Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

BACKGROUND/AIMS: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. METHODS: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). RESULTS: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. CONCLUSION: Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Performance of cut-offs adjusted with positive control band intensity in line-blot assays for myositis-specific antibodies.

The diagnostic performance of band intensity (BI) cut-offs, adjusted by a positive control band (PCB) in a line-blot assay (LBA) for myositis-related autoantibodies (MRAs) is investigated. Sera from 153 idiopathic inflammatory myositis (IIM) patients with available immunoprecipitation assay (IPA) data and 79 healthy controls were tested using the EUROLINE panel. Strips were evaluated for BI using the EUROLineScan software, and the coefficient of variation (CV) was calculated. Sensitivity and specificity, area under the curve (AUC), and the Youden's index (YI) were estimated at non-adjusted or PCB-adjusted cut-off values. Kappa statistics were calculated for IPA and LBA. Although inter-assay CV for PCB BI was 3.9%, CV was 12.9% in all samples, and a significant correlation was found between BIs of PCB and seven MRAs (all P < 0.05). At adjusted BI (aBI) > 10, the negative conversion rate of myositis-specific autoantibody (MSA)-positivity at BI > 10 was 11.5% in controls and 1.3% in patients. The specificity, AUC, and YI for MSAs at aBI > 10 or > 20 were higher than those at non-adjusted cut-off values. Additionally, AUC (0.720), YI (0.440), and the prevalence of MRAs with kappa > 0.60 (58.3%) were the highest at aBI > 20. The overall sensitivity and specificity for MSAs were 50.3% and 93.7% at aBI > 20, respectively, and 59.5% and 65.8% with BI > 10, respectively. The diagnostic performance of LBA can be improved using PCB-adjusted BIs. aBI > 20 is the optimal cut-off for IIM diagnosis using the EUROLINE LBA panel.

Lung function trajectory of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: To explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD). METHODS: The Korean Rheumatoid Arthritis-Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories. RESULTS: This study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were 'improving' [n = 11 (7.9%)], 'stable' [n = 68 (38.4%)], 'slowly declining' [n = 54 (48.6%)] and 'rapidly declining' [n = 7 (5.0%)]. Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)]. CONCLUSION: Most patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory.

Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). METHODS: The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. RESULTS: Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. CONCLUSION: None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.

Pleuroparenchymal fibroelastosis in rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD) featuring dense fibrosis of the visceral pleura and subpleural parenchyma, mostly in the upper lobes. PPFE can present in other ILDs, including rheumatoid arthritis-associated ILD (RA-ILD). The aim of this retrospective study was to investigate the prevalence and clinical implications of coexistent PPFE in RA-ILD. METHODS: Overall, 477 patients with RA-ILD were recruited from two cohorts; their clinical data and HRCT images were analysed. The criteria for diagnosing PPFE were (1) pleural thickening with bilateral subpleural dense fibrosis in the upper lobes, (2) evidence of disease progression, and (3) absence of other identifiable aetiologies. RESULTS: The median follow-up duration was 3.3 years. The mean age of the patients was 63.4 years, and 60.0% were women. PPFE was identified in 31 patients (6.5%). The PPFE group showed significantly lower body mass index and forced vital capacity (FVC) and more frequent usual interstitial pneumonia (UIP)-like pattern on HRCT than no-PPFE group. The risk factors for all-cause mortality were older age, lower FVC, and the presence of UIP-like pattern on HRCT; PPFE was not significantly associated with mortality in both all patients and a subgroup with a UIP-like pattern. The presence of PPFE was associated with a significantly increased risk of pneumothorax and greater decline in diffusing capacity. CONCLUSIONS: PPFE was not rare in patients with RA-ILD and was significantly associated with an increased risk of pneumothorax and greater lung function decline, though we found no significant association with mortality.

A Case of Macrophage Activation Syndrome During the Treatment of Adult-onset Still's Disease With Tocilizumab.

Macrophage activation syndrome (MAS) is a fatal complication of adult-onset Still's disease (AOSD). Although anti-cytokine agents have been recommended for refractory AOSD or complicated with MAS, MAS cases have been rarely reported during anti-cytokine treatment. Herein, we describe the first AOSD case complicated with MAS during the treatment with tocilizumab in Korea. Two years after tocilizumab maintenance therapy, high fever and hypertransaminasemia recurred. MAS was diagnosed based on hyperferritinemia, elevated soluble IL-2 receptor levels, and the presence of hemophagocytic histiocytes in the bone marrow. However, she had normal white blood cell counts and acute phase reactant levels. High-dose glucocorticoid and anakinra therapies were not effective, but her disease improved with etoposide. This case shows that tocilizumab may not prevent MAS development and can modify clinical features making it challenging to diagnose. Cytotoxic therapy such as etoposide may be required in MAS cases that develop during anti-cytokine therapy.

Multisystem Inflammatory Syndrome in an Adult after COVID-19 Vaccination: a Case Report and Literature Review.

As the number of people vaccinated increases, people who complain of adverse reactions continue to occur. We experienced a case characterized by low blood pressure, persistent fever, edema due to increased systemic vascular permeability, and systemic inflammation confirmed by image and laboratory examinations after ChAdOx1 coronavirus disease 2019 (COVID-19) vaccination. The diagnostic criteria for multisystem inflammatory syndrome (MIS) in adults are known as fever of 3 days or more in adults, 2 or more mucocutaneous/gastrointestinal/neurologic symptoms, elevation of inflammatory markers, and clinical/imaging diagnosis of heart failure. A 67-year-old man who was medicated for hypertension and diabetes was admitted complaining of fever, maculopapular rash, diarrhea, headache, chills, and dizziness 6 days after the first vaccination of ChAdOx1 nCoV-19 in Korea. The COVID-19 test was negative but with low blood pressure, leukocytosis, skin rash, pulmonary edema, and increased inflammation markers. His lab findings and clinical course were consistent with those of MIS after COVID-19 vaccination. He was medicated with methylprednisolone 1 mg/kg and diuretics and recovered rapidly. He was discharged after 2 weeks and confirmed cure at outpatient clinic. We report an MIS case after COVID-19 vaccination in Korea.

Clinical utility of quantitative analysis of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis.

BACKGROUND: The purpose of this study was to investigate the efficiency of quantitative parameters of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis. METHODS: We retrospectively enrolled 65 patients with rheumatoid arthritis who underwent bone scintigraphy for diagnostic work-up. Quantitative analysis of bone scintigraphy images was conducted using an in-house software, and joint uptake ratio of 28 joints was measured for the calculation of the disease activity score of 28 joints using erythrocyte sedimentation rate (DAS28-ESR). The relationship between joint uptake ratio and clinical findings and the efficiency of joint uptake ratio in detecting clinically active joint and high disease activity were assessed. RESULTS: Clinically active joint (tender and/or swollen joints) showed significantly higher joint uptake ratio than did other non-affected joints (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of joint uptake ratio for identifying clinically active joint were 78.7%, 52.0%, 32.9%, and 89.1%, respectively, and those of the summed joint uptake ratio for detecting high disease activity were 92.9%, 66.8%, 43.3%, and 97.1%, respectively; the joint uptake ratio showed high detection ability, especially for active joints of the elbow, wrist, and metacarpo-phalangeal joint areas. The summed joint uptake ratio of 28 joints showed a significantly strong positive correlation with DAS28-ESR (p < 0.001; correlation coefficient, 0.725). CONCLUSION: Quantitative parameters of bone scintigraphy showed high sensitivity and NPV for detecting clinically active joint and high disease activity in patients with rheumatoid arthritis.

Clinical utility of F-18 sodium fluoride PET/CT for estimating disease activity in patients with rheumatoid arthritis.

BACKGROUND: The present study aimed to investigate the clinical implication of F-18 sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) for assessing the disease activity of rheumatoid arthritis. METHODS: Seventeen patients with rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria were prospectively enrolled. All enrolled patients underwent F-18 NaF PET/CT along with physical examination, blood test, and ultrasonography. On PET/CT images, two quantitative parameters, F-18 NaF uptake of the joint (joint SUV) and joint-to-bone uptake ratio, were measured for each of the 28 joints included in calculating the disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). The relationship between PET/CT parameters and clinical factors and the predictive values of PET/CT parameters for joints with synovitis and high disease activity were evaluated. RESULTS: Tender joints (joint SUV, 13.6±8.4; joint-to-bone uptake ratio, 1.70±1.02) and both tender and swollen joints (joint SUV, 13.9±5.4; joint-to-normal bone uptake ratio, 1.81±0.76) had significantly higher joint SUV and joint-to-bone uptake ratio than joints without synovitis (joint SUV, 6.0±2.4; joint-to-bone uptake ratio, 0.74±0.31; P<0.001). On correlation analysis, summed joint SUV (P=0.002, correlation coefficient=0.705) and summed joint-to-bone uptake ratio (P<0.001, correlation coefficient=0.861) of 28 joints showed strong positive correlation with DAS28-ESR after adjustment for age and body mass index. Summed joint SUV showed significant positive correlations with ultrasonography findings (grey scale ultrasonography: P=0.047, correlation coefficient =0.468; power Doppler ultrasonography: P=0.045, correlation coefficient =0.507). On the receiver operating characteristic curve analysis, the sensitivity and specificity for predicting synovitis were 83.2% and 92.7%, respectively, for joint SUV and 81.5% and 90.7%, respectively, for joint-to-bone uptake ratio. Moreover, the summation of both PET/CT parameters of 28 joints showed a diagnostic accuracy of 100.0% for predicting high disease activity in rheumatoid arthritis. CONCLUSIONS: Summed joint uptake on F-18 NaF PET/CT had a strong positive correlation with DAS28-ESR and accurately predicted high disease activity. F-18 NaF PET/CT parameters might be used as an imaging biomarker for disease activity in rheumatoid arthritis. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service of the Korea (CRIS, http://cris.nih.go.kr/cris/en; registry number, KCT0002597; registered November 2017).

Comparison of the 2017 EULAR/ACR Criteria with Clinicoserologic Criteria for the Classification of Idiopathic Inflammatory Myopathies in Korean Patients.

PURPOSE: To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. MATERIALS AND METHODS: We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. RESULTS: According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with anti-TIF1γ, anti-SRP, and anti-MDA5. CONCLUSION: The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.

A clinical comparison of an endothelin receptor antagonist and phosphodiesterase type 5 inhibitors for treating digital ulcers of systemic sclerosis.

OBJECTIVES: To assess the efficacy of an endothelin receptor antagonist (ERA) and phosphodiesterase type5 inhibitors (PDE5is) for treating SSc-related digital ulcers (DUs). METHODS: This prospective, multicentre, observational cohort study recruited patients with active SSc-related DUs from 13 medical centres in South Korea. The primary outcome was time to cardinal ulcer (CU) healing. A secondary outcome was time to new DU occurrence. Patients were followed up 4, 8, 12 and 24 weeks after treatment initiation. RESULTS: Sixty-three patients were analysed. Their mean age was 49.9 years (s.d. 11.4) and 49 were female. Twenty-eight had limited SSc. Forty-nine patients received ERA, 11 received a PDE5i (9 sildenafil, 1 udenafil and 1 tadalafil) and 3 received other medication. The hazard ratio (HR) for time to CU healing in the ERA group vs the PDE5i group was 0.75 (95% CI 0.35, 1.64; P = 0.47) in an unadjusted model and 0.80 (95% CI 0.36, 1.78; P = 0.59) in a model adjusted for age, sex, use of calcium channel blockers (CCBs), total DU number and initial CU area. The HR for new DU development in the ERA group vs the PDE5i group was 0.39 (95% CI 0.16, 0.93; P = 0.03) in an unadjusted model and 0.32 (95% CI 0.13, 0.81; P = 0.02) in an adjusted model. No patients receiving CCBs developed new DUs at 24 weeks. CONCLUSION: Time to CU healing is comparable for ERA and PDE5i. ERAs are more effective in reducing new DU occurrence than PDE5is. CCBs may be effective as a background medication.

Association of Serum Biomarkers With Pulmonary Involvement of Rheumatoid Arthritis Interstitial Lung Disease: From KORAIL Cohort Baseline Data.

Objective: The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. Methods: We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT) CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). Results: MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=-0267, p=0001; SP-D, r=-0250, p=0002; KL-6, r=-0223, p=0006) and DLCO (MMP-7, r=-0404, p<0001; SP-D, r=-0286, p=0001; KL-6, r=-0226, p=0007) In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0013; SP-D, p<0001; KL-6, p<0001). Conclusion: MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

Clinical Use of Quantitative Analysis of Bone Scintigraphy to Assess the Involvement of Arthritis Diseases in Patients with Joint Symptoms.

We aimed to compare the diagnostic ability of quantitative analysis of bone scintigraphy with that of visual analysis for identifying arthritis disease involvement in patients with joint symptoms. We retrospectively included 93 patients with joint symptoms who underwent Tc-99m methylene diphosphonate bone scintigraphy for evaluating arthritis disease involvement. Bone scintigraphy images were visually and quantitatively analyzed using an in-house software by two reviewers. On quantitative analysis, joint uptake ratio was measured for 64 joints in 14 joints areas. The inter-rater agreement of visual and quantitative analyses was assessed, and diagnostic abilities were compared based on the area under the receiver operating characteristic (ROC) curve (AUC) values. Regarding visual analysis, there was a moderate degree of inter-rater agreement (kappa coefficient of 0.597), while there was a substantial inter-rater agreement (concordance correlation coefficient of 0.987) in the measurement of the joint uptake ratio. The comparisons of ROC curves for the total 5941 joints revealed that the joint uptake ratio had a significantly higher AUC value (0.789) to detect the affected joint than that of the visual analysis (p < 0.001). Quantitative analysis using joint uptake ratio showed substantial reproducibility and higher diagnostic ability to detect joints involving arthritis diseases than visual analysis on bone scintigraphy.

Prevalence of feet and ankle arthritis and their impact on clinical indices in patients with rheumatoid arthritis: a cross-sectional study.

BACKGROUND: We aimed to evaluate the prevalence of foot and/or ankle arthritis (FAA) and its impact on clinical indices in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study used data from the Korean College of Rheumatology Biologics & Targeted therapy registry to observe clinical outcomes of patients undergoing biologics therapy and conventional therapy. FAA was defined as ≥1 tender or swollen joint in the ankle and/or 1st-5th metatarsophalangeal (MTP) joints. Disease Activity Score 28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) were assessed. RESULTS: Among 2046 patients, 598 had FAA. The ankle joint was the most commonly involved joint in FAA (tender joint, 71.4%; swollen joint, 59.5%), followed by the third and second MTP joints. Patients with FAA showed higher DAS28, RAPID3, SDAI, and CDAI scores. FAA presence was significantly associated with non-remission as per DAS28-ESR (odds ratio, 3.4; 95% confidence interval, 2.0-5.8), DAS28-CRP (3.6, 2.4-5.3), SDAI (6.3, 2.8-14.6), CDAI (7.6, 2.4-24.3), and RAPID3 (5.6, 2.7-11.5) indices on adjusting for age, sex, disease duration, presence of rheumatoid factor, presence of anti-cyclic citrullinated peptide antibody, lung disease, use of methotrexate, and previous use of biological disease-modifying anti-rheumatic drugs. Patients with FAA were less likely to achieve remission of SDAI (n = 6, 1.0%) and CDAI (n = 3, 0.5%) than that of DAS28-ESR (n = 21, 3.5%), DAS28-CRP (n = 38, 6.4%), and RAPID3 (n = 12, 2.0%). CONCLUSIONS: FAA represents a severe disease activity and is an independent risk factor for non-remission in patients with RA.

Clinical application of dual-phase F-18 sodium-fluoride bone PET/CT for diagnosing surgical site infection following orthopedic surgery.

F-18 sodium-fluoride (NaF) bone positron emission tomography (PET/CT) has been used for diagnosing various bone and joint diseases, and, with using dual-phase scan protocol, it could give the same information obtained by the 3-phase bone scintigraphy. The present study aimed to evaluate the diagnostic ability of dual-phase F-18 NaF bone PET/CT in detecting surgical site infection after orthopedic surgery.Twenty-three patients who underwent dual-phase F-18 NaF bone PET/CT under clinical suspicion of surgical site infection of the bone following orthopedic surgery were enrolled in this study. Dual-phase bone PET/CT consisted of an early phase scan performed immediately after radiotracer injection and a conventional bone-phase scan. All dual-phase PET/CT images were visually assessed, and, for quantitative analysis, 6 parameters of dual-phase PET/CT (lesion-to-blood pool uptake ratio, lesion-to-bone uptake ratio, and lesion-to-muscle uptake ratio on both early phase and bone-phase scans) were measured.Surgical site infection was diagnosed in 14 patients of the 23 patients. The sensitivity, specificity, and accuracy of visual analysis of dual-phase F-18 NaF bone PET/CT for diagnosing surgical site infection of the bone were 92.9%, 100.0%, and 95.7%, respectively. Among the 6 parameters, the lesion-to-blood pool uptake ratio on early phase scan showed the highest area under the receiver operating characteristic curve value (0.857, 95% confidence interval, 0.649-0.966), with the cut-off value of 0.88 showing sensitivity, specificity, and accuracy of 85.7%, 88.9%, and 87.0%, respectively.Our study showed the high diagnostic ability of dual-phase F-18 NaF bone PET/CT for detecting surgical site infection following orthopedic surgery. Further studies are needed to compare the diagnostic ability of dual-phase bone PET/CT with other imaging modalities.

Impact of EUSTAR standardized training on accuracy of modified Rodnan skin score in patients with systemic sclerosis.

OBJECTIVES: To investigate the impact of European Scleroderma Trials and Research (EUSTAR) standardized training on the accuracy of modified Rodnan skin score (mRSS) in patients with systemic sclerosis (SSc). METHODS: Eight SSc patients (four diffuse, four limited) and 10 physicians (4 fellows, 6 professors) were included. Gold-standard mRSS was performed by a senior instructor. Training comprised a video presentation and a live demonstration. Each physician performed mRSS with no clinical information in all patients: (a) before training; (b) after video session; and (c) after live demonstration. Primary outcome was the change in scoring accuracy, which was defined as the difference from the gold-standard skin score, as analyzed using a linear mixed model. RESULTS: Mean (standard deviation) difference from the gold-standard score in all measurements by participants before the training was 7.7 (9.5). Completion of training significantly enhanced mRSS accuracy (adjusted ß = -7.61; 95% CI: -11.91 to -3.32). This was largely attributable to the video presentation (adjusted ß = -5.47; -9.16 to -1.78), although the live demonstration was associated with numerical reduction in the difference from the gold-standard score (adjusted ß = -2.15; -5.84 to 1.55). Effect of training was prominent in fellows whereas professors showed an increase in the difference from gold-standard score after training (P value for interaction <0.001). The intraclass correlation coefficient for physician skin scores was acceptable. However, no significant change was observed after training. CONCLUSION: New EUSTAR standardized mRSS training significantly enhanced mRSS accuracy, especially in participant with less previous experience in skin scoring.

The Clinical Efficacy and Safety of Gumiganghwal-Tang in Knee Osteoarthritis: A Phase II Randomized Double Blind Placebo Controlled Study.

BACKGROUND: Gumiganghwal-tang (GMGHT) is a traditional herbal medicine consisting of nine different herbs. GMGHT inhibits the mRNA expression and production of inflammatory cytokines tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6), and TNF- ß on lipopolysaccharide- (LPS-) stimulated peritoneal macrophages in a dose-dependent manner. It is empirically used for the treatment of inflammatory disease, but there are few reports of clinical trials that investigate its efficacy and safety. The current study aimed to investigate the clinical efficacy and safety of GMGHT in patients with knee osteoarthritis (OA). METHODS: This was a multicenter, two-armed, double-blinded, randomized, placebo controlled study of GMGHT over 6 weeks. Eligible patients who fulfilled the American College of Rheumatology criteria for OA were randomized to receive either GMGHT or the placebo. Clinical assessments included measurement of knee pain and function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. RESULTS: A total of 128 patients were enrolled (91.4% female; mean age, 58.7 ± 8.1 years). At baseline, pain visual analogue score (VAS) was 67.2 ± 1.4, resp. 71.3 ± 1.6 (treatment, resp. placebo group, p=0.84), and total WOMAC score was 55.2 ± 1.6, resp. 55.6 ± 1.5 (p = 0.84). After 6 weeks, the pain VAS was 43.0 ± 2.5, resp. 61.6 ± 2.5 (p < 0.01) and the total WOMAC score was 34.1 ± 2.4, resp. 46.9 ± 1.8 (p < 0.01). No patients withdrew because of treatment emergent adverse events. Expected adverse events including dyspepsia, liver function abnormality, and lower extremity edema were comparable between both groups. CONCLUSIONS: Treatment with GMGHT resulted in significant improvement in pain, function, and global assessment, and it was generally safe and well tolerated in patients with OA.

Clinical and Laboratory Characteristics and Mortality in Korean Patients with Systemic Sclerosis: A Nationwide Multicenter Retrospective Cohort Study.

OBJECTIVE: We aimed to investigate demographic and clinical features and predictors of mortality in Korean patients with systemic sclerosis (SSc). METHODS: We performed a retrospective multicenter medical chart review in Korean patients diagnosed with SSc from 1986 to 2016 at 11 university hospitals representing each geographic area of Korea. SSc patients were defined according to the American College of Rheumatology preliminary classification criteria and subtyped as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc. RESULTS: We enrolled 751 patients (female, 86.7%; mean age at diagnosis, 48.9 yrs). The most common organ involvement was interstitial lung disease (52.7%), followed by gastroesophageal reflux disease (32.9%) and pulmonary arterial hypertension (13.6%). Patients with lcSSc were more common than those with dcSSc (64.8 vs 35.2%), whereas anti-Scl-70 and anticentromere antibody positivity were identified in 302 (42.5%) and 175 (25.5%) patients, respectively. In the 46 (6.1%) patients who developed a malignancy, lung cancer (23.9%) was the most common diagnosis, followed by gastric (13%) and breast cancer (13%). During the study period, 57 (7.6%) patients died, and the 5- and 10-year survival rates were 94% and 87%, respectively. Increased age at diagnosis, cardiovascular involvement, and anti-Scl-70 antibody positivity were significant predictors of death. CONCLUSION: Clinical manifestations and survival rates in Korean SSc patients are similar to those of other populations. However, the prevalence of anti-Scl-70 antibody is higher in Korean SSc patients compared with whites, while the prevalence of anticentromere antibody is lower.

Clinical role of bone scintigraphy in low-to-intermediate Framingham risk patients with atypical chest pain.

OBJECTIVE: The purpose of the study is to evaluate the clinical usefulness of bone scintigraphy for etiological diagnosis of patients with atypical chest pain. PATIENTS AND METHODS: We retrospectively enrolled 225 patients with atypical chest pain who underwent bone scintigraphy for etiological diagnosis. No patients showed any symptoms or signs other than chest pain and had low-to-intermediate Framingham risk with insignificant findings on initial cardiac evaluation. They had no recent traumatic events or history of cerebrovascular and coronary heart diseases. The usefulness of bone scintigraphy for clinical diagnosis in enrolled patients was assessed and compared according to age (<60 vs. ≥60 years). RESULTS: Sixty-two (27.6%) patients were at intermediate Framingham risk and 100 (44.5%) patients were older than or equal to 60 years of age. Bone scintigraphy showed abnormal findings in 111 (49.4%) patients. Clinical diagnoses of chest pain were made in 163 (72.4%) patients. The remaining 62 (27.6%) patients were assessed as having unknown etiology. Bone scintigraphy was helpful for clinical diagnosis in 94 (41.8%) patients. Patients older than or equal to 60 years of age had significantly more frequent abnormal findings and post-traumatic changes on bone scintigraphy than patients younger than 60 years of age (P=0.010 for all). Of 111 patients with abnormal findings on bone scintigraphy, six (5.4%) were diagnosed with coronary heart disease; all of them were older than or equal to 60 years. CONCLUSION: Bone scintigraphy was helpful for etiological diagnosis of atypical chest pain in 41.8% of patients. However, coronary heart disease should be considered in patients older than or equal to 60 years of age, even if patients showed abnormal findings on bone scintigraphy.

Association between endothelin­1 and fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is characterized by widespread chronic musculoskeletal pain, stiffness and pressure hyperalgesia at soft tissue tender points. Patients with FMS may exhibit a tendency towards cold extremities and cold­induced vasospasm. Endothelin­1 (EDN1) is a potent vasoconstrictor that is mainly produced by endothelial cells. The present study aimed to determine whether plasma expression levels avvnd single­nucleotide polymorphism (SNP; rs1800541) of the EDN1 gene were associated with FMS and/or any of its clinical variables. Plasma EDN1 levels were assessed by ELISA, and SNP genotypes were determined using polymerase chain reaction­high­resolution melting curve analysis. Patients with the TG genotype and the G allele may have an elevated risk of FMS. In addition, patients with FMS with the TG genotype and/or T allele exhibited higher plasma EDN1 levels compared with healthy controls. EDN1 levels increased significantly in patients with FMS compared with normal controls. In addition, EDN1 SNP was found to be associated with susceptibility to FMS.