Hip and knee replacement in lower limb amputees: a scoping review.

BACKGROUND: There are many consequences of lower limb amputation, including altered biomechanics of gait. It has previously been shown that these can lead to increased rates of osteoarthritis (OA). A common and successful treatment for severe OA is joint replacement. However, it is unclear whether amputees undergoing this surgery can expect the same outcomes or complication profile compared with non-amputees. Furthermore, there are key technical challenges associated with hip or knee replacement in lower limb amputees. This scoping review aimed to identify and summarise the existing evidence base. METHODS: This was a systematic scoping review performed according to PRISMA guidelines. An electronic database search of MEDLINE (PubMed), Cochrane Library, EMBASE and CINAHL was completed from the date of inception to 1st April 2023. All peer reviewed literature related to hip or knee replacement among lower limb amputees was included. RESULTS: Of the 931 records identified, 40 studies were included in this study. The available literature consisted primarily of case reports and case series, with generally low level of evidence. In total, there were 265 patients of which 195 received total hip replacement (THR), 51 received total knee replacement (TKR) and 21 received hip hemiarthroplasty. The most common reason for amputation was trauma (34.2%), and the main indication for joint replacement was OA (77.1%), occurring more frequently in the contralateral limb (66.7%). The outcomes reported varied widely between studies, with most suggesting good functional status post-operatively. A variety of technical tips were reported, primarily concerned with intra-operative control of the residual limb. CONCLUSION: There is a need for more observational studies to clearly define the association between amputation and subsequent need for joint replacement. Furthermore, comparative studies are needed to identify whether amputees can be expected to achieve similar functional outcomes after surgery, and if they are at higher risk of certain complications.

Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells.

Crumbs 3 (CRB3) is a component of epithelial junctions, which has been implicated in apical-basal polarity, apical identity, apical stability, cell adhesion, and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b. Here, we describe novel data demonstrating that, as with previous studies on CRB3a, CRB3b also promotes the formation of tight junctions (TJs). However, significantly we demonstrate that the 4.1-ezrin-radixin-moesin-binding motif of CRB3b is required for CRB3b functionality and that ezrin binds to the FBM of CRB3b. Furthermore, we show that ezrin contributes to CRB3b functionality and the correct distribution of TJ proteins. We demonstrate that both CRB3 isoforms are required for the production of functionally mature TJs and also the localization of ezrin to the plasma membrane. Finally, we demonstrate that reduced CRB3b expression in head and neck squamous cell carcinoma (HNSCC) correlates with cytoplasmic ezrin, a biomarker for aggressive disease, and shows evidence that while CRB3a expression has no effect, low CRB3b and high cytoplasmic ezrin expression combined may be prognostic for HNSCC.