Background: The American Association of Hip and Knee Surgeons (AAHKS) Annual Scientific Meeting is a leading forum for the presentation and dissemination of research regarding the management of hip and knee pathology making research presented at these meetings a representation of the current literature in the field. The purpose of this study was to quantify the level of evidence of podium presentations presented at the AAHKS annual meeting from 2015 to 2019.
Methods: Two reviewers evaluated the abstracts for the available presentations. Basic science and biomechanical studies were excluded from the review. Economic studies that were not able to be evaluated based on the American Academy of Orthopedic Surgeon guidelines were also excluded. The two reviewers then independently evaluated each abstract and assigned a level of evidence (level I-V) based on the American Academy of Orthopedic Surgeon classification scheme.
Results: A total of 258 podium presentations were included. In total, 17 (7%) abstracts were graded level I evidence, 57 (22%) were graded level II, 85 (33%) were graded level III, and 98 (38%) were graded level IV (Table 1). There was a significant change in the distribution of the level of evidence of podium presentations over time (χ = 24.6, P = .02). The proportion of level I studies has increased between 2015 and 2019 (from 3.9% to 11.8%) with a concomitant decrease in level IV studies (from 42.3% to 21.6%) over that time period.
Conclusions: There has been a significant improvement in the levels of evidence of podium presentations at the AAHKS Annual Meeting from 2015 to 2019.
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http://dx.doi.org/10.1016/j.arth.2021.01.083 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFBackground: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.
Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.
Background: Impaired Aβ clearance plays a key role in the common, late-onset AD. Anti-Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG-PE3 crossing the human blood-brain barrier (BBB) and clearing Aβ with no adverse effect.
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