Persistence of ultrasound synovitis in patients with rheumatoid arthritis fulfilling the DAS28 and/or the new ACR/EULAR RA remission definitions: Results of an observational cohort study

ObjectiveThe primary aim of the study was to evaluate whether rheumatoid arthritis (RA) patients considered to be in remission according to clinical criteria sets still had persisting ultrasound (US) synovitis. We further intended to evaluate the capacity of our US score to discriminate between the patients with a clinically active disease versus those in remission.MethodsThis is an observational study nested within the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) rheumatoid arthritis cohort. A validated US score (SONAR score) based on a semi-quantitative B-mode and Doppler (PwD) score as part of the regular clinical workup by rheumatologists in different clinical settings was used. To define clinically relevant synovitis, the same score was applied to 38 healthy controls and the 90st percentile was used as cut-off for ‘relevant’ synovitis.ResultsThree hundred and seven patients had at least one US examination and concomitant clinical information on disease activity. More than a third of patients in both DAS28 and ACR/EULAR remission showed significant gray scale synovitis (P = 0.01 and 0.0002, respectively) and PwD activity (P = 0.005 and 0.0005, respectively) when compared to controls. The capacity of US to discriminate between the two clinical remission groups and patients with active disease was only moderate.ConclusionThis observational study confirms that many patients considered to be in clinical remission according the DAS and the ACR/EULAR definitions still have residual synovitis on US. The prognostic significance of US synovitis and the exact place of US in patients reaching clinical remission need to be further evaluated.     

The emerging role of ultrasound in detecting interstitial lung disease in patients with rheumatoid arthritis

ObjectiveTo investigate the potential role of US in the detection of ILD in a cohort of patients with RA.MethodsPatients with diagnosis of RA were consecutively enrolled. All patients underwent pulmonary examination, laboratory data, DLCO measure, chest HRCT and radiographs, and US examination. A healthy group was included as control group. US was performed according the 14-intercostal space scanning protocol using the following semiquantitative scale [0 = normal (≤ 5 B-lines); 1 = slight (≥ 6 and ≤ 15 B-lines); 2 = moderate, (≤ 16 and ≥ 30 B-lines); 3 = severe (≥ 30 B-lines)].ResultsA total of 74 RA patients and 74 healthy controls were included. Thirty of 74 patients (40.5%) showed US signs of ILD with respect to the healthy controls (3 subjects, 4.1%) (P < 0.001); whereas HRCT showed ILD in 27 (36.4%) of 74 patients. Among the 30 patients that showed US findings of ILD, 17 (56.6%) were asymptomatic from respiratory view-point. The sensitivity and specificity of US were 92% and 89% respectively. A positive correlation between US and HRCT findings were found (P < 0.001) whereas no correlation was found with chest radiographs and DLCO findings. Positive association between US findings and DAS28-ESR, anti-CCP and RF (P < 0.01 for each respectively) was found. Feasibility, represented by the mean time spent to perform the pulmonary US assessment was 7.8 minutes (± SD 1.2, range 6 to 10 minutes).ConclusionsOur results support the potential of US in detect accurately ILD in patients with RA and provide a rationale to consider it as a friendly screening tool to be implemented in early phases of the disease.     

Atherosclerosis progression in psoriatic arthritis patients despite the treatment with tumor necrosis factor-alpha blockers: A two-year prospective observational study

ObjectiveTo evaluate the progression of subclinical atherosclerosis in Psoriatic Arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)-α agents.MethodsThirty-two PsA patients classified according to the CASPAR criteria and attending the Rheumatology Unit of the University of Padua Medical Center were enrolled in a two-year prospective, observational study. In accordance with the ASAS/EULAR recommendations on the management of these patients, those studied were prescribed biological agents [etanercept (n = 21), adalimumab (n = 6), infliximab (n = 5)]. Plasma lipids, inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), vessel endothelium growth factor (VEGF), osteoprotegerin (OPG), and TNF-α, as well as Disease Activity Score 28 calculated with CRP (DAS 28-CRP) were evaluated at baseline and after two years of treatment. Bilateral carotid B-mode ultrasound measurements [the mean-intima media thickness (mean-IMT), the mean maximum-IMT (M-Max)] of each carotid artery segment (common, bulb, and internal carotid artery) and the post-occlusion flow-mediated dilation (FMD) of the brachial artery were also assessed at baseline and after two years.ResultsDespite an improvement in the DAS 28-CRP score (P < 0.0005) and lower low-density lipoprotein cholesterol (P < 0.013) and triglyceride (P < 0.036) values, there was a significant progression in both the mean-IMT (P < 0.0005) and M-Max (P < 0.0005). Moreover, no recovery in FMD (P = ns) was observed after two years of anti TNF-α treatment. Serum TNF-α levels were increased (P = 0.003) and OPG values were decreased (P = 0.011) at the end of follow- up with respect to baseline values.ConclusionsDespite improvement in clinical status, arterial remodelling was observed in the PsA patients who were treated with anti TNF-α agents for two years.     

Decrement of serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis (RA) patients achieving remission after 6 months of etanercept treatment: Comparison with CRP,IgM-RF,MMP-3 and anti-CCP Ab

ObjectiveThe aim of this study was to evaluate whether serum COMP can estimate the therapeutic response of RA after 6 months of treatment with etanercept.MethodsForty-five RA patients receiving 25 mg of etanercept twice a week for 6 months were registered in this prospective observational study. Clinical response to the therapy was evaluated by DAS 28. Laboratory variables– COMP, CRP, ESR, IgM-RF, MMP-3, and anti-CCP Ab –were assessed at baseline and after 6 months of treatment. We assessed the correlations between serum COMP and other variables and whether serum COMP is associated with DAS28 remission.ResultsSerum COMP correlated with DAS28-ESR (p < 0.05, r = 0.40) at baseline. At 6 months of etanercept treatment, 10 patients entered remission (DAS28-ESR < 2.6) whereas the other 35 patients did not (DAS28-ESR > 2.6). The decrement of serum COMP at 6 months was significant in the remission group (N = 10) but not in the non-remission group (N = 35). On the other hand, CRP, ESR and MMP-3 decreased at 6 months regardless of remission status. IgM-RF titer as well as anti-CCP Ab titer did not differ at 6 months.ConclusionsSerum COMP at baseline reflects clinical disease activity of RA. Serum COMP is a valuable serologic marker to identify the subset of RA patients achieving remission during treatment with etanercept.     

Ultrasonography of shoulders in spondyloarthritis and rheumatoid arthritis: A case-control study

IntroductionShoulders are often involved in spondyloarthritis (SpA) and rheumatoid arthritis (RA). The diagnosis of peripheral SpA and its differential diagnosis with RA could be challenging. A recent ultrasound study showed that ultrasonography (US) of the hands might differentiate psoriatic arthritis to RA. The aim of the study was to compare different US features in SpA, RA and healthy controls.MethodsA total of 38 SpA and 43 RA patients with clinical involvement of shoulders were included and compared to 33 controls. One blinded rheumatologist performed US examinations. The following items were assessed: gleno-humeral effusion, long-head biceps tendon tenosynovitis, subacromial and subdeltoid bursitis, acromio clavicular (AC) synovitis and humeral bone erosion.ResultsThirty-eight SpA (mean age: 49.9 ± 15.4 years, 58% of male), 43 RA patients (52.9 ± 16.6 years, 26% of male) and 33 controls (55.2 ± 16.9 years, 42% of male) were assessed. In comparison to RA, SpA patients had higher frequency of AC synovitis (66% vs 5%, P < 0.0001) but lower prevalence of subacromial and subdeltoid bursitis (39% vs 67%, P = 0.015), gleno-humeral effusion (5% vs 28%, P = 0.008) and humeral bone erosion (10% vs 56%, P < 0.0001). Unilateral abnormalities were found more frequently in SpA patients than in RA (64% vs 26%, P < 0.0001).ConclusionOur results suggest that AC synovitis is highly evocative of SpA in patients with inflammatory painful shoulders. Thus, US might help to diagnose SpA and to differentiate with RA.     

Sex differences in clinical characteristics and their influence on clinical outcomes in an observational cohort of patients with rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) is more prevalent in women, but sex differences remain incompletely understood. This study aimed to elucidate sex differences in clinical characteristics and their potential impact on clinical outcomes in a large Korean cohort of patients with RA.MethodsIn total, 5376 RA patients from the KORean Observational study Network for Arthritis (KORONA) database were examined at baseline and for 3 consecutive years using the disease activity score 28 (DAS28), health assessment questionnaire (HAQ), and patient-reported outcomes (PROs). Within a subgroup with active disease (DAS28 ≥ 3.2) at baseline, sex impacts on clinical outcome during follow-up were analyzed using generalized estimating equation (GEE) models. The factors related to achieving clinical remission were analyzed using Cox-proportional hazard regression.ResultsAt baseline, women (n = 4574) were younger and had more erosive disease and longer disease duration than men (n = 802) with higher scores in DAS28, HAQ, and PROs. The prevalence of interstitial lung disease, cardiovascular disease, and diabetes in men was higher than that of women. In a RA subgroup with active disease at baseline, GEE analyses demonstrated that women RA significantly influenced the rate of change of DAS28 over time. In that group, men are associated with achieving DAS28 sustained remission and point remission.ConclusionsWomen with RA in Korea report higher levels of disease activity and PROs compared to men, whereas most comorbidities were more prevalent in men. The longitudinal change in disease activity and the rate of achieving clinical remission were found to be worse in women with RA.     

Plasma ghrelin and leptin in adult cystic fibrosis patients

BackgroundWeight loss in cystic fibrosis (CF) may be associated with altered levels of appetite stimulating peptide ghrelin and the appetite decreasing peptide leptin. However, prior data on leptin in CF are conflicting, while the data on ghrelin are scarce. We hypothesized that weight loss in CF is associated with low levels ghrelin and elevated levels of leptin.MethodsPlasma ghrelin, leptin, TNF-α, IL-1 and IL-6, BMI, fat free mass (FFM), fat mass (FM) were measured in 74 CF adults and 20 controls. CF subjects were divided into 3 groups based on lung disease: mild (n = 19), moderate (n = 30) and severe (n = 25).ResultsSevere CF patients (% predicted FEV1 27 ± 7; median BMI 21 kg/m²) had significantly elevated ghrelin and decreased leptin compared to controls and other CF subjects. Ghrelin correlated (r value, p value) with BMI (− 0.35,< 0.001), FFM (− 0.22,< 0.05), FM (− 0.41,< 0.0001), FEV1 (− 0.62,< 0.001), TNF-α (0.51,< 0.0001), IL-1 (0.56,< 0.0001), and IL-6 (0.33,< 0.01). Leptin correlated (r value, p value) with BMI (0.40,< 0.0001), FM (0.56,< 0.0001), FEV1 (0.34,< 0.05), IL-1 (− 0.51,< 0.05) and TNF-α (− 0.43,< 0.0001). BMI and FEV1 were independent predictors of ghrelin (− 0.35,< 0.05;−0.59,< 0.001). FM was a predictor of leptin (0.56,< 0.0001). Cytokines were elevated only in severe CF (severe CF vs. controls, pg/ml): TNF-α (3.4 ± 0.6 vs. 1.2 ± 0.4), IL-1 (3.5 ± 1 vs. 0.2 ± 0.1), IL-6 (17.4 ± 4 vs. 2.4 ± 2).ConclusionsElevated ghrelin and decreased leptin levels are a consequence rather than a cause of weight loss in advanced CF.     

Níveis de óxido nítrico mais elevados estão associados à atividade da doença em pacientes egípcios com artrite reumatoide

BackgroundOxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage.ObjectivesTo assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity.Methods80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS‐28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age‐ and sex‐matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method.ResultsA comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean ± SD 82.38 ± 20.46) in comparison to patients without active disease (35.53 ± 7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r = 0.45), arthritis (r = 0.43), platelet count (r = 0.46), erythrocyte sedimentation rate (r = 0.83), C‐reactive protein (r = 0.76) and Disease Activity Score (r = 0.85). Nitric oxide showed a significant positive correlation (r = 0.43) with hand radiographies (Sharp score) in Group I.ConclusionThere are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status.     

The Evaluation of Consistency Between Body Composition Assessments in Pediatric Population Using Pencil Beam and Fan Beam Dual-Energy X-Ray Absorptiometers

The replacement of the old dual-energy X-ray absorptiometry system with a novel one should be preceded by a cross-calibration procedure. Therefore, the study was aimed at investigating the consistency of bone and body composition measures performed in pediatric population using pencil beam (DPX-L; GE Healthcare, GE Healthcare, Madison, WI) and fan beam (Prodigy; GE Healthcare, GE Healthcare, Madison, WI) densitometers. The study group consisted of 212 healthy children aged 4–18 yr. Total body (TB) and lumbar spine (S) (L2–L4) measurements were performed using DPX-L and Prodigy during the same visit. Bland-Altman analysis, linear regressions, and paired t-test were performed to evaluate the consistency of measurements and to establish a cross-calibration equation. The average Prodigy values for TB and lumbar spine bone mineral density (BMD) and content (BMC) were 2.7%, 2.4% and 1.6%, 1.6% higher than those of DPX-L, respectively (p < 0.0001). Prodigy-assessed bone area (BA) was lower by 1.4% for TBBA (p < 0.0001) and 1.1% for SBA (p < 0.001). Lean body mass (LBM) from Prodigy was higher by 6.9% (p < 0.0001), whereas fat mass (FM) was lower by 8.4% compared with those from DPX-L (p < 0.0001). Bland-Altman analyses revealed the effect of magnitude that was nonlinear (2nd degree polynomial) for TBBMD (r = 0.32, p = 0.001), TBBMC (r = 0.51, p < 0.0001), TBBA (r = 0.34, p < 0.0001), and LBM (r = 0.56, p < 0.0001), but not for FM (r = 0.14, not significant [n.s.]). In contrast, in lumbar spine, the magnitude dependence was linear and significant for SBMC (r = 0.46, p < 0.0001) and SBA (r = 0.34, p < 0.0001) but not for SBMD (r = 0.12, n.s.). Both skeletal and body composition variables assessed by DPX-L and Prodigy devices were highly correlated, showing R² values ranging from 0.976 for FM to 0.994 for SBMC. The results of this study document a necessity for implementation of calculated cross-calibration equations to transform DPX-L–based local pediatric references into a novel Prodigy system.     

Can static foot posture measurements predict regional plantar surface area?

BackgroundThe intent of this study was to determine if the use of a single or combination of static foot posture measurements can be used to predict rearfoot, midfoot, and forefoot plantar surface area in individuals with pronated or normal foot types.MethodsTwelve foot measurements were collected on 52 individuals (mean age 25.8 years) with the change in midfoot width used to place subjects in a pronated or normal foot mobility group. Dynamic plantar contact area was collected during walking with a pressure sensor platform. The 12 measures were entered into a stepwise regression analysis to determine the optimal set of measures associated with regional plantar surface area.ResultsA two variable model was found to describe the relationship between the foot measurements and forefoot plantar contact area (r² = 0.79, p < 0.0001). A four variable model was found to describe the relationship between the foot measurements and midfoot plantar contact area (r² = 0.85, p < 0.0001) in those individuals with a 1.26 cm or greater change in midfoot width.ConclusionsThe results indicate that clinicians can use a combination of simple, reliable and time efficient foot measures to explain 79% and 85% of the plantar surface area in the forefoot and midfoot, respectively.     

The effect of aging on the hardness of foot sole skin: A preliminary study

BackgroundFoot problems are common in older people and altered biomechanical parameters under the foot sole has been proposed as a key risk factor for foot lesions. Therefore the aim of this study was to investigate the age-related differences in the hardness of foot sole skin.MethodsTwenty-six healthy volunteers without foot problems, aged from 26 to 65 years, were examined using shore meter. The hardness of the foot sole under the big toe (area 8), 1st metatarsal head (area 5), 3rd metatarsal head (area 6), 5th metatarsal head (area 7), mid foot (area 3, 4) and hind foot (area 1, 2) were measured. The correlation between age and hardness of foot sole was examined and comparisons were made between two age groups.ResultsFrom the result we observe statistical significant (p < 0.05; p < 0.01; p < 0.005) differences in hardness between age groups in hind foot, metatarsal heads (1st, 3rd & 5th) and big toe. Strong positive correlations between age and hardness of the foot sole were found at the big toe (r = 0.57; p < 0.005), 1st metatarsal head (r = 0.567; p < 0.00001), 3rd metatarsal head (r = 0.565; p < 0.00001), 5th metatarsal head (r = 0.55; p < 0.00001), and heel (r = 0.59; p < 0.0001).ConclusionThe loss of compliance in the foot sole may be one of the factors responsible for the higher incidence of foot problems in aged people. Routine foot examination and appropriate therapeutic intervention including the use of foot orthoses and optimal hardness of foot wear insole may help to prevent the serious foot injuries.     

Lengthening scarf osteotomy for recurrent hallux valgus

BackgroundWe describe using the scarf osteotomy to correct a recurrent hallux valgus deformity and lengthen the shortened first metatarsal in symptomatic iatrogenic first brachymetatarsia.MethodsThirty-six lengthening scarf osteotomies were undertaken in 31 patients. Clinical and radiographic measures were taken pre and postoperatively.ResultsMean age at presentation was 53.4 years, and mean followup 3.9 years. The mean lengthening achieved was 4.9 mm. All osteotomies united with no complications. The mean IMA reduction was 4.0° (p < 0.001) and HVA 13.0° (p < 0.001). The mean AOFAS score increase was 33.8 (p < 0.001). There was a positive trend but no correlation (r = 0.28) between amount of metatarsal lengthening and AOFAS score change.ConclusionsWe describe the largest lengthening scarf osteotomy series for recurrent hallux valgus with iatrogenic first brachymetatarsia. The results suggest the procedure is successful, with a low complication rate. We anticipate that restoring first metatarsal length and alignment may reduce biomechanical transfer metatarsalgia over time.     

Relação entre o nível de hemoglobina e a atividade da doença em pacientes com artrite reumatoide

ObjectivesThis study aims to investigate the relationship of hemoglobin level with disease activity in patients with rheumatoid arthritis (RA).Patients and methodsThe hemoglobin level, the 66/68 joint count, the Disease Activity Score 28 joints (DAS28), the Health Assessment Questionnaire (HAQ), the Visual Analog Scales (VAS), the Modified Sharp Score (MSS), and the disease duration in 89 patients with RA were used to analyze the possible relationship. The World Health Organization (WHO) criteria for anemia uses a hemoglobin threshold of < 120 g/L for women and < 130 g/L for men. Pregnant or breastfeeding patients, patients with a history of other inflammatory or no inflammatory arthritis, malignancies, chronic infectious and inflammatory diseases and other diseases in the stage of decompensation were excluded from the study.ResultsAnemia was observed in 64% of the patients (1^st group); the other group (2^nd group) had normal levels of hemoglobin. There was a statistically significant negative correlation between hemoglobin level and swollen and tender joints’ count, DAS28, HAQ score, VAS, MSS, and disease duration (p < 0.001). DAS28, HAQ score, VAS, MSS, swollen and tender joints’ count and disease duration were significantly (p < 0.001) higher in 1^st versus 2^nd group.ConclusionIn conclusion, we determined that low hemoglobin level was significantly related to disability and impairment, disease activity, articular damage, pain and disease duration in RA patients in our study. We believe that by keeping disease activity under control, therefore preventing articular damage, the disability in RA patients can be lessened or possibly even eliminated.     

Long-term effects of therapeutic education for patients with rheumatoid arthritis

IntroductionThe objective of this study was to assess the effects of an educational program on the course of rheumatoid arthritis (RA) after 3 years.MethodsFrom December 2002 to December 2003, 39 RA patients participated in a 3-day education program delivered to groups of four or five patients. Effects of the program were evaluated after 3 years in 33 patients, comparatively to baseline, based on the following variables: knowledge of RA (self-questionnaire), disease activity (DAS 28), functional impairment (health assessment questionnaire [HAQ]) and quality of life (arthritis impact measurement scale 2 [AIMS2], short-form). We also compared patient knowledge in the educational program participants and in 38 controls with RA. Direct questions were used to evaluate the program after 3 years.ResultsPatient knowledge 3 years after the education program was significantly improved compared to baseline (P < 0.0001) and was significantly better than in the controls (P < 0.0001). Disease activity was significantly lower in the education group after 3 years than at baseline (DAS28, 3.1 vs. 3.8, P < 0.005). Neither the HAQ nor the AIMS2 scores changed significantly after 3 years compared to baseline. The replies to the direct questions indicated a very high level of overall satisfaction with the educational program.ConclusionAn educational program tailored to patient needs can produce lasting improvements in knowledge of the disease and may help to control the activity of RA. These results warrant the development of education programs for patients with chronic inflammatory joint disease.     

Randomised Clinical Trial of Prostatic Artery Embolisation Versus a Sham Procedure for Benign Prostatic Hyperplasia

BackgroundProstatic artery embolisation (PAE) has been associated with an improvement of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH), but conclusive evidence of efficacy from randomised controlled clinical trials has been lacking.ObjectiveTo assess the safety and efficacy of PAE compared with a sham procedure in the treatment of LUTS/BPH.Design, setting, and participantsA randomised, single-blind, sham-controlled superiority clinical trial was conducted in 80 males ≥45 yr with severe LUTS/BPH refractory to medical treatment from 2014 to 2019 in a private clinic, with efficacy assessments at 6 and 12 mo after randomisation. One patient in the PAE group and three in the sham group did not complete the study.InterventionPatients were randomised 1:1 upon successful catheterisation of a prostatic artery to either PAE or a sham PAE procedure without embolisation. After 6 mo, all 38 patients randomised to the sham group who completed the single-blind period underwent PAE, and both groups completed a 6-mo open period.Outcome measurements and statistical analysisAn intention-to-treat analysis of all randomised patients was performed. The coprimary outcomes were the change from baseline to 6 mo in the International Prostate Symptom Score (IPSS) and the quality of life (QoL) score at 6 mo, analysed with analysis of covariance and t test, respectively.Results and limitationsMean age was 63.8 ± 6.0 yr, baseline IPSS 26.4 ± 3.87, and QoL score 4.43 ± 0.52. At 6 mo, patients in the PAE arm had a greater improvement in IPSS, with a difference in the change from baseline of 13.2 (95% confidence interval [CI] 10.2–16.2, p < 0.0001), and a better QoL score at 6 mo (difference: 2.13; 95% CI 1.57–2.68, p < 0.0001) than the patients in the sham arm. The improvements in IPSS and QoL in the sham group 6 mo after they performed PAE were, respectively, 13.6 ± 9.19 (p < 0.0001) and 2.05 ± 1.71 (p < 0.0001). Adverse events occurred in 14 (35.0%) patients after PAE and in 13 (32.5%) after sham, with one serious adverse event in the sham group during the open period. No treatment failures occurred. Limitations include a single-centre trial, only severe LUTS/BPH, and follow-up limited to 12 mo.ConclusionsThe improvements in subjective and objective variables after PAE are far superior from those due to the placebo effect.Patient summaryClearly superior efficacy of prostatic artery embolisation (PAE) compared with a sham procedure was found in this study, which supports the use of PAE in patients with typical symptoms associated with benign prostatic hyperplasia.     

Synovium CD20 expression is a potential new predictor of bone erosion progression in very-early arthritis treated by sequential DMARDs monotherapy – A pilot study from the VErA cohort

ObjectiveBecause available biomarkers (rheumatoid factors [RF], anti-cyclic citrullinated autoantibodies [anti-CCP2], erythrocyte sedimentation rate at 1st hour [ESR]/C-reactive peptide [CRP] and bone erosions) are insufficient to predict rheumatoid arthritis (RA) structural damage, to determine whether synovium expression of greater or equal to 1 markers could constitute new prognostic factor(s).MethodThe study was conducted on 18 prospectively enrolled disease-modifying anti-rheumatic drug (DMARD)- and glucocorticoid-naïve, VErA cohort patients with very-early arthritis (median duration: 4 months). Recorded at baseline were: clinical and biological (serum ESR, CRP, RF-isotypes, anti-CCP2, osteoprotegerin, receptor activator of nuclear κB-ligand [RANK-L] and cartilage oligomeric matrix protein [COMP] levels) data; synovium expression (HLA-DR, CD163, CD3, CD20, VEGF, osteoprotegerin, RANK-L, Bcl2 and global inflammation index) for a metacarpophalangeal joint-synovium biopsy. Baseline and 3-year hand-and-foot X-rays were graded with the van der Heijde-modified-Sharp score; the judgment criterion was its progression during follow-up. Pearson's product moment correlation statistics were used to test for association between paired samples.ResultsA baseline, a significant relationship was found between erosive damage and markers of B-cell activation, notably the synovium CD20 expression (r = 0.68; P = 0.0001). Quantified by the modified-Sharp erosion score variation, the 3-year structural damage progression was significantly correlated with: serum levels of RF-IgG (r = 0.75; P = 0.0003), -IgM (r = 0.69; P = 0.001), anti-CCP2 (r = 0.53; P = 0.02) and RANK-L (r = 0.61; P = 0.007); synovium CD20 expression (r = 0.70; P = 0.001).ConclusionThis analysis of the prognostic value of a large panel of synovium markers in a limited sample of prospectively followed, well-documented patients suggested that both synovial CD20 and serum RANK-L levels might be new predictors of structural damage progression in very-early RA.     

Location of atypical femoral fracture can be determined by tensile stress distribution influenced by femoral bowing and neck-shaft angle: a CT-based nonlinear finite element analysis model for the assessment of femoral shaft loading stress

IntroductionLoading stress due to individual variations in femoral morphology is thought to be strongly associated with the pathogenesis of atypical femoral fracture (AFF). In Japan, studies on AFF regarding pathogenesis in the mid-shaft are well-documented and a key factor in the injury is thought to be femoral shaft bowing deformity. Thus, we developed a CT-based finite element analysis (CT/FEA) model to assess distribution of loading stress in the femoral shaft.Patients and MethodsA multicenter prospective study was performed at 12 hospitals in Japan from August 2015 to February 2017. We assembled three study groups—the mid-shaft AFF group (n = 12), the subtrochanteric AFF group (n = 10), and the control group (n = 11)—and analyzed femoral morphology and loading stress in the femoral shaft by nonlinear CT/FEA.ResultsFemoral bowing in the mid-shaft AFF group was significantly greater (lateral bowing, p < 0.0001; anterior bowing, p < 0.01). Femoral neck-shaft angle in the subtrochanteric AFF group was significantly smaller (p < 0.001). On CT/FEA, both the mid-shaft and subtrochanteric AFF group showed maximum tensile stress located adjacent to the fracture site. Quantitatively, there was a correlation between femoral bowing and the ratio of tensile stress, which was calculated between the mid-shaft and subtrochanteric region (lateral bowing, r = 0.6373, p < 0.0001; anterior bowing, r = −0.5825, p < 0.001).ConclusionsCT/FEA demonstrated that tensile stress by loading stress can cause AFF. The location of AFF injury could be determined by individual stress distribution influenced by femoral bowing and neck-shaft angle.     

Time-averaged DAS28 and HAQ predict cardiovascular disease in patients with rheumatoid arthritis: Data from KORONA registry

ObjectiveTo evaluate the predictive role of time-averaged disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ) on cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA).MethodsPatients with RA were recruited from 23 tertiary hospitals. Baseline and annual follow-up data of demographic, laboratory, questionnaire, RA-associated parameters, and occurrence of CVD were collected. Patients were divided into three groups according to time-averaged DAS28: 1) remission (< 2.6), 2) low (2.6–3.2), 3) moderate (3.2–5.1), and 4) high (> 5.1). Kaplan–Meier curves was performed to compare the cumulative probability of CVD. Hazard ratios of each factor on the occurrence of CVD were obtained using Cox regression analyses.ResultsA total of 4,034 RA patients with 826 for remission, 938 for low, 2,002 for moderate, and 268 for high time-averaged DAS28 groups were included. Baseline age, disease duration, ESR, CRP, DAS28, and HAQ scores were higher in the high time-averaged DAS28 group. The incidence rate of CVD was 2.86, 2.71, 3.53, and 8.13 events per 1,000 person-years for the remission, low, moderate, and high time-averaged DAS28 groups, respectively. The incidence rate ratio of CVD in the high time-averaged DAS28 group were 3.01 (95% CI 1.20–8.50) when compared to low time-averaged DAS28 group. The cumulative hazard for CVD in the high time-averaged DAS28 group was significantly high (log-rank P < 0.01). In multivariate Cox regression analysis, age, high time-averaged DAS28, and time-averaged HAQ > 0.5, were positively associated with CVD events in RA patients.ConclusionsIn patients with RA, time-averaged DAS28 and HAQ could predict the occurrence of CVD.Trial RegistrationClinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.     

Effect of one anesthetic exposure on long-term behavioral changes in children

Study ObjectiveTo determine the association between one anesthetic exposure and behavioral outcome at age 10 to 12 years.DesignRetrospective comparative study.SettingUniversity-affiliated pediatrics department.MeasurementsThe medical records of children who underwent anesthesia between January 2004 and December 2005 at our institution were reviewed. The records of 292 children were included in the study group and 300 children in the control group. The study group involved children who had one anesthetic exposure before age of 4 years and the control group had children who were not exposed to anesthesia. The primary outcome was behavioral change as assessed by the Eyberg Child Behavior Inventory (ECBI) questionnaire.Main ResultsThe rate of behavioral abnormalities before the age of 11 years was 28.4% in the study group (P < 0.001) and 5.7% in the control group. The risk of developing behavioral abnormalities was prominent in children being exposed to surgery versus those exposed during a diagnostic procedure (32.4% vs 4.8%; P < 0.0001). Eighty-three point nine percent of the children who were exposed to longer duration anesthesia (more than 3 hrs) had behavioral abnormalities (P < 0.0001), while 48.8% of children who received anesthesia at younger ages (0 - 6 mos) had behavioral abnormalities (P < 0.0001). Exposure to multiple anesthetic agents versus one anesthetic agent was a significant risk factor for development of behavioral abnormalities (P < 0.0001).ConclusionThe incidence of behavioral abnormalities increased when anesthesia and surgery were accompanied by younger age, longer duration of surgery, and use of multiple anesthetic agents.     

Bilateral sphenopalatine ganglion block as adjuvant to general anaesthesia during endoscopic trans-nasal resection of pituitary adenoma

BackgroundThis study was conducted to investigate the anaesthetic, vasodilator, and post-operative analgesic sparing effect of bilateral sphenopalatine ganglion block (SPGB) in patients undergoing endoscopic endo-nasal trans-sphenoidal surgery.MethodsThirty adult patients of ASA (I, II), aged 20–60 years, were randomly allocated to either the block group or the non-block group (n = 15, for each). After establishment of general anesthesia with sevoflurane and 100% oxygen, the patients received bilateral SPGB with 1.5 ml of either 0.5% bupivacaine (block group) or 0.9% NaCl (non-block group). Intra-operative mean arterial pressure (MAP) was maintained at 60–65 mmHg by using nitroglycerine. End-tidal sevoflurane concentration required to maintain bispectral index values (40–50) throughout the operation was recorded. Nitroglycerine and propranolol consumption, blood loss, recovery profile, perioperative catecholamines, post-operative pain and meperidine consumption were evaluated.ResultsBlock group showed significant decrease in sevoflurane and nitroglycerine consumption, blood loss, emergence time and time needed to achieve ?9 Aldrete score, P < 0.0001. All patients in non-blockade group (100%) were supplemented by nitroglycerine to achieve the target MAP versus 9 patients (60%) in the block group (P < 0.01). Propranolol administration was necessary in 9 patients (60%) in the non-block group versus 3 patients (20%) in the block group, P < 0.05. At PACU, visual analogue pain score and number of patients received meperidine analgesia were significantly less in the block group versus non-block group, P < 0.0001 and P < 0.001, respectively. Intra- and post-operative plasma epinephrine and nor-epinephrine levels were significantly higher in the non-block group than the block group, P < 0.05.ConclusionBilateral SPGB has anaesthetic, vasodilator and analgesic sparing effect when combined with general anaesthesia during endoscopic endo-nasal trans-sphenoidal resection of pituitary adenoma.