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The infrapatellar fat pad (IPFP) has been implicated as a source of postoperative knee pain. Imaging the IPFP is challenging in patients with total knee arthroplasty (TKA) due to metallic susceptibility artifact. Multi‐Acquisition Variable‐Resonance Image Combination (MAVRIC)‐based T2 Mapping has been developed to mitigate this artifact and can generate quantitative T2 data. Objectives of this study were to (1) measure T2 values of the IPFP in patients with TKAs using a MAVRIC based T2 mapping technique and (2) determine if IPFP T2 values are related to the degree of fat pad scarring or clinical magnetic resonance imaging (MRI) findings. Twenty‐eight subjects (10 males, 18 females, Age: 66 + 7.2 years [Mean ± standard deviations]) undergoing clinical MRIs were sequentially recruited. Morphological imaging and quantitative T2 mapping sequences were performed on a clinical 1.5 T scanner. The morphologic images were graded for the presence and severity of fat pad scarring and clinical outcomes. T2 values were calculated in the total fat pad volume, a normal regions of interest (ROI), and an abnormal ROI. T2 values were shortened in the total IPFP volume (p = 0.001) and within abnormal regions (p = 0.003) in subjects with more severe IPFP scarring. The difference between T2 values in normal−abnormal regions was greater in subjects with severe versus no scarring (+1426.1%, p = 0.008). T2 values were elevated in patients with MRI findings of osteolysis (+32.3%, p = 0.02). These findings indicate that MAVRIC‐based T2 Mapping may be used as a quantitative biomarker of postoperative IPFP scarring in individuals following TKA. [ABSTRACT FROM AUTHOR]

Abstract: CRISPR/Cas9 technology enables targeted gene editing; yet, the efficiency and specificity remain unsatisfactory, particularly for the nonvirally delivered, plasmid‐based CRISPR/Cas9 system. To tackle this, a self‐assembled micelle is developed and evaluated for human papillomavirus (HPV) E7 oncogene disruption. The optimized micelle enables effective delivery of Cas9 plasmid with a transient transgene expression profile, benefiting the specificity of Cas9 recognition. Furthermore, the feasibility of using the micelle is explored for another nucleic acid‐guided nuclease system, Natronobacterium gregoryi Argonaute (NgAgo). Both systems are tested in vitro and in vivo to evaluate their therapeutic potential. Cas9‐mediated E7 knockout leads to significant inhibition of HPV‐induced cancerous activity both in vitro and in vivo, while NgAgo does not show significant E7 inhibition on the xenograft mouse model. Collectively, this micelle represents an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine‐based therapeutics. [ABSTRACT FROM AUTHOR]

Background: Several previous studies have described broad histologic classifications of peri-prosthetic reactions that likely reflect the underlying mechanism of arthroplasty failure; however, a consensus has not yet been reached about the relative importance of individual observations., Question/purpose: The purpose of this study was to evaluate the inter-examiner repeatability of commonly used histopathologic grading methods, and to determine the utility of assigning a more simple, global categorization in patients undergoing revision THA surgery of implants with a variety of bearing combinations., Methods: Between March 2013 and February 2020, a total of 2131 patients underwent revision hip arthroplasty surgery at a one center, of which 12% (248 of 2131) of patients were enrolled. Two pathologists independently reviewed microscope slides of periprosthetic tissue from these patients, of which 425 slides (229 hips, 222 subjects) were reviewed by both pathologists. Separate slides were used for a priori training of the pathologists. Slides were evaluated with the Campbell Aseptic Lymphocyte-dominant Vasculitis-Associated Lesion (ALVAL) score, the Oxford ALVAL score as modified by Grammatopolous, the Fujishiro and Natu scores, and a proposed simplified pattern classification, similar to that of Krenn et al., that incorporates individual factors of these existing scoring methods and was previously shown to correspond to Magnetic Resonance Imaging findings. Inter-rater agreement was assessed using Gwet's AC1 and AC2 coefficients and correspondence analysis was used to examine associations between individual factors of prior scoring methods with the proposed major pattern., Results: Almost perfect inter-rater repeatability (Gwet's AC2 > 0.8) was found for 71% (15/21) of the individual factors, and substantial interrater agreement was found for the proposed major overall pattern (Gwet's AC1: 0.80, 95%CI: 0.72-0.85). Correspondence analysis was able to explain 89-91% of data variability and was able to identify individual features not commonly associated with a major pattern, but discriminatory of the major pattern, such as "Lymph Cuff Thickness 0.25-0.5″ with ALVAL., Conclusion: In contrast to prior examinations, excellent interrater agreement was found that may be attributable to a priori training of raters with a test set of slides or difficulty of interpreting grading criteria. The proposed simplified major pattern classification may facilitate evaluation of histopathologic tissue samples., (Copyright © 2021 Elsevier GmbH. All rights reserved.)