Diagnostic accuracy of serum biomarkers to identify giant cell arteritis in patients with polymyalgia rheumatica.

INTRODUCTION: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are frequently overlapping conditions. Unlike in GCA, vascular inflammation is absent in PMR. Therefore, serum biomarkers reflecting vascular remodelling could be used to identify GCA in cases of apparently isolated PMR. MATERIALS AND METHODS: 45 patients with isolated PMR and 29 patients with PMR/GCA overlap were included. Blood samples were collected before starting glucocorticoids for all patients. Serum biomarkers reflecting systemic inflammation (interleukin-6 (IL-6), CXCL9), vascular remodelling (MMP-2, MMP-3, MMP-9) and endothelial function (sCD141, sCD146, ICAM-1, VCAM-1, vWFA2) were measured by Luminex assays. RESULTS: Patients with GCA had higher serum levels of sCD141 (p=0.002) and CXCL9 (p=0.002) than isolated PMR. By contrast, serum levels of MMP-3 (p=0.01) and IL-6 (p=0.004) were lower in GCA than isolated PMR. The area under the curve (AUC) was calculated for sCD141, CXCL9, IL-6 and MMP-3. Separately, none of them were >0.7, but combinations revealed higher diagnostic accuracy. The CXCL9/IL-6 ratio was significantly increased in patients with GCA (p=0.0001; cut-off >32.8, AUC 0.76), while the MMP-3/sCD141 ratio was significantly lower in patients with GCA (p<0.0001; cut-off <5.3, AUC 0.79). In patients with subclinical GCA, which is the most difficult to diagnose, sCD141 and MMP-3/sCD141 ratio demonstrated high diagnostic accuracy with AUC of 0.81 and 0.77, respectively. CONCLUSION: Combined serum biomarkers such as CXCL9/IL-6 and MMP-3/sCD141 could help identify GCA in patients with isolated PMR. It could allow to select patients with PMR in whom complementary examinations are needed.

Predictive Factors of Giant Cell Arteritis in Polymyalgia Rheumatica Patients.

Polymyalgia rheumatica (PMR) is an inflammatory rheumatism of the shoulder and pelvic girdles. In 16 to 21% of cases, PMR is associated with giant cell arteritis (GCA) that can lead to severe vascular complications. Ruling out GCA in patients with PMR is currently a critical challenge for clinicians. Two GCA phenotypes can be distinguished: cranial GCA (C-GCA) and large vessel GCA (LV-GCA). C-GCA is usually suspected when cranial manifestations (temporal headaches, jaw claudication, scalp tenderness, or visual disturbances) occur. Isolated LV-GCA is more difficult to diagnose, due to the lack of specificity of clinical features which can be limited to constitutional symptoms and/or unexplained fever. Furthermore, many studies have demonstrated the existence-in varying proportions-of subclinical GCA in patients with apparently isolated PMR features. In PMR patients, the occurrence of clinical features of C-GCA (new onset temporal headaches, jaw claudication, or abnormality of temporal arteries) are highly predictive of C-GCA. Additionally, glucocorticoids' resistance occurring during follow-up of PMR patients, the occurrence of constitutional symptoms, or acute phase reactants elevation are suggestive of associated GCA. Research into the predictive biomarkers of GCA in PMR patients is critical for selecting PMR patients for whom imaging and/or temporal artery biopsy is necessary. To date, Angiopoietin-2 and MMP-3 are powerful for predicting GCA in PMR patients, but these results need to be confirmed in further cohorts. In this review, we discuss the diagnostic challenges of subclinical GCA in PMR patients and will review the predictive factors of GCA in PMR patients.

Optimization of dual energy computed tomography post-processing to reduce lower limb artifacts in gout.

BACKGROUND: In gout, several types of dual-energy computed tomography (DECT) artifacts have been described (nail bed, skin, beam hardening, submillimeter and vascular artifacts), which can lead to overdiagnosis. The objective of this study was to determine the optimal DECT settings for post processing in order to reduce the frequency of some common artifacts in patients with suspected gout. METHODS: Seventy-seven patients hospitalized for suspected gout (feet/ankles and/or knees) who received a DECT imaging were included (final diagnosis of 43 gout and 34 other rheumatic disorders). Different post-processing settings were evaluated using Syngovia software: nine settings (R1 to R9) were evaluated with a combination of different ratio (1.28, 1.36 and 1.55) and attenuation coefficient (120, 150, 170 HU). RESULTS: Among the nine settings tested, the R2 setting (170 HU, ratio =1.28) significantly reduced the presence of knee and foot/ankle artifacts compared to the standard R1 setting (85% and 94% decrease in beam hardening and clumpy artifacts in the ankle and foot, respectively (P<0.001); a decrease of 71%, 60% and 88% respectively of meniscal beam hardening, beam hardening and submillimeter artifacts in the knee (P<0.001). Compared to standard settings, the use of R2 settings decreased sensitivity [0.79 (95% CI: 0.65, 0.88) versus 0.90 (95% CI: 0.78, 0.96)] and increased specificity [0.86 (95% CI: 0.71, 0.93) versus 0.63 (95% CI: 0.47, 0.77)] (P<0.001). Settings using an attenuation coefficient to 120 HU and/or a ratio to 1.55 were all associated with a significant increasing of artifacts, especially clumpy and beam hardening artifacts. CONCLUSIONS: Applying a ratio of 1.28 and a minimum attenuation of 170 HU in DECT post-processing eliminates the majority of artifacts located in the lower limbs, particularly clumpy artifacts and beam hardening.

Dynamic global sagittal alignment in patients with lumbar spinal stenosis: Analysis of the effects of decompression surgery on gait adaptations.

BACKGROUND: Lumbar spinal stenosis (LSS) leads patients to adapt their posture and walking parameters. Pelvic retroversion might be a compensation mechanism of pain. Pelvic and lower limbs compensations during gait are still not precisely understood, as well as the effect of a surgical decompression on them. These dynamic parameters can be studied through three-dimensional gait analysis. RESEARCH QUESTION: Is the dynamic pelvic tilt modified after decompression surgery in LSS patients compared to asymptomatic subjects? MATERIAL AND METHODS: 50 asymptomatic subjects (C-group) and 37 patients operated on for lumbar decompression underwent a three-dimensional gait analysis one month before (M0) and six months after (M6) the surgery. 3D gait analysis was performed and hip and knee flexion, trunk kinematics, walking speed, stride length and pelvic tilt during gait or dynamic pelvic tilt (dPT) were recorded. Health-related quality of life (HRQL) scores (Oswestry Disability Index (ODI) and Visual Analogic Scales (VAS)) and radiological assessment were performed preoperatively and postoperatively. RESULTS: Mean values of maximum and minimum dPT in the LSS-group preoperatively were significantly higher compared to the C-group (respectively 10.9 (6.2)° versus 7.3 (5.6)°, p = 0.003; 7.7 (6.1)° versus 4.8 (5.8)°, p = 0.011), and were significantly lowered at M6 (respectively 10.9 (6.2)° versus 8.1 (4.8)°, p = 0.0087; and 7.7 (6.1)° versus 5.1 (4.7)°, p = 0.012), and became similar to the C-group. The dPT range of motion at M0 and M6 were similar, and were both significantly higher than control values. Mean values of maximum and minimum hip flexion were significantly higher at M0 compared to the C-group, and were significantly lowered at M6. No difference was found between the pre- and postoperative radiographic pelvic tilt. The VAS for lumbar pain, the VAS for radicular pain and the ODI were significantly decreased at M6. SIGNIFICANCE: Compared to asymptomatic people, LSS patients walked with a pelvic anteversion, a hip flessum and a knee flessum before surgery, which tended to disappear after the surgical decompression. These differences were not noticed on static radiographs.

The frequency of occult solid malignancy in patients with polymyalgia rheumatica-like symptoms.

AIMS: We aim to evaluate the clinical usefulness of systematic screening for occult cancer in patients with polymyalgia rheumatic (PMR)-like symptoms in real-life practice. METHODS: All patients seen by rheumatologists in Burgundy, France, between March 2016 and December 2018 for new-onset PMR that met the 2012 ACR/EULAR classification criteria were prospectively included. Patients underwent systematic screening including determination of the erythrocyte sedimentation rate, serum C-reactive protein levels, thoracic, abdominal and pelvic computed tomography (CT-TAP) and, in men, serum prostate-specific antigen. The standardized incidence ratio (SIR) for cancers was calculated using 2012 national estimates of cancer incidence. Potential predictive factors for the diagnosis of cancer were then evaluated using univariate and multivariate analyses. RESULTS: Among the 118 patients included, nine cases of cancer were confirmed and diagnosed with CT-TAP: kidney carcinoma (n = 4), lung cancer (n = 2), pancreatic, colon, and ampullary carcinoma (n = 1 each). Among these cancers, five were localized (four kidney, and one ampullary carcinoma) and were treated with complete surgical resection. The expected incidence of cancer in the general population was 1.95, leading to an overall SIR of 4.6 (95% CI 2.4-8.9, p < 0.0001). An additional analysis was performed for the kidney carcinoma, and it showed a highly significant increase in SIR: 80.8 (95% CI 30.3-215.4). In 80% of patients, the PMR-like syndrome regressed during cancer treatment. No other predictive factors for cancer were found. CONCLUSION: Systematic screening for cancer including CT-TAP in real-life practice revealed occult solid malignancy, mostly early-stage cancer, in a relevant proportion of patients presenting PMR-like symptoms. The high proportion of kidney cancer (40%) is worth highlighting, especially considering that it is not one of the most frequent cancers after 50 years of age.

A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients.

Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16-0.61), p = 0.001). No association was found with any of the other SNPs tested.

Is the Pelvis-Thorax Coordination a Valuable Outcome Instrument to Assess Patients With Hip Osteoarthritis?

Objective: The evaluation of the disease severity in hip osteoarthritis (OA) patients being currently based on subjective instruments. It would be of interest to develop more objective instruments, for example based on gait analysis. The aims of this study were to explore if pelvis-thorax coordination parameters could be valuable instrument outcomes to achieve this evaluation by assessing their reliability, discriminant capacity and responsiveness. Methods: Three groups of subjects; healthy, hip OA patients with severe disease (defined as indication to surgery), hip OA patients with less severe disease (no indication to surgery) were included. Hip OA patients with severe disease were evaluated before and 6 months after surgery. Subjects had to perform a gait analysis at comfortable speed, and pelvis-thorax coordination was evaluated. The correlations with clinical and structural parameters, as well as reliability, discriminant capacities and responsiveness, were assessed. Results: The pelvis-thorax coordination in the coronal plane during walking was correlated to clinical and to structural severity in hip OA patients (R 2 = 0.13). The coronal plane coordination allowed to discriminate healthy subjects from all hip OA patients (sensibility = 0.86; specificity = 0.59). Moreover, when comparing OA patients only, coronal plane coordination allows to discriminate patients with indication of surgery from those with no indication of surgery (sensibility = 0.72; specificity = 0.72). Moreover, the pelvis-thorax coordination demonstrated an excellent reliability and a good responsiveness. Conclusion: Changes in the pelvis-thorax coordination might refer to different mechanisms, from analgesia to motor control plasticity, and might be a possible explanation for the weak correlation between structure and symptoms in hip OA patients. Moreover, such parameter might be used as an objective outcome in hip OA clinical trials. Clinical Trials Registration: www.ClinicalTrials.gov, identifier: NCT02042586 and NCT01907503.

Role of dual-energy CT in the diagnosis and follow-up of gout: systematic analysis of the literature.

The aim of this systematic review was to determine the potential role of dual-energy CT in the diagnosis and follow-up of gout with regard to the Outcome Measures in Rheumatology (OMERACT) filter. A systematic analysis of the literature was conducted using the MEDLINE and Cochrane databases and published abstracts of international congresses, according to the criteria of the OMERACT filter: feasibility, reproducibility, validity versus laboratory (serum urate, MSU synovial fluid aspirate) and other imaging modalities for gout, and its sensitivity to change in patients on urate lowering therapy (ULT). Thirty-two articles were found representing a total of 1502 patients. The data on feasibility showed that the examination took little time and involved low levels of radiation but had current limited availability. Intra- and inter-observer reproducibility was excellent, with intra-class correlation coefficients > 0.9. Validity in comparison with polarized-light microscopy showed good sensitivity and specificity (> 80%). The diagnostic performance was better than that of radiography and conventional CT-scan and at least equivalent to that of ultrasonography. The sensitivity to change varied with effect sizes from 0.05 (low) to 1.24 (high) for decrease in the tophus volume following different ULT in gout patients. Dual-energy CT-scan is a reproducible and accurate imaging modality for the diagnosis of gout, particularly for tophaceous gout (intra- or extra-articular). It can become a second-line imaging modality of choice in cases of diagnostic doubt, such as ultrasonography. Its role remains uncertain in the follow-up of gout patients treated with ULT and needs further clarification.

Röttinger approach with dual-mobility cup to improve functional recovery in hip osteoarthritis patients: biomechanical and clinical follow-up.

PURPOSE: We assumed that the combination of dual-mobility total hip arthroplasty (THA) using the minimally-invasive Röttinger anterolateral approach could guarantee hip stability with faster functional recovery. We objectively analyzed functional improvement after dual-mobility THA by quantitative gait analysis. METHODS: We compared the results achieved following two different surgical approaches: Röttinger's versus Moore's approach (posterolateral approach). We included 70 patients in an open prospective single-centre study: 38 by Rottinger's approach (age = 67yo) and 32 by Moores's approach (age = 68yo). Clinical and biomechanical analysis (kinematic and kinetic parameters of the hip) were conducted at the pre-operative period and at six months post-op RESULTS: We found a significant improvement in all clinical scores and all biomechanical parameters but no difference was found between the two approaches. However, the study showed marked clinical, biomechanical and functional improvements for patients treated with dual-mobility THA for osteoarthritis without complete hip recovery compared with a control group. CONCLUSIONS: The combination of the Röttinger approach with a dual-mobility cup remains a valid choice for primary THA without functional advantage at midterm.

Patient-perceived flares in rheumatoid arthritis: A sub-analysis of the STRASS treatment tapering strategy trial.

OBJECTIVES: Patient's and physician's perspective can differ in rheumatoid arthritis (RA). The aim was to define the concept of patient-reported flares. METHODS: Post-hoc analysis of a randomized controlled trial of a step-down strategy in RA patients treated with anti-TNF, in DAS28-remission for ≥6 months, randomized to either "spacing" or "maintaining" anti-TNF. The occurrence of patient-reported flares (PRF) was evaluated every 3 months for 18 months by: "Over the last 3 months, did you experience symptoms suggestive of disease exacerbation?". Visits with and without PRF were compared, using a linear mixed effects model, in terms of symptoms, disability based on the Health Assessment Questionnaire, quality of life based on Short Form 36 Health Survey and DAS28-based relapses (DBR), defined as an increase of DAS28>0.6 and an absolute value of DAS28>2.6. The agreement between PRF and DBR was measured by the kappa coefficient on repeated data. RESULTS: In all, 137 patients were analyzed: mean age 55±11 years, females 78%, mean RA duration 9.5±8.0 years. Over the 18 months, PRF concerned 27.2% of the 940 available visits. DBR and PRF were observed in 24% and 16% of 940 visits for 137 patients respectively. All the items were associated with PRF with standardized effect size between -0.58 (SF36 PCS) and 0.87 (DAS28). The agreement between PRF and DBR was moderate (κ=0.44). CONCLUSION: The concept of flare refers to more than just RA disease activity.

Response to tocilizumab in rheumatoid arthritis is not influenced by the body mass index of the patient.

OBJECTIVE: To assess the relationship between the body mass index (BMI) and the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA). METHODS: We conducted a retrospective study in 222 patients with RA followed by 5 centers. The European League Against Rheumatism response was evaluated at 6 months. Univariate and multivariate logistic regressions were performed. RESULTS: No significant association between the BMI and the response to TCZ at 6 months was found after adjustment for potential confounding factors (adjusted OR 0.45, 95% CI 0.16-1.24, p = 0.13 and OR 1.19, 95% CI 0.31-4.48, p = 0.78 for BMI 25-30 kg/m(2) and BMI > 30 kg/m(2), respectively, compared to BMI < 25 kg/m(2)). CONCLUSION: Response to TCZ in patients with RA is not influenced by the baseline BMI, in contrast to anti-tumor necrosis factor drugs.

Predictors of response and remission in a large cohort of rheumatoid arthritis patients treated with tocilizumab in clinical practice.

OBJECTIVE: The objective of this study was to identify predictors of response and remission to tocilizumab (TCZ) in RA patients seen in daily routine clinical practice. METHODS: The efficacy of TCZ was evaluated after 12 and 24 weeks of treatment by the European League Against Rheumatism (EULAR) response criteria. Regression analysis was performed to study the association between remission or EULAR response and the following characteristics: gender, age, current smokers, prior cardiovascular disease (CVD), 28-joint disease activity score (DAS28), CRP, RF or ACPA positivity, combination therapy with DMARDs and TCZ as the first biological therapy or after failure of at least one biological therapy. RESULTS: In total, 204 patients were included with a mean DAS28 score of 5.14. EULAR response and remission were obtained in 86.1% and 40% of patients, respectively, at week 24. In multiple regression analysis, a high baseline CRP level [odds ratio (OR) 4.454 (95% CI 1.446, 13.726)] was significantly associated with EULAR response at week 24 and, inversely, age >55 years [OR 0.285 (95% CI 0.086, 0.950)] and prior CVD [OR 0.305 (95% CI 0.113, 0.825)] were significantly associated with lower EULAR response at week 24. Older age was also associated with less remission at week 24 [OR 0.948 (95% CI 0.920, 0.978)]. No additional effectiveness was found when TCZ was used in combination with a DMARD or when patients were naive to biological agents. CONCLUSION: In daily practice we identified three predictors of a better response for TCZ therapy in RA: a younger age, a high baseline CRP level and no history of CVD.

Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients.

BACKGROUND: Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. METHODS: A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone markers evaluations. RESULTS: Ninety-five (36%) patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001), hsCRP (p = 0.04), increased serum C-Telopeptides X (CTX) (p = 0.005) and Parathyroid Hormon (PTH) (p < 0.0001) levels. In multivariate analysis, SHD deficiency correlated significantly with increased IL-6, high serum CTX levels, lower mean daily exposure to the sun, current or past smoking, hepatitis C, and functional status (falls), but not with the time spent on the current HAART (by specific drug or overall). CONCLUSIONS: SHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.

Clinical interest of bone marrow aspiration in rheumatology: a practice-based observational study of 257 bone marrow aspirations.

Bone marrow aspiration (BMA) can be performed by rheumatologists for diagnostic purposes in clinical practice. The aim of the study was to assess professional practices of hospital-based rheumatologists with regard to BMA in order to identify the relevant indications. A retrospective observational study in patients hospitalised in a French university hospital was conducted between 2005 and 2011. All of the patients who had a BMA in the rheumatology department during the study period were included. Clinical indication, number and results of BMA and of bone marrow biopsy (BMB) were collected. Stage and treatment of the haematological disease implemented following the BMA were described. Two hundred fifty-seven BMAs and 79 BMBs were performed during the study period. Of the BMAs, 14.1 % were pathological: myeloma (n = 12), malignant B cell non-Hodgkin's lymphoma (n = 6), myelodysplastic syndrome (n = 6), chronic lymphoid leukaemia (n = 4), Waldenstrom's disease (n = 3), chronic myelomonocytic leukaemia (n = 2), hairy cell leukaemia (n = 1) and acute lymphoblastic leukaemia (n = 1). Eight of the 14 pathological BMBs were associated with normal BMA. BMAs were performed equally for gammaglobulin abnormalities (monoclonal peak = 45 % of indications, hypogammaglobulinemia = 6 %) and for other reasons (haemogram abnormality = 24 %, skeletal osteolysis = 6 %, unexplained inflammatory syndrome = 5 %, lymph node disease = 4 % and others). In clinical rheumatology, BMA may reveal two major types of malignant haematological diseases: myeloma with poor prognostic factors justifying polychemotherapy and autologous grafts and, in contrast, slowly evolving B cell lymphoid haemopathies. Given the additional risk in some types of chronic inflammatory rheumatism, BMB should be performed more frequently in certain specific situations (skeletal or lymph node tumour and unexplained inflammatory syndrome).

Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis.

OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. CONCLUSION: This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.

Do hip OA patients referred to orthopedic surgeons by general practitioners and rheumatologists differ?

There is no consensus regarding indications for total hip arthroplasty (THA) in hip osteoarthritis (OA). Patients can be referred to surgeons either by a general practitioner (GP) or a rheumatologist. The aim of this study was to determine whether patients referred to orthopedic surgeons by GP and rheumatologists differed. GPs and rheumatologists were asked to include one patient suffering from hip OA for whom a consultation with a surgeon was planned to determine if THA was indicated. Surgeons' decisions were obtained by follow-up questionnaires. Univariate and then multivariate statistical analysis evaluated differences between patients referred by GPs and those referred by rheumatologists. A total of 558 patients were included. THA was prescribed in 71.6 % of patients referred by rheumatologists vs. 57.6 % of patients referred by GPs (p = 0.008). Patients referred by rheumatologists were younger (66.3 vs. 69.3 years; p = 0.006), less frequently retired (72.9 vs. 84.2 %; p = 0.007), and presented with a higher New Zealand score (54.3 vs. 48.1; p = 0.0009). On multivariate analysis, the variables related to patients referred by rheumatologists were the SF-12 mental score, the New Zealand score, and the surgeon's decision. Patients consulting a surgeon to discuss THA were more likely to be operated on when referred by a rheumatologist, which might be due to differences in the rheumatologists' and GPs' opinions on the right time to perform surgery or due to differences in the populations followed by rheumatologists and GPs, those followed by rheumatologists being younger, more active, more urban, with a greater willingness to undergo surgery.

Brief report: inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis.

OBJECTIVE: From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti-interleukin-6 (anti-IL-6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL-6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL-6 blockade on the balance between Th17 cells and Treg cells in patients with active RA. METHODS: Patients with active RA for whom TCZ had been prescribed by a rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed, and the Disease Activity Score in 28 joints (DAS28) was assessed. Serum cytokine levels and other parameters of inflammation were measured before the first infusion and after the third infusion of TCZ (8 mg/kg). RESULTS: Compared to controls, levels of Th17 cells (CD4+IL-17+) were increased and Treg cells (CD4+CD25(high) FoxP3+) were decreased in the peripheral blood of patients with active RA. The suppressive function of circulating Treg cells was not impaired in patients with active RA. TCZ treatment induced a significant decrease in the DAS28 associated with a significant decrease in the percentage of Th17 cells (from a median of 0.9% to 0.45%; P = 0.009) and an increase in the percentage of Treg cells (from a median of 3.05% to 3.94%; P = 0.0039) in all patients. CONCLUSION: This study demonstrates for the first time that inhibition of IL-6 function by TCZ corrects the imbalance between Th17 cells and Treg cells in patients with RA.