Prevalence and Potentially Reversible Factors Associated With Anorexia Among Older Nursing Home Residents: Results from the ULISSE Project

ObjectiveThe principal aims of the present study were to explore the prevalence of anorexia and the factors correlated to anorexia in a large population of older people living in nursing home. Secondary, we evaluated the impact of anorexia on 1-year survival.MethodsData are from baseline evaluation of 1904 participants enrolled in the Un Link Informatico sui Servizi Sanitari Esistenti per l’Anziano study, a project evaluating the quality of care for older persons living in an Italian nursing home. All participants underwent a standardized comprehensive evaluation using the Italian version of the inter Resident Assessment Instrument Minimum Data Set (version 2.0) for Nursing Home. We defined anorexia as the presence of lower food intake. The relationship between covariates and anorexia was estimated by deriving ORs and relative 95% CIs from multiple logistic regression models including anorexia as the dependent variable of interest. Hazard ratios and 95% CIs for mortality by anorexia were calculated.ResultsMore than 12% (240 participants) of the study sample suffered from anorexia, as defined by the presence of decreased food intake or the presence of poor appetite. Participants with functional impairment, dementia, behavior problems, chewing problems, renal failure, constipation, and depression, those treated with proton pump inhibitors and opioids had a nearly 2-fold increased risk of anorexia compared with participants not affected by these syndromes. Furthermore, participants with anorexia had a higher risk of death for all causes compared with nonanorexic participants (hazard ratio 2.26, 95% CI: 2.14–2.38).ConclusionsThe major finding is that potentially reversible causes, such as depression, pharmacologic therapies, and chewing problems, were strongly and independently associated with anorexia among frail older people living in nursing home. Furthermore, anorexia was associated with higher rate of mortality, independently of age and other clinical and functional variables.     

Aged PrP null mice show defective processing of neuregulins in the peripheral nervous system

A prion, a protease-resistant conformer of the cellular prion protein (PrP(C)), is the causative agent of transmissible spongiform encephalopathies or prion diseases. While this property is well established for the aberrantly folded protein, the physiological function of PrP(C) remains elusive. Among different putative functions, the non-pathogenic protein isoform PrP(C) is involved in several cellular processes. Here, we show that PrP(C) regulates the cleavage of neuregulin-1 proteins (NRG1). Neuregulins provide key axonal signals that regulate several processes, including glial cells proliferation, survival and myelination. Interestingly, mice devoid of PrP(C) (Prnp?/?) were recently shown to have a late-onset demyelinating disease in the peripheral nervous system (PNS) but not in the central nervous system (CNS). We found that NRG1 processing is developmentally regulated in the PNS and, by comparing wildtype and Prnp?/? mice, that PrP(C) influences NRG1 processing in old, but not in young, animals. In addition, we found that also the processing of neuregulin-3, another neuregulin family member, is altered in the PNS of Prnp?/? mice. These differences in neuregulin proteins processing are not paralleled in the CNS, thus suggesting a different cellular function for PrP(C) between the CNS and the PNS.     

Neurodegeneration in familial amyloidotic polyneuropathy

Familial amyloid polyneuropathies (FAP) constitute a group of inherited amyloidoses that affect peripheral nerves. One common form of FAP is caused by transthyretin (TTR) misfolding and deposition in the peripheral nervous system, leading to neuronal toxicity and death. The molecular mechanisms responsible for this toxicity are unclear; however, there is good biochemical and histopathological evidence that the toxicity of TTR mutations is correlated to their aggregation state. In addition, neuronal calcium dysregulation is a mechanism that has been suggested to drive the pathogenesis of FAP. Amyloidogenic TTR mutations cause significant calcium influx via L-type calcium channels in neuronal cell lines, while in primary sensory neurons, TTR mediates a calcium influx via a novel mechanism of transient receptor potential melanostatin (TRPM8) and voltage-gated sodium and calcium channel activation. Significantly, calcium dysregulation is a pathological hallmark of other neurodegenerative diseases involving amyloidosis, for example Alzheimer's disease, and this mechanism could explain the molecular events that drive amyloid toxicity in other neurodegenerative diseases.     

Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases

Background:

This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and irinotecan-based systemic chemotherapy regimens.

Methods:

Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9–2.2).

Results:

Of 50 eligible patients, 38 (76%) had received ⩾4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25–50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1–2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0–18.3); 2-year survival was 19.6%.

Conclusion:

Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC.