BioMed Research International: Rheumatology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Ultrasonography-Guided Lumbar Periradicular Injections for Unilateral Radicular Pain Thu, 30 Mar 2017 09:07:14 +0000 Objective. The aim of this study was to compare the accuracy and efficacy of sonographically guided lumbar periradicular injections through in-plane or out-of-plane approach techniques for patients with unilateral lower lumbar radicular pain. The feasibility and accuracy of these techniques were studied by means of computed tomography (CT). Methods. A total of 46 patients with chronic unilateral lumbar radicular pain were recruited and randomly assigned to either the in-plane or out-of-plane injection group. A mixture of 3 mL 1% lidocaine and 7 mg betamethasone was injected. The visual analog scale (VAS) was used to assess pain before and after treatment. Results. The pain intensity, as measured by VAS, significantly decreased in both in-plane and out-of-plane injection groups. Conclusions. The sonographically guided periradicular injections are feasible and effective in treating lumbar unilateral radicular pain. Qing Wan, Shaoling Wu, Xiao Li, Caina Lin, Songjian Ke, Cuicui Liu, Wenjun Xin, and Chao Ma Copyright © 2017 Qing Wan et al. All rights reserved. A Review on Real-Time 3D Ultrasound Imaging Technology Sun, 26 Mar 2017 07:28:32 +0000 Real-time three-dimensional (3D) ultrasound (US) has attracted much more attention in medical researches because it provides interactive feedback to help clinicians acquire high-quality images as well as timely spatial information of the scanned area and hence is necessary in intraoperative ultrasound examinations. Plenty of publications have been declared to complete the real-time or near real-time visualization of 3D ultrasound using volumetric probes or the routinely used two-dimensional (2D) probes. So far, a review on how to design an interactive system with appropriate processing algorithms remains missing, resulting in the lack of systematic understanding of the relevant technology. In this article, previous and the latest work on designing a real-time or near real-time 3D ultrasound imaging system are reviewed. Specifically, the data acquisition techniques, reconstruction algorithms, volume rendering methods, and clinical applications are presented. Moreover, the advantages and disadvantages of state-of-the-art approaches are discussed in detail. Qinghua Huang and Zhaozheng Zeng Copyright © 2017 Qinghua Huang and Zhaozheng Zeng. All rights reserved. Molecular Mechanism of Rheumatic Diseases and Efficacy of Current Therapies Wed, 15 Mar 2017 07:12:32 +0000 Sadiq Umar, Abdul M. Tyagi, Anil K. Singh, and Abdul Haseeb Copyright © 2017 Sadiq Umar et al. All rights reserved. Semianalytical Solution for the Deformation of an Elastic Layer under an Axisymmetrically Distributed Power-Form Load: Application to Fluid-Jet-Induced Indentation of Biological Soft Tissues Wed, 08 Mar 2017 06:13:04 +0000 Fluid-jet-based indentation is used as a noncontact excitation technique by systems measuring the mechanical properties of soft tissues. However, the application of these devices has been hindered by the lack of theoretical solutions. This study developed a mathematical model for testing the indentation induced by a fluid jet and determined a semianalytical solution. The soft tissue was modeled as an elastic layer bonded to a rigid base. The pressure of the fluid jet impinging on the soft tissue was assumed to have a power-form function. The semianalytical solution was verified in detail using finite-element modeling, with excellent agreement being achieved. The effects of several parameters on the solution behaviors are reported, and a method for applying the solution to determine the mechanical properties of soft tissues is suggested. Minhua Lu, Shuai Huang, Xianglong Yang, Lei Yang, and Rui Mao Copyright © 2017 Minhua Lu et al. All rights reserved. Ultrasound-Guided versus Fluoroscopy-Guided Deep Cervical Plexus Block for the Treatment of Cervicogenic Headache Thu, 23 Feb 2017 09:12:53 +0000 Objective. The aim of this study was to compare the efficacy of ultrasound-guided deep cervical plexus block with fluoroscopy-guided deep cervical plexus block for patients with cervicogenic headache (CeH). Methods. A total of 56 patients with CeH were recruited and randomly assigned to either the ultrasound-guided (US) or the fluoroscopy-guided (FL) injection group. A mixture of 2–4 mL 1% lidocaine and 7 mg betamethasone was injected along C2 and/or C3 transverse process. The measurement of pain was evaluated by patients’ ratings of a 10-point numerical pain scale (NPS) before and 2 wks, 12 wks, and 24 wks after treatments. Results. The blocking procedures were well tolerated. The pain intensity, as measured by NPS, significantly decreased at 2 wks after injection treatment in both US and FL groups, respectively, compared with that of baseline (P < 0.05). The blocking procedures had continued, and comparable pain relieving effects appeared at 12 wks and 24 wks after treatment in both US and FL groups. There were no significant differences observed in the NPS before and 2 wks, 12 wks, and 24 wks after treatment between US and FL groups. Conclusions. The US-guided approach showed similar satisfactory effect as the FL-guided block. Ultrasonography can be an alternative method for its convenience and efficacy in deep cervical plexus block for CeH patients without radiation exposure. Qing Wan, Haiyun Yang, Xiao Li, Caina Lin, Songjian Ke, Shaoling Wu, and Chao Ma Copyright © 2017 Qing Wan et al. All rights reserved. Semiquantitative Evaluation of Extrasynovial Soft Tissue Inflammation in the Shoulders of Patients with Polymyalgia Rheumatica and Elderly-Onset Rheumatoid Arthritis by Power Doppler Ultrasound Wed, 15 Feb 2017 08:42:38 +0000 Objectives. To develop a scoring system for evaluating the extrasynovial soft tissue inflammation of the shoulders in patients with polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis with PMR-like onset (pm-EORA) using ultrasound. Methods. We analyzed stored power Doppler (PD) images obtained by the pretreatment examination of 15 PMR patients and 15 pm-EORA patients. A semiquantitative scoring system for evaluating the severity of PD signals adjacent to the anterior aspect of the subscapularis tendon was designed. Results. A four-point scale scoring for the hyperemia on the subscapularis tendon was proposed as follows in brief: 0 = absent or minimal flow, 1 = single vessel dots or short linear-shape signals, 2 = long linear-shape signals or short zone-shape signals, or 3 = long zone-shape signals. This scoring system showed good intra- and interobserver reliability and good correlation to quantitative pixel-counting evaluation. By using it, we demonstrated that inflammation in PMR is dominantly localized in extrasynovial soft tissue as compared with pm-EORA. Conclusions. We proposed a reliable semiquantitative scoring system using ultrasound for the evaluation of extrasynovial soft tissue inflammation of the shoulders in patients with both PMR and pm-EORA. This system is simple to use and can be utilized in future investigations. Takeshi Suzuki, Ryochi Yoshida, Akiko Okamoto, and Yu Seri Copyright © 2017 Takeshi Suzuki et al. All rights reserved. Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis Mon, 13 Feb 2017 00:00:00 +0000 Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD16− monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6. Inês P. Perpétuo, Joana Caetano-Lopes, Ana Maria Rodrigues, Raquel Campanilho-Marques, Cristina Ponte, Helena Canhão, Mari Ainola, and João E. Fonseca Copyright © 2017 Inês P. Perpétuo et al. All rights reserved. Ultrasonographic Validation of Anatomical Landmarks for Localization of the Tendon of the Long Head of Biceps Brachii Sun, 12 Feb 2017 07:15:22 +0000 Objectives. To establish anatomical landmarks for biceps tendon groove localization based on intrinsic anatomical relations and to validate the localization with ultrasonographic measurement. Design. Perspective, observational, single-blinded pilot study. Participants. 25 healthy male and female volunteers ages 24–50 years. Methods. We used two anatomical landmarks, the medial epicondyle vertical line related landmark and the coracoid process landmark. The distance from the groove skin mark to the medial epicondyle vertical line and the coracoid process was measured horizontally and was measured at 0° and 45° of shoulder external rotation, respectively. Results. Medial epicondyle vertical lines were 9.3 mm/21.5 mm medial to the groove at 0°/45° of shoulder external rotation, respectively. Correlation coefficients were 0.04/0.10, 0.32/0.42, and 0.26/0.37 for weight, height, and BMI in 0°/45° of shoulder external rotation, respectively. The distance between the coracoid process and the groove was 44.0 mm/62.2 mm in 0°/45° of shoulder external rotation, respectively. Correlation coefficients were 0.36/0.41, 0.36/0.54, and 0.18/0.12 for weight, height, and BMI in 0°/45° of shoulder external rotation, respectively. Conclusions. The medial epicondyle vertical line and the coracoid process landmark are both useful anatomical landmarks to localize the biceps groove. The anatomical landmark based localization is essentially not correlated with subject’s weight, height, or BMI. Saiyun Hou, John Harrell, and Sheng Li Copyright © 2017 Saiyun Hou et al. All rights reserved. Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure? Sun, 12 Feb 2017 00:00:00 +0000 Background. Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods. The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results. Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research. Claudia Celletti, Filippo Camerota, Marco Castori, Federica Censi, Laura Gioffrè, Giovanni Calcagnini, and Stefano Strano Copyright © 2017 Claudia Celletti et al. All rights reserved. Ultrasonic Measurement of Dynamic Muscle Behavior for Poststroke Hemiparetic Gait Mon, 23 Jan 2017 09:32:56 +0000 Quantitative evaluation of the hemiparesis status for a poststroke patient is still challenging. This study aims to measure and investigate the dynamic muscle behavior in poststroke hemiparetic gait using ultrasonography. Twelve hemiparetic patients walked on a treadmill, and EMG, joint angle, and ultrasonography were simultaneously recorded for the gastrocnemius medialis muscle. Pennation angle was automatically extracted from ultrasonography using a tracking algorithm reported previously. The characteristics of EMG, joint angle, and pennation angle in gait cycle were calculated for both (affected and unaffected) sides of lower limbs. The results suggest that pennation angle could work as an important morphological index to continuous muscle contraction. The change pattern of pennation angle between the affected and unaffected sides is different from that of EMG. These findings indicate that morphological parameter extracted from ultrasonography can provide different information from that provided by EMG for hemiparetic gait. Xin Chen, Xudong Zhang, Wenxiu Shi, Jun Wang, Yun Xiang, Yongjin Zhou, and Wan-Zhang Yang Copyright © 2017 Xin Chen et al. All rights reserved. PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue Mon, 16 Jan 2017 11:24:42 +0000 Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation. P. Klinger, S. Lukassen, F. Ferrazzi, A. B. Ekici, T. Hotfiel, B. Swoboda, T. Aigner, and K. Gelse Copyright © 2017 P. Klinger et al. All rights reserved. Early Detection of Tibial Cartilage Degradation and Cancellous Bone Loss in an Ovariectomized Rat Model Sun, 15 Jan 2017 14:20:48 +0000 This study aimed to investigate degradation of the articular cartilage and loss of the cancellous bone in an ovariectomized (OVX) rat model simulating early human menopausal stage. Fourteen health female Sprague-Dawley rats were randomly divided into two groups ( per group): an OVX group that underwent bilateral ovariectomy to create an OVX model with low estrogen levels and a sham group in which only the periovarian fatty tissue was exteriorized. All the animals were sacrificed at 3 weeks after ovariectomy. The left tibiae were harvested. The articular cartilage at medial tibial plateau (MTP) and lateral tibial plateau (LTP) was assessed with quantitative high-frequency ultrasound. The cancellous bone was evaluated with micro-CT. The results indicated that, in comparison with the sham rats, the OVX rats exhibited significant alterations in acoustic parameters of the articular cartilage but insignificant changes in microarchitectural parameters of the cancellous bone in early stage of low estrogen levels. The results of this study suggest that cartilage degradation induced by estrogen reduction was detected earlier with quantitative ultrasound than that of the cancellous bone loss in 3 wk OVX rats. Yinong Wang, Zhiwei Liu, Qing Wang, Qianjin Feng, and Wufan Chen Copyright © 2017 Yinong Wang et al. All rights reserved. Transverse and Oblique Long Bone Fracture Evaluation by Low Order Ultrasonic Guided Waves: A Simulation Study Sun, 15 Jan 2017 07:58:02 +0000 Ultrasonic guided waves have recently been used in fracture evaluation and fracture healing monitoring. An axial transmission technique has been used to quantify the impact of the gap breakage width and fracture angle on the amplitudes of low order guided wave modes and under a 100 kHz narrowband excitation. In our two dimensional finite-difference time-domain (2D-FDTD) simulation, the long bones are modeled as three layers with a soft tissue overlay and marrow underlay. The simulations of the transversely and obliquely fractured long bones show that the amplitudes of both and decrease as the gap breakage widens. Fixing the crack width, the increase of the fracture angle relative to the cross section perpendicular to the long axis enhances the amplitude of , while the amplitude of shows a nonmonotonic trend with the decrease of the fracture angle. The amplitude ratio between the and modes is used to quantitatively evaluate the fracture width and angles. The study suggests that the low order guided wave modes and have potentials for transverse and oblique bone fracture evaluation and fracture healing monitoring. Ying Li, Dan Liu, Kailiang Xu, Dean Ta, Lawrence H. Le, and Weiqi Wang Copyright © 2017 Ying Li et al. All rights reserved. Gray Matter Atrophy within the Default Mode Network of Fibromyalgia: A Meta-Analysis of Voxel-Based Morphometry Studies Mon, 26 Dec 2016 11:10:46 +0000 Over the years, studies have demonstrated morphological changes in the brain of fibromyalgia (FMS). We aimed to conduct a coordinate-based meta-analytic research through systemic review on voxel-based morphometry (VBM) imaging results to identify consistent gray matter (GM) difference between FMS patients and healthy subjects. We performed a comprehensive literature search in PubMed (January 2000–December 2015) and included six VBM publication on FMS. Stereotactic data were extracted from 180 patients of FMS and 123 healthy controls. By means of activation likelihood estimation (ALE) technique, regional GM reduction in left medial prefrontal cortex and right dorsal posterior cingulate cortex was identified. Both regions are within the default mode network. In conclusion, the gray matter deficit is related to the both affective and nonaffective components of pain processing. This result also provided the neuroanatomical correlates for emotional and cognitive symptoms in FMS. Chemin Lin, Shwu-Hua Lee, and Hsu-Huei Weng Copyright © 2016 Chemin Lin et al. All rights reserved. Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor Sun, 18 Dec 2016 14:18:48 +0000 Objective. Prenatal glucocorticoids (GC) can induce long term effects on offspring health. However, reports and related studies regarding the prolonged effects of prenatal GC on the development of autoimmunity are limited. Here, we aimed to explore the immunological effects of dexamethasone (DEX) exposure on young adults and whether glucocorticoid receptor (GR) is involved in this process. Methods. Wistar rats were given DEX during pregnancy. Susceptibility to autoimmunity in offspring was assessed using experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis (AIA) animal models. To reveal the possible mechanism, glucocorticoid response, GR expression, and methylation status were measured in peripheral blood mononuclear cells (PBMCs). Results. Our results showed that the DEX-treated rats had greater susceptibility to EAE (100% versus 62.5%, ) and AIA (63.6% versus 0%, ) than saline control group. Glucocorticoid response and GR expression were decreased in DEX rats. Significant difference was also found in the methylation levels of GR exon 1-10 to exon 1-11 region. Conclusions. Prenatal DEX administration increases the susceptibility to autoimmune diseases, which is potentially mediated by programming GR methylation status and glucocorticoid sensitivity. Yanhong Sun, Xiaoyan Wan, Juan Ouyang, Renfeng Xie, Xueping Wang, and Peisong Chen Copyright © 2016 Yanhong Sun et al. All rights reserved. Combination of Salivary Gland Ultrasonography and Virtual Touch Quantification for Diagnosis of Sjögren’s Syndrome: A Preliminary Study Sun, 18 Dec 2016 12:23:14 +0000 A total of 136 subjects (51 SS patients, 35 sicca syndrome patients without SS, and 50 healthy volunteers) were enrolled in this study. The mean SWV value for salivary glands of SS patients was statistically higher than that of controls (2.81 ± 0.66 m/s versus 1.85 ± 0.28 m/s for parotid glands and 2.29 ± 0.34 m/s versus 1.82 ± 0.25 m/s for submandibular glands, resp.). Combining SWV values of parotid and submandibular glands gives a sensitivity of 88.2% (95% CI: 76.1–95.6%) and specificity of 96.0% (95% CI: 86.3–99.5%) at the cutoff point of 2.19 m/s, with an AUROC of 0.954 (95% CI: 0.893–0.986). In addition, combining SGUS score and SWV value yields a sensitivity of 98.0% (95% CI: 89.6–100%), specificity of 90.0% (95% CI: 78.2–96.7%), and AUROC of 0.962 (95% CI: 0.904–0.990). Classification tree considering the sequential use of SGUS score and SWV value achieved 92.1% accuracy for diagnosis of SS. Similarly, the ROC curve of combined SGUS scores and SWV values yields an AUROC of 0.954 (95% CI: 0.885–0.987), sensitivity of 97.1% (95% CI: 85.1–99.9%), and specificity of 92.2% (95% CI: 81.1–97.8%) for separating sicca syndrome patients (without SS) from SS patients. Combining SGUS and VTQ provides a promising tool for diagnosis of SS. Shaoqi Chen, Yukai Wang, Guohong Zhang, and Shigao Chen Copyright © 2016 Shaoqi Chen et al. All rights reserved. Combined Ultrasound Imaging and Biomechanical Modeling to Estimate Triceps Brachii Musculotendon Changes in Stroke Survivors Thu, 08 Dec 2016 16:21:52 +0000 The aim of this study was to investigate the changes of musculotendon parameters of triceps brachii in persons after stroke based on subject-specific biomechanical modeling technique combined with in vivo ultrasound measurement. Five chronic stroke survivors and five normal control subjects were recruited. B-mode ultrasound was applied to measure muscle pennation angle and the optimal length of three heads of triceps’ brachii at different joint angle positions in resting and isometric contraction. Measured ultrasound data were used to reduce the unknown parameters during the modeling optimization process. The results showed that pennation angles varied with joint angles, and the longhead TRI pennation from stroke group was smaller than the literature value. The maximum isometric muscle stress from persons after stroke was significantly smaller than that found in the unimpaired subjects. The prediction of joint torque fits well with the measured data from the control group, whereas the prediction error is larger in results from persons after stroke. In vivo parameters from ultrasound data could help to build a subject-specific biomechanical model of elbow extensor for both unimpaired and hemiplegic subjects, and then the results driven from the model could enhance the understanding of motor function changes for persons after stroke. Le Li and Raymond Kai-yu Tong Copyright © 2016 Le Li and Raymond Kai-yu Tong. All rights reserved. Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients Mon, 05 Dec 2016 11:18:51 +0000 Lupus nephritis is one of the most severe Systemic Lupus Erythematosus features, defining treatment modality and prognosis. Our retrospective study, including 178 patients treated for lupus nephritis during 23 years with mostly cyclophosphamide-based initial regimens followed by azathioprine or mycophenolic acid, demonstrates 84.8% of renal response with 19.2% of flares, 15-year patient survival 78.7% and kidney survival 76.3%, and low damage accrual. Both patient and kidney survival significantly differ for subgroups that achieved complete or partial renal response and nonresponders: patient 15-year survival 95% versus 65% versus 35%; kidney 15-year survival 100% versus 58% versus 0%, respectively. 51% (24 out of 47) of patients evaluated at the end of the study period sustained complete renal response; however, only 9 of them had 0 disease activity according to SELENA SLEDAI scale, while 13 patients had scores 2–4 due to the serological abnormalities only. We conclude that (1) initial treatment with cyclophosphamide followed by azathioprine is effective and can be used in agreement with International Guidelines until the evidence for biological treatments benefits becomes available; (2) complete and even partial renal response have positive prognostic value, and failure to achieve renal response negatively influences kidney and patient survival; (3) the validity of complete renal response in SLE is questioned by the absence of conventional definition of SLE remission. Elena V. Zakharova, Tatiana A. Makarova, Elena V. Zvonova, Alina M. Anilina, and Ekaterina S. Stolyarevich Copyright © 2016 Elena V. Zakharova et al. All rights reserved. Rebamipide, an Amino Acid Analog of 2(1H)-Quinolinone, Inhibits the Formation of Human Osteoclasts Mon, 14 Nov 2016 13:38:59 +0000 Objectives. Drug repositioning or drug reprofiling (DR) has recently been growing in importance. DR has a significant advantage over traditional drug development because the repositioned drug has already passed toxicity tests; its safety is known, and the risk of adverse toxicology is reduced. In the current study, we investigated the role of rebamipide, a mucosa-protecting agent, with recently reported anti-inflammatory function, in human osteoclastogenesis. Methods. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of M-CSF and sRANKL. Osteoclast formation was evaluated by immunohistological staining for CD51/61 (vitronectin receptors). Osteoclast formation, in the presence or absence of rebamipide (0, 1, and 3 mM), was observed by time-lapse photography and actin ring formation. The number of absorption sites and area of absorption were calculated using Osteologic™ plates. Pit formation was studied by 3D-SEM. Results. Rebamipide inhibited human osteoclast formation at 3 mM, a pharmacological concentration, and inhibited resorbing activity dose-dependently. Rebamipide induced the degradation of actin rings in mature osteoclasts. This mechanism may involve inhibiting the osteoclast fusion pathway through reducing the expression of DC-specific transmembrane protein (DC-STAMP). Conclusions. The present study suggests that rebamipide would be useful as a novel agent for osteoporosis and rheumatoid arthritis. Yuki Nanke, Tsuyoshi Kobashigawa, Toru Yago, Manabu Kawamoto, Hisashi Yamanaka, and Shigeru Kotake Copyright © 2016 Yuki Nanke et al. All rights reserved. RANK Expression and Osteoclastogenesis in Human Monocytes in Peripheral Blood from Rheumatoid Arthritis Patients Sun, 16 Oct 2016 08:31:04 +0000 Rheumatoid arthritis (RA) appears as inflammation of synovial tissue and joint destruction. Receptor activator of NF-κB (RANK) is a member of the TNF receptor superfamily and a receptor for the RANK ligand (RANKL). In this study, we examined the expression of and CCR6 on CD14+ monocytes from patients with RA and healthy volunteers. Peripheral blood samples were obtained from both the RA patients and the healthy volunteers. Osteoclastogenesis from monocytes was induced by RANKL and M-CSF in vitro. To study the expression of and CCR6 on CD14+ monocytes, two-color flow cytometry was performed. Levels of expression of RANK on monocytes were significantly correlated with the level of osteoclastogenesis in the healthy volunteers. The expression of on CD14+ monocyte in RA patients without treatment was elevated and that in those receiving treatment was decreased. In addition, the high-level expression of RANK on CD14+ monocytes was correlated with the high-level expression of CCR6 in healthy volunteers. Monocytes expressing both RANK and CCR6 differentiate into osteoclasts. The expression of CD14+ in untreated RA patients was elevated. RANK and CCR6 expressed on monocytes may be novel targets for the regulation of bone resorption in RA and osteoporosis. Yuki Nanke, Tsuyoshi Kobashigawa, Toru Yago, Manabu Kawamoto, Hisashi Yamanaka, and Shigeru Kotake Copyright © 2016 Yuki Nanke et al. All rights reserved. The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis Wed, 21 Sep 2016 12:18:12 +0000 Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07–1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05–2.3; ), or CC (RR = 1.83; 95% CI = 1.07–3.14; ). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03–1.72; ). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF. A. J. Ruiz-Padilla, J. I. Gamez-Nava, A. M. Saldaña-Cruz, J. D. Murillo-Vazquez, M. L. Vazquez-Villegas, S. A. Zavaleta-Muñiz, B. T. Martín-Márquez, J. M. Ponce-Guarneros, N. A. Rodriguez Jimenez, A. Flores-Chavez, F. Sandoval-Garcia, J. C. Vasquez-Jimenez, E. G. Cardona-Muñoz, S. E. Totsuka-Sutto, and L. Gonzalez-Lopez Copyright © 2016 A. J. Ruiz-Padilla et al. All rights reserved. Effects of Berberine on NLRP3 and IL-1β Expressions in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation Mon, 05 Sep 2016 13:23:40 +0000 Background. Urate crystals-induced inflammation is a critical factor during the initiation of gouty arthritis. Berberine is well known for its anti-inflammatory activity. However, the underlying effects of berberine on monosodium urate crystals-induced inflammation remain obscure. Objectives. This study is set to explore the protective effect and mechanism of berberine on monosodium urate crystals-induced inflammation in human monocytic THP-1 cells. Methods. The mRNA levels of NLRP3 and IL-1β were measured by Real-Time PCR, and the protein levels of NLRP3 and IL-1β were determined by ELISA, Western blot, and immunofluorescence. Results. The NLRP3 and IL-1β expressions were significantly increased in model group compared to that in normal group (). Meanwhile, there was significant reduction in the expressions of NLRP3 and IL-1β mRNA in groups 6.25 μM berberine and 25 μM berberine when compared with model group (). Conclusions. Therefore, berberine alleviates monosodium urate crystals-induced inflammation by downregulating NLRP3 and IL-1β expressions. The regulatory effects of berberine may be related to the inactivation of NLRP3 inflammasome. Ya-Fei Liu, Cai-Yu-Zhu Wen, Zhe Chen, Yu Wang, Ying Huang, and Sheng-Hao Tu Copyright © 2016 Ya-Fei Liu et al. All rights reserved. Association between Toll-Like Receptor 4 Polymorphisms and Systemic Lupus Erythematosus Susceptibility: A Meta-Analysis Mon, 29 Aug 2016 11:53:37 +0000 Family aggregation was observed among systemic lupus erythematosus (SLE) cases, suggesting the genetic factor may contribute to the susceptibility. Toll-like receptors (TLR) play key role in human immune system; in order to gain better insight on the association between TLR4 polymorphisms and SLE risk, a meta-analysis was conducted. In total 4 case-control studies have been included, involving 503 SLE cases and 636 healthy controls. The association between TLR4 polymorphisms and SLE risk was evaluated by calculating pooled odd ratio (OR) and its 95% confidential interval (CI). The -test and statistic were used to estimate the degree of heterogeneity. Publication bias among enrolled studies was examined by using Egger’s test and Begg’s test. Overall, there was no evidence of positive association between SLE risk and D299G and T399I polymorphisms in TLR4. The meta-analysis reported a null association between TLR4 polymorphisms and SLE risk in included study populations, but the role of TLR4 polymorphisms in developing SLE among other populations remains undetermined. Moreover, some laboratory studies still discovered the involvement of TLR4 in SLE process. Therefore, the association between TLR4 polymorphisms and SLE risk requires further investigation both in laboratory and in epidemiological efforts. Weiping Hu, Senchao Wu, Yanlin Zhang, Keshav Raj Sigdel, Yong Lin, and Hongbin Zhong Copyright © 2016 Weiping Hu et al. All rights reserved. The Expression of Osteopontin and Wnt5a in Articular Cartilage of Patients with Knee Osteoarthritis and Its Correlation with Disease Severity Sun, 31 Jul 2016 11:00:37 +0000 Objectives. This study is undertaken to investigate the relation between osteopontin (OPN) and Wnt5a expression in the progression and pathogenesis of osteoarthritis (OA). Methods. 50 cartilage tissues from knee OA patients and normal controls were divided into four groups of severe, moderate, minor, and normal lesions based on the modified grading system of Mankin. Immunohistochemistry and real-time PCR were utilized to analyze the OPN and Wnt5a expression in articular cartilage. Besides, the relations between OPN and Wnt5a expression and the severity of OA were explored. Results. OPN and Wnt5a could be identified in four groups’ tissues. Amongst the groups, the intercomparisons of OPN expression levels showed statistical differences (). Besides, the intercomparisons of Wnt5a expression degrees showed statistical differences (), except that between the minor and normal groups (). The scores of Mankin were demonstrated to relate to OPN expression (, ) and Wnt5a expression in every group (, ). Also, a positive correlation can be observed between the OPN and Wnt5a expression (, ). Conclusion. In articular cartilage, the expressions of OPN and Wnt5a are positively related to progressive damage of knee OA joint. The correlation between Wnt5a and OPN might be important to the progression and pathogenesis of knee OA. Yusheng Li, Wenfeng Xiao, Minghua Sun, Zhenhan Deng, Chao Zeng, Hui Li, Tuo Yang, Liangjun Li, Wei Luo, and Guanghua Lei Copyright © 2016 Yusheng Li et al. All rights reserved. Effect of Anti-TNF Antibodies on Clinical Response in Rheumatoid Arthritis Patients: A Meta-Analysis Sun, 31 Jul 2016 09:24:46 +0000 Background. Antitumor necrosis factor (anti-TNF) drugs have been applied for rheumatoid arthritis (RA) treatment; however, patients having anti-drug antibodies (ADAbs) do not benefit from these drugs. The meta-analysis aims to comprehensively assess the relationship between ADAb positive (ADAb+) and anti-TNF response in RA patients. Methods. Observational studies comparing different clinical response between ADAb+ and ADAb negative groups were included. Odds ratio (OR) with its corresponding 95% confidence interval (CI) was used as effect size. Subgroup analyses stratified by TNF inhibitor types and assay methods for ADAb detection were performed. Results. Totally, 10 eligible studies containing 1806 subjects were included. ADAb+ was significantly associated with reduced anti-TNF response to RA at all the time points after follow-up (). Subgroup analysis also supported this significant association (), except for enzyme-linked immunosorbent assay (ELISA) group at 3 months, infliximab (INF) and enzyme-linked immunosorbent assay (ELISA) groups at 6 months, and Immunological Multi-Parameter Chip Technology (IMPACT) group at 12 months. Conclusion. ADAb+ was significantly associated with reduced clinical response in RA patients, and other alternatives should be considered in RA patients presenting ADAb+. Chunxiao Wu, Shengxu Wang, Peifeng Xian, Lu Yang, Ying Chen, and Xianjie Mo Copyright © 2016 Chunxiao Wu et al. All rights reserved. Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk? Mon, 27 Jun 2016 09:36:31 +0000 Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA), primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE), dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren’s syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors. Sujani Yadlapati and Petros Efthimiou Copyright © 2016 Sujani Yadlapati and Petros Efthimiou. All rights reserved. MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis Sun, 26 Jun 2016 13:28:32 +0000 MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway. Ying Chen, Pei-Feng Xian, Lu Yang, and Sheng-Xu Wang Copyright © 2016 Ying Chen et al. All rights reserved. Oxidative Stress Relevance in the Pathogenesis of the Rheumatoid Arthritis: A Systematic Review Tue, 31 May 2016 13:01:48 +0000 Rheumatoid arthritis (RA) is an autoimmune inflammatory disease whose pathogenic mechanisms remain to be elucidated. The oxidative stress and antioxidants play an important role in the disease process of RA. The study of oxidants and antioxidants biomarkers in RA patients could improve our understanding of disease pathogenesis; likely determining the oxidative stress levels in these patients could prove helpful in assessing disease activity and might also have prognostic implications. To date, the usefulness of oxidative stress biomarkers in RA patients is unclear and the evidence supporting them is heterogeneous. In order to resume and update the information in the status of oxidants and antioxidants and their connection as biomarkers in RA, we performed a systematic literature search in the PubMed database, including clinical trials published in the last five years using the word combination “rheumatoid arthritis oxidative stress”. In conclusion, this review supports the fact that the oxidative stress is an active process in RA pathogenesis interrelated to other better known pathogenic elements. However, some controversial results preclude a definite conclusion. Celia María Quiñonez-Flores, Susana Aideé González-Chávez, Danyella Del Río Nájera, and César Pacheco-Tena Copyright © 2016 Celia María Quiñonez-Flores et al. All rights reserved. Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis Thu, 26 May 2016 13:18:39 +0000 Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis. Tong-ling Yuan, Jin Chen, Yan-li Tong, Yan Zhang, Yuan-yuan Liu, James Cheng-Chung Wei, Yi Liu, Yi Zhao, and Martin Herrmann Copyright © 2016 Tong-ling Yuan et al. All rights reserved. Ratio of Circulating IFNγ+ “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project Thu, 12 May 2016 11:31:12 +0000 Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. Shigeru Kotake, Yuki Nanke, Toru Yago, Manabu Kawamoto, Tsuyoshi Kobashigawa, and Hisashi Yamanaka Copyright © 2016 Shigeru Kotake et al. All rights reserved. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161+Th1 Cells) to CD161+Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients Wed, 30 Mar 2016 14:20:34 +0000 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161+Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161+Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase. Shigeru Kotake, Yuki Nanke, Toru Yago, Manabu Kawamoto, Tsuyoshi Kobashigawa, and Hisashi Yamanaka Copyright © 2016 Shigeru Kotake et al. All rights reserved. Clinical Manifestations and Myositis-Specific Autoantibodies Associated with Physical Dysfunction after Treatment in Polymyositis and Dermatomyositis: An Observational Study of Physical Dysfunction with Myositis in Japan Tue, 26 Jan 2016 13:10:20 +0000 Objective. The physical function of PM/DM patients after remission induction therapy remains unknown adequately. The aim of our study was to evaluate the present status of physical dysfunction and to clarify the clinical manifestations and myositis-specific autoantibodies (MSAs) associated with physical dysfunction after treatment in PM/DM. Methods. We obtained clinical data including the age at disease onset, gender, disease duration, laboratory data prior to initial treatment, and the specific treatment administered. We evaluated disease activity and physical dysfunction after treatment using the core set provided by the International Myositis Assessment and Clinical Studies Group. Results. 57% of the 77 enrolled patients with PM/DM had troubles in daily living after treatment. At the enrolment, disease activity evaluated by physicians was only revealed in 20% of patients. In a multivariate analysis, the age at disease onset, female gender, and CK levels before treatment were significantly associated with the severity of physical dysfunction after treatment. Anti-SRP positivity was associated with more severe physical dysfunction after treatment than anti-ARS or anti-MDA5. Conclusions. Half of the PM/DM patients showed physical dysfunction after treatment. Age at disease onset, gender, CK level before treatment, and anti-SRP were significant predictors associated with physical dysfunction after treatment in PM/DM. Hidenaga Kawasumi, Takahisa Gono, Yasushi Kawaguchi, Masataka Kuwana, Hirotaka Kaneko, Yasuhiro Katsumata, Sayuri Kataoka, Masanori Hanaoka, and Hisashi Yamanaka Copyright © 2016 Hidenaga Kawasumi et al. All rights reserved. Establishment of a Rat Adjuvant Arthritis-Interstitial Lung Disease Model Mon, 04 Jan 2016 06:28:02 +0000 Introduction. Development of an animal model of rheumatoid arthritis-interstitial lung disease (RA-ILD) and improved knowledge of the pathogenesis of RA-ILD may facilitate earlier diagnosis and the development of more effective targeted therapies. Methods. Adult male Wistar rats were studied in an adjuvant arthritis (AA) model induced by the injection of Freund’s complete adjuvant (FCA). Rats were sacrificed on days 7, 14, 21, and 28 after FCA injection. Lung tissue was obtained for histopathological examination and evaluation of Caveolin-1 (Cav-1) and transforming growth factor-β (TGF-β1) protein expression levels. Results. Pulmonary inflammation was evident in lung tissue from day 21 after FCA injection. Inflammation and mild fibrosis were observed in lung tissue on day 28 after FCA injection. Cav-1 protein expression was significantly decreased from day 7 through day 28 and TGF-β1 protein expression was significantly increased on day 28 after FCA injection compared to control (). Conclusion. We established an AA rat model that exhibited the extra-articular complication of RA-ILD. We identified Cav-1 and TGF-β1 as protein biomarkers of RA-ILD in this model and propose their signaling pathway as a possible target for therapeutic intervention. Liu-nan Song, Xiao-dan Kong, Hong-jiang Wang, and Li-bin Zhan Copyright © 2016 Liu-nan Song et al. All rights reserved. CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells Mon, 30 Nov 2015 13:59:29 +0000 MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-B ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA. Weixia Jing, Xuewu Zhang, Wenyan Sun, Xiujuan Hou, Zhongqiang Yao, and Yuelan Zhu Copyright © 2015 Weixia Jing et al. All rights reserved. Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice Sun, 29 Nov 2015 12:30:01 +0000 Human and murine lymphocytes express dopamine (DA) D2-like receptors including DRD2, DRD3, and DRD4. However, their roles in rheumatoid arthritis (RA) are less clear. Here we showed that lymphocyte DRD2 activation alleviates both imbalance of T-helper (Th)17/T-regulatory (Treg) cells and inflamed symptoms in a mouse arthritis model of RA. Collagen-induced arthritis (CIA) was prepared by intradermal injection of chicken collagen type II (CII) in tail base of DBA/1 mice or Drd2−/− C57BL/6 mice. D2-like receptor agonist quinpirole downregulated expression of proinflammatory Th17-related cytokines interleukin- (IL-) 17 and IL-22 but further upregulated expression of anti-inflammatory Treg-related cytokines transforming growth factor- (TGF-) β and IL-10 in lymphocytes in vitro and in ankle joints in vivo in CIA mice. Quinpirole intraperitoneal administration reduced both clinical arthritis score and serum anti-CII IgG level in CIA mice. However, Drd2−/− CIA mice manifested more severe limb inflammation and higher serum anti-CII IgG level and further upregulated IL-17 and IL-22 expression and downregulated TGF-β and IL-10 expression than wild-type CIA mice. In contrast, Drd1−/− CIA mice did not alter limb inflammation or anti-CII IgG level compared with wild-type CIA mice. These results suggest that DRD2 activation is involved in alleviation of CIA symptoms by amelioration of Th17/Treg imbalance. Jian-Hua Lu, Yi-Qian Liu, Qiao-Wen Deng, Yu-Ping Peng, and Yi-Hua Qiu Copyright © 2015 Jian-Hua Lu et al. All rights reserved. Fear of Falling in Women with Fibromyalgia and Its Relation with Number of Falls and Balance Performance Thu, 05 Nov 2015 11:53:27 +0000 Objective. To evaluate fear of falling, number of falls, and balance performance in women with FM and to examine the relationship between these variables and others, such as balance performance, quality of life, age, pain, and impact of fibromyalgia. Methods. A total of 240 women participated in this cross-sectional study. Of these, 125 had fibromyalgia. Several variables were assessed: age, fear of falling from 0 to 100, number of falls, body composition, balance performance, lower limb strength, health-related quality of life, and impact of fibromyalgia. Results. Women with fibromyalgia reported more falls and more fear of falling. Fear of falling was associated with number of falls in the last year, stiffness, perceived balance problems, impact of FM, and HRQoL whereas the number of falls was related to fear of falling, balance performance with eyes closed, pain, tenderness to touch level, anxiety, self-reported balance problems, impact of FM, and HRQoL. Conclusion. FM has an impact on fear of falling, balance performance, and number of falls. Perceived balance problems seem to be more closely associated with fear of falling than objective balance performance. D. Collado-Mateo, J. M. Gallego-Diaz, J. C. Adsuar, F. J. Domínguez-Muñoz, P. R. Olivares, and N. Gusi Copyright © 2015 D. Collado-Mateo et al. All rights reserved. Nailfold Capillaroscopy in Rheumatic Diseases: Which Parameters Should Be Evaluated? Tue, 01 Sep 2015 13:52:28 +0000 Video nailfold capillaroscopy (NFC), considered as an extension of the widefield technique, allows a more accurate measuring and storing of capillary data and a better defining, analyzing, and quantifying of capillary abnormalities. Capillaroscopic study is often performed on the patients suspected of having microcirculation problems such as Raynaud’s phenomenon as the main indication for nailfold capillaroscopy. Capillaroscopic findings based on microcirculation studies can provide useful information in the fields of pathophysiology, differential diagnosis, and monitoring therapy. Nailfold capillaroscopy provides a vital assessment in clinical practices and research; for example, its reputation in the early diagnosis of systemic sclerosis is well established and it is also used as a classification criterion in this regard. This review focuses on the manner of performing video nailfold capillaroscopy and on a common approach for measuring capillary dimensions in fingers and toes. Mahnaz Etehad Tavakol, Alimohammad Fatemi, Abdolamir Karbalaie, Zahra Emrani, and Björn-Erik Erlandsson Copyright © 2015 Mahnaz Etehad Tavakol et al. All rights reserved. The Application of Fluorescence Optical Imaging in Systemic Sclerosis Tue, 18 Aug 2015 17:27:11 +0000 Objective. The aim of this study was to visualize soft tissue inflammation using FOI on patients with Systemic Sclerosis (SSc) characterized by SSc-related Raynaud’s phenomenon and to detect the therapeutic response to treatment with iloprost or alprostadil. Methods. Twenty-one patients with SSc and Raynaud’s phenomenon and twenty-six healthy controls were prospectively included. The SSc patients were intravenously treated with iloprost or alprostadil over seven days. FOI was performed at baseline and after seven days using an intravenous application of indocyanine green (ICG). The hands were divided into nineteen segments per hand. All segments were quantitatively evaluated to determine changes in ICG. Results. The sensitivity and specificity of FOI in the detection of ICG enhancement in patients with SSc were 95% versus 96%. At baseline, 31.5% hand segments showed ICG enhancement. After seven days of either iloprost or alprostadil therapy a significant reduction in the ICG was observed which ranged from 40.9% to 24.7%. Conclusion. The study demonstrates that the FOI technique is able to visualize soft-tissue inflammation with both high sensitivity and specificity. The anti-inflammatory therapeutic effects of iloprost were slightly stronger than alprostadil. FOI offers promising benefits in the diagnosis and therapy of patients with SSc-associated Raynaud’s phenomenon. Alexander Pfeil, Karl F. Drummer, Joachim Böttcher, Christian Jung, Peter Oelzner, Diane M. Renz, Marcus Franz, Andreas Hansch, and Gunter Wolf Copyright © 2015 Alexander Pfeil et al. All rights reserved. Spine and Rheumatic Diseases Tue, 28 Jul 2015 07:44:01 +0000 James Cheng-Chung Wei, Yi Liu, Hsi-Kai Tsou, and Irene Eva van der Horst-Bruinsma Copyright © 2015 James Cheng-Chung Wei et al. All rights reserved. MUTYH Gene Polymorphisms as Risk Factors for Rheumatoid Arthritis Mon, 27 Jul 2015 12:56:58 +0000 Objectives. MUTYH glycosylase involved in DNA repair pathways may be associated with the risk of autoimmune diseases such as rheumatoid arthritis (RA). Therefore, the association between polymorphisms in the MUTYH gene and RA was evaluated. Methods. We recruited 192 RA patients and 192 healthy subjects in Taiwan. The 4 MUTYH polymorphisms (rs3219463, rs3219476, rs3219489, and rs3219493) were detected and haplotype analysis was performed using the Bayesian method. The genotype and allelic frequency distributions of the polymorphisms in both RA patients and healthy patients were compared by the chi-square test. Results. Comparison of the genotype/allele frequencies between individuals with RA and the control groups revealed significant differences in 2 MUTYH gene polymorphisms, rs3219463 and rs3219476. After we performed a haplotype-specific analysis, the haplotypes Ht6-GTGC and Ht8-GGCG had lower presenting rates in RA patients than in the control groups. Furthermore, the genotype frequency of rs3219463 G/  was significantly increased among patients with immunoglobulin M rheumatoid factors, whereas that of rs3219476 was not. Conclusion. We demonstrated that the rs3219463 and rs3219476 polymorphisms in RA patients from a Taiwan Chinese population were associated with disease susceptibility. These data indicate that the MUTYH gene may play a role in the progression of RA. Yung-Jen Kung, Kun Shi Tsai, Chung-Ming Huang, Hui-Ju Lin, Ter-Hsin Chen, Yu-An Hsu, Ching-Yao Chang, Yong-San Huang, and Lei Wan Copyright © 2015 Yung-Jen Kung et al. All rights reserved. The Anthropometric Measurement of Schober’s Test in Normal Taiwanese Population Mon, 27 Jul 2015 12:02:10 +0000 The measurement of lower back mobility is essential in the assessment of lower back pain including ankylosing spondylitis. Original Schober’s test (OST) and modified Schober’s test (MST) are popularly conducted in daily rheumatology and orthopedics clinical practices. To our knowledge, this report is the only anthropometric reference study in a normal oriental population. The OST declined with age from 5.0 cm in the youngest (20–30 years old) to 3.1 cm in the aged (70–80 years old) male subjects and from 3.6 cm to 2.4 cm in the female subjects. The male OST was significantly more than the female OST. There was a good correlation between OST and MST in each of the three age groups of both sexes. Yong-Ren Yen, Jin-Fan Luo, Ming-Li Liu, Fung-Jou Lu, and Soo-Ray Wang Copyright © 2015 Yong-Ren Yen et al. All rights reserved. Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients Mon, 27 Jul 2015 11:27:22 +0000 T-614 (also named as iguratimod), a novel antirheumatic drug, could attenuate joint inflammation and articular damage in rheumatoid arthritis (RA) patients, providing a new therapy for RA. Here, we tested the role T-614 on the IL-6-induced receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG), IL-17, and MMP-3 expression in synovial fibroblasts from rheumatoid arthritis (RASFs) patients. T-614 decreased RANKL expression and RANKL/OPG ratio in IL-6-induced RASFs. We confirmed this effect by a decrease of the mRNA and protein RANKL and mRNA RANKL/OPG in RASFs exposed in vitro to T-614 or MTX. Markedly decreased levels of IL-17, retinoid-related orphan receptor C (RORc), and MMP-3 mRNA expression were also observed in IL-6-induced RASFs in the presence of T-614 or MTX compared with those in its absence. Furthermore, T-614 blocked expression of p-ERK1/2 protein without affecting ERK1/2 expression, indicating that the way that T-614 regulated RANKL expression might be ERK1/2 pathway. Our results suggest that T-614 yields a strong improvement in arthritis via exact suppression of RANKL/OPG, IL-17, and MMP-3 expression in RASFs. Yu Wei, Xiaoxun Sun, Minhui Hua, Wenfeng Tan, Fang Wang, and Miaojia Zhang Copyright © 2015 Yu Wei et al. All rights reserved. Disorders of MicroRNAs in Peripheral Blood Mononuclear Cells: As Novel Biomarkers of Ankylosing Spondylitis and Provocative Therapeutic Targets Sun, 26 Jul 2015 12:48:19 +0000 Background. MicroRNAs can potentially regulate every aspect of cellular activity. In this study, we investigated whether AS pathogenesis involves microRNAs disorders. Result. The expression of 2 microRNAs, hsa-miR-126-3p and hsa-miR-29a, was significantly lower in active AS group before etanercept therapy than in control group. Marched fold changes of them were 3.76 and 16.22. Moreover, expressions of hsa-miR-126-3p and hsa-miR-29a were dramatically upregulated after 12-weeks etanercept treatment. Fold changes were 2.20 and 3.18. All regulations of microRNAs expression mentioned before were statistically significant (fold change >2 and ). The expression disorders of the 2 microRNAs did not statistically significantly correlated with BASDAI, CRP, and ESR. Conclusion. AS pathogenesis involved dysregulation of microRNAs. Hsa-miR-126-3p and hsa-miR-29a will probably become the potential biomarkers and provocative therapeutic targets of AS. Qing Lv, Qiuxia Li, Peizhuo Zhang, Yingjuan Jiang, Xinwei Wang, Qiujing Wei, Shuangyan Cao, Zetao Liao, Zhiming Lin, Yunfeng Pan, Jianlin Huang, Tianwang Li, Ou Jin, Yuqiong Wu, and Jieruo Gu Copyright © 2015 Qing Lv et al. All rights reserved. Serum Vitamin D and Pyridinoline Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in Patients with Ankylosing Spondylitis Sun, 26 Jul 2015 12:48:16 +0000 Objective. To assess the serum vitamin D and ICTP levels in patients with ankylosing spondylitis (AS) and investigate their relationship with disease activity and bone mineral density (BMD). Method. 150 patients and 168 controls were included. Serum 25(OH)D, ICTP, C-reaction protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Hip BMD were assessed in patients. 25(OH)D and ICTP were detected in controls. Results. The serum 25(OH)D in AS was 57.92 ± 24.42 nmol/L, significantly lower than controls (91.24 ± 42.02 nmol/L). Serum ICTP in AS was 5.72 ± 3.88 ug/L, significantly higher than controls (3.69 ± 1.26 ug/L). ICTP level was higher in men than in women patients (6.07 ± 4.05 versus 3.84 ± 1.96 ug/L, ); it was also higher in JAS than in AAS (9.52 ± 3.79 versus 5.27 ± 3.65 ug/L, ). Furthermore, 25(OH)D was negatively correlated with ICTP. Low 25(OH)D and high ICTP were one of the reasons of AS patients’ low hip BMD. Besides, a significant relationship was found between serum ICTP and CRP. Conclusion. There was a high incidence of vitamin D inadequacy in AS. Serum ICTP level was elevated in AS, especially in JAS and male patients. 25(OH)D and ICTP seem to be valuable markers to detect bone loss in AS. Pingping Zhang, Qiuxia Li, Qiujing Wei, Zetao Liao, Zhiming Lin, Linkai Fang, and Jieruo Gu Copyright © 2015 Pingping Zhang et al. All rights reserved. Management of Deep Infection after Instrumentation on Lumbar Spinal Surgery in a Single Institution Sun, 26 Jul 2015 12:42:00 +0000 Postoperative surgical site infections (SSIs) are more common complications after spinal surgery. SSIs often require extended hospitalisation and may worsen overall clinical outcomes. A retrospective database review of consecutive patients with traditional open lumbar spinal surgery was performed. SSIs patients were identified and reviewed for clinically relevant details, and postoperative SSIs’ incidence was calculated for the entire cohort as well as for subgroups with or without spinal implants. In 15 years, 1,176 patients underwent open lumbar spinal surgery with spinal implants and 699 without. Thirty-eight developed postoperative SSIs. Total SSI rate for the entire group was 2.03%. The incidence of postoperative SSIs in the nonimplant group was relatively low. Patients received antibiotics, hyperbaric oxygen therapy, and wet dressing. We provided the precise rates of postoperative SSIs in traditional open spinal surgery obtained from a single-centre data. Patients with spinal implants had higher SSIs’ incidence than those without. Jung-Tung Liu, Wen-Jui Liao, Cheng-Siu Chang, and Yung-Hsiang Chen Copyright © 2015 Jung-Tung Liu et al. All rights reserved. Clinical Features in Juvenile-Onset Ankylosing Spondylitis Patients Carrying Different B27 Subtypes Sun, 26 Jul 2015 11:57:31 +0000 Background. Ankylosing spondylitis (AS) is a common rheumatic disease and is characterized by inflammation of the axial skeleton. HLA-B27 is strongly associated with AS. Juvenile-onset AS (JAS) with disease onset before 16 years of age differs from adult-onset AS (AAS) in many respects. Objective. To compare the clinical features in JAS with different B27 subtypes and analyze the differences between JAS and AAS. Methods. 145 JAS and 360 AAS patients were included. The demographic data, clinical manifestations, laboratory markers, Bath AS indices, and B27 subtypes were recorded. Results. Peripheral arthritis, enthesitis, BASDAI, ESR, and CRP were significantly higher in JAS patients with HLA-2704 than those with B27-negative. Enthesitis and ESR were significantly higher in patients with HLA-2705 than those with B27-negative. The onset age of HLA-2715 group was much earlier than the other groups. The peripheral arthritis, enthesitis, and hip joint involvement in JAS with HLA-2704 were significantly higher than those in AAS with HLA-2704. Conclusion. JAS with different B27 subtypes had similar features in most of manifestations; JAS and AAS patients with the same subtype could have distinctive courses. Early diagnosis, hip detection, and control of systemic active inflammation in JAS patients will be helpful for improving the prognosis. Yikun Mou, Pingping Zhang, Qiuxia Li, Zhiming Lin, Zetao Liao, Qiujing Wei, and Jieruo Gu Copyright © 2015 Yikun Mou et al. All rights reserved. Association between Hyperuricemia and Metabolic Syndrome: An Epidemiological Study of a Labor Force Population in Taiwan Sun, 26 Jul 2015 11:53:53 +0000 The increasing prevalence of metabolic syndrome (MetS) has become an important issue worldwide. Metabolic comorbidities of hypertension, obesity, and hyperlipidemia are shown as important risk factors for incident gout. The purpose of this study was to investigate the relationship between hyperuricemia and MetS. This is a cross-sectional study. The effective sample included 21,544 individuals who received worker health examinations at a local teaching hospital in Changhua County from 2008~2012. We used multiple logistic regression analysis to investigate the influences of hyperuricemia on MetS. The results showed that individuals with MetS had significantly higher blood pressure, fasting plasma glucose, triglycerides, waist circumference, and high-density lipoprotein cholesterol than those without MetS . Multiple logistic regression analysis revealed hyperuricemia to be an important factor of MetS. The risk of developing MetS is higher with high levels of serum uric acid (SUA) and the odds ratio (OR) of having MetS is 4.98 times higher for Tertile 3 than for Tertile 1 (95% CI = 4.16–5.97) and 4 times higher for Quartile 4 than for Quartile 1 (95% CI = 3.59–4.46). In conclusion, males are more likely to develop MetS than females, and the risk of having MetS increases with age and SUA concentration. Cheng-Yu Wei, Chia-Cheng Sun, James Cheng-Chung Wei, Hsu-Chih Tai, Chien-An Sun, Chian-Fang Chung, Yu-Ching Chou, Pi-Li Lin, and Tsan Yang Copyright © 2015 Cheng-Yu Wei et al. All rights reserved. Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients Sun, 26 Jul 2015 10:04:46 +0000 Objectives. To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. Methods. Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. Results. Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; ), CRP (AUC = 0.75; ), and ASDAS (AUC = 0.778, ) significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, ) significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald , , and wald , ). Conclusions. Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients. Zhiming Lin, Zetao Liao, Jianlin Huang, Maixing Ai, Yunfeng Pan, Henglian Wu, Jun Lu, Shuangyan Cao, Li Li, Qiujing Wei, Deshen Tang, Yanlin Wei, Tianwang Li, Yuqiong Wu, Manlong Xu, Qiuxia Li, Ou Jin, Buyun Yu, and Jieruo Gu Copyright © 2015 Zhiming Lin et al. All rights reserved. The Surgical Treatment Principles of Atlantoaxial Instability Focusing on Rheumatoid Arthritis Sun, 26 Jul 2015 09:58:36 +0000 Object. This retrospective review was conducted to determine the surgical treatment principle for rheumatoid arthritis (RA) patients with atlantoaxial instability (AAI). Methods. Thirteen patients with AAI, including 5 RA patients, received preoperative computed tomography- (CT-) based image-guided navigation system (IGS) in C1 lateral mass-C2 pedicle screw-rod system fixation (LC1-PC2 fixation). These 13 patients were analyzed for 52 screws inserted into C1 and C2. We defined these patients as non-RA group (8 patients, 32 screws) and RA group (5 patients, 20 screws). The neurological status for RA group was evaluated using the Ranawat classification. The causes of AAI, surgical indications, complications, surgical method revolution, and CT-based navigation application are discussed. Results. None of the 13 patients expressed neurological function deterioration. The non-RA group screw accuracy was 100%. In the RA group, 1 RA patient developed left C2 screw loosening at 1+ months after operation due to screw malposition. The screw accuracy for this group was 95%. Conclusions. Higher intraoperative surgical complication rate was described in RA patients. Preoperative CT-based IGS in LC1-PC2 fixation can provide good neurological function and screw accuracy results. However, for higher screw accuracy in RA patients, intraoperative CT-based IGS application may be considered. Yu-Tung Shih, Ting-Hsien Kao, Hung-Chuan Pan, Hsien-Te Chen, and Hsi-Kai Tsou Copyright © 2015 Yu-Tung Shih et al. All rights reserved. Analysis of Erythrocyte C4d to Complement Receptor 1 Ratio: Use in Distinguishing between Infection and Flare-Up in Febrile Patients with Systemic Lupus Erythematosus Sun, 26 Jul 2015 09:53:16 +0000 Objective. Fever in systemic lupus erythematosus (SLE) can be caused by infection or flare-up of the disease. This study aimed to determine whether the ratio of the level of erythrocyte-bound C4d to that of complement receptor 1 (C4d/CR1) can serve as a useful biomarker in the differentiation between infection and flare-up in febrile SLE patients. Methods. We enrolled febrile SLE patients and determined the ratio on the day of admission. The patients were divided into 2 groups according to the subsequent clinical course. Results. Among the febrile SLE patients, those with flare-up had higher ratios and lower C-reactive protein (CRP) levels than those with infection. Cut-off values of <1.2447 and >4.67 for C4d/CR1 ratio and CRP, respectively, were 40.91% sensitive and 100.0% specific for the presence of infection in febrile SLE patients; similarly, cut-off values of >1.2447 and <2.2, respectively, were 80% sensitive and 100% specific for the absence of infection in febrile SLE patients. Conclusion. The C4d/CR1 ratio is a simple and quickly determinable biomarker that enables the differentiation between infection and flare-up in febrile SLE patients at initial evaluation. Further, when combined with the CRP level, it is useful to evaluate disease activity in SLE patients with infection. Chen-Hung Chen, Shun-Ban Tai, Hsiang-Cheng Chen, Deng-Ho Yang, Ming-Yieh Peng, and Yuh-Feng Lin Copyright © 2015 Chen-Hung Chen et al. All rights reserved. Regulation of Cell Cycle Regulators by SIRT1 Contributes to Resveratrol-Mediated Prevention of Pulmonary Arterial Hypertension Sun, 26 Jul 2015 09:51:02 +0000 Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in rheumatic diseases. Vascular remodeling due to the proliferation of pulmonary arterial smooth muscle cells (PASMCs) is central to the development of PAH. To date, it is still unclear if Silence Information Regulator 1 (SIRT1) regulates cell cycle regulators in the proliferation of PASMCs and contributes to prevention of PAH by resveratrol. In this study, we found that a significant decrease of SIRT1 expression levels in platelet-derived growth factor BB (PDGF-BB) treated human PASMCs (HPASMCs) and in monocrotaline (MCT) induced PAH rat. Overexpression of SIRT1 induced G1 phase arrest and increased p21 expression but decreased cyclin D1 expression in PDGF-BB treated HPASMCs. Moreover, resveratrol attenuated pulmonary arterial remodeling, decreased pulmonary arterial pressure, and upregulated SIRT1 and p21 expression but downregulated cyclin D1 expression in MCT induced PAH rat. Notably, knockdown of SIRT1 eliminated the regulation of resveratrol on p21 and cyclin D1 expression in PDGF-BB treated HPASMCs. These results demonstrated that SIRT1 mediated the regulation of resveratrol on the expression of cell cycle regulatory molecules. It suggests that SIRT1 exerts a protective role in PAH associated with rheumatic diseases and can be a potential treatment target. Shuang Zhou, Meng-Tao Li, Yu-Yan Jia, Jin-Jing Liu, Qian Wang, Zhuang Tian, Yong-Tai Liu, Hou-Zao Chen, De-Pei Liu, and Xiao-Feng Zeng Copyright © 2015 Shuang Zhou et al. All rights reserved. Can Whole-Body Cryotherapy with Subsequent Kinesiotherapy Procedures in Closed Type Cryogenic Chamber Improve BASDAI, BASFI, and Some Spine Mobility Parameters and Decrease Pain Intensity in Patients with Ankylosing Spondylitis? Sun, 26 Jul 2015 09:46:54 +0000 The present study investigated whether whole-body cryotherapy (WBC) procedures could potentially have more beneficial effects on index of BASDAI and BASFI, pain intensity, and spine mobility parameters: Ott test, modified Schober test, chest expansion in ankylosing spondylitis (AS) patients, than kinesiotherapy procedures used separately. AS patients were exposed to a cycle of WBC procedures lasting 3 minutes a day, with a subsequent 60 minutes of kinesiotherapy or 60 minutes of kinesiotherapy only, for 10 consecutive days excluding weekend. After the completion of the cycle of WBC procedures with subsequent kinesiotherapy in the AS patients, BASDAI index decreased about 40% in comparison with the input value, whereas in the group of patients who received only kinesiotherapy it decreased only about 15% in comparison with the input value. After the completion of the treatment in the WBC group, BASFI index decreased about 30% in comparison with the input value, whereas in the kinesiotherapy group it only decreased about 16% in comparison with the input value. The important conclusion was that, in WBC group with subsequent kinesiotherapy, we observed on average about twice better results than in the group treated only by kinesiotherapy. Agata Stanek, Armand Cholewka, Jolanta Gadula, Zofia Drzazga, Aleksander Sieron, and Karolina Sieron-Stoltny Copyright © 2015 Agata Stanek et al. All rights reserved. Elevated Serum Levels of Soluble CD30 in Ankylosing Spondylitis Patients and Its Association with Disease Severity-Related Parameters Sun, 26 Jul 2015 09:36:15 +0000 Soluble CD30 (sCD30), a transmembrane glycoprotein that belongs to the tumor necrosis factor receptor (TNFR) superfamily, has been shown to be associated with various pathological conditions. This study was designed to measure the levels of serum sCD30 in patients with ankylosing spondylitis (AS) and to evaluate the relationships between serum sCD30 levels and other disease severity-related indexes, including bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS), and bath ankylosing spondylitis functional index (BASFI). Our results demonstrated significantly elevated sCD30 levels in AS patients compared to healthy controls (HCs) with mean values of and  ng/mL, respectively , suggesting a potential role of sCD30 in the pathogenesis of AS. However, no significant correlations of sCD30 with BASDAI, ASDAS, or BASFI were detected in our study . Therefore, sCD30 cannot be used as a reliable marker for reflecting disease activity and functional ability of AS patients. Rongfen Gao, Wei Sun, Yu Chen, Yuying Su, Chenqiong Wang, and Lingli Dong Copyright © 2015 Rongfen Gao et al. All rights reserved. A Minimally Invasive Endoscopic Surgery for Infectious Spondylodiscitis of the Thoracic and Upper Lumbar Spine in Immunocompromised Patients Sun, 26 Jul 2015 08:05:51 +0000 This study evaluates the safety and effectiveness of computed tomography- (CT-) assisted endoscopic surgery in the treatment of infectious spondylodiscitis of the thoracic and upper lumbar spine in immunocompromised patients. From October 2006 to March 2014, a total of 41 patients with infectious spondylodiscitis underwent percutaneous endoscopic surgery under local anesthesia, and 13 lesions from 13 patients on the thoracic or upper lumbar spine were selected for evaluation. A CT-guided catheter was placed before percutaneous endoscopic surgery as a guide to avoid injury to visceral organs, major vessels, and the spinal cord. All 13 patients had quick pain relief after endoscopic surgery without complications. The bacterial culture rate was 77%. Inflammatory parameters returned to normal after adequate antibiotic treatment. Postoperative radiographs showed no significant kyphotic deformity when compared with preoperative films. As of the last follow-up visit, no recurrent infections were noted. Traditional transthoracic or diaphragmatic surgery with or without posterior instrumentation is associated with high rates of morbidity and mortality, especially in elderly patients, patients with multiple comorbidities, or immunocompromised patients. Percutaneous endoscopic surgery assisted by a CT-guided catheter provides a safe and effective alternative treatment for infectious spondylodiscitis of the thoracic and upper lumbar spine. Hsin-Chuan Chen, Teng-Le Huang, Yen-Jen Chen, Hsi-Kai Tsou, Wei-Ching Lin, Chih-Hung Hung, Chun-Hao Tsai, Horng-Chaung Hsu, and Hsien-Te Chen Copyright © 2015 Hsin-Chuan Chen et al. All rights reserved. Patient Acceptable Symptom State in Self-Report Questionnaires and Composite Clinical Disease Index for Assessing Rheumatoid Arthritis Activity: Identification of Cut-Off Points for Routine Care Thu, 18 Jun 2015 11:35:44 +0000 Objective. To provide information on the value of Patient Acceptable Symptom State (PASS) in rheumatoid arthritis (RA) by the identification of PASS thresholds for patient-reported outcomes (PROs) composite scores. Methods. The characteristics of RA patients with affirmative and negative assignment to PASS were compared. Contributors to physician response were estimated by logistic regression models and PASS thresholds by the 75th percentile and receiver-operating characteristic (ROC) curve methods. Results. 303 RA patients completed the study. All PROs were different between the PASS (+) and PASS (−) groups (). The thresholds with the 75th percentile approach were 2.0 for the RA Impact of Disease (RAID) score, 2.5 for the PRO-CLinical ARthritis Activity (PRO-CLARA) index, and 1.0 for the Recent-Onset Arthritis Disability (ROAD) questionnaire. The cut-off values for Clinical Disease Activity Index (CDAI) were in the moderate range of disease activity. Assessing the size of the logistic regression coefficients, the strongest predictors of PASS were the disease activity () and functional state level (0.006). Conclusion. PASS thresholds were relatively high and many patients in PASS had moderate disease activity states according to CDAI. Factors such as disease activity and physical function may influence a negative PASS. Fausto Salaffi, Marina Carotti, Marwin Gutierrez, Marco Di Carlo, and Rossella De Angelis Copyright © 2015 Fausto Salaffi et al. All rights reserved. Inflammatory Joint Diseases Thu, 21 May 2015 11:21:56 +0000 Guixiu Shi, Julian L. Ambrus, Shuang Ye, and Long Shen Copyright © 2015 Guixiu Shi et al. All rights reserved. Temporomandibular Disorders and Oral Parafunctions: Mechanism, Diagnostics, and Therapy Thu, 14 May 2015 08:09:32 +0000 Klaus Boening, Mieszko Wieckiewicz, Anna Paradowska-Stolarz, Piotr Wiland, and Yuh-Yuan Shiau Copyright © 2015 Klaus Boening et al. All rights reserved. Assessment of the TMJ Dysfunction Using the Computerized Facebow Analysis of Selected Parameters Mon, 11 May 2015 07:11:17 +0000 The Purpose of the Paper. Qualitative and quantitative analysis of selected parameters of mandible movements, electronically registered in patients with temporomandibular joint dysfunction and healthy ones. Material. Function test of the mandible movements was conducted in 175 patients. Gender distribution was 143 women and 32 men, aged 9 to 84. Methods. The studied population, after accurate clinical examination, was divided into age groups with the range of five years. All the patients had Zebris JMA computerized facebow examination done, according to the generally accepted principles and procedures. Results. Mean values of mouth opening calculated to 45.6 mm in healthy group and 37.6 mm in TMJ dysfunction group. Mean length of condylar path amounted to % of the maximum value of mouth opening in the group of healthy people, % in the case of muscle-based disorders, and % with joint-based. The mean value of the condylar path inclination oscillated in the range of 25° to 45°. Conclusions. The ratio of length of the condylar path to the size of mouth opening may be a significant value characterising the type and degree of intensification of the TMJ dysfunctions. Edward Kijak, Danuta Lietz-Kijak, Bogumiła Frączak, Zbigniew Śliwiński, and Jerzy Margielewicz Copyright © 2015 Edward Kijak et al. All rights reserved. Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice Tue, 05 May 2015 07:56:07 +0000 Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion. Xiaoqing Zhang, Sibo Liu, Shentao Li, Yuxuan Du, Yunpeng Dou, Zhanguo Li, Huihui Yuan, and Wenming Zhao Copyright © 2015 Xiaoqing Zhang et al. All rights reserved. Association between Serum 25-Hydroxyvitamin D Level and Rheumatoid Arthritis Mon, 04 May 2015 11:56:17 +0000 The objective of this study is to examine and evaluate whether serum 25(OH)D is associated with disease activity in patients with rheumatoid arthritis (RA). Our results suggested that serum 25(OH)D in RA groups has significant lower level ( nmol/L) than that in the normal groups ( nmol/L, ). Based on the DAS28, patients with RA were divided into four subgroups, and no differences were found in the four groups (). The 25(OH)D levels in complete remission, low disease activity, middle disease activity, and high disease activity group were , , , and  nmol/L, respectively. Based on the serum 25(OH)D levels, patients with RA were divided into inadequate group and normal group, and there were no significant differences in baseline characteristics and disease activity in the two groups. Our results showed that serum 25(OH)D levels in the inadequate group are significantly lower than those in the normal group. However, no correlations were found between 25(OH)D levels and disease activity among 116 patients with RA. The present findings will help to understand the association between 25(OH)D and disease activity of RA. Xiaomin Cen, Yuan Liu, Geng Yin, Min Yang, and Qibing Xie Copyright © 2015 Xiaomin Cen et al. All rights reserved. Pim-2/mTORC1 Pathway Shapes Inflammatory Capacity in Rheumatoid Arthritis Synovial Cells Exposed to Lipid Peroxidations Mon, 04 May 2015 11:54:27 +0000 Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of multiple joints, with disruption of joint cartilage. The proliferation of synovial fibroblasts in response to multiple inflammation factors is central to the pathogenesis of rheumatoid arthritis. Our previous studies showed that 4-HNE may induce synovial intrinsic inflammations by activating NF-κB pathways and lead to cell apoptosis. However, the molecular mechanisms of how synovial NF-κB activation is modulated are not fully understood. Here, the present findings demonstrated that 4-HNE may induce synovial intrinsic inflammations by mTORC1 inactivation. While ectopic activation of mTORC1 pathway by the overexpression of Pim-2 may disrupt the initiation of inflammatory reactions and maintain synovial homeostasis, our findings will help to uncover novel signaling pathways between inflammations and oxidative stress in rheumatoid arthritis development and imply that Pim-2/mTORC1 pathway may be critical for the initiation of inflammatory reactions in human rheumatoid arthritis synovial cells. Geng Yin, Yan Li, Min Yang, Xiao-min Cen, and Qi-bing Xie Copyright © 2015 Geng Yin et al. All rights reserved. Medication Adherence in Patients with Rheumatoid Arthritis: The Effect of Patient Education, Health Literacy, and Musculoskeletal Ultrasound Tue, 28 Apr 2015 06:53:42 +0000 Background. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting <1% of the population. Incompletely controlled RA results in fatigue, joint and soft tissue pain, progressive joint damage, reduced quality of life, and increased cardiovascular mortality. Despite an increasing range of disease modifying agents which halt disease progression, poor patient adherence with medication is a significant barrier to management. Objective. The goal of this review was to examine the effectiveness of measures to improve patient medication adherence. Methods. Studies addressing treatment adherence in patients with RA were identified by trawling PsycINFO, Medline, Cochrane, Pubmed, and ProQuest for studies published between January 2000 and October 2014. Articles were independently reviewed to identify relevant studies. Results. Current strategies were of limited efficacy in improving patient adherence with medications used to treat RA. Conclusion. Poor medication adherence is a complex issue. Low educational levels and limited health literacy are contributory factors. Psychological models may assist in explaining medication nonadherence. Increasing patient knowledge of their disease seems sensible. Existing educational interventions appear ineffective at improving medication adherence, probably due to an overemphasis on provision of biomedical information. A novel approach to patient education using musculoskeletal ultrasound is proposed. Samantha Joplin, Rick van der Zwan, Fredrick Joshua, and Peter K. K. Wong Copyright © 2015 Samantha Joplin et al. All rights reserved. Influence of Immunogenicity on the Efficacy of Long-Term Treatment with TNF α Blockers in Rheumatoid Arthritis and Spondyloarthritis Patients Mon, 27 Apr 2015 13:36:32 +0000 Objective. To analyze the clinical relevance of the levels of TNFα blockers and anti-drug antibodies (anti-drug Ab) in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) for a prolonged period of time. Methods. Clinical characteristics (disease activity, and adverse events), serum TNFα blockers, and anti-drug Ab levels were evaluated in 62 RA and 81 SpA patients treated with TNFα blockers for a median of 28 months. Results. Anti-ADA Ab were detected in 1 (4.0%) and anti-INF Ab in 14 out of 57 (24.6%) RA and SpA patients. Patient with anti-ADA Ab and 57.1% patients with anti-INF Ab were considered nonresponders to treatment. Anti-ETA Ab were not found in any of 61 ETA treated patients. Anti-ADA and anti-INF Ab levels differ between responders and nonresponders . Three (5.3%) patients with high serum anti-INF Ab levels developed infusion related reactions. Patients with anti-INF Ab more often required changing to another biologic drug (OR 11.43 (95% CI 1.08–120.93)) and treatment discontinuation (OR 9.28 (95% CI 1.64–52.52)). Conclusion. Patients not responding to treatment had higher serum anti-ADA and anti-INF Ab concentrations. Anti-INF Ab formation is related to increased risk of infusion related reactions, changing to another biologic drug, and treatment discontinuation. Inesa Arstikyte, Giedre Kapleryte, Irena Butrimiene, and Algirdas Venalis Copyright © 2015 Inesa Arstikyte et al. All rights reserved. Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids Mon, 27 Apr 2015 11:39:14 +0000 Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA) mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo. Hongsik Cho, Andrew Walker, Jeb Williams, and Karen A. Hasty Copyright © 2015 Hongsik Cho et al. All rights reserved. Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register, Mon, 27 Apr 2015 11:27:02 +0000 Objectives. To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria. Methods. We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders. Results. Tocilizumab-treated patients () presented higher baseline disease activity and were less frequently naïve to biologics compared to TNFi users (). Multivariate logistic regression analysis including the propensity score for receiving tocilizumab showed that patients treated with tocilizumab were more likely to achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6–21.6/3.2–12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2–6.5/1.3–5.5), or SDAI (OR = 3.6/2.5, 95% CI 1.5–8.7/1.1–5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4–12.0). However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8–4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8–4.5). Conclusions. Compared with TNFi, tocilizumab was associated with greater likelihood of achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean remission and EULAR good/moderate response did not differ significantly between groups. Vasco C. Romão, Maria José Santos, Joaquim Polido-Pereira, Cátia Duarte, Patrícia Nero, Cláudia Miguel, José António Costa, Miguel Bernardes, Fernando M. Pimentel-Santos, Filipe Barcelos, Lúcia Costa, José António Melo Gomes, José Alberto Pereira da Silva, Jaime Cunha Branco, José Canas da Silva, José António Pereira da Silva, João Eurico Fonseca, and Helena Canhão Copyright © 2015 Vasco C. Romão et al. All rights reserved. Isotypes of Epstein-Barr Virus Antibodies in Rheumatoid Arthritis: Association with Rheumatoid Factors and Citrulline-Dependent Antibodies Mon, 27 Apr 2015 10:33:13 +0000 In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were investigated by enzyme-linked immunosorbent assays (ELISA). Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs, IgG) and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection). Notably, for IgM and IgA (but not IgG), these were associated with the presence of characteristic RA autoantibodies. Marie Wulff Westergaard, Anette Holck Draborg, Lone Troelsen, Søren Jacobsen, and Gunnar Houen Copyright © 2015 Marie Wulff Westergaard et al. All rights reserved. Jaw Dysfunction Is Associated with Neck Disability and Muscle Tenderness in Subjects with and without Chronic Temporomandibular Disorders Thu, 26 Mar 2015 13:00:49 +0000 Purpose. Tender points in the neck are common in patients with temporomandibular disorders (TMD). However, the correlation among neck disability, jaw dysfunction, and muscle tenderness in subjects with TMD still needs further investigation. This study investigated the correlation among neck disability, jaw dysfunction, and muscle tenderness in subjects with and without chronic TMD. Participants. Forty females between 19 and 49 years old were included in this study. There were 20 healthy controls and 20 subjects who had chronic TMD and neck disability. Methods. Subjects completed the neck disability index and the limitations of daily functions in TMD questionnaires. Tenderness of the masticatory and cervical muscles was measured using an algometer. Results. The correlation between jaw disability and neck disability was significantly high (, ). The correlation between level of muscle tenderness in the masticatory and cervical muscles with jaw dysfunction and neck disability showed fair to moderate correlations (). Conclusion. High levels of muscle tenderness in upper trapezius and temporalis muscles correlated with high levels of jaw and neck dysfunction. Moreover, high levels of neck disability correlated with high levels of jaw disability. These findings emphasize the importance of considering the neck and its structures when evaluating and treating patients with TMD. A. Silveira, I. C. Gadotti, S. Armijo-Olivo, D. A. Biasotto-Gonzalez, and D. Magee Copyright © 2015 A. Silveira et al. All rights reserved. The Diagnostic Value of Pressure Algometry for Temporomandibular Disorders Thu, 26 Mar 2015 12:29:26 +0000 The aim of this study is to determine the diagnostic value of pressure algometry in temporomandibular disorders. Two hundred volunteers aged 19.3 to 27.8 (mean 21.50, SD 0.97) participated in this study. An analogue pressure algometer was used for the evaluation of muscle tenderness of the following masticatory muscles: superficial and deep parts of the masseter muscle; anterior and posterior parts of the temporal muscle; and the tissues adjacent to the lateral and dorsal part of the temporomandibular joint capsule. Each patient described the algometry result for the individual components of the masticatory motor system, by selecting each time the intensity of pain on a 100 mm Visual Analogue Scale (VAS) ruler. The area under the receiver operating characteristic (ROC) curve, indicating the discriminatory efficiency for asymptomatic subjects and patients with temporomandibular dysfunction according to the dysfunction Di index, was the largest for the mean pain value (AUC = 0.8572; SEM = 0.0531). The 7.4 VAS cut-off point marked 95.3% specificity for this variable in identifying healthy subjects and 58.4% sensitivity in identifying patients with symptoms of dysfunctions (accuracy 68.1%). Assuming comparable sensitivity (74.9%) and specificity (74.2%) for a diagnostic test, there was test accuracy of 74.5% at the 4.2 VAS cut-off point. Włodzimierz Więckiewicz, Krzysztof Woźniak, Dagmara Piątkowska, Liliana Szyszka-Sommerfeld, and Mariusz Lipski Copyright © 2015 Włodzimierz Więckiewicz et al. All rights reserved. The Electrical Activity of the Temporal and Masseter Muscles in Patients with TMD and Unilateral Posterior Crossbite Thu, 26 Mar 2015 12:12:37 +0000 The aim of this study was to assess the influence of unilateral posterior crossbite on the electrical activity of the temporal and masseter muscles in patients with subjective symptoms of temporomandibular dysfunctions (TMD). The sample consisted of 50 patients (22 female and 28 male) aged 18.4 to 26.3 years (mean 20.84, SD 1.14) with subjective symptoms of TMD and unilateral posterior crossbite malocclusion and 100 patients without subjective symptoms of TMD and malocclusion (54 female and 46 male) aged between 18.4 and 28.7 years (mean 21.42, SD 1.06). The anamnestic interviews were conducted according to a three-point anamnestic index of temporomandibular dysfunction (Ai). Electromyographical (EMG) recordings were performed using a DAB-Bluetooth Instrument (Zebris Medical GmbH, Germany). Recordings were carried out in the mandibular rest position and during maximum voluntary contraction (MVC). Analysis of the results of the EMG recordings confirmed the influence of unilateral posterior crossbite on variations in spontaneous muscle activity in the mandibular rest position and maximum voluntary contraction. In addition, there was a significant increase in the Asymmetry Index (As) and Torque Coefficient (Tc), responsible for a laterodeviating effect on the mandible caused by unbalanced right and left masseter and temporal muscles. Krzysztof Woźniak, Liliana Szyszka-Sommerfeld, and Damian Lichota Copyright © 2015 Krzysztof Woźniak et al. All rights reserved. Identification of Mastication Organ Muscle Forces in the Biocybernetic Perspective Thu, 26 Mar 2015 09:23:41 +0000 Purpose of the Paper. This paper is an attempt to mathematically describe the mastication organ muscle functioning, taking into consideration the impact of the central nervous system. Material. To conduct model tests, three types of craniums were prepared: short, normal, and long. The necessary numeric data, required to prepare the final calculation models of different craniofacial types, were used to identify muscle and occlusion forces generated by muscles in the area of incisors and molars. The mandible in model tests was treated as a nondeformable stiff form. Methods. The formal basis for the formulated research problem was reached using the laws and principles of mechanics and control theory. The proposed method treats muscles as “black boxes,” whose properties automatically adapt to the nature of the occlusion load. The identified values of occlusion forces referred to measurements made in clinical conditions. Results. The conducted verification demonstrated a very good consistency of model and clinical tests’ results. The proposed method is an alternative approach to the so far applied methods of muscle force identification. Identification of muscle forces without taking into account the impact of the nervous system does not fully reflect the conditions of mastication organ muscle functioning. Edward Kijak, Jerzy Margielewicz, Damian Gąska, Danuta Lietz-Kijak, and Włodzimierz Więckiewicz Copyright © 2015 Edward Kijak et al. All rights reserved. The Influence of Emotional State on the Masticatory Muscles Function in the Group of Young Healthy Adults Thu, 26 Mar 2015 07:45:41 +0000 Stress may affect the function of all the components of the masticatory system and may ultimately lead to differentiated symptoms and finally to systemic and structural dysfunctions. Objective. To determine the effect of stress on the masticatory muscles function in young healthy adults. Material and Methods. A total of 201 young, Angle’s first class, healthy volunteers, 103 female and 98 male, in the age between 18 and 21 years were recruited into the study. All the participants underwent clinical examination according to the Slavicek scheme, questionnaire survey according to Perceived Stress Scale, and assessment of masticatory muscles function in central occlusion. Results. Symptoms of masticatory system dysfunction were found in the group of 86 subjects (46,24%). All the muscles activity in central occlusion was comparable in female and male groups. Mean values of masseters activities in the group of low stress subjects (75,52 µV ± 15,97) were statistically different from the groups with medium (82,43 µV ± 15,04) and high (81,33 ± 12,05) perceived stress . Conclusion. Chronic stress may reveal or exacerbate symptoms of masticatory dysfunction. Stocka Anna, Kuc Joanna, Sierpinska Teresa, Golebiewska Maria, and Wieczorek Aneta Copyright © 2015 Stocka Anna et al. All rights reserved. Muscle Fatigue in the Temporal and Masseter Muscles in Patients with Temporomandibular Dysfunction Thu, 26 Mar 2015 07:25:54 +0000 The aim of this study is to evaluate muscle fatigue in the temporal and masseter muscles in patients with temporomandibular dysfunction (TMD). Two hundred volunteers aged 19.3 to 27.8 years (mean 21.50, SD 0.97) participated in this study. Electromyographical (EMG) recordings were performed using a DAB-Bluetooth Instrument (Zebris Medical GmbH, Germany). Muscle fatigue was evaluated on the basis of a maximum effort test. The test was performed during a 10-second maximum isometric contraction (MVC) of the jaws. An analysis of changes in the mean power frequency of the two pairs of temporal and masseter muscles (MPF%) revealed significant differences in the groups of patients with varying degrees of temporomandibular disorders according to Di (). The study showed an increase in the muscle fatigue of the temporal and masseter muscles correlated with the intensity of temporomandibular dysfunction symptoms in patients. The use of surface electromyography in assessing muscle fatigue is an excellent diagnostic tool for identifying patients with temporomandibular dysfunction. Krzysztof Woźniak, Mariusz Lipski, Damian Lichota, and Liliana Szyszka-Sommerfeld Copyright © 2015 Krzysztof Woźniak et al. All rights reserved. Enhanced Cardiovascular Risk in Rheumatoid Arthritis: Elucidation, Assessment, and Management Thu, 12 Mar 2015 07:19:52 +0000 Patrick H. Dessein, Anne G. Semb, Miguel A. González-Gay, and Calin D. Popa Copyright © 2015 Patrick H. Dessein et al. All rights reserved. Assessment of the Body Composition and Parameters of the Cardiovascular Risk in Juvenile Idiopathic Arthritis Mon, 09 Mar 2015 13:02:29 +0000 The study was aimed to evaluate cardiovascular risk parameters, body mass index (BMI) centiles for sex and age, and body fat percentage using the electric bioimpedance method in children with juvenile idiopathic arthritis (JIA). 30 children with JIA participated in the study. A control group included 20 children. Patients were well matched for the age and sex. The body mass and body fat percentage were determined using the segmental body composition analyser; the BMI centiles were determined. All patients had the following parameters determined: lipid profile, hsCRP, homocysteine, and IL-6. The intima media thickness (IMT) was measured. Patients with JIA had significantly lower body weight, BMI, and the BMI centile compared to the control group. The IL-6 levels were significantly higher in patients with JIA compared to the control group. There were no differences between two groups with regard to the lipid profile, % content of the fat tissue, homocysteine levels, hsCRP, and IMT. Further studies are necessary to search for reasons for lower BMI and BMI centile in children with JIA and to attempt to answer the question of whether lower BMI increases the cardiovascular risk in these patients, similarly as in patients with rheumatoid arthritis (RA). Ewa Jednacz and Lidia Rutkowska-Sak Copyright © 2015 Ewa Jednacz and Lidia Rutkowska-Sak. All rights reserved. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors Mon, 02 Mar 2015 11:35:32 +0000 The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (), and lower levels of high density lipoprotein cholesterol (HDL-c) (). The cIMT correlated with levels of anti-CCP (, ), CRP (, ), TNFα (, ), and IL-6 (, ). In multiple regression analysis, cIMT was associated with CRP () and anti-CCP levels (). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. Mónica Vázquez-Del Mercado, Lourdes Nuñez-Atahualpa, Mauricio Figueroa-Sánchez, Eduardo Gómez-Bañuelos, Alberto Daniel Rocha-Muñoz, Beatriz Teresita Martín-Márquez, Esther Guadalupe Corona-Sanchez, Erika Aurora Martínez-García, Héctor Macias-Reyes, Laura Gonzalez-Lopez, Jorge Ivan Gamez-Nava, Rosa Elena Navarro-Hernandez, María Alejandra Nuñez-Atahualpa, and Javier Andrade-Garduño Copyright © 2015 Mónica Vázquez-Del Mercado et al. All rights reserved. Lack of Association between JAK3 Gene Polymorphisms and Cardiovascular Disease in Spanish Patients with Rheumatoid Arthritis Sun, 01 Mar 2015 13:08:11 +0000 Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. JAK/STAT signalling pathway is involved in autoimmune diseases and in the atherosclerotic process. JAK3 is a highly promising target for immunomodulatory drugs and polymorphisms in JAK3 gene have been associated with CV events in incident dialysis patients. Therefore, the aim of this study was to assess the potential role of JAK3 polymorphisms in the development of CV disease in patients with RA. 2136 Spanish RA patients were genotyped for the rs3212780 and rs3212752 JAK3 gene polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 539 of these patients by carotid ultrasonography (US). No statistically significant differences were found when each polymorphism was assessed according to carotid intima-media thickness values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV events after adjusting for potential confounders. In conclusion, our results do not confirm association between JAK3 polymorphisms and CV disease in RA. Mercedes García-Bermúdez, Raquel López-Mejías, Fernanda Genre, Santos Castañeda, Alfonso Corrales, Javier Llorca, Carlos González-Juanatey, Begoña Ubilla, José A. Miranda-Filloy, Trinitario Pina, Carmen Gómez-Vaquero, Luis Rodríguez-Rodríguez, Benjamín Fernández-Gutiérrez, Alejandro Balsa, Dora Pascual-Salcedo, Francisco J. López-Longo, Patricia Carreira, Ricardo Blanco, Javier Martín, and Miguel A. González-Gay Copyright © 2015 Mercedes García-Bermúdez et al. All rights reserved. EULAR Task Force Recommendations on Annual Cardiovascular Risk Assessment for Patients with Rheumatoid Arthritis: An Audit of the Success of Implementation in a Rheumatology Outpatient Clinic Sun, 01 Mar 2015 11:23:04 +0000 Objective. EULAR recommendations for cardiovascular disease (CVD) risk management include annual CVD risk assessments for patients with rheumatoid arthritis (RA). We evaluated the recording of CVD risk factors (CVD-RF) in a rheumatology outpatient clinic, where EULAR recommendations had been implemented. Further, we compared CVD-RF recordings between a regular rheumatology outpatient clinic (RegROC) and a structured arthritis clinic (AC). Methods. In 2012, 1142 RA patients visited the rheumatology outpatient clinic: 612 attended RegROC and 530 attended AC. We conducted a search in the patient journals to ascertain the rate of CVD-RF recording. Results. The overall CVD-RF recording rate was 40.1% in the rheumatology outpatient clinic, reflecting a recording rate of 59.1% in the AC and 23.6% in the RegROC. The odds ratios for having CVD-RFs recorded for patients attending AC compared to RegROC were as follows: blood pressure: 12.4, lipids: 5.0-6.0, glucose: 9.1, HbA1c: 6.1, smoking: 1.4, and for having all the CVD-RFs needed to calculate the CVD risk by the systematic coronary risk evaluation (SCORE): 21.0. Conclusion. The CVD-RF recording rate was low in a rheumatology outpatient clinic. However, a systematic team-based model was superior compared to a RegROC. Further measures are warranted to improve CVD-RF recording in RA patients. Eirik Ikdahl, Silvia Rollefstad, Inge C. Olsen, Tore K. Kvien, Inger Johanne Widding Hansen, Dag Magnar Soldal, Glenn Haugeberg, and Anne Grete Semb Copyright © 2015 Eirik Ikdahl et al. All rights reserved. Increased Incidence of Atrial Fibrillation in Patients with Rheumatoid Arthritis Sun, 01 Mar 2015 08:48:04 +0000 Objective. To investigate the incidence of atrial fibrillation (AF) among patients with rheumatoid arthritis (RA) compared to the general population. Methods. A population-based inception cohort of Olmsted County, Minnesota, residents with incident RA in 1980–2007 and a cohort of non-RA subjects from the same population base were assembled and followed until 12/31/2008. The occurrence of AF was ascertained by medical record review. Results. The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 (SD:15.7) years, 68% women in both cohorts). The prevalence of AF was similar in the RA and non-RA cohorts at RA incidence/index date (4% versus 3%; ). The cumulative incidence of AF during follow-up was higher among patients with RA compared to non-RA subjects (18.3% versus 16.3% at 20 years; ). This difference persisted after adjustment for age, sex, calendar year, smoking, and hypertension (hazard ratio: 1.46; 95% CI: 1.07, 2.00). There was no evidence of a differential impact of AF on mortality in patients with RA compared to non-RA subjects (hazard ratio 2.5 versus 2.8; interaction ). Conclusion. The incidence of AF is increased in patients with RA, even after adjustment for AF risk factors. AF related mortality risk did not differ between patients with and without RA. A. Kirstin Bacani, Cynthia S. Crowson, Véronique L. Roger, Sherine E. Gabriel, and Eric L. Matteson Copyright © 2015 A. Kirstin Bacani et al. All rights reserved. The Draining Lymph Node in Rheumatoid Arthritis: Current Concepts and Research Perspectives Sun, 22 Feb 2015 11:05:10 +0000 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of unknown aetiology, leading to progressive damage of bone and cartilage with functional impairment and disability. Whilst the synovial membrane represents the epicentre of the immune-inflammatory process, there is growing evidence indicating the potential involvement of additional anatomical compartments, such as the lung, bone marrow, and secondary lymphoid tissues. Draining lymph nodes represent the elective site for tissue immune-surveillance, for the generation of adaptive immune responses and a candidate compartment for the maintenance of peripheral tolerance. Despite the precise role of the juxta- and extra-articular lymph node stations in the pathogenesis of RA remaining poorly defined, several lines of research exploiting new technological approaches are now focusing on their assessment as a potential new source of pathobiologic information, biomarkers, and complementary therapeutic targets. In this review we present an updated overview of the main concepts driving lymph node research in RA, highlighting the most relevant findings, current hypothesis, and translational perspectives. Francesca Benaglio, Barbara Vitolo, Martina Scarabelli, Elisa Binda, Serena Bugatti, Roberto Caporali, Carlomaurizio Montecucco, and Antonio Manzo Copyright © 2015 Francesca Benaglio et al. All rights reserved. Prevalence and Possible Risk Factors of Low Bone Mineral Density in Untreated Female Patients with Systemic Lupus Erythematosus Sun, 08 Feb 2015 14:25:53 +0000 Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation. Different studies have shown decreased bone mineral density (BMD) in patients with SLE. The objective of this study was to investigate the prevalence and possible risk factors of low BMD in untreated female patients with SLE in Chinese population. A total of 119 untreated female patients with SLE were included. BMD was measured at lumbar spine and at total hip by dual-energy X-ray absorptiometry. The associations between decreased BMD and demographic variables, clinical variables, and bone metabolism variables were analyzed. These SLE patients had the following characteristics: mean age was years, mean disease duration was months, and mean SLEDAI was . Osteopenia was present in 31.1% of the patients and osteoporosis in 8.5%. A significant negative association between low density lipoprotein cholesterol (LDL-c) and BMD at the lumbar spine (correlation coefficient = −0.242; ) and total hip (correlation coefficient = −0.259; ) was shown. These results seem to indicate that increased LDL-c may be an important risk factor for low BMD at lumbar spine and total hip in untreated female SLE patients. Yi-Ning Sun, Xiu-Yuan Feng, Lan He, Ling-Xia Zeng, Zhi-Ming Hao, Xiao-Hong Lv, and Dan Pu Copyright © 2015 Yi-Ning Sun et al. All rights reserved. Identification of Potential Transcriptomic Markers in Developing Ankylosing Spondylitis: A Meta-Analysis of Gene Expression Profiles Thu, 22 Jan 2015 11:14:09 +0000 The goal of this study was to identify potential transcriptomic markers in developing ankylosing spondylitis by a meta-analysis of multiple public microarray datasets. Using the INMEX (integrative meta-analysis of expression data) program, we performed the meta-analysis to identify consistently differentially expressed (DE) genes in ankylosing spondylitis and further performed functional interpretation (gene ontology analysis and pathway analysis) of the DE genes identified in the meta-analysis. Three microarray datasets (26 cases and 29 controls in total) were collected for meta-analysis. 905 consistently DE genes were identified in ankylosing spondylitis, among which 482 genes were upregulated and 423 genes were downregulated. The upregulated gene with the smallest combined rank product (RP) was GNG11 (combined ). The downregulated gene with the smallest combined RP was S100P (combined ). In the gene ontology (GO) analysis, the most significantly enriched GO term was “immune system process” (). The most significant pathway identified in the pathway analysis was antigen processing and presentation (). The consistently DE genes in ankylosing spondylitis and biological pathways associated with those DE genes identified provide valuable information for studying the pathophysiology of ankylosing spondylitis. Fang Fang, Jian Pan, Lixiao Xu, Gang Li, and Jian Wang Copyright © 2015 Fang Fang et al. All rights reserved. Computer-Aided Quantification of Interstitial Lung Disease from High Resolution Computed Tomography Images in Systemic Sclerosis: Correlation with Visual Reader-Based Score and Physiologic Tests Mon, 05 Jan 2015 14:08:05 +0000 Objective. To evaluate the performance of a computerized-aided method (CaM) for quantification of interstitial lung disease (ILD) in patients with systemic sclerosis and to determine its correlation with the conventional visual reader-based score (CoVR) and the pulmonary function tests (PFTs). Methods. Seventy-nine patients were enrolled. All patients underwent chest high resolution computed tomography (HRCT) scored by two radiologists adopting the CoVR. All HRCT images were then analysed by a CaM using a DICOM software. The relationships among the lung segmentation analysis, the readers, and the PFTs results were calculated using linear regression analysis and Pearson’s correlation. Receiver operating curve analysis was performed for determination of CaM extent threshold. Results. A strong correlation between CaM and CoVR was observed (). The CaM showed a significant negative correlation with forced vital capacity (FVC) () and the single breath carbon monoxide diffusing capacity of the lung (DLco) (). A CaM optimal extent threshold of 20% represented the best compromise between sensitivity (75.6%) and specificity (97.4%). Conclusions. CaM quantification of SSc-ILD can be useful in the assessment of extent of lung disease and may provide reliable tool in daily clinical practice and clinical trials. Fausto Salaffi, Marina Carotti, Silvia Bosello, Alessandro Ciapetti, Marwin Gutierrez, Elisabetta Bichisecchi, Gianmarco Giuseppetti, and Gianfranco Ferraccioli Copyright © 2015 Fausto Salaffi et al. All rights reserved. Expression of Phosphocitrate-Targeted Genes in Osteoarthritis Menisci Sun, 23 Nov 2014 07:42:13 +0000 Phosphocitrate (PC) inhibited calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms remain elusive. This study sought to determine PC targeted genes and the expression of select PC targeted genes in OA menisci to test hypothesis that PC exerts its disease modifying activity in part by reversing abnormal expressions of genes involved in OA. We found that PC downregulated the expression of numerous genes classified in immune response, inflammatory response, and angiogenesis, including chemokine (C-C motif) ligand 5, Fc fragment of IgG, low affinity IIIb receptor (FCGR3B), and leukocyte immunoglobulin-like receptor, subfamily B member 3 (LILRB3). In contrast, PC upregulated the expression of many genes classified in skeletal development, including collagen type II alpha1, fibroblast growth factor receptor 3 (FGFR3), and SRY- (sex determining region Y-) box 9 (SOX-9). Immunohistochemical examinations revealed higher levels of FCGR3B and LILRB3 and lower level of SOX-9 in OA menisci. These findings indicate that OA is a disease associated with immune system activation and decreased expression of SOX-9 gene in OA menisci. PC exerts its disease modifying activity on OA, at least in part, by targeting immune system activation and the production of extracellular matrix and selecting chondroprotective proteins. Yubo Sun, David R. Mauerhan, Nury M. Steuerwald, Jane Ingram, Jeffrey S. Kneisl, and Edward N. Hanley Jr. Copyright © 2014 Yubo Sun et al. All rights reserved. Breast Cancer Risk in Rheumatoid Arthritis: An Update Meta-Analysis Mon, 27 Oct 2014 12:25:25 +0000 Background. The incidence of breast cancer in RA patients remains controversial. Thus we performed a meta-analysis to investigate the impact of RA on breast cancer. Methods. Published literature was available from PubMed, Embase, and Cochrane Library. Pooled standardized incidence rate (SIR) was computed by random-effect model analysis. Results. We identified 16 separate studies in the present study, in which the number of patients ranged from 458 to 84,475. We did not find the increased cancer risk in RA patients (, 95% –1.02). However, subgroup analysis showed that breast cancer risk in RA patients was positively different in Caucasians (, 95% –0.93) and non-Caucasians (, 95% –1.23), respectively. In subgroup analysis by style, a reduced incidence was found in hospital-based case subjects (, 95% –0.97). Similarly, subgroup analysis for adjusted factors indicated that in A3 (age and sex) and A4 (age, sex, and race/ethnicity) the risk was decreased (, 95% –0.99; , 95% –0.67). Conclusions. The meta-analysis revealed no increased breast cancer risk in RA patients. However, in the subgroup analysis, the risk of breast cancer is increased in non-Caucasians patients with RA while it decreased in Caucasian population, hospital-based case subjects, and A3 group. Such relationship may provide preference for risk of breast cancer in different population. Guo Tian, Jia-Ning Liang, Zhuo-Yun Wang, and Dian Zhou Copyright © 2014 Guo Tian et al. All rights reserved. Serum Samples That Have Been Stored Long-Term (>10 Years) Can Be Used as a Suitable Data Source for Developing Cardiovascular Risk Prediction Models in Large Observational Rheumatoid Arthritis Cohorts Thu, 11 Sep 2014 11:30:55 +0000 Objective. There is an unmet need for a specific cardiovascular risk (CV) algorithm for rheumatoid arthritis (RA) patients. Lipoprotein data are often not available in RA cohorts but could be obtained from frozen blood samples. The objective of this study was to estimate the storage effect on lipoproteins in long-term (>10 years) frozen serum samples. Methods. Data were used from an inception RA cohort. Multiple serum samples from 152 patients were analyzed for lipoproteins, being frozen for 1–26 years at −20°C. Storage effect on lipoproteins was estimated using longitudinal regression analyses and a lipid decay correction factor was developed. Clinical impact of the storage effect on lipoproteins was assessed by calculating the number of patients reclassified to another CV risk group according to the SCORE risk calculator after applying the decay correction factor. Results. There was a significant effect of storage time on total cholesterol (TC) (P < 0.001) and high density lipoprotein cholesterol (HDL-c) levels (P < 0.001), not LDL-c (P = 0.83). The lipid decay correction factor was 0.03 mmol/L and 0.024 mmol/L per additional year of storage for TC and HDL-c, respectively. The TC : HDL ratio decreased after correction for storage effect. After correction, only 5% of patients were reclassified to another CV risk group. Conclusion. A modest storage decay effect on lipoproteins was found that is unlikely to significantly affect CV risk stratification. Serum samples that have been stored long-term (>10 years) can be used to obtain valid lipid levels for developing CV risk prediction models in RA cohorts, even without applying a decay correction factor. Elke E. A. Arts, Calin D. Popa, Jacqueline P. Smith, Onno J. Arntz, Fons A. van de Loo, Rogier Donders, Anne Grete P. Semb, George D. Kitas, Piet L. C. M. van Riel, and Jaap Fransen Copyright © 2014 Elke E. A. Arts et al. All rights reserved. IGF-1 and ADMA Levels Are Inversely Correlated in Nondiabetic Ankylosing Spondylitis Patients Undergoing Anti-TNF-Alpha Therapy Thu, 11 Sep 2014 00:00:00 +0000 Like rheumatoid arthritis, ankylosing spondylitis (AS) is also an inflammatory disease associated with accelerated atherosclerosis and the presence of metabolic syndrome (MeS) features. AS patients often display osteoporosis as well as new bone formation. Insulin-like growth factor 1 (IGF-1) is a protein involved in both inflammation and bone metabolism. In the present study we assessed whether disease activity, systemic inflammation, MeS features, adipokines, and biomarkers of endothelial activation were associated with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels in a series of 30 nondiabetic AS patients without CV disease undergoing TNF- antagonist-infliximab therapy. All determinations were made in the fasting state, immediately before an infliximab infusion. Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA), an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (; ). However, no significant association was found between IGF-1 and IGFBP-3 levels and disease activity, systemic inflammation, metabolic syndrome features, or adipokines. In conclusion, in nondiabetic patients with AS undergoing periodic anti-TNF- therapy, IGF-1 and ADMA are inversely correlated. Fernanda Genre, Raquel López-Mejías, Javier Rueda-Gotor, José A. Miranda-Filloy, Begoña Ubilla, Aurelia Villar-Bonet, Beatriz Carnero-López, Inés Gómez-Acebo, Ricardo Blanco, Trinitario Pina, Carlos González-Juanatey, Javier Llorca, and Miguel A. González-Gay Copyright © 2014 Fernanda Genre et al. All rights reserved. Combined Home Exercise Is More Effective Than Range-of-Motion Home Exercise in Patients with Ankylosing Spondylitis: A Randomized Controlled Trial Sun, 07 Sep 2014 08:06:07 +0000 Home exercise is often recommended for management of patients with ankylosing spondylitis (AS); however, what kind of home exercise is more beneficial for patients with AS has not been determined yet. We aimed to compare the effectiveness of combined home exercise (COMB) and range-of-motion home exercise (ROM) in patients with AS. Nineteen subjects with AS completed either COMB () or ROM () program. The COMB program included range-of-motion, strengthening, and aerobic exercise while the ROM program consisted of daily range-of-motion exercise only. After exercise instruction, subjects in each group performed home exercise for 3 months. Assessment included cardiopulmonary exercise test, pulmonary function test, spinal mobility measurement, chest expansion, Bath Ankylosing Spondylitis Functional Index (BASFI), and other functional ability and laboratory tests. After exercise, the COMB group showed significant improvement in peak oxygen uptake (12.3%, ) and BASFI (), and the changed score between pre- and postexercise data was significantly greater in the COMB group regarding peak oxygen uptake and BASFI. Significant improvement in finger-to-floor distance after 3-month exercise was found only in the COMB group (). This study demonstrates that a combined home exercise is more effective than range-of-motion home exercise alone in aerobic capacity and functional ability. Lin-Fen Hsieh, Chih-Cheng Chuang, Ching-Shiang Tseng, James Cheng-Chung Wei, Wei-Chun Hsu, and Yi-Jia Lin Copyright © 2014 Lin-Fen Hsieh et al. All rights reserved. Acknowledged Signatures of Matrix Metalloproteinases in Takayasu’s Arteritis Wed, 03 Sep 2014 08:32:02 +0000 Takayasu’s arteritis (TA) was reported as an eye disease in the year 1905 and later was confirmed as a vasculitis. Since then, the etiology of the disease remains unknown; however, characteristic clinical features suggest multiple causative factors. Recent progress in vascular biology and other disciplines enlightens the pathophysiology of TA and demonstrated induction of various nonspecific inflammatory symptoms and destruction of the arterial wall, which leads to aneurysms and rupture of the affected arteries. Matrix metalloproteinases (MMPs) as an enzyme family have well-established roles in several vascular pathologies including intima formation, atherosclerosiss and aneurysms. MMPs have been proposed to be one of the molecules with a potential of having dual role in the course of TA, first as an active participant in pathophysiology and secondly as a diagnostic biomarker for TA disease. The desire to improve our understanding of the importance of MMPs and their endogenous inhibitors (TIMPs) in TA disease and for the development of therapeutic agents has inspired basic and clinical scientists for over a decade. In the present paper, we summarized the scientific rationale which highlights the signatures of matrix metalloproteinases and their endogenous inhibitors in pathophysiology as well as their being a potential candidate as biomarker for Takayasu’s arteritis. Gang Wu, Nitin Mahajan, and Veena Dhawan Copyright © 2014 Gang Wu et al. All rights reserved. Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy Wed, 27 Aug 2014 00:00:00 +0000 Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, , and to 56.0 mg/dL at 24 weeks, a 25.1% increase, ), while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, ). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks and also in TNF-α  . Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α. Norma Alejandra Rodriguez-Jimenez, Carlos E. Garcia-Gonzalez, Karina Patricia Ayala-Lopez, Benjamin Trujillo-Hernandez, Erika Anita Aguilar-Chavez, Alberto Daniel Rocha-Muñoz, Jose Clemente Vasquez-Jimenez, Eva Olivas-Flores, Mario Salazar-Paramo, Esther Guadalupe Corona-Sanchez, Monica Vazquez-Del Mercado, Evangelina Varon-Villalpando, Adolfo Cota-Sanchez, Ernesto German Cardona-Muñoz, Jorge I. Gamez-Nava, and Laura Gonzalez-Lopez Copyright © 2014 Norma Alejandra Rodriguez-Jimenez et al. All rights reserved. Health Technology Assessment of Belimumab: A New Monoclonal Antibody for the Treatment of Systemic Lupus Erythematosus Sun, 17 Aug 2014 11:04:47 +0000 Objective. Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy. Methods. SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed. Results. Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2–5-fold increase in mortality. Belimumab with SoC may prevent 4,742 flares in three years being cost-effective with an incremental cost-effectiveness ratio of €32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial. Conclusions. The assessment supports the use of belimumab into the SLE treatment paradigm in Italy. Maria Lucia Specchia, Chiara de Waure, Maria Rosaria Gualano, Andrea Doria, Giuseppe Turchetti, Lara Pippo, Francesco Di Nardo, Silvio Capizzi, Chiara Cadeddu, Flavia Kheiraoui, Luca Iaccarino, Francesca Pierotti, Ilaria Palla, Maria Assunta Veneziano, Daniela Gliubizzi, Antonella Sferrazza, Nicola Nicolotti, Rolando Porcasi, Giuseppe La Torre, Maria Luisa Di Pietro, and Walter Ricciardi Copyright © 2014 Maria Lucia Specchia et al. All rights reserved. Psychoeducation Program on Strategies for Coping with Stress in Patients with Temporomandibular Joint Dysfunction Wed, 13 Aug 2014 00:00:00 +0000 Lack of educational projects in the available literature was an inspiration to develop a psychoeducational program. The objective was to provide patients with basic information on the contribution of stressors in the occurrence of temporomandibular joint dysfunction and educate on methods for coping with stress most commonly used in psychology. In the course of three meetings, patients are familiarised with the issue of experienced stress as a potential source of psychosomatic illnesses (in particular, temporomandibular joint dysfunction). Preliminary patients’ opinions, expressed through self-report methods, indicate significant usefulness of the developed psychoeducational program for the process of treatment and the quality of patients’ lives. Joanna Biegańska and M. Pihut Copyright © 2014 Joanna Biegańska and M. Pihut. All rights reserved. Autoimmune Rheumatic Diseases Tue, 05 Aug 2014 08:37:14 +0000 Juan-Manuel Anaya, Yehuda Shoenfeld, Frank Buttgereit, and Miguel A. Gonzalez-Gay Copyright © 2014 Juan-Manuel Anaya et al. All rights reserved. Evaluation of Pain Regression in Patients with Temporomandibular Dysfunction Treated by Intra-Articular Platelet-Rich Plasma Injections: A Preliminary Report Sun, 03 Aug 2014 09:47:45 +0000 Objective. The objective of this study was to evaluate the regression of temporomandibular pain as a result of intra-articular injections of platelet-rich plasma (PRP) to patients with temporomandibular joint dysfunction previously subjected to prosthetic treatment. Materials and Methods. The baseline study material consisted of 10 patients, both males and females, aged 28 to 53 years, previously treated due to painful temporomandibular joint dysfunction using occlusal splints. All patients were carried out to a specialist functional assessment of the dysfunction using the Polish version of the RDC/TMD questionnaire axis I and II. Intra-articular injections were preceded by a preparation of PRP. The injection sites were determined by the method used during arthroscopic surgical procedures. Following aspiration, 0.5 mL of plasma was injected into each temporomandibular joint. Results. The comparison of the intensity of pain during all examinations suggests a beneficial effect of the procedure being performed as the mean VAS score was 6.5 at examination I, 2.8 at examination II, and 0.6 at examination III. Conclusion. Application of the intra-articular injections of platelet-rich plasma into the temporomandibular joints has a positive impact on the reduction of the intensity of pain experienced by patients treated for temporomandibular joint dysfunction. M. Pihut, M. Szuta, E. Ferendiuk, and D. Zeńczak-Więckiewicz Copyright © 2014 M. Pihut et al. All rights reserved. Cardiovascular Disease Risk amongst African Black Patients with Rheumatoid Arthritis: The Need for Population Specific Stratification Wed, 23 Jul 2014 11:34:56 +0000 Rheumatoid arthritis (RA) enhances the risk of cardiovascular disease to a similar extent as diabetes. Whereas atherogenesis remains poorly elucidated in RA, traditional and nontraditional risk factors associate similarly and additively with CVD in RA. Current recommendations on CVD risk stratification reportedly have important limitations. Further, reported data on CVD and its risk factors derive mostly from data obtained in the developed world. An earlier epidemiological health transition is intrinsic to persons living in rural areas and those undergoing urbanization. It is therefore conceivable that optimal CVD risk stratification differs amongst patients with RA from developing populations compared to those from developed populations. Herein, we briefly describe current CVD and its risk factor profiles in the African black population at large. Against this background, we review reported data on CVD risk and its potential stratification amongst African black compared to white patients with RA. Routinely assessed traditional and nontraditional CVD risk factors were consistently and independently related to atherosclerosis in African white but not black patients with RA. Circulating concentrations of novel CVD risk biomarkers including interleukin-6 and interleukin-5 adipokines were mostly similarly associated with both endothelial activation and atherosclerosis amongst African black and white RA patients. Ahmed Solomon, Linda Tsang, Angela J. Woodiwiss, Aletta M. E. Millen, Gavin R. Norton, and Patrick H. Dessein Copyright © 2014 Ahmed Solomon et al. All rights reserved. Cardiovascular Involvement in Autoimmune Diseases Tue, 22 Jul 2014 08:44:38 +0000 Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. Jenny Amaya-Amaya, Laura Montoya-Sánchez, and Adriana Rojas-Villarraga Copyright © 2014 Jenny Amaya-Amaya et al. All rights reserved. Psychosocial Aspects of Bruxism: The Most Paramount Factor Influencing Teeth Grinding Sun, 13 Jul 2014 00:00:00 +0000 In clinical practice, patients suffering from an occlusal parafunctional activity have increased. It can be observed that a negative influence of environment aggravates patient’s health. The aim of this paper is to present the impact of environment and development of human civilization on the prevalence of bruxism and the correlation between them. The authors grasp the most relevant aspects of psychological and anthropological factors changing over time as well as their interactions and describe a relationship between chronic stress and bruxism. Current literature shows how contemporary lifestyle, working environment, diet, and habits influence the patient’s psychoemotional situation and the way these factors affect the occluso-muscle condition. Mieszko Wieckiewicz, Anna Paradowska-Stolarz, and Wlodzimierz Wieckiewicz Copyright © 2014 Mieszko Wieckiewicz et al. All rights reserved. Prevalence and Correlation between TMD Based on RDC/TMD Diagnoses, Oral Parafunctions and Psychoemotional Stress in Polish University Students Wed, 09 Jul 2014 13:25:24 +0000 The aim of the study was to assess the prevalence of temporomandibular disorders (TMD) and oral parafunctions, as well as their correlation with psychoemotional factors in Polish university students. The research was conducted in a group of 456 students (). The examination form comprised of two parts: survey and clinical examination. The research diagnostic criteria for temporomandibular disorders (RDC/TMD) was used in order to assess TMD. Symptoms of TMD were observed in 246 (54%) students after clinical examination. The largest group involved students with disc displacement (women: 132, 29%; men: 70, 15%). Women (164; 36%) suffered more frequently than men (82; 18%) from problems related to the stomatognathic system (), described themselves as easily excitable and emotionally burdened, and reported symptoms as tightness of the facial and neck muscles (). In 289 (64%) students intraoral symptoms concerning occlusal parafunctions were observed. In 404 (89%) examined students, nonocclusal parafunctions were recorded. A significant correlation between TMD and psychoemotional problems could be detected. TMD symptoms more often concern women. Emotional burden and excitability are factors predisposing muscular disorders. Mieszko Wieckiewicz, Natalia Grychowska, Kamil Wojciechowski, Anna Pelc, Michal Augustyniak, Aleksandra Sleboda, and Marek Zietek Copyright © 2014 Mieszko Wieckiewicz et al. All rights reserved. Involvement of the Inconstant Bursa of the Fifth Metatarsophalangeal Joint in Psoriatic Arthritis: A Clinical and Ultrasonographic Study Tue, 01 Jul 2014 08:02:43 +0000 Objective. To evaluate the involvement of the bursa located next to the head of the 5th metatarsal bone in patients with psoriatic arthritis (PsA) in comparison with the other seronegative spondyloarthritis (SpA). Methods. All patients with PsA seen during a period of 24 months were enrolled. The control group included healthy subjects and patients with the other SpA. All subjects underwent clinical and ultrasound (US) examination of the lateral surface of the 5th metatarsal. Results. 150 PsA patients (88 M; 62 F), 172 SpA (107 M; 65 F), and 95 healthy controls (58 M; 37 F) were evaluated. Based on clinical and US evaluation, bursitis was diagnosed in 17/150 (11.3%) PsA patients but in none of the SpA () and healthy () controls. In detecting bursitis, US was more sensitive than clinical examination, although the difference did not reach statistical significance (). Conclusion. The bursa of the 5th metatarsophalangeal joint appears to be involved in PsA more frequently than by chance. If confirmed by other studies, this finding could be considered as a distinctive clinical sign of PsA, useful for differential diagnosis with the other SpA. In asymptomatic patients, US proved to be more sensitive in the detection of bursitis. Giovanni Ciancio, Stefania Volpinari, Maria Fotinidi, Federica Furini, Ilaria Farina, Alessandra Bortoluzzi, Manuela Ferracin, Francesca Bandinelli, Carlo Orzincolo, Francesco Trotta, and Marcello Govoni Copyright © 2014 Giovanni Ciancio et al. All rights reserved. Myorelaxant Effect of Bee Venom Topical Skin Application in Patients with RDC/TMD Ia and RDC/TMD Ib: A Randomized, Double Blinded Study Tue, 24 Jun 2014 06:51:56 +0000 The aim of the study was the evaluation of myorelaxant action of bee venom (BV) ointment compared to placebo. Parallel group, randomized double blinded trial was performed. Experimental group patients were applying BV for 14 days, locally over masseter muscles, during 3-minute massage. Placebo group patients used vaseline for massage. Muscle tension was measured twice (TON1 and TON2) in rest muscle tonus (RMT) and maximal muscle contraction (MMC) on both sides, right and left, with Easy Train Myo EMG (Schwa-medico, Version 3.1). Reduction of muscle tonus was statistically relevant in BV group and irrelevant in placebo group. VAS scale reduction was statistically relevant in both groups: BV and placebo. Physiotherapy is an effective method for myofascial pain treatment, but 0,0005% BV ointment gets better relief in muscle tension reduction and analgesic effect. This trial is registered with NCT02101632. Aleksandra Nitecka-Buchta, Piotr Buchta, Elżbieta Tabeńska-Bosakowska, Karolina Walczyńska-Dragoń, and Stefan Baron Copyright © 2014 Aleksandra Nitecka-Buchta et al. All rights reserved. Incidence of Otolaryngological Symptoms in Patients with Temporomandibular Joint Dysfunctions Tue, 24 Jun 2014 06:45:05 +0000 The functional disorders of the masticatory organ are the third stomatological disease to be considered a populational disease due to its chronicity and widespread prevalence. Otolaryngological symptoms are a less common group of dysfunction symptoms, including sudden hearing impairment or loss, ear plugging sensation and earache, sore and burning throat, difficulties in swallowing, tinnitus, and vertigo. The diagnostic and therapeutic problems encountered in patients with the functional disorders of the masticatory organ triggered our interest in conducting retrospective studies with the objective of assessing the incidence of otolaryngological symptoms in patients subjected to prosthetic treatment of the functional disorders of masticatory organ on the basis of the analysis of medical documentation containing data collected in medical interviews. Material and Methods. Retrospective study was conducted by analyzing the results of medical interviews of 1208 patients, who had reported for prosthetic treatment at the Functional Disorders Clinic of the Department of Dental Prosthetics of Jagiellonian University Medical College in Cracow between 2008 and March 14, 2014. Results. Otolaryngological symptoms were observed in 141 patients. The most common symptoms in the study group were earache and sudden hearing impairment; no cases of sudden hearing loss were experienced. E. Ferendiuk, K. Zajdel, and M. Pihut Copyright © 2014 E. Ferendiuk et al. All rights reserved. Correlation between TMD and Cervical Spine Pain and Mobility: Is the Whole Body Balance TMJ Related? Thu, 19 Jun 2014 12:06:44 +0000 Temporomandibular dysfunction (TMD) is considered to be associated with imbalance of the whole body. This study aimed to evaluate the influence of TMD therapy on cervical spine range of movement (ROM) and reduction of spinal pain. The study group consisted of 60 patients with TMD, cervical spine pain, and limited cervical spine range of movements. Subjects were interviewed by a questionnaire about symptoms of TMD and neck pain and had also masticatory motor system physically examined (according to RDC-TMD) and analysed by JMA ultrasound device. The cervical spine motion was analysed using an MCS device. Subjects were randomly admitted to two groups, treated and control. Patients from the treated group were treated with an occlusal splint. Patients from control group were ordered to self-control parafunctional habits. Subsequent examinations were planned in both groups 3 weeks and 3 months after treatment was introduced. The results of tests performed 3 months after the beginning of occlusal splint therapy showed a significant improvement in TMJ function , cervical spine ROM, and a reduction of spinal pain. The conclusion is that there is a significant association between TMD treatment and reduction of cervical spine pain, as far as improvement of cervical spine mobility. Karolina Walczyńska-Dragon, Stefan Baron, Aleksandra Nitecka-Buchta, and Ewaryst Tkacz Copyright © 2014 Karolina Walczyńska-Dragon et al. All rights reserved. Subchondral Bone Plate Thickening Precedes Chondrocyte Apoptosis and Cartilage Degradation in Spontaneous Animal Models of Osteoarthritis Wed, 18 Jun 2014 09:04:32 +0000 Osteoarthritis (OA) is the most common joint disorder characterised by bone remodelling and cartilage degradation and associated with chondrocyte apoptosis. These processes were investigated at 10, 16, 24, and 30 weeks in Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs that develop OA spontaneously. Both strains had a more pronounced chondrocyte apoptosis, cartilage degradation, and subchondral bone changes in the medial than the lateral side of the tibia, and between strains, the changes were always greater and faster in DH than BS2. In the medial side, a significant increase of chondrocyte apoptosis and cartilage degradation was observed in DH between 24 and 30 weeks of age preceded by a progressive thickening and stiffening of subchondral bone plate (Sbp). The Sbp thickness consistently increased over the 30-week study period but the bone mineral density (BMD) of the Sbp gradually decreased after 16 weeks. The absence of these changes in the medial side of BS2 may indicate that the Sbp of DH was undergoing remodelling. Chondrocyte apoptosis was largely confined to the deep zone of articular cartilage and correlated with thickness of the subchondral bone plate suggesting that cartilage degradation and chondrocyte apoptosis may be a consequence of continuous bone remodelling during the development of OA in these animal models of OA. Zaitunnatakhin Zamli, Kate Robson Brown, John F. Tarlton, Mike A. Adams, Georgina E. Torlot, Charlie Cartwright, William A. Cook, Kristiina Vassilevskaja, and Mohammed Sharif Copyright © 2014 Zaitunnatakhin Zamli et al. All rights reserved. Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing Sun, 15 Jun 2014 05:49:10 +0000 Determination of anti-citrullinated peptide antibodies (ACPA) plays a relevant role in the diagnosis of rheumatoid arthritis (RA). To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies for the diagnosis of RA. We compared three groups: RA (), chronic inflammatory disease (CIRD, ), and clinically healthy subjects (CHS, ) to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR) of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2%) as compared with anti-MCV (81.0%). When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis. Miriam Lizette Díaz-Toscano, Eva Maria Olivas-Flores, Soraya Amali Zavaleta-Muñiz, Jorge Ivan Gamez-Nava, Ernesto German Cardona-Muñoz, Manuel Ponce-Guarneros, Uriel Castro-Contreras, Arnulfo Nava, Mario Salazar-Paramo, Alfredo Celis, Nicte Selene Fajardo-Robledo, Esther Guadalupe Corona-Sanchez, and Laura Gonzalez-Lopez Copyright © 2014 Miriam Lizette Díaz-Toscano et al. All rights reserved. Renal Transplantation in Systemic Lupus Erythematosus: Outcome and Prognostic Factors in 50 Cases from a Single Centre Wed, 11 Jun 2014 06:14:42 +0000 Background. End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Objectives. To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Results. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36 ± 10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (), acute rejection (), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft () and positive anti-HCV antibodies () negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Conclusion. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure. Ernesto Cairoli, Carolina Sanchez-Marcos, Gerard Espinosa, Constanza Glucksmann, Guadalupe Ercilla, Federico Oppenheimer, and Ricard Cervera Copyright © 2014 Ernesto Cairoli et al. All rights reserved. Low Levels of CD36 in Peripheral Blood Monocytes in Subclinical Atherosclerosis in Rheumatoid Arthritis: A Cross-Sectional Study in a Mexican Population Mon, 09 Jun 2014 07:20:13 +0000 Patients with rheumatoid arthritis (RA) have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC) and carotid intima-media thickness (cIMT) in patients with RA. Methods. We included 67 patients with RA from the Rheumatology Department of Hospital Civil “Dr. Juan I. Menchaca,” Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNF were tested. Results. We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (). CD36 mean fluorescence intensity had negative correlations with cIMT (r = −0.578, ), ox-LDL (r = −0.427, P = 0.05), TNF (r = −0.729, ), and IL-6 (r = −0.822, ). Conclusion. RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA. Eduardo Gómez-Bañuelos, Beatriz Teresita Martín-Márquez, Erika Aurora Martínez-García, Mauricio Figueroa-Sanchez, Lourdes Nuñez-Atahualpa, Alberto Daniel Rocha-Muñoz, Pedro Ernesto Sánchez-Hernández, Rosa Elena Navarro-Hernandez, Perla Monserrat Madrigal-Ruiz, Adan Alberto Saldaña-Millan, Sergio Duran-Barragan, Laura Gonzalez-Lopez, Jorge Ivan Gamez-Nava, and Mónica Vázquez-Del Mercado Copyright © 2014 Eduardo Gómez-Bañuelos et al. All rights reserved. Differential Diagnostics of Pain in the Course of Trigeminal Neuralgia and Temporomandibular Joint Dysfunction Wed, 04 Jun 2014 07:28:00 +0000 Chronic oral and facial pain syndromes are an indication for intervention of physicians of numerous medical specialties, while the complex nature of these complaints warrants interdisciplinary diagnostic and therapeutic approach. Oftentimes, lack of proper differentiation of pain associated with pathological changes of the surrounding tissues, neurogenic pain, vascular pain, or radiating pain from idiopathic facial pain leads to improper treatment. The objective of the paper is to provide detailed characterization of pain developing in the natural history of trigeminal neuralgia and temporomandibular joint dysfunction, with particular focus on similarities accounting for the difficulties in diagnosis and treatment as well as on differences between both types of pain. It might seem that trigeminal neuralgia can be easily differentiated from temporomandibular joint dysfunction due to the acute, piercing, and stabbing nature of neuralgic pain occurring at a single facial location to spread along the course of the nerve on one side, sometimes a dozen or so times a day, without forewarning periods. Both forms differ significantly in the character and intensity of pain. The exact analysis of the nature, intensity, and duration of pain may be crucial for the differential diagnostics of the disorders of our interest. M. Pihut, M. Szuta, E. Ferendiuk, and D. Zeńczak-Więckiewicz Copyright © 2014 M. Pihut et al. All rights reserved. Diagnosis of Latent Tuberculosis in Patients with Systemic Lupus Erythematosus: T.SPOT.TB versus Tuberculin Skin Test Wed, 28 May 2014 08:06:53 +0000 Early studies in patients with systemic lupus erythematosus (SLE) reported increased incidence of tuberculosis. The tuberculin skin test (TST) is the technique of choice to detect latent tuberculosis infection (LTBI) but has several limitations. Objectives. We compared TST and the newer T.SPOT.TB test to diagnose LTBI in SLE patients. Methods. In this observational cohort study conducted between August 2009 and February 2012, we recruited 92 patients from those attending the SLE clinic of our university hospital. Data recorded were epidemiological and sociodemographic characteristics. Laboratory analyses included TST and T.SPOT.TB tests. Results. Of the patients studied, 92% were women with an average age of 42.7 years. Overall, the degree of correlation between the two tests was low (Kappa index = 0.324) but was better in patients not receiving corticosteroids (CTC)/immunosuppressive (IS) therapy (Kappa = 0.436) and in those receiving hydroxychloroquine (Kappa = 0.473). While TST results were adversely affected by those receiving CTC and/or IS drugs (), the T.SPOT.TB results were not. Conclusion. Although the TST test remains a useful tool for diagnosing LTBI in SLE patients, the T.SPOT.TB test is perhaps better employed when the patient is receiving CTC and/or IS drugs. Maria Del Mar Arenas Miras, Carmen Hidalgo-Tenorio, Pilar Jimenez-Gamiz, and Juan Jiménez-Alonso Copyright © 2014 Maria Del Mar Arenas Miras et al. All rights reserved. Commercial Bovine Proteoglycan Is Highly Arthritogenic and Can Be Used as an Alternative Antigen Source for PGIA Model Tue, 27 May 2014 12:29:23 +0000 Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies. Larissa Lumi Watanabe Ishikawa, Priscila Maria Colavite, Larissa Camargo da Rosa, Bianca Balbino, Thais Graziela Donegá França, Sofia Fernanda Gonçalves Zorzella-Pezavento, Fernanda Chiuso-Minicucci, and Alexandrina Sartori Copyright © 2014 Larissa Lumi Watanabe Ishikawa et al. All rights reserved. Occlusal Disorders among Patients with Total Clefts of Lip, Alveolar Bone, and Palate Tue, 27 May 2014 10:10:21 +0000 Clefts are common birth defects. They are accompanied by various malformations, including disturbances in facial look as well as skeletal disorders that include malocclusions, most frequently crossbites and class III anomalies. The aim of the study was to present the commonest malocclusions in patients with total cleft of the lip, alveolar bone and palate () and compare the results to the healthy on-cleft patients (). Normal occlusion, characteristic for I angle class, was observed in 50% of the control group and 30% of the examined. In the examined patients with clefts, most frequently crossbite and open bite on the cleft side was observed. In patients with clefts, only 2 out of 154 patients presented isolated dental anomalies. In healthy individuals the commonest occlusal disorder was distal occlusion and dental anomalies. The commonest malocclusions among patients with clefts are crossbites and class III malocclusions. Anna Paradowska-Stolarz and Beata Kawala Copyright © 2014 Anna Paradowska-Stolarz and Beata Kawala. All rights reserved. Attenuation of Collagen-Induced Arthritis in Mice by Salmon Proteoglycan Thu, 22 May 2014 09:26:05 +0000 Rheumatoid arthritis (RA) is a serious autoimmune disease caused by chronic inflammation of connective tissues. The basic principle of RA treatment is aimed to reduce joint inflammation. Our previous studies demonstrated that salmon cartilage proteoglycan (PG) suppresses excess inflammation in different mouse inflammatory diseases. In this study, we investigated the prophylactic effect of PG on the progression of RA using an experimental mouse model, collagen-induced arthritis (CIA). Clinical and histological severity of CIA was attenuated by daily oral administration of PG. In the joints of PG-administered mice, infiltration of macrophages and neutrophils and also osteoclast accumulation were limited. In comparison to nonadministered mice, anti-collagen antibodies in the sera of PG-administered mice did not alter. On the other hand, local expression of interleukin-17A (IL-17A), IL-6, IL-1β, interferon-γ (IFN-γ), C-C chemokine ligand 2 (CCL2), C-X-C chemokine ligand 1 (CXCL1), and CXCL2 in the joints of PG-administered mice decreased. Moreover, in the response of type II collagen- (CII-) restimulation ex vivo, IL-17A and IFN-γ production by splenocytes from PG-administered mice was less than that of control mice. These data suggested that daily ingested PG attenuated CIA pathogenesis by modulating immune response of splenocytes to CII stimulation and local production inflammatory cytokines and chemokines in the joints. Sayuri Yoshimura, Krisana Asano, and Akio Nakane Copyright © 2014 Sayuri Yoshimura et al. All rights reserved. Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of MTHFR rs1801133 and ATIC rs4673993 Polymorphisms Wed, 21 May 2014 11:28:42 +0000 Objective. Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; ) and ATIC 675T carriers (OR = 5.16; ) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; ), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; ) and antinuclear antibodies (OR = 2.28; ), with higher health assessment questionnaire score (OR = 2.42; ), and nonsteroidal anti-inflammatory drug users (OR = 2.77; ) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; ) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment. Aurea Lima, Joaquim Monteiro, Miguel Bernardes, Hugo Sousa, Rita Azevedo, Vitor Seabra, and Rui Medeiros Copyright © 2014 Aurea Lima et al. All rights reserved. Monitoring Drug and Antidrug Levels: A Rational Approach in Rheumatoid Arthritis Patients Treated with Biologic Agents Who Experience Inadequate Response While Being on a Stable Biologic Treatment Tue, 20 May 2014 09:32:20 +0000 Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response () with lower DAS28 and SDAI scores ( and ). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response ( and ), DAS28 score ( and ), and SDAI score ( and ). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN. Diana Mazilu, Daniela Opriş, Cecilia Gainaru, Mihaela Iliuta, Natalia Apetrei, Giorgiana Luca, Andreea Borangiu, Tania Gudu, Alexandra Peltea, Laura Groseanu, Cosmin Constantinescu, Ioana Saulescu, Violeta Bojinca, Andra Balanescu, Denisa Predeteanu, and Ruxandra Ionescu Copyright © 2014 Diana Mazilu et al. All rights reserved. Disease Activity in Psoriatic Arthritis: Comparison of the Discriminative Capacity and Construct Validity of Six Composite Indices in a Real World Tue, 20 May 2014 09:15:22 +0000 Objective. To compare, “in a real world,” the performance of the most common composite activity indices in a cohort of PsA patients. Methods. A total of 171 PsA patients were involved. The following variables were evaluated: peripheral joint assessment, patient reported of pain, physician and patient assessments of disease activity, patient general health status, dactylitis digit count, Leeds Enthesitis Index, Health Assessment Questionnaire (HAQ), physical and mental component summary score of the Medical Outcome Survey (SF-36), Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). To measure the disease activity, the Disease Activity Score (DAS28-ESR and DAS28-CRP), Simple Disease Activity Index (SDAI), Composite Psoriatic Disease Activity Index (CPDAI), disease activity in psoriatic arthritis (DAPSA), and Psoriatic Arthritis Disease Activity Score (PASDAS) have been calculated. The criteria for minimal disease activity (MDA) and remission were applied as external criterion. Results. The ROC were similar in all the composite measures. Only the CPDAI showed less discriminative ability. There was a high degree of correlation between all the indices (). The highest correlations were between DAPSA and SDAI (rho = 0.996) and between DAPSA and DAS28-CRP (rho = 0.957). CPDAI, DAPSA, and PASDAS had the most stringent definitions of remission and MDA category. DAS28-ESR and DAS28-CRP had the highest proportions in remission and MDA. Conclusions. Although a good concurrent validity and discriminant capacity of six disease activity indices were observed, the proportions of patients classified in the disease activity levels differed. In particular, the rate of patients in remission was clearly different among the respective indices. Fausto Salaffi, Alessandro Ciapetti, Marina Carotti, Stefania Gasparini, and Marwin Gutierrez Copyright © 2014 Fausto Salaffi et al. All rights reserved. The Effect of Rilonacept versus Placebo on Health-Related Quality of Life in Patients with Poorly Controlled Familial Mediterranean Fever Thu, 15 May 2014 11:58:34 +0000 Objective. To examine the effect of rilonacept on the health-related quality of life (HRQoL) in patients with poorly controlled familial Mediterranean fever (FMF). Methods. As part of a randomized, double-blinded trial comparing rilonacept and placebo for the treatment of FMF, patients/parents completed the modified Child Health Questionnaire (CHQ) at baseline, and at the start and end of each of 4 treatment courses, 2 each with rilonacept and placebo. Results. Fourteen subjects were randomized; mean age was 24.4 ± 11.8 years. At baseline the physical HRQoL score was significantly less (24.2 ± 49.5) but the psychosocial score was similar to the population norm (49.5 ± 10.0). There were significant improvements in most HRQoL concepts after rilonacept but not placebo. Significant differences between rilonacept and placebo were found in the physical (33.7 ± 16.4 versus 23.7 ± 14.5, ) but not psychosocial scores (51.4 ± 10.3 versus 49.8 ± 12.4, ). The physical HRQoL was significantly impacted by the treatment effect and patient global assessment. Conclusion. Treatment with rilonacept had a beneficial effect on the physical HRQoL in patients with poorly controlled FMF and was also significantly related to the patient global assessment. This trial is registered with Identifier NCT00582907. Philip J. Hashkes, Steven J. Spalding, Rula Hajj-Ali, Edward H. Giannini, Anne Johnson, Karyl S. Barron, Michael H. Weisman, Noune Pashinian, Andreas O. Reiff, Jonathan Samuels, Dowain Wright, Daniel J. Lovell, and Bin Huang Copyright © 2014 Philip J. Hashkes et al. All rights reserved. The Use of Hyaluronic Acid after Tendon Surgery and in Tendinopathies Thu, 08 May 2014 00:00:00 +0000 Viscosupplementation with hyaluronic acid is safe and effective in the management of osteoarthritis, but its use in the treatment of tendon disorders has received less attention. The aim of this review is to summarize the current knowledge on this topic, evaluating experimental and clinical trials. A search of English-language articles was performed using the key search terms “hyaluronic acid” or “viscosupplementation” combined with “tendon,” “tendinopathy,“ “adhesions,“ or “gliding,“ independently. In quite all the experimental studies, performed after surgical procedures for tendon injuries or in the treatment of chronic tendinopathies, using different hyaluronic acid compounds, positive results (reduced formation of scars and granulation tissue after tendon repair, less adhesions and gliding resistance, and improved tissue healing) were observed. In a limited number of cases, hyaluronic acid has been employed in clinical practice. After flexor tendon surgery, a greater total active motion and fingers function, with an earlier return to work and daily activities, were observed. Similarly, in patients suffering from elbow, patellar, and shoulder tendons disorders, pain was reduced, and function improved. The positive effect of hyaluronic acid can be attributed to the anti-inflammatory activity, enhanced cell proliferation, and collagen deposition, besides the lubricating action on the sliding surface of the tendon. Michele Abate, Cosima Schiavone, and Vincenzo Salini Copyright © 2014 Michele Abate et al. All rights reserved. Comparison of Selected Kinematic Facebows Applied to Mandibular Tracing Wed, 07 May 2014 09:35:49 +0000 The study focused on the comparison between mechanical and computerized registration methods used by the two selected kinematic facebows. The material consisted of 35 women aged 18 to 35, studied using the Gerber Dynamic Facebow and the computerized ARCUSdigma II axiograph. To compare the devices the condylar path inclination (CPI) was recorded according to the Camper’s line, enabling the acquisition of easily comparable values based on which the devices were objectively and subjectively analyzed. Statistics was performed for the obtained data. The study showed that the values for the CPI registrated by the ARCUSdigma II are significantly higher than those obtained by using the Gerber Dynamic Facebow. The significant difference in the records of the CPI is most likely a result of the differences in the registration techniques assumptions. ARCUSdigma II provides the user with more diagnostic options than Gerber Dynamic Facebow. Mechanical facebow handling has a higher risk of hand-measuring errors in tracing procedure. Due to high discrepancy of achieved results from different systems the authors recommend to use articulator compatible with facebow whose measurement has been done. Mieszko Wieckiewicz, Marek Zietek, Danuta Nowakowska, and Wlodzimierz Wieckiewicz Copyright © 2014 Mieszko Wieckiewicz et al. All rights reserved. B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers Tue, 29 Apr 2014 07:46:11 +0000 The therapeutic benefit of depleting B cells in rheumatoid arthritis (RA) has refocused attention on B cells with increasing awareness on their role in autoimmunity and their function beyond autoantibody production. The rapid increase in our comprehension of B-cell pathobiology is progressively opening novel perspectives in the area of B cell-targeted therapies with the expectation to define more specific approaches able to preserve the homeostasis of the humoral response while disrupting the pathogenic components. In parallel, B-cell activity in RA is starting to be explored in its clinical value, in search of novel biomarkers embedded in the pathogenic process that could help classifying the disease and predicting its heterogeneous outcome beyond inflammation dynamics. In this review, we summarize current knowledge on the multiple roles that B cells play in several aspects of RA. We also analyze their distribution and potential function in different anatomic compartments with specific reference to the main sites in which the disease may be sustained and exert its detrimental effects: the systemic circulation, synovium, bone marrow, and draining lymph nodes. We also highlight novel data encouraging further research in the field of biomarkers related to B cells and their regulatory factors. Serena Bugatti, Barbara Vitolo, Roberto Caporali, Carlomaurizio Montecucco, and Antonio Manzo Copyright © 2014 Serena Bugatti et al. All rights reserved. Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease Thu, 10 Apr 2014 08:20:37 +0000 This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient’s stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. José Manuel López-Cacho, Soledad Gallardo, Manuel Posada, Miriam Aguerri, David Calzada, Teodoro Mayayo, María Luisa González-Rodríguez, Antonio María Rabasco, Carlos Lahoz, and Blanca Cárdaba Copyright © 2014 José Manuel López-Cacho et al. All rights reserved. IL-6, IL-8, and IL-10 Are Associated with Hyperferritinemia in Rapidly Progressive Interstitial Lung Disease with Polymyositis/Dermatomyositis Tue, 01 Apr 2014 07:57:13 +0000 Objective. Hyperferritinemia is frequently accompanied by rapidly progressive (RP) interstitial lung disease (ILD) with polymyositis (PM)/dermatomyositis (DM). To clarify the mechanism of RP-ILD with hyperferritinemia, we investigated the associations between serum ferritin levels and various cytokines in patients with PM/DM. Methods. This retrospective study included 38 patients admitted to our hospital with PM/DM. Levels of serum ferritin and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-18, TNF-α, IFN-α, IFN-γ, and IP-10) were measured. Disease activity was evaluated using the tool proposed by the International Myositis Assessment and Clinical Studies Group. We analyzed the associations between disease activity and levels of serum ferritin and cytokines. Results. The levels of serum ferritin, IL-8, IL-10, IL-18, and TNF-α, were significantly correlated with disease activity. In a multivariate analysis, IL-6 , IL-8 , and IL-10 significantly contributed to serum ferritin levels. The levels of serum ferritin, IL-6, IL-8, and IL-10, were higher in the RP-ILD subset than in the non-ILD subset or the chronic ILD subset. Conclusion. IL-6, IL-8, and IL-10 are significant contributors to hyperferritinemia in PM/DM. The regulation of these cytokines might offer a possible treatment strategy for RP-ILD with PM/DM. Hidenaga Kawasumi, Takahisa Gono, Yasushi Kawaguchi, Hirotaka Kaneko, Yasuhiro Katsumata, Masanori Hanaoka, Sayuri Kataoka, and Hisashi Yamanaka Copyright © 2014 Hidenaga Kawasumi et al. All rights reserved. CD20+ B Cell Depletion in Systemic Autoimmune Diseases: Common Mechanism of Inhibition or Disease-Specific Effect on Humoral Immunity? Thu, 27 Mar 2014 08:54:44 +0000 Autoimmunity remains a complex physiologic deviation, enabled and perpetuated by a variety of interplayers and pathways. Simplistic approaches, targeting either isolated end-effectors of more centrally placed interactors of these mechanisms, are continuously tried in an effort to comprehend and halt cascades with potential disabling and deleterious effects in the affected individuals. This review focuses on theoretical and clinically proved effects of rituximab-induced CD20+ B cell depletion on different systemic autoimmune diseases and extrapolates on pathogenetic mechanisms that may account for different interindividual or interdisease responses. Panagiotis Pateinakis and Athina Pyrpasopoulou Copyright © 2014 Panagiotis Pateinakis and Athina Pyrpasopoulou. All rights reserved. Imbalance between Endothelial Damage and Repair: A Gateway to Cardiovascular Disease in Systemic Lupus Erythematosus Wed, 26 Mar 2014 13:41:28 +0000 Atherosclerosis is accelerated in patients with systemic lupus erythematosus (SLE) and it leads to excessive cardiovascular complications in these patients. Despite the improved awareness of cardiovascular disease and advent of clinical diagnostics, the process of atherogenesis in most patients remains clinically silent until symptoms and signs of cardiovascular complications develop. As evidence has demonstrated that vascular damage is already occurring before clinically overt cardiovascular disease develops in lupus patients, intervention at the preclinical stage of atherogenesis would be plausible. Indeed, endothelial dysfunction, one of the earliest steps of atherogenesis, has been demonstrated to occur in lupus patients even when they are naïve for cardiovascular disease. Currently known “endothelium-toxic” factors including type 1 interferon, proinflammatory cytokines, inflammatory cells, immune complexes, costimulatory molecules, neutrophils extracellular traps, lupus-related autoantibodies, oxidative stress, and dyslipidemia, coupled with the aberrant functions of the endothelial progenitor cells (EPC) which are crucial to vascular repair, likely tip the balance towards endothelial dysfunction and propensity to develop cardiovascular disease in lupus patients. In this review, altered physiology of the endothelium, factors leading to perturbed vascular repair contributed by lupus EPC and the impact of proatherogenic factors on the endothelium which potentially lead to atherosclerosis in lupus patients will be discussed. Anselm Mak and Nien Yee Kow Copyright © 2014 Anselm Mak and Nien Yee Kow. All rights reserved. The Interrelationship between Leukotriene B4 and Leukotriene-A4-Hydrolase in Collagen/Adjuvant-Induced Arthritis in Rats Thu, 20 Feb 2014 07:56:04 +0000 This study aimed to check the involvement of lipid mediator leukotriene (LT) B4 and the activity of LTA4 hydrolase (LTA4H) in the development of arthritis induced in rats by collagen and adjuvant (CIA). High-performance liquid chromatography (HPLC) and enzyme immunoassay (EIA) were used for measurements of LTB4 and LTA4H in plasma, synovial fluid (SF), soluble (SO), and solubilized membrane-bound fraction (MB) from synovial tissue (ST) and peripheral blood mononuclear cells (PBMCs) of CIA-arthritic and CIA-resistant. EIA process is simple, clean, and rapid and offered advantages over HPLC, showing that in SF and MB-PBMCs of CIA-arthritic and CIA-resistant, and in MB-ST of CIA-resistant, LTB4 and LTA4H were altered in parallel and were positively related. In the plasma and SO-ST and SO-PBMCs of CIA-arthritic and CIA-resistant, and in MB-ST of CIA-arthritic, this pattern was not found. The primordial role played by LTA4H in the biosynthesis of LTB4 was confirmed together with the existence of alternative steps that regulate LTB4 without participation of LTA4H. The involvement of compartmentalized and coupled changes of LTB4 and LTA4H in the resistance and development of arthritis in CIA model was demonstrated for the first time. Mariana Trivilin Mendes and Paulo Flavio Silveira Copyright © 2014 Mariana Trivilin Mendes and Paulo Flavio Silveira. All rights reserved. Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis Wed, 29 Jan 2014 00:00:00 +0000 Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4+ T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity. A. Hanyecz, K. Olasz, O. Tarjanyi, P. Nemeth, K. Mikecz, T. T. Glant, and F. Boldizsar Copyright © 2014 A. Hanyecz et al. All rights reserved. Regular Aerobic Training Combined with Range of Motion Exercises in Juvenile Idiopathic Arthritis Wed, 22 Jan 2014 17:03:49 +0000 Objective. To assess the effects of regular aerobic training combined with range of motion (ROM) exercises on aerobic capacity, quality of life, and function in children with juvenile idiopathic arthritis (JIA). Methods. Thirty patients with JIA and 20 healthy age-matched controls (mean age ± SD, 11.3 ± 2.4 versus 11.0 ± 2.3, resp.; ) were included. All patients performed aerobic walking (4 days a week for 8 weeks) and active and passive ROM exercises of involved joints. All patients completed the childhood health assessment questionnaire (CHAQ) and the child health questionnaire. ROM measurements of joints were performed by using universal goniometer. Aerobic capacity was determined by measuring peak oxygen uptake () during an incremental treadmill test. Results. Peak oxygen uptake and exercise duration were significantly lower in JIA group than in controls (32.5 ± 6.6 versus 35.9 ± 5.8 and 13.9 ± 1.9 versus 15.0 ± 2.0, resp.; for both). Eight-week combined exercise program significantly improved exercise parameters of JIA patients (baseline versus postexercise and exercise duration, 32.5 ± 6.6 to 35.3 ± 7.9 and 13.9 ± 1.9 to 16.3 ± 2.2, resp.; for both). Exercise intervention significantly improved CHAQ scores in JIA patients (0.77 ± 0.61 to 0.20 ± 0.28, ). Conclusion. We suggest that regular aerobic exercise combined with ROM exercises may be an important part of treatment in patients with JIA. Mine Doğru Apti, Özgür Kasapçopur, Murat Mengi, Gülnur Öztürk, and Gökhan Metin Copyright © 2014 Mine Doğru Apti et al. All rights reserved. Interleukin 6 and Rheumatoid Arthritis Sun, 12 Jan 2014 11:48:08 +0000 Interleukin-6 (IL-6) is a representative cytokine featuring pleiotropic activity and redundancy. A transient synthesis of IL-6 contributes to host defense against infectious agents and tissue injuries by inducing acute phase reactions and immunological and hematopoietic responses. However, uncontrolled persistent production of IL-6 may lead to the development of several immune-mediated diseases. Rheumatoid arthritis (RA) is a chronic disease with joint and systemic inflammation resulting from immunological abnormalities and it has been found that IL-6 plays a key role in the development of this disease. Clinical trials in various parts of the world of tocilizumab, a humanized anti-IL-6 receptor antibody, have proved its efficacy and tolerable safety either as monotherapy or in combination with disease-modifying antirheumatic drugs. As a result, it is currently used as a first-line biologic for the treatment of moderate-to-severe RA in more than 100 countries. Clarification of the mechanism(s) through which tocilizumab exerts its effect on RA and of the reason(s) why IL-6 is continuously produced in RA can be expected to lead to the best use of this agent for RA patients and aid in investigations into the pathogenesis of RA. Yuji Yoshida and Toshio Tanaka Copyright © 2014 Yuji Yoshida and Toshio Tanaka. All rights reserved. Statins Do Not Influence Long-Term Rituximab Clinical Efficiency in Rheumatoid Arthritis Patients Wed, 08 Jan 2014 13:06:48 +0000 Objective. This longitudinal study aims to determine if statins inhibit the response to rituximab in rheumatoid arthritis (RA) patients. Methods. 41 patients initiating rituximab were included; 17 patients were exposed to the combination of statins and rituximab. The total cholesterol, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. The clinical response was evaluated using Disease Activity Score (DAS28) and European League against Rheumatism (EULAR) response at 6 and 18 months. Results. A tendency of increasing in DAS28 was observed in statin-exposed group but the correlation was very weak (at 18 months: , ). The statin-exposed status was negatively and very weakly correlated with EULAR response at 6 months (, ) and 18 months (, ). There was a negative correlation between statin-exposed status and inflammatory markers values (ESR and CRP); however, the correlation was very weak. The use of statin did not influence the cardiovascular risk measured by modified Systematic Coronary Risk Evaluation (mSCORE). Conclusions. Long-term significant inhibitory effects of statins on rituximab treatment in RA have not been proved using clinical response scores or biologic markers. Diana Mazilu, Tania Gudu, Ruxandra Ionescu, and Daniela Opris Copyright © 2014 Diana Mazilu et al. All rights reserved. Serum Levels of Three Angiogenic Factors in Systemic Lupus Erythematosus and Their Clinical Significance Mon, 06 Jan 2014 14:06:05 +0000 Our research investigates the serum levels of three angiogenic factors in the AF family, namely, placenta growth factor (PlGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), in 54 patients with SLE (SLE group) and 28 healthy controls (normal control) through ELISA measurement. And their interrelationships were also systematically analyzed. The SLE patients were then divided into active SLE group and inactive SLE group according to the SLEDAI score. The results show that serum levels of PlGF, bFGF, and VEGF in all SLE group and active SLE group were higher than those in normal controls. Serum levels of PlGF and bFGF in inactive SLE group were higher than those in normal controls. The level of PlGF was positively correlated with VEGF in SLE patients and positive correlation is also shown in bFGF with VEGF. The levels of PlGF and VEGF in SLE patients were positively correlated with both ESR and SLEDAI score. Thus a tentative conclusion can be drawn that the serum levels of the angiogenic factors, for example, PlGF, bFGF, and VEGF, may be relevant in the pathogenesis of SLE, and the concentrations of PlGF and VEGF seem to be the markers of SLE activity. Ling Zhou, Guoyuan Lu, Lei Shen, Linfeng Wang, and Mingjun Wang Copyright © 2014 Ling Zhou et al. All rights reserved. Intensity-Dependent Effect of Treadmill Running on Knee Articular Cartilage in a Rat Model Tue, 31 Dec 2013 17:53:20 +0000 Objective. To understand the changes of femoral cartilage in response to treadmill running with different intensities in the hope of differentiating “moderate” and “strenuous” running in a rat model. Method. A total of 24 male Wistar rats were randomly assigned into groups of sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR). Rats in LIR, MIR, and HIR groups underwent 8 weeks’ treadmill running programs. After sacrificed, femoral condyles were collected to take histomorphometric analysis and immunohistochemistry for collagen II. Results. Gross and histological observation showed osteoarthritic changes in group HIR. In comparison to SED group, there was significant increase in cartilage thickness, number of chondrocytes, and GAG content in groups LIR and MIR. Conversely, decrease in cartilage thickness, chondrocyte number, and GAG content was found in rats of HIR group, without significant difference though. In addition, in comparison to SED group, HIR group exhibited disorganization of collagen fibril and significantly lower content of collagen type II. Conclusion. An intensity-dependent effect was suggested on the articular cartilage. Our results also demonstrated that running with low-to-medium intensity applied in the present study should be regarded as “moderate” running, whereas high-intensity running as “strenuous” running. Guo-Xin Ni, Sheng-Yao Liu, Lei Lei, Zhe Li, Yue-Zhu Zhou, and Li-Qiong Zhan Copyright © 2013 Guo-Xin Ni et al. All rights reserved. Rare Variants in the TREX1 Gene and Susceptibility to Autoimmune Diseases Wed, 09 Oct 2013 09:59:50 +0000 TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE. Nadia Barizzone, Sara Monti, Simona Mellone, Michela Godi, Maurizio Marchini, Raffaella Scorza, Maria G. Danieli, and Sandra D’Alfonso Copyright © 2013 Nadia Barizzone et al. All rights reserved. Behcet’s Disease: Systemic and Ocular Manifestations Thu, 03 Oct 2013 17:43:39 +0000 Aim. The aim of this study was to evaluate if patients with Behcet’s disease who have ocular involvement have a more severe form of this disease as compared to patients with Behcet’s disease alone. Methods. A total of 99 patients were included in the study. 76 patients were used as part of the examined group, and 23 patients formed a control group. Results. The following are the results of examined and control groups, respectively: recurrent oral aphthous ulcers 89.5%, 95.7%; genital ulcers 61.8%, 97.0%; articular involvement 72.4%, 65.2%; vasculitis 81.6%, 60.9%; positive pathergy test 25.0%, 47.8%. Higher frequency of genital ulcerations was noted in control group (). More than two major criteria were met in 100% of the cases. HLA B51 was present in 78.9% of the cases in the examined group and 43.5% of the cases in control group; thus there is significant difference between them (). Visual acuity >0.5 occurred in 76% (examined group). Most frequent ocular manifestations in the examined group were retinal periphlebitis 81.6%, periphlebitis and periarteritis 65%, and serofibrinous uveitis 63.2%. Macular edema as a complication was present in 63.2%. The majority of patients (55.3%) were treated with combined therapy consisting of cyclosporine A and systemic corticosteroids. In 38.2% of patients, laser photocoagulation was used on retinal periphery. Jelena Paovic, Predrag Paovic, and Vojislav Sredovic Copyright © 2013 Jelena Paovic et al. All rights reserved. The Effects of Pterostilbene on Neutrophil Activity in Experimental Model of Arthritis Mon, 30 Sep 2013 08:12:19 +0000 It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophils in vitro. However, little is known about its effects on neutrophils during inflammation in vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model. Lewis rats were injected by a single intradermal injection of heat-killed Mycobacterium butyricum in Freund’s adjuvant to develop arthritis. Another group of arthritic animals received pterostilbene 30 mg/kg, daily, p.o. The number and activity of neutrophils in blood were measured on a weekly basis during the whole experiment. Moreover, the total radical trapping potential in plasma was measured at the end of the experiment. In the pterostilbene treated arthritic group, the treatment significantly lowered the number of neutrophils in blood on days 14 and 21 without significant downregulation of neutrophil oxidative burst. Pterostilbene nonsignificantly increased total radical trapping potential in arthritic animals. These results indicate that the promising effects of pterostilbene on reactive oxygen species operate by different mechanisms in vitro and in the animal model of inflammation. In conclusion, the positive effects of pterostilbene in the model of arthritis may be attributed to regulation of neutrophil number. Tomas Perecko, Katarina Drabikova, Antonin Lojek, Milan Ciz, Silvester Ponist, Katarina Bauerova, Radomir Nosal, Juraj Harmatha, and Viera Jancinova Copyright © 2013 Tomas Perecko et al. All rights reserved. Cancer Morbidity in Rheumatoid Arthritis: Role of Estrogen Metabolites Tue, 17 Sep 2013 18:16:39 +0000 Estrogen metabolites have been implicated in rheumatoid arthritis (RA) and cancer, although the mechanism remains unestablished. Some estrogen metabolites, which are used for the assessment of cancer risk, play an important role in RA. The pathways by which malignancies associated with RA remain elusive. Possible mechanism involves enzymatic or nonenzymatic oxidation of estrogen into catecholestrogen metabolites through semiquinone and quinone redox cycle to produce free radicals that can cause DNA modifications. Modifications of DNA alter its immunogenicity and trigger various immune responses leading to elevated levels of cancer and RA antibodies. However, the role of different estrogen metabolites as a mediator of immune response cannot be ruled out in various immune-related diseases. Wahid Ali Khan and Mohd Wajid Ali Khan Copyright © 2013 Wahid Ali Khan and Mohd Wajid Ali Khan. All rights reserved. Leflunomide as a Corticosteroid-Sparing Agent in Giant Cell Arteritis and Polymyalgia Rheumatica: A Case Series Wed, 11 Sep 2013 08:48:14 +0000 Objectives. Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) affect individuals older than 50 years of age and corticosteroids are the mainstay of treatment. The aim of our study was to explore the role of leflunomide as a corticosteroid-sparing agent in GCA and PMR patients. Methods. Patients with difficult-to-treat GCA and PMR were retrospectively identified in the period from 2010 to 2013. The doses of corticosteroids and CRP values were noted before, after three months, and at the end of the treatment with leflunomide (for patients continuing treatment, censoring date was January 1, 2013). Results. Twenty-three patients were identified (12 with PMR and 11 with GCA). A reduction of 6 mg/dL (CI 95% –10.9–34.2, ) in CRP and 3.7 mg (CI 95% 0.5–7.0, ) in prednisolone dose was observed in the PMR group. In GCA patients, the reduction was 12.4 mg/dL (CI 95% 0.7–25.5, ) in CRP and 6.6 mg (CI 95% 2.8–10.3, ) in prednisolone dose. Conclusion. Leflunomide seems to be effective as a corticosteroid-sparing agent in patients with difficult-to-treat GCA and PMR. Randomized controlled trials are warranted in order to confirm the usefulness of leflunomide in the therapy of GCA/PMR. Andreas P. Diamantopoulos, Helene Hetland, and Geirmund Myklebust Copyright © 2013 Andreas P. Diamantopoulos et al. All rights reserved. Serum Proteome Analysis in Patients with Rheumatoid Arthritis Receiving Therapy with Tocilizumab: An Anti-Interleukin-6 Receptor Antibody Thu, 22 Aug 2013 12:38:33 +0000 Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the synovial membrane that results in the destruction of bone and cartilage in affected joints. Tocilizumab is a biological agent and an anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6-mediated inflammatory processes in RA patients. In order to identify novel disease-related proteins and candidate biomarkers, we analyzed the changes in the serum proteome profiles of patients with RA who were treated with tocilizumab. Serum samples were collected from the RA patients before and after tocilizumab treatment. Following immunodepletion of major proteins, the proteins were digested and labeled with isobaric tag, iTRAQ reagent. The proteins were identified and quantified using liquid chromatography-tandem mass spectrometry. Among a total of 311 proteins identified, seven were decreased and 16 were increased by tocilizumab treatment. Although some of the proteins are known to be related to RA, several are currently unknown with respect to their relationship to RA and may be involved in the development of this disease. This study is the first to perform a comparative serum proteomic analysis of RA patients treated with tocilizumab. Our results may contribute to the identification of novel disease-related proteins and enhance the understanding of the pathogenesis of RA. Mitsuaki Yanagida, Mikiko Kawasaki, Maki Fujishiro, Masako Miura, Keigo Ikeda, Kazuhisa Nozawa, Hiroshi Kaneko, Shinji Morimoto, Yoshinari Takasaki, Hideoki Ogawa, Kenji Takamori, and Iwao Sekigawa Copyright © 2013 Mitsuaki Yanagida et al. All rights reserved. Topical Application of Ketoprofen Improves Gait Disturbance in Rat Models of Acute Inflammation Wed, 07 Aug 2013 11:50:15 +0000 Arthritis is a disabling health problem and commonly develops in the late stages of life; the condition is typically accompanied by chronic pain. For the assessment of pain severity and therapeutic effects of analgesic drugs, we recently developed a gait analysis system, which provides an index of pain severity based on walking stride disturbance. Using this system, we evaluated the therapeutic effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) in rat models of acute inflammation. We found that the gait analysis system is more sensitive than conventional evaluation methods, such as measurement of swelling or analgesia, which indicated the superiority of our system for drug screening. The approach also indicated that ketoprofen is superior to other NSAIDs for providing pain relief because of its higher skin permeability. To the best of our knowledge, this is the first report demonstrating the effectiveness of topical NSAIDs in experimental animal models of acute inflammation. Yosuke Amagai, Akane Tanaka, Akira Matsuda, Kumiko Oida, Kyungsook Jung, Sho Nishikawa, Hyosun Jang, Saori Ishizaka, and Hiroshi Matsuda Copyright © 2013 Yosuke Amagai et al. All rights reserved. In Systemic Sclerosis, Anxiety and Depression Assessed by Hospital Anxiety Depression Scale Are Independently Associated with Disability and Psychological Factors Mon, 29 Jul 2013 16:18:04 +0000 Background. Anxious and depressive symptoms are frequent in Systemic Sclerosis (SSc). Our objective is to assess their prevalence and association with district and global disability and psychological variables. Methods. 119 SSc patients were assessed by Hospital Anxiety Depression Scale (HADS). Clinical depression and anxiety were defined for HADS score cutoff ≥8. Patients were assessed for psychological symptoms (RSES, COPE-NIV), hand (HAMIS, CHFDS, fist closure, and hand opening) and face disability (MHISS, mouth opening), global disability, and fatigue (HAQ, FACIT). Results. Both depression and anxiety in SSc are 36%. Depressive patients with comorbid anxiety have higher HADS-D score than patients with depression only (). HADS-A and -D are positively correlated with global disability, hands and mouth disability, fatigue, self-esteem and avoidance coping strategy, and, only HADS-A, also with social support (). By multiple regression, HADS-D is independently associated with FACIT-F (), RSES (), and MHISS total score (), together explaining 50% of variance. HADS-A is independently associated with RSES (), COPE-NIV SA (), COPE-NIV SS (), FACIT-F (), and MHISS mouth opening (), explaining 41% of variance. Conclusions. In SSc depression and anxiety correlate to local and global disabilities and psychological characteristics. Depressive patients with comorbid anxiety have higher level of depressive symptoms. Angela Del Rosso, Svetlana Mikhaylova, Marco Baccini, Ilaria Lupi, Marco Matucci Cerinic, and Susanna Maddali Bongi Copyright © 2013 Angela Del Rosso et al. All rights reserved. IL-17 in the Rheumatologist’s Line of Sight Thu, 25 Jul 2013 13:19:26 +0000 Over the past decades, the identification of several new cytokines, including interleukin (IL)-17 and IL-23, and of new T helper cell subsets, including Th17 cells, has changed the vision of immunological processes. The IL-17/Th17 pathway plays a critical role during the development of inflammation and autoimmunity, and targeting this pathway has become an attractive strategy for a number of diseases. This review aims to describe the effects of IL-17 in the joint and its roles in the development of autoimmune and inflammatory arthritis. Furthermore, biotherapies targeting directly or indirectly IL-17 in inflammatory rheumatisms will be developed. Marie-Elise Truchetet, M. Djavad Mossalayi, and Katia Boniface Copyright © 2013 Marie-Elise Truchetet et al. All rights reserved. From the Mediterranean to the Sea of Japan: The Transcontinental Odyssey of Autoinflammatory Diseases Tue, 23 Jul 2013 09:04:30 +0000 Autoinflammatory diseases are comprehensively caused by aberrant production of proinflammatory cytokines and are revealed by cyclically and spontaneously occurring inflammatory events. Over the last decade, there has been a revolution in the understanding of periodic fever syndromes, cryopyrinopathies, and skin disorders with pyogenic, granulomatous, or dystrophic features, which have been recognized across different countries spanning from the Mediterranean basin to the Japanese archipelago. Many children and adults with autoinflammatory diseases continue to elude diagnosis, and the diagnostic delay of many years puts these patients at risk of long-term severe complications, such as amyloidosis. Any hint of suspicion of autoinflammatory disease thus needs to be highlighted in various medical specialties, and this review examines their frequencies around the world, trying to match them with geographic location, ethnic and genetic data, in an attempt to realize a geoepidemiologic map for most of these conditions. Donato Rigante, Bruno Frediani, Mauro Galeazzi, and Luca Cantarini Copyright © 2013 Donato Rigante et al. All rights reserved. Pain Coping Strategies for Children with Arthritis Wed, 17 Jul 2013 11:02:33 +0000 Objective. To present information on pain management strategies for children with juvenile idiopathic arthritis (JIA). Methods. The second author developed a manual to present pain management strategies to children. The use of the manual was pilot-tested with a group of children with JIA. Telephone interviews were used to gather information on implementation of pain management strategies. Results. Children were able to implement the pain management strategies. Children reported a reduction in daily pain experiences related to JIA when using the pain management strategies. Conclusions. The pain management strategies were successful as an adjunctive intervention for short-term pain management. Pain symptoms related to JIA can severely limit children's participation in daily activities. Further study on how children use pain management strategies to improve their involvement in daily activities will provide useful clinical information. Kim J. Rosenzweig and Laura Nabors Copyright © 2013 Kim J. Rosenzweig and Laura Nabors. All rights reserved. Evaluation of Kinesiophobia and Its Correlations with Pain and Fatigue in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type Sun, 14 Jul 2013 16:26:54 +0000 Ehlers-Danlos syndrome hypermobility type a. k. a. joint hypermobility syndrome (JHS/EDS-HT) is a hereditary musculoskeletal disorder associating generalized joint hypermobility with chronic pain. Anecdotal reports suggest a prominent role for kinesiophobia in disease manifestations, but no study has systematically addressed this point. Objective. To investigate the impact of kinesiophobia and its relationship with pain, fatigue, and quality of life in JHS/EDS-HT. Design. Cross-sectional study. Subjects/Patients. 42 patients (40 female and 2 male) with JHS/EDS-HT diagnosis following standardized diagnostic criteria were selected. Methods. Disease features were analyzed by means of specific questionnaires and scales evaluating kinesiophobia, pain, fatigue, and quality of life. The relationships among variables were investigated using the Spearman bivariate analysis. Results. Kinesiophobia resulted predominantly in the patients’ sample. The values of kinesiophobia did not correlate with intensity of pain, quality of life, and (or) the single component of fatigue. A strong correlation was discovered between kinesiophobia and general severity of fatigue. Conclusions. In JHS/EDS-HT, the onset of pain-avoiding strategies is related to the presence of pain but not to its intensity. The clear-cut correlation between kinesiophobia and severity of fatigue suggests a direct link between musculoskeletal pain and fatigue. In JHS/EDS-HT, the underlying mechanism is likely to be facilitated by primary disease characteristics, including hypotonia. Claudia Celletti, Marco Castori, Giuseppe La Torre, and Filippo Camerota Copyright © 2013 Claudia Celletti et al. All rights reserved. Biological Activities of Phosphocitrate: A Potential Meniscal Protective Agent Thu, 11 Jul 2013 09:52:11 +0000 Phosphocitrate (PC) inhibited meniscal calcification and the development of calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the mechanisms remain elusive. This study sought to examine the biological activities of PC in the absence of calcium crystals and test the hypothesis that PC is potentially a meniscal protective agent. We found that PC downregulated the expression of many genes classified in cell proliferation, ossification, prostaglandin metabolic process, and wound healing, including bloom syndrome RecQ helicase-like, cell division cycle 7 homolog, cell division cycle 25 homolog C, ankylosis progressive homolog, prostaglandin-endoperoxide synthases-1/cyclooxygenase-1, and plasminogen activator urokinase receptor. In contrast, PC stimulated the expression of many genes classified in fibroblast growth factor receptor signaling pathway, collagen fibril organization, and extracellular structure organization, including fibroblast growth factor 7, collagen type I, alpha 1, and collagen type XI, alpha 1. Consistent with its effect on the expression of genes classified in cell proliferation, collagen fibril organization, and ossification, PC inhibited the proliferation of OA meniscal cells and meniscal cell-mediated calcification while stimulating the production of collagens. These findings indicate that PC is potentially a meniscal-protective agent and a disease-modifying drug for arthritis associated with severe meniscal degeneration. Yubo Sun, Andrea Roberts, David R. Mauerhan, Andrew R. Sun, H. James Norton, and Edward N. Hanley Jr. Copyright © 2013 Yubo Sun et al. All rights reserved. Joint Involvement in Primary Sjögren’s Syndrome: An Ultrasound “Target Area Approach to Arthritis” Mon, 08 Jul 2013 08:52:23 +0000 Objective. To characterize the ultrasound (US) pattern of joint involvement in primary Sjögren’s syndrome (pSS). Methods. Seventeen patients with pSS, 18 with secondary Sjögren’s syndrome (sSS), and 17 healthy controls underwent US examinations of various articular regions. Synovitis (synovial hypertrophy/joint effusion), power Doppler (PD) signals, and erosions were assessed. Results. In patients with pSS, synovitis was found in the metacarpophalangeal joints (MCP, 76%), wrists (76%), and knees (76%), while the proximal interphalangeal joints, elbows, and ankles were mostly unscathed. Intra-articular PD signals were occasionally detected in wrists (12%), elbows (6%), and knees (6%). Erosions were evident in the wrists of three (18%) patients with pSS, one of these also having anti-cyclic citrullinated peptide (anti-CCP) antibodies. While US synovitis does not discriminate between sSS and pSS, demonstration of bone erosions in the 2nd MCP joints showed 28.8% sensitivity and 100% specificity for diagnosing sSS; in comparison, these figures were 72.2 and 94.1% for circulating anti-CCP antibodies. Conclusions. In pSS, the pattern of joint involvement by US is polyarticular, bilateral, and symmetrical. Synovitis is the US sign most commonly found in patients with pSS, especially in MCP joints, wrists, and knees, and bone erosions also may occur. Luis M. Amezcua-Guerra, Fritz Hofmann, Angelica Vargas, Pedro Rodriguez-Henriquez, Carla Solano, Cristina Hernández-Díaz, Diana Castillo-Martinez, Lucio Ventura-Ríos, Marwin Gutiérrez, and Carlos Pineda Copyright © 2013 Luis M. Amezcua-Guerra et al. All rights reserved. A Replication Study from Chinese Supports Association between Lupus-Risk Allele in TNFSF4 and Renal Disorder Mon, 01 Jul 2013 11:25:19 +0000 A recent phenotypic association study of genetic susceptibility loci in SLE suggested that TNFSF4 gene might be useful to predict renal disorder in lupus patients. To replicate the association, two single-nucleotide polymorphisms (SNPs: rs2205960 and rs10489265) were genotyped in 814 SLE patients. Correlations between genotypes and TNFSF4 expression were determined. The stainings of TNFSF4 in renal biopsy specimens were checked by immunohistochemistry. The SNPs of TNFSF4 were associated with renal involvement in lupus patients from the Chinese population ( values for rs2205960 and rs10489265 were 0.014 and 0.005 in additive model, resp.). An association between risk genotypes and low C3 levels was also observed (). Functional prediction suggested that rs2205960 had a regulatory feature. The risk alleles seemingly correlated with lower TNFSF4 expression. Strong TNFSF4 expression was detected in lymph nodes and “apparently normal” paratumor renal biopsy but not in renal biopsies from lupus nephritis. In genome-wide expression data, TNFSF4 was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies. However, the associations were marginally significant. Our data firstly replicated the association of TNFSF4 with renal disorder in SLE patients in the Chinese population, which supported that TNFSF4 may act as a marker of lupus nephritis. The detailed mechanisms of its role in pathogenesis will still be further needed. Xu-jie Zhou, Fa-juan Cheng, Yuan-yuan Qi, Ming-hui Zhao, and Hong Zhang Copyright © 2013 Xu-jie Zhou et al. All rights reserved. Is Neutrophil/Lymphocyte Ratio Associated with Subclinical Inflammation and Amyloidosis in Patients with Familial Mediterranean Fever? Thu, 20 Jun 2013 08:16:10 +0000 Background. The purpose of the present study is to determine the association between neutrophil/lymphocyte ratio and both subclinical inflammation and amyloidosis in familial Mediterranean fever. Methods. Ninety-four patients with familial Mediterranean fever and 60 healthy volunteers were included in the study. Of the patients, 12 had familial Mediterranean fever related amyloidosis. The neutrophil/lymphocyte ratio of the patients was obtained from the hematology laboratory archive. Results. The neutrophil/lymphocyte ratio was significantly higher among persons with familial Mediterranean fever compared to healthy individuals (). Also, neutrophil/lymphocyte ratio was significantly higher in patients with amyloidosis than in amyloidosis-free patients (). Since NLR was evaluated in nonamyloid and amyloid stages of the same patient population (type 1 phenotype), we obtained significant statistical differences ( versus , , resp.). With the cutoff value of neutrophil/lymphocyte ratio >2.21 and AUC = 0.734 (), it was a reliable marker in predicting the development of amyloidosis. Conclusion. The neutrophil/lymphocyte ratio, an emerging marker of inflammation, is higher in patients with familial Mediterranean fever in attack-free periods. The neutrophil/lymphocyte ratio may be a useful marker in predicting the development of amyloidosis. Ali Ugur Uslu, Koksal Deveci, Serdal Korkmaz, Bahattin Aydin, Soner Senel, Enver Sancakdar, and Mehmet Sencan Copyright © 2013 Ali Ugur Uslu et al. All rights reserved. Treatment with Anti-Interleukin 23 Antibody Ameliorates Disease in Lupus-Prone Mice Thu, 06 Jun 2013 10:30:49 +0000 Interleukin 23 receptor expressing IL-17 producing T cells have been shown to be important in the development of murine lupus. The usefulness of IL-23 inhibition in ameliorating lupus nephritis is unknown. We hypothesized that inhibition of IL-23 will ameliorate nephritis in lupus-prone mice. To this end, we treated MRL/lpr lupus-prone mice for 6 weeks with a rat anti-IL-23p19 antibody, which resulted in delaying the onset of nephritis without affecting the production of anti-dsDNA antibodies. The effect of the treatment was hampered by the production of murine anti-rat IgG antibodies. The amelioration of murine lupus by IL-23 inhibition strengthens the rationale for targeting IL-23 in patients with systemic lupus erythematosus. Vasileios C. Kyttaris, Ourania Kampagianni, and George C. Tsokos Copyright © 2013 Vasileios C. Kyttaris et al. All rights reserved. Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis Thu, 21 Feb 2013 08:59:16 +0000 Phosphocitrate (PC), a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity. We found that PC inhibited the proliferation of OA fibroblast-like synoviocytes in the absence of calcium crystals. Consistent with its effect on cell proliferation, PC downregulated the expression of numerous genes classified in cell proliferation. PC also downregulated the expression of many genes classified in angiogenesis and inflammatory response including prostaglandin-endoperoxide synthase 2, interleukin-1 receptor, type I, and chemokine (C-C motif) ligand 2. In contrast, PC upregulated the expression of many genes classified in musculoskeletal tissue development, including aggrecan, type I collagen, and insulin-like growth factor binding protein 5. These findings suggest that PC is not only a promising disease-modifying drug for crystal-associated OA but also for noncrystal-associated OA. Yubo Sun, David R. Mauerhan, Atiya M. Franklin, James Norton, Edward N. Hanley Jr., and Helen E. Gruber Copyright © 2013 Yubo Sun et al. All rights reserved. Healthcare Utilization and Costs of Systemic Lupus Erythematosus in Medicaid Wed, 05 Dec 2012 08:16:04 +0000 Objective. Healthcare utilization and costs associated with systemic lupus erythematosus (SLE) in a US Medicaid population were examined. Methods. Patients ≥ 18 years old with SLE diagnosis (ICD-9-CM 710.0x) were extracted from a large Medicaid database 2002–2009. Index date was date of the first SLE diagnosis. Patients with and without SLE were matched. All patients had a variable length of followup with a minimum of 12 months. Annualized healthcare utilization and costs associated with SLE and costs of SLE flares were assessed during the followup period. Multivariate regressions were conducted to estimate incremental healthcare utilization and costs associated with SLE. Results. A total of 14,777 SLE patients met the study criteria, and 14,262 were matched to non-SLE patients. SLE patients had significantly higher healthcare utilization per year than their matched controls. The estimated incremental annual cost associated with SLE was $10,984, with the highest increase in inpatient costs (). Cost per flare was $11,716 for severe flares, $562 for moderate flares, and $129 for mild flares. Annual total costs for patients with severe flares were $49,754. Conclusions. SLE patients had significantly higher healthcare resource utilization and costs than non-SLE patients. Patients with severe flares had the highest costs. Hong J. Kan, Xue Song, Barbara H. Johnson, Benno Bechtel, Donna O'Sullivan, and Charles T. Molta Copyright © 2013 Hong J. Kan et al. All rights reserved. Dermal Ultrastructure in Low Beighton Score Members of 17 Families with Hypermobile-Type Ehlers-Danlos Syndrome Wed, 03 Oct 2012 08:06:46 +0000 The distinction between the Ehlers-Danlos syndrome hypermobile type (EDSH) and the benign joint hypermobility syndrome (BJHS) is unclear. The aim of the present study was to compare skin ultrastructural abnormalities of EDSH and BJHS among different families. Skin of 23 EDSH, 27 BJHS, and 41 asymptomatic subjects from 17 families was examined using transmission electron microscopy. Similar ultrastructural abnormalities were found irrespective of the Beighton score. Flower-like collagen fibrils represented the key change and elastic fibers were altered as well. Beighton score is a clinical parameter rating joint mobility that appeared unrelated to quantitative and qualitative collagen ultrastructural alterations in the skin. Some EDSH family members fit with BJHS diagnosis. BJHS possibly represents a mild variant of EDSH. Trinh Hermanns-Lê, Marie-Annick Reginster, Claudine Piérard-Franchimont, Philippe Delvenne, Gérald E. Piérard, and Daniel Manicourt Copyright © 2012 Trinh Hermanns-Lê et al. All rights reserved. The Effect of Bradykinin B2 Receptor Polymorphisms on the Susceptibility and Severity of Osteoarthritis in a Chinese Cohort Wed, 03 Oct 2012 08:04:33 +0000 Background. The B2-bradykinin receptor (BDKRB2) has been reported to associate with onset and development of Osteoarthritis (OA); however, the role of BDKRB2 genetic polymorphisms in OA remains unknown. Method. A total of 245 patients with primary knee OA and 264 healthy volunteer were recruited. BDKRB2 gene polymorphisms, −58T/C and +9/−9 bp polymorphisms, were genotyped. Results. The genotype distributions and allele frequencies of +9/−9 bp polymorphisms significantly differed between OA and control subjects. Logistic regression analysis showed carriers with −9/−9 genotype had a significantly increased risk for knee OA compared with the +9/+9 genotype (adjusted , ). The OR for −9 allele carriage was significantly higher than +9 allele carriage (adjusted , ). The +9/−9 bp polymorphisms also determined the OA radiographic severity. The presence of −9 bp was associated with severer OA. The −58T/C polymorphisms did not affect OA risk and severity. Conclusion. The +9/−9 bp polymorphisms of BDKRB2 gene may be used as a genetic marker for the susceptibility and severity of OA. Shuo Chen, Yong Zhou, Jun Li, Le-Qun Shan, and Qing-Yu Fan Copyright © 2012 Shuo Chen et al. All rights reserved.