Treatment of Gouty Arthritis is Associated With Restoring Gut Microbiota And Promoting Production of Short Chain Fatty Acids

Introduction: Although factors initiating the inflammatory response to monosodium urate crystals have been identified, the role of the gut microbiota and their metabolites on gout remain unknown. This study aimed to investigate changes in both gut microbiota and short chain fatty acids (SCFAs) according to inflammatory states of gout in the same patients.Methods: This study enrolled 20 patients with gout in the acute state who had active joints and were followed-up until the recovery state with no active joints. Blood and fecal samples were simultaneously collected within 3 days for each disease state. The stool microbiome was analyzed using 16S rRNA sequencing, and serum SCFAs were measured by gas chromatography-mass spectrometry. Differences in gut microbiome and serum SCFAs were compared between the acute and recovery states.Results: Beta diversity of the microbiome was significantly different between the acute and recovery states in terms of weighted UniFrac distance. In the recovery state, Prevotellaceae (p = 0.006) and the genus Prevotella (p = 0.009) were significantly enriched, whereas Enterobacteriaceae (p = 0.019) and its derivative genus Shigella (p = 0.023) were significantly decreased compared to the acute state. Similarly, the levels of acetate was dramatically increased in the recovery state compared to the acute state (p < 0.010). Levels of propionate and butyrate tended to increase but without statistical significance.Conclusion: Substantial alterations of bacterial composition with promotion of SCFA formation (especially acetate) were found after treatment in patients with gouty arthritis.

AB0745 BONE STATUS IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS (JIA) ON T2T THERAPY

Background:In recent years approaches to both the diagnosis and treatment of JIA have changed. Among it key positions for bone health are reducing the time to make a diagnosis and initiation of basic therapy, as well as reducing the timing and doses of corticosteroids. The interdependence of osteopenia in children with JIA with established impairment of vitamin D status, the prevalence of which remains very high in this cohort of patients, has also not been definitively elucidated.Objectives:To study the condition of bone tissue in children with JIA in modern disease management and to identify adverse factors for the development of osteopenia among the clinical manifestations signs.Methods:The study included 35 children with JIA aged 7 to 17 years, mostly female (77.1%), with oligo - (25.7)%, poly - (60.0%) and undifferentiated (14.3 %) arthritis, 53.4% have not yet received basic therapy. No corticosteroid therapy was available. The study of bone tissue was performed by two-energy X-ray absorptiometry (Explorer QD W-Hologic). All patients were tested for serum parathyroid hormone (PTH), the level of 25-hydroxyvitamin D [25(OH)D], the total and ionized calcium and blood phosphorus. The control group consisted of 12 healthy children of the same age with a normal level of 25 (OH) D.Results:The average level of 25(OH)D was 20.41±1.35 ng/ml, which is considered insufficient and was lower than in the control group (30.03±2.53 ng/ml, p<0.05). Studies of calcium and phosphorus in the blood showed that children with JIA have no deviations from the normative values. The majority of examined patients (98.37%) had normal values of PTH, in average was 30.43±0.90 pg/ml. The PTH was significantly different in children with different variants of JIA, the highest content was recorded in non-differential arthritis (34.33±1.80 pg/ml), the lowest - in the oligoarticular variant (28.36±1.43, p<0,05). PTH had a negative correlation with 25(OH)D status (r = -0.41; p <0.05) and did not depend on the sex and disease activity.The incidence of osteopenia was 28.57%, its prevalence was almost the same in different variants of arthritis and did not depend on the sex and age of patients, positivity for RF. Osteopenia was more common in ANA-positive than in ANA-negative variant (46.15% vs. 18.18%; pφ<0.05). In 30.0% patients with osteopenia decreased BMD reached the values of osteoporosis (more than 2.5σ). This group consisted of girls with predominantly polyarticular and undifferentiated JIA, with RF-negative and ANA-positive variant.Deviations from the age normative values of BMD (Z-score) were associated with BMI (r=0.33; p <0.05), JADAS scale results (r=0.35; p<0.04), the number of active joints (r=0.34; p<0.05), ANA (r=-0.34; p<0.05). In children with osteopenia it was correlated with the duration of the disease (r=-0.67; p<0.05), the number of active joints (r=-0.62; p<0.05), blood phosphorus level (r=0.74; p<0.05) and JADAS scale results (r=0.59; p<0.05). In children with preserved BMD correlations was supplemented by 25(OH)D status (r=-0.33; p<0.05) and BMI (r=-0.40; p<0.05). Analysis of the interdependence of the formation of osteopenia and clinical manifestations signs established the total significance of the main parameters of the disease with the highest coefficient of determination in the polyarticular variant: -112.65 + 0.09(patient’s age, mo)+4.33 (patient’s sex)-3.74 (ANA, units)-1.80 (RF, units)+0.01 (age of onset, months)-0.34 (number of affected joints)-0.18 (number of active joints)-0.18 (ESR, mm/h)+71.58 (ionized calcium, mmol/l)+5.19 (phosphorus, mmol/l)-0.01 (PTH, ng/ml)+0.18 (25(OH)D, ng/ml)(R2=99.99%; p<0.001).Conclusion:With modern JIA management a quarter of children have osteopenia. The state of the bone tissue is more associated with the prevalence, immunological and inflammatory activity of the disease against the background of preserved calcium-phosphorus homeostasis and vitamin D deficiency, and is not associated with the present therapy.Disclosure of Interests:None declared

OP0166 DISEASE ACTIVITY IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS AFTER SIMULTANEOUS PCV13 AND HIB VACCINATION: A COHORT STUDY

Background:The safety of vaccination of children with rheumatic diseases is determined not only by the risk of adverse events but also by the risk of exacerbation of the disease. The simultaneous administration of several vaccines can increase the likelihood of these events.Objectives:To evaluate the clinical and laboratory signs of disease activity in children with juvenile idiopathic arthritis (JIA) after simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) infections.Methods:We included hospitalized patients with JIA ages 2 through 18 without serious comorbidity, immunized with polysaccharide conjugate vaccines against pneumococcal (PCV13) and Hib infections. Vaccines were administered (0.5 ml each) concurrently subcutaneously into the deltoid area. In all children before and 3 weeks after vaccination, clinical (joints with active arthritis, uveitis activity) and laboratory signs (increased ESR, concentrations of highly sensitive C-reactive protein – hsCRP, and calprotectin) of JIA activity were assessed. Serum hsCRP and calprotectin were quantified by ELISA. The upper limit of the reference interval for hsCRP was considered (according to the manufacturer’s instructions) a value of 8.2 mg/L, for calprotectin – 2.9 μg/ml, and for ESR – > 10 mm/h.Results:The study included 430 patients with JIA (girls 60.9%), median (IQR) age – 11.1 years (7.3 to 14.4), onset of JIA – 4.7 years (2.4 to 8.6). Patients with persistent oligoarticular JIA numbered 149 (34.7%), polyarticular RF-negative – 148 (34.4%), systemic – 101 (23.4%), enthesitis-related – 20 (4.7%), and polyarticular RF-positive JIA – 12 (2.8%). Biologic disease-modifying antirheumatic drugs (DMARDs) were administered to 278 (64.7%), non-biologic DMARDs (mostly methotrexate) – 282 (65.6%), corticosteroids – 45 (10.5%), and NSAIDs – 18 (4.2%) patients. Three weeks after vaccination, out of 100 (23.3%) patients with initially active joints, signs of active arthritis remained in 96 patients, of which 16 patients had a decrease in the median (IQR) number of active joints by 4 (2 to 8). Among patients without active joints at baseline, signs of active arthritis were not subsequently detected. Before vaccination, 9 patients had uveitis in the exacerbation phase, 7 - in the subactive phase, and 41 - in the remission phase. After vaccination, exacerbation of uveitis persisted in 4 patients. There were no new cases of uveitis or its exacerbation. The dynamics of laboratory signs of JIA activity are presented in Table 1. Initially, the high concentration of calprotectin was found in 191 (44.4%) patients, and after vaccination – in 220 (51.2%) patients; the difference was 6.7% (95% CI 1.0 - 12.5); hsCRP - in 34 (7.9%) and 51 (11.9%) patients; the difference was 4.0% (95% CI 0.6 - 7.3); high ESR – in 76 (17.7%) and 41 (9.5%) patients; the difference was -8.1% (95% CI -11.6 to -4.7), respectively. An independent predictor of new cases of high concentration of hsCRP (n = 36), but not new cases of high concentration of calprotectin (n = 94), was the initial number of joints with active arthritis – odds ratio 2.37 (95% CI 1.14 - 4.93).Table 1.Laboratory signs of JIA activity after simultaneous administration of vaccines against pneumococcal (PCV13) and Hib-infectionsVariablesBaselineAfter 3 weeksRatio*p**Geometric mean (95% CI)Calprotectin, μg/ml2.93 (2.70 – 3.17)3.15 (2.92 – 3.40)1.08 (0.99 – 1.17)0.087hsCRP, mg/L0.69 (0.60 – 0.78)0.79 (0.69 – 0.90)1.15 (0.99 – 1.33)0.073ESR, mm/h4.4 (4.0 – 4.8)3.7 (3.4 – 4.0)0.84 (0.78 – 0.90)0.001Note. CI – confidence interval. * Ratios of paired observations (95% CI). ** P-value calculated in paired samples t-test.Conclusion:Simultaneous vaccination against pneumococcal (PCV13) and Hib-infections in children with JIA produced no negative dynamics of the traditional indicators of disease activity (joint activity, uveitis, high ESR). At the same time, 3 weeks after vaccination, an increase in the concentration of calprotectin and hsCRP was found in a small number of patients (<10%).Disclosure of Interests:None declared

Investigation of Active Disassembly in Large Force Applications

Active disassembly (AD) is an emerging field of research in design for disassembly that enables a cost-effective nondestructive separation of product components. It is based on using active joints and fasteners that enables the self-disassembly of products without any direct contact between the product and the operator, where these joints and fasteners must be inserted in the product during its design and manufacturing phases. Generally, active joints and fasteners are made of smart materials such as shape memory alloys (SMAs), that can generate the necessary disassembly forces required to separate the different components of the product. Most of the exerted effort in this field of research was focused on separating products requiring small disassembly forces either in the electronic or automotive sectors. All these active disassembly applications were based on using shape memory alloy snap fits, clips, or wires that are characterized by their ability to generate small forces with large displacements. As, up to the authors knowledge, none of the exerted efforts were concerned with investigating the possibility of using the large disassembly forces that could be generated using shape memory alloy actuators in large force active disassembly applications. Consequently, the presented research aims to examine the possibility of applying active disassembly with products requiring large disassembly forces, having tapered surfaces and large mechanical structure. By presenting two case studies to validate the possibility of using active disassembly with large force applications, in addition to investigating the capability of using shape memory alloy actuators assembled either concentric or eccentric with the product structure.

Load Reduction Control on Tool-Insertion Port for Laparoscopic Surgical Robot Using Semi-Active Joints

In robotic surgery, the load exerted on the insertion port in the patient’s abdominal wall due to misalignment of the robot’s remote center of motion and the insertion port or external forces acting on the tip of the forceps during surgery, can not only stress the patient’s body but also increase the friction between the robotic forceps and the trocar, and adversely affect fine surgical manipulations or the accuracy of force estimation. To reduce such loads on the insertion port in robotic surgery, this study proposes a control method for a surgical assist robotic arm with semi-active joints. The control method was implemented on a six-degree-of-freedom pneumatically driven vertical multi-joint robotic arm with a two-axis gimbal joint (two semi-active joints) that only executes torque control, which was previously developed by the authors, and verified through an experiment. The load on the insertion port is reduced by applying torque control on the semi-active joints to compensate for the external forces on the forceps. We constructed a control system that includes a disturbance compensator and conducted a velocity-control experiment by subjecting the forceps constrained by the insertion port to an external force. The results showed that when the torque was compensated for by the semi-active joints, the load on the insertion port was reduced by 65% and 52% when the external force on the tip of the forceps was 0 N and 3 N, respectively.

Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis

Objective This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1(sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in non-systemic JIA patients with clinical and inflammatory biomarker indicators of disease activity. Methods Plasma sLRP1 and 46 inflammation-related biomarkers were measured at enrollment and six months later in a cohort of 96 newly diagnosed Canadian non-systemic JIA patients. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits. Results At enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 60.7 and 47.8, respectively; p=0.032). Participants with four or fewer active joints compared to those with five or more active joints, had significantly higher sLRP1 levels (mean ranks: 60.6, and 44.7, respectively; p=0.007). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r=-0.235; p=0.017). In the entire cohort, sLRP1 levels at enrollment and six months after correlated with 13 and six pro-and anti-inflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor negative polyarticular JIA, oligoarticular JIA, enthesitis related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later. Conclusion Plasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.

SAT0493 CLINICAL PROFILE OF JIA PATIENTS WITH THE CERVICAL SPINE INVOLVEMENT: A SINGLE CENTER RETROSPECTIVE CONTINUOUS STUDY.

Background:JIA is the most common chronic condition in pediatric rheumatology. The cervical spine (CS) involvement is associated with severe disease activity and disability and has been recognized as a factor of a poor prognosis. Data about the CS involvement is contradictory due to silent CS involvement in some patients.Objectives:the aim of our study was to provide a clinical profile of the patients with the CS involvement.Methods:753 patients for last 10 years with JIA were analyzed. Patients were divided depending on the CS involvement, which was confirmed by clinical (pain, LOM) and radiological features (effusion in the CS joints). We evaluated active joints and routine tests, such as CRP, ESR, ANA-positivity and HLA B27Results:The CS involvement was in 101 patients (13.4%). The data are in the table. The CS involvement was more frequently associated with joints of upper body, such as TMJ (23.7% vs 2.9%, p=0.000001), shoulder (29.7% vs 2.9%, p=0.000001), elbow (34.2% vs 12.2%, p=0.000001), wrist (61.4% vs 21.8%, p=0.0000001), MCP (43.6% vs 18.4%, p=0.0000001), PIP (52.5% vs 21.3%, p=0.0000001), DIP (23.8% vs 7.1%, p=0.0000001) and hip (44.6% vs 16.6%, p=0.0000001), and ankle (60.4% vs 40.2%, p=0.0001) from lower body.ParametersCS, yes (n=101)CS, no (n=652)pFemale, n (%)69 (68.3)388 (59.5)0.092ANA-positivity, n (%)22/57 (38.6)190/403 (47.2)0.226HLA B27-positivity, n (%)12/33 (36.4)88/275 (32.0)0.613Onset age, years5.3 (2.7-10.1)6.1 (3.0- 10.4)0.241ESR, mm/h12.0 (5.0-31.0)7.0 (3.0- 18.0)0.0006CRP, mg/l3.9 (0.0- 20.0)1.1 (0.0-9.2)0.002Active joints, n (%)16.0 (9.0-28.0)5.0 (3.0-10.0)0.000000Time before remission, years2.9 (1.5-5.1)2.2 (1.1-4.6)0.046OligoarthritisPolyarthritisPsoriatic arthritisEnthesitis-related arthritisSystemic arthritis5 (5.0)48 (48.0)7 (7.0)22 (21.8)19 (18.9)199 (30.5)217 (33.3)33 (5.1)164 (25.2)39 (6.0)0.0000001Uveitis, n (%)9/76 (11.9)107/444 (24.1)0,018Oral glucocorticosteroids, n (%)37 (36.7)115/651 (17.7)0.00001Biologic, n (%)68 (67.3)283 (43.4)0.000007Remission, n (%)57 (56.4)428 (65.6)0.072Flare, n (%)10 (9.9)128/651 (19.7)0.018Conclusion:The main risk factors of CS involvement in JIA were polyarthicular and systemic arthritis, high inflammatory activity and involvement of joints of upper body. Patients with CS involvement required more often biologics.Disclosure of Interests:None declared

Kinematic calibration of the 3-degree-of-freedom redundantly actuated spatial parallel module of a five-axis hybrid machine

As a new type of manufacturing equipment, redundant hybrid machines have the theoretical advantage over the traditional serial machines in efficiently processing large structural parts with high material removal ratio and complex parts with curved surfaces. In order to solve the accuracy problem of the redundantly actuated spatial parallel module of a five-axis hybrid machine, an improved kinematic calibration method is proposed in this article. First, different from error modeling for the corresponding non-redundant parallel module, the geometric error model of the redundantly actuated spatial parallel module considers the deformations at active joints caused by actuation redundancy as an error source. Then, the applicable error model is developed using projection technique to remove the need of active joints’ stiffness measurement or modeling. Later, the practical error model is derived from model reduction method to avoid using additional sensors or gratings. Finally, three forms of relative measurement and step identification are adopted for the calibration work, and the bilinear interpolation compensation function is introduced to ensure the calibration effect. On this basis, the kinematic calibration of the redundantly actuated spatial parallel module is conducted. The max position errors are reduced from original −0.192 to 0.075 mm after RM1 and SI1, and then further reduced to 0.014 mm after bilinear interpolation compensation, while the max orientation errors are reduced from −0.017° and 0.249° to −0.005° and −0.007° after RM2 and SI2, and RM3 and SI3, respectively. A contrasting experiment is also carried out with the previous method for the corresponding non-redundant parallel module. As a result, the proposed method shows better convergence value and speed in identifying error parameters, and therefore the effectiveness and efficiency of the proposed method for the redundantly actuated spatial parallel module are validated.

Kinematic and Dynamic Characteristics of the Free-Floating Space Manipulator with Free-Swinging Joint Failure

For the free-floating space manipulator with free-swinging joint failure, motions among its active joints, passive joints, free-floating base, and end-effector are coupled. It is significant to make clear all motion coupling relationships, which are defined as “kinematic coupling relationships” and “dynamic coupling relationships,” inside the system. With the help of conservation of system momentum, the kinematic model is established, and velocity mapping relation between active joints and passive joints, velocity mapping relation between active joints and base, velocity mapping relation between active joints and end-effector. We establish the dynamic model based on the Lagrange equation, and the system inertia matrix is partitioned according to the distribution of active joints, passive joints, and the base. Then, kinematic and dynamic coupling relationships are explicitly derived, and coupling indexes are defined to depict coupling degree. Motions of a space manipulator with free-swinging joint failure simultaneously satisfy the first-order nonholonomic constraint (kinematic coupling relationships) and the second-order nonholonomic constraint (dynamic coupling relationships), and the manipulator can perform tasks through motion planning and control. Finally, simulation experiments are carried out to verify the existence and correctness of the first-order and second-order nonholonomic constraints and display task execution effects of the space manipulator. This research analyzes the kinematic and dynamic characteristics of the free-floating space manipulator with free-swinging joint failure for the first time. It is the theoretical basis of free-swinging joint failure treatment for a space manipulator.