Screening of a Panel of Low Molecular Weight Compounds That Inhibit Synovial Fibroblast Invasion in Rheumatoid Arthritis.

Increased invasion of synovial fibroblasts and their involvement in cartilage damage are characteristic phenotypes of rheumatoid arthritis (RA). To identify low molecular weight compounds that suppress synovial fibroblast invasion, a panel of inhibitors (n = 330) was initially screened using a real-time cell analysis system for human synovial fibroblasts that were enzymatically isolated from surgical samples of RA patients. To evaluate the effects of the inhibitors identified in the screen, synovial fibroblast migration was measured using a wound-healing assay, and phosphorylation of intracellular signaling molecules was determined by immunoblots. Several candidate inhibitors were identified in the screen, including inhibitors against platelet-derived growth factor receptor (PDGFR), Akt, PI3K, and glycogen kinase synthetase 3 (GSK-3). These inhibitors strongly suppressed synovial fibroblast migration after 72 h and downregulated phosphorylation of Akt (Ser473) at 48 h. When the inhibitors were removed from the culture conditions, both migration and phosphorylated Akt (Ser473) levels were restored. Furthermore, all the categories of inhibitors except for PDGFR inhibitor IV decreased cell proliferation as well as IL-6 production in synovial fibroblasts. Interestingly, GSK-3 inhibitors increased anti-inflammatory cytokine IL-10 production but suppressed IL-23 production from LPS-primed macrophages obtained from healthy donors. In conclusion, blocking PDGFR, PI3K, or GSK-3 could have therapeutic value as an RA treatment that targets the invasion/migration of synovial fibroblasts.

Outcomes after decompression surgery without fusion for patients with lumbar spinal stenosis and substantial low back pain.

PURPOSE: The aim of this study was to evaluate the efficacy of decompression surgery alone for patients with intolerable low back pain. METHODS: We retrospectively identified 222 patients who underwent spinal decompression without fusion surgery who had substantial preoperative low back pain (preoperative numerical rating scale score ≥ 5). Their clinical outcomes were assessed using the numerical rating scale and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) preoperatively and at 3 months and 1 year after surgery. RESULTS: At 3 months and 1 year after surgery compared with baseline, there was a significant improvement in the overall mean numerical rating scale scores for low back pain (baseline = 6.8, 3 months = 2.1, 1 year = 2.7), leg pain (6.8, 2.1, 2.7), and leg numbness (6.4, 2.9, 3.2) (P < 0.05). The efficacy rate assessed by JOABPEQ was 68.1% for pain-related disorders, 47.0% for lumbar spine dysfunction, 63.3% for walking ability, 48.2% for social life dysfunction, and 21.6% for psychological disorders. When patients were classified into three groups depending on their degree of leg pain (mild, moderate, and severe), there was no significant difference in the efficacy rate between the three groups. CONCLUSION: Decompression surgery can improve low back pain, regardless of the degree of preoperative leg pain, but the average score for LBP and leg pain slightly worsened between 3 months and 1 year after surgery. These slides can be retrieved under Electronic Supplementary Material.

Prognostic Factors for Drop Foot Due to Lumbar Degenerative Diseases: The Impact of Surgical Timing on Postoperative Recovery.

STUDY DESIGN: Retrospective clinical series. OBJECTIVE: To investigate the prognostic factors for the improvement of drop foot caused by degenerative lumbar disease after surgery. SUMMARY OF BACKGROUND DATA: Drop foot may be caused by lumbar spinal diseases and may affect daily life. There are limited data regarding predictors of drop foot, especially surgical timing. METHODS: We retrospectively reviewed data from 87 patients with drop foot. Prognostic factors and precise timing of surgery affecting drop foot improvement were examined by multivariate logistic regression analysis. RESULTS: Forty patients (46.0%) recovered from drop foot after surgery. Age [odds ratio (OR)=0.93; 95% confidence interval (CI), 0.87-0.98; P=0.01], preoperative anterior tibialis muscle strength (OR=12.0; 95% CI, 2.41-59.9; P=0.002), and duration of drop foot before surgery (OR=3.59; 95% CI, 1.09-11.8; P=0.04) were significant prognostic factors. Two months was the most appropriate cutoff for surgery after appearance of symptoms. CONCLUSIONS: Age, preoperative tibialis anterior muscle strength, and duration of drop foot were statistically significant prognostic factors of recovery from drop foot. Surgery within 2 months after the onset of drop foot may improve postoperative outcome.

Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging of Cystic Lesions of the Spinal Cord.

BACKGROUND: Cystic lesions of the spinal cord such as spinal intradural arachnoid cysts (SIACs) and spinal extradural arachnoid cysts (SEACs) contain cerebrospinal fluid (CSF). The pathology of these lesions is often difficult to understand because it is difficult to detect abnormal CSF flow by conventional magnetic resonance imaging (MRI) or myelography. We preliminarily evaluated the usefulness of time-spatial labeling inversion pulse magnetic resonance imaging (T-SLIP MRI) of cystic lesions of the spinal cord. METHODS: T-SLIP MRI was applied to the following 6 consecutive cystic lesions of the spinal cord: 3 SEACs, 1 SIAC, 1 spinal intramedullary cyst associated with adhesive arachnoiditis, and 1 chronic pseudomeningocele. Information obtained by T-SLIP MRI was evaluated with regard to the following: 1) whether exclusive pathologic information was obtained, 2) whether this information affected the therapeutic strategy, and 3) the time required for T-SLIP MRI. RESULTS: Exclusive information was obtained in all 6 cases. In SEACs and the intramedullary cyst, pathologic CSF flow into the cyst was directly visualized, enabling us to narrow the therapeutic intervention targets. In SIAC, exclusive information involved detection of the cystic cranial wall and the absence of the caudal wall, enabling us to omit the exploration of the caudal wall. The examination required as long as 80 minutes for SIAC and <30 minutes for the other cases. CONCLUSIONS: T-SLIP MRI is useful for obtaining pathologic information about cystic lesions of the spinal cord.

In vivo kinematic effects of ball and socket third condyle as a post-cam mechanism in tri-condylar knee implants.

BACKGROUND: Tri-condylar implants containing a ball and socket third condyle as a post-cam mechanism were developed to accommodate a lifestyle requiring frequent deep flexion activities. The purpose of the current study was to examine the kinematic effects of the ball and socket third condyle during a deep knee bend activity, and to confirm the contact status of the ball and socket joint. METHODS: Seventeen knees implanted with tri-condylar implants were analyzed using a 3D to 2D registration approach. A distance of less than 1mm denoted ball and socket contact. Medial and lateral contact positions and axial rotation were compared before and after contact. Moreover, the contact position at the third condyle and the center of the ball joint were analyzed. RESULTS: After the third condyle contact, posterior translation of the medial and lateral contact positions increased considerably. Meanwhile, the angular rotation remained still. The center of the third condyle did not move after contact, and the contact position at the third condyle remained low. CONCLUSIONS: The third condyle induced intensive posterior translation of both condyles, and did not prevent axial rotation, which was proved to work properly as a posterior stabilizing post-cam mechanism.

Detection of the communicating hole(s) of spinal extradural arachnoid cysts using time-spatial labeling inversion pulse magnetic resonance imaging.

STUDY DESIGN: Report of 2 cases. OBJECTIVE: To report the usefulness of time-spatial labeling inversion pulse magnetic resonance imaging (T-SLIP MRI) for detection of the communicating hole(s) of spinal extradural arachnoid cysts (SEACs). SUMMARY OF BACKGROUND DATA: SEACs normally communicate with the subarachnoid space via small communicating hole(s) in the dura. It is necessary to identify the accurate locations of these communicating hole(s) before attempting to close them through limited laminotomy/laminectomy. Myelocomputed tomography or conventional MRI may fail to detect the locations of the hole(s) because they comprise small dural defects. METHODS: Case 1: A 33-year-old female presented with an SEAC at the T11­L2 vertebral level. Case 2: An 82-year-old female presented with an SEAC at T12­L4 vertebral level. RESULTS: Case 1: T-SLIP MR image of the left parasagittal plane (not the midsagittal or right parasagittal plane) revealed cerebrospinal fluid flow from the subarachnoid space into the cyst at L1. After limited laminotomy at T12­L1 and partial cyst resection, we identified 2 contiguous dural holes immediately medial to the left L1 pedicle; this corroborated the preoperative T-SLIP MRI findings. The holes were sutured. Postoperative conventional MR image confirmed significant cyst shrinkage. Case 2: T-SLIP MR image revealed a curved line at the L1 pedicle in the right parasagittal plane. After L1 laminectomy and partial cyst resection, a dural hole was identified L1 pedicle, which was in agreement with the preoperative T-SLIP MRI findings. After surgery, the lower extremity pain disappeared. Postoperative conventional MR image revealed significant cyst shrinkage. CONCLUSION: T-SLIP MRI is useful for detection of the communicating hole(s) of SEACs. LEVEL OF EVIDENCE: N/A.

Can post-cam function be replaced by addition of a third condyle in PS TKA?

The purpose of the study was to analyze the effectiveness of an additional ball and socket articulation in implanted knees and whether it can replicate post-cam function. Fifteen knees implanted with a cruciate substituting (CS) polyethylene without a post and ten knees implanted with a posterior stabilized (PS) polyethylene with a post were analyzed using 3D model fitting approach. Two types of designs showed similar posterior translation and similar axial rotation. Most of the contact points at the ball and socket joint stayed within the socket height for the PS group. This study indicates that the ball and socket joint is able to function as a replacement of the post-cam mechanism, which might serve as a new way to achieve posterior stability.

Degenerative osteoarthritis after Perthes' disease: a 36-year follow-up.

BACKGROUND: Although the prognosis of Perthes' disease at skeletal maturity is considered favorable, little is known about the long-term results after middle age. METHODS: We retrospectively analyzed the radiographic and functional outcomes of 67 patients (70 hips) who had been treated for Perthes' disease. Of these patients, 28 patients (29 hips) were evaluated using JOA (Japanese Orthopaedic Association) score and radiographs at follow-up (Group 1), 39 patients (41 hips) were evaluated by a postal questionnaire (Group 2). The mean follow-up period was 36.1 years. The mean age at follow-up was 43.1 years. RESULTS: Group 1, good radiographic results (Stulberg class I or II) were achieved in 59% of hips. No osteoarthritis (Tönnis Grade 0) was observed in only 48% of hips. The clinical results were good (JOA score ≥ 70) in 79% of hips. Disturbance of walking ability and activities of daily living was little. The Tönnis grade and JOA score declined after 40 years of age. All patients older than 50 years showed severe osteoarthritis. The severity of osteoarthritis correlated significantly with age at follow-up. Group 2, the clinical results were good (JOA score ≥ 56) in 76% of hips. In both groups, no patient had undergone total hip arthroplasty. Younger age at diagnosis (<8 years) correlated significantly with a better result. The JOA score correlated significantly with age at follow-up. CONCLUSION: Patients who were treated for Perthes' disease have a risk of osteoarthritis and a clinically poor outcome after the age of 40-50 years.

Deep flexion-oriented bisurface-type knee joint and its tibial rotation that attributes its high performance of flexion.

In 1989, we developed an artificial knee prosthesis that could accommodate the oriental lifestyle where people would sit more often on the floor than on a chair. The knee had a bisurface feature with an auxiliary joint of a ball and socket at the center of the posterior part aiming at an improved flexional function. The auxiliary joint functions not only to facilitate a rollback movement but also to add a rotational movement. It was investigated whether this knee prosthesis could show an internal rotation of the tibia during flexion such as the physiologic movement of the knee. The internal rotation of the tibia was evaluated for the patients who could sit on legs in the oriental style after total knee arthroplasty. The average flexion angle of patients who achieved this style of sitting was 144.1°, and the average internal rotation was estimated as 14.3° by a pattern matching method using a computer-assisted design system.

[The principles and techniques of cast application].

In this chapter, the chemical properties of the plaster cast and synthetic cast, the techniques of the plaster bandage, and its complications are discussed. The plaster cast is one of the useful materials in the treatment of the orthopedic surgery. Orthopedic surgeon must improve the skill of plaster bandage.

A modification of the retrograde medullary screw for the treatment of bilateral pubic ramus nonunions: a case report.

We describe a patient with bilateral pubic ramus nonunions who was treated successfully with a modification of the retrograde medullary screw technique, in which the screw orientation was altered so that it engaged the cancellous bone in the inferior part of the anterior column and the anterior-inferior cortex of the fossa acetabuli. The modification should be one option when the original technique is judged to be difficult to perform.