this poster are the Virleukocyte subsets, the T Cell functions, and the intracellular/secreted cytokine profiles. Other assays were performed, but are not included in this presntation

From Space to the Patient: A New Cytokine Release Assay to Monitor the Immune Status of HIV Infected Patients and Sepsis Patients

Monitoring of humans either in the healthy men under extreme environmental stress like space flight, in human immunodeficiency virus (HIV) infected patients or in sepsis is of critical importance with regard to the timing of adequate therapeutic (counter-)measures. The in vivo skin delayed-type hypersensitivity test (DTH) served for many years as a tool to evaluate cell mediated immunity. However, this standardised in vivo test was removed from the market in 2002 due to the risk of antigen stabilization. To the best of our knowledge an alternative test as monitoring tool to determine cell mediated immunity is not available so far. For this purpose we tested a new alternative assay using elements of the skin DTH which is based on an ex vivo cytokine release from whole blood and asked if it is suitable and applicable to monitor immune changes in HIV infected patients and in patients with septic shock

The ESA-NASA 'CHOICE' Study: Winterover at Concordia Station, Interior Antarctica, as an Analog for Spaceflight-Associated Immune Dysregu1ation

For ground-based space physiological research, the choice of analog must carefully match the system of interest. Antarctica winter-over at the European Concordia Station is potentially a ground-analog for spaceflight-associated immune dysregulation (SAID). Concordia missions consist of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation, disrupted circadian rhythms and international crews. The ESA-NASA CHOICE study assess innate and adaptive immunity, viral reactivataion and stress factors during Concordia winter-over deployment. To date, not all samples have been analyzed. Here, only data will be preliminary presented for those parameters where sample/data analysis is completed (i.e., Leukocyte subsets, T cell function, and intracellular/secreted cytokine profiles.

Immune System Dysregulation and Latent Herpesvirus Reactivation During Winterover at Concordia Station, Dome C, Antarctica

Immune system dysregulation occurs during spaceflight and consists of altered peripheral leukocyte distribution, reductions in immunocyte function and altered cytokine production profiles. Causes may include stress, confinement, isolation, and disrupted circadian rhythms. All of these factors may be replicated to some degree in terrestrial environments. NASA is currently evaluating the potential for a ground-based analog for immune dysregulation, which would have utility for mechanistic investigations and countermeasures evaluation. For ground-based space physiology research, the choice of terrestrial analog must carefully match the system of interest. Antarctica winter-over, consisting of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation and disrupted circadian rhythms, is potentially a good ground-analog for spaceflight-associated immune dysregulation. Of all Antarctica bases, the French-Italian Concordia Station, may be the most appropriate to replicate spaceflight/exploration conditions. Concordia is an interior base located in harsh environmental conditions, and has been constructed to house small, international crews in a station-environment similar to what should be experienced by deep space astronauts. The ESA-NASA CHOICE study assessed innate and adaptive immunity, viral reactivation and stress factors during Concordia winterover deployment. The study was conducted over two winterover missions in 2009 and 2010. Final study data from NASA participation in these missions will be presented

Headache under simulated microgravity is related to endocrine, fluid distribution, and tight junction changes

Paroxysmal Cerebral Disorder

Pitfalls in PSMA imaging: [18F]rhPSMA-7-PET/CT reveals presence of chrondrosarcoma

Purpose!#!Reporting of adverse drug reactions (ADRs) by patients is essential for a comprehensive risk-benefit evaluation of drugs after marketing, but only few data are available regarding patient-centred web-based ADR reporting systems. Hence, we aimed to analyze ADRs reported by patients with a particular emphasis on novel drugs and serious ADRs not yet labelled in the respective summary of product characteristics (SPC).!##!Methods!#!All ADR reports received by a web-based, patient-centred platform ( www.nebenwirkungen.de ) between April 1, 2019, and September 1, 2020, were descriptively analyzed. ADRs and drugs were coded automatically according to MedDRA and ATC classification system. SPC labelling of reported ADRs for novel drugs marketed since 2015 was checked manually.!##!Results!#!In total, 13,515 patient reports including 29,529 ADRs were received during the study period (serious ADRs [SADRs] n = 1,318; 4.5%). Women were affected in more than two-thirds of ADR reports. The most common patient-reported ADRs were nausea, dizziness and headache, whereas arrhythmia, intestinal obstruction and erectile dysfunction were the most frequent SADRs. Ciprofloxacin, levothyroxine and venlafaxine were the compounds most frequently suspected for causing both ADRs and SADRs. Regarding novel compounds, 289 reports including 739 ADRs were received (mainly fatigue, headache and myalgia). Three hundred thirty-one (44.8%) out of those ADRs were not yet labelled in the respective SPC, whereof twelve were SADRs.!##!Conclusion!#!The majority of patient-reported ADRs were non-serious. However, a relevant number of non-labelled even serious ADRs was reported for novel compounds by patients. Despite well-known limitations of patient-reported ADRs, this web-based ADR reporting system contributes to the identification of new ADRs and thus can help to improve patients' safety complementing other pharmacovigilance instruments

Five days of head-down-tilt bed rest induces noninflammatory shedding of L-selectin

Head-down-tilt bed rest (HDTBR) is a popular model, simulating alterations of gravitation during space missions. The aim of this study was to obtain a better insight into the complexly orchestrated regulations of HDTBR-induced immunological responses, hypothesizing that artificial gravity can mitigate these HDTBR-related physiological effects. This crossover-designed 5 days of HDTBR study included three protocols with no, or daily 30 min of centrifugation or 6 X 5 min of centrifugation. Twelve healthy, male participants donated blood pre-HDTBR, post-HDTBR, and twice during HDTBR. Cellular immune changes were assessed either by enumerative and immune cell phenotyping assays or by functional testing of responses to either recall antigens or receptor-dependent activation by chemotactic agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and with TNF-alpha. The expression of the adhesion molecule L-selectin (CD62L) on the surface of granulocytes and its shedding into plasma samples were measured. In parallel, other humoral factor, such as interleukin-6 and interleukin-8, parameters of endothelial damage (glycocalyx) were determined. Hematocrit and hemoglobin were significantly increased during HDTBR. Although immune functional tests did not indicate a change in the immune performance, the expression of CD62L on resting granulocytes was significantly shed by 50% during HDTBR. Although the latter is normally associated to an activation of inflammatory innate immune responses and during interaction of granulocytes with the endothelium, CD62L shedding was, however, not related either to a systemic inflammatory alteration or to shedding of the endothelial glycocalyx during bed rest. This suggests a noninflammatory or "mechanical" shedding related to fluid shifts during head-down intervention and not to an acute inflammatory process