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International audience; Background/Aim: Multiple myeloma (MM) is characterized by high production of immunoglobulins resulting in a constant source of endoplasmic reticulum (ER)-stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF) was identified as a possible circulating biomarker that could help in monitoring ER-stress mediated diseases. Materials and Methods: To assess the relevance of MANF in MM, we performed in silico and in vitro analysis in malignant cell lines including the myeloma cell line RPMI 8226. Serum MANF concentration was compared between healthy subjects (n=60), patients with MM (n=68), or those with monoclonal gammopathy of undetermined significance (MGUS) (n=73). Results: MANF mRNA expression was upregulated in the RPMI 8226 cell line, and higher secretion of MANF was measured in RPMI 8226 supernatant. Serum MANF levels were not significantly different between MM or MGUS patients and those in age-and sex-matched healthy controls. Conclusion: MANF was not validated as a biomarker of interest in MM patients. Its potential implication in myeloma pathogenesis should be investigated.

We saw an increase in this condition related to emergence of Streptococcus pneumoniae serotype 23B., We conducted a retrospective study on all cases of pneumococcal septic arthritis (SA) in patients >18 years of age reported to the Picardie Regional Pneumococcal Network in France during 2005–2016. Among 1,062 cases of invasive pneumococcal disease, we observed 16 (1.5%) SA cases. Although SA is uncommon in adult patients, the prevalence of pneumococcal SA in the Picardie region increased from 0.69% during 2005–2010 to 2.47% during 2011–2016 after introduction of the pneumococcal 13-valent conjugate vaccine. We highlight the emergence of SA cases caused by the 23B serotype, which is not covered in the vaccine.

Objective Adult-onset Still's disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD. Methods We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi's or Fautrel's criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated. Results We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade. Conclusion Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.

To compare clinical and imaging characteristics of patients with giant cell arteritis (GCA) and upper extremity (UE) arterial involvement to patients with Takayasu arteritis (TAK).A cohort of patients seen at the Mayo Clinic with TAK diagnosed between 1984 and 2009 and a cohort of patients with GCA and UE arterial involvement diagnosed between 1999 and 2008 were studied.The TAK cohort consisted of 125 patients (91% female); the mean age (±SD) at diagnosis was 30.9 (±10) years. The cohort of patients with GCA and UE involvement comprised of 120 patients (80% female); the mean age (±SD) at diagnosis was 67.8 (±7.5) years. The mean time from onset of symptoms to diagnosis was significantly longer in TAK (3.2 years) than GCA (0.5 years), p0.001. UE claudication was reported in 40% with TAK and 53% with GCA, p = 0.04. UE blood pressure discrepancy was present in 65% with TAK versus 28% with GCA, p0.001. Involvement of the thoracic aorta, abdominal aorta, carotid arteries, innominate artery, mesenteric artery, and left renal artery was more frequently observed in TAK (p0.05). Among patients with luminal changes of the thoracic aorta, stenotic/occlusive lesions were predominant in TAK (81% compared to 0% in GCA), whereas aneurysmal disease was more common in GCA (100% compared with 19% in TAK, p0.001).Patients with GCA and UE involvement differ from patients with TAK in clinical and imaging characteristics. Aortic aneurysms were more common in GCA, while stenotic changes of the aorta were more common in TAK, suggesting different pathophysiologic mechanisms or vascular response to injury.

Objectives The prevalence of atherosclerotic risk factors and disease in Takayasu's arteritis (TAK) has not been well defined. We aimed to assess the frequency of cardiovascular (CV) risk factors and the incidence of CV events (CVEs) in patients with TAK from two ethnically different populations. Methods Patients with TAK followed at Mayo Clinic, Rochester, MN, USA and Marmara University, Istanbul, Turkey were included in this retrospective study. Patients with TAK were compared with age-, sex- and calendar year-matched controls from the same geographical region without TAK. The 2008 Framingham 10-year general CV risk score (FRS) was used for the evaluation of CV risk at the time of TAK incidence/index date. Results In total, 191 patients with TAK and 191 non-TAK controls were included. Hypertension and the prevalence of lipid-lowering treatments were significantly more frequent in TAK. Prior to the incidence/index date, occurrence of CVE was significantly higher in TAK. The FRS was significantly higher in TAK compared with non-TAK at incidence/index date. The cumulative incidence of CVE was 15.4% at 10 years in TAK vs 5.8% in non-TAK; the risk of CVE was increased among patients with TAK (hazard ratio = 4.36; 95% CI: 1.25, 15.13). Conclusion CV risk factors are more common in patients with TAK, particularly hypertension. The FRS is higher in patients with TAK at the time of diagnosis. The cumulative incidence of CVE was also significantly higher during follow-up in TAK. Our results suggest that patients with TAK should undergo careful assessment of CV risk factors, and an aggressive risk modification approach is warranted.

To evaluate cardiopulmonary (CP) involvement in patients with Takayasu's arteritis (TAK) and assess the impact on disease outcomes.A retrospective cohort of patients with newly diagnosed TAK from 1984 to 2009 was assembled. Demographics, baseline disease characteristics, relapse events, surgeries and mortality were abstracted from direct medical record review. Angiograms, advanced imaging and cardiac studies were reviewed for evidence of CP involvement. Cox models with time-dependent covariates were used to assess the association between CP involvement and outcomes.A total of 124 patients with TAK were identified. Forty-five (36%) patients had at least one objective CP abnormality observed within 6 months of TAK diagnosis. Age at diagnosis was higher in those with CP involvement than those without (34.6 vs 30.1 yrs; p=0.04). Baseline characteristics and symptoms were similar, except shortness of breath, which was more frequently observed at TAK diagnosis in patients with CP involvement compared to those without (53% vs 21%; p=0.001). Composite CP involvement was not associated with risk of first surgery [Hazard ratio (95% CI): 1.21 (0.64-2.30); p=0.56]. However, pulmonary hypertension (PH) on echocardiogram was significantly associated with risk of first surgery [HR (95% CI): 12.9 (1.86- 89.14); p=0.01]. CP involvement was not significantly associated with mortality [HR (95% CI): 2.51 (0.45- 14.02); p=0.29].Cardiopulmonary abnormalities in TAK are common at the time of initial presentation. In this population, the presence of PH predicted a 13-fold increased risk for vascular or valvular surgery. In this cohort, the presence of CP involvement did not increase mortality.

To describe the clinical features, treatment, and outcomes in a longitudinal cohort of patients with Takayasu arteritis (TAK).We retrospectively studied patients with newly diagnosed TAK evaluated from January 1, 1984, through December 31, 2009.The cohort included 126 patients who were predominantly white (85/103; 82.5%) and female (115/126; 91%). The median age at diagnosis was 31.6 years (interquartile range, 22.9-39.8 years). Median delay in diagnosis was 17.5 months (interquartile range, 7-41.8 months). Thirty-one patients (25%) were 40 years or older at diagnosis. Median delay in diagnosis for patients 40 years or older was 44.8 months compared with 28.3 months for those younger than 40 years (P.001). Limb claudication was the presenting symptom in 64 of 123 patients (52%). Hata type V arteriographic abnormalities were the most common (57/100; 57%). Renal artery abnormalities were observed in 24 of 41 patients (58%) with new-onset hypertension. Inflammatory markers were elevated at diagnosis in 85 of 119 patients (71%). Vascular interventions were performed in 69 patients (55%). Seventy-nine patients (63%) were followed up for more than 1 year (median follow-up, 5.5 years; interquartile range, 2.9-10.0 years). In this subset, treatment consisted of corticosteroids in 73 patients (92%) and additional immunosuppressants in 52 patients (66%). At 5 years, 96% experienced at least one remission of any duration. The overall survival was 97% at 10 years and 86% at 15 years. Mortality was increased compared with the general population (standardized mortality ratio, 3.0; 95% CI, 1.0-8.9).There continues to be an unacceptably long delay in the diagnosis of TAK. Awareness of TAK in patients older than 40 years is needed. Morbidity was high despite immunosuppressive treatment. Survival was decreased in this cohort.

Interstitial lung disease (ILD) has been reported in 3 to 11% of patients with primary Sjogren's syndrome (pSS). The aims of this retrospective multicenter study were to: 1) analyze characteristics and outcome of ILD in pSS; and 2) evaluate predictive factors associated with ILD onset and deterioration. Twenty-one of 263 patients with pSS (8%) developed ILD. ILD onset preceded pSS diagnosis (n=5), was concurrently identified in association with pSS (n=6) and developed after pSS onset (n=9). Presenting ILD manifestations were: acute/subacute (n=11) onset of ILD, symptomatic progressive onset of ILD (n=5), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT-scan (n=5). ILD therapy included: steroids (n=21), cyclophosphamide (n=1), azathioprine (n=4) and rituximab (n=1). The course of ILD was as follows: improvement (15.8%), stabilization (47.4%) or deterioration (36.8%). Predictive parameters of ILD onset were: older age (p=0.044), Raynaud's phenomenon (p=0.001) and esophageal involvement (p=0.001). Factors associated with ILD deterioration were: older age (p=0.038) and esophageal involvement (p=0.038). Thus, this study underscores the poor outcome of ILD during pSS; thus, systematic screening of pulmonary involvement is required in pSS patients, resulting in both diagnosis and management at early stage of ILD. We also suggest that patients presenting predictive factors of ILD deterioration may need a closer follow-up and a more aggressive therapy.

Objective.(1) To examine the association between statin use and giant cell arteritis (GCA); (2) to compare the clinical features and disease course of GCA among statin users and nonusers.Methods.For this retrospective study, we reviewed the medical records of all patients with biopsy-positive GCA diagnosed between 1998 and 2008. Using a case-control design, we compared the frequency of statin use in GCA patients to non-GCA population-based subjects who were randomly selected and individually matched by sex, age, and calendar year to the GCA cases. Statin use at diagnosis or index date and during followup was abstracted. In subjects with GCA, clinical information at diagnosis and followup was collected.Results.We included 594 patients, 297 with GCA (73% female), mean age at diagnosis 75 years. The rate of statin exposure at index date was 18.1% for GCA patients versus 33.3% for controls (p < 0.001). Patients using statins were less likely to develop GCA compared with patients not using statins (OR 0.31, 95% CI 0.15–0.6, p < 0.001), even after adjustment for cardiovascular risk factors. Among patients with GCA, the presenting clinical features and acute-phase reactants were similar in patients receiving statins compared to those not on statin therapy. These 2 groups were also similar with regard to relapse rate, prednisone tapering, and overall survival.Conclusion.Patients using statins may be less likely to develop GCA compared to patients who are not using statins. Statin use does not appear to modify the clinical presentation or the course of the disease.

Objective To report a single-center experience with the use of tumor necrosis factor (TNF) inhibitors in patients with Takayasu arteritis (TA). Methods We retrospectively studied a cohort of patients with refractory TA evaluated at our institution and treated with TNF inhibitors. American College of Rheumatology criteria for TA were used for inclusion. Disease activity was assessed according to the National Institutes of Health criteria. Results We included 20 patients (19 women, 17 white) with a mean ± SD age of 33 ± 10.2 years and a median disease duration of 15.9 months (interquartile range [IRQ] 2–32.7 months) prior to the use of TNF inhibitors. Before the use of TNF inhibitors, all 20 patients received prednisone. Other medication use included methotrexate (18 patients), azathioprine (5 patients), mycophenolate mofetil (3 patients), and cyclophosphamide (3 patients). Seventeen patients (85%) received infliximab, 2 patients (10%) received adalimumab, and 1 patient (5%) received etanercept. The median duration of treatment with TNF inhibitors was 23.0 months (IQR 8.7–38.9 months). Treatment with TNF inhibitors resulted in disease remission in 18 (90%) of 20 patients and sustained remission in 10 patients (50%). Ten (83%) of 12 patients were able to taper prednisone below 10 mg and 7 patients discontinued prednisone. However, 6 of the 18 patients achieving remission experienced relapse while receiving TNF inhibitors. Eleven patients (55%) discontinued TNF inhibitors for the following reasons: relapse, persistently active disease, lack of corticosteroid-sparing effect, adverse effects (4 patients), and other reasons (4 patients). Conclusion In this study, treatment with TNF inhibitors induced remission, including sustained remission in patients with refractory TA. However, 33% of patients experienced disease relapse while receiving TNF inhibitors and 20% discontinued treatment because of adverse events.

Backgrounds Among anti-double-strand (ds)DNA antibody assays, Farr radioimmunoassay is decreasingly used because it requires radioactive material and is labor intensive. We evaluated the performance of Farr, three commercial enzyme immunoassays (EIAs) and the Crithidia luciliae immunofluorescence test (CLIFT) in systemic lupus erythematosus (SLE). Methods Anti-dsDNA antibodies were determined in 99 SLE patients, 101 healthy subjects, and 53 patients with autoimmune rheumatic diseases. Results Farr performed better than the 3 EIAs and CLIFT for the diagnosis of SLE at the manufacturer's cut off and at the cut off set to achieve a specificity of 95%. To achieve a similar level of specificity, some EIAs had a decrease in sensitivity which was dramatic for some tests. Farr was also the best at distinguishing patients with quiescent to mildly active disease from patients with more active disease at the cut off value of 93 IU/ml. Using manufacturer's cut off did not allow distinguishing between patients with quiescent and active SLE. Conclusions Farr was the best global test to assess the level of anti-dsDNA antibodies for both diagnosis and disease activity evaluation in SLE with adequately determined cut off values. Some EIA had low performances limiting their use in decision-making regarding diagnosis and/or treatment.