Immunogenicity of tocilizumab in patients with rheumatoid arthritis

Objective

The immunogenicity of tocilizumab (TCZ) has been poorly studied. We assessed the immunogenicity of TCZ and serum TCZ trough levels in rheumatoid arthritis (RA) patients and the preexisting TCZ-specific CD4+ T cell repertoire in healthy controls.

Norwegian Crusted Scabies: An Unusual Case Presentation

Scabies is a contagious condition that is transmitted through direct contact with an infected person and has been frequently associated with institutional and healthcare-facility outbreaks. The subtype Norwegian crusted scabies can masquerade as other dermatologic diseases owing to the heavy plaque formation. Successful treatment has been documented in published reports, including oral ivermectin and topical permethrin. Few case studies documenting the treatment of Norwegian crusted scabies have reported the use of surgical debridement as an aid to topical and/or oral treatment when severe plaque formation has been noted. A nursing home patient was admitted to the hospital for severe plaque formation of both feet. A superficial biopsy was negative for both fungus and scabies because of the severity of the plaque formation on both feet. The patient underwent a surgical, diagnostic biopsy of both feet, leading to the diagnosis of Norwegian crusted scabies. A second surgical debridement was then performed to remove the extensive plaque formation and aid the oral ivermectin and topical permethrin treatment. The patient subsequently made a full recovery and was discharged back to the nursing home. At 2 and 6 months after treatment, the patient remained free of scabies infestation, and the surgical wound had healed uneventfully. The present case presentation has demonstrated that surgical debridement can be complementary to the standard topical and oral medications in the treatment of those with Norwegian crusted scabies infestation.     

Pain and function in eight hundred and fifty nine patients comparing shoulder hemiprostheses, resurfacing prostheses, reversed total and conventional total prostheses

Purpose

Functional results of reversed total prostheses (RTP) have—to a very limited degree—been compared with those of other shoulder prosthesis types. The aim of our study was to compare results of four different types of shoulder prostheses in terms of function, pain, and quality of life (QoL).

Methods

Questionnaires were completed by 859 patients with shoulder prostheses registered in the Norwegian Arthroplasty Register. Patients with osteoarthritis (OA), rheumatoid arthritis (RA), or fracture sequela (FS) were included. Symptoms and function were assessed using the Oxford Shoulder Score (OSS, scale 0–48), and the EuroQoL-5D (EQ-5D) was used to assess QoL.

Results

Best functional results were obtained using conventional total prostheses (TPs) and RTPs —mean OSS improvement 18 and 16 units, respectively, vs 11 with hemiprostheses (HPs). For patients with OA, TPs performed best; for those with RA and FS, RTPs performed best; and those with HPs had the worst results in all diagnostic groups. The greatest improvement in QoL was seen in patients with TPs and RTPs.

Conclusions

Conventional TPs provide the best improvement in pain, function and QoL in OA patients; RTPs are superior in patients with RA and FS.     

Immunologie der entzündlichen Systemerkrankungen

Background

Inflammatory rheumatic diseases are generally systemic diseases resulting from immune system dysfunction.

Methods

Relevant pathophysiological processes in the immune system are discussed using laboratory results and autoantibody tests, as well as in terms of new drugs in particular. Furthermore, an immunologically focused overview of clinically relevant approaches is presented.

Results

The pathophysiological role of both T and B lymphocytes as well as that of autoantibodies demonstrates that diseases such as rheumatoid arthritis (RA), connective tissue diseases, and vasculitides are autoimmune diseases. While tumor necrosis factor is apparently involved in many entities, other cytokines differentiate between RA (interleukin-6, IL-6) and spondylarthritides (IL-17, IL-23). In contrast, in crystal arthritides, IL-1 appears essential.

     

A cohort study comparing the serum levels of pro- or anti-inflammatory cytokines in patients with lumbar radicular pain and healthy subjects

Purpose

The factors influencing the presence or absence of pain in sciatica secondary to disc herniation remain incompletely understood. We hypothesized that the imbalance in inflammatory cytokines is implicated in the generation of pain. In our study, serum levels of pro-inflammatory and anti-inflammatory cytokines were investigated among patients with severe sciatica; the serum levels were compared with those of patients with mild sciatica and healthy subjects.

Methods

In this prospective study, blood protein levels of the pro-inflammatory cytokines, namely, interleukin-6 (IL-6), interleukin-8 (IL-8),and tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokines, namely, interleukin-4 (IL-4) and interleukin-10 (IL-10), of 58 patients with severe sciatica, 50 patients with mild sciatica, and 30 healthy control subjects were analyzed through ELISA. Physical and mental health symptoms were determined using the Oswestry Disability Index (ODI) and short form-36 (SF-36) questionnaire. Spearman rank correlation coefficient was also determined to calculate the correlation between the scores obtained from the questionnaires and the serum levels of cytokines.

Results

IL-6 protein was detected in the three groups and median levels were about 1.5 times higher in patients with severe sciatica than the mild sciatica group (p = 0.02) and the controls (p = 0.03). Median levels of IL-8 in sciatica patients were higher than those of the healthy controls (p = 0.001 for severe sciatica, p = 0.02 for mild sciatica). The TNF-α protein values were approximately twofold higher in the severe sciatica group than in the mild sciatica group (p < 0.01) and in the healthy control group (p < 0.01). Median levels of IL-4 were about 2.5-fold higher in mild sciatica (p < 0.01) and about twofold higher in patients with severe sciatica (p = 0.012) when compared with controls. Median protein levels of IL-10 showed a trend to be higher in patients with mild sciatica compared with severe sciatica (p < 0.01) and with healthy controls (p < 0.01). ODI was significantly correlated with IL-6 (r = 0.394, p = 0.013), TNF-α (r = 0.629, p < 0.001), and IL-10 (r = ?0.415, p = 0.009). ODI was not significantly correlated with IL-4 (r = ?0.174, p = 0.29) and IL-8 (r = ?0.133, p = 0.418).

Conclusions

These findings support our hypothesis that sciatica pain is accompanied by the imbalance in inflammatory cytokines.

     

Cross-cultural validation of the Educational Needs Assessment Tool in RA in 7 European countries

Background

The Educational Needs Assessment Tool (the ENAT) is a 39-item patient questionnaire originally developed in the UK to assess educational needs of patients with rheumatoid arthritis (RA). The objective of this study was to assess the cross-cultural validity of the ENAT in 7 European countries.

Methods

The ENAT was translated into Dutch, Finnish, Norwegian, Portuguese, Spanish and Swedish versions by using Beaton's cross-cultural adaptation process, and was completed by a convenience sample of patients with RA in each country. The generated country-specific data were assessed for construct validity and were then pooled and assessed for cross-cultural invariance using Rasch analysis.

Results

Individual country-specific analysis showed adequate fit to the Rasch model after adjustment for local dependency within domains. When data from the different countries were pooled, the 39 items deviated significantly from Rasch model's expectations (X² = 977.055, DF = 351, p = 0.000, PSI = 0.976). Again, most items within domains were found to be locally dependent, significantly affecting the fit. Consequently each domain was treated as a unit (i.e. testlet) and the ENAT was re-analysed as a seven-testlet scale resulting into a good fit to the Rasch model (X² = 71.909; DF = 63; p = 0.207, PSI = 0.951). A test of strict unidimensionality confirmed that all domains contributed to measuring a single construct. Cross-cultural non-invariance was discounted by splitting domains for DIF maintaining an excellent fit to the Rasch model. This allowed calibration of the ENAT into an interval scale.

Conclusion

The ENAT is a simple tool, which is a valid measure of educational needs of people with RA. Adjustment for cross-cultural non-invariance is available if data from the 7 European countries are to be pooled or compared.

     

Inflammatory factors in the circulation of patients with active rheumatoid arthritis stimulate osteoclastogenesis via endogenous cytokine production by osteoblasts

Summary

The combination of cytokines present in the circulation of patients with active rheumatoid arthritis might contribute to the generalized bone loss that commonly occurs in these patients, by directly inhibiting osteoblast proliferation and differentiation, but especially by enhancing endogenous cytokine (i.e., receptor activator of nuclear factor-kappa B ligand (RANKL) and interleukin-6 (IL)-6) production by osteoblasts, thereby stimulating osteoclastogenesis.

Introduction

Generalized bone loss, as occurs in patients with rheumatoid arthritis (RA), is related to elevated levels of circulating cytokines. Individual cytokines have deleterious effects on proliferation and differentiation of osteoblast cell lines, but little is known about the effect of the interaction between inflammatory factors in the circulation of patients with active RA on human osteoblast function, including their communication towards other bone cells. We investigated whether serum from patients with active RA enhances cytokine production by osteoblasts, thereby effectively altering osteoblast-stimulated osteoclastogenesis.

Methods

Serum was obtained from 20 patients with active RA (active RA sera) and from the same patients in clinical remission (remission RA sera). To determine osteoclastogenesis, RA serum-pretreated primary human osteoblast cultures were established in direct contact with human osteoclast precursors in the presence or absence of osteoprotegerin (OPG) or IL-6 inhibitor.

Results

Compared to remission RA sera, active RA sera inhibited osteoblast proliferation and differentiation in vitro as demonstrated by a reduced DNA content and gene expression of KI-67, collagen type 1, osteopontin, and osteocalcin. Active RA sera inhibited OPG expression and enhanced RANKL and IL-6 expression but did not alter IL-8 expression in osteoblasts. IL-1β, IL-17, and tumor necrosis factor-α (TNF-α) expression were undetectable. In coculture, active RA sera treatment of osteoblasts stimulated while addition of OPG or IL-6 inhibitory antibodies significantly reduced the number of osteoclasts.

Conclusion

Active RA sera contain circulating factors, likely cytokines and chemokines, that might contribute to bone loss by directly inhibiting osteoblast proliferation and differentiation, but especially, these factors modulate endogenous cytokine production by osteoblasts, thereby affecting osteoclastogenesis.     

Reverse shoulder prosthesis in patients with rheumatoid arthritis: a systematic review

Purpose

To obtain detailed information on the outcomes of patients with rheumatoid arthritis (RA) undergoing reverse shoulder arthroplasty (RSA)

Methods

A literature search was conducted for studies reporting on the use of RSA in RA patients from 1990 to 2014. The inclusion criteria were a report of sufficient information on pre-operative status and surgical outcome allowing evaluation of the therapeutic potential of RSA in RA. The literature search resulted in 586 hits, but only five studies that met the inclusion criteria were assessed.

Results

There were 100 shoulders that had been operated on, of which 87 were followed for a mean of 55.4 months, the longest follow-up being 11.9 years Most patients had glenohumeral erosive lesions of Larsen Grade III or IV. The Delta III prosthesis was implanted in most cases and in three studies bone graft was used for severe glenoid lesions. The main outcome measures employed were the Constant score (Cs) and ASES questionnaire. The mean increase in Cs and ASES score after surgery was 42.4 and 54 points, respectively. The mean post-operative forward elevation was 120.6°, the average increment being 51° and the mean increase of abduction was 58.5°. The mean prevalence of scapular notching was 35.4 %. The rate of adverse events was 31 %, but the vast majority were of minor severity. Eight prostheses underwent revision, due to infection in four.

Conclusions

RSA implanted in RA patients would appear to give similar results to those obtained in massive cuff tears with or without arthropathy.

     

'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background

Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA.

Methods

Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain.

Results

The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were open-type footwear. More than 70% of patients' footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear.

Conclusions

The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA.

     

Ghrelin gene polymorphisms in rheumatoid arthritis

Objectives

Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA).

Methods

The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis.

Results

The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group.

Conclusion

A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA.     

Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the Papillary Muscle Approximation trial

Objective

The symmetry of mitral valve tethering and regional left ventricle wall dysfunction are reported to play a fundamental role in the outcomes and long-term durability of surgical repair in ischemic mitral regurgitation (IMR). We recently demonstrated in a randomized clinical trial (the Papillary Muscle Approximation trial) the superiority of papillary muscle approximation (PMA) in combination with standard restrictive annuloplasty (RA) in severe IMR over annuloplasty alone in terms of adverse left ventricular remodeling and mitral regurgitation (MR) recurrence. This approach, however, failed to produce a survival advantage and was still plagued by a high incidence of reoperation. We therefore performed a subanalysis of the PMA trial on the basis of preoperative parameters to elucidate the value of subvalvular surgery in certain subcategories of patients with the aim of creating a decisional algorithm on the best operative strategy.

Cementless total hip arthroplasty for patients with rheumatoid arthritis: a more than 10-year follow-up

Background/purpose

In this study, cementless THA was performed for RA patients, and its clinical outcomes, as well as radiographic findings and implant survival rates, were examined more than 10 years after surgery in comparison with the outcomes of the same procedure performed for patients with hip osteoarthritis (OA) during the same period.

Method

We studied 28 cases of THA for RA clinically and radiologically at a minimum follow-up duration of 10 years. The patients consisted of 4 males and 22 females, with a mean age at the time of surgery of 53.1. The clinical and radiographic results were compared with an age-matched and sex-matched group of patients who had undergone THA for the diagnosis of primary or secondary OA.

Results

In the RA group, the mean Harris hip score was 48.3 before surgery, and improved to 76.8 at the time of the final survey. In the control group, the score also improved from 46.8 before to 86.5 after surgery, while revealing significant differences between the groups (p = 0.0002). In the RA group, 2 joints required revision THA on the acetabular side due to aseptic loosening, while such revision was not performed on the femoral side despite the presence of more than 2 mm of subsidence in 2 joints. The implant survival rate was 92.9 and 100 % in the RA and control groups, respectively, without significant differences (p = 0.493).

Conclusions

Although its clinical outcomes were significantly different from those for OA, a satisfactory implant survival rate was achieved, at 92.9 % in RA patients.

     

Epidemiologic data and trends concerning the use of regional anaesthesia for shoulder arthroscopy in the United States of America

Background

Despite a growing body of literature illustrating the benefits of regional anaesthesia in shoulder arthroscopy, data on actual use of the technique in the United States is lacking. This study analyses epidemiologic data to describe current trends in anaesthetic practice for these procedures in the United States and highlights key associations with patient and provider demographic variables that may provide further insight.

Methods

We analysed the large database from the National Anesthesia Clinical Outcomes Registry of the Anesthesia Quality Institute. Of the 26,568,734 records available and after applying our exclusion criteria, we identified 169,878 shoulder arthroscopies performed from 2010 to 2014. The cases concerned all types of arthroscopic surgical procedures performed regardless of pathology (e.g. arthritis, instability, rotator cuff tears) These cases were sorted into three anaesthetic types consisting of general anaesthesia alone (GA, 62 %), general plus regional anaesthesia (GA+RA, 36 %) and RA alone (RA, 2 %).

Results

RA alone was more highly associated with board-certified anaesthesiologists practicing at university hospitals, older patients, patients with higher American Society of Anesthesiologists (ASA) classification and shorter procedures. RA is rarely used as the primary anaesthetic for these procedures across the country, while there is a steadily growing rate of GA+RA combination anaesthetics.

Conclusions

Numerous advantages have been reported for utilizing RA and avoiding GA. The low rate at which RA is used as the sole anesthetic may represent room for improvement nationwide. GA+RA combination technique quickly became the predominant anaesthetic choice for shoulder arthroscopy during the five years of this analysis.Level of Evidence: III

     

Interleukin-35 upregulates OPG and inhibits RANKL in mice with collagen-induced arthritis and fibroblast-like synoviocytes

Summary

IL-35 is a novel anti-inflammatory cytokine, but the exact role of IL-35 in the progression of RA remains unclear, especially associated with osteoporosis and bone erosion. The present research has not been reported. Our purpose is to study how IL-35 affects RA bone destruction.

Introduction

This study investigated the effect of interleukin-35 (IL-35) on OPG and RANKL expression in collagen-induced arthritis (CIA) in rats and in cultured fibroblast-like synoviocytes (FLS).

Methods

Thirty DBA/1J mice were randomly assigned to three groups (n?=?10 per group): the control group, the CIA group, and the CIA?+?IL-35 group. Collagen-induced arthritis was induced by immunization with collagen. IL-35 was intraperitoneally injected daily for 10 days, starting from the 24^th day after immunization. FLS cells were isolated and cultured from CIA. The expression of IL-17, RANKL, and OPG was determined by RT-PCR and Western blot. Each experiment was repeated three times.

Results

CIA mice exhibited arthritis symptoms on day 24, followed by a rapid progression of arthritis. The expression of IL-17 and RANKL was increased and the expression of OPG was decreased in CIA mice compared with control mice. IL-35 treatment inhibited the development of arthritis in CIA mice, accompanied by a decrease in the expression of IL-17 and RANKL and an increase in the expression of OPG. Furthermore, IL-35 dose-dependently inhibited the expression of RANKL and increased the expression of OPG in cultured FLS cells.

Conclusion

IL-35 inhibits RANKL expression and increases OPG expression in CIA mice. IL-35 may be used for treating rheumatoid arthritis.

     

Short- and long-term results of radial artery and saphenous vein grafts in the right coronary system: a propensity-matched study

Purpose

The selection of optimal grafts for the right coronary artery remains controversial. This study aims to evaluate the short- and long-term results of radial artery (RA) grafts and saphenous vein grafts (SVGs) to the right coronary artery.

Methods

We reviewed, retrospectively, isolated coronary artery bypass grafts, placed between 1997 and 2007, and compared the long-term results of patients who received RA (n = 110) grafts with those of patients who received SVGs (n = 264) using propensity-score matching for risk. The preoperative predictors of graft occlusion were investigated on a per case basis.

Results

Superior survival was noted in the unmatched RA group, but late outcomes after propensity-score matching yielded 91 patient pairs that were similar in the two groups. Graft failure was not correlated with mortality, but showed strong correlation with cardiac events in all patients. The predictors of graft occlusion in the RA group were mild proximal stenosis and low indexing glomerular filtration rates for body surface area, whereas those in the SVG were female gender and off-pump coronary artery bypass grafting.

Conclusions

There were no significant differences in long-term outcomes between the RA and SVG groups. Predictors of graft occlusion differed between the groups. Notably, renal dysfunction impaired radial patency, emphasizing the importance of careful graft selection.

     

The relationship between preoperative needle electromyography findings and muscle power restoration after surgery in severe carpal tunnel syndrome patients

Purpose

Needle electromyography provides essential information about the functional aspects of the muscle. But little attention has been given in the literature to needle electromyography examinations in carpal tunnel syndrome. We examined the relationship between preoperative needle electromyography findings and functional recovery of the abductor pollicis brevis (APB) muscle in severe carpal tunnel syndrome patients.

Clinical practice guidelines for the foot and ankle in rheumatoid arthritis: a critical appraisal

Background

Clinical practice guidelines are recommendations systematically developed to assist clinical decision-making and inform healthcare. In current rheumatoid arthritis (RA) guidelines, management of the foot and ankle is under-represented and the quality of recommendation is uncertain. This study aimed to identify and critically appraise clinical practice guidelines for foot and ankle management in RA.

Methods

Guidelines were identified electronically and through hand searching. Search terms ‘rheumatoid arthritis’, ‘clinical practice guidelines’ and related synonyms were used. Critical appraisal and quality rating were conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.

Results

Twenty-four guidelines were included. Five guidelines were high quality and recommended for use. Five high quality and seven low quality guidelines were recommended for use with modifications. Seven guidelines were low quality and not recommended for use. Five early and twelve established RA guidelines were recommended for use. Only two guidelines were foot and ankle specific. Five recommendation domains were identified in both early and established RA guidelines. These were multidisciplinary team care, foot healthcare access, foot health assessment/review, orthoses/insoles/splints, and therapeutic footwear. Established RA guidelines also had an ‘other foot care treatments’ domain.

Conclusions

Foot and ankle management for RA features in many clinical practice guidelines recommended for use. Unfortunately, supporting evidence in the guidelines is low quality. Agreement levels are predominantly ‘expert opinion’ or ‘good clinical practice’. More research investigating foot and ankle management for RA is needed prior to inclusion in clinical practice guidelines.

     

Hypervitaminosis A is prevalent in children with CKD and contributes to hypercalcemia

Background

Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia.

Methods

We studied the relationship between vitamin A intake, serum retinoid levels, and serum calcium in 105 children with CKD stages 2–5 on dialysis and posttransplant. Serum retinoid measures included retinol (ROH), its active retinoic acid (RA) metabolites [all-trans RA (at-RA) and 13-cis RA] and carrier proteins [retinol-binding protein-4 (RBP4) and transthyretin (TTR)]. Dietary vitamin A intake was assessed using a food diary.

Results

Twenty-five children were in CKD 2–3, 35 in CKD 4–5, 23 on dialysis and 22 posttransplant; 53 % had vitamin A intake above the Reference Nutrient Intake (RNI) value. Children receiving supplemental feeds compared with diet alone had higher vitamin A intake (p?=?0.02) and higher serum ROH (p?<?0.001). Notably, increased ROH was seen as early as CKD stage 2. For every 10 ml/min/1.73 m² fall in estimated glomerular filtration rate (eGFR), there was a 13 % increase in ROH. RBP4 levels were increased in CKD 3–5 and dialysis patients. The lowest ratios of ROH:RBP4 were seen in dialysis compared with CKD 2–3 (p?=?0.03), suggesting a relative increase in circulating RBP4. Serum ROH, RBP4 and at-RA were associated with serum calcium. On multivariable analysis RBP4 levels and alfacalcidol dose were significant predictors of serum calcium (model R ² 32 %) in dialysis patients.

Conclusions

Hypervitaminosis A is seen in early CKD, with highest levels in children on supplemental feeds compared with diet alone. Serum retinoid levels significantly predict hypercalcemia.

     

Rheumatoid Arthritis of Knee Joints: MRI–Pathological Correlation

Objective

To evaluate the correlation between features of knee joint rheumatoid arthritis (RA) identified on MRI and histological examination as a means of elucidating the pathogenesis of joint destruction in RA.

Methods

This is a prospective analysis of 26 knee joints of 22 patients who underwent total knee arthroplasty (TKA) for the treatment of RA. Based on the degree of destruction of articular cartilage and the menisci, the occurrence of bone marrow edema and bone erosion, and synovial thickening, the stage of the knee joints were classified using MRI by two radiologists. Differences in the severity of destruction of the articular cartilage of the medial and lateral femoral condyles and medial and lateral tibial plateaus, the medial and lateral menisci, and bone were compared using analysis of variance with a post‐hoc test, and the Mann–Whitney U ‐test. Samples of cartilage, subchondral bone, menisci, and synovium were obtained from the resected knee specimens during TKA and analyzed semiquantitatively using microscopy and immunohistochemistry. Histological differences between areas of bone erosion and bone marrow edema were evaluated using a Mann–Whitney U ‐test.

Results

The extent of articular destruction was classified as grade 4 for the medial and lateral femoral condyles and the medial and lateral tibial plateaus for most patients, with an average destruction grade of 3.6 (F = 5.455, P = 0.002), with the least amount of destruction identified on the lateral femoral condyle. The majority of knee joints in the RA patients were at stage 3 (21/26, 80.8%), followed by stage 4 (4/26, 15.4%). Fibrosis, thinning and destruction, and hyperplasia were the most severe pathological changes in cartilage. In a total of 26 specimens, 36 areas of bone marrow edema and 68 areas of bone erosion were identified, with fibrosis, a mosaic structure of bone, and lymphocyte infiltration being the most severe changes in these areas. The degree of meniscus destruction was classified as grade 4 in the majority patients for both the medial and lateral meniscus, with an average degree of meniscal destruction over all specimens of 3.85, and greater destruction of the medial meniscus than of the lateral meniscus (Z = 2.062, P = 0.039). Fibrosis and engulfing calcified debris were the most severe pathological manifestations. Synovitis was also identified in all 26 specimens, with hyperplasia of intima cells and lymphocyte and plasma cell infiltration being the most severe pathological manifestations.

Conclusions

Severe destruction of the articular cartilage and menisci is a characteristic feature of RA. Bone marrow edema and bone erosion can both also be found, but are less characteristic. Synovial infiltration may be the triggering mechanism of the destruction of the cartilage, menisci, and bone marrow. However, the origin of bone marrow edema requires further investigation.

     

Factors influencing spinal sagittal balance,bone mineral density,and Oswestry Disability Index outcome measures in patients with rheumatoid arthritis

Purpose

To identify the factors influencing spinal sagittal alignment, bone mineral density (BMD), and Oswestry Disability Index (ODI) outcome measures in patients with rheumatoid arthritis (RA).

Methods

We enrolled 272 RA patients to identify the factors influencing sagittal vertical axis (SVA). Out of this, 220 had evaluation of bone mineral density (BMD) and vertebral deformity (VD) on the sagittal plane; 183 completed the ODI questionnaire. We collected data regarding RA-associated clinical parameters and standing lateral X-ray images via an ODI questionnaire from April to December 2012 at a single center. Patients with a history of spinal surgery or any missing clinical data were excluded. Clinical parameters included age, sex, body mass index, RA disease duration, disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR), serum anti-cyclic citrullinated peptide antibody, serum rheumatoid factor, serum matrix metalloproteinase-3, BMD and treatment type at survey, such as methotrexate (MTX), biological disease-modifying anti-rheumatic drugs, and glucocorticoids. We measured radiological parameters including pelvic incidence (PI), lumbar lordosis (LL), and SVA. We statistically identified the factors influencing SVA, BMD, VD, and ODI using multivariate regression analysis.

Results

Multivariate regression analysis showed that larger SVA correlated with older age, higher DAS28-ESR, MTX nonuse, and glucocorticoid use. Lower BMD was associated with female, older age, higher DAS28-ESR, and MTX nonuse. VD was associated with older age, longer disease duration, lower BMD, and glucocorticoid use. Worse ODI correlated with older age, larger PI-LL mismatch or larger SVA, higher DAS28-ESR, and glucocorticoid use.

Conclusions

In managing low back pain and spinal sagittal alignment in RA patients, RA-related clinical factors and the treatment type should be taken into consideration.