There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and ...neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.
This paper outlines a novel approach to optimising teams for Daily Fantasy Sports (DFS) contests. To this end, we propose a number of new models and algorithms to solve the team formation problems ...posed by DFS. Specifically, we focus on the National Football League (NFL) and predict the performance of real-world players to form the optimal fantasy team using mixed-integer programming. We test our solutions using real-world data-sets from across four seasons (2014-2017). We highlight the advantage that can be gained from using our machine-based methods and show that our solutions outperform existing benchmarks, turning a profit in up to 81.3% of DFS game-weeks over a season.
Background:
Anterior cruciate ligament (ACL) tears are common in contact athletics and have a significant effect on the athletic performance and well-being of affected players. The prevalence, ...timing, and characteristics of ACL tears in National Football League (NFL) athletes are lacking.
Purpose:
To define the epidemiology of ACL tears among NFL athletes.
Study Design:
Descriptive epidemiology study.
Methods:
This retrospective study includes all ACL injuries entered into the NFL injury database through the centralized leaguewide electronic health record system for the 2015-2019 seasons.
Results:
A total of 314 ACL injuries occurred during the 5-year study period, with a mean of 62 per year. The overall 1-season injury risk of an NFL player sustaining an ACL injury was 1.9% (95% CI, 1.7%-2.1%). Most ACL injuries occurred during games (n = 199), with a higher rate observed in the preseason games as compared with the regular season games (6.1 vs 2.7 per 10,000 player-plays; P < .01). NFL players with ≤3 of experience had a higher preseason injury rate (9.57 ACL tears per 1000 player-seasons) than those with ≥4 years of experience (5.12 ACL tears per 1000 player-seasons; P < .01). NFL athletes playing on special teams had the highest rate of ACL injuries (7.6 per 10,000 player-plays) in comparison with all other player positions.
Conclusion:
ACL injury incidence was fairly consistent across all years studied and occurred more frequently in players with ≤3 years of NFL experience. Tears were more common during games, special teams play, and the preseason.
Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for ...the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model.
Introduction
No large‐scale characterizations of neurofilament light chain (NfL) have been conducted in diverse populations.
Methods
Baseline data were analyzed among n = 890 Mexican Americans and ...n = 813 non‐Hispanic Whites from the multi‐ethnic Health & Aging Brain among Latino Elders (HABLE) study. Plasma NfL was measured on the Simoa platform.
Results
In unadjusted models, NfL was significantly associated with age (P < .001), hypertension (P < .001), dyslipidemia (P = .02), and diabetes (P < .001). Covarying for age and sex, NfL was associated with neurodegeneration (P < .001) and global amyloid burden levels (P = .02) in a subset with available data. NfL levels were significantly associated with diagnostic groups (Normal Cognition NC, mild cognitive impairment MCI, Dementia; P < .001); however, there was no cut‐score that yielded acceptable diagnostic accuracy. NfL levels produced a sensitivity of 0.60 and specificity of 0.78 with negative predictive value of 89% for detecting amyloid positivity.
Discussion
Plasma NfL levels are significantly impacted by age and medical co‐morbidities that are common among older adults, which complicate its utility as a diagnostic biomarker
Background
Neurofilament proteins have been extensively studied in relapsing–remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role ...in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions.
Methods
A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies.
Results
Differences in neurofilament light between relapsing–remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent.
Conclusions
Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a
group
level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.
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Glioblastomas are the most frequent and aggressive cancer of the nervous system. The standard treatment is composed of neurosurgery followed by radiotherapy and chemotherapy, but the ...median survival remains very low. The NFL-TBS.40-63 peptide, also known as NFL-peptide, is capable to specifically penetrating all glioblastoma cell lines tested so far (rat, mouse and human), where it alters their microtubule network. Consequently, the peptide inhibits selectively the in vitro cell division of glioblastoma cells and their tumor development in vivo. When lipid nanocapsules are functionalized with the NFL-peptide, their uptake is targeted into glioblastoma cells both in vitro and in vivo. Here, we evaluated the impact of the NFL-peptide on J3T cells derived from a canine spontaneous glioblastoma, and its activity when functionalized to nanocapsules. Both flow cytometry and confocal microscopy experiments indicate that the NFL-peptide interacts with these cells and affects their biology, but it cannot enter in cells. By functionalizing lipid nanoparticles with the NFL-peptide, their uptake is also increased, while the peptide stays outside. This investigation reveals similarities and major differences between these canine cells and other glioblastoma cells, which are important aspects to consider when using this type of drug delivery system or performing pre-clinical studies with this animal model.
Purpose
Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL ...to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO
2
), arterial oxygen tension (PaO
2
), and mean arterial pressure (MAP).
Methods
We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1–2 and poor outcome as CPC 3–5.
Results
Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range IQR 11–31) pg/ml in patients with good outcome and 2343 (587–5829) pg/ml in those with poor outcome,
p
< 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval CI 0.97–1.00) at 24 h, 0.98 (0.97–1.00) at 48 h, and 0.98 (0.95–1.00) at 72 h. NfL concentrations were lower in the higher MAP (80–100 mmHg) group than in the lower MAP (65–75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml,
p
= 0.04). PaCO
2
and PaO
2
targets did not associate with NfL levels.
Conclusions
NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.
There is a widely recognized need for blood biomarkers to assist clinical decisions surrounding mild traumatic brain injury (mTBI). Serum neurofilament light (NfL), an indicator of neuroaxonal ...damage, is one such candidate, with early mTBI clinical investigations demonstrating significant promise. To facilitate the translation of pre-clinical mTBI findings, clinically relevant outcomes should be integrated into animal studies wherever possible. Despite this, the temporal profile and potential utility of NfL as a blood biomarker in pre-clinical mTBI is poorly understood. Here, we quantified serum NfL at 2-h, 1-, 3-, 7- and 14-days following mTBI in rats and compared these to pre-injury levels. We also investigated cumulative effects of repeat-mTBI by delivering 0, 1 or 5 mTBIs separated by 24 h. Sensorimotor performance was evaluated with the beam task at 1- and 4-h after mTBI, and serum was collected 1-day after the final procedure. We found that serum NfL levels were substantially elevated at all acute and sub-acute time-points after a single-mTBI, peaked at 1-day, and remained elevated 14-days post-injury. An mTBI dose-dependent effect on serum NfL levels was also observed, with substantially higher NfL levels found at 1-day post repeat-mTBI when compared to single-mTBI and sham-injured rats. Furthermore, NfL levels were found to be greatest in rats with the highest degree of sensorimotor impairment. In conclusion, these findings have described the temporal profile of serum NfL elevations following a single-mTBI in rats, and indicate a profile with some similarities and differences to that seen in the clinical condition. Moreover, we found that serum NfL levels were potentiated by repeat-mTBI, and that this biomarker may have utility as an indicator of injury severity. As such, future pre-clinical TBI studies may benefit from incorporating measures of serum NfL as an objective injury outcome.
This study investigated metacarpal fracture occurrences, characteristics, treatments, and return-to-play times for National Football League (NFL) athletes.
NFL players who sustained metacarpal ...fractures during the 2012 to 2018 seasons were reviewed. All players on the 32 NFL team active rosters with metacarpal fractures recorded through the NFL Injury Database were included. Player age, time in the league, player position, injury setting, injury mechanism, fractured ray, management, and return-to-play were recorded.
There were 208 injury occurrences resulting in 1 or more metacarpal fractures, identified in 205 players. Of these, 81 (39%) injuries were operated. Return-to-play data were available for 173 (83%) injured players. The median return-to-play time for all athletes was 15 days (interquartile range, 1–55 days). Of the injured players, 130 (71%) missed time but returned the same season. Within this 130-player subset, 69 (53%) were treated nonsurgically and 61 (47%) operatively with median return-to-play times of 16 days (interquartile range, 6–30 days) and 20 days (interquartile range, 16–42 days) respectively. Eighteen individuals in this 130-player subgroup sustained a thumb metacarpal fracture. The return-to-play time was slower for patients sustaining thumb metacarpal fractures compared to other metacarpal fractures, and was significantly longer (median, 55 days) following nonsurgical treatment of thumb fractures compared with operative intervention (median, 24 days). A regression analysis revealed no trend or difference in return to football with respect to player age, time in the league, injury setting (practice vs game), injury mechanism, articular involvement, multiple concomitant injuries, or player position.
Most NFL players who sustain metacarpal fractures miss less than 3 weeks and return to play the same season. The only variables that lessen the return-to-play time are involvement of lesser digit metacarpals and operative intervention for treatment of thumb metacarpal fractures.
Prognostic IV.
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