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Objective: Although the close interactions between the epidermis and dermis of the skin have been widely explored, the skin barrier functions of the stratum corneum (SC) in patients with systemic sclerosis (SSc) and primary Sjögren's syndrome (pSS) are not well known. We aimed to investigate the biophysical characteristics of the skin, including transepidermal water loss (TEWL), the SC water content, erythema, and the melanin index, in patients with SSc and pSS., Methods: This case-control study included 34 patients with SSc, 31 patients with pSS, and 25 healthy controls. All parameters were measured on the extensor surface of the forearm and compared between patients and healthy controls. In patients with SSc, we performed subgroup analyses by disease subtype (diffuse and limited cutaneous SSc), the modified Rodnan skin sclerosis score (>6 or ≤6), and comorbid secondary SS status. In patients with pSS, subgroup analyses were performed by anti-Ro/SSA antibody status and the findings of salivary gland ultrasound., Results: No statistically significant differences were observed in TEWL or skin hydration between patients with SSc and pSS and healthy controls. In the pSS group, only the erythema index was significantly increased compared to the control group. In subgroup analyses, no significant differences were observed in the extent of TEWL or skin hydration by disease subtype, severity, autoantibody profile, or comorbidities., Conclusion: Patients with SSc or pSS did not exhibit specific impairments of skin barrier function or skin hydration. Further studies with larger sample sizes and age-matched controls are required., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, behavioral, and cognitive impairments and significant impacts on patient quality of life. This evidence-based review, conducted by the Korean Huntington Disease Society task force, systematically examines current pharmacological and nonpharmacological interventions for symptomatic management of HD. Following PRISMA guidelines, databases were searched for studies up to August 2022 that focused on 23 symptoms across four domains: motor, neuropsychological, cognition, and others. This review provides a comprehensive and systematic approach to the management of HD, highlighting the need for more high-quality clinical trials to develop robust evidence-based guidelines.

Background/aims: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD)., Methods: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation., Results: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable., Conclusion: Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

The exosome multiprotein complex plays a critical role in RNA processing and degradation. This system governs the regulation of mRNA quality, degradation in the cytoplasm, the processing of short noncoding RNA, and the breakdown of RNA fragments. We determined two crystal structures of exosome components from Thermoplasma acidophilum ( Taci ): one with a resolution of 2.3 Å that reveals the central components ( Taci Rrp41 and Taci Rrp42), and another with a resolution of 3.5 Å that displays the whole exosome ( Taci Rrp41, Taci Rrp42, and Taci Rrp4). The fundamental exosome structure revealed the presence of a heterodimeric complex consisting of Taci Rrp41 and Taci Rrp42. The structure comprises nine subunits, with Taci Rrp41 and Taci Rrp42 arranged in a circular configuration, while Taci Rrp4 is located at the apex. The RNA degradation capabilities of the Taci Rrp4:41:42 complex were verified by RNA degradation assays, consistent with prior findings in other archaeal exosomes. The resemblance between archaeal exosomes and bacterial PNPase suggests a common mechanism for RNA degradation. Despite sharing comparable topologies, the surface charge distributions of Taci Rrp4 and other archaea structures are surprisingly distinct. Different RNA breakdown substrates may be responsible for this variation. These newfound structural findings enhance our comprehension of RNA processing and degradation in biological systems.

Importance: Although intravascular ultrasonography (IVUS) guidance promotes favorable outcomes after percutaneous coronary intervention (PCI), many catheterization laboratories worldwide lack access., Objective: To investigate whether systematic implementation of quantitative coronary angiography (QCA) to assist angiography-guided PCI could be an alternative strategy to IVUS guidance during stent implantation., Design, Setting, and Participants: This randomized, open-label, noninferiority clinical trial enrolled adults (aged ≥18 years) with chronic or acute coronary syndrome and angiographically confirmed native coronary artery stenosis requiring PCI. Patients were enrolled in 6 cardiac centers in Korea from February 23, 2017, to August 23, 2021, and follow-up occurred through August 25, 2022. All principal analyses were performed according to the intention-to-treat principle., Interventions: After successful guidewire crossing of the first target lesion, patients were randomized in a 1:1 ratio to receive either QCA- or IVUS-guided PCI., Main Outcomes and Measures: The primary outcome was target lesion failure at 12 months, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. The trial was designed assuming an event rate of 8%, with the upper limit of the 1-sided 97.5% CI of the absolute difference in 12-month target lesion failure (QCA-guided PCI minus IVUS-guided PCI) to be less than 3.5 percentage points for noninferiority., Results: The trial included 1528 patients who underwent PCI with QCA guidance (763; mean [SD] age, 64.1 [9.9] years; 574 males [75.2%]) or IVUS guidance (765; mean [SD] age, 64.6 [9.5] years; 622 males [81.3%]). The post-PCI mean (SD) minimum lumen diameter was similar between the QCA- and IVUS-guided PCI groups (2.57 [0.55] vs 2.60 [0.58] mm, P = .26). Target lesion failure at 12 months occurred in 29 of 763 patients (3.81%) in the QCA-guided PCI group and 29 of 765 patients (3.80%) in the IVUS-guided PCI group (absolute risk difference, 0.01 percentage points [95% CI, -1.91 to 1.93 percentage points]; hazard ratio, 1.00 [95% CI, 0.60-1.68]; P = .99). There was no difference in the rates of stent edge dissection (1.2% vs 0.7%, P = .25), coronary perforation (0.2% vs 0.4%, P = .41), or stent thrombosis (0.53% vs 0.66%, P = .74) between the QCA- and IVUS-guided PCI groups. The risk of the primary end point was consistent regardless of subgroup, with no significant interaction., Conclusions and Relevance: Findings of this randomized clinical trial indicate that QCA and IVUS guidance during PCI showed similar rates of target lesion failure at 12 months. However, due to the lower-than-expected rates of target lesion failure in this trial, the findings should be interpreted with caution., Trial Registration: ClinicalTrials.gov Identifier: NCT02978456.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs., (© 2024. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Aging and menopause are associated with oxidative stress and inflammation. Here, we evaluated the antioxidant properties of pumpkin ( Cucurbita pepo L.) seed extract and assessed its ameliorative effects on aging- and menopause-related diseases using Saos-2 cells and ovariectomized rats. The seed extract had bioactive components that exhibited antioxidant activity. The extract increased the alkaline phosphatase (ALP) activity of Saos-2 cells. The oral administration of the extract to ovariectomized rats for 12 weeks decreased their body weight, fat weight, and cardiac risk indices. It also contributed to reductions in the levels of reactive oxygen species, oxidative stress, and inflammation, as assessed by measuring the serum levels of malondialdehyde and analyzing gene expression in rats. Furthermore, the administration of the extract also promoted an enhancement of the transcription of nuclear factor erythroid 2-related factor ( Nrf2 ), heme oxygenase-1 ( Ho-1 ), and catalase ( Cat ), involved in antioxidant activity; endothelial nitric oxide synthase ( eNos ), involved in vasculoprotective activity; and PR/SET domain 16 ( Prdm16 ) and peroxisome proliferator-activated receptor-gamma coactivator (Pgc1α ), involved in brown adipogenesis and thermogenesis. Our results using ovariectomized rats show that pumpkin seed extract may have ameliorative effects on menopause-related diseases by increasing ALP activity, evaluating the antioxidant system, ameliorating oxidative stress and thermogenesis, and enhancing lipid profiles.

The gut microbiome is well known for its influence on human physiology and aging. Therefore, we speculate that the gut microbiome may affect muscle strength in the same way as the host's own genes. To demonstrate candidates for gut microbes affecting muscle strength, we remodeled the original gut microbiome of mice into human intestinal microbiome through fecal microbiome transplantation (FMT), using human feces and compared the changes in muscle strength in the same mice before and three months after FMT. After comparing before and after FMT, the mice were divided into three groups based on the observed changes in muscle strength: positive, none, and negative changes in muscle strength. As a result of analyzing the α-diversity, β-diversity, and co-occurrence network of the intestinal microbial community before and after FMT, it was observed that a more diverse intestinal microbial community was established after FMT in all groups. In particular, the group with increased muscle strength had more gut microbiome species and communities than the other groups. Fold-change comparison showed that Eisenbergiella massiliensis and Anaeroplasma abactoclasticum from the gut microbiome had positive contributions to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense had negative effects. This study identifies candidates for the gut microbiome that contribute positively and those that contribute negatively to muscle strength.

Interstitial lung disease (ILD) is often observed in connective tissue diseases (CTDs), frequently in rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and inflammatory myositis. Early detection of ILDs secondary to rheumatic diseases is important as timely initiation of proper management affects the prognosis. Among many imaging modalities, high-resuloution computed tomography (HRCT) serves the gold standard for finding early lung inflammatory and fibrotic changes as well as monitoring afterwards because of its superior spatial resolution. Additionally, lung ultrasound (LUS) and magnetic resonance imaging (MRI) are the rising free-radiation imaging tools that can get images of lungs of CTD-ILD. In this review article, we present the subtypes of ILD images found in each CTD acquired by HRCT as well as some images taken by LUS and MRI with comparative HRCT scans. It is expected that this discussion would be helpful in discussing recent advances in imaging modalities for CTD-ILD and raising critical points for diagnosis and tracing of the images from the perspective of rheumatologists., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

Background and Purpose: The SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention (SUPERBRAIN) proved the feasibility of multidomain intervention for elderly people. One-quarter of the Korean population over 65 years of age has mild cognitive impairment (MCI). Digital health interventions may be cost-effective and have fewer spatial constraints. We aim to examine the efficacy of a multidomain intervention through both face-to-face interactions and video communication platforms using a tablet personal computer (PC) application in MCI., Methods: Three hundred participants aged 60-85 years, with MCI and at least one modifiable dementia risk factor, will be recruited from 17 centers and randomly assigned in a 1:1 ratio to the multidomain intervention and the waiting-list control groups. Participants will receive the 24-week intervention through the tablet PC SUPERBRAIN application, which encompasses the following five elements: managing metabolic and vascular risk factors, cognitive training, physical exercise, nutritional guidance, and boosting motivation. Participants will attend the interventions at a facility every 1-2 weeks. They will also engage in one or two self-administered cognitive training sessions utilizing the tablet PC application at home each week. They will participate in twice or thrice weekly online exercise sessions at home via the ZOOM platform. The primary outcome will be the change in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end., Conclusions: This study will inform the effectiveness of a comprehensive multidomain intervention utilizing digital technologies in MCI., Trial Registration: ClinicalTrials.gov Identifier: NCT05023057., Competing Interests: Conflict of Interest: CHH received research support from Eisai Korea Inc. SYM, CHH, JHJ, YKP, HRN, and SHC are shareholders of Rowan Inc. JHJ and SHC consult for PeopleBio Co. Ltd. JJ reported being an employee of Rowan Inc. MC reported being the head of Exercowork. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Korean Dementia Association.)

Objective: This is the first prospective cohort study of Huntington's disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers., Methods: From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups., Results: Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38-65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson-Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers' demographics, blood relation, and marital and social status did not affect the burden significantly., Conclusion: HD patients' neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

Flavonoids and phenolic acid are two of the rich polyphenols found in cinnamon ( Cinnamomum zeylanicum ). The effects of cinnamon extract on the inhibition of adipocyte differentiation in 3T3-L1 fibroblast cells and prohibitory lipid accumulation in male mice fed a high-fat diet were examined. Upon treating 3T3-L1 cells with cinnamon for 3 days, the cinnamon inhibited lipid accumulation and increased gene expression levels, such as those of adiponectin and leptin. In in vivo experiments, mice were randomized into four groups after a one-week acclimation period, as follows: normal diet, normal diet + 1% cinnamon extract, high-fat diet, and high-fat diet + 1% cinnamon extract. After 14 weeks of supplementation, we found that cinnamon extract increased the expression of lipolysis-related proteins, such as AMPK, p-ACC, and CPT-1, and reduced the expression of lipid-synthesis-related proteins, such as SREBP-1c and FAS, in liver tissue. Our results show that cinnamon extract may exhibit anti-obesity effects via the inhibition of lipid synthesis and adipogenesis and the induction of lipolysis in both 3T3-L1 fibroblast cells and mice fed a high-fat diet. Accordingly, cinnamon extract may have potential anti-obesity effects.

Background: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy., Methods: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters., Results: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline., Conclusions: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate neurofilament light chain (NfL), phosphorylated tau (p-Tau) and total tau (t-Tau) as plasma markers for clinical severity in Korean Huntington's disease (HD) cohort., Methods: Genetically-confirmed 67 HD patients participated from 13 referral hospitals in South Korea. The subjects were evaluated with the Unified Huntington's Disease Rating Scale (UHDRS), total motor score (TMS) and total functional capacity (TFC), Mini-Mental Status Examination (K-MMSE), Montreal Cognitive Assessment (MoCA-K), and Beck's depression inventory (K-BDI). We measured plasma NfL, p-Tau and t-Tau concentrations using single-molecule array (SIMOA) assays. Stages of HD were classified based on UHDRS-TFC score and plasma markers were analyzed for correlation with clinical severity scales., Results: Plasma NfL was elevated in both 6 premanifest and 61 full manifest HD patients compared to the reference value, which increased further from premanifest to manifest HD groups. The NfL level was not significantly correlated with UHDRS TMS or TFC scores in manifest HD patients. Plasma p-Tau was also elevated in HD patients (p = 0.038). The level was the highest in stage III-V HD (n = 30) group (post-hoc p < 0.05). The p-Tau was correlated with UHDRS TFC scores (adjusted p = 0.002). Plasma t-Tau neither differed among the groups nor associated with any clinical variables., Conclusions: This study supports plasma NfL being a biomarker for initial HD manifestation in Korean cohort, and a novel suggestion of plasma p-Tau as a potential biomarker reflecting the clinical severity in full-manifest HD., Competing Interests: Declaration of Competing Interest Authors declare that there is no conflict of interest in this work., (Copyright © 2023. Published by Elsevier B.V.)

The Pivot Mandu is an innovative device featuring a leak-tight adjustable 3D balloon spacer, incorporating inner mesh support, an outer e-PTFE layer, and a compliant balloon in the middle layer with a specialized detachable system. To assess its feasibility, proof of concept was rigorously evaluated through bench testing and survival porcine animal experiments. The results demonstrated successful remote inflation of the balloon system, with the balloon spacer exhibiting sustained patent and functional integrity over an extended observation period of up to 6 months. A noteworthy feature of the newly designed 3D balloon spacer is its capability for easy size adjustment during procedures, enhancing its adaptability and practicality in clinical settings. This three-layered 3D balloon spacer, with its established long-term patency, exhibits highly encouraging outcomes that hold promise in overcoming the current limitations of spacer devices for heart valve diseases. Given the compelling results from preclinical investigations, the translation of the Pivot Mandu into human trials is strongly warranted.

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

Introduction: Kyung-Ok-Ko (KOK) is a popular traditional medicine used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms in Asia. Pueraria lobata Ohwi ( P. lobata ) is rich in isoflavones and has been traditionally used in combination with other herbs to produce synergistic and pharmaceutical effects via a multi-target approach for disease treatment. We aimed to investigate the phytoestrogenic effects of KOK extract against postmenopausal symptoms in ovariectomized (OVX) rats and confirm its efficacy by mixing KOK and P. lobata extracts., Methods: OVX rats were daily oral administrated with KOK and KOK +  P. lobata mixture extracts (300-400 mg/kg) and their body weight and tail temperature were monitored for 12 weeks. The biochemical parameters, estradiol levels, and bone turnover markers were measured in the serum samples. Moreover, the estrogen receptor, ER-α and ER-β expression in the uterus and the uterus morphology were evaluated. AMPK, ATG1/ULK1, and mTOR protein expression in the liver were assessed., Results: The 12-week treatment with KOK and KOK +  P. lobata mixture extracts did not cause liver damage or hormonal changes in the OVX rats. The treatments reduced the high lipid accumulation-related body weight gain and the tail temperature increase that was induced by ovariectomy. Further, it exhibited protective effects against hyperlipidemia and osteoporosis. No significant difference was observed in uterine weight compared to the OVX-treated group, while endometrial thickness reduction inhibition was observed due to ovariectomy. Bone mineral density (BMD) and serum osteocalcin levels, which decreased in OVX rats, increased with both treatments. Western blotting analysis showed that ER-α and ER-β were not expressed in the treated rats, whereas these proteins were expressed in Sham-operated rats. No significant differences in the phosphorylation of AMPK were observed; however, the ATG1/ULK1 and mTOR protein phosphorylation levels were upregulated and downregulated in the treated rats compared to those of OVX rats, respectively., Conclusion: This is the first in vivo study observing the efficacy and synergistic effects of the mixture of KOK and P. lobata . Our results suggest the potential of KOK and KOK +  P. lobata mixture as an alternative therapy for alleviating menopausal symptoms., Competing Interests: YK, H-JK, and JJ were employed by Kwangdong Pharm Co. Ltd. The authors declare that this study received funding from Kwangdong Pharm Co. Ltd. The funder had the following involvement in the study: study design, investigation, and the decision to submit it for publication., (Copyright © 2023 Kim, Kim, Oh, Zhou, Ahn, Koo, Kim and Jang.)

Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

This single-center, retrospective study aimed to investigate the course and prognostic factors of patients with primary Sjögren syndrome-associated interstitial lung disease (pSS-ILD). We included 120 pSS patients who underwent at least two high-resolution computed tomography (HRCT) scans between 2013 and 2021. Clinical symptoms, laboratory data, HRCT findings, and pulmonary function test results were collected. Two thoracic radiologists reviewed the HRCT findings. In patients with pSS without ILD at baseline (n = 81), no development of ILD was found on follow-up (median, 2.8 years). In patients with pSS-ILD (n = 39), total disease extent, extent of coarse reticulation, and traction bronchiectasis increased on HRCT, whereas the extent of ground glass opacity (GGO) decreased at follow-up (median, 3.2 years) (each p < 0.001). In progressive group of pSS-ILD (48.7%), the extent of coarse reticulation and coarseness score of fibrosis were increased at follow-up (p < 0.05). Usual interstitial pneumonia pattern on CT (OR, 15.237) and follow-up duration (OR, 1.403) were independent risk factors for disease progression in patients with pSS-ILD. In both progressive and non-progressive pSS-ILD, GGO decreased, whereas the extent of fibrosis increased even after treatment with glucocorticoid and/or immunosuppressants. In conclusion, progression occurred in approximately half of the pSS-ILD patients with slow gradual deterioration. Our study identified a definite group of progressive pSS-ILD who did not respond to current anti-inflammatory treatment., (© 2023. The Author(s).)

Spondyloarthritis (SpA) is characterized by inflammatory back pain. Magnetic resonance imaging (MRI) was the earlier gold standard technique for detecting early inflammatory change. We reassessed the diagnostic utility of sacroiliac joint/sacrum (SIS) ratios of single-photon emission computed tomography/computed tomography (SPECT/CT) for identifying sacroiliitis. We aimed to investigate of SPECT/CT in diagnosing SpA using a rheumatologist's visual scoring of SIS ratios assessment. We conducted a single-center, medical records review study of patients with lower back pain who underwent bone SPECT/CT from August 2016 to April 2020. We employed semiquantitative visual bone scoring methods of SIS ratio. The uptake of each sacroiliac joint was compared to that of the sacrum (0-2). A score of 2 for the sacroiliac joint of either side was considered diagnostic of sacroiliitis. Of the 443 patients assessed, 40 had axial SpA (axSpA), 24 being radiographic axSpA and 16 being nonradiographic axSpA. The sensitivity, specificity, and positive and negative predictive values of SIS ratio of SPECT/CT for axSpA were 87.5%, 56.5%, 16.6%, and 97.8%, respectively. In receiver operating curve analysis, MRI better diagnosed axSpA than did SIS ratio of SPECT/CT. Although the diagnostic utility of SIS ratio of SPECT/CT was inferior to MRI, visual scoring of SPECT/CT affords high sensitivity and negative predictive value in axSpA. When MRI is inappropriate for certain patients, SIS ratio of SPECT/CT is an alternative tool for identifying axSpA in real practice.

Idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD) is often rapidly progressive with a poor prognosis; however, no standard therapeutic regimen has been identified. This study aimed to investigate the efficacy and safety of rituximab in IIM-ILD patients. Five patients who had been administered rituximab for IIM-ILD at least once between August 2016 and November 2021 were included. Lung function decline was compared one year before and after rituximab. Disease progression, defined as a greater than 10% relative decline in forced vital capacity (FVC) compared to the baseline, was also compared before and after treatment. Adverse events were recorded for safety analysis. Five IIM-ILD patients received eight cycles. FVC-predicted values significantly decreased from 6 months before rituximab administration to those at the baseline (54.1% predicted (pre-6 months) vs. 48.5% predicted (baseline), p = 0.043); however, the FVC decline stabilized after rituximab. The rate of disease progression before rituximab showed a tendency to decrease after rituximab (75% (before) vs. 12.5% (6 months after, p = 0.059) vs. 14.3% (12 months after, p = 0.102)). Three adverse events developed, but none resulted in death. Rituximab can stabilize lung function decline with tolerable safety in Korean IIM patients with refractory ILD.

Rheumatoid arthritis (RA) increases the risk of cardiovascular disease. This study aimed to evaluate the clinical outcomes of elderly patients with and without RA who underwent percutaneous coronary intervention (PCI). The Korean National Health Insurance Service claims database was used to extract data on 74,623 patients (14,074 with RA and 60,549 without RA) aged ≥ 65 years who were diagnosed with acute coronary syndrome and underwent PCI between 2008 and 2019. The primary outcome was survival of elderly patients with and without RA. The secondary outcome was survival in the RA subgroup. During a 10-year follow-up, the all-cause mortality survival rate was lower in patients with RA than that in patients without (53.7% vs. 58.3%, respectively, log-rank: p < 0.001). In the all-cause mortality RA subgroup, patients with elderly-onset RA had poor survival outcomes, whereas patients with young-onset RA had good survival outcomes compared with that in patients without RA (48.1% vs. 73.7% vs. 58.3%, respectively, log-rank: p < 0.001). Elderly patients with RA who underwent PCI had an increased mortality risk, particularly those with elderly rather than young-onset RA.

Background: Because human fetal ventral mesencephalic tissue grafts provide promising results in ameliorating Parkinson's disease-implicated motor dysfunctions, human fetal midbrain-derived dopamine neuronal precursor cells are considered good candidates for cell-based therapy for Parkinson's disease in that large quantities of cells can be supplied through a good manufacturing practice-compliant system., Objective: We conducted a prospective, phase I/IIa, dose-escalation, open-label "first-in-human" clinical trial with fetal neural precursor cells to assess their safety and therapeutic efficacy in patients with idiopathic Parkinson's disease., Methods: Fifteen patients were assigned to receive three different doses of cells (4 × 10 6 , 12 × 10 6 , and 40 × 10 6 cells) and completed a 12-month follow-up. The primary outcome was safety, by measuring the presence of grade 3 or higher cells according to National Cancer Institute guidelines and any contaminated cells. Secondary outcomes assessed motor and neurocognitive function, as well as the level of dopamine transporters, by positron emission tomography-computed tomography., Results: Although a pronation-supination and hand/arm movement performance was remarkably enhanced in all three groups (all P < 0.05), the medium- and high-dose-treated groups exhibited significant improvement in Unified Parkinson's Disease Rating Scale Part III only up to 26.16% and 40%, respectively, at 12 months after transplantation without any serious clinical complications or graft-induced dyskinesia in all patients. However, the motor improvements did not correlate with increase in the dopamine transporter on positron emission tomography images., Conclusions: Our results primarily demonstrate the safety and plausible dose-dependent efficacy of human fetal midbrain-derived dopamine neuronal precursor cells for idiopathic Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Background: Development of an accessible method to routinely evaluate the clonality of strains is needed in microbiology laboratories. We compared the discriminatory power of the Fourier-transform infrared (FTIR) spectroscopy-based IR Biotyper (Bruker Daltonics GmbH, Bremen, Germany) to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), using whole-genome sequencing (WGS) as the reference method., Methods: Eighty-three extended-spectrum β-lactamase-producing Escherichia coli isolates were tested using WGS, MALDI-TOF MS, and IR Biotyper. Simpson's diversity index (SDI), a statistical analysis for testing the homogeneity of a dendrogram, and the adjusted Rand index (aRI) were used to compare the discriminatory ability between typing tests., Results: The SDI (95% confidence interval) was 0.969 (0.952-0.985) for WGS, 0.865 (0.807-0.924) for MALDI-TOF MS, and 0.974 (0.965-0.983) for IR Biotyper. Compared with WGS, IR Biotyper showed compatible diversity, whereas MALDI-TOF MS did not. The concordance and aRI improved from 66.3% to 84.3% and from 0.173 to 0.538, respectively, for IR Biotyper versus MALDI-TOF MS with WGS as the reference method. IR Biotyper showed substantially improved performance in strain typing compared with MALDI-TOF MS., Conclusions: IR Biotyper is useful for diversity analysis with improved discriminatory power over MALDI-TOF MS in comparison with WGS as a reference method. IR Biotyper is an accessible method to evaluate the clonality of strains and could be applied in epidemiological analysis during an outbreak of a health care facility, as well as for research on the transmission of resistant bacteria in community settings.

Assessing fracture risk is important for managing patients with systemic sclerosis (SSc). Vertebral fracture (VF) is the most common fracture and is associated with future VF and non-VF. We aimed to evaluate the predictive value of FRAX, trabecular bone score (TBS), and bone mineral density (BMD) for VFs, compared to rheumatoid arthritis (RA) patients and postmenopausal women, and to identify risk factors for VFs in SSc. In this cross-sectional study, prevalent VFs, 10-year probability of major osteoporotic fracture by FRAX (FRAX-MOF), TBS, and BMD were assessed in women with SSc (n = 69) and RA (n = 58), and postmenopausal women (n = 38). Risk factors for osteoporosis, modified Rodnan total skin score (mRSS), organ involvement, and patterns of nailfold capillaroscopy (NFC) were also evaluated. The accuracy of BMD (T-score ≤ -2.5), TBS and FRAX-MOF, with and without TBS adjustment, to detect prevalent VF was assessed by determining the area under the receiver operating characteristic (ROC) curve. Patients with SSc (14.5%) and RA (17.2%) had significantly more VFs than postmenopausal women (0%) (P = .031). Non-significant differences were observed in TBS and BMD of all groups. The FRAX-MOF were higher in RA (9.2%) than SSc group (6.1%) and postmenopausal women (5.5%) (P < .001). Based on the ROC curve, TBS-adjusted FRAX-MOF (0.803) showed largest area under curve (AUC) to detect the prevalent VFs, followed by FRAX-MOF (0.796), TBS (0.765), and BMD (0.588) in the SSc group. In the RA group, FRAX-MOF had the largest AUC (0.896), followed by TBS-adjusted FRAX-MOF (0.863), TBS (0.736), and BMD (0.686). The cutoffs for FRAX-MOF and TBS-adjusted FRAX-MOF for detecting VFs were 8.95% and 9.7% for SSc, and 14.5% and 14% for RA. No association between VFs and SSc subtypes, organ involvement, mRSS or NFC patterns was found. FRAX-MOF, with or without TBS, had better predictive value for VFs than BMD and TBS in SSc. However, FRAX-MOF underestimated the probability of VFs in SSc compared with RA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Mechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations., Materials and Methods: This retrospective study included women with r-axSpA aged 19-49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2-4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0-522) and SIJ scores (0-40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs., Results: A total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1-Q3) CTSS at baseline in the delivery group and controls was 19 (16-23) and 20 (13.25-27.75), and the median progression was 1 (0-3) and 0 (0-1) during the median 2.9-year follow-up, respectively. The median (Q1-Q3) SIJ score at baseline in the delivery group and controls was 13 (8-22) and 11 (6-22), and the median progression was 1.5 (0-3) and 1 (0-2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method., Conclusion: Pregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Lee, Kim, Kim, Kim and Lee.)

Microbiome research has been on the rise recently for a more in-depth understanding of gout. Meanwhile, there is a need to understand the gut microbiome related to uric acid-lowering drug resistance. In this study, 16S rRNA gene-based microbiota analysis was performed for a total of 65 stool samples from 17 healthy controls and 48 febuxostat-treated gout patients (including 28 controlled subjects with decreased uric acid levels and 20 uncontrolled subjects with non-reduced uric acid levels). Alpha diversity of bacterial community decreased in the healthy control, controlled, and uncontrolled groups. In the case of beta diversity, the bacterial community was significantly different among groups (healthy control, controlled, and uncontrolled groups). Taxonomic biomarker analysis revealed the increased population of g-Bifidobacterium in healthy controls and g-Prevotella in uncontrolled patients. PCR further confirmed this result at the species level. Additionally, functional metagenomics predictions led to the exploration of various functional biomarkers, including purine metabolism. The results of this study can serve as a basis for developing potential new strategies for diagnosing and treating gout from microbiome prospects., (© 2022. Author(s).)

Purpose: To grasp public opinion accurately, we conducted an opinion poll on beliefs and attitudes toward physician-assisted suicide (PAS)., Methods: A randomized telephone survey ensuring a representative sample was conducted, 1,007 participants aged 18 years or older (response rate, 9.5%)., Results: The main results are as follows i) 61.1% of participants thought that the current social support system for terminally ill patients and their families is insufficient; ii) 60% of participants did not recognize the term "hospice and palliative care"; iii) 81.7% of participants would not like to receive life-sustaining treatment if there is no possibility of recovery; iv) 58.4% of participants would like to receive hospice and palliative care if they are diagnosed with a terminal illness; v) the priorities for dignified dying were preparing a support system to reduce the burden of care (28.6%), economic support including reduction of medical expenses (26.7%), expansion of hospice and palliative care services (25.4%), and legalization of PAS (13.6%); and vi) 58.3% of participants agreed that the expansion of hospice and palliative care should precede the legalization of PAS., Conclusion: Koreans currently want other efforts, including expansion of hospice and palliative care services, instead of the legalization of PAS., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by Korean Society for Hospice and Palliative Care.)

Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/ or publication of this article. Hanlim Pharmaceutical Company had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Hanlim Pharmaceutical Company.

A new device called the Pivot-TR system was designed to treat tricuspid regurgitation with a novel spacer crossing the valve vertically. Its unique atraumatic anchoring system composed of both the elephant long nose and the inferior vena cava spiral anchor, in addition to the relatively easy implantation mechanism, enabled easy retrieval of the system later on. The system showed promising feasibility and safety results in this swine-based animal experiment, which should encourage human translation study., Competing Interests: This work was supported by the Korea Medical Device Development Fund grant funded by the South Korean government (Ministry of Science and Information and Communication Technologies, Ministry of Trade, Industry and Energy, Ministry of Health and Welfare, and Ministry of Food and Drug Safety) (project no. RS-2020-KD000104, 1711138183). Tau-PNU Medical provided the Pivot-TR devices. Dr. J.W. Park is a medical consultant for Tau-PNU Medical. Dr. J.H. Kim is an inventor of the Pivot-TR device, is a stockholder of Tau-PNU-Medical; and is clinical director of Tau-PNU Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Copper oxide nanoparticles (CuO NPs) were intratracheally instilled into lungs at concentrations of 0, 0.15, and 1.5 mg/kg bodyweight to 7-week-old Sprague-Dawley rats. The cytotoxicity, immunotoxicity, and oxidative stress were evaluated, followed by proteomic analysis of bronchoalveolar lavage fluid (BALF) and lungs of rats. The CuO NPs-exposed groups revealed dose-dependent increases in total cells, polymorphonuclear leukocytes, lactate dyhydrogenase, and total protein levels in BALF. Inflammatory cytokines, including macrophage inflammatory protein-2 and tumor necrosis factor-α, were increased in the CuO NPs-treated groups. The expression levels of catalase, glutathione peroxidase-1, and peroxiredoxin-2 were downregulated, whereas that of superoxide dismutase-2 was upregulated in the CuO NPs-exposed groups. Five heat shock proteins were downregulated in rats exposed to high concentrations of CuO NPs. In proteomic analysis, 17 proteins were upregulated or downregulated, and 6 proteins were validated via Western blot analysis. Significant upregulation of 3-hydroxy-3-methylglutaryl-CoA synthase and fidgetin-like 1 and downregulation of annexin II, HSP 47 and proteasome α1 occurred in the CuO NPs exposed groups. Taken together, this study provides additional insight into pulmonary cytotoxicity and immunotoxicity as well as oxidative stress in rats exposed to CuO NPs. Proteomic analysis revealed potential toxicological biomarkers of CuO NPs, which also reveals the toxicity mechanisms of CuO NPs.

Background: Age-related changes and different patterns of salivary gland abnormalities according to age may affect the diagnostic performance of unstimulated salivary flow rate (USFR) and salivary gland ultrasound (SGUS) for primary Sjögren's syndrome (pSS). We aimed to evaluate the threshold and diagnostic performance of USFR and whether incorporating SGUS or replacing USFR with SGUS affects the performance of the ACR/EULAR criteria for pSS according to age., Materials and Methods: This medical chart review study included patients with suspected pSS who completed evaluations for pSS. Patients were classified based on age at pSS evaluation: elderly (≥65 years), middle-aged (40-64), and young (< 40). The USFR's optimal thresholds were evaluated using the ROC curve. The diagnostic performances of the USFR and modified ACR/EULAR criteria were compared., Results: In total, 239 pSS patients and 92 patients with idiopathic sicca syndrome were included. The cut-off of USFR ≤ 0.1 mL/min was irrelevant to age, demonstrating the best sensitivity (44.3-53.0%) and specificity (74.1-90.9%). SGUS had a significantly better AUC than USFR in the young ( p < 0.01) and middle-aged groups ( p < 0.01). The middle-aged group demonstrated better diagnostic performance of the ACR/EULAR criteria incorporating SGUS (AUC 0.957) ( p < 0.01) and criteria replacing USFR with SGUS (AUC 0.957) ( p < 0.001) compared to the original criteria (AUC 0.916). In the young and elderly groups, adding SGUS to the ACR/EULAR criteria or replacing USFR with SGUS did not significantly increase the AUC., Conclusions: The thresholds of USFR ≤ 0.1 mL/min was optimal, irrespective of age. Using SGUS can improve diagnostic accuracy of ACR/EULAR criteria by supplementing the USFR, especially in middle-aged patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Kim, Kim and Kim.)

Purpose: This study aimed to describe nurses' perceived needs and barriers to pediatric palliative care (PPC)., Methods: Mixed methods with an embedded design were applied. An online survey was conducted for nurses who participated in the End-of-Life Nursing Education Consortium- Pediatric Palliative Care (ELNEC-PPC) train-the-trainer program, of whom 63 responded. Quantitative data were collected with a survey questionnaire developed through the Delphi method. The 47 items for needs and 15 items for barriers to PPC were analyzed with descriptive statistics. Qualitative data were collected through open- ended questions and analyzed with topic modeling techniques., Results: The mean scores of most subdomains of the PPC needs were 3.5 or higher out of 4, and those of PPC barriers ranged from 3.22 to 3.56, indicating the items in the questionnaire developed in this study properly reflect each factor. The needs for PPC were divided into 4 categories "children and adolescents," "families," "PPC management system," and "community-based PPC." Meanwhile, PPC barriers were divided into 3 categories "healthcare delivery system," "healthcare provider," and "client." The keywords derived from the topic modeling were perception, palliative, children, and education for necessities and lack, perception, medical care, professional care providers, service, and system for barriers to PPC., Conclusion: In this study, by using mixed-methods, items of nurses' perceived needs and barriers to PPC were identified, categorized, and weighted, and their meanings were explored. For the stable establishment of PPC, the priority should be given to improving perceptions of PPC, establishing an appropriate system, and training professional care providers., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by Korean Society for Hospice and Palliative Care.)

Background: The predictors affecting the gait efficiency were not known for the arm sling, including general and stroke-related characteristics., Purpose: This study investigated the predictors of gait efficiency when walking with and without an arm sling in individuals with hemiplegia with shoulder subluxation., Methods: A total of 57 individuals with shoulder subluxation were recruited. Individuals assigned odd numbers walked with the arm sling first and those with even numbers walked without the arm sling first in a pre-post design. Outcome measures were the energy cost, energy consumption, and heart rate during a 6-min walk test and a 10-m walk test. Gait efficiency is defined as energy consumption divided by the distance walked, with lower energy costs reflecting higher gait efficiency. Age, MMSE scores adjusted for education, and significant variables ( p < .01) in the univariate analyses were entered into multiple regression analyses, to identify the predictors of changes of gait efficiency., Results: Energy cost and energy consumption were lower and walking endurance was higher when walking with an arm sling than when without an arm sling. Spasticity ( p = .02), shoulder pain ( p = .03), consistency of handedness and sling position worn ( p = .02), function of upper extremity ( p = .03) and walking aids ( p = .01) were predictors of gait efficiency., Conclusion: An arm sling may improve gait efficiency in individuals with hemiplegia and shoulder subluxation able to walk with a single cane, who have consistency in handedness and sling position, and with good upper extremity function, including no shoulder pain and reduced spasticity.

Objectives: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophe nyl)nortropane ( 18 F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting., Methods: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18 F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18 F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18 F-FP-CIT PET per participant and substantia nigra (SN)., Results: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18 F-FP-CIT PET (p > 0.05, for both SN and participant)., Conclusions: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism., Key Points: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

Lipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes., (© 2022. The Author(s).)

Introduction: Angiography remains the gold standard for guiding percutaneous coronary intervention (PCI). However, it is prone to suboptimal stent results due to the visual estimation of coronary measurements. Although the benefit of intravascular ultrasound (IVUS)-guided PCI is becoming increasingly recognised, IVUS is not affordable for many catheterisation laboratories. Thus, a more practical and standardised angiography-based approach is necessary to support stent implantation., Methods and Analysis: The Quantitative Coronary Angiography versus Intravascular Ultrasound Guidance for Drug-Eluting Stent Implantation trial is a randomised, investigator-initiated, multicentre, open-label, non-inferiority trial comparing the quantitative coronary angiography (QCA)-guided PCI strategy with IVUS-guided PCI in all-comer patients with significant coronary artery disease. A novel, standardised, QCA-based PCI protocol for the QCA-guided group will be provided to all participating operators, while the PCI optimisation criteria will be predefined for both strategies. A total of 1528 patients will be randomised to either group at a 1:1 ratio. The primary endpoint is the 12-month cumulative incidence of target-lesion failure defined as a composite of cardiac death, target-vessel myocardial infarction or ischaemia-driven target-lesion revascularisation. Clinical follow-up assessments are scheduled at 1, 6 and 12 months for all patients enrolled in the study., Ethics and Dissemination: Ethics approval for this study was granted by the Institutional Review Board of Asan Medical Center (no. 2017-0060). Informed consent will be obtained from every participant. The study findings will be published in peer-reviewed journal articles and disseminated through public forums and academic conference presentations. Cost-effectiveness and secondary imaging analyses will be shared in secondary papers., Trial Registration Number: NCT02978456., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We investigated the diagnostic value of the maximum standardized uptake value (SUV) at hand and wrist joints for differentiating rheumatic diseases via bone single-photon emission computed tomography (SPECT)/computed tomography (CT). A total of 84 patients manifesting hand and wrist pain (58 women; age, 49.8 ± 15.4 years) were finally diagnosed with rheumatoid arthritis (RA, n = 42), osteoarthritis (OA, n = 16), fibromyalgia (FM, n = 2), and other rheumatic diseases (n = 24). The SUV of each patient was measured in 32 joints including the distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal (MCP), and wrist joints bilaterally. Differences in pain and SUVs between specific rheumatic diseases were assessed using the chi-squared test or one-way analysis of variance. Using the highest SUV (hSUV) in each patient, the diagnostic performance in differentiating specific diseases was evaluated by receiver operating characteristic (ROC) curve analysis. Pain symptoms were present in 886 (33.0%) sites in a total of 2688 joints. In four joint groups (DIP, PIP, MCP, and wrist), the SUVs of joints with pain were significantly higher than those of pain-free joints (all P < 0.001). Active joint sites with higher SUVs than the median value of each joint group were the most common in RA (55.1%). RA showed the greatest hSUV in the PIP (3.0 ± 2.4), MCP (3.5 ± 3.4), and wrist (3.3 ± 1.9) joint groups. FM was characterized by the lowest hSUV of all joint groups. In ROC curve analysis, the cumulative hSUV of the PIP, MCP, and wrist joint groups showed good performance for evaluating RA (area under the curve (AUC), 0.668; P = 0.005). The summation of the hSUVs at all joint groups had an excellent predictive performance for FM (AUC, 0.878; P < 0.001). Consequently, the arthritic activity of the hand and wrist joints based on SUV differed according to specific rheumatic diseases. Quantitative SPECT/CT may provide objective information related to arthritic activity for differentiating specific rheumatic diseases., (© 2022. The Author(s).)

Objectives: To evaluate the pregnancy-related risk factors and incidence rate (IR) of systemic sclerosis (SSc) in primipara using the Health Insurance Review and Assessment database, covering all medical claims in South Korea., Methods: From the database, 2,260,952 primipara aged 18-49 years from 2008 to 2018 were identified. The patients were followed up after their index delivery until December 2019. A Cox proportional hazard analysis was performed to identify the association of pregnancy-related factors with SSc development., Results: The SSc IR was 0.62 cases per 100,000 patient-years. Primipara had a higher risk of developing SSc after 3 years postpartum than in the first 3 years of delivery (OR = 1.98, 95% CI: 1.36-2.78, p < .001). A multivariate analysis showed that older age (35-49 years) (HR = 2.14, 95% CI: 1.05-4.35, p = .037) and a Caesarean section (CS) (HR = 1.86, 95% CI: 1.10-3.15, p = .021) are risk factors for SSc. At 3 years postpartum, CS (HR = 2.97, 95% CI: 1.39-6.32, p = .005) and a female infant (HR = 2.28, 95% CI: 1.11-4.71, p = .026) were associated with SSc development., Conclusion: Having a CS, late childbirth, and a female infant are the risk factors for SSc in primipara. This study establishes the IR of SSc in primipara., (© 2021 Japan College of Rheumatology.)

Competing Interests: The authors declare no conflict of interest.

Background/aims: Systemic sclerosis (SSc) is associated with a wide range of gastrointestinal (GI) changes. The University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) instrument is a self-administered GI assessment instrument for patients with SSc. We developed a Korean version of the UCLA SCTC GIT 2.0 instrument and evaluated its reliability and internal consistency., Methods: The participants were 37 Korean patients with SSc. Translation and cross-cultural adaptation of the UCLA SCTC GIT 2.0 were performed according to international standardized guidelines. We evaluated reproducibility by calculating the intraclass correlation coefficients and assessed the internal consistency of the Korean version of the UCLA SCTC GIT 2.0. We assessed its construct validity by evaluating its correlations with the Short Form Health Survey version 2 and EQ-5D scores by means of Spearman correlation analyses., Results: Patients with SSc were mostly women (89.19%) with a mean age of 52.2 years, median disease duration of 24 months, and median modified Rodnan total skin score of 4. The median total GIT score on the UCLA SCTC GIT 2.0 was 0.3. The UCLA SCTC GIT 2.0 Korean version showed excellent internal consistency (Cronbach's α of total GIT score = 0.863). Most domains of the ULCA SCTC GIT 2.0 were correlated with those of the EuroQol (EQ)-5D score., Conclusion: The Korean version of the UCLA SCTC GIT 2.0 has acceptable internal consistency, reliability, and validity. Therefore, it can be used to assess GIT involvement in Korean patients with SSc.

Aging, a critical risk factor of several diseases, including neurodegenerative disorders, affects an ever-growing number of people. Cacao supplementation has been suggested to improve age-related neuronal deficits. Therefore, this study investigated the protective effects of raw cacao powder on oxidative stress-induced aging. Male Sprague-Dawley rats were divided into 4 groups: Control (C), D-galactose-induced aging (G), D-galactose injection with 10% (LC), and 16% (HC) cacao powder mixed diet. D-galactose (300 mg/3 mL/kg) was intraperitoneally injected into all but the control group for 12 weeks. Cacao supplemented diets were provided for 8 weeks. The levels of serum Malondialdehyde (MDA), Advanced Glycation End-products (AGEs), brain and liver MDA, the indicators of the D-galactose induced oxidative stress were significantly decreased in LC and HC but increased in G. The Acetylcholinesterase (AChE) activity of brain showed that the cholinergic impairment was significantly lower in LC, and HC than G. Furthermore, the expression levels of catalase (CAT), phospho-Akt/Akt, and procaspase-3 were significantly increased in LC and HC. In conclusion, cacao consumption attenuated the effects of oxidative stress, cholinergic impairment and apoptosis, indicating its potential in future clinical studies., (© 2021. The Author(s).)

Aim: To evaluate the ability of the trabecular bone score (TBS) to discriminate vertebral fracture (VF) and fragility fracture (FF) in patients with chronic inflammatory rheumatic diseases on long-term and low-dose glucocorticoid (GC) treatment and those without exposure to GC., Methods: This study assessed TBS and bone mineral density (BMD) in chronic GC users, defined as ≥2.5 mg/d of prednisone for >3 months (n = 89, mean age: 62.5 ± 11 years), and in controls (n = 59, mean age: 60.3 ± 9.6 years). Osteoporosis risk factors, radiographs of the thoracolumbar spine, non-VF history, osteoporosis drugs, and current/cumulative GC doses were collected. Patients were classified as high (TBS <1.23), intermediate (1.23-1.31), or low risk (>1.31), according to the fracture risk based on a recent meta-analysis., Results: The mean current dose and duration of GC treatment were 3.9 ± 1.9 mg/d and 3.9 ± 4.2 years, respectively. The prevalence of VF was significantly higher in chronic GC users than in controls (20.2% vs 5.1%, P = .010), although the prevalence of non-VF was similar (11.2% vs 5.1%). The GC group had significantly lower L1-L4 TBS and femur total BMD than did the controls (all with P < .01) without significantly different lumbar BMD. TBS (<1.31) showed a higher sensitivity for patients with VF and FF (83.3% and 81.8%, respectively) than with densitometric osteoporosis in the GC group (61.1% and 59.1%, respectively). Using the receiver operating characteristic curve, TBS <1.31 showed better diagnostic accuracy than TBS <1.23 and BMD in chronic GC users., Conclusion: TBS is more sensitive than BMD in detecting VF and FF in chronic GC users, even at a lower dose., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: To investigate whether human HLA-homozygous induced pluripotent stem cell (iPSC)-derived neural precursor cells (iPSC-NPCs) can provide functional benefits in Huntington's disease (HD), we transplanted them into the YAC128 transgenic HD mouse model., Materials and Methods: CHAi001-A, an HLA-homozygous iPSC line (A*33:03-B*44:03-DRB1*13:02), was differentiated into neural precursor cells, and then, they were transplanted into 6 months-old YAC128 mice. Various behavioural and histological analyses were performed for five months after transplantation., Results: Motor and cognitive functions were significantly improved in transplanted animals. Cells transplanted in the striatum showed multipotential differentiation. Five months after transplantation, the donor cells had differentiated into neurons, oligodendrocytes and astrocytes. Transplantation restored DARPP-32 expression, synaptophysin density, myelin basic protein expression in the corpus callosum and astrocyte function., Conclusion: Altogether, these results strongly suggest that iPSC-NPCs transplantation induces neuroprotection and functional recovery in a mouse model of HD and should be taken forward for clinical trials in HD patients., (© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Objective: To assess the clinical, laboratory, and salivary gland ultrasound (SGUS) characteristics of elderly-onset of primary Sjögren's syndrome (EopSS)., Methods: We included pSS patient from two referral hospitals over a 4-year period. The SGUS scores (0-48) and SG volumes were assessed. Clinical, laboratory, and SGUS data were compared according to age at onset: EopSS (≥65 years), adult-onset (AopSS) (≥40 and <65 years), and young-onset (YopSS) (<40 years)., Results: This cross-sectional study included a total of 221 patients, 43 (19.5%) of which had EopSS. Subjective sicca symptoms, results of the Schirmer's test, and unstimulated salivary flow rate revealed no significant differences between the groups. EopSS patients presented a significantly higher frequency of interstitial lung disease (ILD) (EopSS: 51.2% vs. AopSS: 13.5% vs. YopSS: 8.7%, P<0.001) and lower frequency of arthritis (7% vs. 22.6% vs. 39.1%, P<0.01). They also had significantly lower positivity of anti-Ro/SSA (51.2%) and anti-La/SSB (7.0%) and lower levels of rheumatoid factor, C4, and IgG. The EopSS group had significantly lower SGUS positivity (defined as total scores ≥14) (44.2% vs. 64.5% vs. 78.3%, P<0.05), lower SGUS scores, and smaller submandibular gland volume., Conclusion: We report a specific phenotype of EopSS, characterised by high prevalence of ILD, less involvement of the peripheral joint, and low biological activity. SGUS evaluation showed less parenchymal abnormalities but more atrophic changes in major SGs in EopSS patients. Considering the low positivity of anti-Ro/SSA and SGUS in EopSS, SG biopsy remains the only way to confirm the diagnosis of pSS, especially in elderly patients., (Copyright © 2021 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)