Dickkopf-1 (Dkk-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. The aim of this study was to examine plasma and synovial fluid Dkk-1 levels of patients with primary knee OA and to investigate their relationship with disease severity.</p> <p>Methods</p> <p>Thirty-five patients aged 55-83 years with knee OA and 15 healthy individuals were recruited into this study. Disease severity was determined using weight-bearing anteroposterior radiographs of the affected knee. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. Dkk-1 levels in both plasma and synovial fluid were evaluated using enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>The average concentration of circulating Dkk-1 in the knee OA patients was remarkably lower than that of healthy controls (396.0 ± 258.8, 95%CI 307.1-484.9 vs 2348.8 ± 2051.5, 95%CI 1164.3-3533.3 pg/ml, p < 0.0001). Dkk-1 levels in synovial fluid were significantly lower than in paired plasma samples (58.6 ± 31.8, 95%CI 47.7-69.6 vs 396.0 ± 258.8, 95%CI 307.1-484.9 pg/ml, p < 0.001). Furthermore, both plasma and synovial fluid Dkk-1 levels were inversely correlated with radiographic severity (r = -0.78, p < 0.001 and r = -0.42, p = 0.01, respectively). Plasma Dkk-1 levels were also significantly correlated with synovial fluid Dkk-1 levels (r = 0.72, p < 0.001).</p> <p>Conclusions</p> <p>Dkk-1 levels in plasma and synovial fluid are inversely related to the severity of joint damage in knee OA. Dkk-1 could serve as a biochemical marker for determining disease severity and might play a potential role in the pathogenesis of the degenerative process of OA.</p

Minimally invasive total knee replacement : techniques and results

In this review, we outlined the definition of minimally invasive surgery (MIS) in total knee replacement (TKR) and described the different surgical approaches reported in the literature. Afterwards we went through the most recent studies assessing MIS TKR. Next, we searched for potential limitations of MIS knee replacement and tried to answer the following questions: Are there selective criteria and specific patient selection for MIS knee surgery? If there are, then what are they? After all, a discussion and conclusion completed this article. There is certainly room for MIS or at least less invasive surgery (LIS) for appropriate selected patients. Nonetheless, there are differences between approaches. Mini medial parapatellar is easy to master, quick to perform and potentially extendable, whereas mini subvastus and mini midvastus are trickier and require more caution related to risk of hematoma and VMO nerve damage. Current evidence on the safety and efficacy of mini-incision surgery for TKR does not appear fully adequate for the procedure to be used without special arrangements for consent and for audit or continuing research. There is an argument that a sudden jump from standard TKR to MIS TKR, especially without computer assistance such as navigation, patient specific instrumentation (PSI) or robotic, may breach a surgeon's duty of care toward patients because it exposes patients to unnecessary risks. As a final point, more evidence is required on the long-term safety and efficacy of this procedure which will give objective shed light on real benefits of MIS TKR

Occupational advice for Patients undergoing Arthroplasty of the Lower limb: An intervention development and feasibility study (The OPAL Study)

Background Hip and knee replacements are regularly performed for patients who work. There is little evidence about these patients’ needs and the factors influencing their return to work. There is a paucity of guidance to help patients return to work after surgery and a need for structured occupational advice to enable them to return to work safely and effectively. Objective(s) To develop an occupational advice intervention to support early recovery to usual activities including work which is tailored to the requirements of patients undergoing hip and knee replacements. To test the acceptability, practicality and feasibility of this intervention within current care frameworks Design An intervention mapping (IM) approach was used to develop the intervention. The research methods employed were: rapid evidence synthesis; qualitative interviews with patients and stakeholders; prospective cohort study; survey of clinical practice; modified Delphi consensus process. The developed intervention was implemented and assessed during the final feasibility stage of the IM process. Setting Orthopaedic departments within NHS secondary care. Participants Patients in work, and intending to return to work following primary elective hip and knee replacement surgery; healthcare professionals and employers. Interventions Occupational advice intervention. Main outcome measures Development of an occupational advice intervention. Fidelity of the developed intervention when delivered in a clinical setting. Patient and clinician perspectives of the intervention. Preliminary assessments of intervention effectiveness and cost. Results A cohort study (154 patients), 110 stakeholder interviews, survey of practice (152 respondents) and evidence synthesis provided the necessary information to develop the intervention. The intervention included information resources, personalized return to work plan and co-ordination from the healthcare team to support the delivery of 13 patient and 20 staff performance objectives (POs). To support delivery, a range of tools (e.g. occupational checklists, patient workbooks, employer information), roles (e.g. return-to-work coordinator) and training resources were created. Feasibility was assessed in 21 of the 26 patients recruited from 3 NHS trusts. Adherence with the defined performance objectives was 75% for patient POs and 74% for staff POs. The intervention was generally well received although the short timeframe available for implementation and concurrent research evaluation led to some confusion amongst patients and those delivering the intervention regarding its purpose and the roles and responsibilities of key staff. Limitations Implementation and uptake of the intervention was not standardized and was limited by the study timeframe. Evaluation of the intervention involved a small number of patients which limited the ability to assess it. Conclusions The developed occupational advice intervention supports best practice. Evaluation demonstrated good rates of adherence against defined performance objectives. However, a number of operational and implementation issues require further attention Future work The intervention warrants a randomised controlled trial to assess its clinical and cost effectiveness to improve rates and timing of sustained return to work after surgery. This research should include the development of a robust implementation strategy to ensure adoption is sustained. Funding This project was funded by the NIHR Health Technology Assessment programme (project number 15/28/02) Trial Registrations International Standard Randomised Controlled Trials Number Trial ID: ISRCTN27426982 International prospective register of systematic reviews (PROSPERO) Registration: CRD4201604523

Using a discrete choice experiment to elicit patients’ preferences and willingness-to-pay for knee osteoarthritis treatments in Thailand

Abstract Osteoarthritis is the most common type of joint disease among elderly patients around the world. In response to the need for patient-centered care, patients’ and physicians’ preferences for knee osteoarthritis treatments have been studied in multiple countries, but not in Thailand. The objective of this study was to investigate Thai patients’ preferences and their willingness to pay (WTP) for knee osteoarthritis treatments by using a discrete choice experiment (DCE). Six knee osteoarthritis treatment attributes, including pain relief, delayed disease progression, gastrointestinal side effects, kidney side effects, cardiovascular side effects, and cost, were used to develop a paper-based, DCE questionnaire survey. Patients with knee osteoarthritis, who were at least 18 years old and who provided written informed consent, were recruited from the orthopedic department in a tertiary care hospital in Thailand via convenience sampling. The conditional logit model was used to determine patients’ preferences and WTP. The Institutional Review Board at Chulalongkorn University approved this study before it started. A total of 232 patients were collected and analyzed in this study. Patients preferred treatments with a higher efficacy (pain relief and delayed disease progression), a lower probability of side effects (gastrointestinal, kidney, and cardiovascular side effects), and a lower cost. Regarding efficacy and side effects, the patients weighted the importance of a 1% change in cardiovascular side effects (− 0.08) more heavily than 1% changes in kidney (− 0.07) and gastrointestinal (− 0.02) side effects, delayed disease progression (0.02), and pain relief (0.01). Patients were willing to pay 29.56 Thai Baht (THB) and 41.84 THB per month for every 1% increase in pain relief and delayed disease progression, respectively. Conversely, patients were willing to pay 52.04 THB, 145.18 THB and 164.23 THB per month for every 1% decrease in gastrointestinal, kidney, and cardiovascular side effects, respectively. In conclusion, pain relief, delayed disease progression, gastrointestinal side effects, kidney side effects, cardiovascular side effects, and the cost of treatment were significant factors among patients undergoing knee osteoarthritis treatment. Additionally, patients had a higher WTP for delayed disease progression than pain relief and a higher WTP for a reduced probability of cardiovascular side effects than gastrointestinal and kidney side effects. These findings could be used to support treatment decisions for knee osteoarthritis patients in Thailand

Immune Mediators in Osteoarthritis: Infrapatellar Fat Pad-Infiltrating CD8+ T Cells Are Increased in Osteoarthritic Patients with Higher Clinical Radiographic Grading

Osteoarthritis is a condition of joint failure characterized by many pathologic changes of joint-surrounding tissues. Many evidences suggest the role of both innate and adaptive immunity that interplay, resulting either in initiation or in progression of osteoarthritis. Adaptive immune cells, in particular T cells, have been demonstrated to play a role in the development of OA in animal models. However, the underlying mechanism is yet unclear. Our aim was to correlate the frequency and phenotype of tissue-infiltrating T cells in the synovial tissue and infrapatellar fat pad with radiographic grading. Our results show that CD8+ T cells are increased in osteoarthritic patients with higher radiographic grading. When peripheral blood CD8+ T cells were examined, we show that CD8+ T cells possess a significantly higher level of activation than its CD4+ T cell counterpart (P<0.0001). Our results suggest a role for CD8+ T cells and recruitment of these activated circulating peripheral blood CD8+ T cells to the knee triggering local inflammation within the knee joint