Popliteus impingement after TKA may occur with well-sized prostheses

To determine the mechanisms and extents of popliteus impingements before and after TKA and to investigate the influence of implant sizing. The hypotheses were that (1) popliteus impingements after TKA may occur at both the tibia and the femur, and (2) even with an apparently well-sized prosthesis, popliteal tracking during knee flexion is modified compared to the preoperative situation. The location of the popliteus in three cadaver knees was measured using computed tomography, before and after implantation of plastic TKA replicas, by injecting the tendon with radiopaque liquid. The pre- and post-operative positions of the popliteus were compared from full extension to deep flexion using normosized, oversized, and undersized implants (one size increments). At the tibia, TKA caused the popliteus to translate posteriorly, mostly in full extension: 4.1 +/- 2 mm for normosized implants, and 15.8 +/- 3 mm with oversized implants, but no translations were observed when using undersized implants. At the femur, TKA caused the popliteus to translate laterally at deeper flexion angles, peaking between 80A degrees and 120A degrees: 2 +/- 0.4 mm for normosized implants and 2.6 +/- 0.5 mm with oversized implants. Three-dimensional analysis revealed prosthetic overhang at the posterosuperior corner of normosized and oversized femoral components (respectively, up to 2.9 mm and 6.6 mm). A well-sized tibial component modifies popliteal tracking, while an undersized tibial component maintains more physiologic patterns. Oversizing shifts the popliteus considerably throughout the full arc of motion. This study suggests that both femoro- and tibio-popliteus impingements could play a role in residual pain and stiffness after TKA

Imaging the implant-soft tissue interactions in total knee arthroplasty

BACKGROUND: In Total Knee Arthroplasty (TKA), residual pain may be secondary to soft tissue impingements, which are difficult to visualize around chromium-cobalt implants using medical imaging, so their interactions remain poorly understood. The goal of this work was to establish a protocol for in-vitro imaging of the soft tissues around TKA, usable during throughout the range of motion (ROM). METHODS: The full size range of a commercially available TKA prosthesis was manufactured by 3D-printing in non-magnetic and non-radiopaque polymer and implanted in 12 cadaveric knees. The relations between these implants and the soft tissues (Popliteus tendon, Medial and Lateral Collateral Ligament, Patellar and Quadriceps tendons) were analyzed, using MRI (5 embalmed specimens) and CT scans after injection of the tissues with barium-sulfate (3 embalmed and 4 fresh-frozen specimens). RESULTS: Both MRI and CT scans enabled good identification of the soft tissues before TKA implantation. MRI produced minimal loss in signal and contrast, and neither the low temperature nor the embalming fluids compromised image quality. CT scans were more precise after TKA implantation, particularly the borders of the implant and the differentiation of soft tissues. Full ROM investigation, manual segmentation and three-dimensional reconstructions were possible only with the CT scan. CONCLUSION: The experimental approach described in this study was successful in visualizing the interactions between the soft tissue and the implants before and after TKA and during the full ROM. The coordinate system allows to localize precisely the different anatomic structures and to quantify any change due to prosthetic implantation

Platelets in Patients with Premature Coronary Artery Disease Exhibit Upregulation of miRNA340* and miRNA624*

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective stud

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Supplementary Figure S5 from Neoantigen Targetability in Progressive Advanced Melanoma

Putative neoantigens in early and later metastatic lesions.</p

Supplementary Figure S6 from Neoantigen Targetability in Progressive Advanced Melanoma

Expression of tumor associated antigens in early and later metastatic lesions.</p

Supplementary Figure S3 from Neoantigen Targetability in Progressive Advanced Melanoma

T cell recognition of melanoma cell lines derived from early and later metastatic lesions.</p