Patients Undergoing Knee Replacement Surgery Research Articles

Preoperative Education and Training for Patients Undergoing Knee Replacement Surgery: A Systematic Review

Preoperative Education and Training for Patients Undergoing Knee Replacement Surgery: A Systematic Review

Relationship between Femoral Intercondylar Notch Narrowing in Radiography and Anatomical and Histopathologic Integrity of Anterior Cruciate Ligament in Patients Undergoing Total Knee Replacement Surgery.

The presence of cruciate ligaments is very important for normal knee kinematics. Knee arthroplasty prostheses, in which these ligaments are maintained, have better kinematics. The aim of the present study was to investigate the association between femoral intercondylar notch (FIN) narrowing in radiography and clinical and histopathologic integrity of anterior cruciate ligament (ACL) in patients undergoing knee replacement surgery. FIN index was measured in tunnel view radiography of the knees of 102 candidates of knee replacement surgery. The anatomical status of ACL was also examined during total knee arthroplasty (TKA). ACL was removed and sent for histopathologic examination to assess its degeneration rate. The association between the FIN index and the clinical and histopathological health of ACL was investigated. Among 102 patients with mean age of 69.73 ± 7.81 years , 39 patients (38.32%) had no or torn ACL, 31 patients (30.39%) had weak ACL, and 32 (31.37%) had normal ACL. There was a significant association between age and clinical status of ACL during surgery (P=0.017). There was a significant difference in FIN and ACL health status during surgery between the two groups with an index of more and less than 0.252 (P=0.019 and P=0.019, respectively). There was no significant difference in the mean total degeneration score (TDS) of ACL between the two groups with FIN more and less than 0.252 (P=0.816). There was a significant difference between the age and FIN narrowing (less than 0.252) as well as ACL clinical status during surgery. FIN narrowing had no significant effect on the severity of ACL degeneration and there was no significant difference in the severity of degenerative histopathologic changes between healthy and attenuated ACLs. This indicates that if ACL exists, although apparently attenuated, it has the histologic characteristic of a healthy ligament.

Investigation of the functional status of patients with unicondylar knee prosthesis

Purpose: Knee osteoarthritis (OA) is common and problems from OA increase with age. Knee and foot / ankle pathology is probably present in patients undergoing knee replacement surgery. However, the condition of the foot / ankle against the valgus or varus deformity is not clearly understood. Unicompartmental knee arthroplasty (UKA) is an effective treatment option for rapid functional recovery. Is UKA an effective method in the treatment of unicompartmental knee osteoarthritis, especially in the development of functional status and performance, and does foot/ankle affect the outcome of the surgery and the performance of the patients? The aim of this study was to invastigate the functional status of patients with uicondylar knee prosthesis. Methods: Patients who underwent unicondylar knee arthroplasty between 2012-2018 in the orthopedics and traumatology clinic were evaluated. Descriptive data of the patients and the presence of problems related to the foot / ankle were recorded with a prepared form. The pain level of the patients at rest, sleep, and walking before and after surgery was evaluated by using visual analog scale. The range of motion and Q angles of the affected knees of the patients were evaluated using universal goniometry; quadriceps and hamstring muscle strength were evaluated using the handheld dynamotre. Stance test was performed on one foot with eyes closed for balance assessment. Functional status of patients was determined by The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), short physical performance battery (SPPB) and disease-related quality of life. Results: Twenty-five women and 5 men with a mean age of 58.08 ± 8.66 years were included in the study. Thirteen patients (52%) were affected by dominant side and 12 (48%) patients had nondominant affected sides. The majority of the patients were housewives (68%). There were 7 (28%) patients with foot / ankle problems. There was a statistically significant decrease (p = 0.000) when the pain level of the patients were compared before and after surgery. Affected and unaffected sides were compared with NEHA, Q angle, quadriceps and hamstring muscle strength and eyes closed balance durations on one leg. There was a statistically significant difference (p = 0.005) in knee flexion ROM in favor of the unaffected side whereas there was no significant difference in all other parameters (p> 0.05). Patients' complaints of pain and stiffness were low and their physical functions (31.19 ± 22.37) and physical performances (X = 8.37 ± 2.48) were good, and health-related quality of life (physical status X = 38.89 ± 12.40, mental status X = 52.48 ± 17.51) was moderate level. When the patients with and without foot / ankle problems were compared, it was found that there was no difference in pain, ROM, muscle strength, physical function and performance status (p> 0.05) Conclusions: There was a significant decrease in activity and perceived pain level at rest after surgery. Affected side extension AEHA, Q angle, quadriceps and hamstring muscle strength, balance status did not differ with the unaffected side. Physical function and performance were found to be good and quality of life was moderate level. The functional status of patients with foot / ankle problems such as pain, swelling and stiffness is not affected. Since our study was a preliminary study, the patients' foot / ankle status and problems, physical functions and performances were not evaluated before the surgery. Comprehensive evaluations before surgery, foot / ankle status and problems are evaluated and studies with more participants are needed.

Transient receptor potential ankyrin 1 (TRPA1) as a factor and drug target in osteoarthritis: TRPA1 mediates fibroblast growth factor 2 expression in chondrocytes

Purpose: Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, which is known to be involved in nociception and neurogenic inflammation. TRPA1 is widely expressed in neurons, and according to more recent findings, also in non-neuronal cells, including synoviocytes and keratinocytes. TRPA1 acts as a chemosensor of pungent environmental compounds, but it is also activated by agents formed endogenously in inflammatory and hypoxic conditions such as those found in osteoarthritic joints. We have recently shown in monosodium iodoacetate-induced experimental osteoarthritis that TRPA1 activation mediates inflammation, cartilage degradation and pain (Moilanen et al. Osteoarthritis Cartilage 2015). We have also shown that TRPA1 is functionally expressed in human chondrocytes, where it mediates inflammatory effects (Nummenmaa et al. Arthritis Res Ther 2016). Further, we found that anti-inflammatory drugs dexamethasone and aurothiomalate downregulate the expression of TRPA1 in human chondrocytes (Nummenmaa et al. RMD Open 2017), revealing TRPA1 as a potential mediator and drug target in osteoarthritis. Fibroblast growth factor 2 (FGF-2) belongs to the fibroblast growth factor family, which is a large group of molecules involved in the regulation of connective tissue development and metabolism. FGF-2 is found in the synovial fluid and cartilage of osteoarthritis patients, and has previously been associated with the pathogenesis of osteoarthritis. In the present study, we investigated the functional consequences of TRPA1 activation in chondrocytes focusing in particularly on the expression of FGF-2. Methods: Chondrocytes were isolated from cartilage tissue from wild type (WT) and TRPA1 deficient (knock-out, KO) mice and cultured in the absence or presence of IL-1β. Total RNA was isolated and genome-wide expression analysis was carried out with next generation RNA sequencing (NGS) method with Illumina HiSeq2500 at the Institute for Molecular Medicine Finland. Results from the RNA sequencing analysis were verified by quantitative RT-PCR. Primary human OA chondrocytes were isolated from cartilage samples obtained from patients undergoing knee replacement surgery. Chondrocytes were cultured in the presence of the TRPA1-inducing cytokine IL-1β alone and together with the selective TRPA1 antagonist HC-030031. For experiments investigating the effects of FGF-2 in chondrocytes, the cells were cultured in the presence of FGF-2. Expression of FGF-2 subsequent to TRPA1 activation was measured by quantitative RT-PCR, and aggrecan, collagen II and MMP-enzymes by quantitative RT-PCR/immunoassay. Results: The expression of FGF-2 was significantly downregulated in chondrocytes from TRPA KO mice compared to WT mice. The downregulation of FGF-2 was verified by performing quantitative RT-PCR analysis on the sequenced samples, and on a larger set of corresponding samples. The results were confirmed using primary human OA chondrocytes. Pharmacological inhibition of TRPA1 with the selective antagonist HC-030031 downregulated FGF-2 expression in these cells. We further investigated the effects of FGF-2 in human OA chondrocytes, and found that FGF-2 upregulated the production of cartilage matrix degrading enzymes MMP-1 and MMP-13, and downregulated the expression of cartilage matrix components aggrecan and collagen II. Conclusions: The results revealed a hitherto unknown role for TRPA1 in the regulation of FGF-2 expression in chondrocytes. Further, FGF-2 was confirmed to have catabolic and anti-anabolic effects in human OA chondrocytes. Inhibition of TRPA1 and subsequent downregulation of FGF-2 could therefore have beneficial effects on the balance of catabolic and anabolic mediators within OA cartilage. These results together with our recent data discussed above support the concept of TRPA1 as a potential mediator and drug target in osteoarthritis.

Downregulation of microsomal prostaglandin E synthase-1 (mPGES-1) expression in chondrocytes is regulated by MAP kinase phosphatase-1 (MKP-1)

ObjectivesMicrosomal prostaglandin E synthase-1 (mPGES-1) catalyses the formation of PGE2 in inflammatory tissues. It is considered a potential drug target in inflammatory conditions to achieve clinical benefits comparable to NSAIDs with a better tolerability. Inhibitors of mPGES-1 are under development but the pharmacological regulation of mPGES-1 expression remains poorly known. MAP kinase phosphatase-1 (MKP-1) is an enzyme that limits the activity of pro-inflammatory MAP kinases p38 and JNK. In the present study, we discovered that dexamethasone down-regulates mPGES-1 expression in articular chondrocytes in an MKP-1 and p38 kinase dependent manner. MethodsPrimary human chondrocytes were isolated from cartilage samples obtained from osteoarthritis (OA) patients undergoing knee replacement surgery. Primary mouse chondrocytes were isolated from cartilage samples of MKP-1 deficient (knock-out, KO) and corresponding wild type (WT) mice. Expression of mPGES-1 and MKP-1 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot, and MAP kinase phosphorylation by Western blot. ResultsDexamethasone inhibited the expression of mPGES-1 in primary human chondrocytes and in chondrocytes from wild type but not from MKP-1 deficient mice. Dexamethasone enhanced MKP-1 expression in chondrocytes from wild type mice as well as in primary human OA chondrocytes. Dexamethasone induced the dephosphorylation of both p38 and JNK, whereas mPGES-1 expression was downregulated by selective inhibitors of p38 only. ConclusionsThe results show that MKP-1 is a crucial mediator of pharmacological control of inflammatory mPGES-1 expression by glucocorticoids, and underline MKP-1 as a potential anti-inflammatory drug target.

A qualitative exploration of social and environmental factors affecting diet and activity in knee replacement patients.

To examine perceived social and environmental barriers and facilitators for healthy eating and activity before and after knee replacement. Many patients undergoing knee replacement surgery are overweight or obese. While obesity treatment guidelines encourage diet and activity modifications, gaps exist in understanding social and environmental determinants of these behaviours for knee replacement patients. Identifying these determinants is critical for treatment, as they are likely amplified due to patients' mobility limitations, the nature of surgery and reliance on others during recovery. This qualitative study used semi-structured interviews. Twenty patients (M=64.7±9.8years, 45% female, 90% Caucasian, body mass index 30.8±5.5kg/m2 ) who were scheduled for or had recently undergone knee replacement were interviewed. Participants were asked to identify social and environmental factors that made it easier or harder to engage in healthy eating or physical activity. Deidentified transcripts were analysed via constant comparative analysis to identify barriers and facilitators to healthy eating and activity. This paper was written in accordance with COnsolidated criteria for REporting Qualitative research standards. Identified social and environmental healthy eating barriers included availability of unhealthy food and attending social gatherings; facilitators included availability of healthy food, keeping unhealthy options "out of sight," and social support. Weather was the primary activity barrier, while facilitators included access to physical activity opportunities and social support. Results provide salient factors for consideration by clinicians and behavioural programmes targeting diet, activity, and weight management, and patient variables to consider when tailoring interventions. Practitioners treating knee replacement patients would be aided by an understanding of patients' perceived social and environmental factors that impede or facilitate surgical progress. Particularly for those directly interacting with patients, like nurses, physiotherapists, or other professionals, support from health professionals appears to be a strong facilitator of adherence to diet and increased activity.

Identifying individuals with chronic pain after knee replacement: a population-cohort, cluster-analysis of Oxford knee scores in 128,145 patients from the English National Health Service

BackgroundApproximately one in five patients undergoing knee replacement surgery experience chronic pain after their operation, which can negatively impact on their quality of life. In order to develop and evaluate interventions to improve the management of chronic post-surgical pain, we aimed to derive a cut-off point in the Oxford Knee Score pain subscale to identify patients with chronic pain following knee replacement, and to characterise these patients using self-reported outcomes.MethodsData from the English Patient-Reported Outcome Measures (PROMs) programme were used. This comprised patient-reported data from 128,145 patients who underwent primary knee replacement surgery in England between 2012 and 2015. Cluster analysis was applied to derive a cut-off point on the pain subscale of the Oxford Knee Score.ResultsA high-pain group was identified, described by a maximum of 14 points in the Oxford Knee Score pain subscale six months after surgery. The high-pain group, comprising 15% of the sample, was characterised by severe and frequent problems in all pain dimensions, particularly in pain severity, night pain and limping, as well as in all dimensions of health-related quality of life.ConclusionsPatients with Oxford Knee Score pain subscale scores of 14 or less at six months after knee replacement can be considered to be in chronic pain that is likely to negatively affect their quality of life. This derived cut-off can be used for patient selection in research settings to design and assess interventions that support patients in their management of chronic post-surgical pain.

Patient Experience-based Value Sets: Are They Stable?

Although societal preference weights are desirable to inform resource-allocation decision-making, patient experienced health state-based value sets can be useful for clinical decision-making, but context may matter. To estimate EQ-5D value sets using visual analog scale (VAS) ratings for patients undergoing knee replacement surgery and compare the estimates before and after surgery. We used the Patient Reported Outcome Measures data collected by the UK National Health Service on patients undergoing knee replacement from 2009 to 2012. Generalized least squares regression models were used to derive value sets based on the EQ-5D-3 level using a development sample before and after surgery, and model performance was examined using a validation sample. A total of 90,450 preoperative and postoperative valuations were included. For preoperative valuations, the largest decrement in VAS values was associated with the dimension of anxiety/depression, followed by self-care, mobility, usual activities, and pain/discomfort. However, pain/discomfort had a greater impact on VAS value decrement in postoperative valuations. Compared with preoperative health problems, postsurgical health problems were associated with larger value decrements, with significant differences in several levels and dimensions, including level 2 of mobility, level 2/3 of usual activities, level 3 of pain/discomfort, and level 3 of anxiety/depression. Similar results were observed across subgroups stratified by age and sex. Findings suggest patient experience-based value sets are not stable (ie, context such as timing matters). However, the knowledge that lower values are assigned to health states postsurgery compared with presurgery may be useful for the patient-doctor decision-making process.

Effects of Reiki on Pain, Anxiety, and Blood Pressure in Patients Undergoing Knee Replacement: A Pilot Study.

This blinded, controlled pilot study investigated the effects of Reiki on 46 patients undergoing knee replacement surgery. Of the 3 groups, Reiki, Sham Reiki, and Standard of Care, only the Reiki group showed significant reductions in pain, blood pressure, respiration rate, and state anxiety, which provides evidence for a full-scale clinical study.

Analysis of characteristics of cognitive function of elderly patients after total knee arthroplasty

Objective To study the influencing factors of postoperative cognitive dysfunction (POCD) in elderly patients after knee joint replacement. Methods 165 cases of elderly patients undergoing knee replacement surgery were recruited in the study. According to whether there was POCD, the patients were divided into POCD group (35 cases) and non POCD group (130 cases). The gender, age, educational level, medical history, physical exercise, operation mode(cruciate-retaining total knee arthroplasty and posterior stabilized total knee arthroplasty), operation time, blood loss, preoperative depression score and postoperative pain score were recorded and compared.The logistic multiveariate regression analysis was conducted to analyze the risk factors of POCD in elderly patients with knee replacement. Results (1)There were statistically significant differences in the total score of MoCA, visual space and executive function, naming and delaying recall between non-POCD group and POCD group after the operation (Z=-5.327, P=0.000; Z=-3.140, P=0.002; Z=-2.910, P=0.004; Z=-3.333, P=0.001). (2)The results of logistic multiveariate regression analysis showed the age>70 years old (OR=3.708, 95%CI=1.037-13.261, P 4 (OR=3.149, 95%CI=1.072~9.251, P<0.05) were risk factors of POCD, and physical exercise (OR=4.330, 95%CI=1.294-14.488, P<0.05) and CR-TKA(OR=0.187, 95%CI=0.045-0.781, P<0.05) were the protective factors of POCD. Conclusion The overall level of cognitive function in elderly patients after knee replacement surgery is low. The advanced age, hypertension, diabetes, lack of physical exercise, choice of operation method, postoperative pain and preoperative depression are important influence factors of POCD. Key words: Elderly; Knee arthroplasty; Postoperative cognitive dysfunction; Risk factors

Expression of IL-1β Receptor Antagonist in Patients with Severe Osteoarthritis of the Knee–The Mechanism Limiting the Inflammation in Osteoarthritis

Introduction: Expression of interleukin-1β (IL-1β) in the synovial fluid of patients with osteoarthritis has been confirmed. The overall effect of this cytokine can be described as a chondrocyte-dependent cartilage destructive potential. The interleukin-1β receptor antagonist (IL-1Ra) blocks the interaction between IL-1β and its receptor on the cell surface. Human chondrocytes and synoviocytes produce IL-1Ra in a response to stimulation by IL-1β and IL-6. The local production of IL-1Ra in the joint has a protective effect against the catabolic action of IL-1β. Material and Methods: Synovial fluid and blood serum were obtained from 31 patients undergoing knee replacement surgery because of osteoarthritis. For comparison, samples were obtained from another 30 patients during diagnostic or therapeutic arthroscopy performed because of knee injury. The samples were analyzed for IL-1β and IL-1Ra using enzyme-linked immunosorbent assay. The U Mann-Whitney test and Spearman's test, as well as receiver operating characteristic (ROC) were used for statistical analysis. Results: Statistical analysis showed that the concentration of IL-1Ra in serum was significantly higher in the osteoarthritis group compared to the injury group (p=0.0001), and there was a positive correlation of IL-1Ra concentration in the serum and in the synovial fluid (correlation coefficient R=0.41; significance p=0.02). In the osteoarthritis group there was a very high negative correlation between the intensity of pain and the concentration of IL-1Ra in the synovial fluid (correlation coefficient R=-0.75; significance p<0.000001). Furthermore very high negative correlation was observed between the intensity of pain and level of this cytokine in serum (R=0.86; p<0.000001). For the measurements of IL-1Ra in serum the sensitivity of this test was 71.0%, specificity 70.0%, positive prediction of a result was 71.0%, negative prediction 70.0%, and the area under the ROC curve was 0.792. Conclusion: Late stage osteoarthritis is characterized by a systemic inflammatory reaction with high concentration of IL-1Ra in serum, which is positively correlated with its concentration in the synovial fluid. Pain in patients with late stage osteoarthritis may be reduced due to the high concentration of anti-inflammatory IL-1Ra both in the synovial fluid and in blood serum. The measurement of IL-1Ra in serum is a reliable immunoassay test that determines the status of osteoarthritis.

Infrapatellar fat pad-derived mesenchymal stromal cells from osteoarthritis patients: In vitro genetic stability and replicative senescence.

Different sources of mesenchymal stromal cells can be considered for regenerative medicine applications. Here we analyzed human adipose-derived stromal cells from infrapatellar fat pad (IFPSC) of osteoarthritis patients, representing a very interesting candidate for cartilage regeneration. No data are available concerning IFPSC stability after in vitro expansion. Indeed, replicative potential and multipotency progressively decrease during culture passages while DNA damage and cell senescence increase, thus possibly affecting clinical applications. To investigate whether in vitro expansion influences the genetic stability and replicative senescence of IFPSC, we performed long-term cultures and comparatively analyzed cells at different culture passages. Stromal vascular fraction was harvested from infrapatellar fat pad of 11 osteoarthritis patients undergoing knee replacement surgery. Cell recovery, growth kinetics, surface marker profile, and differentiation ability in inductive culture conditions were recorded. Genetic integrity maintenance was estimated by microsatellite instability analysis and mismatch repair gene expression, whereas telomere length and telomerase activity were assessed to evaluate replicative senescence. Anchorage-dependent growth was tested by soft agar culture. IFPSC displayed a phenotype similar to mesenchymal stromal cells from subcutaneous fat and showed differentiation ability. No microsatellite instability was documented even at advanced culture times in accordance to a sustained expression of mismatch repair genes, thus highlighting stability of short repeated sequences in the genome. No significant telomere attrition nor telomerase activity were documented during culture and cells did not lose anchorage-dependent growth ability. The presented data support the suitability and safety of in vitro expanded IFPSC from osteoarthritis patients for applications in regenerative medicine approaches. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1029-1037, 2017.

Systematic review of measurement properties of patient-reported outcome measures used in patients undergoing hip and knee arthroplasty.

ObjectivesTo identify patient-reported outcome measures (PROMs) that have been developed and/or used with patients undergoing hip or knee replacement surgery and to provide a shortlist of the most promising generic and condition-specific instruments.MethodsA systematic review of the literature was performed to identify measures used in patients undergoing hip and knee replacement and extract and evaluate information on their methodological quality.ResultsThirty-two shortlisted measures were reviewed for the quality of their measurement properties. On the basis of the review criteria, the measures with most complete evidence to date are the Oxford Hip Score (OHS) (for patients undergoing hip replacement surgery) and the Oxford Knee Score (OKS), with OKS-Activity and Participation Questionnaire (for patients undergoing knee replacement surgery).ConclusionA large number of these instruments lack essential evidence of their measurement properties (eg, validity, reliability, and responsiveness) in specific populations of patients. Further research is required on almost all of the identified measures. The best-performing condition-specific PROMs were the OKS, OHS, and Western Ontario and McMaster Universities Osteoarthritis Index. The best-performing generic measure was the Short Form 12. Researchers can use the information presented in this review to inform further psychometric studies of the reviewed measures.

E2 regulates MMP-13 via targeting miR-140 in IL-1β-induced extracellular matrix degradation in human chondrocytes.

BackgroundEstrogen deficiency is closely related to the development of menopausal arthritis. Estrogen replacement therapy (ERT) shows a protective effect against the osteoarthritis. However, the underlying mechanism of this protective effect is unknown. This study aimed to determine the role of miR-140 in the estrogen-dependent regulation of MMP-13 in human chondrocytes.MethodsPrimary human articular chondrocytes were obtained from female OA patients undergoing knee replacement surgery. Normal articular chondrocytes were isolated from the knee joints of female donors after trauma and treated with interleukin-1 beta (IL-1β). Gene expression levels of miR-140, MMP-13, and ADAMTS-5 were detected by quantitative real-time PCR (qRT-PCR). miR-140 levels were upregulated or downregulated by transfecting cells with a miRNA mimic and inhibitor, respectively, prior to treatment with IL-1β. MMP-13 expression was then evaluated by Western blotting and immunofluorescence. Luciferase reporter assays were performed to verify the interaction between miR-140 and ER.Results17-β-estradiol (E2) suppressed MMP-13 expression in human articular chondrocytes. miR-140 expression was upregulated after estrogen treatment. Knockdown of miR-140 expression abolished the inhibitory effect of estrogen on MMP-13. In addition, the estrogen/ER/miR-140 pathway showed an inhibitory effect on IL-1β-induced cartilage matrix degradation.ConclusionsThis study suggests that estrogen acts via ER and miR-140 to inhibit the catabolic activity of proteases within the chondrocyte extracellular matrix. These findings provide new insight into the mechanism of menopausal arthritis and indicate that the ER/miR-140 signaling pathway may be a potential target for therapeutic interventions for menopausal arthritis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0997-y) contains supplementary material, which is available to authorized users.

Factor XI and factor XII as targets for new anticoagulants

Although the non-vitamin antagonist oral anticoagulants produce less intracranial bleeding than warfarin, serious bleeding still occurs. Therefore, the search for safer anticoagulants continues. Factor XII and factor XI have emerged as promising targets whose inhibition has the potential to prevent thrombosis with little or no disruption of hemostasis. Thus, thrombosis is attenuated in mice deficient in factor XII or factor XI and patients with congenital factor XII deficiency do not bleed and those with factor XI deficiency rarely have spontaneous bleeding. Strategies targeting factor XII and XI include antisense oligonucleotides to decrease their synthesis, inhibitory antibodies or aptamers, and small molecule inhibitors. These strategies attenuate thrombosis in various animal models and factor XI knockdown with an antisense oligonucleotide in patients undergoing knee replacement surgery reduced postoperative venous thromboembolism to a greater extent than enoxaparin without increasing bleeding. Therefore, current efforts are focused on evaluating the efficacy and safety of factor XII and factor XI directed anticoagulant strategies.

Development and validation of a questionnaire assessing discrepancy between patients' pre-surgery expectations and abilities and post-surgical outcomes following knee replacement surgery.

The discrepancy between patient-desired outcomes and achievable functional outcomes is a source of patient dissatisfaction. This paper reports development and validation of a questionnaire to assess this discrepancy in patients undergoing knee replacement surgery. The initial questionnaire (Knee Surgery Perception Questionnaire, KSPQ) comprised two parts. Part A, assessed patients' perception of their current level of function and pain, and Part B, assessed patients' desired outcomes of the surgery. Validation was carried out for Part A and then applied to Part B using a one-factor congeneric model and was tested in 185 patients preceding surgery. A discrepancy score between patients' expectations and desired outcome (Part B) and their perception of current function (Part A) was also calculated. Pearson correlations were used between the KSPQ total score and subscales and other knee-specific questionnaires to determine construct validity. The final best set of models included four items for each subscale with a Chi-square value of 7.3 (n.s). The subscales and the total KSPQ showed significant strong to moderate correlations with knee-specific questionnaires. The discrepancy score in each subscale and the overall score showed relatively large discrepancy between patients' expectations and their perception of current function; with higher discrepancy score reported for pain and walking. The KSPQ is a valid questionnaire to assess patients' expected and desired outcomes of knee replacement surgery and their perception of their current abilities and function, and discrepancy between these. The KSPQ now requires further investigation at different stages of recovery following surgery. III.

The contribution of bone and cartilage to the near-infrared spectrum of osteochondral tissue.

Near-infrared (NIR) spectroscopy has been used to assess hyaline cartilage quality in human and animal osteochondral tissues. However, due to the lack of NIR signal from bone phosphate and the relatively deep penetration depth of the radiation, the separate contributions of cartilage and bone to the spectral signatures have not been well defined. The objectives of the current study were (1) to improve the understanding of the contributions of bone and cartilage to NIR spectra acquired from osteochondral tissue and (2) to assess the ability of this nondestructive method to predict cartilage thickness and modified Mankin grade of human tibial plateau articular cartilage. Near-infrared spectra were acquired from samples of bovine bone and cartilage with varying thicknesses and from 22 tibial plateaus harvested from patients undergoing knee replacement surgery. The spectra were recorded from regions of the tibial plateaus with varying degrees of degradation, and the cartilage thickness and modified Mankin grade of these regions were assessed histologically. The spectra from bone and cartilage samples of known thicknesses were investigated to identify spectral regions that were distinct for these two tissues. Univariate and multivariate linear regression methods were used to correlate modified Mankin grade and cartilage thickness with NIR spectral changes. The ratio of the NIR absorbances associated with water at 5270 and 7085 cm(-1) was the best differentiator of cartilage and bone spectra. The NIR prediction models for thickness and Mankin grade calculated using partial least squares regression were more accurate than were univariate-based prediction models, with a root mean square errors of cross-validation of 0.42 mm (for thickness) and 1.3 (for modified Mankin grade). We conclude that NIR spectroscopy may be used to simultaneously assess articular cartilage thickness and modified Mankin grade, based in part on differences in spectral contributions from bone and cartilage.

Peripheral opioid receptor blockade increases postoperative morphine demands—A randomized, double-blind, placebo-controlled trial

Experimental studies suggest that a large proportion of opioid analgesia can be mediated by peripheral opioid receptors. This trial examined the contribution of such receptors to clinical analgesia induced by intravenous morphine. We hypothesized that the selective blockade of peripheral opioid receptors by methylnaltrexone (MNX) would increase the patients’ demand for morphine to achieve satisfactory postoperative pain relief. In a double-blind, placebo-controlled, sequential 2-center trial, 50 patients undergoing knee replacement surgery were randomized (1:1) to receive either subcutaneous MNX (0.9mg/kg) (hospital I: n=14; hospital II: n=11) or saline (hospital I: n=13; hospital II: n=12) at the end of surgery. The primary endpoint was the cumulative amount of intravenous morphine administered during the first 8hours. Secondary endpoints were pain scores at rest and during movement (by numerical rating scale and McGill Questionnaire), vital signs, adverse side effects, and withdrawal symptoms. After MNX, demands for morphine were strongly (by about 40%) increased (hospital I: 35.31±12.99mg vs 25.51±7.92mg, P=0.03; hospital II: 35.42±11.73mg vs 24.80±7.84mg, P=0.02; pooled data: P<.001; means±SD). Secondary endpoints were similar in all groups (P>.05). Thus, a significant proportion of analgesia produced by systemically administered morphine is mediated by peripheral opioid receptors. Drugs that selectively activate such receptors should have the potential to produce powerful clinical pain relief.

Resistin as a factor in osteoarthritis: synovial fluid resistin concentrations correlate positively with interleukin 6 and matrix metalloproteinases MMP-1 and MMP-3

Objectives: Resistin is an adipocytokine that has been related to inflammation and insulin resistance. Following knee injury, elevated levels of resistin have been found in synovial fluid (SF) while very little is known about the role of resistin in osteoarthritis (OA). The aim of the present study was to investigate resistin levels in OA joints and to determine if it is associated with inflammatory and catabolic factors in the joints.Method: SF, plasma, and cartilage samples were collected from 88 OA patients undergoing knee replacement surgery. Resistin levels were measured by enzyme-linked immunosorbent assay (ELISA) in SF, plasma, and cartilage culture media.Results: Significant levels of resistin [0.75 (0.67) ng/mL; median (IQR)] were found in SF from OA patients. Resistin correlated positively with interleukin (IL)-6 (r = 0.39, p < 0.001) and with matrix metalloproteinases MMP-1 (r = 0.31, p = 0.004) and MMP-3 (r = 0.24, p = 0.024) in SF. Resistin was also released from cultured OA cartilage and it correlated with resistin levels in SF (r = 0.39, p < 0.001). In addition, resistin levels in plasma correlated positively with those in SF (r = 0.44, p < 0.001). There were no differences in SF or plasma resistin concentrations between females and males or between non-diabetic and diabetic patients, and resistin did not correlate with body mass index (BMI).Conclusions: Resistin is present in OA joints and is released from OA cartilage. Levels of resistin in SF are associated with inflammatory and catabolic factors, suggesting that resistin has a role to play in the pathogenesis of, and as a possible drug target in, OA.

Effects of low-intensity pulsed ultrasound and hyperbaric oxygen on human osteoarthritic chondrocytes

BackgroundAlthough the individual effects of hyperbaric oxygen (HBO) and low-intensity pulsed ultrasound (LIPUS) on osteoarthritic (OA) chondrocytes have been reported, the effects of HBO combined with LIPUS treatment are unknown.MethodsOA chondrocytes were obtained from patients undergoing knee replacement surgery. RNA was isolated for real-time polymerase chain reaction (PCR) analysis of inducible nitric oxide synthase (iNOS), type-II collagen, and aggrecan gene expression. The protein levels of MMP-3 and TIMP-1 were quantified by enzyme-linked immunosorbent assay (ELISA) after LIPUS or HBO treatment. The data are given as mean ± standard deviation (SD) of the results from three independent experiments. A p value less than 0.05 was defined as statistically significant.ResultsOur data suggested that ultrasound and HBO treatment increased cell bioactivity of OA chondrocytes. Real-time PCR analysis showed that HBO treatment increased the mRNA of type-II collagen, aggrecan, and TIMP-1 but suppressed the iNOS expression of OA chondrocytes. LIPUS treatment increased the type-II collagen and iNOS expression of OA chondrocytes. ELISA data showed that HBO or LIPUS treatment increased TIMP-1 production of OA chondrocyte. MMP-3 production was suppressed by HBO treatment. HBO combined with LIPUS treatments resulted in additive effect in TIMP-1 production and compensatory effect in iNOS expression.ConclusionHBO combined with LIPUS treatment-induced increase of the anabolic factor (TIMP-1)/catabolic factor (MMP-3) ratio may provide an additive therapeutic approach to slow the course of OA degeneration.