Frailty is a common negative consequence of ageing. Sarcopenia, the syndrome of loss of muscle mass, quality and strength, is more common in older adults and has been considered a precursor syndrome or the physical manifestation of frailty. The pathophysiology of both syndromes is incompletely described with multiple causes, inter-relationships and complex pathways proposed. Age-associated changes to the immune system (both immunesenescence, the decline in immune function with ageing, and inflammageing, a state of chronic inflammation) have been suggested as contributors to sarcopenia and frailty but a direct causative role remains to be established. Frailty, sarcopenia and immunesenescence are commonly described in older adults but are not ubiquitous to ageing. There is evidence that all three conditions are reversible and all three appear to share common inflammatory drivers. It is unclear whether frailty, sarcopenia and immunesenescence are separate entities that co-occur due to coincidental or potentially confounding factors, or whether they are more intimately linked by the same underlying cellular mechanisms. This review explores these possibilities focusing on innate immunity, and in particular associations with neutrophil dysfunction, inflammation and known mechanisms described to date. Furthermore, we consider whether the age-related decline in immune cell function (such as neutrophil migration), increased inflammation and the dysregulation of the phosphoinositide 3-kinase (PI3K)-Akt pathway in neutrophils could contribute pathogenically to sarcopenia and frailty.

There has been increasing interest and research into sarcopenia in community-dwelling older adults since the European Working Group on Sarcopenia in Older People (EWGSOP) agreed a consensus definition in 2010. Sarcopenia has been defined as loss of muscle mass with loss of muscle function (strength or physical performance), with measurements two Standard Deviations (SDs) below the mean of a young reference population. This definition does not necessitate longitudinal measurements, or the absence of acute illness and diagnosis can be made from single measurements. We hypothesise that hospitalisation, due to a combination of acute inflammatory burden and muscle disuse, leads to an acute decline in muscle mass and function and may lead to some individuals meeting criteria for sarcopenia, acutely, based on the EWGSOP definition. This may be partially recoverable or may lead to increased risk of developing sarcopenia long-term. We have denoted the term “acute sarcopenia” to refer to acute loss of muscle mass and function associated with hospitalisation. This review discusses some of the current available research in this context and also identifies some of the knowledge gaps and potential areas for future research.

The COVID-19 pandemic has had a devastating global impact, with older adults being most at risk of death from the disease. However, acute sarcopenia occurs in survivors of COVID-19; older adults and the most critically unwell patients are the most at risk. Acute sarcopenia is an under-recognised condition of acute muscle insufficiency, defined by declines in muscle function and/or quantity within six months, usually following a stressor event. This commentary reviews definition and mechanisms of acute sarcopenia in COVID-19 and suggests recommendations for research and clinical practice. Research should now focus on the longer-term consequences of acute sarcopenia in patients who have suffered from COVID-19. At the same time, clinicians need to be increasingly aware of the condition, and measurements of muscle strength, quantity, and physical performance should be embedded into clinical practice. Clinicians should consider the risks of acute sarcopenia when weighing up the risks and benefits of treatment (e.g. dexamethasone), and instigate multidisciplinary treatment including dietetics input.

In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness.OBJECTIVE To investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia. DESIGN, SETTING, AND PARTICIPANTSA randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018.INTERVENTIONS Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474).MAIN OUTCOMES AND MEASURES Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications. RESULTS Among 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). CONCLUSIONS AND RELEVANCEIn patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia.

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Introduction Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

We present an ultrafast neural network (NN) model, QLKNN, which predicts core tokamak transport heat and particle fluxes. QLKNN is a surrogate model based on a database of 300 million flux calculations of the quasilinear gyrokinetic transport model QuaLiKiz. The database covers a wide range of realistic tokamak core parameters. Physical features such as the existence of a critical gradient for the onset of turbulent transport were integrated into the neural network training methodology. We have coupled QLKNN to the tokamak modelling framework JINTRAC and rapid control-oriented tokamak transport solver RAPTOR. The coupled frameworks are demonstrated and validated through application to three JET shots covering a representative spread of H-mode operating space, predicting turbulent transport of energy and particles in the plasma core. JINTRAC-QLKNN and RAPTOR-QLKNN are able to accurately reproduce JINTRAC-QuaLiKiz T i,e and n e profiles, but 3 to 5 orders of magnitude faster. Simulations which take hours are reduced down to only a few tens of seconds. The discrepancy in the final source-driven predicted profiles between QLKNN and QuaLiKiz is on the order 1%-15%. Also the dynamic behaviour was well captured by QLKNN, with differences of only 4%-10% compared to JINTRAC-QuaLiKiz observed at mid-radius, for a study of density buildup following the L-H transition. Deployment of neural network surrogate models in multi-physics integrated tokamak modelling is a promising route towards enabling accurate and fast tokamak scenario optimization, Uncertainty Quantification, and control applications.

BackgroundDelirium is a common severe neuropsychiatric condition secondary to physical illness, which predominantly affects older adults in hospital. Prior to this study, the UK point prevalence of delirium was unknown. We set out to ascertain the point prevalence of delirium across UK hospitals and how this relates to adverse outcomes.MethodsWe conducted a prospective observational study across 45 UK acute care hospitals. Older adults aged 65 years and older were screened and assessed for evidence of delirium on World Delirium Awareness Day (14th March 2018). We included patients admitted within the previous 48 h, excluding critical care admissions.ResultsThe point prevalence of Diagnostic and Statistical Manual on Mental Disorders, Fifth Edition (DSM-5) delirium diagnosis was 14.7% (222/1507). Delirium presence was associated with higher Clinical Frailty Scale (CFS): CFS 4–6 (frail) (OR 4.80, CI 2.63–8.74), 7–9 (very frail) (OR 9.33, CI 4.79–18.17), compared to 1–3 (fit). However, higher CFS was associated with reduced delirium recognition (7–9 compared to 1–3; OR 0.16, CI 0.04–0.77). In multivariable analyses, delirium was associated with increased length of stay (+ 3.45 days, CI 1.75–5.07) and increased mortality (OR 2.43, CI 1.44–4.09) at 1 month. Screening for delirium was associated with an increased chance of recognition (OR 5.47, CI 2.67–11.21).ConclusionsDelirium is prevalent in older adults in UK hospitals but remains under-recognised. Frailty is strongly associated with the development of delirium, but delirium is less likely to be recognised in frail patients. The presence of delirium is associated with increased mortality and length of stay at one month. A national programme to increase screening has the potential to improve recognition.