Atlantoaxial Instability after Treatment of Atlantoaxial Rotatory Fixation: A Case Report.

Introduction: We encountered a case of atlantoaxial subluxation (AAS) after treatment of atlantoaxial rotatory fixation (AARF). Reports of developing AAS after AARF are extremely rare. Case Report: An 8-year-old male who feels neck pain was diagnosed with AARF type II according to the Fielding classification. Computed tomography (CT) showed that the atlas was rotated 32° to the right relative to the axis. Neck collar, Glisson traction, and reduction under anesthesia were performed. Five months after the onset of AARF, the patient was diagnosed with AAS due to dilatation of atlantodental interval (ADI) and underwent posterior cervical fusion. Conclusion: AARF treatments, such as long-term Glisson traction and reduction under general anesthesia, which exert a stress on the cervical spine, may damage the alar ligaments, apical ligaments, lower longitudinal band, and Gruber's ligament. Transverse ligament damage can also occur during the treatment of AARF, especially if AARF is refractory or requires long-term treatment. In addition, knowledge of the pathophysiology of atlantoaxial instability after AARF treatment is important.

A Rare Case of Cervical Myelopathy Caused by an Anomaly of the Axis: A Case Report and a Review of Current Comprehensive Literature.

Introduction: Cervical myelopathy due to anomalies of the posterior elements of the axis is rare, and limited cases have been reported. This study reports such a unique case of congenital anomaly of the laminae of the axis, which is treated by partial removal of the anomalous bony structure surgically, and provides a comprehensive review of the present literature on this pathological condition. Case Presentation: A 65-year-old man presented with a 3-year history of numbness in both arms with a sensory change in the right arm. Six months before admission, he noticed weakness in his right upper extremities and stiffness of the right lower extremity. Magnetic resonance imaging (MRI) showed a bilaterally compressed spinal cord with an anomalous bony structure at the C2-3 level. Computed tomography (CT) showed an invaginated abnormal bony structure at the C2-3 level and an abnormal lateral mass on the right side at the C2-3 level. The patient underwent posterior decompression surgery using the conventional open approach. One year after surgery, his myelopathy partially ameliorated, with his cervical radiograph showing no signs of the secondary instability and MRI showing sufficient decompression of the spinal cord. The age of onset, symptoms, and surgical treatment in our case was similar to those in the 14 previously reported cases; however, the morphology of the anomaly had variations. Conclusion: This is a report of a rare anomaly in the laminae of the axis. MRI and reconstructed CT scans were useful for the treatment of this case. Partial surgical removal was an appropriate treatment for this patient, resulting in a satisfactory outcome.

Ectopic gas in the fibular graft after anterior cervical corpectomy and fusion.

BACKGROUND: Ectopic gas in the graft is occasionally encountered upon follow-up computed tomography (CT) after anterior cervical corpectomy and fusion (ACCF). However, most cases lack inflammatory responses and manifestations of infection. Although the clinical significance of ectopic gas in the graft has not yet been established, to the best of our knowledge, no previous studies have described ectopic gas in the graft after ACCF. This study evaluated ectopic gas in the fibular graft upon follow-up CT after ACCF. METHODS: We reviewed 112 patients who underwent ACCF and follow-up CT, with a minimum follow-up period of 3 years. CT images were retrospectively reviewed to confirm the presence of ectopic gas in the graft and bone fusion. Bone fusion was defined as follows: mobility less than 2 mm between spinous processes on the flection-extension radiograph or a bone bridge on CT images. RESULTS: Of the 112 patients, 30 (27%) patients had ectopic gas in the fibular grafts. Among them, ectopic gas was initially observed 3 months after surgery (early onset) in 23 (77%) patients and 6 months after surgery (late-onset) in the remaining seven (23%) patients. Upon the latest follow-up CT, ectopic gas more frequently remained in late-onset (4/7, 57%) rather than in early-onset (3/23, 13%) cases (p = 0.033). Bone fusion was not observed when CT images exhibited ectopic gas in the graft, whereas ectopic gas was not observed when CT images exhibited bone fusion. CONCLUSION: Ectopic gas in the fibular graft was observed at both early and late-onset after ACCF; late-onset gas remained significantly. The remaining gas was strongly associated with pseudoarthrosis; therefore, pseudoarthrosis should be considered when ectopic gas in the graft is observed on CT images.

Correlation between mutated genes and forearm deformity in patients with multiple osteochondroma.

BACKGROUNDS: Exostosin-1 (EXT1) and exostosin-2 (EXT2) cause multiple osteochondromas (MO). In this study, we investigated the correlation between forearm deformity and mutant EXTs in Japanese families with MO. METHODS: We evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. Of these, 28 patients were selected and underwent radiography for their forearms since they had gross forearm deformities. We measured the radial articular angle (RAA), ulna variance (UV), carpal slip (CS), and percentage of radial bowing (%RB) to compare between patients with mutant EXT1 or EXT2 and those with missense or other mutations using Student's t-test. RESULTS: Twenty-two (78.6%) and 6 (11.4%) out of 28 patients had mutations in EXT1 and EXT2, respectively. Nine (32.1%) and 19 (67.9%) of the 28 patients had missense and other mutations, respectively. The mean age of patients with EXT1 and EXT2 were 25.9 ± 20.3 and 33.5 ± 25.4 years, respectively and those with missense mutation and other mutations were 28.7 ± 27.0 and 24.6 ± 17.0 years, respectively. There were no significant differences in RAA, UV, and RB between patients harbouring mutant EXT1 or EXT2 (RAA, 40.1 ± 8.7 and 31.5 ± 13.9°; UV, -2.7 ± 5.7 and -3.1 ± 3.7 mm; %RB, 8.6 ± 1.5 and 8.3 ± 2.0%). CS was significantly greater in patients with mutant EXT1 than that in those with mutant EXT2 (EXT1, 44.1 ± 16.8%; EXT2, 18.6 ± 14.0%). There were no significant differences in RAA, UV, CS and %RB between patients with missense and other mutations. CONCLUSIONS: Patients with mutant EXT1 displayed greater CS than patients with mutant EXT2, indicating that patients with MO harbouring EXT1 mutations sustain more severe ulnar drift deformities than those with EXT2 mutations.

Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas.

Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.

Bilateral vocal cord palsy after a posterior cervical laminoplasty.

PURPOSE: To report a patient with bilateral vocal cord palsy following cervical laminoplasty, who survived following a tracheotomy and intensive respiratory care. METHODS: Acute respiratory distress is a fatal complication of cervical spinal surgery. The incidence of bilateral vocal cord palsy after posterior cervical decompression surgery is extremely rare. The authors report a 71-year-old woman who suffered from cervical myelopathy due to ossification of the posterior longitudinal ligament. Open-door laminoplasty from C2 to C6 and laminectomy of C1 were performed. Following surgery, extubation was successfully conducted. Acute-onset dysphagia and stridor had occurred 2 h following extubation. A postoperative fiber optic laryngoscope revealed bilateral vocal cord palsy. After a tracheotomy and intensive respiratory care, she had completely recovered 2 months after surgery. DISCUSSION: One potential cause of this pathology was an intraoperative hyper-flexed neck position, which likely induced mechanical impingement of the larynx, resulting in swelling and edema of the vocal cords and recurrent laryngeal nerve paresis. Direct trauma of the vocal cords during intubation and extubation could have also induced vocal cord paralysis. CONCLUSIONS: We reported a case of bilateral vocal cord palsy associated with posterior cervical laminoplasty. Airway complications following posterior spinal surgery are rare, but they do occur; therefore, spine surgeons should be aware of them and take necessary precautions against intraoperative neck position, intubation technique, even positioning of the intratracheal tube.

Osteoblastic heparan sulfate regulates osteoprotegerin function and bone mass.

Bone remodeling is a highly coordinated process involving bone formation and resorption, and imbalance of this process results in osteoporosis. It has long been recognized that long-term heparin therapy often causes osteoporosis, suggesting that heparan sulfate (HS), the physiological counterpart of heparin, is somehow involved in bone mass regulation. The role of endogenous HS in adult bone, however, remains unclear. To determine the role of HS in bone homeostasis, we conditionally ablated Ext1, which encodes an essential glycosyltransferase for HS biosynthesis, in osteoblasts. Resultant conditional mutant mice developed severe osteopenia. Surprisingly, this phenotype is not due to impairment in bone formation but to enhancement of bone resorption. We show that osteoprotegerin (OPG), which is known as a soluble decoy receptor for RANKL, needs to be associated with the osteoblast surface in order to efficiently inhibit RANKL/RANK signaling and that HS serves as a cell surface binding partner for OPG in this context. We also show that bone mineral density is reduced in patients with multiple hereditary exostoses, a genetic bone disorder caused by heterozygous mutations of Ext1, suggesting that the mechanism revealed in this study may be relevant to low bone mass conditions in humans.

Sagittal Alignment of a Strut Graft Affects Graft Subsidence and Clinical Outcomes of Anterior Cervical Corpectomy and Fusion.

STUDY DESIGN: Retrospective study. PURPOSE: The purpose of this study was to investigate the influence of sagittal alignment of the strut graft on graft subsidence and clinical outcomes after anterior cervical corpectomy and fusion (ACCF). OVERVIEW OF LITERATURE: ACCF is a common technique for the treatment of various cervical pathologies. Although graft subsidence sometimes occurs after ACCF, it is one cause for poor clinical results. Malalignment of the strut graft is probably one of the factors associated with graft subsidence. However, to the best of our knowledge, no prior reports have demonstrated correlations between the alignment of the strut graft and clinical outcomes. METHODS: We evaluated 56 patients (33 men and 23 women; mean age, 59 years; range, 33-84 years; 45 with cervical spondylotic myelopathy and 11 with ossification of the posterior longitudinal ligament) who underwent one- or two-level ACCF with an autogenous fibular strut graft and anterior plating. The Japanese Orthopaedic Association (JOA) score recovery ratio for cervical spondylotic myelopathy was used to evaluate clinical outcomes. The JOA score and lateral radiograms were evaluated 1 week and 1 year postoperatively. Patients were divided into two groups (a straight group [group I] and an oblique group [group Z]) based on radiographic assessment of the sagittal alignment of the strut graft. RESULTS: Group I showed a significantly greater JOA score recovery ratio (p<0.05) and a significantly lower graft subsidence than group Z (p<0.01). CONCLUSIONS: Our findings suggest that a straight alignment of the strut graft provides better clinical outcomes and lower incidence of graft subsidence after ACCF. In contrast, an oblique strut graft can lead to significantly increased strut graft subsidence and poor clinical results.

A Pilot Study of Post-Operative Adjuvant Vaccine for Advanced Gastric Cancer.

BACKGROUND: Previously, we had performed a clinical study using human leukocyte antigen (HLA)-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides derived from DEPDC1, URLC10, FOXM1, KIF20A and VEGFR1 for advanced gastric cancer (AGC) patients who were refractory to chemotherapy. We applied the cocktail vaccine to the combination therapy with S-1 for patients with AGC as a post-operative adjuvant therapy and performed this clinical pilot study. METHODS: AGC patients who had curative surgery and were classified as pathologically stage III were enrolled. At each 6-week treatment cycle, patients received weekly subcutaneous administration of the cocktail vaccine with 5 continuous injections and one break for the first 4 cycles and with bi-weekly injections for the following 4 cycles. S-1 (80 mg/m2) was administered orally for 4 weeks with 2-week rest for all 8 cycles. The primary endpoint was the safety of the combination therapy and the secondary was the relative dose intensity for S-1. RESULTS: Fourteen patients were enrolled. Six patients with HLA-A*2402 had received S-1 plus the cocktail vaccine as an adjuvant therapy and the remaining 8 had S-1 monotherapy for eight cycles. Five out of 6 patients subjected to the combination group completed the therapy and one patient discontinued because of Grade 3 injection-site reaction. No adverse events of grade 3 or higher were observed except injection-site reactions shown in 5 out of 6 patients who had vaccine therapy. The mean and median relative dose intensities for S-1 were 75.5% and 88% in the combination group and 67% and 80.5% in S-1. CONCLUSION: The vaccine therapy combined with S-1 was manageable and safe adjuvant therapy for stage III gastric cancer. Furthermore, the optimal relative dose intensity of S-1 was achieved in combination group, although the injection-site reaction should be considered.

Multiple therapeutic peptide vaccines for patients with advanced gastric cancer.

We performed a clinical trial using HLA-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides for advanced gastric cancer (GC). Thirty-five GC patients who had shown resistance to the standard therapy were enrolled in this clinical trial using vaccinations with a mixture of multiple peptides derived from DEPDC1, URLC10, FoxM1, Kif20A and VEGFR1. The safety, the overall survival (OS), and the immunological responses based on an ELISPOT assay were determined to assess differences in patients who were HLA-A24-positive [24(+)] and HLA-A24-negative [24(-)]. No severe adverse effects were observed except for severe skin reactions in 4 patients. The differences in OS were not significant between patients who were 24(+) and 24(-). In the 24(+) group, patients who showed T cell responses specific to antigen peptides had a tendency towards better survival than those who showed no response, especially to the DEPDC1 peptide. The patients with local skin reactions had significantly better OS than the others. Peptide vaccine therapy was found to be safe and is expected to induce specific T cell responses in patients with advanced GC. The survival benefit of peptide vaccine monotherapy may not have been shown and further trials are needed to confirm these results.

Morbidity & Mortality Survey of Spinal Deformity Surgery in 2012-Report by the Japanese Scoliosis Society.

INTRODUCTION: The Japanese Scoliosis Society (JSS) planned to make a longitudinal survey of the mortality and morbidity (M&M) of spinal deformity surgery and established the M&M Committee in 2012. We reported the analysis of the surgical complication (M&M) survey in 2012. METHODS: A request to participate in this survey was mailed to all JSS members. Questionnaires were sent by email to members who agreed to cooperate, and their answers were obtained. Diagnosis was grouped into idiopathic scoliosis, congenital scoliosis, neuromuscular scoliosis, spondylolisthesis, pediatric kyphosis, and adult spinal deformity. Complications were grouped into death, blindness, neurological deficit, infection, massive bleeding, hematoma, pneumonia, cardiac failure, DVT/PE, gastrointestinal perforation, and instrumentation failure. RESULTS: A total of 2,906 patients were reported from sixty-eight hospitals: idiopathic 488, congenital 91, neuromuscular 82, others 214, spondylolisthesis 1,241, pediatric kyphosis 41, and adult spinal deformity 749. Complications were death in 3, neurological deficit in 49, early infection in 37, late infection in 14, massive bleeding in 91, hematoma in 18, pneumonia in 6, cardiac failure in 1, DVT/PE in 9, gastrointestinal perforation in 2, and instrumentation failure in 73. The complication rate of having a neurological deficit, massive bleeding, and instrumentation failure was 4.88%, 7.32%, and 4.88% respectively in patients with pediatric kyphosis, and 3.07%, 8.01%, and 5.21% respectively in patients with an adult spinal deformity. The complication rate of early infection was 4.88% in the patients with pediatric kyphosis. CONCLUSIONS: The complication rates of pediatric kyphosis and adult spinal deformity were high.

Large-scale mutational analysis in the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas.

BACKGROUND: Multiple osteochondroma (MO) is an autosomal dominant skeletal disorder characterized by the formation of multiple osteochondromas, and exostosin-1 (EXT1) and exostosin-2 (EXT2) are major causative genes in MO. In this study, we evaluated the genetic backgrounds and mutational patterns in Japanese families with MO. RESULTS: We evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. The exons and exon/intron junctions of EXT1 and EXT2 were directly sequenced after PCR amplification. Fifty-two mutations in 47 families with MO in either EXT1 or EXT2, and 42.3% (22/52) of mutations were novel mutations. Twenty-nine families (40.8%) had mutations in EXT1, and 15 families (21.1%) had mutations in EXT2. Interestingly, three families (4.2%) had mutations in both EXT1 and EXT2. Twenty-four families (33.8%) did not exhibit mutations in either EXT1 or EXT2. With regard to the types of mutations identified, 59.6% of mutations were inactivating mutations, and 38.5% of mutations were missense mutations. CONCLUSIONS: We found that the prevalence of EXT1 mutations was greater than that of EXT2 mutations in Japanese MO families. Additionally, we identified 22 novel EXT1 and EXT2 mutations in this Japanese MO cohort. This study represents the variety of genotype in MO.

Clinical Outcomes of Surgical Treatments for Traumatic Spinal Injuries due to Snowboarding.

STUDY DESIGN: Retrospective study. PURPOSE: To assess treatment outcomes of snowboarding-related spinal and spinal cord injuries. OVERVIEW OF LITERATURE: Snowboarding-related spinal or spinal cord injury have a great impact on social and sporting activities. METHODS: A retrospective review of 19 cases of surgically treated snowboard-related injury was done. Analyzed parameters included site of injury, type of fracture, peri- and postoperative complications, pre- and postoperative neurological status, activities of daily living, and participation in sports activities at the final follow-up. RESULTS: The major site of injury was the thoracolumbar junction caused by fracture-dislocation (13/19 cases). The remaining 6 cases had cervical spine injuries. Over 60% of the patients had Frankel A and B paralysis. All patients were surgically treated by posterior fusion with instrumentation. Five underwent additional anterior fusion. Surgical outcome was restoration of ambulatory capacity in 12 patients (63.2%). Ultimately, 15 patients (78.9%) could return to work. Patients with complete paralysis upon admission showed reduced ambulatory capacity compared to those with incomplete paralysis. None of the patients again participated in any sports activities, including snowboarding. CONCLUSIONS: Snowboarding-related spinal or spinal cord injury has a great impact on social as well as sports activities. It is necessary to enhance promotion of injury prevention emphasizing the snowboarders' responsibility code.

Morphologic Changes in Contralateral Lumbar Foramen in Unilateral Cantilever Transforaminal Lumbar Interbody Fusion Using Kidney-type Intervertebral Spacers.

STUDY DESIGN: A retrospective study of 58 patients undergoing cantilever transforaminal lumbar interbody fusion (c-TLIF). OBJECTIVES: To evaluate morphologic changes in the intervertebral foramen (IVF) on the side contralateral to spacer insertion in patients undergoing c-TLIF using plain x-ray films and computed tomography scan. SUMMARY OF BACKGROUND DATA: The morphologic changes in the contralateral lumbar foramen in c-TLIF using unilateral insertion of spacers have not been well studied. MATERIALS AND METHODS: Fifty-eight consecutive patients with lumbar dysplastic changes or degenerative disk diseases underwent c-TLIF using 96 kidney-type spacers with local bone grafts. Radiographic findings (sagittal disk angle), computed tomography scan findings (coronal disk angle, disk height, foraminal height (FH), foraminal width, and cross-sectional area of IVF in contralateral lumbar foramen) were compared between preoperative period and 6 months after surgery. The correlations between contralateral lumbar foraminal dimensions and disk height, sagittal disk angle, and coronal disk angle were analyzed. RESULTS: After c-TLIF, sagittal angle, disk height, FH, foraminal width, and cross-sectional area of the IVF were significantly increased. Increase in posterior disk height showed a positive correlation with increases in FH, foraminal width, and cross-sectional area of IVF (r=0.235-0.511). However, the increase in sagittal disk angle showed a negative correlation with changes in foraminal width and cross-sectional area of IVF (r=-0.256 to -0.206). CONCLUSIONS: Lumbar foraminal dimensions on the side contralateral to spacer insertion increased significantly after c-TLIF, suggesting that c-TLIF enables indirect decompression of the contralateral nerve root. Although increase in posterior disk height was shown to be an important factor to increase contralateral foraminal size, segmental lordosis was a risk factor for a decrease in contralateral foraminal size.

Increased blood flow in the anterior humeral circumflex artery correlates with night pain in patients with rotator cuff tear.

BACKGROUND: Night pain is a particularly vexing symptom in patients with rotator cuff tear. It disturbs sleep and decreases quality of life, and there is no consensus regarding its etiology. Based on arthroscopic surgical observations of synovitis around the rotator interval or capsule surface in rotator cuff tear, we hypothesized that blood flow from the artery feeding the capsule increases blood supply to the synovium. This study aimed to investigate the relationship between blood flow and night pain using pulse Doppler ultrasonography. METHODS: A series of 47 consecutive patients with rotator cuff tear was evaluated. The peak systolic velocity and resistance index of blood flow in the ascending branch of the anterior humeral circumflex artery were evaluated using pulse Doppler ultrasonography. We also investigated 20 normal shoulders in healthy volunteers. The peak systolic velocity and resistance index were compared between affected and unaffected sides in patients and between dominant and nondominant sides in controls. RESULTS: Anterior humeral circumflex artery peak systolic velocity and resistance index did not differ between sides in control subjects or in patients with rotator cuff tear without night pain. However, anterior humeral circumflex artery peak systolic velocity and resistance index did differ significantly between sides in patients with rotator cuff tear with night pain. CONCLUSIONS: This study revealed anterior humeral circumflex artery hemodynamics in patients with rotator cuff tear and normal subjects using Doppler ultrasonography. Night pain, particularly involving aching, appears to be related to the hemodynamics. These findings suggest that investigating the hemodynamics of patients with rotator cuff tear with night pain may lead to greater understanding of the etiology of this symptom.

Cervical symmetric dumbbell ganglioneuromas causing severe paresis.

We report an extremely rare case with bilateral and symmetric dumbbell ganglioneuromas of the cervical spine in an elderly patient. A 72-year-old man came by ambulance to our hospital due to progressive incomplete paraplegia. Magnetic resonance imaging demonstrated bilateral symmetric dumbbell tumors at the C1/2 level. We performed total resection of the intracanalar tumor, aiming at complete decompression of the spinal cord, and partial and subtotal resection of foraminal outside portions. Histopathological examination of the surgical specimen indicated the tumor cells to be spindle cells with the presence of ganglion cells and no cellular pleomorphism, suggesting a diagnosis of ganglioneuroma. Although the surgery was not curative, the postoperative course was uneventful and provided a satisfactory outcome. This is the fourth known case of cervical ganglioneuromas of the bilateral symmetric dumbbell type.

Trachea-thoracic vertebral body fistula causing spinal cord injury: a case report.

STUDY DESIGN: A case report and review of the literature. OBJECTIVE: To discuss the significance of identifying trachea-thoracic vertebral body fistula. SUMMARY OF BACKGROUND DATA: Several authors have reported the occurrence of communication between the trachea and the spinal canal or paraspinal abscess. However, trachea-thoracic vertebral body fistulas have not been reported. METHODS: A 77-year-old male experienced gradually worsening lower-extremity palsy. Fifteen years before presentation, he had undergone retrosternal esophageal reconstruction with a gastric tube for esophageal cancer. RESULTS: Computed tomographic scan revealed compression of the Th5 vertebral body; the trachea and the Th5 vertebral body were connected by a fistula, and air seemed to enter Th5 from the trachea. Magnetic resonance image showed severe spinal canal stenosis. Posterior thoracic decompression and fusion was performed. Five months after the procedure, he regained the ability to walk with a cane, and computed tomographic scan revealed closure of the fistula and the bony fusion. CONCLUSION: To our knowledge, this is the first case report of a trachea-thoracic vertebral body fistula. Because the trachea is adjacent to the anterior aspect of the thoracic vertebrae, in cases of retrosternal esophageal reconstruction, trachea-vertebral body fistula should be a differential diagnosis for destructive changes in thoracic vertebrae without any signs of trauma.

Clinical significance of brachial flow-mediated dilation in patients with rheumatoid arthritis.

AIM: This study aimed to clarify whether different anti-tumor necrosis factor (TNF) drugs can improve endothelial function better than conventional disease-modifying anti-rheumatic drugs (DMARDs) in a series of Japanese patients with rheumatoid arthritis (RA). METHOD: Twenty-five patients who met the American College of Rheumatology 1987 revised diagnostic criteria for RA were randomly selected for this study. The percentage of brachial flow-mediated dilation (%FMD) and maximum carotid intima-media thickness were examined by ultrasonography. RESULTS: The %FMD in the group treated with anti-TNF therapy was significantly higher than that in the group treated with DMARDs (P < 0.001). The %FMD was significantly correlated with anti-TNF therapy (r = 0.684, P < 0.001) and Disease Activity Score C-reactive protein (r = -0.404, P < 0.05). Multiple regression analysis revealed that anti-TNF therapy was significantly associated with %FMD (ß = 0.684, P < 0.001). CONCLUSION: Anti-TNF therapy may influence endothelial function more than conventional DMARD therapy. Prospective longitudinal studies examining whether anti-TNF therapy was able to improve endothelial function are required.

Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center, randomized, open-label, non-inferiority trial.

INTRODUCTION: While many of the commonly used conservative treatments for knee osteoarthritis (OA) have been recognized to be effective, there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA. However, frequent and serious adverse effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and improve joint function. However, there has been no qualified direct comparison study of the efficacy and safety between IA-HA and NSAIDs for patients with knee OA. The aim of this study was to clarify the efficacy and safety of early-phase IA-HA in comparison to those of NSAIDs for patients with knee OA. METHODS: This multicenter, randomized, open-label, parallel-group, non-inferiority comparison study with an oral NSAID involved a total of 200 patients with knee OA. An independent, computer-generated randomization sequence was used to randomly assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n = 100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned regarding any adverse events during treatment. The full analysis set (FAS) was used for analysis. The margin of non-inferiority was 10%. RESULTS: The analyses of primary endpoint included 98 patients in the IA-HA group and 86 patients in the NSAID group. The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2% (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were significantly lower than those in the NSAID group (P = 0.026 and 0.004, respectively). CONCLUSIONS: The early efficacy of IA-HA is suggested to be not inferior to that of NSAIDs, and that the safety of the early phase of IA-HA is superior to that of NSAIDs for patients with knee OA. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000001026.

Malignant solitary fibrous tumor of the lumbar spinal root mimicking schwannoma: a case report.

BACKGROUND CONTEXT: Malignant solitary fibrous tumors (SFTs) arising from the spinal cord are extremely rare and poorly understood mesenchymal neoplasms. To date, only one malignant SFT located in the spinal canal of the sacrum has been described, but none arising from the lumbar nerve root have been reported. Although most SFTs with benign histological features can be treated by complete surgical excision alone, malignant SFTs may require adjuvant therapy. However, systemic chemotherapy and radiotherapy have not been shown effective in patients with malignant SFTs. PURPOSE: To describe a patient with a malignant SFT arising from the lumbar nerve root. STUDY DESIGN: A case report and review of literature. METHODS: We describe the clinical course of the patient and the radiological and pathological findings of the tumor. The effect of systemic chemotherapy was evaluated and the relevant literature was reviewed. This work has no disclosure of funding and was approved by the Institutional Review Board of Gifu University. RESULTS: The tumor had been resected previously at another hospital, but it recurred and showed multiple metastatic lesions on both lungs within 3 months. Although the patient received systemic chemotherapy, both primary and metastatic lesions were found to be stable disease according to Response Evaluation Criteria in Solid Tumors. The patient died due to cachexia 6 months after her first visit. CONCLUSION: This patient presented with a highly unusual tumor. Even if a tumor is a dumbbell-shaped mass, similar to a neural tumor, SFT should be considered in the differential diagnosis.