Routine screening in the general hospital: what happens after discharge to those identified as at risk of dementia?

Cognitive screening is recommended for older patients with unplanned hospital admission. We determined rates of reassessment/specialist memory referral after routine inclusion of at risk of dementia status in discharge documentation to primary care. Questionnaires were sent to relevant GP practices on consecutive patients aged ≥75 years identified as at risk and discharged 6 months earlier. Among 53 patients (mean age ±SD = 87.3±6.0 years, mean±SD Abbreviated Mental Test Score = 4.4±2.7), 49 (92%) patients had been reviewed since discharge, and 12/43 (28%) without previously known cognitive problem had had a cognitive reassessment. The most common reasons for non-assessment/referral included clinical factors (eg terminal illness/comorbidities) (n=15) and patient/family wishes (n=5) and that confusion was expected in unwell older patients (n=5). Routine cognitive reassessment/specialist referral appears unjustified in patients identified as at risk of dementia during unplanned hospital admission. However, the prognostic value of delirium/confusion in acute illness is under-recognised and could be used to highlight those at risk.

Mutation of Fnip1 is associated with B-cell deficiency, cardiomyopathy, and elevated AMPK activity.

Folliculin (FLCN) is a tumor-suppressor protein mutated in the Birt-Hogg-Dubé (BHD) syndrome, which associates with two paralogous proteins, folliculin-interacting protein (FNIP)1 and FNIP2, forming a complex that interacts with the AMP-activated protein kinase (AMPK). Although it is clear that this complex influences AMPK and other metabolic regulators, reports of its effects have been inconsistent. To address this issue, we created a recessive loss-of-function variant of Fnip1 Homozygous FNIP1 deficiency resulted in profound B-cell deficiency, partially restored by overexpression of the antiapoptotic protein BCL2, whereas heterozygous deficiency caused a loss of marginal zone B cells. FNIP1-deficient mice developed cardiomyopathy characterized by left ventricular hypertrophy and glycogen accumulation, with close parallels to mice and humans bearing gain-of-function mutations in the γ2 subunit of AMPK. Concordantly, γ2-specific AMPK activity was elevated in neonatal FNIP1-deficient myocardium, whereas AMPK-dependent unc-51-like autophagy activating kinase 1 (ULK1) phosphorylation and autophagy were increased in FNIP1-deficient B-cell progenitors. These data support a role for FNIP1 as a negative regulator of AMPK.

The expression of mouse CLEC-2 on leucocyte subsets varies according to their anatomical location and inflammatory state.

Expression of mouse C-type lectin-like receptor 2 (CLEC-2) has been reported on circulating CD11b(high) Gr-1(high) myeloid cells and dendritic cells (DCs) under basal conditions, as well as on a variety of leucocyte subsets following inflammatory stimuli or in vitro cell culture. However, previous studies assessing CLEC-2 expression failed to use CLEC-2-deficient mice as negative controls and instead relied heavily on single antibody clones. Here, we generated CLEC-2-deficient adult mice using two independent approaches and employed two anti-mouse CLEC-2 antibody clones to investigate surface expression on hematopoietic cells from peripheral blood and secondary lymphoid organs. We rule out constitutive CLEC-2 expression on resting DCs and show that CLEC-2 is upregulated in response to LPS-induced systemic inflammation in a small subset of activated DCs isolated from the mesenteric lymph nodes but not the spleen. Moreover, we demonstrate for the first time that peripheral blood B lymphocytes present exogenously derived CLEC-2 and suggest that both circulating B lymphocytes and CD11b(high) Gr-1(high) myeloid cells lose CLEC-2 following entry into secondary lymphoid organs. These results have significant implications for our understanding of CLEC-2 physiological functions.