No abstract

The integration of advance care planning (ACP) as part of the comprehensive geriatric assessment (CGA) of hospitalised frail elderly patients, together with the clinical and demographic factors that determine successful ACP discussion, has not been previously explored. METHODSA cross-sectional study on patients and family caregivers admitted under the geriatric medicine department of a tertiary hospital was conducted from October 2015 to December 2016. RESULTS Among 311 eligible patients, 116 (37.3%) patients completed ACP discussion while 166 (53.4%) patients declined, with 62 (37.3%) of the decliners providing reasons for refusal. Univariate logistic regression analysis showed that older age, higher Charlson Comorbidity Index, poorer functional status and cognitive impairment had statistically significant associations with agreeing to ACP discussion (p < 0.05). On multivariate logistic regression analysis, only poorer functional status was significantly associated (odds ratio 2.22 [95% confidence interval 1.27-3.87]; p = 0.005). Among those who completed ACP discussion, a majority declined cardiopulmonary resuscitation (79.3%), preferred limited medical intervention or comfort care (82.8%), and opted for blood transfusion (62.9%), antibiotics (73.3%) and intravenous fluid (74.1%) but declined haemodialysis (50.9%). Decision-making was divided for enteral feeding. Among decliners, the main reasons for refusal were 'not keen' (33.9%), 'deferring to doctors' decision' (11.3%) and 'lack of ACP awareness' (11.3%). CONCLUSIONThe feasibility and utility of integrating ACP as part of CGA has been demonstrated. Poorer functional status is significantly associated with successful ACP discussion. Greater public education on end-of-life care choices (besides cardiopulmonary resuscitation) and follow-up with decliners are recommended.

Molecular excitations in the liquid-phase environment are renormalized by the surrounding solvent molecules. Herein, we employ the GW approximation to investigate the solvation effects on the ionization energy of phenol in various solvent environments. The electronic effects differ by up to 0.4 eV among the five investigated solvents. This difference depends on both the macroscopic solvent polarizability and the spatial decay of the solvation effects. The latter is probed by separating the electronic subspace and the GW correlation self-energy into fragments. The fragment correlation energy decays with increasing intermolecular distance and vanishes at ∼9 Å, and this pattern is independent of the type of solvent environment. The 9 Å cutoff defines an effective interacting volume within which the ionization energy shift per solvent molecule is proportional to the macroscopic solvent polarizability. Finally, we propose a simple model for computing the ionization energies of molecules in an arbitrary solvent environment.

Calcific aortic valve disease (CAVD) is a complex cardiovascular pathology, culminating in aortic stenosis, heart failure and premature mortality, with no comprehensive treatment strategy, except valve replacement. While T cells have been identified within the valve, their contribution to pathogenesis remains unclear. To elucidate the heterogeneous phenotype of the immune populations present within patients with CAVD, deep phenotypic screens of paired valve and peripheral blood cells were conducted via flow cytometry (n=20) and immunohistochemistry (n=10). Following identification of a significant population of memory T cells; specifically, CD8+ T cells within the valve, single cell RNA sequencing and paired single T cell receptor sequencing was conducted on a further 4 patients on CD45+ CD3+, CD4+ or CD8+ T cells. Through unsupervised clustering, 7 T cell populations were identified within the blood and 10 identified within the valve. Tissue resident memory (TRM) T cells were detected for the first time within the valve, exhibiting a highly cytotoxic, activated, and terminally differentiated phenotype. This pan-pro-inflammatory signal was differentially identified in T cells originating from the valve, and not observed in the blood, indicative of an adaptive, local not-systemic inflammatory signature in CAVD patients. T cell receptor analysis identified hyperexpanded clones within the CD8+ T cell central memory (TCM) population, with TRM cells comprising the majority of large and medium clonal expansion within the entire T cell population. Clonal interaction network analysis demonstrated the greatest proportion of clones originating from CD8+ T cell effector memory (TEM) and CD4+ naive / TCM populations and ending in the CD8+ TRM and CD8+ TCM clusters, suggesting a clonal expansion and predicted trajectory of T cells towards a tissue resident, cytotoxic environment within the valve. CDR3 epitope predictive analysis identified 7 potential epitope targets, of which GALNT4 and CR1L have previously been implicated in a cardiovascular context as mediators of inflammation. Taken together, the data identified T cell sub-populations within the context of CAVD and further predicted possible epitopes responsible for the clonal expansion of the valvular T cells, which may be important for propagating inflammation in CAVD.