Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated ...interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters.
This retrospective study included 549 Korean patients with rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and other CTDs with or without concurrent ILD. Serum KL-6 concentration (U/mL) was measured using the latex-enhanced immunoturbidimetric assay method. CT and PFT results were collected within 1 year of serum collection. A semiquantitative grade of ILD extent was evaluated through CT scan (grade 1, 0-25%; grade 2, 26-50%; grade 3, 51-75%; grade 4, 76-100%).
CTD-ILD patients (n = 165) had elevated serum KL-6 levels compared to CTD patients without ILD (n = 384) (p < 0.001), and those findings were preserved after adjusting for age, sex, and CTD type. The semiquantitative grade of ILD on CT scan was significantly proportional to the KL-6 level, and the optimal cut-off KL-6 value effectively differentiated each ILD grade. The percent diffusing capacity of the lung for carbon monoxide (DLCO) (p < 0.001) and forced vital capacity (FVC) (p < 0.001) parameters had a moderate, negative correlation with the KL-6 level.
Serum KL-6 levels were increased in CTD-ILD patients and had a positive correlation with CT grade and a negative correlation with FVC and DLCO. Serum KL-6 levels may reflect CTD-ILD severity.
Objective
This clinical trial was conducted to investigate whether discontinuing methotrexate (MTX) for 1 week after seasonal influenza vaccination is noninferior to discontinuing for 2 weeks after ...vaccination in patients with rheumatoid arthritis (RA).
Methods
In this multicenter, prospective, randomized, parallel‐group noninferiority trial, RA patients receiving a stable dose of MTX were randomly assigned at a ratio of 1:1 to discontinue MTX for 1 week or for 2 weeks after they received the quadrivalent 2021–2022 seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains. The primary outcome measure was the proportion of patients with a satisfactory vaccine response, which was defined as ≥4‐fold increase in antibody titers, as determined with the hemagglutination inhibition assay, against ≥2 of the 4 vaccine strains at 4 weeks after vaccination.
Results
The modified intent‐to‐treat population included 90 patients in the 1‐week MTX hold group and 88 patients in the 2‐week MTX hold group. The mean ± SD MTX doses were 12.6 ± 3.4 mg/week in the 1‐week MTX hold group and 12.9 ± 3.3 mg/week in the 2‐week MTX hold group. The proportion of satisfactory vaccine responses did not differ between the groups (68.9% versus 75.0%; P = 0.364). The rate of seroprotection and the fold increase in antibody titers for each of the 4 influenza antigens were similar between the groups.
Conclusion
A temporary discontinuation of MTX for 1 week after vaccination was noninferior to a discontinuation of MTX for 2 weeks after vaccination, regarding induction of a satisfactory vaccine response to a seasonal influenza vaccine in patients with RA receiving a stable dose of MTX.
Treatment of glioblastoma, the most common and aggressive type of primary brain tumors, is a major medical challenge and the development of new alternatives requires simple yet realistic models for ...these tumors. In vitro spheroid models offer attractive platforms to mimic the tumor behavior in vivo and have thus, been increasingly applied for assessment of drug efficacy in various tumors. The aim of this study was to produce and characterize size-controlled U251 glioma spheroids towards application in glioma drug evaluation studies. To this end, we fabricated agarose hydrogel microwells with cylindrical shape and diameters of 70-700 μm and applied these wells without any surface modification for glioma spheroid formation. The resultant spheroids were homogeneous in size and shape, exhibited high cell viability (> 90%), and had a similar growth rate to that of natural brain tumors. The final size of spheroids depended on cell seeding density and microwell size. The spheroids' volume increased linearly with the cell seeding density and the rate of this change increased with the well size. Lastly, we tested the therapeutic effect of an anti-cancer drug, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) on the resultant glioma spheroids and demonstrated the applicability of this spheroid model for drug efficacy studies.
Objective
To investigate the impact of tumor necrosis factor inhibitor (TNFi) treatment and inflammation control on radiographic progression in early ankylosing spondylitis (AS) over 4 years.
Methods
...We included a total of 215 patients with early AS (symptom duration <10 years) treated with TNFi (the TNFi group; n = 135) or with nonsteroidal antiinflammatory drugs (NSAIDs) (the control group; n = 80). Two blinded readers assessed radiographic progression using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Inflammation control was inferred from C‐reactive protein (CRP) levels time‐averaged between 2 radiologic assessments. Linear mixed modeling was used to estimate mSASSS changes over radiographic intervals as well as the impact of clinical factors on outcomes.
Results
The TNFi group had longer disease duration, a higher baseline CRP level, and a higher Bath Ankylosing Spondylitis Disease Activity Index than did controls. The time‐averaged CRP level over radiographic intervals was lower with TNFi treatment than with NSAID treatment (mean ± SD 0.27 ± 0.30 mg/dl versus 0.61 ± 0.68 mg/dl; P < 0.001). Overall, mean ± SD mSASSS change over the 2‐year interval was 1.30 ± 2.97 units. In the multivariable model adjusted for age, smoking status, baseline CRP level, and the presence of syndesmophytes at baseline, the TNFi group showed less mSASSS change over the 2‐year interval (β = −0.90 95% confidence interval {95% CI} −1.51, −0.29). However, when a time‐averaged CRP level was additionally included, it significantly influenced the mSASSS change (β = 1.02 95% CI 0.32, 1.71), decreasing the estimated group difference (β = −0.52 95% CI −1.17, 0.14). NSAID indices of both groups were not associated with either time‐averaged CRP levels or mSASSS changes.
Conclusion
Effective suppression of inflammation by TNFi treatment decreases radiographic progression in early AS.
To identify a specific population of patients with rheumatic diseases receiving rituximab treatment for whom the benefit from primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) ...outweighs the risk of adverse events (AEs) METHODS: This study included 818 patients treated with rituximab for rheumatic diseases. Of these, 419 received prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) with rituximab while the remainder did not. Differences in 1-year PJP incidence between the groups were estimated using Cox regression. Risk-benefit assessment was performed in the subgroup stratified according to risk factors based on the number needed to treat (NNT) to prevent one case of PJP and the number needed to harm (NNH) due to severe AEs. Inverse probability of treatment weighting was applied to minimize the confounding by indication.
During the 663.1 person-years, there were 11 PJP cases, with a mortality rate of 63.6%. Concomitant use of high-dose glucocorticoids (≥30mg/day of prednisone during 4 weeks after rituximab administration) was the most important risk factor. The PJP incidence (per 100 person-years) was 7.93 (2.91-17.25) in the subgroup receiving high-dose glucocorticoids, compared with 0.40 (0.01-2.25) in the subgroup without high-dose glucocorticoids. Although prophylactic TMP-SMX significantly reduced the overall PJP incidence (HR 0.11 0.03-0.37), the NNT to prevent one PJP was higher than the NNH (146 vs. 86). In contrast, the NNT fell to 20 (10.7-65.7) in patients receiving concomitant high-dose glucocorticoids.
The benefit associated with primary PJP prophylaxis overweighs the risk of severe AEs in patients receiving rituximab and concomitant high-dose glucocorticoid treatment. This article is protected by copyright. All rights reserved.
The emerging role of microglia in neurological disorders requires a novel method for obtaining massive amounts of adult microglia. We aim to develop a new method for obtaining bankable and expandable ...adult-like microglia in mice.
The head neuroepithelial layer (NEL) that composed of microglial progenitor and neuroepithelial cells at mouse E13.5 was dissected and then cultured or banked. Microglia (MG) isolated from the cultured NEL by magnetic-activated cell sorting system were obtained and named NEL-MG.
The NEL included microglia progenitors that proliferate and ramify over time with neuroepithelial cells as feeder. In functional analysis, NEL-MG exhibited microglial functions, such as phagocytosis (microbeads, amyloid β, synaptosome), migration, and inflammatory response following lipopolysaccharide (LPS) stimulation. NEL was passage cultured and the NEL-MG exhibited a higher expression of microglia signature genes than the neonatal microglia, a widely used in vitro surrogate. Banking or long-term passage culture of NEL did not affect NEL-MG characteristics. Transcriptome analysis revealed that NEL-MG exhibited better conservation of microglia signature genes with a closer fidelity to freshly isolated adult microglia than neonatal microglia. NEL-MG could be re-expandable when they were plated again on neuroepithelial cells.
This new method effectively contributes to obtaining sufficient matured form of microglia (adult-like microglia), even when only a small number of experimental animals are available, leading to a broad application in the field of neuroscience.
To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea.
Using 2009-2019 Korea National Health Insurance Service ...database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users.
We included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00-2.80) for HZ, 1.04 (0.71-1.52) for SBI, and 0.25 (0.09-0.73) for OI.
This population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.
Recent studies have suggested that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) are emerging markers of disease activity and prognosis in patients with chronic ...inflammatory diseases, cardiovascular diseases, or malignancies. Therefore, we investigated the clinical significance and prognostic value of the NLR and CAR in adult patients with polymyositis and dermatomyositis. The medical records of 197 patients with newly diagnosed polymyositis/dermatomyositis between August 2003 and November 2016 were retrospectively reviewed. Survival and causes of death were recorded during an average 33-month observational period. Clinical and laboratory findings were compared between survivors and non-survivors. Using receiver operating characteristic curves, the NLR and CAR cut-off values for predicting survival were calculated. Univariate and multivariate analyses using Cox proportional hazard models were performed to identify factors associated with survival. Twenty-six patients (13.2%) died during the study period, and the 5-year survival-rate was estimated to be 82%. The non-survivor group exhibited older age and a higher prevalence of interstitial lung disease (ILD), acute interstitial pneumonia, and acute exacerbation of ILD compared to that in the survivor group. NLR and CAR values were significantly higher in the non-survivors and in patients with polymyositis/dermatomyositis-associated ILD, and the death rates increased across NLR and CAR quartiles. Furthermore, when stratified according to the NLR or CAR optimal cut-off values, patients with a high NLR (>4.775) or high CAR (>0.0735) had a significantly lower survival rate than patients with low NLR or CAR, respectively. In addition, old age (>50 years), the presence of acute interstitial pneumonia, hypoproteinemia (serum protein <5.5 g/dL), and high NLR (but not high CAR) were independent predictors for mortality. The results indicate that a high NLR is independently associated with worse overall survival. Thus, the baseline NLR level may be a simple, cost-effective prognostic marker in patients with polymyositis/dermatomyositis.
Organic electronic materials are rapidly emerging as superior replacements for a number of conventional electronic materials, such as metals and semiconductors. Conducting polymers, carbon nanotubes, ...graphenes, organic light‐emitting diodes, and diamond films fabricated via chemical vapor deposition are the most popular organic bioelectronic materials that are currently under active research and development. Besides the capability to translate biological signals to electrical signals or vice versa, organic bioelectronic materials entail greater biocompatibility and biodegradability compared to conventional electronic materials, which makes them more suitable for biomedical applications. When patterned, these materials bring about numerous capabilities to perform various tasks in a more‐sophisticated and high‐throughput manner. Here, we provide an overview of the unique properties of organic bioelectronic materials, different strategies applied to pattern these materials, and finally their applications in the field of biomedical engineering, particularly biosensing, cell and tissue engineering, actuators, and drug delivery.
Organic electronic materials are emerging as ideal materials for electronics interfacing biology. Offering excellent conductivity along with biocompatibility, these materials receive much interest in the biomedical engineering field. Patterning such materials extends the scope of their applications in sophisticated biomedical technologies. These materials, techniques employed to pattern them, and their applications in biomedicine, particularly biosensing, cell/tissue engineering, and drug delivery, are reviewed.
This study evaluated the shear bond strength (SBS) and biaxial flexural strength (BFS) of resin cements according to the surface treatment method using low-temperature hot etching with hydrofluoric ...acid (HF) on a yttrium-stabilized tetragonal zirconia (Y-TZP) surface; 96 discs and 72 cubes for BFS and SBS tests for Y-TZP were randomly divided into four groups of BFS and three groups of SBS. Specimens were subjected to the following surface treatments: (1) no treatment (C), (2) air abrasion with 50 μm Al
O
particles (A), (3) hot etching with HF at 100 °C for 10 min (E), and (4) air abrasion + hot etching (AE). After treatments, the specimens were coated with primer, and resin cement was applied with molds. The specimens were evaluated for roughness (Ra) via scanning electron microscopy and x-ray diffraction, and the data were analyzed by an analysis of variance (ANOVA) and Kruskal-Wallis tests. Group E produced significantly higher SBS compared to group A and AE before and after thermocycling. The BFSs of all groups showed no significant differences before thermocycling; however, after thermocycling, C and E treatment groups were significantly higher compared to group A and AE. All groups showed phase transformation. Group E was observed lower monoclinic phase transformation compared to other groups.
PDF
