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The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready‐to‐use product with well‐defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte‐MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra‐articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging‐based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications. We summarize the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and trophic factors regulating mesenchymal stromal cell (MSC) activity in vivo, as well as multiple approaches for cell tracking and labeling in vitro and in vivo. Understanding the distribution and persistence of MSCs is necessary to fully realize potential cartilage regeneration techniques and tissue engineering applications.

While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D‐bioassembly platform is introduced to primarily study fusion of cartilage–cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D‐bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type‐II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D‐model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high‐throughput 3D‐bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis. This facile bioassembly platform to study cartilage–cartilage interfaces offers a powerful route to probe multicellular fusion mechanisms in developmental stages of tissue growth and regenerative repair strategies. This hybrid 3D‐bioassembly model provides a bridge between understanding, tissue fusion and cellular differentiation by recapitulating detailed biological mechanisms in vitro—systematically unlocking the potential of tissue growth and subsequent organ engineering.

Background: Arthroscopic meniscectomy often results in rapid recovery and return to preinjury activities; however, postoperative hemarthrosis and swelling can lead to pain, decreased range of motion, and delayed return to work and leisure activities. Tranexamic acid (TXA) is a lysine-based inhibitor of plasminogen to plasmin that has gained popularity in arthroplasty surgery for reducing blood loss and, more recently, in anterior cruciate ligament reconstruction by reducing postoperative hemarthrosis, swelling, and pain while increasing function in the short term. Purpose: To determine whether there is a role for TXA in improving the short-term results of swelling, pain, and function following arthroscopic meniscectomy. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: We performed a prospective double-blinded randomized controlled trial in 41 patients undergoing arthroscopic meniscectomy by comparing patients treated with intravenous TXA with those treated with a placebo (normal saline). A single surgeon treated all patients. Following randomization, a dose of 1 g of TXA in 100 mL of normal saline (treatment group) or 100 mL of normal saline (placebo group) was given intravenously at induction prior to tourniquet inflation by the anesthetist. The anesthetist administering the TXA or placebo was not blinded, but all other clinicians involved were. Patients were evaluated by a blinded observer at postoperative days 3, 14, and 30, with the range of motion, swelling, pain levels (visual analog scale), and Lysholm and Tegner knee scores recorded. Results: Patient demographics were similar in both groups. In the treatment group, there was a nonsignificant improvement in range of motion (P = .056) and swelling (P = .384) at 14 days; however, there was a significant improvement in the Tegner score at 3 days (P = .0064). The complication profile was similar between the groups. Conclusion: The administration of 1 g of intravenous TXA in routine arthroscopic meniscectomy may improve early functional recovery without increased risk. A larger study is required to confirm these results and further evaluate any potential benefit. Registration: ACTRN12618001600235 (Australian New Zealand Clinical Trials Registry).

Purpose We examined associations between self-reported and clinician-assessed comorbidity and quality of life (QOL) outcomes after hip and knee replacement. Methods This is a cross-sectional, questionnaire-based national survey. Participants aged 45 years or older ( n  = 409) were recruited from the New Zealand Joint Registry six months after a total hip (THR), total knee (TKR) or unicompartmental knee replacement (UKR). The main outcome QOL was measured using an 8-item short form of the World Health Organisation Quality of Life (WHOQOL-Bref) questionnaire six months following joint replacement surgery. The WHOQOL is a generic and non-health condition specific measure of QOL. Results Participants were on average 68 years of age, with more men (54%) than women (46%). Number of coexisting conditions and body mass index were correlated with age, pain and function scores, and QOL ( p  < 0.01), but not with each other. Linear regression analyses showed that comorbidities such as number of comorbid conditions and BMI had moderate associations with QOL outcomes. Conclusion This study showed that general QOL outcomes following hip and knee joint replacement, while generally high, were associated with comorbidity burden and BMI. Future prospective research examining change in QOL before and following surgery would help to advance understandings of the various factors that contribute to patient satisfaction with their joint replacement.

Purpose Reducing participant burden is important in health research and clinical assessment. We examined the psychometric properties of the EUROHIS-QOL 8-item index, a short version of the 26-item World Health Organisation Quality of Life questionnaire (WHOQOL-Bref), in a sample of people receiving joint replacement surgery. Methods Participants (n = 1008) completed the WHOQOL-Bref at either 6, 12, 24 or 60 months after hip or knee replacement. The factor structure, differential item functioning (DIF) and unidimensionality of the EUROHIS-QOL 8-item index were examined using exploratory and confirmatory factor analyses and Rasch analyses. Convergent validity was examined using correlations with the parent measure and other patient-reported outcome measures (Oxford scores, Western Ontario and McMaster Universities Osteoarthritis Index). Discriminant validity was assessed between groups reporting high versus low pain and function, and by joint replaced. Results The measure demonstrated high internal consistency (α = 0.86), adequate convergent (r = 0.47-0.82, p < 0.001) and discriminant validity (p < 0.001). Factor and Rasch analyses supported a unidimensional structure. However, there were also indications of multidimensionality, with support for a two-factor model focusing on general health and function, and psychosocial aspects of QOL. There was minimal evidence of DIF, with just one item evaluating energy level showing DIF for age. Conclusions The EUROHIS-QOL 8-item index demonstrated adequate properties as a unidimensional scale and as a two-factor scale evaluating general health and function, and psychosocial aspects of quality of life. It is low on clinical and participant burden, showed minimal ceiling effects and showed good concurrent and discriminant validity.

Objectives To quantify iodine uptake in articular cartilage as a marker of glycosaminoglycan (GAG) content using multi-energy spectral CT. Methods We incubated a 25-mm strip of excised osteoarthritic human tibial plateau in 50 % ionic iodine contrast and imaged it using a small-animal spectral scanner with a cadmium telluride photon-processing detector to quantify the iodine through the thickness of the articular cartilage. We imaged both spectroscopic phantoms and osteoarthritic tibial plateau samples. The iodine distribution as an inverse marker of GAG content was presented in the form of 2D and 3D images after applying a basis material decomposition technique to separate iodine in cartilage from bone. We compared this result with a histological section stained for GAG. Results The iodine in cartilage could be distinguished from subchondral bone and quantified using multi-energy CT. The articular cartilage showed variation in iodine concentration throughout its thickness which appeared to be inversely related to GAG distribution observed in histological sections. Conclusions Multi-energy CT can quantify ionic iodine contrast (as a marker of GAG content) within articular cartilage and distinguish it from bone by exploiting the energy-specific attenuation profiles of the associated materials. Key points • Contrast-enhanced articular cartilage and subchondral bone can be distinguished using multi-energy CT. • Iodine as a marker of glycosaminoglycan content is quantifiable with multi-energy CT. • Multi-energy CT could track alterations in GAG content occurring in osteoarthritis.

Performs a retrospective audit of patient characteristics, surgical management practices, rehabilitation practices and outcomes, osteoporosis treatment prescription and mortality for patients with hip fractures admitted to Christchurch Hospital. Compares outcomes for four groups : 1) publicly funded aged residential care (ARC) residents discharged directly from acute orthopaedics, 2) non-ARC residents discharged directly from acute orthopaedics, 3) patients discharged after orthogeriatric rehabilitation and 4) patients discharged after general geriatric rehabilitation. Looks also at the differences between orthogeriatric and general geriatric rehabilitation groups in respect to length of stay, comorbidities, functional status and treatment for osteoporosis. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Describes rehabilitation used before and after joint replacement in NZ and evaluates variation based on geography and ethnicity. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Background Osteoarthritis (OA) is a common cause of pain and disability. Currently available analgesics are often insufficiently effective or have unacceptable adverse effects. Tricyclic antidepressants may offer a useful centrally-acting analgesic. Nortriptyline is a readily-available, cheap and comparatively well-tolerated tricyclic antidepressant. Methods/Design We will conduct a parallel group, two-arm, participant and investigator-blinded, randomised controlled superiority trial comparing nortriptyline with placebo. Two hundred participants with primary knee OA will be enrolled. Participants will take study medication for 14 weeks. The primary outcome is difference between treatment arms in mean pain score measured on the Western Ontario and McMaster Universities (WOMAC) pain scale at 14 weeks. Discussion This protocol describes the first randomised controlled trial of a tricyclic antidepressant in the treatment of OA. The results of the study may have significant implications for the management of this common and painful condition. Trial registration The trial was registered with the Australian New Zealand Clinical Trials Registry on 27 June 2014. The trial registration number is: ACTRN12614000683639 .

AIMS: Our objective was to describe rehabilitation used before and after joint replacement in New Zealand and evaluate variation based on geography and ethnicity. METHODS: In this descriptive cross-sectional questionnaire-based study we recruited participants 45 years or older (n=608) from the New Zealand Joint Registry six months after primary total hip, total knee or uni-compartmental knee replacement. RESULTS: The cohort was predominantly New Zealand European (89.9%). The average age of participants was 68.2 years. Less rehabilitation was used pre-operatively (31.0%) than post-operatively (79.6%) and total hip replacement participants reported using less rehabilitation (63.3%) than those after total knee (90.7%) or uni-compartmental knee (80.3%) replacement (p<0.01). There were trends towards more pre-operative rehabilitation for participants living in larger urban areas, most evident for total hip replacement (p<0.05). CONCLUSIONS: Participants reported generally positive outcomes six months after primary total hip, knee and uni-compartmental knee replacement. However, differences in use of rehabilitation services before and after joint replacement were evident depending on joint replaced. Broadening setting options for rehabilitation might improve use of rehabilitation resources. In this study we surveyed New Zealanders six months after a hip or knee replacement to find out whether they used rehabilitation before and/or after their operation and if the amount of rehabilitation they used varied depending on where they lived. There were 608 people in the study sample. Most reported very good outcomes after their operations but delays starting rehabilitation post-operatively were associated with poorer pain and function outcomes. More rehabilitation was used after joint replacement compared with before, especially for people having knee replacements. Most rehabilitation was clinic-based physiotherapy and there were trends to more use of rehabilitation by people living in larger urban centres. Our findings suggested that broadening options for rehabilitation, for example home-based and telemedicine opportunities, might improve use of rehabilitation resources.