Frailty, sarcopenia and immunesenescence: shared mechanisms and clinical insights

Frailty, the increased vulnerability of an individual to stressors, and sarcopenia, the loss of muscle mass with age, share many of the same clinical outcomes, associations and suggested pathophysiology. The pathophysiology of both conditions is incompletely characterised but it is postulated the immune system is central to development and propagation. 40 healthy young, 40 healthy older, and 37 frail older adults were recruited to three groups. A further 73 healthy young adults were recruited for ultrasound assessment of muscle. Ultrasound was reviewed as a diagnostic technique in the identification of sarcopenia using a simple scanning protocol to produce the bilateral anterior thigh thickness (BATT). The BATT was measured in a reference population, 113 in total, and proposed criteria for the identification of low muscle mass in older adults was based on this reference population. Neutrophils exhibit a frailty related decline in migratory accuracy towards chemoattractants; this was both independent of age and associated with physical and cognitive parameters of frailty. Incubation of neutrophils from frail older adults with PI3kinase inhibitors class 1A $\delta$ and class lB y restored migratory accuracy and this presents a novel therapeutic target for management of frailty

Exceeding the recruitment target in a primary care paediatric trial:an evaluation of the Choice of Moisturiser for Eczema Treatment (COMET) feasibility randomised controlled trial

BACKGROUND: Recruiting to target in randomised controlled trials of investigational medicinal products (CTIMPs) in primary care and paediatric populations is notoriously difficult. More evidence is needed for effective recruitment strategies in these settings. We report on the impact of different recruitment strategies used in the Choice of Moisturiser in Eczema Treatment (COMET) study – a feasibility trial comparing the effectiveness of four emollients for the treatment of childhood eczema – recruiting via general practitioner (GP) surgeries. METHODS: Initially, 16 GP practices invited potentially eligible children to take part in the trial by sending an invitation letter (self-referral pathway) or by consenting and randomising them into the study during a visit to the practice (in-consultation referral). Measures implemented during the study to maximise accrual included signing up six additional GP practices, increasing the upper age limit eligibility criterion from 3 to 5 years, and permitting healthcare professionals other than doctors to confirm participant eligibility. We used descriptive statistics and univariate linear regression models to explore associations with practice recruitment rates. RESULTS: A total of 197 participants were recruited, exceeding the target of 160. Of these, 107 children entered via self-referral and 90 by in-consultation pathways. Of the recruited population, 12.6 % were aged between 3 and 5 years (the raised upper age limit). The six additional practices contributed 37.4 % (40 of 107) of participants recruited by self-referral. Only almost one-third (18 of 56 [32.1 %]) of potential recruiting clinicians recruited one or more participants in-consultation, which was a more problematic pathway because of data verification issues. Three research nurses and a pharmacist from four practices recruited 48.9 % (44 of 90) of participants via this pathway. Univariate linear regression models showed no evidence of association between the number of children recruited via the self-referral pathway by practice and practice list size (p = 0.092) or practice deprivation decile (p = 0.270), but practice deprivation was associated with a higher number of children recruited in-consultation (p = 0.020) by practice. CONCLUSIONS: Self-referral and in-consultation recruitment yielded similar numbers, but the in-consultation pathway was more problematic. Future trials of this type should consider the condition, normal care pathway and number of potentially eligible children and be prepared to use multiple recruitment strategies to achieve recruitment targets. TRIAL REGISTRATION: ISRCTN21828118. Registered on 1 May 2014. EudraCT2013-003001-26. Registered on 23 Dec 2013

Innate immune cells in liver inflammation

Innate immune system is the first line of defence against invading pathogens that is critical for the overall survival of the host. Human liver is characterised by a dual blood supply, with 80% of blood entering through the portal vein carrying nutrients and bacterial endotoxin from the gastrointestinal tract. The liver is thus constantly exposed to antigenic loads. Therefore, pathogenic microorganism must be efficiently eliminated whilst harmless antigens derived from the gastrointestinal tract need to be tolerized in the liver. In order to achieve this, the liver innate immune system is equipped with multiple cellular components; monocytes, macrophages, granulocytes, natural killer cells, and dendritic cells which coordinate to exert tolerogenic environment at the same time detect, respond, and eliminate invading pathogens, infected or transformed self to mount immunity. This paper will discuss the innate immune cells that take part in human liver inflammation, and their roles in both resolution of inflammation and tissue repair

The challenges of muscle biopsy in a community based geriatric population

Additional file 1. Participant factors, both absolute and relative contra-indications. Table of participant factors present in the frail older adult population that are contra-indications to muscle biopsy. Absolute contra-indications cannot be ameliorated. Relative contra-indications could be ameliorated with appropriate resources