Clonal restriction and predominance of regulatory T cells in coronary thrombi of patients with acute coronary syndromes

Aims Regulatory T cells (Treg) exert anti-inflammatory and atheroprotective effects in experimental atherosclerosis. Treg can be induced against specific antigens using immunization strategies associated with clonal restriction. No data exist on Treg in combination with clonal restriction of T cells in patients with acute coronary syndromes (ACS). Methods and results Among T cell subsets characterized by flow cytometry, Treg (CD4+ CD25+ CD127low) were twice as frequent in coronary thrombi compared with peripheral blood. Treg prevailed among T cell subsets identified in coronary thrombi. To evaluate clonal restriction, genomic DNA was extracted from coronary thrombi and peripheral blood in order to evaluate T cell receptor (TCR) β chain diversity by means of Multi-N-plex PCR using a primer specific for all TCR β V gene segments and another primer specific for TCR β J gene segments. T cell receptor diversity was reduced in thrombi compared with peripheral blood (intra-individual comparisons in 16 patients) with 8 gene rearrangements in the TCR common in at least 6 out of 16 analysed coronary thrombi. Compared with age-matched healthy controls (n = 16), TCR diversity was also reduced in peripheral blood of patients with ACS; these findings were independent of peripheral T cell numbers. Conclusion We provide novel evidence for a perturbed T cell compartment characterized by clonal restriction in peripheral blood and coronary thrombi from patients with ACS. Our findings warrant further studies on Treg as novel therapeutic targets aimed at enhancing this anti-inflammatory component of adaptive immunity in human atherothrombosi

Strategic engagement: new models of relationship management for academic librarians

How do we best bridge the gap between the Library and the diverse academic communities it serves? Librarians need new strategies for engagement. Traditional models of liaison, aligning solutions to disciplines, are yielding to functional specialisms, including a focus on building partnerships. This paper offers a snapshot of realignment across the Russell Group from subject support to relationship management. It then follows the journey of a newly-formed Faculty and School Engagement Team. Techniques are explored for building relationship capital, anchored to a model Strategic Engagement Cycle. Theory is contrasted with the challenges of securing real buy-in to new ways of working amid diverging agendas and assumptions, notably within the Library itself. Consideration is given to the retention of aspects of subject librarian roles. Investment in a relationship management function demands staunch and ongoing commitment to fulfil its promise, not only from its performers but from across the library community

COVID-19 — Toward a comprehensive understanding of the disease

The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a compre­hensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on

Systematic review and meta-analysis appraising efficacy and safety of adrenaline for adult cardiopulmonary resuscitation

BACKGROUND: There is a beneficial effect of adrenaline during adult cardiopulmonary resuscitation (CPR) from cardiac arrest but there is also uncertainty about its safety and effectiveness. The aim of this study was to evaluate the use of adrenaline versus non-adrenaline CPR. METHODS: PubMed, ScienceDirect, Embase, CENTRAL (Cochrane Central Register of Controlled Trials) and Google Scholar databases were searched from their inception up to 1st July 2020. Two reviewers independently assessed eligibility and risk of bias, with conflicts resolved by a third reviewer. Risk ratio (RR) or mean difference of groups were calculated using fixed or random-effect models. RESULTS: Nineteen trials were identified. The use of adrenaline during CPR was associated with a significantly higher percentage of return of spontaneous circulation (ROSC) compared to non-adrenaline treatment (20.9% vs. 5.9%; RR = 1.87; 95% confidence interval [CI] 1.37-2.55; p < 0.001). The use of adrenaline in CPR was associated with ROSC at 19.4% and for non-adrenaline treatment - 4.3% (RR = 3.23; 95% CI 1.89-5.53; p < 0.001). Survival to discharge (or 30-day survival) when using adrenaline was 6.8% compared to non-adrenaline treatment (5.5%; RR = 0.99; 95% CI 0.76-1.30; p = 0.97). However, the use of adrenaline was associated with a worse neurological outcome (1.6% vs. 2.2%; RR = 0.57; 95% CI 0.42-0.78; p < 0.001). CONCLUSIONS: This review suggests that resuscitation with adrenaline is associated with the ROSC and survival to hospital discharge, but no higher effectiveness was observed at discharge with favorable neurological outcome. The analysis showed higher effectiveness of ROSC and survival to hospital discharge in non-shockable rhythms. But more multicenter randomized controlled trials are needed in the future

COVID-19 — Toward a comprehensive understanding of the disease

The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a compre­hensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on

Noninvasive Imaging of Endothelial Damage in Patients with different HbA1c-levels, a Proof-of-Concept Study

The aim of this study was to compare endothelial permeability, which is considered a hallmark of CAD, between patients with different HbA1c-levels using an albumin-binding-MR-probe. This cross-sectional-study included 26 patients with clinical indication for x-ray-angiography, which were classified into 3 groups according to their HbA1c-levels (HbA1c&lt;5.7%,&lt;39mmol/mol; HbA1c=5.7-6.4%,39-47mmol/mol; HbA1c≥6.5%,48mmol/mol). Subjects underwent gadofosveset-enhanced-coronary-magnetic-resonance and x-ray-angiography including optical-coherence-tomography (OCT) within 24hours. Contrast-to-noise-ratios were assessed to measure the probe-uptake in the coronary-wall by coronary segment, excluding those with culprit lesions in x-ray-angiography. In the group of patients with HbA1c-levels between 5.7-6.4% 0.30 increased normalized CNR values were measured, compared to patients with HbA1c-levels &lt;5.7% (0.30; 95% CI:[0.04, 0.57]). In patients with HbA1c levels ≥6.5%, we found 0.57 higher normalized CNR values as compared to patients with normal HbA1c-levels (0.57;95% CI:[0.28,0.85]) and 0.26 higher CNR values for patients with HbA1c-level≥6.5% as compared to patients with HbA1c-levels between 5.7-6.4% (0.26; 95% CI: [-0.04, 0.57]). Additionally late atherosclerotic lesions were more common in patients with high HbA1c-levels (HbA1c ≥6.5%:n=14 (74%); HbA1c 5.7-6.4%:n=6 (60%); HbA1c&lt;5.7%:n=10 (53%)).In conclusion, coronary-magnetic-resonance imaging in combination with an albumin-binding probe suggests that both patients with intermediate and high HbA1c-levels are associated with a higher extent of endothelial damage of the coronary arteries as compared to patients with HbA1c-levels below 5.7.</p