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Purpose: No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China., Patients and Methods: Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority., Results: Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group ( P = .019)., Conclusion: CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.

Background: Local delivery agents (LDA) have the advantage of delivering the antibiotics at high concentrations to the targeted sites. However, the constant flow of gingival crevicular fluids and saliva may restrict their efficacy. Therefore, the drug sustainability and pharmacodynamic properties of any proposed LDA should be evaluated., Methods: Four dental implants were placed unilaterally in the edentulous mandible of six beagle dogs. Peri-implantitis were experimentally induced using silk-ligatures. Each implant was randomly allocated to receive one of the following four treatments: (i) MC (Chitosan-alginate (CA) minocycline), (ii) MP (CA-without minocycline), (iii) PG (Polyacrylate-glycerin minocycline), and (iv) Control (mechanical debridement only). Mechanical therapies and LDAs were administered into the gingival sulcus two times at a 4-week interval. Drug sustainability as well as clinical, radiographical, and immunohistochemical (IHC) analyses were conducted to evaluate the efficacies of treatments., Results: Reduced mean probing depth was observed in all of the test groups after the second delivery. A minimal marginal bone level change was observed during the treatment period (MP (-0.06 ± 0.53 mm) to PG (-0.25 ± 0.42 mm)). The distribution of IHC cell marker analysis of all targeted antibodies ranged from 6.34% to 11.33%. All treatment outcomes between the test groups were comparable. A prolonged retention of LDA was observed from CA microspheres (MC and MP) at both administrations ( p < 0.017) and prolonged sustainability of bacteriostatic effect was observed from MC compared to PG after the second administration ( p < 0.05)., Conclusions: Prolonged retention of CA microspheres was observed and the longer bacteriostatic effect was observed from the MC group. Mechanical debridement with adjunct LDA therapy may impede peri-implantitis progression, however, prolonged drug action did not lead to improved treatment outcome.

Objectives: To evaluate and compare the clinical implications of common inflammatory markers in systemic rheumatic diseases (SRDs)., Method: We investigated the profiles of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and white blood cell (WBC) count in treatment-naïve patients with SRDs, osteoarthritis and pneumonia diagnosed at Seoul National University Hospital during 2004-2016. SRDs included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM) and adult-onset Still's disease (AOSD). Associations between inflammatory markers were evaluated using Pearson's correlation and regression analysis. ROC curve analysis was performed to examine the predictive value of inflammatory markers for SRD diagnosis., Results: We identified a total of 1191 patients. Leukocytosis was present in < 20% SRD patients. There was marked variability in ESR and CRP levels among different SRDs. The highest mean CRP levels (mean ± SD, mg/dL) were observed in AOSD (11.3 ± 7.9), followed by RA (2.0 ± 3.3), IIM (1.8 ± 3.5), SLE (1.5 ± 3.1), SSc (0.6 ± 1.3) and AS (0.08 ± 0.1). Mean ESR (mm/h) was also highest in AOSD (71.2 ± 31.0), followed by SLE (47.3 ± 34.2), RA (45.5 ± 30.6), IIM (40.8 ± 24.8) and SSc (27.8 ± 26.0). All SRDs showed significant positive correlations between ESR and CRP: greatest in RA (r = 0.53, p < 0.001) and weakest in SLE (r = 0.20, p = 0.03). WBC correlated weakly with CRP but not with ESR in most SRDs. While the AUC for WBC count was less than that of ESR or CRP, the AUC for ESR and CRP were similar in SRD. The optimal cuff-off values for inflammatory markers predicting SRD were within or slightly above the normal limit., Conclusions: ESR, CRP and WBC are not always elevated in treatment-naïve patients with SRD. Individual SRDs have a unique profile of inflammatory markers. However, routine inflammatory markers should still be interpreted with caution when diagnosing and assessing disease activity in those with SRD. Key Points •Leukocytosis and elevation of ESR and CRP are not always present in all systemic rheumatic diseases. •Inflammatory markers are often dissociated and they are not specific for disease diagnosis. •Better biomarkers, which measure disease-specific local and systemic inflammation, are needed.

Objective: To investigate the content validity of several patient-reported outcome measures (PROMs) in patients with idiopathic inflammatory myopathies (IIM)., Methods: Seven individual PROM instruments were selected by the Outcome Measures in Rheumatology (OMERACT) Myositis Working Group relating to the following domains: pain, fatigue, physical function and physical activity. Twenty patients from the Johns Hopkins Myositis Center were selected for one-on-one face-to-face or phone interviews for cognitive interviewing of individual PROMs to assess comprehension and content validity. Additionally, patients were asked if they thought muscle symptoms, an area originally identified in qualitative studies, were encapsulated by the other four domains., Results: The majority of patients (>70%) felt that each of the instruments was clear, easy to read and understand, and could be used for assessment of its domain. Two-thirds (66%) of patients felt that 'muscle symptoms' were captured by the other domains., Conclusions: We provided evidence to support adequate content validity for several PROMs. Further research is needed to determine whether 'muscle symptoms' warrant a separate domain., Competing Interests: Declaration of Competing Interests The authors have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Use of redox mediators (RMs) is an effective strategy to enhance reaction kinetics of multi-electron sulfur electrochemistry. However, the soluble small-molecule RMs usually aggravate the internal shuttle and thus further reduce the battery efficiency and cyclability. A semi-immobilization strategy is now proposed for RM design to effectively regulate the sulfur electrochemistry while circumvent the inherent shuttle issue in a working battery. Small imide molecules as the model RMs were co-polymerized with moderate-chained polyether, rendering a semi-immobilized RM (PIPE) that is spatially restrained yet kinetically active. A small amount of PIPE (5 % in cathode) extended the cyclability of sulfur cathode from 37 to 190 cycles with 80 % capacity retention at 0.5 C. The semi-immobilization strategy helps to understand RM-assisted sulfur electrochemistry in alkali metal batteries and enlightens the chemical design of active additives for advanced electrochemical energy storage devices., (© 2020 Wiley-VCH GmbH.)

Purpose: To investigate the effect of chemotherapy and radiotherapy timing after breast conserving surgery (BCS) on recurrence and survival of women with early-stage breast cancer., Patients and Methods: We retrospectively analyzed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy. Of these, 488 women received chemotherapy first (CT-first group) while the other 412 received radiotherapy first (RT-first group). Locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching (PSM) and the Cox proportional hazards model. The optimal cut-off value of interval time from surgery to the start of chemotherapy was calculated by Maxstat., Results: The median follow-up was 7.1 years. In pre-match analysis, the CT-first group had a significantly higher 8-year DFS than the RT-first group (90.4% vs. 83.1%, P = 0.005). PSM analysis of 528 patients indicated that the 8-year DFS (91.0% vs. 83.3%, P = 0.005) and DM (8.6% vs. 14.6%, P = 0.017) were significantly better in the CT-first group, but that the OS ( P = 0.096) and LRR ( P = 0.434) were similar. We found the optimal cut-off value of interval from surgery to chemotherapy was 12 weeks. Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes., Conclusion: For women with breast cancer who require both chemotherapy and radiotherapy after BCS, adjuvant chemotherapy should be started within 12 weeks. Delaying the initiation of radiotherapy, for administration of long-course chemotherapy, does not compromise outcomes., (Copyright © 2020 Chen, Tang, Wang, Song, Fang, Wang, Jing, Zhang, Sun, Zhao, Jin, Liu, Chen, Qi, Li, Tang, Lu, Ren, Yu and Li.)

In South Korea, the gradual increase in particulate matter generation has received significant attention from central and local governments. Exhaust gas, which contains nitrogen oxides (NO x ), is one of the main sources of particulate matter. In this study, the reduction of NO x using a coating material mixed with a titanium dioxide (TiO 2 ) photocatalyst was demonstrated. The NO x reduction performance of the TiO 2 photocatalyst-infused coating was evaluated by applying the ISO 22197-1: 2007 standard. Subsequently, the performance was evaluated by changing the NO gas concentration and ultraviolet (UV)-A irradiance under standard experimental conditions. It was determined that NO x reduction can be achieved even if the NO gas concentration and UV-A irradiance are lower than those under the standard conditions when the TiO 2 photocatalyst-infused coating was used. This study revealed that NO x reduction can be realized through TiO 2 photocatalyst-infused coating in winter or cloudy days with a low solar altitude. It was also confirmed that compared with the UV-A irradiance, the NO gas concentration has a greater effect on the NO x reduction performance of the TiO 2 photocatalyst-infused coating. These findings can be used to evaluate a variety of construction materials with TiO 2 photocatalysts in the future.

Background: The effects of oral contrast agents (OCAs) on dosimetry have not been studied in detail. Therefore, this study aimed to examine the influence of OCAs on dose calculation in volumetric-modulated arc therapy plans for rectal cancer., Methods: From 2008 to 2016, computed tomography (CT) images were obtained from 33 rectal cancer patients administered OCA with or without intravenous contrast agent (ICA) and 14 patients who received no contrast agent. CT numbers of organs at risk were recorded and converted to electronic densities. Volumetric-modulated arc therapy plans were designed before and after the original densities were replaced with non-enhanced densities. Doses to the planned target volume (PTV) and organs at risk were compared between the plans., Results: OCA significantly increased the mean and maximum densities of the bowels, while the effects of ICA on these parameters depended on the blood supply of the organs. With OCA, the actual doses for PTV were significantly higher than planned and doses to the bowel increased significantly although moderately. However, the increase in the volume receiving a high-range doses was substantial (the absolute change of intestine volume receiving ≥52 Gy: 1.46 [0.05-3.99, cubic centimeter range: -6.74 to 128.12], the absolute change of colon volume receiving ≥50 Gy: 0.34 [0.01-1.53 cc, range: -0.08 to 3.80 cc]. Dose changes due to ICA were insignificant. Pearson correlation showed that dose changes were significantly correlated with a high intestinal volume within or near the PTV (ρ > 0.5, P < 0.05) and with the density of enhanced intestine (ρ > 0.3, P < 0.05)., Conclusions: Contrast agents applied in simulation cause underestimation of doses in actual treatment. The overdose due to ICA was slight, while that due to OCA was moderate. The bowel volume receiving ≥50Gy was dramatically increased when OCA within the bowel was absent. Physicians should be aware of these issues if the original plan is barely within clinical tolerance or if a considerable volume of enhanced intestine is within or near the PTV.

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we present data from the completed Phase 3 randomised controlled trial (RCT) ORAL Scan (NCT00847613), which evaluated the impact of tofacitinib on patient-reported outcomes (PROs) through 24 months in patients with active RA and inadequate responses to methotrexate (MTX-IR)., Methods: Patients were randomised 4:4:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID), or placebo advanced to tofacitinib 5 or 10 mg, plus background MTX. Patients receiving placebo advanced to tofacitinib at month 3 (non-responders) or month 6 (remaining patients). Mean changes from baseline in PROs, assessed at months 1-24, included Health Assessment Questionnaire-Disability Index, Patient Global Assessment of disease activity (visual analogue scale [VAS]), Patient Assessment of Arthritis Pain (VAS), health-related quality of life (Short Form-36 version 2), Functional Assessment of Chronic Illness Therapy-Fatigue and Medical Outcomes Study-Sleep., Results: Overall, 539/797 (67.6%) patients completed 24 months' treatment. At month 3, tofacitinib-treated patients reported signi cant (p<0.05) mean changes from baseline versus placebo across all PROs, and significantly more patients reported improvements ≥ minimum clinically important differences versus placebo. Improvements in PROs with tofacitinib were sustained to month 24. Following advancement to tofacitinib, placebo-treated patients generally reported changes of similar magnitude to tofacitinib-treated patients., Conclusions: Patients with RA and MTX-IR receiving tofacitinib 5 or 10 mg BID plus MTX reported significant and clinically meaningful improvements in PROs versus placebo at month 3, which were sustained through 24 months.

Puerarin 6″-O-xyloside is a tumor suppressive derivate of Puerarin that is recently characterized as a lysine-specific demethylase 6B inhibitor. Here we investigated the effects of Puerarin 6″-O-xyloside in hepatocellular carcinoma (HCC) cell lines SMMC-7721 and HepG2. Cell viability, proliferation, stemness, protein expression, and autophagy were tested by CCK-8, colony formation, sphere formation, western blotting, and LC3B GFP puncta per cell, respectively. Apoptosis, CD133-positive cells, and JC-1-labeled mitochondrial membrane potential were measured by flow cytometry. The effects of Puerarin 6″-O-xyloside in vivo were explored in HepG2 xenograft mice. Puerarin 6″-O-xyloside inhibited cell viability, proliferation, and stemness, and promoted apoptosis in both SMMC-7721 and HepG2 cells. Further experiments showed promoted autophagy and decreased mitochondrial membrane potential, and decreased expression of p-PI3K, p-AKT, and p-mTOR in HepG2 cells. Co-administration of 3-MA with Puerarin 6″-O-xyloside obviously augmented these effects including inhibited protein expression of p-PI3K, p-AKT, and p-mTOR, and inhibited proliferation, promoted apoptosis, and decreased stemness. In HepG2 xenograft mice, 100 mg/kg/d Puerarin 6″-O-xyloside significantly suppressed tumor growth, stemness, and apoptosis. In conclusion, our study indicated that Puerarin 6″-O-xyloside decreased cell viability, proliferation, and stemness, and promoted autophagy and mitochondria-dependent apoptosis of HCC, at least partly through inhibiting PI3K/AKT/mTOR. These results highlighted Puerarin 6″-O-xyloside as a promising prodrug that could inhibit both PI3K/AKT/mTOR and epigenetic demethylation., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: The aim of this study was to determine whether radiation-induced lymphopenia affects the survival of patients with breast cancer., Methods and Materials: Post hoc analysis was conducted on data from 598 patients with breast cancer from a randomized controlled trial comparing postmastectomy hypofractionated radiation therapy (HFRT; 43.5 Gy in 15 fractions over 3 weeks) with conventional fractionated radiation therapy (CFRT; 50 Gy in 25 fractions over 5 weeks). Mean peripheral lymphocyte count (PLC) at different time points in the 2 groups was compared by the t test. Disease-free survival and overall survival were analyzed by the Kaplan-Meier method and compared between groups by the log-rank test., Results: Baseline PLC (pre-PLC) was comparable between HFRT and CFRT patients (1.60 ± 0.57 × 10 9 /L vs 1.56 ± 0.52 × 10 9 /L; P = .33). In both groups, the PLC declined steadily during the course of radiation therapy but started to recover at 1 month after radiation therapy. Incidence of lymphopenia was significantly lower in HFRT patients (45.4% vs 55.7%; P = .01). Nadir-PLC was significantly higher in HFRT patients (1.08 ± 0.37 × 10 9 /L vs 0.97 ± 0.31× 10 9 /L; P < .001), as was the nadir-PLC/pre-PLC ratio (0.72 ± 0.28 vs 0.67 ± 0.28; P = .02). Median follow-up was 57.6 months (interquartile range, 38.5-81.4). The 5-year disease-free survival was significantly lower in patients with a nadir-PLC/pre-PLC ratio <0.8 than in those with a ratio ≥0.8 (71.8% vs 82.6%; P = .01); however, overall survival was comparable between the groups (85.8% vs 90.6%; P = .24)., Conclusions: The risk of radiation-induced lymphopenia in patients with breast cancer is lower with HFRT than with CFRT. A low nadir-PLC/pre-PLC ratio may predict poor prognosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To identify the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1~2 positive axillary sentinel lymph node (SLN) and construct an accurate prediction model. Methods: Retrospective chart review was performed in 917 breast cancer patients who underwent surgery treatment between 2002 and 2017 and pathologically confirmed 1-2 positive SLNs. According to the date of surgery, patients were divided into training group (497 cases) and validation group (420 cases). A nomogram was built to predict nSLN metastasis and the accuracy of the model was validated. Results: Among the 917 patients, 251 (27.4%) had nSLN metastasis. Univariate analysis showed tumor grade, lymphovascular invasion (LVI), extra-capsular extension (ECE), the number of positive and negative SLN and macro-metastasis of SLN were associated with nSLN metastasis (all P <0.05). Multivariate Logistic regression analysis showed the numbers of positive SLN, negative SLN and macro-metastasis of SLN were independent predictors of nSLN metastasis (all P <0.05). A nomogram was constructed based on the 6 factors. The area under the receiver operating characteristic curve was 0.718 for the training group and 0.742 for the validation group. Conclusion: We have developed a nomogram that uses 6 risk factors commonly available to accurately estimate the likelihood of nSLN metastasis for individual patient, which might be helpful for radiation oncologists to make a decision on regional nodal irradiation.

Background: The role of postmastectomy radiotherapy (PMRT) in women with pT1-T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT., Methods: The authors retrospectively evaluated 4869 patients with pT1-T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease-free survival and OS rates were calculated using the Kaplan-Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model., Results: After a median follow-up of 65.9 months, the 5-year OS, disease-free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate-risk (P < .001) and high-risk groups (P = .004), but not in the low-risk group (P = .728)., Conclusions: The authors developed a nomogram that is predictive of OS among women with pT1-T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT., (© 2020 American Cancer Society.)

Background: To assess the soft tissue dimension following tooth extraction and alveolar ridge preservation in the posterior maxilla compared to spontaneous healing., Methods: Thirty-five patients randomly assigned to alveolar ridge preservation (ARP) and spontaneous healing (SH) after maxillary molar extraction. The crestal, buccal, and palatal gingival thickness at 6 months was measured around virtually placed implant fixtures using superimposed cone-beam computed tomography and intraoral scan taken at 6 months. Buccal mucogingival junction (MGJ) level change over 6 months was estimated using intraoral scans obtained at suture-removal and 6 months., Results: The crestal gingiva was significantly thinner in group ARP (-1.16 mm) compared to group SH ( p < 0.05). The buccal and palatal gingiva was significantly thinner at the implant shoulder (IS) level in group ARP (buccal: -0.75 mm; palatal: -0.85 mm) compared to group SH ( p < 0.05). The thickness at 2 mm below the IS of both sides and the buccal MGJ level change were similar in both groups ( p > 0.05)., Conclusions: ARP in the posterior maxilla resulted in a thinner soft tissue on top of and at the prospective level of the implant shoulder at 6 months. The buccal MGJ level changed minimal for 6 months in both groups.

Purpose: This study was conducted to assess the efficacy of prophylactic gingival grafting in the mandibular anterior labial area for preventing orthodontically induced gingival recession., Methods: Eight mongrel dogs received gingival graft surgery at the first (I1) and third (I3) mandibular incisors on both sides based on the following group allocation: AT group (autogenous connective tissue graft on I1), AT-control group (contralateral side in the AT group), CM group (xenogeneic cross-linked collagen matrix graft on I3) and CM-control group (contralateral side in the CM group). At 4 weeks after surgery, 6 incisors were splinted and proclined for 4 weeks, followed by 16 weeks of retention. At 24 weeks after surgery, casts were made and compared with those made before surgery, and radiographic and histomorphometric analyses were performed., Results: Despite the proclination of the incisal tip (by approximately 3 mm), labial gingival recession did not occur. The labial gingiva was thicker in the AT group (1.85±0.50 mm vs. 1.76±0.45 mm, P >0.05) and CM group (1.90±0.33 mm vs. 1.79±0.20 mm, P >0.05) than in their respective control groups., Conclusions: The level of the labial gingival margin did not change following labial proclination of incisors in dogs. Both the AT and CM groups showed enhanced gingival thickness., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Korean Academy of Periodontology.)

Objectives: Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA)., Methods: HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA)., Results: Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect., Conclusion: The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.

Background: The objective of this is preclinical investigation was to evaluate the differential drug sustainability and pharmacodynamic properties of two local minocycline microsphere carriers: chitosan-coated alginate (CA) and poly(meth)acrylate-glycerin (PG)., Methods: Four dental implants were placed unilaterally in the edentulous mandible of six beagle dogs. Each implant was randomly assigned to receive one of the following four treatments: (i) CA (CA-based minocycline), (ii) placebo (CA substrate without minocycline), (iii) PG (PG-based minocycline) and (iv) control (mechanical debridement only). After inducing peri-implant mucositis, the randomly assigned treatments were administered into the gingival sulcus twice at a 4-week interval using a plastic-tipped syringe. Drug sustainability and pharmacodynamic (clinical, radiographical and cell marker intensity) evaluations were performed after each administration., Results: The CA microspheres remained longer around the healing abutment compared to the PG microspheres at both administrations and a longer bacteriostatic effect was observed from CA (7.0 ± 5.7 days) compared to PG (1.2 ± 2.6 days). The efficacy of the applied therapies based on clinical, radiographical and histological analyses were comparable across all treatment groups., Conclusions: CA microspheres showed longer carrier and bacteriostatic effect sustainability when compared to PG microspheres, however, longer drug sustainability did not lead to improved treatment outcomes.

Objective: To examine the construct of illness perception (IP) as measured by the Brief Illness Perception Questionnaire (BIPQ) using network analysis in patients with rheumatic diseases (RD) and with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS). Design: Cross-sectional and multicentre survey. Main Outcome Measures: The BIPQ and the Hospital Anxiety and Depression Scale. Results: BIPQ network structures did not differ between patients with RD and HIV/AIDS. Community analysis identified two clusters: one comprised consequences, timeline, identity, concern and emotional response; and the other consisted of personal control, treatment control and comprehensibility. Centrality indices indicate that concern, consequences and emotional response are central dimensions of the BIPQ. Directed acyclic graph analysis revealed that concern was a dominant network item, activating emotional response, consequences, identity and comprehensibility. Emotional response and consequences were bridging items linking IP to anxiety and depression. Conclusion: Perceived impact of illness on life and emotion and illness concern are central dimensions of the BIPQ that link IP to anxiety and depression in patients with RD and HIV/AIDS. Care of patients with RD and HIV/AIDS may benefit from addressing IP, particularly concern, emotional response and consequences to prevent clinical anxiety and depression.

An amendment to this paper has been published and can be accessed via the original article.

Objective: To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery, and to investigate the correlation between cardiac injury and hypofractionated radiotherapy dose. Methods: We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation after breast conserving surgery using either deep inspiration breath-hold (DIBH) or free breathing (FB) radiotherapy technique. Cardiac examinations that included N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and myocardial perfusion imaging were performed routinely before and after radiotherapy. The effects of heart dose, systemic therapy and individual factors (Framingham score) on the incidence of cardiac events were analyzed. Results: The median age was 48 years. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) were 4.0, 16.9, 6.3, and 4.4 Gy, respectively. With a median follow-up of 13.4 months, no patient had clinical cardiac abnormalities. The incidence rates of subclinical cardiac events at 1- 6- and 12-month were 23.5%, 31.6%, and 41.3%, respectively. The DIBH group had a lower mean dose, maximum dose, and V5-V40 in the heart, LAD, LV, and RV than the FB group ( P <0.001). Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean >4 Gy, LAD V40 > 20%, LV Dmean >6 Gy, RV Dmean >7 Gy, or cumulative doses of anthracycline or taxane > 300 mg/m(2) (All P <0.05). Anti-HER2 targeted therapy, endocrine therapy and Framingham score were not associated with the incidence of subclinical cardiac events (all P >0.05). Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events. Conclusions: Early subclinical heart injury are found in patients with left-sided breast cancer after hypofractionated radiotherapy. The increased incidence of subclinical cardiac events after radiotherapy is positively associated with the cardiac radiation doses.

Background: Causes of weight change after tocilizumab treatment are unclear. We aimed to investigate the effects of tocilizumab treatment on body weight and serum adipokine levels in patients with rheumatoid arthritis (RA)., Methods: In this retrospective cohort study, we evaluated weight changes in patients with RA who received methotrexate (Cohort I) or tocilizumab with methotrexate (Cohorts II and III) for 24 weeks. Adipokine concentrations at baseline and 24 weeks were analyzed in Cohorts I and III. Cohorts I and II received tocilizumab therapy for an additional 48 weeks, during which weight changes were monitored (24-72 weeks)., Results: No significant weight change occurred after 24 weeks of methotrexate treatment (mean difference, -0.2 kg; P = 0.630), but was observed after 24 weeks of tocilizumab treatment (mean difference, +0.9 kg; P = 0.010). Weight changed regardless of the treatment response in both treatment groups. The leptin-adiponectin ratio ( P = 0.015) and levels of adiponectin ( P < 0.001), leptin ( P < 0.001), and resistin ( P = 0.003) increased significantly after 24 weeks of tocilizumab, but not methotrexate treatment. After 24, 48 and 72 weeks of tocilizumab treatment in Cohort II, mean (95% confidence interval [CI]) weight changes from baseline were +0.7 (0.0-1.4), +1.2 (0.4-2.0) and +1.1 (0.2-2.0) kg, respectively, and mean (95% CI) percent weight changes from baseline were +1.3% (0.1%-2.6%), +2.2% (0.7%-3.6%), and +2.0% (0.4%-3.7%) at 24, 48, and 72 weeks, respectively., Conclusion: Weight and the leptin-adiponectin ratio increased after tocilizumab treatment. Given that cardiovascular (CV) risk factors may deteriorate in patients with RA who receive tocilizumab, further studies are required to determine the effects of weight gain on CV outcomes in these patients., Competing Interests: IA Choi received a research grant from Chungbuk National University Hospital in 2018. She received a research grant from LG Chem and AbbVie Korea, which is not relevant to this study. EY Lee received the grants from the Ministry of Science, ICT and Future planning (NRF-2019M3A9A8065574). EB Lee has received research grants from Pfizer Korea, and has been a consultant for Pfizer. YW Song received a research grant from JW Pharmaceuticals during the clinical trials (NCT01211834 and NCT01256736). The use of clinical data and serum samples in this study were supported by JW Pharmaceuticals. The present study received grants from the Ministry of Science, ICT and Future planning (NRF-2015M3A9B6052011, 2019M3A9A8065574) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1277)., (© 2020 The Korean Academy of Medical Sciences.)

Diagnoses based on oral fluid biomarkers have been introduced to overcome limitations of periodontal probe-based diagnoses. Diagnostic ability of certain biomarkers for periodontitis have been identified and widely studied, however, such studies targeting gingivitis is scarce. The aims of this study were to determine and compare the efficacies and accuracies of eight biomarkers in diagnosing gingivitis with the aid of receiver operating characteristic (ROC) curves. The probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) were examined in 100 participants. Gingival crevicular fluid was collected using paper points, and whole-saliva samples were collected using cotton roll. Samples were analyzed using enzyme-linked immunosorbent assay kits for the different biomarkers. The levels of matrix metalloproteinase (MMP)-8, MMP-9, lactoferrin, cystatin C, myeloperoxidase (MPO), platelet-activating factor, cathepsin B, and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen were analyzed. MPO and MMP-8 levels in saliva were strongly correlated with gingivitis, with Pearson's correlation coefficients of 0.399 and 0.217, respectively. The area under the curve (AUC) was largest for MMP-8, at 0.814, followed by values of 0.793 and 0.777 for MPO and MMP-9, respectively. The clinical parameters of GI and PI showed strong correlations and large AUC values, whereas PD and CAL did not. MMP-8 and MPO were found to be effective for diagnosing gingivitis. Further investigations based on the results of this study may identify clinically useful biomarkers for the accurate and early detection of gingivitis.

Background: The infliximab biosimilar CT-P13 has widely received regulatory approval in all indications of reference infliximab, including rheumatoid arthritis (RA) and ankylosing spondylitis (AS)., Objective: This retrospective analysis investigated drug survival and long-term safety and effectiveness of CT-P13 in patients with RA or AS in the Republic of Korea., Methods: This non-interventional, retrospective, multicenter analysis collected medical record data for adult patients with RA or AS who received CT-P13 treatment at five Korean referral hospitals (2012-2017). Drug survival and long-term safety were primary outcomes. The secondary outcome was long-term effectiveness, assessed by disease activity measures., Results: Overall, 491 patients were treated with CT-P13 (154 patients with RA [135 infliximab-naïve; 19 switched from reference infliximab]; 337 patients with AS [219 infliximab-naïve; 118 switched from reference infliximab]). Drug survival was similar in naïve and switched patients. Treatment-emergent adverse events (TEAEs) occurred in 31.8% and 29.4% of patients with RA and AS, respectively; incidence was similar in naïve and switched groups. Upper respiratory tract infection, influenza-like illness, and urticaria were the most common TEAEs. Overall, nine (1.8%) patients experienced serious adverse events (SAEs) deemed potentially drug-related; SAEs led to permanent CT-P13 discontinuation in five (1.0%) patients, including three with tuberculosis. Disease activity decreased over time., Conclusion: Up to 5 years of CT-P13 treatment was safe and effective in patients with RA and AS, based on drug survival, incidence of TEAEs, and disease activity. Drug survival and safety were similar in naïve patients and switched groups, supporting switching from reference infliximab to CT-P13.

An amendment to this paper has been published and can be accessed via the original article.

Background: The tumor necrosis factor (TNF) superfamily cytokine TNF-like protein 1A (TL1A) and its receptor DR3 are essential for diverse animal models of autoimmune disease and may be pathogenic in rheumatoid arthritis (RA). However, the relationship of TL1A to disease duration, activity, and response to anti-TNF and other therapies in RA is not clear., Methods: We measured soluble TL1A in synovial fluid (SF), serum, or plasma from RA first-degree relatives (FDRs) and in early RA and established disease. We measured the effects of anti-TNF and methotrexate (MTX) therapy on circulating TL1A from multiple independent RA treatment trials. We also determined the ability of a blocking anti-TL1A antibody to inhibit clinical disease and articular bone destruction in the murine collagen-induced arthritis (CIA) model of human RA., Results: Soluble TL1A was specifically elevated in the blood and SF of patients with RA compared to patients with other diseases and was elevated early in disease and in at-risk anti-cyclic citrullinated peptide (CCP) (+) first-degree relatives (FDRs). Therapeutic TNF inhibition reduced serum TL1A in both responders and non-responders, whereas TL1A declined following MTX treatment only in responders. In murine CIA, TL1A blockade was clinically efficacious and reduced bone erosions., Conclusions: TL1A is specifically elevated in RA from early in the disease course and in at-risk FDRs. The decline in TL1A after TNF blockade suggests that TL1A levels may be a useful biomarker for TNF activity in RA. These results support the further investigation of the relationship between TL1A and TNF and TL1A blockade as a potential therapeutic strategy in RA.

Small molecules including sodium butyrate (SB) and dimethyloxalylglycine (DMOG) can promote bone regeneration via inhibitive effects eliciting cellular responses through signaling cascades. The purpose of this study was to determine the synergistic effects of SB and DMOG loaded on calcium sulfate (CaS) on bone regeneration in the challenging vertical augmentation model in the rabbit calvarium. Four plastic cylinders screwed on the calvarium of each of 10 rabbits were randomly grafted with CaS, CaS/SB, CaS/DMOG, or CaS/DMOG/SB. All specimens were assessed by radiographic, histologic, and histomorphometric analyses. In the radiographic analysis, three different layers (new bone, degraded CaS, and pristine CaS layers) could be distinguished within the cylinder in all groups at 2 weeks. Newly formed bone grew up from basal bone, and CaS in contact with newly formed bone was degraded into small particles to form a different layer. At 8 weeks, most of the pristine CaS had been absorbed and hardly seen within the cylinder. In the histomorphometric analysis, all groups showed comparable new bone areas and heights at 2 and 8 weeks. The DMOG group showed a significant increase in new bone area at 8 weeks compared with 2 weeks, but there was no significant difference among the groups at 8 weeks. The DMOG group showed significantly lower values for the residual material area than the control group at 2 weeks. Within the limitations of this study, SB and DMOG seem to exert smaller synergistic effects on bone regeneration compared to CaS alone in vertical bone augmentation., (© 2019 Wiley Periodicals, Inc.)

Background: Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety for the treatment of rheumatoid arthritis (RA) in randomized, controlled trials of up to 52 weeks' duration. However, safety and effectiveness after long-term treatment have not been assessed., Methods: This was an interim analysis of an ongoing open-label, multicenter extension study in RA patients who completed phase 2b (RAJ1; 12 weeks) and phase 3 (RAJ3 and RAJ4; 52 weeks) peficitinib studies in Asia (mainly Japan). Eligible patients (n = 843) received oral peficitinib once daily (100 mg, or 50 mg for patients transferring from RAJ1). The peficitinib dose could be increased (up to 150 mg) or reduced (to 50 mg) at the discretion of the investigator. Efficacy variables assessed included American College of Rheumatology (ACR) response rates, ACR components, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP)., Results: Results up to May 2018 are summarized. Mean peficitinib duration of exposure was 22.7 months and the maximum dose was 100 mg in most (66.5%) patients. ACR responses were maintained during the extension study, with ACR20/50/70 response rates of 71.6%, 52.1%, and 34.7% at week 0 and 78.9%, 61.4%, and 42.7% at end of treatment, respectively. ACR components and DAS28-CRP showed improvements from baselines of the preceding studies and continued to show improvements during the extension study. Treatment-emergent adverse events (TEAEs) were reported in 757/843 (89.8%) patients, the most common being nasopharyngitis (39.7%) and herpes zoster (11.7%). The majority of TEAEs were severity grade 1/2. Drug-related TEAEs leading to permanent study drug discontinuation occurred in 55/843 (6.5%) patients. Regarding AEs of special interest, the incidence per 100 patient-years of serious infections was 2.3 (95% CI 1.6 - 3.1), herpes zoster-related disease 6.8 (95% CI, 5.6 - 8.3), and malignancies 1.1 (95% CI, 0.7 - 1.8). One death from diffuse large B cell lymphoma during the study and one death from uterine sarcoma after the study were considered probably and possibly related to study drug, respectively., Conclusions: The effectiveness of peficitinib was maintained or improved during long-term administration and treatment up to 6 years was well tolerated in Asian patients with RA., Trial Registration: ClinicalTrials.gov, NCT01638013, registered retrospectively 11 July 2012.

Myricetin is a commonly found dietary flavonoid. In the present study, we investigated the effects of myricetin on migration and invasion of radioresistant lung cancer cells (A549-IR). Transcriptome analysis of A549-IR cells identified several differentially expressed genes (DEGs) in A549-IR cells compared to parental A549 cells. Functional enrichment analysis revealed that most of the DEGs were linked with PI3K-AKT signaling, proteoglycans, focal adhesion, and ECM-receptor interactions. A549-IR cells demonstrated enhanced migratory potential with increased expression of vimentin, snail and slug, and reduced expression of E-cadherin. A549-IR cells exposed to myricetin displayed reduced migration and suppressed MMP-2 and MMP-9 expression. Notably, myricetin inhibited the phosphorylation of focal adhesion kinase (FAK) and altered the F-actin/G-actin ratio in A549-IR cells, without modulation of EMT markers. These findings suggest that myricetin can inhibit migration of A549-IR cells by suppressing MMP-2 and MMP-9 expressions through inhibition of the FAK-ERK signaling pathway., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)

Background/aims: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS., Methods: Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed., Results: The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation- 2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance., Conclusion: Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.

Aim: The purpose of this retrospective study was to determine clinical benefits of ridge preservation in terms of surgical invasiveness of implant placement compared to natural healing in the maxilla., Materials & Methods: This study included 178 patients with 206 implants placed at ridge-preserved sites and 493 patients with 656 implants placed at naturally healed sites in maxillary anterior and posterior regions. Patient- and implant-related data were collected from electronic dental records including additional augmentation procedures performed before or during implant placement and surgical complications. Cumulative survival rate was assessed using Kaplan-Meier method. The annual peri-implant marginal bone loss between the two groups was compared using the Mann-Whitney U test., Results: The follow-up period was 24.4 ± 18.1 months (mean ± standard deviation) for ridge-preserved sites and 45.7 ± 29.6 months for naturally healed sites. Sinus augmentation was performed at similar frequencies in the two groups, but lateral approach was applied significantly more at naturally healed sites (37.2%) than ridge-preserved sites (8.3%, p ≤ .001). There was no intergroup difference in the cumulative survival rate or annual peri-implant marginal bone loss., Conclusion: Ridge preservation can be clinically beneficial for minimizing the invasiveness of implant surgery by simplifying the procedure when sinus augmentation is expected in the maxilla., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To investigate the effects of short-term discontinuation of methotrexate (MTX) on disease activity in patients with rheumatoid arthritis (RA) taking a stable dose of MTX. A post-hoc analysis of two randomized controlled trials was used to investigate the effects of temporary MTX discontinuation (for 2 weeks or 4 weeks) on responses to seasonal influenza vaccination. The impact of MTX discontinuation on the RA disease activity score (DAS28) and RA flare rate during discontinuation and after reintroduction was examined. The DAS28 increased during the 4-week MTX discontinuation period, before returning to baseline after reintroduction. The overall flare-free survival period did not differ between the groups (log rank p = 0.142). However, during the 4-week MTX discontinuation period, more patients in the MTX-hold group than in the MTX-continue group experienced a flare (20.5% vs. 7.4%, respectively; p = 0.058). After resumption of MTX, the flare rate did not differ between groups. The flare rates in the MTX-continue group and the 2-week and 4-week MTX-hold groups were 5.8%, 10.8% and 20.5%, respectively (p < 0.01). The change in the DAS28 from baseline did not differ significantly between the MTX-continue and the 2-week MTX-discontinue groups. However, there was a significant difference between the 4-week MTX-hold group and the MTX-continue group (p = 0.005). Short-term discontinuation of MTX for up to 2 weeks is safe, whereas discontinuation for 4 weeks is associated with a transient increase in disease flares and activity in RA patients taking a stable MTX dose.Key Points• Methotrexate discontinuation for 2 weeks is safe.• Methotrexate discontinuation for 4 weeks transiently increases flare risk and disease activity.• Disease flare risk and disease activity return to baseline after restarting methotrexate treatment.

Objectives: This study histologically analyzed biopsy samples obtained from sites of damaged extraction socket grafting using deproteinized bovine bone mineral (DBBM) or deproteinized porcine bone mineral (DPBM) with coverage by a collagen membrane., Material and Methods: One hundred patients participated in this randomized controlled clinical trial of extraction socket grafts performed in cases of periodontally compromised teeth. All participants were blinded to their group allocations, and each material was grafted with coverage by collagen membranes after extraction of the tooth and removal of granulation tissue. At implant placement at 4 months, a biopsy was harvested at the implant site using a trephine was analyzed histologically., Results: Eighty-five biopsy samples were acquired, of which 81 were finally included in the histologic analysis (42 in DBBM and 39 in DPBM group). Both DBBM and DPBM groups showed comparable proportions of residual biomaterial (12.37 ± 5.67% and 12.21 ± 5.75%, respectively), newly formed bone (15.07 ± 10.52% and 18.47 ± 11.47%, respectively), and nonmineralized tissue (72.56 ± 10.07% and 71.55 ± 15.47%, respectively). There were no significant differences in these histologic parameters between the two groups with different biomaterials., Conclusion: Comparable histologic bone formation was found in both socket grafted groups with DBBM or DPBM covered by collagen membranes in periodontally damaged extraction sockets. However, a wide variation in new bone formation was found after 4 months of postsurgical healing and a tendency of higher new bone formation was shown at damaged sockets that had an intact unilateral residual wall regardless of buccal or lingual side., (© 2019 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Objective: In this retrospective single institution study, we investigated the clinicopathologic features and treatment characteristics of 90 patients with congenital corneal opacities (CCO) (117 eyes) who were 3 years and younger and treated at our hospital., Subject and Methods: We reviewed the clinical data of patients with CCO who presented for the first time for treatment at our hospital between January 1, 2017, and December 31, 2017. CCO were classified using the "STUMPED" (Sclerocornea, Tears in Descement's membrane, Metabolic, Peters, Endothelial dystrophy and Dermoid) method and confirmed by pathological examination. -Results: Seventy percent of the patients had unilateral CCO. Iridocorneal adhesions (61 eyes, 52.1%) and cataracts (22 eyes, 18.8%) were the 2 most common ocular abnormalities. Systemic abnormalities were present in 5 patients (5.6%), including growth retardation (4 patients) and congenital brain defects (1 patient). Eighty-five eyes (72.6%) underwent penetrating keratoplasty (PK), and lamellar keratoplasty (LK) was performed in 30 (25.6%) eyes. Forty-seven (95.9%) eyes with Peters anomaly and all 16 eyes with sclerocornea received PK, and all 24 eyes with dermoids were treated with LK., Conclusion: Our study demonstrates that CCO has varied manifestations in infants and young children in China. A thorough medical history, careful clinical examination, and the use of accessory examinations such as ultrasound biomicroscopy are critical for the accurate diagnosis and classification of CCO and to provide guidance on therapeutic choices., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Objectives: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women., Methods: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry., Results: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups., Conclusion: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Optical tomographic imaging (OTI) was reported to be a novel technique for the early diagnosis and disease activity assessment of rheumatoid arthritis (RA). This study aimed to evaluate the clinical utility of OTI for the detection of hand synovitis of RA patients. Manu-scan was used to perform imaging targeting the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in 12 RA patients and three controls. The enrolled RA patients also underwent magnetic resonance imaging (MRI) and bone scintigraphy (BS) to provide reference images. Of the 181 joints feasible for OTI analysis, 140 joints (111 in RA patients and 29 in controls, 77.3%) in which the difference of the OTI indices in the two measurements was within 20% were evaluated. The OTI indices in RA joints were significantly lower than those in control joints (p < 0.001). Overall, the OTI indices in RA joints decreased as the synovitis grades on MRI or BS increased. Moreover, OTI was able to discriminate between RA and control joints (AUC = 0.815, 95% CI 0.739-0.891), even if RA joints were normal on physical examination (AUC = 0.714, 95% CI 0.594-0.834). OTI was in good agreement (kappa = 0.60) with MRI for evaluating synovitis in RA patients and showed positive results in 11.4% of clinically asymptomatic joints. OTI in this study showed the potential to be a supplementary imaging modality for the quantification of synovial inflammation in PIP and MCP joints of RA patients. Further large-scale trials are needed to confirm these findings.

Objective: To compare cardiovascular (CV) risk among gout patients initiating allopurinol vs febuxostat., Methods: Using 2002-2015 Korean National Health Insurance Service data for the entire Korean population, we conducted a cohort study on gout patients initiating allopurinol or febuxostat. The primary outcome was a composite CV end point of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. Secondary outcomes were individual components of the primary outcome, and all-cause mortality. We used propensity score-matching with a 4:1 ratio for allopurinol and febuxostat initiators to control for confounding. Competing risk analyses were done for non-fatal outcomes accounting for deaths., Results: We included 39 640 allopurinol initiators propensity score-matched on 9910 febuxostat initiators. The mean age was 59.1 years and 78.4% were male. The incidence rate per 100 person-years for the primary outcome was 1.89 for allopurinol and 1.84 for febuxostat initiators. The corresponding hazard ratio comparing allopurinol vs febuxostat initiators was 1.09 (95% CI: 0.90, 1.32). No significant difference was found for the secondary outcomes, including all-cause mortality (hazard ratio 0.96; 95% CI: 0.79, 1.16). Subgroup analyses limited to those at high CV risk and to equipotent-dose initiators (i.e. allopurinol ⩾300 mg/day vs febuxostat ⩾40 mg/day) showed similar results., Conclusion: Overall, this large Korean population-based study suggests no difference in the risk of non-fatal CV events and all-cause mortality between allopurinol and febuxostat initiators. These findings are consistent with the recent US Medicare population study, although the current study population consisted of younger Asians., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The small-molecule phosphodiesterase 4 inhibitor apremilast modulates cytokines that are up-regulated in Behçet's syndrome. In a phase 2 trial involving patients with Behçet's syndrome, apremilast reduced the incidence and severity of oral ulcers. Data on the efficacy and safety of apremilast in patients with Behçet's syndrome who had active oral ulcers and had not previously received biologic agents are limited., Methods: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who had Behçet's syndrome with active oral ulcers but no major organ involvement to receive either apremilast at a dose of 30 mg or placebo, administered orally, twice daily for 12 weeks, followed by a 52-week extension phase. The primary end point was the area under the curve (AUC) for the total number of oral ulcers during the 12-week placebo-controlled period (with lower values indicating fewer ulcers). There were 13 secondary end points, including complete response of oral ulcers, change from baseline in pain associated with oral ulcers, disease activity, and change from baseline in the Behçet's Disease Quality of Life score (range, 0 to 30, with higher scores indicating greater impairment in quality of life). Safety was also assessed., Results: A total of 207 patients underwent randomization (104 patients to the apremilast group and 103 to the placebo group). The AUC for the number of oral ulcers was 129.5 for apremilast, as compared with 222.1 for placebo (least-squares mean difference, -92.6; 95% confidence interval [CI], -130.6 to -54.6; P<0.001). The change from baseline in the Behçet's Disease Quality of Life score was -4.3 points in the apremilast group, as compared with -1.2 points in the placebo group (least-squares mean difference, -3.1 points; 95% CI, -4.9 to -1.3). Adverse events with apremilast included diarrhea, nausea, and headache., Conclusions: In patients with oral ulcers associated with Behçet's syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache. (Funded by Celgene; ClinicalTrials.gov number, NCT02307513.)., (Copyright © 2019 Massachusetts Medical Society.)

Purpose: The purpose of this study was to evaluate the effectiveness of conventional sandblasted, large-grit, acid-etched (SLA) surface coated with a pH buffering solution based on surface wettability, blood protein adhesion, osteoblast affinity, and platelet adhesion and activation., Methods: Titanium discs and implants with conventional SLA surface (SA), SLA surface in an aqueous calcium chloride solution (CA), and SLA surface with a pH buffering agent (SOI) were prepared. The wetting velocity was measured by the number of threads wetted by blood over an interval of time. Serum albumin adsorption was tested using the bicinchoninic acid assay and by measuring fluorescence intensity. Osteoblast activity assays (osteoblast adhesion, proliferation, differentiation, mineralization, and migration) were also performed, and platelet adhesion and activation assays were conducted., Results: In both the wetting velocity test and the serum albumin adsorption assay, the SOI surface displayed a significantly higher wetting velocity than the SA surface ( P =0.000 and P =0.000, respectively). In the osteoblast adhesion, proliferation, differentiation, and mineralization tests, the mean values for SOI were all higher than those for SA and CA. On the osteoblast migration, platelet adhesion, and activation tests, SOI also showed significantly higher values than SA ( P =0.040, P =0.000, and P =0.000, respectively)., Conclusions: SOI exhibited higher hydrophilicity and affinity for proteins, cells, and platelets than SA. Within the limits of this study, it may be concluded that coating an implant with a pH buffering agent can induce the attachment of platelets, proteins, and cells to the implant surface. Further studies should be conducted to directly compare SOI with other conventional surfaces with regard to its safety and effectiveness in clinical settings., Competing Interests: Conflict of Interest: Su-Kyoung Kim is a staff member and researcher at Osstem Implant Co., Ltd. and participated in the in vitro experiments and writing process. All other authors declare no conflict of interest associated with this study., (Copyright © 2019. Korean Academy of Periodontology.)

We investigated the optical and electrical properties of a β -Ga₂O₃/Ag/ β -Ga₂O₃ multilayer transparent conductive electrode deposited on an α -Al2O₃ (0001) substrate. For the deposition of a continuous Ag layer, we preliminarily performed anultraviolet-ozone pretreatment of the Ga₂O₃ bottom layer. To obtain a stable β -phase of Ga₂O₃, the β -Ga₂O₃/Ag/ β -Ga₂O₃ multilayer was annealed at 700 °C under N₂ atmosphere. The transmittance and sheet resistance of the β -Ga₂O₃/Ag/ β -Ga₂O₃ multilayer were critically affected by the surface morphology and thickness of the Ag interlayer. The multilayer with optimized thicknesses ( β -Ga₂O₃ top layer: 30 nm; Ag interlayer: 12 nm; β -Ga₂O₃ bottom layer: 60 nm) exhibited a resistance of 8.48 Ωsq -1 , an average optical transmittance of 87.16% in the ultraviolet wavelength range from 300 to 350 nm, and a figure of merit of 29.81 × 10 -3 Ω -1 .

Aim: This study aimed to investigate the clinical features and risk factors of gout attacks during anti-tuberculosis (TB) treatment in South Korea., Method: We investigated the clinical characteristics of 49 patients who suffered from gout attacks while taking anti-TB medications. Among them, 25 TB patients having newly developed gout attacks without prior history of gout were set to the gout group. Seventy-five age- and sex-matched TB patients without gout attacks during anti-TB therapy were randomly selected as the control group. The demographics, clinical features, and laboratory findings between the two groups were compared to establish risk factors of gout attack during anti-TB treatment., Results: The gout patients had a mean age of 67.7 ± 13.2 years and 39 patients (79.6%) were male. Approximately half of the patients experienced an attack within 2 months of treatment initiation. The attacks typically involved lower extremity joints (87.8%). The serum uric acid (SUA) levels were significantly elevated at 2 and 6 months after starting anti-TB medication compared with those at baseline. In the case-control study, the factors associated with gout attack were higher body mass index (BMI), higher pre-treatment SUA levels, dyslipidemia, and reduced renal function. In the multivariate model, higher BMI, chronic kidney disease (CKD), and pre-treatment hyperuricemia (SUA ≥ 6.8 mg/dL) were independent risk factors of gout attack while taking anti-TB medication., Conclusions: Patients with high BMI, CKD, and pre-treatment hyperuricemia are at a higher risk of gout attack during TB treatment., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: HLA genes are a major genetic risk factor for myositis and myositis specific antibodies (MSAs), exhibiting unique HLA backgrounds for myositis in different ethnic groups. This is the first large scale Korean study to genotype the HLA-DRB1 and -DPB1 alleles and to examine their association with myositis and MSAs., Methods: HLA-DRB1 and HLA-DPB1 alleles and MSAs were examined in 179 patients with dermatomyositis (DM, n = 129) or polymyositis (PM, n = 50) and healthy controls (n = 800 for HLA-DRB1, n = 548 for HLA-DPB1). Associations between individual HLA alleles and myositis/MSA were examined. Bonferroni correction was applied for multiple testing comparing patients and controls., Results: A total of 33 HLA-DRB1 and 24 HLA-DPB1 alleles were genotyped in patients and controls. MSAs were found in 67.0% of patients. Anti-MDA5 (26.8%) and anti-aminoacyl-tRNA synthetase antibodies (15.6%) were most common, followed by anti-Mi2 (9.5%) and anti-TIF1γ antibodies (8.9%). HLA-DRB1*12:02 and HLA-DRB1*14:03 were associated with DM and PM, respectively. HLA-DRB1*12:02 was associated with anti-MDA5, HLA-DRB1*08:03 with anti-ARS, HLA-DRB1*14:03 with anti-SRP, and HLA-DRB1*07:01 with anti-Mi2 antibodies. Although HLA-DRB1*13:01 was associated with anti-TIF1γ antibodies, the frequency of HLA-DRB1*13:01 was rare. HLA-DPB1*02:01 was negatively associated with myositis and PM while HLA-DPB1*17:01 was associated with anti-Mi2 positive DM., Conclusions: Unique immunogenetic background was observed for Korean patients with myositis. Novel myositis susceptibility alleles, HLA-DRB1*12:02 and HLA-DRB1*14:03, were identified, together with MSA-associated HLA alleles unique to Korean patients with myositis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To investigate the efficacy and safety of peficitinib, an oral Janus kinase inhibitor, in patients with rheumatoid arthritis (RA)., Methods: In this double-blind phase III study, patients with RA and an inadequate response to prior disease-modifying anti-rheumatic drugs (DMARDs) were randomised to peficitinib 100 mg once daily, peficitinib 150 mg once daily, placebo or open-label etanercept for 52 weeks' treatment; placebo-treated patients were switched at week 12 to peficitinib 100 or 150 mg once daily. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12/early termination (ET). Secondary endpoints (assessed throughout) included ACR20, ACR50 and ACR70 response, changes from baseline in disease activity scores (DAS)28 and ACR core parameters, adverse events (AEs) and changes in clinical or laboratory measurements., Results: In total, 507 patients received treatment. ACR20 response rates at week 12/ET were significantly higher in the peficitinib 100 mg (57.7%) and 150 mg (74.5%) groups versus placebo (30.7%) (p<0.001). ACR50/70 response rates were also higher for both peficitinib doses versus placebo. Improvements in ACR response were maintained until week 52. Changes from baseline in DAS28-C-reactive protein/erythrocyte sedimentation rate and the ACR core set were significantly greater for both peficitinib doses versus placebo at week 12/ET (p<0.001). AE incidence was similar across treatment arms. Incidence of serious infection and herpes zoster-related disease was higher with peficitinib versus placebo, but with no clear dose-dependent increase., Conclusions: In patients with RA and inadequate response to DMARDs, peficitinib 100 mg once daily or 150 mg once daily was efficacious in reducing RA symptoms and was well tolerated compared with placebo., Trial Registration Number: NCT02308163., Competing Interests: Competing interests: YT reports speaking fees and/or honoraria from Daiichi Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, AbbVie, Pfizer, YL Biologics, Bristol-Myers Squibb, GlaxoSmithKline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen and Asahi Kasei, and research grants from Mitsubishi Tanabe, Bristol-Myers Squibb, Eisai, Chugai, Takeda, AbbVie, Astellas, Daiichi Sankyo, Ono, MSD and Taisho Toyama. TT has received grants from Astellas Pharma, Inc., Chugai Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Takeda Pharmaceutical Co. Ltd, AbbVie GK, Asahi Kasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan, Inc., Eisai Co. Ltd, AYUMI Pharmaceutical Corp., Nippon Kayaku Co. Ltd, and Novartis Pharma K.K.; speaking fees from AbbVie GK, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma Co., Pfizer Japan, Inc., Astellas Pharma, Inc., Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Sanofi K.K., Teijin Pharma Ltd, Takeda Pharmaceutical Co. Ltd, and Novartis Pharma K.K.; consultancy fees from Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., AbbVie GK, Nippon Kayaku Co. Ltd, Janssen Pharmaceutical K.K., Astellas Pharma, Inc., Taiho Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd, Taisho Toyama Pharmaceutical Co. Ltd, GlaxoSmithKline K.K., and UCB Japan Co. Ltd. ST reports personal fees from Amgen, Inc., Asahi Kasei Pharma Corporation, Amgen Astellas BioPharma K.K., Ono Pharmaceutical Co. Ltd, KYOCERA Medical Corporation, Daiichi Sankyo Co. Ltd, Teijin Pharma Ltd, Eli Lilly Japan K.K., and Pfizer Japan, Inc.; endowments from Astellas Pharma, Inc., AYUMI Pharmaceutical Corporation, Pfizer Japan, Inc., Bristol-Myers Squibb, Daiichi Sankyo Co. Ltd, and Chugai Pharmaceutical Co. Ltd; and grants from Japan Agency for Medical Research and Development (AMED), Japan Society for the Promotion of Science (JSPS)/Grant-in-Aid for Scientific Research (A), and Japan Society for the Promotion of Science (JSPS)/Grant-in-Aid for Exploratory Research outside the submitted work. AK reports grants from AbbVie, Eisai, Mitsubishi-Tanabe, Pfizer Japan, Takeda Pharmaceutical, Astellas Pharma, MSD, Ono Pharmaceutical, Teijin Pharma, Kyowa Hakko-Kirin, Sumitomo-Dainippon Pharma, Kissei Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Otsuka Pharmaceutical, Chugai Pharmaceutical, Santen Pharmaceutical and Daiichi Sankyo; participation in speakers’ bureaux for AbbVie, Eisai, Takeda Pharmaceutical, Ono Pharmaceutical, Astellas Pharma, Mitsubishi-Tanabe, Pfizer Japan, Chugai Pharmaceutical, MSD, and Bristol-Myers Squibb K.K.; and consultant fees from Astellas Pharma and Janssen Pharmaceutical K.K. YWS reports a grant from Astellas Pharma, Inc.YHC reports grants for research and clinical trials from Taiwan Ministry of Science and Technology, Taiwan Department of Health, Taichung Veterans General Hospital, National Yang-Ming University, GlaxoSmithKline, Pfizer, Bristol-Myers Squibb, Novartis, AbbVie, Johnson & Johnson, Roche, Sanofi, Chugai Pharma Taiwan Ltd, Boehringer Ingelheim, UCB, MSD, AstraZeneca and Astellas; and honoraria and consultant fees from Pfizer, Novartis, AbbVie, Johnson & Johnson, Bristol-Myers Squibb, Roche, Lilly, GlaxoSmithKline, AstraZeneca, Sanofi, MSD, Chugai Pharma Taiwan Ltd, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma and Thermo Fisher. MR, HI, SU, YK, RA, TS and EY are employees of Astellas Pharma, Inc., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis and pachydermia with defects in the degradation of prostaglandin E2 (PGE2). Mutations in SLCO2A1 gene-encoding prostaglandin transporter (PGT) resulted in PHO, autosomal recessive 2 (PHOAR2). The spectrum of mutations and variable clinical complications of PHOAR2 has been delineated. In this study, we investigated a Chinese PHO family with a manifestation of Bartter-like hypokalemia., Methods: Clinical manifestations were collected and genetic analyses were performed in the PHO family., Results: The 33-year-old male proband had severe hypokalemia due to potassium loss from the kidney, while his brother had mild hypokalemia. After being treated with etoricoxib, the serum potassium level of the patient increased rapidly to the normal range which corresponded with the reduction in his serum PGE2 and PE2 metabolite (PGEM) levels. A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in this family., Conclusions: The present findings supported that the Bartter-like hypokalemia is a new complication of PHOAR2 caused by the high level of PGE2. Etoricoxib was demonstrated to be effective for the renal hypokalemia in PHO patients.

Lithium-sulfur (Li-S) batteries hold great promise to serve as next-generation energy storage devices. However, the practical performances of Li-S batteries are severely limited by the sulfur cathode regarding its low conductivity, huge volume change, and the polysulfide shuttle effect. The first two issues have been well addressed by introducing mesoporous carbon hosts to the sulfur cathode. Unfortunately, the nonpolar nature of carbon materials renders poor affinity to polar polysulfides, leaving the shuttling issue unaddressed. In this contribution, atomic cobalt is implanted within the skeleton of mesoporous carbon via a supramolecular self-templating strategy, which simultaneously improves the interaction with polysulfides and maintains the mesoporous structure. Moreover, the atomic cobalt dopants serve as active sites to improve the kinetics of the sulfur redox reactions. With the atomic-cobalt-decorated mesoporous carbon host, a high capacity of 1130 mAh g S -1 at 0.5 C and a high stability with a retention of 74.1% after 300 cycles are realized. Implanting atomic metal in mesoporous carbon demonstrates a feasible strategy to endow nanomaterials with targeted functions for Li-S batteries and broad applications., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018., Methods: Based on results from international focus groups and Delphi surveys, a draft core set was developed., Results: Domains muscle symptoms, fatigue, level of physical activity, and pain reached ≥ 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018., Conclusion: We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections.

Objectives: To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis., Methods: This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis., Results: One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001-0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2-1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1-8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001-2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3-71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17-226)) was lower than the number needed to harm by serious ADR (45 (15-∞))., Conclusion: Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.

Objectives: We examined the association between socioeconomic status (SES) and comorbidity distribution among patients with RA., Methods: Information on comprehensive health status of 1088 RA patients (weighted n = 612 303) was obtained from the 2007-2015 Korea National Health and Nutrition Examination Survey database. SES components were household equivalence income, education and area of residence. To minimize confounding by age, patients were stratified by median age (63 years). Age-adjusted odds ratio (OR) with 95% confidence interval (95% CI) was estimated, comparing weighted prevalence of individual comorbidities between low and high SES groups in each age stratum., Results: Among RA patients aged <63 years (mean 49 years, 70% female), we observed age-adjusted associations of depression (OR 2.13, 95% CI 1.01, 4.53), depressive mood (OR 2.68, 95% CI 1.54, 4.65), suicide ideation (OR 3.01, 95% CI 1.79, 5.07), diabetes (OR 3.09, 95%CI 1.31, 7.29), obesity (OR 2.04, 95% CI 1.30, 3.20), hypertriglyceridemia (OR 2.36, 95% CI 1.28, 4.34) and osteoarthritis (OR 2.12, 95% CI 1.13, 3.99) with low income, of suicide ideation with low education (OR 2.25, 95% CI 1.14, 4.44), but no association of any comorbidities with area of residence. Unhealthy behavior patterns were comparable between low- and high-income groups but patients with low income reported a numerically higher rate of failed access to necessary healthcare services. We did not find any association between SES and comorbidities among those aged ⩾63 years (mean 72 years, 83% female)., Conclusion: Among Korean RA patients aged <63 years, socioeconomic inequalities of multiple comorbidities in mental, cardiometabolic and musculoskeletal systems were found., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/aims: This study aimed to investigate the inf luence of poor sleep quality on clinical features of primary Sjögren's syndrome (pSS)., Methods: Sleep quality was cross-sectionally assessed using the Pittsburgh Sleep Quality Index (PSQI), and demographic, clinical, and laboratory data were collected from 115 Korean patients with pSS. The patients completed questionnaires on the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI), quality of life (EuroQOL five dimensions questionnaire [EQ-5D]), fatigue (fatigue severity score [FSS]), and depression (Beck Depression Inventory [BDI] II]). Symptoms and patient global assessment (PGA) were evaluated with a 100-mm visual analogue scale (VAS). The EULAR sicca score (ESS), ESSPRI, and EULAR SS Disease Activity Index (ESSDAI) were calculated at study enrollment., Results: Fifty-three patients (46.1%) had poor sleep quality and 32.4% of 71 patients without depression were poor sleepers. Poor sleepers had a significantly lower EQ-5D or ESSDAI and a significantly higher FSS, BDI-II, PGA, ESS, ESSPRI, or VAS scores for extra-glandular symptoms than good sleepers. Neutrophil and lymphocyte counts were significantly higher and immunoglobulin G levels tended to decrease in poor sleepers. Additionally, PSQI was negatively correlated with EQ-5D and ESSDAI and positively with ESS, FSS, BDI-II, PGA, VAS scores for their symptoms, and ESSPRI. Multivariate analysis revealed that poor sleep quality remained the independent determinants of the unsatisfactory symptom state (ESSPRI ≥ 5)., Conclusion: Our results showed that poor sleep quality could significantly affect the patient-oriented outcomes and physician-reported activity index of pSS patients through the various effects of sleep quality on the psychological or somatic symptoms and the immune system.