Accelerometer Measurement of Trunk Lateral Fluctuation During Walking Following Total Knee Arthroplasty in Patients With Osteoarthritis.

This study aimed to clarify the effect of total knee arthroplasty (TKA) on trunk fluctuation and regularity of gait in patients with knee osteoarthritis by an accelerometer. The participants included 18 patients with knee osteoarthritis undergoing TKA. The gait at a comfortable velocity was assessed pre- and post-TKA by a triaxial accelerometer attached to the neck and lumbar regions. Measurement post-TKA was performed 4 weeks after surgery. Trunk fluctuation was estimated by the root mean square (RMS) of acceleration and RMS ratio (the ratio of RMS in each direction to the total RMS). Regularity of gait was estimated using the autocorrelation function. The results showed that TKA significantly decreased the RMS ratio in mediolateral acceleration of the neck and lumbar regions and reduced gait regularity. TKA appears to reduce compensatory trunk motion through the improvement of knee function. An assessment of trunk fluctuation using an accelerometer is useful for the clinical assessment of patients with knee osteoarthritis pre- and post-TKA.

Serum-soluble folate receptor ß as a biomarker for the activity of rheumatoid arthritis synovitis and the response to anti-TNF agents.

This study aims to develop a sandwich ELISA system for the measurement of soluble folate receptor ß (sFRß) and evaluate whether base line levels of serum sFRß are a biomarker for the activity of RA synovitis and the response to anti-TNF agents. Serum sFRß from normal controls (41 samples), patients with OA (29 samples), and patients with RA (27 samples) and synovial fluid sFRß from patients with RA (17 samples) were measured by sandwich ELISA, using anti-FRαß and anti-FRß antibodies as capture and detection antibodies, respectively. Baseline levels of serum sFRß before therapy were evaluated in relation with DAS28-CRP or CRP and response to anti-TNF agents at 3-month follow-up. sFRß levels in RA synovial fluids were higher than those in RA sera, and sFRß levels in RA sera were higher than those in osteoarthritis and normal control sera. A significant relationship was observed between serum sFRß levels and the DAS28-CRP scores or CRP values. The area under curve (AUC) values for receiver-operating characteristic curves defined using the serum sFRß levels of RA patients before therapy had a higher predictive capacity than DAS28-CRP and CRP for the effective response of anti-TNF agents. The high serum sFRß levels with a cutoff value of 8 ng/mL were 100% specificity for the effective response of anti-TNF agents. The findings support that the serum sFRß levels in patients with RA act as a disease activation biomarker and that high serum sFRß levels act as a predictive biomarker for the response to anti-TNF agents.

Predictive factors for effectiveness and safety of enoxaparin for total knee arthroplasty in aged Japanese patients: a retrospective review.

BACKGROUND: The aims of this study were to investigate predictive factors involved in effectiveness and safety of enoxaparin for prevention of postoperative venous thromboembolism in aged Japanese total knee arthroplasty (TKA) patients. METHODS: Japanese patients over 65 years old who were administered enoxaparin for TKA were enrolled in this study. Their medical records were retrospectively reviewed. Data were corrected at the Izumi Regional Medical Center, from September 2009 to March 2014. Patients were stratified into groups according to whether enoxaparin was effective (no deep vein thrombosis event up to postoperative day 7) or not, and whether they had an adverse drug event (ADE) or not. RESULTS: A total of 128 patients were included in this study. One hundred five (82.0%) patients were in the effective group and 20 (15.6%) in the adverse drug event (ADE) group. Anemia (13 patients), abnormalities in liver function tests (4 patients), clinically relevant non-major bleeding (4 patients) and urticaria (1 patient) were observed as ADEs. Multivariate logistic regression analysis showed that the serum total protein level at postoperative day 1 (POD1, before enoxaparin administration), was associated with effectiveness of enoxaparin, while the serum total protein and hemoglobin level at POD1 were involved in ADE caused by enoxaparin. CONCLUSIONS: Although further large scale studies will be warranted, our results suggest that serum total protein level just before enoxaparin treatment for TKA relates to the effectiveness and safety of enoxaparin in a Japanese aged population. In addition, the results indicate that the development of anemia should be carefully monitored during enoxaparin treatment for TKA, particularly in patients with lower levels of serum hemoglobin before treatment.

Risk factors for venous thromboembolism after spine surgery.

The efficacy and safety of chemical prophylaxis to prevent the development of deep venous thrombosis (DVT) or pulmonary embolism (PE) following spine surgery are controversial because of the possibility of epidural hematoma formation. Postoperative venous thromboembolism (VTE) after spine surgery occurs at a frequency similar to that seen after joint operations, so it is important to identify the risk factors for VTE formation following spine surgery. We therefore retrospectively studied data from patients who had undergone spinal surgery and developed postoperative VTE to identify those risk factors. We conducted a retrospective clinical study with logistic regression analysis of a group of 80 patients who had undergone spine surgery at our institution from June 2012 to August 2013. All patients had been screened by ultrasonography for DVT in the lower extremities. Parameters of the patients with VTE were compared with those without VTE using the Mann-Whitney U-test and Fisher exact probability test. Logistic regression analysis was used to analyze the risk factors associated with VTE. A value of P < 0.05 was used to denote statistical significance. The prevalence of VTE was 25.0% (20/80 patients). One patient had sensed some incongruity in the chest area, but the vital signs of all patients were stable. VTEs had developed in the pulmonary artery in one patient, in the superficial femoral vein in one patient, in the popliteal vein in two patients, and in the soleal vein in 18 patients. The Mann-Whitney U-test and Fisher exact probability test showed that, except for preoperative walking disability, none of the parameters showed a significant difference between patients with and without VTE. Risk factors identified in the multivariate logistic regression analysis were preoperative walking disability and age. The prevalence of VTE after spine surgery was relatively high. The most important risk factor for developing postoperative VTE was preoperative walking disability. Gait training during the early postoperative period is required to prevent VTE.

Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate receptor beta.

Tumor-associated macrophages (TAMs) are frequently found in glioblastomas and a high degree of macrophage infiltration is associated with a poor prognosis for glioblastoma patients. However, it is unclear whether TAMs in glioblastomas promote tumor growth. In this study, we found that folate receptor beta (FR beta) was expressed on macrophages in human glioblastomas and a rat C6 glioma implanted subcutaneously in nude mice. To target FR beta-expressing TAMs, we produced a recombinant immunotoxin consisting of immunoglobulin heavy and light chain Fv portions of an anti-mouse FR beta monoclonal antibody and Pseudomonas exotoxin A. Injection of the immunotoxin into C6 glioma xenografts in nude mice significantly depleted TAMs and reduced tumor growth. The immunotoxin targeting FR beta-expressing macrophages will provide a therapeutic tool for human glioblastomas.

In vitro and in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells.

OBJECTIVE: To investigate the effects of the recombinant immunotoxin dsFv anti-FRbeta-PE38, which consists of the disulfide-stabilized Fv fragment (dsFv) of the anti-folate receptor beta (anti-FRbeta) antibody and the 38-kd portion of Pseudomonas exotoxin A (PE38), on the activation and proliferation of cells that function in inflammatory and degradative processes in rheumatoid arthritis (RA) synovial tissue. METHODS: The Ig VH-PE38 fusion protein and the Ig VL protein were produced in Escherichia coli, and then joined with a disulfide bond by engineering cysteine residues in the framework regions of these proteins. The effects of dsFv anti-FRbeta-PE38 on the activation and proliferation of cells in RA synovial tissue were investigated by immunohistochemistry; the numbers of cells expressing CD68, vascular cell adhesion molecule 1, angiopoietin 1, CD34, proliferating cell nuclear antigen, and interleukin-6 and the numbers of apoptotic cells were counted in RA synovial tissue engrafted into SCID mice treated or not treated with dsFv anti-FRbeta-PE38. The effects of dsFv anti-FRbeta-PE38 on the generation of osteoclasts from RA adherent synovial mononuclear cells in vitro was investigated by counting the number of resorption pits on dentin slices treated or not treated with dsFv anti-FRbeta-PE38. RESULTS: Administration of dsFv anti-FRbeta-PE38 reduced the numbers of macrophages, activated fibroblast-like cells, endothelial cells, and proliferating cells and increased the numbers of apoptotic cells in RA synovial tissue engrafted into SCID mice. In vitro, the generation of osteoclasts from RA adherent synovial mononuclear cells was largely suppressed by treatment with dsFv anti-FRbeta-PE38. CONCLUSION: Our findings show that dsFv anti-FRbeta-PE38 immunotoxin would be a promising tool for the treatment of RA synovitis, especially when administered intraarticularly.