Mortality Risk from Neurodegenerative Disease in Sports Associated with Repetitive Head Impacts: Preliminary Findings from a Systematic Review and Meta-Analysis.

BACKGROUND: Professional athletes seem to have a lower overall mortality risk than the general population, but controversy exists about whether athletes in sports associated with repetitive head impacts have a higher risk of mortality from neurodegenerative diseases. OBJECTIVE: We aimed to determine the risk of mortality from neurodegenerative diseases in sports associated with repeated head impacts compared with the general population or compared with athletes with no such exposure. METHODS: We conducted a systematic review with meta-analysis, systematically searching PubMed, Web of Science, Scopus, and SPORTDiscus (since inception to 14 May 2021) for studies comparing the risk of death from neurodegenerative disease in athletes participating in contact sports in which their heads recurrently receive blows from the bodies of other participants or from a ball versus a control group or dataset representing the general population. RESULTS: Six moderate- to high-quality retrospective studies including data from 41,699 athletes participating in contact sports (boxing, basketball, ice hockey, American Football and soccer) met all inclusion criteria to be included in the systematic review. Of these, three studies (N = 37,065 male professional soccer players) could be meta-analysed. Despite no differences in the risk of all-cause (p = 0.138), cardiovascular (p = 0.085) and cancer-related mortality (p = 0.136), soccer players presented with a significantly higher mortality risk from motor neuron disease (standard mortality rate 8.43; 95% confidence interval 3.07-23.13; p < 0.001). CONCLUSIONS: Although more research is needed (particularly in other contact sports and with neurodegenerative disease as the cause of death), preliminary evidence suggests that participation in professional soccer might increase the risk of mortality from motor neuron disease compared with the general population. The present findings highlight the need for the design of preventive measures and for adequate neuropsychological monitoring in these athletes. PROSPERO REGISTRATION: CRD42020195647.

Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood-brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.