Stiffness in total knee arthroplasty

Stiffness is a relatively uncommon complication after total knee arthroplasty. It has been defined as a painful limitation in the range of movement (ROM). Its pathogenesis is still unclear even if some risk factors have been identified. Patient-related conditions may be difficult to treat. Preoperative ROM is the most important risk factor, but an association with diabetes, reflex sympathetic dystrophy, and general pathologies such as juvenile rheumatoid arthritis and ankylosing spondylitis has been demonstrated. Moreover, previous surgery may be an additional cause of an ROM limitation. Postoperative factors include infections, arthrofibrosis, heterotrophic ossifications, and incorrect rehabilitation protocol. Infections represent a challenging problem for the orthopaedic surgeon, and treatment may require long periods of antibiotics administration. However, it is widely accepted that an aggressive rehabilitation protocol is mandatory for a proper ROM recovery and to avoid the onset of arthrofibrosis and heterotrophic ossifications. Finally, surgery-related factors represent the most common cause of stiffness; they include errors in soft-tissue balancing, component malpositioning, and incorrect component sizing. Although closed manipulation, arthroscopic and open arthrolysis have been proposed, they may lead to unpredictable results and incomplete ROM recovery. Revision surgery must be proposed in the case of well-documented surgical errors. These operations are technically demanding and may be associated with high risk of complications; therefore they should be accurately planned and properly performed

Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-β

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-β and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-α, IL-6, IL-10 and IL-1β in monocytes than did lysates. Secreted IL-18, which, like IL-1β, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine production by TLR2-deficient murine macrophages was only moderately diminished in response to live Bb but was drastically impaired against lysates; TLR2 deficiency had no significant effect on uptake and degradation of spirochetes. As with PBMCs, live Bb was a much more potent inducer of IFN-β and ISGs in isolated monocytes than were lysates or a synthetic TLR2 agonist. Collectively, our results indicate that the enhanced innate immune responses of monocytes following phagocytosis of live Bb have both TLR2-dependent and -independent components and that the latter induce transcription of type I IFNs and ISGs

Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes

Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising--and degradable--nanomedicine vector