Objectives. The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. Methods. We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs). Gene ontology (GO) enrichment analysis was conducted by DAVID. The protein association networks of gene modules were generated by STRING. Results. For RA synovium, the top-ranked gene module is HLA-A, containing TAP2, HLA-A, HLA-C, TAPBP and LILRB1 genes. For RA PBMCs, the top-ranked gene module is GRB7, consisting of HLA-DRB5, HLA-DRA, GRB7, CD63 and KIT genes. Functional enrichment analysis identified three significant GO terms for RA synovium, including antigen processing and presentation of peptide antigen via major histocompatibility complex class I (false discovery rate (FDR) = 4.86 × 10 – 4), antigen processing and presentation of peptide antigen (FDR = 2.33 × 10 – 3) and eukaryotic translation initiation factor 4F complex (FDR = 2.52 × 10 – 2). Conclusion. This study reported several RA-associated gene modules and their functional association networks. Cite this article: X. Xiao, J. Hao, Y. Wen, W. Wang, X. Guo, F. Zhang. Genome-wide association studies and gene expression profiles of rheumatoid arthritis: an analysis. Bone Joint Res 2016;5:314–319. DOI: 10.1302/2046-3758.57.2000502

1. Clinical, radiological and pathological findings in seven cases of rheumatoid arthritis with giant bone cysts are presented. 2. In three cases the large cysts represented massive involvement of subchondral bone by rheumatoid granulation tissue; in two cases the cysts were due to rheumatoid nodules, and in two other cases the diagnosis was made only on the radiological findings. 3. The pathogenesis of this condition is discussed. It is suggested that cystic bone lesions in rheumatoid arthritis can arise either by replacement of subchondral bone by the rheumatoid process, or by the formation of rheumatoid nodules within the bone

Between September 1993 and September 1996, we performed 34 Kudo 5 total elbow replacements in 31 rheumatoid patients. All 22 surviving patients were reviewed at a mean of 11.9 years (10 to 14). Their mean age was 56 years (37 to 78) at the time of operation. All had Larsen grade IV or V rheumatoid changes on X-ray. Nine (three bilateral replacements and six unilateral) had died from unrelated causes. One who had died before ten years underwent revision for dislocation. Of the 22 total elbow replacements reviewed six had required revision, four for aseptic loosening (one humeral and three ulnar) and two for infection. Post-operatively, one patient had neuropraxia of the ulnar nerve and one of the radial nerve. Two patients had valgus tilting of the ulnar component. With revision as the endpoint, the mean survival time for the prosthesis was 11.3 years (95% confidence interval (10 to 13) and the estimated survival of the prosthesis at 12 years according to Kaplan-Meier survival analysis was 74% (95% confidence interval 0.53 to 0.91). Of the 16 surviving implants, ten were free from pain, four had mild pain and two moderate. The mean arc of flexion/extension of the elbow was 106° (65° to 130°) with pronation/supination of 90° (30° to 150°) with the joint at 90° of flexion. The mean Mayo elbow performance score was 82 (60 to 100) with five excellent, ten good and one fair result. Good long-term results can be expected using the Kudo 5 total elbow replacement in patients with rheumatoid disease, with a low incidence of loosening of the components

Aims. The aims of this study were to evaluate the clinical and radiological outcomes of the Universal-2 total wrist arthroplasty (TWA) in patients with rheumatoid arthritis. Patients and Methods. This was a retrospective review of all 95 Universal-2 TWAs which were performed in our institution between 2003 to 2012 in patients with rheumatoid arthritis. A total of six patients were lost to follow-up and two died of unrelated causes. A total of ten patients had bilateral procedures. Accordingly, 75 patients (85 TWAs) were included in the study. There were 59 women and 16 men with a mean age of 59 years (26 to 86). The mean follow-up was 53 months (24 to 120). Clinical assessment involved recording pain on a visual analogue score, range of movement, grip strength, the Quick Disabilities of the Arm, Shoulder and Hand (DASH) and Wrightington wrist scores. Any adverse effects were documented with particular emphasis on residual pain, limitation of movement, infection, dislocation and the need for revision surgery. Radiographic assessment was performed pre-operatively and at three, six and 12 months post-operatively, and annually thereafter. Arthroplasties were assessed for distal row intercarpal fusion and loosening. Radiolucent zones around the components were documented according to a system developed at our institution. Results. The mean worst pain was 8.1 (3 to 10) pre-operatively and 5.4 (0 to 10) at latest follow-up (p <  0.001). Movements were preserved with mean dorsiflexion of 29. o . (0. o. to 70. o. ) and palmar flexion of 21. o. (0. o. to 50. o. ). The mean grip strength was 4.8 kg (1.7 to 11.5) pre-operatively and 10 kg (0 to 28) at final follow-up (p < 0.001). The mean QuickDASH and Wrightington wrist scores improved from 61 (16 to 91) to 46 (0 to 89) and 7.9 (1.8 to 10) to 5.7 (0 to 7.8) (p <  0.001). A total of six patients (7%) had major complications; three required revision arthroplasty and three an arthrodesis. The Kaplan-Meier probability of survival using removal of the components as the endpoint was 91% at 7.8 years (95% confidence interval 84 to 91). Conclusion. The Universal-2 TWA is recommended for use in patients with rheumatoid arthritis. Cite this article: Bone Joint J 2016;98-B:1642–7

1. Synovectomy was carried out in thirty-four knees, of which thirty-one were certainly or probably afflicted by rheumatoid arthritis. 2. Synovectomy was considered only when adequate medical and physical treatment had failed to afford relief. Its purpose is to preserve useful function, and one of the principal factors influencing the decision to operate was the retention of a normal or good radiographic joint space in a persistently painful, warm and swollen knee. 3. Radiographic appearances constituted a useful but not infallible guide to the true state of the articular surfaces. 4. The method of operation, findings and subsequent care are described. 5. Up to two years after operation it appeared that improvement might be related to the state of the articular surfaces, but after two years this relationship was not evident and an attempt to explain this difference has been made. 6. It seems clear that the longer-term results are determined mainly by the course taken by the rheumatoid process. An unfavourable course was associated with considerably less satisfactory results than was a favourable course. 7. It is concluded that in rheumatoid arthritis which has resisted rest and medical treatment synovectomy of the knee is most likely to be successful when the radiographic joint space is good or normal, and when the rheumatoid process follows a favourable course. To undertake the operation at an early stage in the disease is to leave in doubt the outcome, as this is dependent upon the as yet undeclared general course of the disease. Even so, early synovectomy is worth considering when nothing else has given relief. The fact that arthrodesis has only once been necessary after synovectomy appears to justify the policy of salvage described

We studied 11 patients (14 elbows) with gross rheumatoid deformity of the elbow, treated by total arthroplasty using the Kudo type-5 unlinked prosthesis, and who were evaluated between five and 11 years after operation. Massive bone defects were augmented by autogenous bone grafts. There were no major complications such as infection, subluxation or loosening. In most elbows relief from pain and stability were achieved. The results, according to the Mayo Elbow Performance Score, were excellent in eight, good in five and fair in one. In most elbows there was minimal or no resorption of the grafted bone. There were no radiolucent lines around the stems of the cementless components. This study shows that even highly unstable rheumatoid elbows can be replaced successfully using an unlinked prosthesis, with augmentation by grafting for major defects of bone

We report seven cases of patients with seropositive rheumatoid arthritis in whom involvement of the thoracic and lumbar vertebrae occurred. Histological corroboration is presented in four. Pathological lesions comprised various combinations of paravertebral joint erosions, erosive discitis, anteroposterior and rotatory instability, major lumbar nerve root compression, and vertebral collapse. Specific radiological features are presented, enabling a distinction to be made between pure degenerative spondylosis and rheumatoid spondylitis. We submit that subcervical rheumatoid spondylitis is commoner than is generally believed, though less common than rheumatoid involvement of the cervical spine

Between 1993 and 2002, 58 GSB III total elbow replacements were implanted in 45 patients with rheumatoid arthritis by the same surgeon. At the most recent follow-up, five patients had died (five elbows) and six (nine elbows) had been lost to follow-up, leaving 44 total elbow replacements in 34 patients available for clinical and radiological review at a mean follow-up of 74 months (25 to 143). There were 26 women and eight men with a mean age at operation of 55.7 years (24 to 77). At the latest follow-up, 31 excellent (70%), six good (14%), three fair (7%) and four poor (9%) results were noted according to the Mayo elbow performance score. Five humeral (11%) and one ulnar (2%) component were loose according to radiological criteria (type III or type IV). Of the 44 prostheses, two (5%) had been revised, one for type-IV humeral loosening after follow-up for ten years and one for fracture of the ulnar component. Seven elbows had post-operative dysfunction of the ulnar nerve, which was transient in five and permanent in two. Despite an increased incidence of loosening with time, the GSB III prosthesis has given favourable mid-term results in patients with rheumatoid arthritis

1. Three cases of a degenerative type of rheumatoid arthritis, with large cystic cavities filled with pus-like material, are described. They may arise from bursae or breaking-down nodules. 2. Four cases in which necrosis and subluxation complicated rheumatoid disease of the cervical column are recorded. 3. The pathogenesis of necrotic and cystic areas in rheumatoid arthritis is discussed

1. Eleven patients with juvenile rheumatoid arthritis, most of them young adults at a terminal stage, were found to have structural scoliosis with curves measuring between 20 and 80 degrees. 2. The common feature was severe and protracted rheumatoid disease. 3. The characteristics of the spinal curves are analysed; the longer curves may have been caused by muscle imbalance and the shorter curves possibly by asymmetrical involvement of the inter-apophyseal joints. 4. It is suggested that juvenile rheumatoid arthritis is an unusual etiological factor of scoliosis

1. The incidence of failure of wound healing by primary intention due to infection, haematoma and gaping of wound edges, has been compared in 100 patients with rheumatoid arthritis and in 100 matched controls following a variety of orthopaedic operations. 2. There were thirty-one cases of failure of wound healing in the patients with rheumatoid arthritis and sixteen in the controls (P< ·02). There was no significant difference in the numbers of infected wounds or in those in which a haematoma developed. However, there was a significant excess of wound edge separation in the rheumatoid patients (thirteen) compared with the controls (four) (P< ·05). 3. The problems of wound healing were minor since there was no difference in the mean number of days ±1 standard deviation to wound healing between the patients: l6·6±7·5 days; and the controls: 15·2±7·9 days. 4. There was no correlation between duration or severity of rheumatoid disease and wound healing. 5. There was no difference in wound healing between patients with sero-positive and seronegative disease. 6. Forty-nine patients received corticosteroid therapy in small dosage. This was associated with an increased incidence of wound infection. Treatment for more than three years was associated with a significant increase in the mean number of days to wound healing. 7. The results are discussed in the light of the increased incidence of infection in several sites in patients with rheumatoid arthritis and of the effect of corticosteroid therapy on wound healing in man and experimental animals. It is suggested that more marked abnormalities might have been expected, and that these findings may need to be considered in the future surgical management of such patients

Proximal osteotomies for forefoot deformity in patients with rheumatoid arthritis have hitherto not been described. We evaluated combination joint-preserving surgery involving three different proximal osteotomies for such deformities. A total of 30 patients (39 feet) with a mean age of 55.6 years (45 to 67) underwent combined first tarsometatarsal fusion and distal realignment, shortening oblique osteotomies of the bases of the second to fourth metatarsals and a fifth-ray osteotomy. The mean follow-up was 36 months (24 to 68). The mean foot function index scores for pain, disability and activity subscales were 18, 23, and 16 respectively. The mean Japanese Society for Surgery of the Foot score improved significantly from 52.2 (41 to 68) to 89.6 (78 to 97). Post-operatively, 14 patients had forefoot stiffness, but had no disability. Most patients reported highly satisfactory walking ability. Residual deformity and callosities were absent. The mean hallux valgus and intermetatarsal angles decreased from 47.0° (20° to 67°) to 9.0° (2° to 23°) and from 14.1° (9° to 20°) to 4.6° (1° to 10°), respectively. Four patients had further surgery including removal of hardware in three and a fifth-ray osteotomy in one. With good peri-operative medical management of rheumatoid arthritis, surgical repositioning of the metatarsophalangeal joint by metatarsal shortening and consequent relaxing of surrounding soft tissues can be successful. In early to intermediate stages of the disease, it can be performed in preference to joint-sacrificing procedures

Thirteen patients suffering from rheumatoid arthritis had 19 stress fractures of the tibia or fibula. These patients characteristically presented with sudden, severe, unexplained pain with localised tenderness just below the knee or above the ankle. In seven patients examination of the adjacent joint indicated a flare-up of disease activity or a pyogenic arthritis. In six patients the diagnosis was delayed by the late appearance of callus in minute fractures. All patients had rheumatoid deformities of the ipsilateral lower limb: valgus deformities of the knee and subtalar joints occurred most frequently. All patients had osteoporosis; all except two had received steroid treatment and five had abnormalities of calcium metabolism. We suggest that deformities of the knee and ankle predispose patients with rheumatoid arthritis and osteoporosis to stress fractures of the tibia and fibula

We have measured the three-dimensional patterns of carpal deformity in 20 wrists in 20 rheumatoid patients in which the carpal bones were shifted ulnarwards on plain radiography. Three-dimensional bone models of the carpus and radius were created by computerised tomography with the wrist in the neutral position. The location of the centroids and rotational angle of each carpal bone relative to the radius were calculated and compared with those of ten normal wrists. In the radiocarpal joint, the proximal row was flexed and the centroids of all carpal bones translocated in an ulnar, proximal and volar direction with loss of congruity. In the midcarpal joint, the distal row was extended and congruity generally well preserved. These findings may facilitate more positive use of radiocarpal fusion alone for the deformed rheumatoid wrist

Aims. We assessed the long-term (more than ten-year) outcomes of the Kudo type-5 elbow prosthesis in patients with rheumatoid arthritis (RA). Materials and Methods. We reviewed 41 elbows (Larsen Grade IV, n = 21; Grade V, n = 20) in 31 patients with RA who had undergone a Kudo type-5 total elbow arthroplasty (TEA) between 1994 and 2003, and had been followed up for more than ten years. The humeral component was cementless and the all-polyethylene ulnar component cemented in every patient. Clinical outcome was assessed using the Mayo elbow performance score. We calculated the revision rate and evaluated potential risk factors for revision. The duration of follow-up was a mean 141 months (120 to 203). Results. Aseptic loosening of the ulnar component occurred in 11 elbows. There was no radiolucency around any humeral component. There was one deep infection. The survival rate according to Kaplan-Meier survivorship analysis was 87.8% after five years and 70.7% after ten years. The range of extension/flexion was a mean -38° (-80° to 0°)/105° (30° to 150°) before surgery and -40° (-70° to -20°)/132° (100° to 150°) at the final follow-up, while the mean Mayo elbow performance score was 43 before surgery and 80 at final follow-up. Disease duration of RA up to the TEA of < 15 years and a pre-operative range of movement (ROM) of > 85° were significant risk factors for revision or aseptic loosening. Conclusion. Although Kudo type-5 prostheses gave satisfactory results in the short-term, aseptic loosening increased after five years. In most cases, elbow function was maintained in the long-term without loosening of the implant. A short duration from the onset of RA to TEA and a large pre-operative ROM were significant risk factors for revision or aseptic loosening. Cite this article: Bone Joint J 2017;99-B:818–23

We describe the longer term clinical and radiological findings in a prospectively followed series of 49 rheumatoid patients (58 shoulders) who had undergone Neer II total shoulder replacement. The early and intermediate results have been published previously. At a mean follow-up of 19.8 years (16.5 to 23.8) 14 shoulders survived. Proximal migration of the humeral component was associated with progressive loosening of the glenoid and humeral components, but was independent of the state of the rotator cuff at the time of operation. Despite these changes the range of movement was preserved. Most patients had little or no pain in the shoulder, could sleep undisturbed and could attend to personal hygiene and grooming

1. The results of synovectomy of the knee in eighty-five patients with rheumatoid arthritis are presented. 2. When reviewed between five and nine years after operation 55 per cent of 122 knees still had improvement in pain. 3. Only 31 per cent of knees lost movement. 4. Recurrence of symptoms in nearly all cases was related to the recurrence of active rheumatoid synovitis. 5. Recurrence of symptoms was a little less likely when the generalised disease improved, when the Rose-Waaler test was negative, when only one knee was involved and when the operation had been carried out within three years of the onset of disease in that knee

We present a study of 30 fusion operations in 26 rheumatoid arthritics with cervical spine instability. Atlanto-axial instability was present in 15, of whom 12 were fused; three had cord involvement and all made a partial or complete recovery following fusion. Cranial settling necessitated cranio-cervical fusion in four patients; all fused, and one with myelopathy was relieved. Subaxial instability required fusion in seven cases; two postoperative deaths followed the only two anterior interbody fusions. Posterior fusion was successful in the other five, with remission of neurological compromise in the three with myelopathy and one with radiculopathy. We conclude that neurological compromise in an unstable but mobile rheumatoid cervical spine can usually be brought to remission by immobilisation alone, so decompressive procedures are unnecessary in the first instance

We present the outcome of 47 Souter-Strathclyde replacements of the elbow with a mean follow-up of 82 months (12 to 129). The clinical results were assessed using a condition-specific outcome measure. The mean total score (maximum 100) before the operation was 47.21 and improved to 79.92 (p < 0.001). The mean pain score (maximum 50) improved from 21.41 to 46.70 (p < 0.001) and the mean functional component of the score (maximum 30) from 11.19 to 18.65 (p < 0.001). There was negligible change in the score for the range of movement although a significant improvement in mean flexion from 124° to 136° was noted (p < 0.001). Revision surgery was required in four patients, for dislocation, wound dehiscence and early infection in one, late infection in two and aseptic loosening in one. The cumulative survival was 75% at nine years for all causes of failure and 97% at ten years for aseptic loosening alone. Our study demonstrates the value of the Souter-Strathclyde total elbow arthroplasty in providing relief from pain and functional improvement in rheumatoid patients

We made a prospective study of 58 consecutive Neer II total shoulder replacements in 49 rheumatoid patients. Cemented glenoid and press-fit humeral components had been used. After a mean follow-up of 9.5 years (7 to 13), 11 patients (15 shoulders) had died, one shoulder had been arthrodesed and five patients (five shoulders) had been lost to follow-up. Of the remaining 37 shoulders 29 were painfree or had only slight discomfort, four had pain on unusual activity, and four had moderate or severe pain. There were satisfactory improvements in the mean range of active elevation (53° to 75°) and external rotation (5° to 38°); satisfactory performance of the activities of daily living had been maintained throughout follow-up. Radiographs showed loosening in ten shoulders of nine glenoid and nine humeral components but of these only three had significant symptoms. Three loose glenoid components and two loose humeral components required revision. We consider that the Neer total shoulder replacement provides a reasonable medium to long-term outcome in rheumatoid arthritis, but recommend that the humeral component should be routinely cemented