Formulation of Japanese Orthopaedic Association (JOA) clinical practice guideline for the management of low back pain- the revised 2019 edition.

BACKGROUND: The latest clinical guidelines are mandatory for physicians to follow when practicing evidence-based medicine in the treatment of low back pain. Those guidelines should target not only Japanese board-certified orthopaedic surgeons, but also primary physicians, and they should be prepared based entirely on evidence-based medicine. The Japanese Orthopaedic Association Low Back Pain guideline committee decided to update the guideline and launched the formulation committee. The purpose of this study was to describe the formulation we implemented for the revision of the guideline with the latest data of evidence-based medicine. METHODS: The Japanese Orthopaedic Association Low Back Pain guideline formulation committee revised the previous guideline based on a method for preparing clinical guidelines in Japan proposed by Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Two key phrases, "body of evidence" and "benefit and harm balance" were focused on in the revised version. Background and clinical questions were determined, followed by literature search related to each question. Appropriate articles were selected from all the searched literature. Structured abstracts were prepared, and then meta-analyses were performed. The strength of both the body of evidence and the recommendation was decided by the committee members. RESULTS: Nine background and nine clinical qvuestions were determined. For each clinical question, outcomes from the literature were collected and meta-analysis was performed. Answers and explanations were described for each clinical question, and the strength of the recommendation was decided. For background questions, the recommendations were described based on previous literature. CONCLUSIONS: The 2019 clinical practice guideline for the management of low back pain was completed according to the latest evidence-based medicine. We strongly hope that this guideline serves as a benchmark for all physicians, as well as patients, in the management of low back pain.

Upper Cervical Compression Myelopathy Caused by the Retro-Odontoid Pseudotumor With Degenerative Osteoarthritis and Calcium Pyrophosphate Dihydrate Disease: A Case Report and Literature Review.

The retro-odontoid pseudotumor is often concurrent with atlantoaxial subluxation (AAS). Therefore, the pseudotumor is relatively common in rheumatoid arthritis (RA) but rare in primary osteoarthritis (OA). This is a case report of an elderly male patient suffering from neck pain and compression myelopathy caused by the craniocervical pseudotumor with OA but without atlantoaxial instability. He had long-lasting peripheral and spinal pain treated by nonsteroidal anti-inflammatory drugs. Imaging found upper cervical spondylosis without AAS or dynamic instability but with periodontoid calcifications and ossifications, suggesting calcium pyrophosphate dihydrate (CPPD) crystal deposition. Based on a comprehensive literature search and review, CPPD disease around the atlantodental joint is a possible contributor to secondary OA development and retro-odontoid pannus formation through chronic inflammation, which can be enough severe to induce compression myelopathy in non-RA patients without AAS. The global increase in the aged population advises caution regarding more prevalent upper cervical spine disorders associated with OA and CPPD.

Surgical and general complications in 2,961 Japanese patients with cervical spondylotic myelopathy: Comparison of different age groups.

Introduction: Details of surgical and general complications for patients with cervical spondylotic myelopathy (CSM) are still uncertain. The purpose of this study was to describe surgeries and their complications among Japanese patients with CSM. Methods: The Japanese Society for Spine Surgery and Related Research performed a nationwide survey on spine surgery and complications in 2011. Data of patients with 2,961 CSM >40 years old were included. The clinicopathological variables were basic demographic and clinical information, surgical information, and surgical and general complications. To examine the influence of age, variables were compared among three age groups: patients 40-64 (n=1,123), 65-74 (n=966), and ≥75 (n=872) years of age. Results: The study included 1,970 males and 991 females and the mean age was 64.3 years old. There were 168 anterior (5.7%) and 2,770 posterior (94.2%) approach surgeries. The vast majority of patients with CSM were treated using the posterior approach, 89.4% of whom had decompression surgery only. Anterior surgeries were more common in the younger age group, but posterior surgeries were equally distributed. The incidence of total complications including surgical/general complications was similar for the anterior (16/168; 9.5%) and posterior (295/2,770; 10.6%) approaches. No patient died on the operating table, but four patients (0.1%) died within one month after surgery. No association was detected between complications and age, comorbidity, and other surgical factors. The incidence of complications was similar for the different age groups. However general complications were predominantly observed in the older group and those who had instrumented surgery. Conclusions: The results indicate that the indication and surgical performance for patients with CSM is favorable in Japan, despite the super-aging population. Few serious complications were reported in this study. However, more detailed informed consent about surgical and, in particular, general complications is necessary for the older patients with CSM.

Complications of spinal surgery for elderly patients with lumbar spinal stenosis in a super-aging country: An analysis of 8033 patients.

BACKGROUND: The Japanese Society for Spine Surgery and Related Research (JSSR) performed a third study on complications in spinal surgery in 2011. The purpose was to present information about surgery and complications in a large amount of elderly patients aged 65 years with lumbar spinal stenosis (LSS) without coexisting spondylolisthesis, spondylolysis, or scoliosis, and to compare patients aged ≥80 years to those aged 65-79 years. METHODS: A recordable optical disc for data storage was sent by JSSR in January 2012 to 1105 surgeons certified by the JSSR in order to collect surgical data. Data were returned by the end of May 2012. RESULTS: Data were accumulated for 8033 patients aged 65 years. The incidence of surgical complications was 10.8%, and did not differ significantly between age groups. The incidence of general complications was 2.7%, and differed significantly between age groups (p < 0.005). The highest incidence of surgical complications was for dural tear (DT) (3.6%), followed by deep wound infection (DWI) (1.4%), neurological complications (1.3%), and epidural hematoma (1.3%). Spinal instrumentation was applied in 30.3%. Incidences of surgical complications in instrumented and noninstrumented surgery were 17.3% and 8.8%. In instrumented surgery, incidences of surgical and general complications were higher in the ≥80 year age group than in the 65-79 year age group. Logistic regression analyses showed patients with microendoscopic surgery at increased risk of DT. Patients with diabetes mellitus and instrumented surgery showed increased risks of DWI. CONCLUSIONS: Incidences of surgical complications did not differ significantly between age groups. Attention should be paid to both surgical and general complications, particularly for postoperative mental disease in instrumented surgery for patients≥80 years old.

Japanese 2011 nationwide survey on complications from spine surgery.

BACKGROUND: The Japanese Society for Spine Surgery and Related Research (JSSR) previously carried out two nationwide surveys in 1994 and 2001 on complications from spine and spinal cord surgery. More than 10 years have now elapsed since 2001. Rapidly ageing populations have major impacts on society, particularly in the medical field. The purpose of this study was therefore to examine the present situation for spine surgery in Japan. METHODS: The JSSR research team prepared a computerized questionnaire made up of two categories in order to capture clinicopathological information and surgical information. A recordable optical disc for data storage was sent to surgeons who were certified for spine surgery by JSSR. The data was analyzed. RESULTS: The JSSR carried out a nationwide survey of complications of 31,380 patients. Patients aged 60 years or older comprised 63.1 % of the overall cohort. This was considerably higher than observed in previous surveys. Degenerative spinal diseases increased 79.7 %. With regard to surgical approach, the incidence of anterior surgery has decreased, while that of posterior surgery has increased compared to the earlier surveys (both p < 0.05). Spinal instrumentation was applied in 30.2 % cases, compared to 27.0 and 34.0 % cases in the 1994 and 2001 surveys, respectively. Intraoperative and postoperative complications were reported in 10.4 % and were slightly increased compared to 8.6 % in the earlier surveys (both p < 0.05). Diseases associated with a high incidence of complication included intramedullary tumor (29.3 %) and primary malignant tumor (22.0 %). The highest incidence of complication was dural tear (2.1 %), followed by neurological complication (1.4 %).

Tibial tubercle osteotomy with screw fixation for total knee arthroplasty.

This study investigated the efficacy of tibial tubercle osteotomy (TTO) with screw fixation as part of the surgical treatment of primary complicated total knee arthroplasty (TKA) and revision TKA. From January 2000 to April 2011, 15 patients (15 knees) underwent revision TKA and 20 patients (21 knees) underwent primary TKA. The average patient age was 68.7±8.7 years. Patients underwent follow-up at the authors' institution for an average of 60.6±32.9 months. Comparison of preoperative and postoperative Knee Society Scores and Knee Society Functional Scores showed significant postoperative improvement (P<.05). Moreover, postoperative range of motion of the knee improved from 88.5°±33.8° to 104.3°±18.2° (P<.05). Radiographic assessment showed that the average period to bone union was 10.8±5 weeks (range, 5-28 weeks), the average length of the bone fragment was 59.4±5.9 mm, the average width at the proximal end was 18.9±2.9 mm, and the average thickness at the proximal end of the osteotomy was 10.3±1.2 mm. Tibial tubercle osteotomy provided wide exposure for TKA while protecting the extensor mechanism. Solid bone-to-bone fixation was achieved using TTO with 2 screws, and although the overall complication rate was 8.3%, none of the complications were associated with TTO itself. It is recommended that the bone fragment be 60 mm long, 20 mm wide, and 10 mm thick at the proximal end. Appropriate size of the osteotomized bone and solid screw fixation are essential to prevent complications during this procedure.

Satisfactory results at 8 years mean follow-up after ADVANCE® medial-pivot total knee arthroplasty.

BACKGROUND: Although good overall results have been reported with TKA, certain problems and limitations remain, primarily due to postoperative differences in joint kinematics, when compared with the normal knee. ADVANCE® Medial-Pivot TKA involves replicating the medial pivoting behavior observed in normal knees. Here, we aimed to investigate the clinical and radiological results and complications of TKA using this implant, at mid-term follow-up. METHODS: From January 2001 to March 2012, we retrospectively selected 76 patients (85 knees; mean age at operation, 70.2±8.1 years; range, 51-88 years) with a mean follow-up period of 93.1±14.3 months (range, 72-132 months). Indications for TKA included primary degenerative osteoarthritis (60 knees), rheumatoid arthritis (22 knees), osteonecrosis (two knees), and osteoarthritis following high tibial osteotomy (one knee). The clinical and radiographic results were evaluated. RESULTS: Kaplan-Meier survivorship analysis indicated a success rate of 98.3% (95% confidence interval, 96.6-99.9%). Comparison of pre- and postoperative knee extension angles and ranges of motion showed significant improvement postoperatively, in both the Knee Society Scores (KSS) and Knee Society Functional Scores (KSFS) (p<0.05). In one case, radiographic assessment indicated implant loosening due to infection; however, despite this complication, significant improvement of postoperative varus or valgus deformity angles were noted in all cases (p<0.05). CONCLUSION: Patients undergoing ADVANCE® Medial-Pivot TKA achieved excellent clinical and radiographic results without any implant-related failures at mid-term follow-up. LEVEL OF EVIDENCE: Level IV.

No difference between double-high insert and medial-pivot insert in TKA.

PURPOSE: To compare the clinical midterm results in ADVANCE total knee arthroplasty (TKA) with double-high (DH) insert, with same type implant with medial-pivot (MP) insert. METHOD: Forty ADVANCE TKAs were randomly divided into two groups, and two different design insert, DH insert, and MP insert were used in each group. At midterm, 4-5 years after surgery, Knee Society Scores (KSS), Knee Society Functional Scores (KSFS), range of motion (ROM), and UCLA activity score were assessed and reported in this study. RESULTS: Midterm clinical results, including ROM and KSS, were comparable with both groups. KSFS and UCLA activity score were equally good between the two groups. CONCLUSION: The results in this study revealed equally good clinical results with these types of implants at midterm follow-up, although the significant better ROM has not achieved by using DH insert. We concluded that the selection of inserts only could not achieve the better clinical results, including ROM and activity level in this study. LEVEL OF EVIDENCE: Therapeutic studies-investigating the results of treatment, Level II.

Neurogenic bladder associated with pure cervical spondylotic myelopathy: clinical characteristics and recovery after surgery.

STUDY DESIGN: Retrospective study. OBJECTIVE: To examine the prevalence of lower urinary tract symptoms (LUTS) and neurogenic bladder (NB), and surgical outcomes in pure cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: The inclusion of various types of cervical diseases, NB, and no obvious definition of NB provided the wide range of NB prevalence frequency among previous reports. METHODS: Of the 220 operated patients with cervical myelopathy, 54 were selected by excluding other cervical and/or concomitant diseases contributing to LUTS. All patients with LUTS were referred to urologists and recommended to undergo urodynamic study (UDS). The presence of NB was judged by abnormal findings of UDS according to the most recent criteria and a congruity between LUTS and the course of cervical myelopathy. Patients were divided into 4 groups: no symptoms, positive symptoms without UDS examination, positive symptoms with positive NB, and positive symptoms with negative NB. Evaluation scores were compared among the groups before and after surgery. RESULTS: There were no particular LUTS in NB patients. Prevalence of LUTS was 53.7% and that of NB was at least 20.4% in the patients with pure cervical spondylotic myelopathy. The scores of all 4 groups improved after surgery (P < 0.05); however, the recovery rate of NB group (47.1%) was the worst among the groups (no-symptoms group, 69.3%; negative-NB group, 53.5%; and positive symptoms without UDS group, 57.1%). Preoperative part scores showed no difference among the groups, whereas NB group demonstrated lower scores in finger and lower extremity postoperatively. A post hoc analysis confirmed a significantly poorer recovery rate related to the NB group only in the lower extremities. CONCLUSION: This study is the first to describe the prevalence of LUTS and NB according to the most recent criteria in patients with pure cervical spondylotic myelopathy, which demonstrated that neurological functions in NB patients may recover; however, the extent will be limited to two-thirds of those in patients with no-NB; moreover, the remaining symptoms derive from poor lower limb function.

In vivo comparisons of patellofemoral kinematics before and after ADVANCE Medial-Pivot total knee arthroplasty.

PURPOSE: ADVANCE Medial-Pivot (MP) (Wright Medical Technology, Arlington, TN, USA) total knee arthroplasty (TKA) was developed to replicate normal tibiofemoral knee joint kinematics, allowing medial-pivot knee motion. The design concept of the prosthesis is unique; therefore, the influence on the patellofemoral knee joint remains unclear at present. The purpose of this study was to determine the in vivo patellofemoral kinematics with ADVANCE MP TKA and compare them with the pre-operative conditions. METHODS: ADVANCE MP TKA was performed in ten subjects with osteoarthritis (OA). At before and one month after surgery, lateral radiographs with weight-bearing at maximum extension, 30, 60 and 90° were taken, and patella flexion angle (PF), tibiopatellar angle (TP) and estimated patellofemoral contact point (PC) were evaluated, according to a previously reported method. RESULTS: In PF and TP, there was no statistically significant change between pre-operative and postoperative values. Pre-operative PC reached its peak at 90°; however, its peak was at 60° at one month after surgery. Postoperative PC at maximum extension was significantly higher compared to before surgery. CONCLUSIONS: The results in this study indicated that ADVANCE MP TKA changed patellofemoral joint kinematics compared to before surgery. Early postoperative evaluation is the limitation of this study; however, we consider that the results in this study might be one of the keys to resolving the kinematic features of this prosthesis, helping clinicians to comprehend this prosthesis.

Grade three disc degeneration is a critical stage for anterior spondylolisthesis in lumbar spine.

INTRODUCTION: Little is known about when and how progressive spondylolisthesis occurs. In this report segmental motion related to age and disc degeneration at L4/5 disc was investigated. MATERIALS AND METHODS: 637 patients with low back and/or leg pain underwent radiologic and MRI examinations simultaneously. Because 190 patients with conditions which might impede accurate measurement were excluded, 447 patients, comprising 268 men and 179 women, were included; age range, was 10-86 (mean: 53) years. Three radiologic parameters slip in neutral position (mm), sagittal translation (mm), and segmental angulation (degrees) were examined at the L4/5 segment. On T2-weighted MRI, severity of disc degeneration at L4/5 was classified by Pfirrmann's criteria, grade 1-5. RESULTS: Results showed stage of disc degeneration that progressed according to aging with significant differences except for between grades 4 and 5. Amount of anterior slip was small among grades 1 to 3; however, it greatly increased between grades 3 and 4 and between grades 4 and 5, suggesting that grade 3 disc degeneration has a potential risk of future progression of anterior slip. This finding may also suggest that once significant slip occurs, it will progress to the final grade. Furthermore, the grade 3 degeneration group exhibited large amounts of motion in both angulation and translation, suggesting it was the most unstable group. CONCLUSION: Our results with radiography and MRI indicate that grade 3 disc degeneration is a critical stage for the progression of lumbar spondylolisthesis at L4/5 segment.

Energy consumption during prosthetic walking and physical fitness in older hip disarticulation amputees.

The objective of this study is to investigate energy consumption during prosthetic walking and physical fitness in older hip disarticulation (HD) subjects and to examine the ambulatory outcome in a community setting. The subjects were seven unilateral HD amputees with an average age of 67.7 +/- 3.9 yr. Energy consumption was measured during prosthetic walking at each individual's comfortable walking speed (CWS) by means of a portable telemetric system. An incremental exercise test was performed to evaluate fitness. The average CWS for the subjects was 30.5 +/- 9.6 m/min. The average oxygen consumption rate at each CWS was 18.3 +/- 2.4 mL/kg/min, and the average oxygen cost was 0.639 +/- 0.165 mL/kg/m. The maximum oxygen uptake during exercise as a proportion of predicted maximum oxygen uptake (%VO2max) for the subjects was 57.2 +/- 11.1. Five subjects continued prosthetic walking on return to their communities. Two subjects abandoned prosthetic walking. The %VO2max for the five who continued prosthetic walking after discharge ranged from 55.8 to 72.0. The subjects who abandoned prosthetic walking had lower %VO2max of 43.3 and 44.2. Energy consumption during prosthetic walking at CWS seemed not to be excessive. Older HD amputees in good physical condition were able to successfully walk with a prosthesis in a community setting. A lower level of fitness appears to make community walking prohibitive.

Intimate relationship between instability and degenerative signs at L4/5 segment examined by flexion-extension radiography.

Relationship between lumbar disc degeneration and segmental instability has remained controversial. Using instability factors that found close relations with symptoms in flexion-extension radiographic study, their relationship with degenerative findings was examined. More than (≥) 3 mm slip in neutral position (SN), ≥3 mm translation (ST), and ≥10° angulation (SA) at L4/5 segment were defined as instability factors and were applied on 447 patients who had low back and/or leg pain and satisfied inclusion criteria for accurate measurements. Radiologic findings for degeneration were disc height including three groups with different disc heights divided by mean ± 1 standard deviation, length of the anterior spur formation, presence of vacuum phenomenon, and endplate sclerosis. As results, group with SN factor was the oldest in age and the lowest in disc height; in contrast, group with SA was the youngest in age and the highest in disc height. The group with ST showed a mid-standing position in both age and disc height. These findings indicate that instability factors are intimately related to age and disc height. The three different disc height groups showed more anterior slip according to the progression of the disc height diminution. Presence of the apparent spur formation and/or vacuum phenomenon had an intimate relationship with the ST factor. Disc height was the most important in the examined parameters and showed an intimate relationship with age and instability factors. Although the etiology is still unknown, clinical common knowledge, that a diminution of disc height with progressive degeneration had a close relation with anterior vertebral slippage, was firstly confirmed. This study allows comprehensive understanding of segmental instability and is useful for considering surgical indications.

Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty.

PURPOSE: This is a randomised controlled trial to examine whether intra-articular injection of tranexamic acid (TXA) decreases blood loss, as well as reducing leg swelling after total knee arthroplasty (TKA). METHODS: We performed 100 TKA in osteoarthritis patients. At closure, a total of 2,000 mg/20 ml TXA was injected into the knee joint through a closed suction drain (TXA group). For the control group, the same volume of physiological saline was injected. The pre-operative condition of the patients, post-operative haemoglobin (Hb) levels, discharge volumes from drain, D-dimer and needs for transfusion were compared between these two groups. Furthermore, leg diameters (thigh, suprapatellar portion and calf girth) were measured pre- and post-operatively to investigate whether TXA has an influence on leg swelling after surgery. RESULTS: The results revealed that post-operative decrease in Hb level was significantly reduced in the TXA group. Furthermore, knee joint swelling after operation was significantly suppressed in the TXA group compared to the control group. CONCLUSIONS: The results revealed intra-articular administration of TXA decreased not only blood loss, but also knee joint swelling after TKA.

Mid-term outcomes of computer-assisted total knee arthroplasty.

PURPOSE: The aim of this study is to investigate the clinical results of total knee arthroplasty (TKA) using a navigation system after a minimum of 5 years. METHOD: Thirty cases of posterior-stabilized, TKA-implanted using a computed tomography-free navigation system were compared with 30 cases having matched TKA of the same type implanted via a classical, manual technique. At mid term, a minimum of 5 years after surgery, Knee Society scores (KSSs), Knee Society Functional scores (KSFSs), range of motion (ROM), and radiographic results of 27 patients in each group were assessed and reported in this study. RESULTS: The accuracy of the implantations in relation to the coronal mechanical axis in the navigation group was superior to that of the manual group (P < 0.01). The femoral rotational profile revealed the prosthesis in the navigation group that was implanted with significantly less internal rotation than the manual group. Mid-term 5-year clinical results, including ROMs and KSSs, were significantly better in the navigation group (P < 0.01). KSFSs were equally good in both the groups. CONCLUSION: Better alignment and similarity of good clinical results at mid-term follow up may provide patients who receive navigation TKA with long-term endurance of their implants. Further studies on longer-term outcomes and functional improvements are required to validate these possibilities.

Thermal necrosis after simultaneous tibial osteotomy and total knee arthroplasty using press-fit extension-stem.

One-staged tibial corrective osteotomy and total knee arthroplasty is a challenging but effective treatment for arthritic knees with extra-articular deformity. Although osteocutaneous thermal necrosis is accepted as a complication of intramedullary reamed nailing following long bone fractures, only 15 cases have been reported in the English literature at present. This report illustrates a rare case of thermal necrosis in a patient undergoing tibial corrective osteotomy coincident with long-stemmed total knee arthroplasty. Excessive reaming with a machine reamer is hypothesized as the cause of this serious complication. In this report, we highlight this rare but serious complication after long-stemmed total knee arthroplasty.

The influence of sagittal instability factors on clinical lumbar spinal symptoms.

STUDY DESIGN: Cross-sectional and prospective study. OBJECTIVE: To find the critical order of 3 radiographic factors observed in standing flexion-extension films and to discover their combined effect on lumbar symptoms. SUMMARY OF BACKGROUND DATA: Many previous reports have described relationships between degenerative change in the lumbar disc and segmental instability; however, few reports have attempted to show any relationship between instability and symptoms. Little is known about which type of instability is the most critical in the sagittal plane of the lumbar spine. METHODS: Excessive segmental motion (factors): >3 mm slip, >3 mm translation, and >10 degrees angulation, at the L4/5 segment in 880 patients (389 men and 491 women; mean age, 49.4 y) with low back and/or leg pain were investigated at initial visit. Symptoms of low back and leg pain, and walking ability were evaluated at initial visit and 4.6-year follow-up using Japanese Orthopaedic Association's scoring system. Severity and continuity of symptoms were evaluated and compared among the groups according to various combinations of excessive motion. RESULTS: Of the 3 factors, patients with >3 mm slip had the lowest scores, and patients with >10 degrees angulation had the highest, both at initial visit and follow-up (P<0.001). In the comparative study of various factors, the groups with >3 mm slip had significantly lower scores than the group with no factors, and these groups had significantly lower scores in leg pain and walking ability than the nonfactor group (P<0.05). CONCLUSIONS: Of the 3 factors, >3 mm slip had the strongest effect on symptoms followed by >3 mm translation and then >10 degrees angulation. Therefore, patients with low back and/or leg pain at initial visit and >3 mm slip, may expect symptoms of a duration exceeding 4 years. More than 10 degrees angulation had the least effect on symptoms as shown by the similarity in scores with the nonfactor group.

Delayed dural laceration by hydroxyapatite spacer causing tetraparesis following double-door laminoplasty.

OBJECT: The authors describe 4 cases of delayed dural laceration by hydroxyapatite (HA) spacer causing tetra-paresis following double-door laminoplasty. There are few reports of iatrogenic spinal cord lesions developing after double-door laminoplasty, although some complications such as postoperative C-5 paralysis or axial symptoms have been reported. The purpose of this report is to draw attention to the possibility of delayed dural laceration and its triggering mechanism. METHODS: One hundred thirty patients treated for cervical myelopathy were followed up for an average of 2 years and 9 months after laminoplasty. RESULTS: Four patients experienced aggravation of cervical myelopathy. Anterior dislodgement of HA spacers was shown on plain lateral radiographs. Follow-up T2-weighted magnetic resonance imaging demonstrated that the dislodged HA spacers were surrounded by cerebrospinal fluid at the time of aggravation. The dislodged HA spacers were removed and the dural membrane defects were repaired by patching with the fascia of the gluteus maximus muscle. The preoperative symptoms improved after the second operation in all patients. CONCLUSIONS: It is hypothesized that the loosening of the HA spacer in split spinous processes could occur with the movement of the cervical spine and/or the breakage of the suture before bone bonding. Anterior dislodgement of the HA spacer toward the spinal canal would cause dural laceration by direct friction between the dural membrane and the dislodged HA spacer, resulting in clinical aggravation. Despite the well-documented advantages of using HA spacers for double-door laminoplasty, possible laceration due to a dislodged HA spacer should be considered as a late complication.

Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells.

OBJECTIVE: To examine the promoter activity and protein expression of the death receptor 3 gene DR3, a member of the apoptosis-inducing Fas gene family, with particular reference to the methylation status of its promoter region in rheumatoid arthritis (RA). METHODS: Genomic DNA was prepared from peripheral blood mononuclear cells obtained from healthy individuals and from patients with RA and synovial cells obtained from patients with RA and osteoarthritis. The methylation status of the DR3 promoter was analyzed by bisulfite genomic sequencing and methylation-specific polymerase chain reaction techniques. Gene promoter activity and protein expression were examined using the luciferase reporter and Western blotting techniques. RESULTS: The promoter region of the DR3 gene contained many CpG motifs, including one CpG island that was specifically hypermethylated in synovial cells from patients with RA. Promoter assays showed that the promoter CpG island was essential for the transactivation of the DR3 gene and that forced hypermethylation of the CpG island with the bacterial methylase Sss I in vitro resulted in inhibition of the DR3 gene expression. Furthermore, the expression of DR-3 protein was down-modulated in association with methylation of the promoter CpG island in RA synovial cells. CONCLUSION: The CpG island in the DR3 gene promoter was specifically methylated to down-modulate the expression of DR-3 protein in rheumatoid synovial cells, which may provide resistance to apoptosis in RA synovial cells.