The First ITS Meeting

The first International Transplant Science (ITS) meeting jointly organized by AST, ESOT and TTS was held on November 10-13, 2019 in Clearwater, Florida, to focus on issues related to the basic and translational science of immunology and transplantation. The 148 participants included international experts in transplantation, immunology, cell biology and organ engineering, as well as young investigators and trainees in these areas. The objectives of the meeting were to (1) introduce and discuss the latest discoveries, technologies and concepts in basic science of relevance to transplantation; (2) provide opportunities for every trainee and young investigators to present their work in mini-oral and mentored poster sessions; (3) have programmed networking opportunities to allow for the free exchange of ideas and developing new collaborations. Participants came away from the meeting inspired by the quality of science presented, excited by the opportunities to discuss science with fellow attendees, and enthusiasm for the next ITS meeting in 2020 in Europe

Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73.

The adoptive transfer of regulatory T-cells (Tregs) is a promising therapeutic approach in transplantation and autoimmunity. However, because large cell numbers are needed to achieve a therapeutic effect, in vitro expansion is required. By comparing their function, phenotype and transcriptomic profile against ex vivo Tregs, we demonstrate that expanded human Tregs switch their metabolism to aerobic glycolysis and show enhanced suppressive function through hypoxia-inducible factor 1-alpha (HIF1A) driven acquisition of CD73 expression. In conjunction with CD39, CD73 expression enables expanded Tregs to convert ATP to immunosuppressive adenosine. We conclude that for maximum therapeutic benefit, Treg expansion protocols should be optimised for CD39/CD73 co-expression

Emergency medical services preparedness in dual disasters: war in the era of COVID-19 in Armenia

Introduction: Emergency Medical Services (EMS) is a critical part of Disaster Medicine and has the ability to limit morbidity and mortality in a disaster event with sufficient training and experience. Emergency systems in Armenia are in an early stage of development and there is no Emergency Medicine residency training in the country. As a result, EMS physicians are trained in a variety of specialties. Armenia is also a country prone to disasters, and recently, the ArmenianEMSsystem was challenged by two concurrent disasters when the 2020 Nagorno-Karabakh War broke out in the midst of the SARS-CoV-2/coronavirus disease 2019 (COVID-19) pandemic. Study Objective: This study aims to assess the current state of disaster preparedness of the Armenian EMS system and the effects of the simultaneous pandemic and war on EMS providers. Methods: This was a cross-sectional study conducted by anonymous survey distributed to physicians still working in the Yerevan EMS system who provided care to war casualties and COVID-19 patients. Results: Survey response rate was 70.6%.Most participants had been a physician (52.1%) or EMS physician (66.7%) for three or less years. The majority were still in residency (64.6%). Experience in battlefield medicine was limited prior to the war, with the majority reporting no experience in treating mass casualties (52.1%), wounds from explosives (52.1%), or performing surgical procedures (52.1%), and many reporting minimal to no experience in treating gunshot wounds (62.5%), severe burns (64.6%), and severe orthopedic injuries (64.6%). Participants had moderate experience in humanitarian medicine prior to war. Greater experience in battlefield medicine was found in participants with more than three years of experience as a physician (z-score −3.26; P value <.01) or as anEMS physician (z-score −2.76; P value <.01) as well as being at least 30 years old (z-score −2.11; P value = .03). Most participants felt they were personally in danger during the war at least sometimes (89.6%). Conclusion: Prior to the COVID-19 pandemic and simultaneous 2020 Nagorno-Karabakh War, EMS physicians in Armenia had limited training and experience in Disaster Medicine. This system, and the frontline physicians on whom it relies, was strained by the dual disaster, highlighting the need for Disaster Medicine training in all prehospital medical providers

T cell phenotypes in COVID-19 - a living review

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation

The role and uses of antibodies in COVID-19 infections: a living review

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity

Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries