Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Costotransverse joint ankylosis and their association with syndesmophyte progression in patients with radiographic axial spondyloarthritis.

Background: Abnormal new bone formation can occur not only in the vertebral body but also can occur in facet, costovertebral, and costotransverse joints in radiographic axial spondyloarthritis (r-axSpA) patients. Little is known about the association between syndesmophyte progression and paravertebral joint ankylosis in r-axSpA. Objectives: Costotransverse joint ankylosis in r-axSpA patients was measured. Furthermore, the association between syndesmophyte progression for 2 years assessed by computed tomography syndesmophyte score (CTSS) and facet, costovertebral, and costotransverse joints ankylosis were evaluated. Design: Single-center, prospective, cohort study. Methods: Whole spine CT images taken at baseline and 2-year follow-up were used to calculate the CTSS of the vertebral body. In addition, ankylosis of the facet/costovertebral/costotransverse joints was scored. CTSS (range, 0-552) and facet joint ankylosis (range, 0-46) were assessed at 23 vertebral units. Costovertebral joints at T1-T12 (range, 0-48) and costotransverse joints at T1-T10 (range, 0-20) were also assessed by independent two readers. Intraclass correlation coefficients (ICC) were calculated to determine inter-reader reliability. Odds ratios (OR) were calculated to identify the associations between syndesmophyte progression and the baseline status of facet, costovertebral, and costotransverse joints. Results: In all, 50 patients with r-axSpA were included. Readers 1 and 2 identified C7-T3 (facet joints), T5-T7 and T12 (costovertebral joints), and T8-T9 (costotransverse joints), as common sites of ankylosis at baseline and at 2-year follow-up. The ICCs for the facet, costovertebral, and costotransverse joints at baseline were 0.876, 0.952, and 0.753, respectively. OR of baseline costovertebral and costotransverse joint ankylosis for predicting syndesmophyte progression of the vertebral body was 4.644 [95% confidence interval (CI), 2.295-9.398] and 1.524 (95% CI, 1.036-2.244), respectively. Conclusion: Costotransverse joint ankylosis in r-axSpA patients can be measured semi-quantitatively on whole spine CT, and ankylosis of the costotransverse and costovertebral joints predicts the progression of syndesmophytes.Trial registration: Not applicable.

RORα-GABP-TFAM axis alleviates myosteatosis with fatty atrophy through reinforcement of mitochondrial capacity.

BACKGROUND: Fat infiltration in muscle, called 'myosteatosis', precedes muscle atrophy, which subsequently results in sarcopenia. Myosteatosis is frequently observed in patients with nonalcoholic fatty liver disease (NAFLD). We have previously reported that retinoic acid receptor-related orphan receptor-α (RORα) regulates mitochondrial dynamics and mitophagy in hepatocytes, resulting in an alleviation of NAFLD. In this study, we aimed to investigate the role of RORα in skeletal muscle and to understand molecular mechanisms by which RORα controls mitochondrial capacity, using an NAFLD-associated myosteatosis mouse model. METHODS: To establish a myosteatosis model, 7-week-old C57BL/6N mice were fed with high-fat diet (HFD). After 15 weeks of diet feeding, an adeno-associated virus vector encoding RORα (AAV-RORα) was injected to gastrocnemius (GA) muscles, or after 7 weeks of HFD feeding, JC1-40, an RORα agonistic ligand, was administered daily at a dose of 5 mg/kg/day by oral gavage for 5 weeks. Histological, biochemical and molecular analyses in various in vivo and in vitro experiments were performed. RESULTS: First, the number of oxidative MyHC2a fibres with intensive lipid infiltration increased by 3.8-fold in the red region of the GA of mice with myosteatosis (P < 0.001). RORα was expressed around MyHC2a fibres, and its level increased by 2.7-fold after HFD feeding (P < 0.01). Second, treatment of RORα ligands in C2C12 myoblasts, such as cholesterol sulfate and JC1-40, enhanced the number of oxidative fibres stained for MyHC1 and MyHC2a by two-fold to four-fold (P < 0.01), while it reduced the lipid levels in MyHC2a fibres by 20-50% (P < 0.001) in the presence of palmitic acids. Third, mitochondrial membrane potential (P < 0.01) and total area of mitochondria (P < 0.01) were enhanced by treatment of these ligands. Chromatin immunoprecipitation analysis showed that RORα bound the promoter of GA-binding protein α subunit gene that led to activation of mitochondrial transcription factor A (TFAM) in C2C12 myoblasts (P < 0.05). Finally, intramuscular transduction of AAV-RORα alleviated the HFD-induced myosteatosis with fatty atrophy; lipid contents in MyHC2a fibres decreased by 48% (P < 0.001), whereas the number of MyHC2b fibre increased by 22% (P < 0.001). Also, administration of JC1-40 improved the signs of myosteatosis in that it decreased the level of adipose differentiation-related protein (P < 0.01) but increased mitochondrial proteins such as cytochrome c oxidase 4 and TFAM in GA muscle (P < 0.01). CONCLUSIONS: RORα plays a versatile role in regulating the quantity of mitochondria and the oxidative capacity, ultimately leading to an improvement in myosteatosis symptoms.

Automated non-contact measurement of the spine curvature at the sagittal plane using a deep neural network.

BACKGROUND: Non-radiographical techniques have been suggested to measure the spine curvature at the sagittal plane. However, a neural network has not been used to measure the curvature. METHODS: A single video camera captured images of a standing posture at the sagittal plane from twenty healthy males. Six marker positions along the spine's contour in each image were identified for measuring inclination, thoracic kyphosis, and lumbar lordosis angles. We estimated three inflection points around the neck, hip, and between the neck and hip, followed by identifying two adjacent marker positions per inflection point to compute its tangent. The angular deviation of each tangent line from the horizontal was computed to measure inclination angles. Thoracic kyphosis and lumbar lordosis angles were computed by the angular difference between the two adjacent tangents. A deep neural network was trained with 500,000 iterations using the labeled images from 18 participants (388 and 44 images for training and test set) and then evaluated using the unseen images (2 participants, 48 images; evaluation set). FINDINGS: The mean total training and test errors were <2 pixels (∼ 0.6 cm). The total error in the evaluation set was qualitatively comparable (∼ 3 pixels = âˆ¼ 0.9 cm), suggesting the model performance was maintained in the unseen data. The angle values between labeled and network-predicted marker positions were similar in the evaluation set. INTERPRETATION: The network training with a relatively small number of images was successful based on the small error values observed in the evaluation set. The model may be an affordable, automated, and non-contact measurement tool for the human spine curvature.

Anti-Allergic Inflammatory Effect of Agarum cribrosum and Its Phlorotannin Component, Trifuhalol A, against the Ovalbumin-Induced Allergic Asthma Model.

Asthma is a chronic inflammatory disease involving structural changes to the respiratory system and severe immune responses mediated by allergic cytokines and pro-inflammatory mediators. Agarum cribrosum (AC) is a kind of seaweed which contains a phlorotannin, trifuhalol A. To evaluate its anti-allergic inflammatory effect against asthma, an ovalbumin inhalation-induced mouse asthma model was used. Histologic observations proved that trifuhalol A is minimizing the lung and tracheal structure changes as well as the infiltration of eosinophils and mast cells against ovalbumin inhalation challenge. From the serum and bronchoalveolar lavage fluid, ovalbumin-specific IgE and Th2-specific cytokines, IL-4, -5, and -13, were reduced with trifuhalol A treatment. In addition, IL-1ß, IL-6, and TNF-α concentrations in lung homogenate were also significantly reduced via trifuhalol A treatment. Taken together, trifuhalol A, isolated from AC, was able to protect lung and airways from Th2-specific cytokine release, and IgE mediated allergic inflammation as well as the attenuation of IL-1ß, IL-6, and TNF-α in lung, which results in the suppression of eosinophils and the mast cells involved asthmatic pathology.

Development of microcatheter tube extrusion angle estimation system using convolutional neural network segmentation.

This study presents a deep learning-based monitoring system for estimating extrusion angles in the manufacturing process of microcatheter tubes. Given the critical nature of these tubes, which are directly inserted into the human body, strict quality control is imperative. To mitigate potential quality variations stemming from operator actions, a system utilizing a convolutional neural network to precisely measure the extrusion angle-a parameter with profound implications for tube quality-is developed. Until now, there has been no method to estimate the extrusion angle of resin being extruded in real-time. In this study, for the first time, a method using deep learning to estimate the angle was proposed. This innovative system comprises two RGB cameras capturing both front and side perspectives. The acquired images undergo segmentation via a meticulously trained convolutional neural network. Subsequently, the extrusion angle is accurately estimated through the application of principal component analysis on the segmented image. The usefulness of the proposed system was rigorously confirmed through comprehensive validation measures, including mean intersection over union (mIoU), mean absolute angle error (MAE), and inference time, using a real-world dataset. The attained metrics, with an mIoU of 0.8848, MAE of 0.5968, and an inference time of 0.0546, unequivocally affirm the system's suitability for enhancing the catheter tube extrusion process.

Cloud-based digital healthcare development for precision medical hospital information system.

Aim: This study aims to develop a cloud-based digital healthcare system for precision medical hospital information systems (P-HIS). Methods: In 2020, international standardization of P-HIS clinical terms and codes was performed. In 2021, South Korea's first tertiary hospital cloud was established and implemented successfully. Results: P-HIS was applied at Korea's first tertiary general hospital. Common data model-compatible precision medicine/medical service solutions were developed for medical support. Ultrahigh-quality medical data for precision medicine were acquired and built using big data. Joint global commercialization and dissemination/spreading were achieved using the P-HIS consortium and global common data model-based observational medical outcome partnership network. Conclusion: To provide personalized precision medical services in the future, establishing and using big medical data is essential.

The Clinical Outcomes of Syndesmotic Flexible Fixation for Syndesmotic Injury With Ankle Fracture.

BACKGROUND: We evaluated whether the quality of syndesmotic reduction affects the short-term clinical outcomes of flexible fixation in patients with a rotational ankle fracture. METHODS: This study included 59 patients (32 men and 27 women) who underwent syndesmotic flexible fixation. The degree of syndesmotic reduction was evaluated on computed tomography (CT) images acquired within 3 days after surgery. We measured the divergence between anterior and posterior incisura at 1 cm above the distal tibial articular joint, then evaluated the degree of fibular rotation relative to the tibia. At 1 year after surgery, an objective clinical evaluation was performed using the American Orthopaedic Foot & Ankle Society (AOFAS) score, the visual analog scale (VAS), and the Foot and Ankle Outcome Score (FAOS). Additionally, repeat arthroscopy was performed during routine implant removal at nearly 1 year postoperatively. RESULTS: Among 59 patients who underwent syndesmotic flexible fixation, 56 patients had syndesmotic stability on repeat arthroscopy. At 1 year postoperation, AOFAS, VAS, and FAOS scores were, respectively, 90, 2.0, and 94 in the accurate reduction group (n = 24) and 90, 1.0, and 94.5 in the malreduction group (n = 35). CONCLUSION: Reduction quality after syndesmotic injury with flexible fixation, as determined by early postoperative CT imaging, did not affect patient prognosis. In this cohort, syndesmotic reduction and flexible fixation may produce good clinical outcomes in patients with syndesmotic injury and ankle fracture. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Marine Bacterioplankton Community Dynamics and Potentially Pathogenic Bacteria in Seawater around Jeju Island, South Korea, via Metabarcoding.

Understanding marine bacterioplankton composition and distribution is necessary for improving predictions of ecosystem responses to environmental change. Here, we used 16S rRNA metabarcoding to investigate marine bacterioplankton diversity and identify potential pathogenic bacteria in seawater samples collected in March, May, September, and December 2013 from two sites near Jeju Island, South Korea. We identified 1343 operational taxonomic units (OTUs) and observed that community diversity varied between months. Alpha- and Gamma-proteobacteria were the most abundant classes, and in all months, the predominant genera were Candidatus Pelagibacter, Leisingera, and Citromicrobium. The highest number of OTUs was observed in September, and Vibrio (7.80%), Pseudoalteromonas (6.53%), and Citromicrobium (6.16%) showed higher relative abundances or were detected only in this month. Water temperature and salinity significantly affected bacterial distribution, and these conditions, characteristic of September, were adverse for Aestuariibacter but favored Citromicrobium. Potentially pathogenic bacteria, among which Vibrio (28 OTUs) and Pseudoalteromonas (six OTUs) were the most abundant in September, were detected in 49 OTUs, and their abundances were significantly correlated with water temperature, increasing rapidly in September, the warmest month. These findings suggest that monthly temperature and salinity variations affect marine bacterioplankton diversity and potential pathogen abundance.

Application of specialized word embeddings and named entity and attribute recognition to the problem of unsupervised automated clinical coding.

Notes documented by clinicians, such as patient histories, hospital courses, lab reports and others are often annotated with standardized clinical codes by medical coders to facilitate a variety of secondary processing applications such as billing and statistical analyses. Clinical coding, traditionally manual and labor-intensive, has seen a surge in research interest by deep learning researchers pursuing to automate it. However, deep learning methods require large volumes of annotated clinical data for training and offer little to explain why codes were assigned to pieces of text. In this paper, we propose an unsupervised method which does not need annotated clinical text and is fully interpretable, by using Named Entity and Attribute Recognition and word embeddings specialized for the clinical domain. These methods successfully glean important information from large volumes of clinical notes and encode them effectively in order to perform automatic clinical coding.

Primary Production in the Kara, Laptev, and East Siberian Seas.

Understanding of the primary production of phytoplankton in the Kara Sea (KS), the Laptev Sea (LS), and the East Siberian Sea (ESS) remains limited, despite the recognized importance of phytoplankton in the Arctic Ocean. To address this knowledge gap, we conducted three NABOS (Nansen and Amundsen Basins Observational System) expeditions in 2013, 2015, and 2018 to measure in situ primary production rates using a 13C-15N dual-tracer method and examine their major controlling factors. The main goals in this study were to investigate regional heterogeneity in primary production and derive its contemporary ranges in the KS, LS, and ESS. The daily primary production rates in this study (99 ± 62, 100 ± 77, and 56 ± 35 mg C m-2 d-1 in the KS, LS, and ESS, respectively) are rather different from the values previously reported in each sea mainly because of spatial and regional differences. Among the three seas, a significantly lower primary production rate was observed in the ESS in comparison to those in the KS and LS. This is likely mainly because of regional differences in freshwater content based on the noticeable relationship (Spearman, rs = -0.714, p < 0.05) between the freshwater content and the primary production rates observed in this study. The contemporary ranges of the annual primary production based on this and previous studies are 0.96-2.64, 0.72-50.52, and 1.68-16.68 g C m-2 in the KS, LS, and ESS, respectively. Further intensive field measurements are warranted to enhance our understanding of marine microorganisms and their community-level responses to the currently changing environmental conditions in these poorly studied regions of the Arctic Ocean.

Nailfold capillaroscopy findings of interstitial pneumonia with autoimmune features.

BACKGROUND/AIMS: We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP). METHODS: Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined. RESULTS: A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern. CONCLUSION: NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.

Effect of music on colonoscopy performance: A propensity score-matched analysis.

BACKGROUND: Music has been used to reduce stress and improve task performance during medical therapy. AIM: To assess the effects of music on colonoscopy performance outcomes. METHODS: We retrospectively reviewed patients who underwent colonoscopy performed by four endoscopists with popular music. Colonoscopy performance outcomes, such as insertion time, adenoma detection rate (ADR), and polyp detection rate (PDR), were compared between the music and non-music groups. To reduce selection bias, propensity score matching was used. RESULTS: After one-to-one propensity score matching, 169 colonoscopies were selected from each group. No significant differences in insertion time (4.97 vs 5.17 min, P = 0.795) and ADR (39.1% vs 46.2%, P = 0.226) were found between the two groups. Subgroup analysis showed that the insertion time (3.6 vs 3.8 min, P = 0.852) and ADR (51.1% vs 44.7%, P = 0.488) did not significantly differ between the two groups in experts. However, in trainees, PDR (46.9% vs 66.7%, P = 0.016) and ADR (25.9% vs 47.6%, P = 0.006) were significantly lower in the music than in the non-music group. CONCLUSION: The current study found that listening to music during colonoscopy did not affect procedure performance. Moreover, it suggested that music may distract trainees from appropriately detecting adenomas and polyps.

Spatio-temporal variations in organic carbon composition driven by two different major phytoplankton communities in the Ross Sea, Antarctica.

The compositions of organic carbon could be important in determining biological carbon pump efficiency. However, little information on them in relation to each algal assemblage is currently available in the Ross Sea. Here, we investigated the seasonal variations in organic carbon composition and the relative abundance of each organic carbon, including particulate organic carbon (POC), dissolved organic carbon (DOC), and transparent exopolymer particles (TEPs), characterized by different algal groups in the Ross Sea. The average POC and DOC contributions to the total organic carbon (TOC = POC + DOC) were 13.8 ± 3.7 % and 86.2 ± 3.7 % in mid-January 2019 and 20.9 ± 4.1 % and 79.1 ± 4.1 % in February-March 2018, respectively. The carbon content of TEP (TEP-C) contributed 19.6 ± 11.7 % and 4.6 ± 7.0 % of POC and TOC in mid-January and 36.2 ± 14.8 % and 9.0 ± 6.7 % in February-March, respectively. We found that the organic carbon compositions were affected by seasonal variations in the phytoplankton bloom phase, physical characteristics, and phytoplankton community structure. DOC concentrations and contributions to the TOC increased as phytoplankton cells became senescent in mid-January and decreased in February-March when phytoplankton were relatively active. From February-March, the deepened mixed layer depth encouraged TEP formation, subsequently increasing the TEP contributions. Regardless of the sampling season, all organic carbon concentrations per unit Chl-a were significantly higher in P. antarctica-abundant groups. The DOC contributions to the TOC were correspondingly higher at the P. antarctica-abundant stations in mid-January, which indicates that P. antarctica could be also important in the DOC contributions in the Ross Sea. The rapid alteration in environmental characteristics and phytoplankton community structures in the Ross Sea due to climate change could affect the organic carbon pool at the euphotic layer which consequently could determine the efficiency of the biological pump.

The Superficial Peroneal Nerve Is at Risk during the "All Inside" Arthroscopic Broström Procedure: A Cadaveric Study.

Background: The arthroscopic Broström procedure is a promising treatment for chronic ankle instability. However, little is known regarding the location of the intermediate superficial peroneal nerve at the level of the inferior extensor retinaculum; knowledge about this location is important for procedural safety. The purpose of this cadaveric study was to clarify the anatomical relationship between the intermediate superficial peroneal nerve and the sural nerve at the level of the inferior extensor retinaculum. Methods: Eleven dissections of cadaveric lower extremities were performed. The origin of the experimental three-dimensional axis was defined as the location of the anterolateral portal during ankle arthroscopy. The distances from the standard anterolateral portal to the inferior extensor retinaculum, sural nerve, and intermediate superficial peroneal nerve were measured using an electronic digital caliper. The location of inferior extensor retinaculum, the tract of sural nerve, and intermediate superficial peroneal nerve were checked using average and standard deviations. For the statistical analyses, data are presented as average ± standard deviation, and then they are reported as means and standard deviations. Fisher's exact test was used to identify statistically significant differences. Results: At the level of the inferior extensor retinaculum, the mean distances from the anterolateral portal to the proximal and distal intermediate superficial peroneal nerve were 15.9 ± 4.1 (range, 11.3-23.0) mm and 30.1 ± 5.5 (range, 20.8-37.9) mm, respectively. The mean distances from the anterolateral portal to the proximal and distal sural nerve were 47.6 ± 5.7 (range, 37.4-57.2) mm and 47.2 ± 4.1 (range, 41.0-51.8) mm), respectively. Conclusions: During the arthroscopic Broström procedure, the intermediate superficial peroneal nerve may be damaged by the anterolateral portal; the proximal and distal parts of the intermediate superficial peroneal nerve were located within 15.9 and 30.1 mm, respectively, at the level of the inferior extensor retinaculum in cadavers. These areas should be considered danger zones during the arthroscopic Broström procedure.

Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice.

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis.

Comparisons of treatment satisfaction and health-related quality of life in patients with rheumatoid arthritis treated with tofacitinib and adalimumab.

BACKGROUND: As significant advances in the field of treatment for rheumatoid arthritis (RA), there is a great need to identify the healthcare outcomes such as treatment satisfaction and health-related quality of life (HRQoL) of patients with various treatment options. This study aims to identify the difference in the treatment satisfaction and HRQoL of patients with RA using different treatment options, by comparing the treatment satisfaction and HRQoL in patients with RA treated with tofacitinib and adalimumab in real-world settings in Korea, using propensity score methods. METHODS: In this non-interventional, multicenter, cross-sectional study (NCT03703817), a total of 410 patients with RA diagnosis were recruited in 21 university-based hospitals throughout Korea. The treatment satisfaction and HRQoL were assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) and EQ-5D questionnaires self-reported by the patients. This study compared outcomes between two drug groups in unweighted, greedy matching, and stabilized inverse probability of treatment weight (IPTW) samples using propensity score. RESULTS: In all three samples, tofacitinib group showed higher convenience domain of TSQM than that in the adalimumab group, but not effectiveness, side effects, and global satisfaction domains. Multivariable analysis using the covariates of demographic and clinical characteristics of the participants also showed consistent results in TSQM. No statistical difference in EQ-5D-based HRQoL was identified between two drug groups in all three samples. CONCLUSIONS: This study identified that tofacitinib shows higher treatment satisfaction in the convenience domain of TSQM rather than adalimumab, suggesting that various factors such as drug formulation, route or frequency of administration, and storage can have an impact on the treatment satisfaction, especially the convenience domain. These findings may be useful to patients and physicians when determining treatment options. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03703817.

Interleukin-18 binding protein regulates the apoptosis and necroptosis of fibroblast-like synoviocytes and chondrocytes in rheumatoid arthritis.

OBJECTIVES: Interleukin (IL)-18 plays a pro-inflammatory role in rheumatoid arthritis (RA), and its soluble inhibitor IL-18 binding protein (IL-18BP) has a potential therapeutic role. We investigated the role of IL-18BP on the joint destruction process of RA by accessing the effects of IL-18BP on fibroblast-like synoviocytes (FLSs) and chondrocytes. METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls were cultured under T cell proliferative conditions with 10, 50, or 100 ng/mL of IL-18BP. After three days of culture, flow cytometry for CD4+ T cells was performed using various IL-18BP concentrations. The apoptosis and necroptosis of FLSs and chondrocytes were measured by flow cytometry using annexin V and propidium iodide (PI) and western blot under TNF-α stimulation with IL-18BP (10, 50, and 100 ng/mL). RESULTS: Differentiation of CD4+ IL-17A+ and CD4+ IL-4+ cells decreased and that of CD4+ CD25high Foxp3+ and CD4+ interferon (IFN)-γ+ cells increased on addition of IL-18BP to cultured RA patient-driven PBMCs. RA-FLS migration ability was not suppressed by IL-18BP after 12 or 24 h. IL-18BP increased annexin V+ FLS level and reduced annexin V+ chondrocyte level in a dose-dependent manner, whereas PI+ annexin V- FLS and chondrocyte levels were suppressed by 50, 100 ng/mL IL-18BP in culture. CONCLUSIONS: The administration of IL-18BP regulated the type 17 helper T cell/ regulatory T cell imbalance and attenuated the production of pro-inflammatory cytokines. IL-18BP further increased FLS apoptosis and decreased the necroptosis of FLS/chondrocytes and apoptosis of chondrocytes suggesting the joint preservative potential of IL-18BP.

Risk of cancer, cardiovascular disease, thromboembolism, and mortality in patients with rheumatoid arthritis receiving Janus kinase inhibitors: a real-world retrospective observational study using Korean health insurance data.

OBJECTIVES: This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA). METHODS: We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups. RESULTS: Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups. CONCLUSIONS: In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.