Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Poorer survival after a primary implant during revision total knee arthroplasty

<p>Revision total knee arthroplasty (rTKA) is a complex procedure. Depending on the degree of ligament and bone damage, either primary or revision implants are used. The purpose of this study was to compare survival rates of primary implants with revision implants when used during rTKA.</p><p>A retrospective comparative study was conducted between 1998 and 2009 during which 69 rTKAs were performed on 65 patients. Most common indications for revision were infection (30 %), aseptic loosening (25 %) and wear/osteolysis (25 %). During rTKA, a primary implant was used in nine knees and a revision implant in 60.</p><p>Survival of primary implants was 100 % at one year, 73 % [95 % confidence interval (CI) 41-100] at two years and 44 % (95 % CI 7-81) at five years. Survival of revision implants was 95 % (95 % CI 89-100) at one year, 92 % (95 % CI 84-99) at two years and 92 % (95 % CI 84-99) at five years. Primary implants had a significantly worse survival rate than revision implants when implanted during rTKA [P = 0.039 (hazard ratio = 4.56, 95 % CI 1.08-19.27)].</p><p>Based on these results, it has to be considered whether primary implants are even an option during rTKA.</p>