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Motor-sparing regional anesthesia modalities, such as periarticular infiltration (PAI) and pericapsular nerve group (PENG) block, have become the mainstay of multimodal approaches used during total hip arthroplasty (THA). We hypothesized that the postoperative analgesia of the PENG block was non-inferior to that of the PAI.Sixty patients were randomly allocated into two groups. The PAI group were injected with 100 mL of cocktail solution (ropivacaine 20 mL, ketorolac 2 mL, and epinephrine 1 mL mixed with normal saline) in periarticular tissues directly by the surgeon. The PENG group were injected with 30 mL of 0.5% ropivacaine in the iliopubic eminence plane by ultrasound. The primary outcome was the resting pain score 12 h after surgery, and the prespecified non-inferiority was 1. Additionally, the cumulative opioid consumption and quality of recovery were evaluated.The mean difference in pain score 12 h postoperatively between the PENG and PAI groups was 0.6 [95% confidence interval (CI): -0.8 to 2.0]. The upper 95% CI exceeded the non-inferiority margin of 1 at all postoperative time points. There was no difference in opioid consumptions and quality of recovery scores.PENG block provided comparable analgesia with PAI following THA. It is not conclusive that PENG is inferior or non-inferior to PAI based on our study.Clinical Research information Service (CRIS, https://cris.nih.go.kr, KCT0006049).

Objectives: This study aimed to explore the status of regional variations in acute ischemic stroke (AIS) treatment and investigate the association between the presence of a thrombectomy-capable stroke center (TSC) and the case fatality rate (CFR) of AIS within hospital service areas (HSAs).Methods: This observational cross-sectional study analyzed acute stroke quality assessment program data from 262 hospitals between 2013 and 2016. TSCs were defined according to the criteria of the Joint Commission. In total, 64 HSAs were identified based on the addresses of hospitals. We analyzed the effects of structure factors, process factors, and the presence of a TSC on the CFR of AIS using multivariate logistic regression.Results: Among 262 hospitals, 31 hospitals met the definition of a TSC. Of the 64 HSAs, only 20 had a TSC. At hospitals, the presence of a stroke unit, the presence of stroke specialists, and the rate of endovascular thrombectomy (EVT) treatment were associated with reductions in the CFR. In HSAs, the rate of EVT treatment (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and the presence of a TSC (OR, 0.93; 95% CI, 0.88 to 0.99) significantly reduced the CFR of AIS.Conclusions: The presence of a TSC within an HSA, corresponding to structure and process factors related to the quality of care, contributed significantly to lowering the CFR of AIS. The CFR also declined as the rate of treatment increased. This study highlights the importance of TSCs in the development of an acute stroke care system in Korea.

Background/aims Because ankylosing spondylitis (AS) mainly affects sacroiliac joints, special attention should be given to normal labour and pregnancy outcomes. Here, we investigate pregnancy outcomes in Korean women with AS. Methods Based on data from the Korean Health Insurance Review and Assessment Service claims database since July 2007, maternal complications were compared between women with AS and 1:10 matched general population by maternal age and year of delivery. Additionally, the 27 deliveries from 21 patients with AS who were seen at a tertiary hospital were retrospectively evaluated using 1:4 matched control group by maternal and gestational age. Results In the population-based cohort, there were 1,293 deliveries in 996 patients with AS. Higher maternal age and more comorbidities were reported than in the general population. However, compared to age and delivery-year matched population, only the rate of Caesarean section (CS) was higher in women with AS (odds ratio, 1.52; 95% confidence interval, 1.36 to 1.70). Incidence of other maternal complications was comparable between women with AS and control subjects. In the hospital-based cohort, the CS rate was higher in women with AS (44.4% vs. 20.4%, p = 0.002). Causes of CS was not different in both groups, including previous uterine surgery. There were no significant differences in foetal outcomes, including growth restriction, foetal malformations and Apgar score. Conclusion CS deliveries were performed more often in women with AS. However, other maternal complications and offspring complications were similar between women with AS and healthy control subjects.

The present study compared the effects of pectoral nerve block II (PECS II) and erector spinae plane (ESP) block for postoperative analgesia in patients who underwent modified radical mastectomy by performing a network meta-analysis (NMA) using indirect comparison with systemic analgesia. Studies comparing the analgesic effects of PECS II and ESP block were searched on MEDLINE, PubMed, EMBASE and the Cochrane Library. The primary outcome of this study was cumulative opioid consumption for 24 h postoperatively. Pain score during this period was also assessed. NMA was performed to compare the postoperative analgesic effects of plane blocks and systemic analgesia. A search of databases identified 17 studies, with a total of 1069 patients, comparing the analgesic efficacies of PECS II block, ESP block, and systemic analgesia. Compared with systemic analgesia, mean difference of opioid consumption was − 10 mg (95% credible interval [CrI] − 15.0 to − 5.6 mg) with PECS II block and − 5.7 mg (95% CrI − 11.0 to − 0.7 mg) with ESP block. Relative to systemic analgesia, PECS II block showed lower pain scores over the first postoperative 24 h, whereas ESP block did not. PECS II block showed the highest surface under the cumulative ranking curves for both opioid consumption and pain score. Both PECS II and ESP blocks were shown to be more effective than systemic analgesia regarding postoperative analgesia following modified radical mastectomy, and between the two blocks, PECS II appeared to have favorable analgesic effects compared to ESP block.

Objectives To investigate longitudinal changes of the EULAR SS Patient-Reported Index (ESSPRI) and EULAR SS Disease Activity Index (ESSDAI), and identify factors associated with patient acceptable symptom state (PASS) in patients with primary SS (pSS). Methods We assessed ESSPRI, ESSDAI, clinical ESSDAI (ClinESSDAI), EULAR Sicca Score, EuroQoL 5-dimension (EQ-5D), Fatigue Severity Score, Beck Depression Inventory, and patient global assessment (PGA) for pSS, and visual analogue scale (VAS) scores for glandular and extra-glandular symptoms at baseline and follow-up. The responses to the currently available standards of care were evaluated by the PASS, the minimal clinically important improvement (MCII) of ESSPRI and ESSDAI, and a modified SS Responder Index-30 (mSSRI-30) response. Results Among 115 patients enrolled, 102 (88.7%) completed a median 3-year follow-up. The ESSPRI, ClinESSDAI and EQ-5D levels remained stable, although the PGA and ESSDAI significantly improved (both P Conclusion Although longitudinal changes in ESSPRI and ClinESSDAI are stable in pSS, baseline ESSPRI and ESSDAI could provide prognostic information on the subsequent achievement of PASS, using currently available treatments. A categorization model using ESSPRI and ESSDAI may have clinical implications.

The use of magnetic resonance imaging (MRI) and positron emission tomography (PET) in rheumatology allows a better understanding of the pathophysiology of the disease as well as early diagnosis and appropriate evaluation of the disease status and treatment responses. Despite the limited availability because of the high cost, there is growing evidence for the advantages and clinical application of these modalities to various rheumatic diseases. This review discusses the basic mechanisms and clinical applications of MRI and PET in certain rheumatic diseases, including rheumatoid arthritis, axial spondyloarthritis, idiopathic inflammatory myopathies, large vessel vasculitis, central nervous system disease associated with rheumatic diseases, polymyalgia rheumatica, adult-onset Still’s disease, and immunoglobulin G4-related disease. (J Rheum Dis 2020;27:136-151)

In this population-based cohort study on comparative osteoporotic fracture risks between different biologic disease-modifying drugs among patients with rheumatoid arthritis (RA), we did not find a significant difference in the risk of osteoporotic fractures between RA patients receiving TNF inhibitors versus abatacept or tocilizumab. We aimed to investigate the comparative risk of osteoporotic fractures between rheumatoid arthritis (RA) patients who initiated TNF inhibitors (TNFis) versus abatacept or tocilizumab. Using the Korea National Health Insurance Service datasets from 2002 to 2016, RA patients who initiated TNFis, abatacept, or tocilizumab were identified. The primary outcome was a composite end point of non-vertebral fractures and hospitalized vertebral fractures; secondary outcomes were two components of the primary outcome and fractures occurring at the humerus/forearm. Propensity score (PS) matching with a variable ratio up to 10 TNFi initiators per 1 comparator drug initiator was used to adjust for > 50 baseline confounders. We estimated hazard ratios (HRs) and 95% confidence interval (CI) of fractures comparing TNFi initiators to abatacept and to tocilizumab by Cox proportional hazard models stratified by a matching ratio. After PS-matching, 2307 TNFi initiators PS-matched on 588 abatacept initiators, and 2462 TNFi initiators on 640 tocilizumab initiators were included. A total of 77 fractures occurred during a mean follow-up of 454 days among TNFi and abatacept initiators and 83 fractures during 461 days among TNFi and tocilizumab initiators. The PS-matched HR (95% CI) was 0.91 (0.48–1.71) comparing TNFi versus abatacept initiators, and 1.00 (0.55–1.83) comparing TNFi versus tocilizumab initiators. Analysis on vertebral and non-vertebral fractures showed similar results. In this nationally representative cohort, we did not find a significant difference in the risk of fractures between TNFi initiators versus abatacept or tocilizumab among RA patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting primarily joints and an increased risk of developing malignant lymphomas in RA has been well reported. However, primary lymphoma in a joint in RA patient is rare. We report the case of a 65-year-old man with RA suffering from pain and swelling of left sternoclavicular (SC) joint, which was not relieved by adding low-dose glucocorticoid. Magnetic resonance imaging (MRI) showed a para-osseous soft tissue swelling around the SC joint and a fracture of proximal clavicle. Histology of the soft tissue demonstrated diffuse large B-cell lymphoma and the patient subsequently underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. He was successfully treated with six cycles of R-CHOP chemotherapy, with discontinuation of MTX, resulting in a complete response. We performed a literature review and identified nine cases of lymphoma which involved joints in patients with rheumatoid arthritis. This is the first described case of a primary large B-cell lymphoma involving the unilateral SC joint in a patient with RA, which was initially confused with aggravation of RA. Therefore, malignant lymphoma should be considered in the differential diagnosis when a RA patient develops monoarthritis with spontaneous fracture, even without B symptoms.

Current stem cell-based therapy for cardiac repair and regeneration after myocardial infarction (MI) is not readily translatable into clinical scenarios due to the low retention and survival of the transplanted cells. Here, we evaluated a simple and feasible design of gelatin-hydroxyphenyl propionic acid (GH) hydrogel as an in situ cross-linkable and injectable cell delivery platform for cardiac tissue regeneration. The GH hydrogel exhibited improved cell retention and survival in vitro and in vivo when encapsulating mouse bone marrow-derived mesenchymal stem cells (MSCs) that were used as promising therapeutic candidates for stem cell therapy. Moreover, we demonstrated that MSC-encapsulating GH hydrogels led to a significant improvement in cardiac functional metrics, such as the fractional shortening (FS), ejection fraction (EF), and end-systolic volume (ESV). Similarly, MSC-encapsulating GH hydrogels induced favorable effects in the cardiac structures of the infarcted heart, producing less fibrosis and thicker infarcted walls. These results suggest that GH hydrogels can be used as an instructive cell delivery platform to provide a suitable microenvironment for transplanted cells; therefore, their in vivo applications combined with MSCs may provide great potential for repair and regeneration of injured cardiac tissues after MI.

목적: 과거 연구들에서 내독소혈증이 간경변증의 병인과 합병증에 연관되어 있음이 보고되었다. 내독소는 염증성 사이토카인 분비를 촉진시키고, 이는 간경변증에서 합병증의 발생에 기여한다. 간경변증에서는 문맥 고혈압 장병증으로 인하여 장투과율이 증가하고, 내독소는 장벽 방어 시스템을 쉽게 침범하게 된다. 본 연구에서는 간경변증 환자에서 사이토카인 및 장투과율의 변화를 확인하고 초음파를 이용하여 장벽의 두께 그리고 탄성도를 측정하고자 하였다. 방법: 저자들은 Child-Pugh B와 C로 분류된 간경변증 환자 40명과 건강한 대조군 20명을 모집하였다. 복부 초음파검사를 통하여 상행결장 및 말단 회장에서 장벽 지표를 측정하였다. 장투과율은 락툴로오스와 만니톨을 이용한 이중 설탕 흡수 테스트를 이용하였다. TNF-α 및 IL-10을 측정하기 위하여 혈액 샘플을 수집하였다. 이 지표들에 대하여 간경변증 환자군와 대조군 간의 결과 및 Child-Pugh B와 C 환자군 간의 결과를 비교하였다. 또한 사이토카인, 장투과율과 장벽 지표의 상관관계를 확인해 보았다. 결과: 간경변 환자에서 상행결장의 장벽 탄성은 감소되었으며(20.4 vs. 10.9 kPa, p = 0.048), 말단 회장의 장벽 두께는 증가되었다(4.2 vs. 1.9 mm, p < 0.001). 장 투과율 및 사이토카인(TNF-α 및 IL-10)은 증가되었다(0.219 vs. 0.017, p < 0.001; 22.47 vs. 13.48 pg/mL, p < 0.001; 14.91 vs. 8.57 pg/mL, p = 0.019). 그러나 Child-Pugh B와 C군 간의 유의한 차이는 없었고, 장벽 지표와 장투과율 또는 사이토카인 간의 유의한 상관관계가 없었다. 결론: 간경변증 환자에서 초음파 검사를 통하여 장벽이 두꺼워지고 탄성도가 감소하는 것을 확인하였다. 또한 장투과율 및 사이토카인은 건강한 대조군과 비교하여 유의하게 증가하였다.

Intravenous dexamethasone and dexmedetomidine, in conjunction with peripheral nerve blockade, have each been reported to prolong the duration of analgesia. This study tested whether combined use further prolongs analgesia duration after supraclavicular brachial plexus block (BPB) in patients undergoing orthopedic upper extremity surgery. One hundred twenty patients were randomized 1:1:1:1 to Control (saline bolus and midazolam infusion [0.05 mg/kg loading, 20 µg/kg/h thereafter]); DMED (saline bolus and dexmedetomidine infusion [1 μg/kg loading, 0.4 μg/kg/h thereafter]); DEXA (dexamethasone [10 mg] bolus and midazolam infusion); and DMED-DEXA (dexmedetomidine infusion and dexamethasone bolus) groups. The primary outcome was the duration of postoperative analgesia, defined as the time from the end of the BPB to the first dose of analgesia via a patient-controlled device. Median (interquartile range) times to first dose of analgesia in the Control, DMED, DEXA, and DMED-DEXA groups were 8.1 (6.2–11.6), 9.0 (8.1–11.3), 10.7 (8.1–20.5), and 13.2 (11.5–19.1) hours, respectively (p < 0.001). Pairwise comparisons showed significant prolongation of analgesia in the DEXA included groups compared with the non-DEXA included groups (DEXA vs. control, p = 0.045; DEXA vs. DMED, p = 0.045; DMED-DEXA vs. control, p < 0.001; DMED-DEXA vs. DMED, p < 0.001). A mixed effect model showed that dexamethasone was the only significant factor for the prolongation of analgesia (p < 0.001). Intravenous dexamethasone prolonged the analgesia duration of supraclavicular BPB after orthopedic upper extremity surgery. The concurrent use of mild to moderate sedation dose of intravenous dexmedetomidine in addition to intravenous dexamethasone showed no additional benefit to the prolongation of analgesia.

Lindera obtusiloba extract (LOE), a traditional herbal medicine used to enhance blood circulation and to reduce inflammation, induced NO-mediated endothelium-dependent relaxation, and reduced the formation of reactive oxygen species (ROS). The study investigated whether LOE improves endothelial dysfunction and reduces plaque inflammation and progression by inhibiting ROS generation in a mouse model of atherosclerosis. Eight-week-old apolipoprotein E-deficient (apoE−/−) mice fed with a western diet (WD) were randomized into different groups by administering vehicle (0.5% carboxymethylcellulose (CMC)), LOE (100 mg/kg/day), or losartan (30 mg/kg/day) by gavage until the age of 28 weeks. Fourteen male C57BL/6 mice that were fed normal chow and treated with CMC were used as negative controls. Similar to losartan treatment, LOE treatment induced the concentration-dependent relaxation of aorta rings in WD-fed apoE−/− mice. LOE treatment significantly reduced the vascular ROS formation and expression of NADPH oxidase subunits, including p22phox and p47phox. Compared with WD-fed apoE−/− mice, mice exposed to chronic LOE treatment exhibited reductions in plaque inflammation-related fluorescence signals and atherosclerotic lesions. These effects were greater than those of losartan treatment. In conclusion, LOE treatment improves endothelial dysfunction and reduces plaque inflammation as well as lesion areas by reducing vascular NADPH oxidase-induced ROS generation in a mouse model of atherosclerosis.

This study aimed to investigate drug retention rates for various TNF inhibitors (TNFis) commonly prescribed to Korean patients with ankylosing spondylitis (AS) in the Korean College of Rheumatology Biologics registry (KOBIO; December 2012–June 2016). Discontinuation was defined as switching or stopping the biologic agent. Kaplan–Meier curves and Cox's proportional hazard models were used for further analysis. The reasons for discontinuation of TNFis were also assessed. Univariate and multivariate analyses were used to identify possible predictors of discontinuation. Data from 1,005 patients with AS were analyzed with a median follow-up period of 14 months. Seventy-six percent of patients were first-line biologic users. Discontinuation of TNFis occurred in 24.2% (switching in 9.6%) of patients during follow-up. An estimate of the drug failure showed that the adjusted hazard ratio (HR) for golimumab compared to etanercept was 0.441 (95% confidence interval: 0.277–0.703, p < 0.001). Reasons for discontinuation included lack of efficacy (32.6%), adverse events (23.6%), clinical improvement (11.2%), and others (32.6%). Predictors of discontinuation using a multivariate analysis were a shorter disease duration (HR: 0.973, p = 0.044) and being negative for HLA-B27 (HR: 1.623, p = 0.0093). In conclusion, few Korean patients with AS switched to other TNFis during their treatment. The drug retention rate for golimumab was higher than for other agents.

Background The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2‐[1’H‐indole‐3’‐carbonyl]‐thiazole‐4‐carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T‐cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE‐treated mice exhibited significantly improved systolic function ( P P + (forkhead box protein P3‐positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post‐MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.

The benefits afforded by tocilizumab (TCZ) in patients with adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) have been described in previous studies. However, few reports have evaluated severe hypersensitivity reactions (HSRs) to TCZ in patients with AOSD or SJIA. We describe three instances of TCZ-induced anaphylactic reactions in AOSD/SJIA patients, and review relevant prior reports on patients with various rheumatic diseases. Two of our cases exhibited shock and cardiovascular collapse; TCZ was discontinued in all three cases. All events occurred within 20 min of TCZ infusion, after at least three prior infusions, indicating an IgE-mediated mechanism and previous sensitization to TCZ. In all three cases, mild HSRs had been observed about 1 month before the anaphylactic events, but pre-medication with antihistamines and corticosteroids failed to prevent anaphylaxis. All three cases had active AOSD or SJIA disease, and were refractory to other immunosuppressive agents. It is essential to be aware that severe anaphylaxis to TCZ can develop in patients with active refractory AOSD or SJIA, and to be cautious when medicating certain patients. Anaphylaxis is a serious condition that can be fatal; TCZ infusion should not be re-challenged via pre-medication in patients who exhibited mild HSRs before TCZ without desensitization.

A range of motion (ROM) has been measured using several indices to judge the progress of ankylosing spondylitis (AS). However, measuring and calculating the ROM is time-consuming & labor-intensive and it would be even difficult to measure accurately. Thus, an automated measurement system (AMS) is proposed & developed to measure the ROM more easily without any restraint sensor, and to recognize changes in the ROM more constantly with the same standard of measurement. The measurement items are neck cervical rotation, cervical lateral flexion, finger-to-floor distance, intermalleolar distance, and lumbar side flexion. Data from 30 healthy subjects were collected by the AMS and their motions were recorded simultaneously by installed webcams to acquire gold-standard data compared with the measurement value of the AMS. The accuracy was determined by calculating the standard error of estimation (SEE) and a possibility of replacement of measurement obtained by a physician using a protractor & ruler has been assessed by pattern recognition of Bland-Airman plots. These statistical results exhibit a significant degree of agreement with the novel AMS. The total measurement time for the 5 items using the proposed AMS was less than 5 min, which is faster than manual measurement. However, the measurement was conducted against only healthy subjects; therefore additional tests with AS patients will be required for utilization in clinical practice.

OBJECTIVES To identify factors associated with deterioration of pulmonary function with disproportional decline in diffusing capacity for carbon monoxide (DLCO) relative to forced vital capacity (FVC) in patients with dermatomyositis (DM) and polymyositis (PM). METHODS This retrospective cohort study included patients with DM and PM, in whom serial pulmonary function tests were available. Changes in FVC and DLCO over time were estimated using a linear mixed-effects model. RESULTS A total of 103 patients were included. During follow-up, 31 (30.1%) and 37 (35.9%) had a disproportionally better (ΔDLCO/ΔFVC>mean slope + 95% CI) or a disproportionally worse (ΔDLCO/ΔFVC

Aims With the high prevalence of gout and associated cardiovascular (CV) diseases, information on the comparative CV safety of individual urate-lowering drugs becomes increasingly important. However, few studies examined the CV risk of uricosuric agents. We compared CV risk among patients with gout who initiated allopurinol vs. benzbromarone.Methods and results Using the Korean National Health Insurance claims data (2002–17), we conducted a cohort study of 124 434 gout patients who initiated either allopurinol (n = 103 695) or benzbromarone (n = 20 739), matched on propensity score at a 5:1 ratio. The primary outcome was a composite CV endpoint of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. To account for competing risk of death, we used cause-specific hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes comparing allopurinol initiators with benzbromarone. Over a mean follow-up of 1.16 years, 2258 patients developed a composite CV event. The incidence rate of the composite CV event was higher in allopurinol initiators (1.81 per 100 person-years) than benzbromarone (1.61 per 100 person-years) with a HR of 1.22 (95% CI 1.05–1.41). The HR for all-cause mortality was 1.66 (95% CI 1.43–1.93) among allopurinol initiators compared with benzbromarone.Conclusion In this large population-based cohort of gout patients, allopurinol was associated with an increased risk of composite CV events and all-cause mortality compared to benzbromarone. Benzbromarone may reduce CV risk and mortality in patients with gout, although more studies are necessary to confirm our findings and to advance our understanding of the underlying mechanisms.

Severe cardiac damage following myocardial infarction (MI) causes excessive inflammation, which sustains tissue damage and often induces adverse cardiac remodeling toward cardiac function impairment and heart failure. Timely resolution of post-MI inflammation may prevent cardiac remodeling and development of heart failure. Cell therapy approaches for MI are time-consuming and costly, and have shown marginal efficacy in clinical trials. Here, nanoparticles targeting the immune system to attenuate excessive inflammation in infarcted myocardium are presented. Liposomal nanoparticles loaded with MI antigens and rapamycin (L-Ag/R) enable effective induction of tolerogenic dendritic cells presenting the antigens and subsequent induction of antigen-specific regulatory T cells (Tregs). Impressively, intradermal injection of L-Ag/R into acute MI mice attenuates inflammation in the myocardium by inducing Tregs and an inflammatory-to-reparative macrophage polarization, inhibits adverse cardiac remodeling, and improves cardiac function. Nanoparticle-mediated blocking of excessive inflammation in infarcted myocardium may be an effective intervention to prevent the development of post-MI heart failure.

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of transplanted cells within the injured myocardium, limiting their therapeutic efficacy. Recently, the use of scaffolding biomaterials has gained attention for improving and maximizing stem cell therapy. The objective of this protocol is to introduce a simple and straightforward technique to transplant bone marrow-derived mesenchymal stem cells (MSCs) using injectable hydroxyphenyl propionic acid (GH) hydrogels; the hydrogels are favorable as a cell delivery platform for cardiac tissue engineering applications due to their ability to be cross-linked in situ and high biocompatibility. We present a simple method to fabricate MSC-loading GH hydrogels (MSC/hydrogels) and evaluate their survival and proliferation in three-dimensional (3D) in vitro culture. In addition, we demonstrate a technique for intramyocardial transplantation of MSC/hydrogels in mice, describing a surgical procedure to induce myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation and subsequent MSC/hydrogels transplantation.

Objective Rheumatoid 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. Methods In 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. Results At 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. Conclusions Women 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.

Objective: To identify risk factors of biological disease-modifying anti-rheumatic drugs (bDMARDs) initiation in patients with rheumatoid arthritis (RA). Methods: Using the 2002-2016 Korea National Health Insurance database, we conducted a nested case-control study on seropositive RA patients. Cases (bDMARD users) and controls (users of conventional synthetic DMARDs only) were 1:4 matched on the calendar year/month of RA diagnosis and index dates (bDMARD initiation dates). Potential risk factors from two time periods, 1-year post-RA-diagnosis and 1-year pre-index, were separately assessed on the association with bDMARD initiation by conditional logistic regression analyses. Results: The study included 6,985 cases and 27,940 controls. Older age, female gender, use of methotrexate (MTX), leflunomide, or tacrolimus as a first csDMARD, higher initial MTX dose, and initial csDMARD combination during 1-year post-diagnosis were negatively associated with later bDMARD initiation, while use of sulfasalazine as a first csDMARD, corticosteroid therapy, and higher maximal MTX dose were positively associated. Among covariates from 1-year period before bDMARD initiation, use of leflunomide, sulfasalazine, or tacrolimus, parenteral MTX, higher maximal MTX dose, corticosteroid, and csDMARD combination were positively associated with subsequent bDMARD initiation. Effects of comorbidities on bDMARD initiation were heterogenous across involved systems. Conclusion: In this population-based nationwide study, we identified period-specific risk factors of bDMARD initiation among RA patients in Korea. Overall, initial aggressive RA treatment after diagnosis was associated with less use of later bDMARD, while highly intensive therapy observed just before bDMARD initiation rather reflects refractory nature of RA during this period, and did not prevent bDMARD use.

Background The D-dimer test is a screening tool for venous thromboembolism (VTE); however, its utility for patients with systemic lupus erythematosus (SLE) remains unclear. Here, we examined the utility of the D-dimer test as a screening tool for VTE in SLE patients. Methods SLE patients (n = 276) and age- and sex-matched patients with non-rheumatic disease (n = 1,104), all of whom underwent D-dimer testing to screen for VTE, were enrolled. The sensitivity and specificity and receiver operating characteristics curve of the D-dimer test were compared in both groups. Then, subgroup of SLE patients in whom the D-dimer test can be useful was sought. Results The incidence of VTE was more common in SLE patients than controls (10.9% vs. 4.0%). Although the sensitivity of the D-dimer test was comparable between SLE patients and controls (93.3% vs. 90.9%), the specificity of the test was profoundly lower in SLE patients compared to controls (28.4% vs. 84.4%). The area under the curve (AUC) of the D-dimer for VTE was 0.669 in SLE patients and 0.90 in control group. Multiple linear regression analysis demonstrated that SLE disease activity index-2000 (SLEDAI-2K) was significantly associated with D-dimer levels in SLE patients (β = 0.155; P = 0.022). Subgroup analysis showed that the AUC is moderate (0.768) with low disease activity, while it is low (0.518) with high SLEDAI-2K. Conclusion The D-dimer test may not be a useful screening tool for VTE in patients with active SLE. D-dimer test for predicting VTE in SLE patients should be differentially applied according to disease activity of SLE., Graphical Abstract

To evaluate the efficacy and safety of infliximab biosimilar CT-P13 in patients with active Takayasu arteritis (TAK). In this single-center open-label trial, patients with active TAK received CT-P13 at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks up to week 46. They were followed up until week 54. From week 14 to week 46, patients with inadequate response received increased dose of CT-P13 by 1.5 mg/kg. Concomitant prednisolone was allowed ≤ 10 mg/day. The primary efficacy end point was the achievement of partial or complete remission at week 30. All patients underwent positron emission tomography–computed tomography (PET–CT) at baseline and week 30. Twelve patients with TAK received CT-P13; one patient with protocol violation was excluded from analysis. Nine (81.8%) patients had taken concomitant prednisolone with median dose of 5.0 mg/day. At week 30, three (27.3%) patients achieved complete remission and six (54.5%) patients achieved partial remission. Statistically significant improvements in modified Indian Takayasu Clinical Activity Score (ITAS2010), ITAS-A, and serum levels of erythrocyte sedimentation rate and C-reactive protein were seen at week 30 from baseline. PET parameters were significantly reduced from baseline to week 30, including maximum standardized uptake value, target-to-vein ratio, target-to-liver ratio, and PET Vascular Activity Score. There were no serious adverse events. Treatment with CT-P13 may lead to improvement in clinical, radiographic, and serological activities with lower glucocorticoid requirement in TAK. Trial registration number NCT02457585. Electronic supplementary material The online version of this article (10.1007/s00296-018-4159-1) contains supplementary material, which is available to authorized users.

Based on immunomodulatory actions of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), in vitro or preclinical studies of hUCB-MSCs have been conducted extensively in rheumatoid arthritis (RA). However, few human trials have investigated the outcomes of hUCB-MSC infusions. The CURE-iv trial was a phase I, uncontrolled, open label trial for RA patients with moderate disease activity despite treatment with methotrexate. The patients received a single intravenous infusion of 2.5 × 107, 5 × 107, or 1 × 108 cells of hUCB-MSCs for 30 minutes, three patients in each cluster, with an increment of cell numbers when there was no dose-limited adverse event. Clinical and safety assessments were performed during the study period, and serum cytokines were measured at baseline and 24 hours after the infusion. Out of 11 screened RA patients, 9 were enrolled. The participants were predominantly female (78%) and the mean age was 57.4 years. The mean disease duration was 9.5 years, and baseline 28-joint disease activity score (DAS28; using erythrocyte sedimentation rate) was 4.53. There was no major toxicity in all clusters up to 4 weeks after the infusion. Serum erythrocyte sedimentation rate changes at 4 weeks (n = 9) were −7.9 ± 10.4 (p = .0517) and DAS28 changes were −1.60 ± 1.57 (p = .0159). Reduced levels of IL-1β, IL-6, IL-8, and TNF-α at 24 hours were observed in the cluster infused with 1 × 108 MSCs. This phase Ia hUCB-MSC infusion trial for established RA patients revealed no short-term safety concerns.

Purpose For 3 consecutive years from 2012-2014, we analyzed the causative factors for why the Jeju Island had the highest obesity prevalences of school children among the 15 provinces in Korea. Methods From our analysis of 28,026 elementary school children with obesity or normal weight in the 15 provinces, we analyzed 12 factors related to eating habits, exercise habits, lifestyle, and mental health. The differences between the obese and normal weight children were researched. Finally, Jeju was compared with Seoul, which has the lowest obesity prevalence in school age children. Statistical analysis was performed using the chi square test of PASW Statistics ver. 18.0. Results Compared to the normal weight group, the obese group had significantly higher rates of consuming soft drinks (p

Purpose Regional differences in the incidence of lymphoid malignancies have been reported worldwide, but there has been no large-scale epidemiologic analysis in Korea. The aim of this study was to provide a nationwide population-based statistical analysis of Korean patients with lymphoid malignancies. Materials and Methods The Korea Central Cancer Registry analyzed the incidence and survival of patients with lymphoid malignancies from the Korean National Cancer Incidence Database. Diseases were grouped by clinically relevant categories based on the 2008 World Health Organization classification. Results Overall 65,948 lymphoid diseases were identified between 1999 and 2012. The incidence of most subtypes increased with age, except for precursor cell neoplasms. Male predominance (male:female ratio=1.28:1) was observed. In 2012, annual age-standardized incidence rates per 100,000 persons of Hodgkin’s lymphoma, mature B-cell neoplasm, mature T/natural killer (NK)–cell neoplasm, and precursor cell neoplasm were 0.46, 6.60, 0.95, and 1.50, respectively, and they increased yearly from 1999. Composite Hodgkin’s and non-Hodgkin’s lymphomas were extremely rare. Survival improvement estimated using 5-year relative survival rate was observed in patients with Hodgkin’s lymphoma (71.1%-83.0%), diffuse large B-cell lymphoma (49.5%-61.5%), plasma cell neoplasms (20.2%-36.9%), and lymphoblastic lymphoma/leukemia (41.5%-56.3%) between 1993 and 2012. However, survival rates of T/NK-cell lymphoma (excluding cutaneous T-cell lymphoma) ranged from 40.5%-43.5% during the study period. Survival rates decreased with age in most subtypes. Conclusion This report presented the subtype-specific statistical analysis of lymphoid malignancies in the Korean population, showing increasing incidences and survival rates in most subtypes.

Purpose We aimed to describe the temporal trends and district-level geographical variations in cancer incidences throughout Korea during 1999-2013. Materials and Methods Data were obtained from the Korean National Cancer Incidence Database. We calculated the age-standardized cumulative cancer incidences according to sex and geographical region (metropolitan cities, provinces, and districts) for three 5-year periods (1999-2003, 2004-2008, and 2009-2013). Each quintile interval contained the same number of regions. Disease maps were created to visualize regional differences in the cancer incidences. Results Substantial differences in cancer incidences were observed according to district and cancer type. The largest variations between geographical regions were found for thyroid cancer among both men and women. There was little variation in the incidences of stomach, colorectal, and lung cancer according to geographical region. Substantially elevated incidences of specific cancers were observed in Jeollanam-do (thyroid); Daejeon (colorectum); Jeollanam-do, Gyeongsangbuk-do, and Chungcheongbuk-do (lung); Seocho-gu, Gangnam-gu and Seongnam, Bundang-gu (breast and prostate); Chungcheong and Gyeongsang provinces (stomach); Ulleung-gun and the southern districts of Gyeongsangnam-do and Jeollanam-do (liver); and along the Nakdonggang River (gallbladder and biliary tract). Conclusion Mapping regional cancer incidences in Korea allowed us to compare the results according to geographical region. Our results may facilitate the development of infrastructure for systematic cancer incidence monitoring, which could promote the planning and implementation of region-specific cancer management programs.

Background and Objectives: Propofol-based total intravenous anesthesia (TIVA) is presumed to have more favorable effects on the prognosis of patients with cancer compared with volatile inhaled anesthesia (VIA). We hypothesized that these anesthetics target plasma apurinic apyrimidinic endonuclease/redox effector factor-1 (APE1/Ref-1) as a possible mechanism of action. Materials and Methods: The plasma APE1/Ref-1 level was evaluated three times during surgery for cancer, i.e., before anesthesia, immediately after cancer resection, and finally, in the recovery room. Blood (3 cc) was drawn from the radial artery catheter, and plasma APE1/Ref-1 levels were compared according to measurement time and between the two groups. Spearman’s Rho correlation analysis was performed to determine relationships among body mass index, American Society of Anesthesiologists classification, age, sex, cancer type, and tumor-node-metastasis (TNM) stage. A total of 166 patients (VIA: 129; TIVA: 37) were enrolled. Results: Plasma APE1/Ref-1 level increased significantly (p = 0.028) after cancer resection compared with before surgery, but no significant difference was observed between anesthetics (p = 0.134). The post-resection plasma APE1/Ref-1 level showed a positive correlation with the NM stages, but not the T stage. Conclusions: The plasma APE1/Ref-1 level increased during surgery with more severe lymph node invasion, but there were no significant differences according to the anesthetics used.

Kearns-Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder associated with progressive external ophthalmoplegia, atypical pigmentary degeneration of the retina, and complete heart block. KSS can lead to a risk of sudden death because of the potential progression of conduction abnormalities such as right or left bundle branch block or complete atrioventricular (AV) block. Here we describe the case of a KSS patient with type I diabetes who experienced syncope in the presence of complete AV block, confirmed by muscular biopsy.

We report on a patient with lung adenocarcinoma and a concomitant epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation who developed a disease flare after discontinuing gefitinib. A 63-year-old woman with lung adenocarcinoma and a concomitant activating EGFR mutation and ALK translocation was treated with first-line gefitinib. After 4 months, she discontinued the gefitinib due to disease progression. She was admitted to the emergency room complaining of severe dyspnea and back pain 22 days after discontinuing gefitinib. A chest image showed numerous hematogenous lung metastases and extensive bone metastasis, which was compatible with a previously reported disease flare after stopping EGFR tyrosine kinase inhibitors (TKIs). Aggravated respiratory failure and progression of multiple organ dysfunction led to death 26 days after discontinuing gefitinib. This was a rare case of a disease flare up in patient with a concomitant EGFR mutation and ALK translocation after discontinuing an EGFR-TKI.

We evaluated the relationship between myocardial infarct size and inflammatory response using cardiac magnetic resonance imaging (CMR) in an acute myocardial infarction (AMI) mouse model. Myocardial infarction (MI) was induced in 14 mice by permanent ligation of the left anterior descending artery. Late gadolinium enhancement (LGE), manganese-enhanced MRI (MEMRI), and magnetofluorescent nanoparticle MRI (MNP-MRI) were performed 1, 2, and 3 days after MI, respectively. The size of the enhanced lesion was quantitatively determined using Otsu’s thresholding method in area-based and sector-based approaches and was compared statistically. Linear correlation between the enhanced lesion sizes was evaluated by Pearson’s correlation coefficients. Differences were compared using Bland-Altman analysis. The size of the inflammatory area determined by MNP-MRI (57.1 ± 10.1%) was significantly larger than that of the infarct area measured by LGE (40.8 ± 11.7%, P<0.0001) and MEMRI (44.1 ± 14.9%, P<0.0001). There were significant correlations between the sizes of the infarct and inflammatory lesions (MNP-MRI versus LGE: r=0.3418, P=0.0099; MNP-MRI versus MEMRI: r=0.4764, P=0.0002). MNP-MRI provides information about inflammatory responses in a mouse model of AMI. Thus, MNP-MRI associated with LGE and MEMRI may play an important role in monitoring the disease progression in MI.

Background:Based on the benefit of chemoprophylaxis among patients receiving biologics [1], Health Insurance Review and Assessment (HIRA) service of Korea requires patients to undergo latent tuberculosis (LT) screening before initiation of any biologics and to receive chemoprophylaxis for positive LT.Objectives:To assess the effect of chemoprophylaxis on tuberculosis infection (TI) risk among patients with rheumatoid arthritis (RA) receiving biologics in KoreaMethods:Using 2002-2016 Korea National Health Insurance database, we conducted a cohort study on RA patients initiating biologic drugs (TNF inhibitors, abatacept, tocilizumab) to compare TI risk between those who started isoniazid and/or rifampin within 1 year before biologics initiation (prophylaxis group) versus those who did not (non-prophylaxis group). TI was defined by ICD10 codes plus anti-tuberculosis medications as previously described [2]. Patients were followed-up from biologics initiation to censoring events (TI occurrence, death, biologics discontinuation, initiation of anti-tuberculosis drug due to non-TI cause, and end of database). To control >50 baseline confounders, we used propensity score (PS)-based fine stratification and weighting. A weighted Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs).Results:Before PS stratification (PSS) and weighting, we identified 2,250 and 7,259 RA patients for prophylaxis and non-prophylaxis group, respectively. Mean age was 57.6 years and 81.3% female. Three-fourths of patients in the prophylaxis group completed >70% of recommended treatment periods [3]. The incidence rate of TI per 100 person-years was 0.33 for prophylaxis group versus 0.57 for non-prophylaxis group. 28% of all TI cases (n=34) were extra-pulmonary with gastrointestinal (n=11) and miliary TI (n=9) being most common. The PSS-weighted HR (95% CI) of TI comparing prophylaxis versus non-prophylaxis group was 0.52 (0.32-0.86) (Table 1, Figure 1). Sensitivity analyses showed that the chemoprophylaxis was particularly effective for those with younger age (Table 1.Comparative risk of tuberculosis infection between prophylaxis versus non-prophylaxis groupCrudePSS-weightedNEventsPYIR per100 person-yearsHR (95% CI)Primary as-treated analysis1TotalP2,250185,5320.330.52 (0.32-0.86)NP7,25910017,5030.64ITT analyses11 year ITTP2,250102,1150.470.33 (0.17-0.64)NP7,259976,8331.422 year ITTP2,250213,9070.540.49 (0.31-0.78)NP7,25914012,6981.104 year ITTP2,250316,3050.490.56 (0.38-0.82)NP7,25918121,2780.88Sensitivity AnalysesAge P1,75194,5880.200.39 (0.19-0.78)NP5,3457213,6340.52MaleP54621,3190.150.12 (0.03-0.50)NP1,235282,6241.33Comorbidity score ≥3P82461,9080.310.34 (0.15-0.79)NP2,668526,1290.941As-treated analysis censored patients when they discontinued biologics use, while ITT analysis did not.IR=incidence rate; ITT=intention-to-treat; HR=hazard ratio; PSS=propensity-score stratification; CI=confidence interval; PY=person-years; P=prophylaxis group; NP=non-prophylaxis groupConclusion:We found 48% risk reduction of TI by chemo-prophylaxis among RA patients receiving biologics. Due to HIRA requirements, a majority of non-prophylaxis group were considered negative for LT by screening at biologics initiation [4]. These findings indicate that the risk of TI during bDMARD treatment is still high among RA patients who were negative for LT at baseline but did not undergo chemoprophylaxis, which is double the risk among RA patients who had LT and underwent chemoprophylaxis.References:[1]Carmona L et al. Arthritis Rheum. 2005;52:1766-72.[2]Lee J et al. Ann Am Thorac Soc. 2017;14:690-697.[3]https://www.cdc.gov/tb/topic/treatment/ltbi.htm[4]Kim ES et al. World J Gastroenterol. 2015;21:3308-16.Disclosure of Interests:None declared

Low-cost flexible transparent conductive films (TCFs) with direct writing of metal grids have been explored as a promising alternative to conventional indium-tin-oxide-based TCFs for future flexible electronics. However, flexible TCFs have raised technical concerns because of their disadvantages, such as low resolution, low productivity, poor optoelectrical performance, poor thermal stability, and adverse moiré fringes, which primarily arise from the superposition of periodic patterns. Herein, a facile and highly productive method to fabricate moiré-fringeless TCFs with good optoelectrical characteristics and excellent thermal stability is presented using a single-pass printed random serpentine network of medium-field electrospun silver microfibres (AgMFs) with a line width of 2.32 ± 0.97 μm by exploiting the random serpentine motion of medium-field electrospinning, enabling moiré-fringeless TCFs. The electrical in-plane anisotropy of the TCFs can be kept well below 110.44 ± 1.26% with the in situ junction formation of the AgMFs in the transverse direction. Combined thermal and chemical annealing of the AgMFs enables high productivity by reducing the thermal annealing time by 40%. The good optoelectrical performance, fair electrical in-plane anisotropy, high productivity, and superior thermal stability of the TCFs with the single-pass printed random serpentine network of medium-field electrospun AgMFs are suitable properties for flexible electronics such as ultra-large digital signage with LEDs.

Background Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis of the skin and the involvement of multiple internal organs. Previous studies reported poorer health-related quality of life (HRQoL) in patients with SSc compared with the general population. However, very little is known about how HRQoL in SSc patients compares with that in patients with other systemic autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS). Thus, the main aim of this study was to compare HRQoL in SSc patients, patients with other rheumatic diseases, and the general population. Methods In this cross-sectional study, patients from the rheumatology clinics of Seoul National University Hospital with SSc, RA, SLE, and SjS were enrolled via a random sampling technique. HRQoL was captured by the Short Form (36) health survey (SF-36), the Short Form Six-Dimensional health index (SF-6D), and the EuroQol Five-Dimensional descriptive system (EQ-5D). Demographic characteristics and standardized disease activity for each disease were also obtained. Previously reported data from 600 healthy Koreans were used for the healthy controls. An ANCOVA test was used to compare the SF-36, SF-6D, and EQ-5D values between study subjects with adjustments for age, sex, disease duration, comorbidities, and disease activity status. Results One hundred twenty patients were included in each of the SSc, RA, SLE, and SjS cohorts. Patients with rheumatic diseases had significantly lower SF-36, SF-6D, and EQ-5D scores than healthy controls (all P

Scoring of myocardial infarction (MI) disease extent in cardiac magnetic resonance (CMR) images has been generally presented in terms of area-based infarct size. However, gradual thinning of the infarcted wall and compensatory hypertrophy of the noninfarcted remote wall during left ventricular (LV) remodeling after MI complicate the accuracy of infarct size measurement. In this study, we measured and compared infarct sizes in mice on late gadolinium enhancement (LGE) images using area-, length-, and radial sector-based methods.MI was induced by permanent ligation of the left coronary artery (n = 6). LGE images were acquired 30 minutes after intravenous injection of Gd-DTPA-BMA. Percentages of infarct size (%Area, %Length, and %Sector) on the LGE images were calculated and compared with histological findings.Infarct sizes obtained by an area-based approach were smaller than those obtained by other measurements. The area-based approach underestimated infarct size compared with the length-based approach. Most infarct sizes measured by each method demonstrated a similar trend, with maximum values determined by sector-based measurements using a mean + SD threshold. Spearman's rank correlation coefficients indicated that the 3 measurements were strongly correlated (P < 0.05) to each other. Significant differences and trends were observed between sector-based infarct sizes with different thresholds when 16 or more sectors were used.In conclusion, our study demonstrated that methods used for the histological calculation of infarct size could be applied to CMR analysis. Moreover, our results showed a similar trend to histological assessment. Sector-based CMR approaches can be useful for infarct size measurement.

Background:Due to the shared mechanism of nontraumatic avascular necrosis (AVN) and endothelial dysfunction, the associations of AVN with increased cardiovascular and cerebrovascular events have been suggested in the several population-based studies.Objectives:This study aimed to estimate the prevalence and incidence of nontraumatic AVN in South Korea from the Korean National Health Insurance Service Sample Cohort Database 2.0 (2006-2015) and to evaluate the risk of major cardiovascular and cerebrovascular events among patients with nontraumatic AVN.Methods:We defined an incident case as a newly diagnosed and registered patient in the registry in that year, with a 2-year washout period. Prevalent cases were defined as all patients with nontraumatic AVN in the corresponding year. To evaluate the cardiovascular and cerebrovascular risks in patients with AVN, we set AVN group composed of patients with an initial diagnosis of non-traumatic AVN between 2008 and 2010 (n=1,150). The comparison group was composed of randomly selected subject (5 per patient with AVN; n = 5,750) who were matched to the AVN group according to age, sex, resident area, and year of AVN diagnosis. The development of major cardiovascular and cerebrovascular events was tracked in each sampled patient until 2015. Cox proportional hazard regressions were used to calculate the overall risks for the development of major cardiovascular and cerebrovascular events.Results:From 2008 to 2015, the prevalence of nontraumatic AVN increased gradually, but its incidence did not change, with an annual average incidence of 413 per 1 million population and the male-to-female ratio of 1.2:1. The peak incidence occurred in the 50-59 year age group. The incident AVN was more prevalent in male than in female under 70, but there was female predominance after the age of 70 (Figure 1). The patients with AVN had a higher cumulative incidence of major adverse cardiovascular and cerebrovascular events than controls (19.5% versus 14.9%; p = 0.017). Upon univariate Kaplan-Meier method with the log-rank test, there was a significant difference in major cardiovascular and cerebrovascular events-free survival rates between AVN group and control group (p Conclusion:In this population-based cohort study, we provided the updated epidemiologic data of Korean patients with nontraumatic AVN. The increased risk for major cardiovascular and cerebrovascular events among AVN patients was not observed in the representative Korean population.References:[1]Kang JH, Lin HC. Increased risk for coronary heart disease after avascular necrosis of femoral head: a 3-year follow-up study. Am Heart J. 2010;159:803-8.[2]Sung PH, Yang YH, Chiang HJ, Chiang JY, Chen CJ, Yip HK, et al Cardiovascular and cerebrovascular events are associated with nontraumatic osteonecrosis of the femoral head. Clin Orthop Relat Res 2018;476:865-74.Figure 1.Age- and sex-distributed incidence of patients with nontraumatic avascular necrosis in Korea, 2008-2015Disclosure of Interests:None declared

Background:Biological disease-modifying anti-rheumatic drugs (bDMARDs) have significantly improved clinical prospects for patients with rheumatoid arthritis (RA).Objectives:To identify predictors of bDMARDs initiation in RA patients.Methods:Using 2002-2016 Korea National Health Insurance Service database, we conducted a nested case-control study on RA patients. Four conventional DMARD (cDMARD) users were selected by risk set sampling per each bDMARD user, matched on the calendar year/month of RA diagnosis. Potential predictors were separately assessed for two periods, 1 year after RA diagnosis and 1 year prior to bDMARD initiation, by logistic regression analyses estimating odds ratio (OR) and 95% confidence interval (CI).Results:The study included 27,940 cDMARD users and 6,985 bDMARD users. Younger age, initial use of a less potent cDMARD (sulfasalazine), corticosteroid use, and higher maximal methotrexate (MTX) dose during 1 year post-diagnosis were positive predictors for later bDMARD initiation, while male gender, initial use of a potent cDMARD (MTX, leflunomide, or tacrolimus), initial MTX dose of ≥10mg/wk, and initial cDMARD combination were negative predictors (Table 1). Use of non-MTX DMARDs (leflunomide, sulfasalazine, or tacrolimus), higher # of cDMARD used, subcutaneous administration of MTX, corticosteroid therapy, and higher maximal MTX dose were positive predictors of subsequent bDMARD. Although higher comorbidity score during 1 year before bDMARD initiation was a positive predictor, the effect was heterogenous by involved systems (Table 2).Table 1.Predictors of bDMARD initiation among RA patients during 1-year post-diagnosisPredictorsOR(95% CI)P-valueAge (/1 year)0.977(0.974-0.980)Sex (male vs. female)0.850(0.787-0.918)1st cDMARD at RA diagnosis (yes vs. no) Methotrexate0.540(0.476-0.614) Leflunomide0.463(0.388-0.552) Sulfasalazine1.305(1.197-1.424) Tacrolimus0.181(0.083-0.395)Initial MTX dose (≥10mg/week vs. 0.539(0.506-0.575)Initial cDMARD combination (yes vs. no)0.621(0.530-0.727)Subcutaneous MTX use (yes vs. no)1.456(1.156-1.834)0.001Maximal MTX dose (/1mg)1.012(1.008-1.016)Corticosteroids use (yes vs. no)2.805(2.345-3.355)Table 2.Predictors of bDMARD initiation among RA patients during 1-year prior to bDMARD initiationPredictorsOR(95% CI)P-valueAge (/1 year)0.970(0.967-0.974)Non-MTX cDMARD use (yes vs. no)1 Leflunomide1.765(1.573-1.980) Sulfasalazine1.465(1.297-1.654) Tacrolimus2.070(1.796-2.387) Subcutaneous MTX use (yes vs. no)1.731(1.577-1.900)Maximal MTX dose (/1mg)2.568(1.921-3.433)Glucocorticoid use (yes vs. no)1.015(1.010-1.021)Comorbidity index (/1 point)1.124(1.076-1.175)Individual comorbidities (yes vs. no) Stroke/ transient ischemic attack0.764(0.626-0.932)0.008 Atrial fibrillation0.666(0.455-0.973)0.036 Diabetes mellitus1.208(1.076-1.356)0.001 Joint replacement therapy1.788(1.341-2.384) Hepatitis B infection1.559(1.238-1.964) Hepatitis C infection2.117(1.532-2.925) Chronic obstructive pulmonary disease1.118(1.012-1.234)0.0281MTX was excluded since all bDMARD initiators were required to use MTX before bDMARD initiation.Conclusion:In this population-based nationwide study, we identified period-specific predictors of bDMARD initiation among RA patients in Korea. Overall, initial aggressive RA treatment after RA diagnosis were associated with less use of later bDMARD, while highly intensive therapy observed just before bDMARD initiation reflects refractory nature of RA during this period.Disclosure of Interests:None declared

Background The endovascular coiling procedure to treat cerebral aneurysms using contrast media has become more popular. However, studies of the incidence of, and risk factors for, contrast media-induced nephropathy (CIN) after coiling procedures have been limited. Thus, we evaluated the incidence and risk factors for CIN in patients who had undergone cerebral aneurysmal coiling procedures. Methods We retrospectively reviewed the electric medical records of 380 patients who had undergone cerebral aneurysmal coiling treatment under general anesthesia. CIN was defined as an absolute increase in serum creatinine (≥0.5 mg/dL) or a relative increase (≥25%) in the baseline serum creatinine value at 48–72 hours after exposure to a contrast agent. Results Elective cerebral aneurysmal coiling procedures were performed in 230 patients. Of the 230 patients, CIN developed in 13 (5.6%). The presence of diabetes mellitus (30.8% vs. 9.7%; P = 0.040) and patient age >75 years (30.8% vs. 6.5%; P = 0.012) were risk factors for CIN. Conclusions Our study has demonstrated that the incidence of CIN in patients undergoing elective cerebral aneurysmal coiling procedures is ∼6.0%. We also identified underlying diabetes mellitus and advanced age (≥75 years) as potential risk factors.

Background d-dimer test is widely used as a screening tool for venous thromboembolisms (VTE). Meanwhile, d-dimer can increase in various conditions including severe infection, and inflammation. However, it has been rarely reported whether d-dimer test is useful for screening of VTE in systemic lupus erythematosus (SLE) patients. Objectives We evaluated the role of d-dimer test as a screening tool for VTE in patients with SLE, compared to age-, and sex-matched non-autoimmune disease subjects. Methods In this retrospective cohort study, a total of 283 SLE patients and 1132 age-, and sex-matched control subjects (those who had no rheumatic diseases) who underwent d-dimer test as a screening test for VTE were enrolled at Seoul National University Hospital between January 2000 and July 2017. VTE was defined to be present when a thromboembolism was proven in imaging studies which included computed tomography, lung perfusion scan or duplex ultrasonography. Predictive value of d-dimer test for VTE was compared between SLE patients and control subjects by calculating area under the curves (AUC) in receiver operating characteristics (ROC) curves of d-dimer test. Finally, the usefulness of d-dimer test was evaluated in different subsets of SLE patients by analysing ROC curves. Results The mean (SD) age of the 283 SLE patients was 36.8 (13.5) years and that of 1132 control subjects was 38.2 (12.8) years. The mean (SD) plasma level of d-dimer was 2262.1 (3794.5) ng/ml in SLE patients, while it was 1087.5 (5063.1) ng/ml in the control group (p Conclusions d-dimer test cannot predict VTE in SLE patients as accurately as in general population. In SLE patients, d-dimer’s diagnostic capability for VTE is even lower in the presence of APS Abs. References [1] Chung WS, Lin CL, Chang SN, et al. Systemic lupus erythematosus increases the risks of deep vein thrombosis and pulmonary embolism: a nationwide cohort study. J Thromb Haemost2014;12:452–8. [2] Avina-Zubieta JA, Vostretsova K, De Vera MA, et al. The risk of pulmonary embolism and deep venous thrombosis in systemic lupus erythematosus: A general population-based study. Semin Arthritis Rheum2015;45:195–201. [3] Kristoffersen AH, Ajzner E, Rogic D, et al. Is D-dimer used according to clinical algorithms in the diagnostic work-up of patients with suspicion of venous thromboembolism? A study in six European countries. Thromb Res2016;142:1–7. [4] Ahlehoff O, Wu JJ, Raunso J, et al. Cutaneous lupus erythematosus and the risk of deep venous thrombosis and pulmonary embolism: A Danish nationwide cohort study. Lupus2017;26:1435–9. [5] Wells PS, Ihaddadene R, Reilly A, et al. Diagnosis of Venous Thromboembolism: 20 Years of Progress. Ann Intern Med2018;168:131–40. Disclosure of Interest None declared

Background Drug persistence of tumour necrosis factor-a inhibitors (TNFi) tends to be higher in patients with ankylosing spondylitis (AS) than rheumatoid arthritis but there are few studies of Asian AS patients in the literature. Objectives To investigate drug retention rates of various TNFi used in Korean AS patients. Methods Subjects were AS patients enrolled in the Korean College of Rheumatology Biologics registryKOBIO, Dec 2012 ~). All approved and commonly prescribed TNFi were included in the analysis. Discontinuation was defined as switching or stopping the biologic agent. Kaplan-Meier curve and Cox proportional hazard model were used for further analysis. Reason of TNFi discontinuation was also assessed. Univariate and multivariate analyses were used to identify possible predictors of discontinuation. Results Data of total of 1005 AS patients were analysed (median follow-up period: 14 months). The mean age of patients was 40.7, and 77.4% were males. The mean disease duration was 7.1 years, HLA-B27 were positive in 82.4%, and 33.2% of patients had lesion(s) of syndesmophytes. Seventy-six percent of patients were first-time biologic users. Discontinuation of TNFi occurred in 24.2% (switching in 9.6%) of patients during follow-up. The drug survival function estimate showed that the adjusted hazard ratio (HR) of golimumab (compared with etancercept) was 0.441 (95% CI 0.277–0.703, p Conclusions Our study demonstrates that few AS patients switched to other TNFi during their course of treatment. The drug retention rate of golimumab was higher compared with other agents prescribed in Korean AS patients. Disclosure of Interest None declared

Background Takayasu arteritis (TAK) is a chronic inflammatory disease that predominantly affects the aorta and its main branches. Glucocorticoids (GCs) are the cornerstones of the initial treatment of TAK. However, most patients relapse with steroid withdrawal. Objectives To evaluate the efficacy and safety of infliximab (IFX) in Korean patients with active TAK. Methods Patients with active TAK were enrolled in a single-centre prospective open label trial. Active disease was defined according to the National Institutes of Health (NIH) criteria. Concomitant GCs were tapered to prednisone ≤10 mg/day or equivalent at 2 weeks prior to the initiation of IFX. Patients received intravenous infusions of IFX, at a starting dose of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks, up to week 46, and were followed up to week 54. At week 30, patients with partial remission received increased dose of IFX by 1.5 mg/kg, and patients who failed with IFX terminated the study. At week 38 and 46, patients with symptom of active disease or high serum level of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), were instructed to increase the IFX dose by 1.5 mg/kg, up to 9.5 mg/kg, at each point. All the patients underwent Positron Emission Tomography-Computed Tomography (PET-CT) at baseline and week 30. The primary efficacy end point was the achievement of partial or complete remission at week 30. Results Twelve patients with TAK were enrolled and treated with IFX; 1 patient with study violation was excluded from analysis. At week 30, 3 patients (27.3%) achieved complete remission and 6 patients (54.5%) achieved partial remission. Statistically significant improvements were seen at week 30 for all of major secondary measures, including change from baseline in Indian Takayasu Clinical Activity Score 2010 ITAS 2010 (median 11.0, interquartile range [IQR] 10.0–11.8; 6.0, IQR 5.0–9.0, p=0.004), ITAS.A (14.0, IQR 12.0–14.0; 7.0, IQR 6.0–10.5, p=0.003) and serum levels of ESR (56.0, IQR 44.0–82.5; 26.0, IQR 20.0–56.5, p=0.031) and CRP (1.3, IQR 0.7–2.6; 0.2, IQR 0.1–2.1, p=0.019). PET parameters were significantly reduced, including maximum standardised uptake value (3.50, IQR 3.10–3.84; 3.10, IQR 2.49–3.27, p=0.023), target-to-vein ratio (1.34, IQR 1.13–1.95; 1.31, IQR 1.05–1.45, p=0.032), and target-to-liver ratio (2.38, IQR 1.47–3.05; 1.92, 1.51–2.18, p=0.014) from baseline to week 30. Serum levels of pentraxin-3, soluble human leukocyte antigen-E (sHLA-E), interleukin-6 tended to decrease, while tumour necrosis factor-α level increased after IFX therapy. There were no serious adverse events (SAEs) or AEs necessitating discontinuation of IFX. Conclusions Treatment with IFX may lead to remission or improvement with lower glucocorticoid requirement in TAK (clinicaltrials.gov NCT02457585). Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is a rare autoimmune disease characterised by fibrosis of the skin and multiple internal organ involvement. Previous studies reported a poorer health-related quality of life (HRQoL) in patients with SSc compared to the general population. However, very little is known about HRQoL of SSc as compared with other systemic autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SJS) Objectives To compare the HRQoL of patients with SSc and other systemic autoimmune disease and general population. Methods HRQoL was captured by the Korean short form-36 health survey version 2 (SF-36), short form-6D (SF-6D) and 3 level version of EuroQol five-dimensional (EQ-5D) descriptive system (EQ-5D-3L). Between March and July 2017, consecutive patients with SSc, and randomly chosen patients with RA, SLE and SJS were recruited from the outpatient rheumatology clinics of Seoul National University Hospital, and were asked to answer SF-36 and EQ-5D. Disease activity of RA was evaluated by Disease Activity Score 28-ESR (DAS 28-ESR), SLE by Systemic Lupus Erythematosus Disease Activity Index-2k (SLEDAI-2k), and SJS by EULAR Sjogren’s syndrome disease activity index (ESSDAI). For patients with SSc, Korean version of Health Assessment Questionnaire Disability Index (HAQ-DI) and Systemic sclerosis HAQ-DI (SSc HAQ-DI) were also evaluated. Demographic, clinical, laboratory information were obtained through a medical chart review. Data on representative Korean healthy controls were obtained from a study of psychometric properties of the Korean SF-36 v2 for assessing the general population, which was performed on six hundred healthy Koreans. Results A total of 480 patients with SSc (n=120), RA (n=120), SLE (n=120) and SJS (n=120) and 600 healthy controls were included. The demographic features of patients were similar to the known features of each rheumatic disease group. Patients with rheumatic diseases had significantly lower SF-36 scores (p Conclusions HRQoL of patients with systemic autoimmune diseases is significantly worse and affects all health domains in comparison to healthy controls. Patients with SSc have poorer HRQoL than patients with other rheumatic diseases. Specifically, SSc patients have more impaired mental health than RA patients, and the perception of an individual’s general health is also poor compared to RA. Disclosure of Interest None declared

Head-direction cells preferentially discharge when the head points in a particular azimuthal direction, are hypothesized to collectively function as a single neural system for a unitary direction sense, and are believed to be essential for navigating extra-personal space by functioning like a compass. We tested these ideas by recording medial entorhinal cortex (MEC) head-direction cells while rats navigated on a familiar, continuously rotating disk that dissociates the environment into two spatial frames: one stationary and one rotating. Head-direction cells degraded directional tuning referenced to either of the externally referenced spatial frames, but firing rates, sub-second cell-pair action potential discharge relationships, and internally referenced directional tuning were preserved. MEC head-direction cell ensemble discharge collectively generates a subjective, internally referenced unitary representation of direction that, unlike a compass, is inconsistently registered to external landmarks during navigation. These findings indicate that MEC-based directional information is subjectively anchored, potentially providing for navigation without a stable externally anchored direction sense.