Risk of low bone mineral density in patients with rheumatoid arthritis treated with biologics.

BACKGROUND: Osteoporosis is a complication of rheumatoid arthritis (RA). We identified risk factors for osteoporosis during treatment with biologics. METHODS: Femoral neck bone mineral density (BMD) was measured in 186 patients with biologics-treated RA. We compared the characteristics of those with BMD ≥70% of young adult mean (YAM) and those with BMD <70% of YAM, and undertook multivariable logistic regression analysis to identify risk factors for bone loss. RESULTS: Mean age and disease duration, the proportion of females, scores in the Modified Health Assessment Questionnaire and history of vertebral fracture were significantly greater in the BMD <70% of YAM group, but body mass index (BMI) was significantly lower in the BMD <70% of YAM group. There was no significant difference between the groups in terms of other biomarkers of RA activity, the proportion treated with methylprednisolone, or the duration or choice of biologics. The proportions of patients treated with anti-osteoporosis drugs and parathyroid hormone were significantly higher in the BMD <70% of YAM group. In the multivariable analysis, advanced age, female, longer disease duration, history of past thoracic or lumbar vertebral fracture, higher Steinbrocker classification and lower BMI were significant factors for BMD <70% of YAM. DISCUSSION: We identified risk factors for bone loss in patients with RA treated with biologics. Before suppression of disease activity by biologics, bone loss might already be advanced. CONCLUSIONS: We recommend that patients with RA who possess these risk factors be considered for earlier and more intense treatment to prevent bone loss, as well as addressing RA disease progression.

Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis.

OBJECTIVE: The ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined. METHODS: The amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls. RESULTS: The mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.0005) and patients without infection (P = 0.040). Also, the mean ATP level in patients without infection was significantly lower than that in healthy controls (P = 0.012). There was no correlation between the ATP level and the Disease Activity Score in 28 joints. CONCLUSION: ImmuKnow assay results may be effective in identifying RA patients at increased risk of infection, but the results showed no correlation with RA activity. Larger studies are required to establish the clinical advantages of this assay in RA treatment.

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study.

ABSTRACT: We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.

Direct observation of Tomonaga-Luttinger-liquid state in carbon nanotubes at low temperatures.

The electronic transport properties of conventional three-dimensional metals are successfully described by Fermi-liquid theory. But when the dimensionality of such a system is reduced to one, the Fermi-liquid state becomes unstable to Coulomb interactions, and the conduction electrons should instead behave according to Tomonaga-Luttinger-liquid (TLL) theory. Such a state reveals itself through interaction-dependent anomalous exponents in the correlation functions, density of states and momentum distribution of the electrons. Metallic single-walled carbon nanotubes (SWNTs) are considered to be ideal one-dimensional systems for realizing TLL states. Indeed, the results of transport measurements on metal-SWNT and SWNT-SWNT junctions have been attributed to the effects of tunnelling into or between TLLs, although there remains some ambiguity in these interpretations. Direct observations of the electronic states in SWNTs are therefore needed to resolve these uncertainties. Here we report angle-integrated photoemission measurements of SWNTs. Our results reveal an oscillation in the pi-electron density of states owing to one-dimensional van Hove singularities, confirming the one-dimensional nature of the valence band. The spectral function and intensities at the Fermi level both exhibit power-law behaviour (with almost identical exponents) in good agreement with theoretical predictions for the TLL state in SWNTs.

Serum-soluble folate receptor ß as a biomarker for the activity of rheumatoid arthritis synovitis and the response to anti-TNF agents.

This study aims to develop a sandwich ELISA system for the measurement of soluble folate receptor ß (sFRß) and evaluate whether base line levels of serum sFRß are a biomarker for the activity of RA synovitis and the response to anti-TNF agents. Serum sFRß from normal controls (41 samples), patients with OA (29 samples), and patients with RA (27 samples) and synovial fluid sFRß from patients with RA (17 samples) were measured by sandwich ELISA, using anti-FRαß and anti-FRß antibodies as capture and detection antibodies, respectively. Baseline levels of serum sFRß before therapy were evaluated in relation with DAS28-CRP or CRP and response to anti-TNF agents at 3-month follow-up. sFRß levels in RA synovial fluids were higher than those in RA sera, and sFRß levels in RA sera were higher than those in osteoarthritis and normal control sera. A significant relationship was observed between serum sFRß levels and the DAS28-CRP scores or CRP values. The area under curve (AUC) values for receiver-operating characteristic curves defined using the serum sFRß levels of RA patients before therapy had a higher predictive capacity than DAS28-CRP and CRP for the effective response of anti-TNF agents. The high serum sFRß levels with a cutoff value of 8 ng/mL were 100% specificity for the effective response of anti-TNF agents. The findings support that the serum sFRß levels in patients with RA act as a disease activation biomarker and that high serum sFRß levels act as a predictive biomarker for the response to anti-TNF agents.

Measurement of the two-photon correlation of synchrotron radiation in the VUV region by a delay-time modulation technique.

The two-photon correlation (second-order coherence) of synchrotron radiation in the VUV region (hnu = 55 eV) has been measured using a novel photon-counting method. A new technique has been developed to measure a small bunching effect by using a coincidence unit composed of a constant fraction discriminator, a time-to-amplitude converter (TAC), a single-channel analyzer (SCA) and two solid-state switches. The path of the circuit through which the stop signal for the TAC passes can be changed by a control voltage generated by a function generator, and the relative arrival time of two photons on condition that the output signal from the SCA appears is consequently changed. By modulating the arrival time and measuring the output rate from the SCA with a digital lock-in amplifier, an apparent bunching effect has been observed which is characteristic of the chaotic light. The electron-beam emittance in the horizontal direction was estimated as 39(-8)(+13) nm rad by this experiment, and the value was consistent with the designed value of 36 nm rad.