Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies

10.1038/npjamd.2015.5npj Aging and Mechanisms of Disease1500

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

CMV induces expansion of highly polyfunctional CD4+ T cell subset coexpressing CD57 and CD154.

CD4+ T cells are essential for human CMV infection control. CMV-specific CD4+ T cells possess antiviral functions and participate in anti-CMV humoral/cellular responses. In the elderly, CMV infection impairs immunity to other viruses and has been traditionally associated with T cell senescence; however, recent results suggest that, in younger people, CMV confers immune protection against other pathogens (heterologous immunity). To shed light on this controversy, we analyzed latent CMV infection effects on the quality of young individuals' immune response, specifically, the presence of polyfunctional T cells through an extensive phenotypic and functional characterization of the CD4+ T cell subset. CD154 expression, degranulation (CD107a), and cytokine production (IFN-γ, TNF-α, and IL-2) as well as T cell phenotype markers (CD57, CD28, and CD27) were analyzed. We demonstrate that CD4+ T cells that coexpress CD57 and CD154, which are exclusively present in CMV-positive individuals, are the most polyfunctional CD4+ subset, whereas CD4+CD27+CD28- T cells associate with lower polyfunctionality. Conversely, the frequency of CD4+CD28+ T cells correlates with higher polyfunctionality of CD4+CD57- T cells from CMV-seronegative individuals and CD4+CD57+CD154+ T cells from CMV-seropositive individuals. Thus, polyfunctionality is a property of central memory CD4+ T cells in CMV-seronegative individuals, whereas after CMV infection, polyfunctional T cells become highly differentiated, which allows efficient eradication of infections. We extend previous observations of the impact of CMV on CD8+ T cell functionality to the CD4+ T cell compartment, revealing CD57 as a polyfunctionality marker of T cells which expands after CMV infection. CD57+ T cells have been associated with inflammatory conditions, but their potential role in the response against infectious disease and vaccination should now be investigated

NIHR Liver/Renal Biomarker Programme Final Report: Evaluating the benefits for patients and the NHS of new and existing biological fluid biomarkers in liver and renal disease

Protein biomarkers are naturally occurring substances that can be measured, often in fluids such as blood or urine, and which provide information about a patient and their illness. Different diseases have different biomarkers. When people become ill, changes in biomarker levels may occur before any clinical symptoms or signs become apparent. Measuring biomarkers in blood or urine is simple, safe and may help the doctor diagnose which disease the patient has, determine how severe it is, help choose the best treatment and help detect if the disease is getting worse or better. Unfortunately, for many diseases there are not enough biomarkers that are of proven usefulness in patient care today. New developments in research mean that many more are now being discovered but there is no quick and reliable way to decide which of the markers are good enough to be useful clinically. While our research proposal focusses on diseases of the liver and kidney, in the future it can also serve as the "blueprint" for similar work in other diseases. It is aimed at developing a structure and methods to assess the clinical usefulness of biomarkers as quickly and efficiently as possible. The research is divided into three parallel workstreams : 1. Identification of the best research methods for monitoring disease or treatment with biomarkers - the lack of understanding this has hampered this field so far. 2. The creation of a sample "banking" system for collecting and storing patient samples and relevant clinical data from large numbers of patients. This will allow the immediate testing of potential new biomarkers now and in the future. The best biomarkers would then go on to full trials to see if patients and the NHS would benefit from their use. 3. A clinical trial at multiple hospitals in the UK of three new biomarkers for liver damage (together called the "Enhanced liver fibrosis" or "ELF", test). We will find out if ELF can give early warning of dangerous liver damage (cirrhosis) and therefore reduce the risk of major complications. This trial may radically alter the way in which patients with liver disease can be looked after clinically. This research programme will benefit patients and the NHS by ensuring that biomarkers in the future can be evaluated and introduced more rapidly, improving clinical management for each individual patient and leading to better use of NHS resources