Anti-alpha synuclein and anti-tau immunotherapies: Can a cocktail approach work?

The hypothesis that neurodegenerative diseases are proteinopathies due to toxic effect of different underlying proteins, such as amyloid-beta and 3+4R-tau in Alzheimer's disease (AD) and alpha-synuclein in Parkinson's disease (PD), while still controversial is supported by several studies in the literature. This has led to conduct clinical trials attempting to reduce the load of these allegedly toxic proteins by immunotherapy, mostly but not solely based on antibodies against these proteins. Already completed clinical trials have ranged from initially negative results to recently partial positive outcomes, specifically for anti-amyloid antibodies in AD but also albeit to lesser degree for anti-synuclein antibodies in PD. Currently, there are several ongoing clinical trials in degenerative parkinsonisms with anti-synuclein approaches in PD and multiple system atrophy (MSA), as well as with anti-tau antibodies in 4R-tauopathies such as progressive supranuclear palsy (PSP). While it can be argued that expectations that part of these clinical trials will be positive can be hope or hype, it is reasonable to consider the future possibility of "cocktail" combination of different antibodies after the available experimental evidence of cross-talk between these proteins and neuropathological evidence of coexistence of these proteinopathies more frequently than expected by chance. Moreover, such "cocktail" approaches are widespread and accepted common practice in other fields such as oncology, and the complexity of neurodegenerative parkinsonisms makes reasonable the option for testing and eventually applying such combined approaches, should these prove useful separately, in the setting of patients with evidence of underlying concomitant proteinopathies, for example through biomarkers.

The effect of gum chewing on postoperative ileus in open colorectal surgery patients: A review.

BACKGROUND: Postoperative ileus is a common complication of abdominal surgery, leading to prolonged hospital stay and associated costs. Gum chewing may be a safe, cheap intervention to reduce postoperative ileus. METHODS: The aim was to investigate the effect of gum chewing on postoperative ileus in open colorectal surgery patients. A literature search was conducted between December 2018 and March 2019 on CINAHL, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews, MEDLINE, Academic Search Complete, PubMed, Scopus and Google Scholar. The keywords used included 'ileus', 'chewing gum', 'mastication' and 'sham feeding'. Papers had to include adults undergoing open colorectal surgery. The studies were appraised using Critical Appraisal Skills Programme tools and the results summarised using a narrative review. RESULTS: A total of three systematic reviews and three randomised controlled trials were included in the study. The studies show a significant to highly significant effect of gum chewing on postoperative ileus-related outcomes. The trials however in general utilised a weak design. CONCLUSIONS: Gum chewing decreases postoperative ileus following colorectal surgery. More robust trials are required to confirm these findings. Due to the low risk of harm and cost of using gum chewing, its use is recommended even in the interim.