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Aim: To investigate the association of large joint involvement (LJI) with disease activity and drug retention in patients with rheumatoid arthritis (RA) who started receiving a biological disease‐modifying antirheumatic drug or Janus kinase inhibitor. Methods: Patients with RA from a Japanese multicenter observational registry were enrolled. Our definition of large joints included the shoulder, elbow, hip, knee, and ankle joints. Linear mixed‐effects models were used to examine changes in the clinical disease activity index (CDAI) score at Week 24 as the primary outcome, and drug retention rates were compared between patients with and without LJI using Cox proportional hazards models. We examined the potential effect modifications of changes in the CDAI by baseline characteristics. Results: Overall, 2507 treatment courses from 1721 patients were included (LJI, 1744; no LJI, 763). Although LJI was associated with significantly higher changes in CDAI from baseline at Week 24 (difference in change in CDAI: −5.84 [−6.65 to −5.03], p <.001), CDAI was significantly higher in patients with LJI over time. Retention rates were similar in both groups. The association of LJI with changes in disease activity was more prominent in patients with a short disease duration, negative anti‐citrullinated peptide antibodies, and interleukin‐6 receptor inhibitor (IL‐6Ri) use. Conclusion: Although LJI was associated with a greater reduction in disease activity from baseline, higher disease activity at baseline was not offset over time in patients with LJI, demonstrating that LJI is an unfavorable predictor. An early treat‐to‐target strategy using an IL‐6Ri may be beneficial for patients with LJI. [ABSTRACT FROM AUTHOR]

The aim of this multi-centre retrospective study was to clarify the prognostic factors for respiratory-related death in patients with interstitial lung disease (ILD) complicated rheumatoid arthritis (RA). Patient background data, treatment regimen, and disease activity indicators of RA and ILD at baseline, 6 months after the diagnosis of ILD, and at the last follow-up visit were extracted. A total of 312 patients with RA-ILD (17 patients who died from respiratory-related causes and 295 survivors) were included. Patients who died from respiratory-related causes had an older median age, a higher proportion of being male, and a higher anti-cyclic citrullinated peptide antibody positivity rate than survivors (p =.0001, .038, and .016, respectively); they also had significantly higher baseline serum levels of Krebs von den Lungen-6 (KL-6) than survivors (p =.013). Patients who died from respiratory-related causes showed significantly greater changes in serum KL-6 levels between the 6-month time point and the last visit [ΔKL-6 (6 months - last)] than survivors (p =.011). Multivariate analysis showed that the ΔKL-6 (6 months - last) corrected by disease duration was a predictor of respiratory-disease-related death in patients with RA-ILD (p < .0001). Long-term increase in serum KL-6 levels is associated with respiratory-disease related death in patients with RA-ILD. [ABSTRACT FROM AUTHOR]

This multicenter retrospective study aimed to clarify the prognostic factors for mortality and changes in treatment modalities and disease activities after the onset of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA). Data regarding the clinical background, treatment modalities, and disease activity indicators of RA at the onset of PCP (baseline), and 6 months and 12 months after treatment were extracted. Of the 37 patients with RA-PCP (median age, 69 years; 73% female), chemical prophylaxis was administered to 8.1%. Six patients died during PCP treatment. The serum C-reactive protein (CRP) levels and the prednisolone (PDN) dose at baseline in the PCP death group were significantly higher than those in the survivor group. Multivariate analysis using a Cox regression model showed that PDN dose at baseline was a predictor of death from PCP in patients with RA. During the 12 months from baseline, the RA disease activity significantly decreased. A high dose of corticosteroids for RA may result in a poor prognosis when PCP is complicated. In the future, preventive administration techniques must be established for patients with RA who need PCP prevention. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the serum cytokine profile and address the pathomechanism of interstitial lung disease (ILD) complicated with PM/DM. Methods Forty patients with PM/DM-ILD were enrolled, and principal components analysis and cluster analysis were performed to classify patients into subgroups. Additionally, we compared cytokine profiles between the survivors and dead patients and between anti-melanoma differentiation-associated gene 5 antibody- and anti-aminoacyl tRNA synthetase antibody-positive ILD patients. We also examined the association of various cytokines with disease activity indicators and prognosis of ILD. Results The principal components analysis data allowed classification of the cytokine profile into three groups: group 1, neutrophilic and M1-macrophage-driven cytokines; group 2, type 1 Th cell-driven and M2-macrophage-induced cytokines; and group 3, M2-macrophage-driven cytokines. Cluster analysis showed the presence of PM/DM-ILD patient groups with high or low levels of total cytokines. Ninety percent of patients who died of ILD were included in clusters with high cytokine levels. Serum cytokine levels of all groups were significantly higher in the anti-melanoma differentiation-associated gene 5 antibody-positive patients than in the anti-aminoacyl tRNA synthetase antibody-positive patients. Groups 1 and 2 significantly correlated with known factors for poor prognosis, such as serum ferritin levels and alveolar-arterial oxygen difference. Serum cytokine levels of patients in group 1 were significantly higher initially and at 2 and 4 weeks in those who died. Conclusion These findings suggested that the activation of monocytes, macrophages and type 1 Th cells, and neutrophils play roles in the pathomechanism of PM/DM-ILD, and group 1 cytokines could be useful biomarkers for predicting prognosis of PM/DM-ILD. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of elderly patients (65 years of age or older) with rheumatoid arthritis (RA). Methods: This multi-center, retrospective study assessed 1,098 treatment courses of 661 patients with bDMARDs from 2009 to 2018 (females, 80.7%; baseline age, 71.7 years; disease duration 10.5 years; rheumatoid factor positivity 81.3%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.6; concomitant prednisolone dose 2.8 mg/day (45.6%) and methotrexate dose 4.4 mg/week (56.4%); and 60.2% patients were bio-naïve). Treatment courses included abatacept (ABT; n = 272), tocilizumab (TCZ; n = 234), etanercept (ETN; n = 184), golimumab (GLM; n = 159), infliximab (IFX; n = 101), adalimumab (ADA; n = 97), and certolizumab pegol (CZP; n = 51). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX, starting date and switched number of bDMARDs) by Cox proportional hazards modeling. Results: A total of 51.2% of treatment courses were stopped, with 25.1% stopping due to lack of effectiveness, 11.8% due to toxic adverse events, 9.7% due to non-toxic reasons, and 4.6% due to remission. Drug retention rates for each discontinuation reason were as follows; lack of effectiveness [from 55.4% (ETN) to 81.6% (ABT); with significant differences between groups (Cox P<0.001)], toxic adverse events [from 79.3% (IFX) to 95.4% (ABT), Cox P = 0.043], and remission [from 94.2% (TCZ) to 100.0% (CZP), Cox P = 0.58]. Finally, overall retention rates excluding non-toxic reasons and remission for discontinuation ranged from 50.0% (ETN) to 78.1% (ABT) (Cox P<0.001). Conclusions: ABT showed lowest discontinuation rate by lack of effectiveness and by toxic adverse events, which lead to highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in adjusted model of elderly RA patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether remission can be sustained for rheumatoid arthritis (RA) patients after tapering abatacept (ABT). Method: All patients were naïve to biological disease‐modifying anti‐rheumatic drugs (bDMARDs) and in low or moderate Disease Activity Score of 28 joints with C‐reactive protein (DAS)28‐CRP). ABT was administrated intravenously (IV) or subcutaneously (SC) for 36 weeks to patients with RA, who had not previously received bDMARDs. As the ABT tapering protocol, ABT was administrated SC at 125 mg every 2 weeks for 12 weeks in patients with remission. RA disease activity was assessed by DAS28‐CRP and ultrasonography. Remission was assessed by defining it as DAS28‐CRP <2.3. Results: Of the 51 patients, 84.3% were women (mean age 68.7 ± 10.2 years, mean disease duration 7.7 ± 10.2 years). Twenty‐nine patients achieved remission and a power Doppler (PD) score ≤1 at each joint at 36 weeks, followed by tapering ABT. Of these patients, 25 sustained DAS28‐CRP remission, and DAS28‐CRP was not significantly elevated (1.62 ± 0.41 to 1.69 ± 0.49) at 48 weeks, but the total PD score was significantly elevated (1.52 ± 1.21 to 2.59 ± 2.81 P = 0.049). Longer disease duration, higher DAS28‐CRP at 24 weeks, and higher total PD score at 24 weeks were predictors of an elevated total PD score after tapering ABT therapy. Conclusion: These findings suggest that ABT tapering is a promising short‐term strategy to sustain remission in patients with RA, and ultrasonography is a useful tool for monitoring disease activity after tapering ABT. [ABSTRACT FROM AUTHOR]

Background: Achieving aesthetic results with forehead augmentation procedures remains challenging. We have developed a method of integrated forehead and temporal augmentation using a three-dimensional (3D) printing-assisted methyl methacrylate implant.Objectives: The study objective was to assess the importance of combined temporal augmentation when performing forehead augmentation.Methods: We identified 34 patients (from 2000 to 2010) who underwent forehead augmentation with a methyl methacrylate implant contoured in situ during surgery and 41 patients (from 2010 to 2016) who underwent integrated forehead and temporal augmentation with a prefabricated methyl methacrylate implant. We conducted a retrospective chart review of patient data including operation time, complications, and instances of revision surgery. Two blinded plastic surgeons scored the aesthetic results of the operations on a 4-point scale (1, poor, to 4, excellent) based on preoperative and posttreatment photographs.Results: The integrated augmentation method resulted in a lower frequency of posttreatment implant removal (one [2%] vs. six [18%]; P < .05), a lower frequency of filler injection for touch up (one [2%] vs. six [18%]; P < .05), and higher mean aesthetic scores (3.7 ± 0.5 vs. 2.2 ± 1.0; P < . 001) compared to the forehead augmentation method. There was no statistically significant difference in surgical complications between the two groups.Conclusions: Integrated forehead and temporal augmentation using a 3D printing-assisted methyl methacrylate implant may be the optimal available procedure, enabling the custom fabrication of contours requested by the patient and providing a rejuvenating and balancing effect on facial appearance.Level Of Evidence3: [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling. [ABSTRACT FROM AUTHOR]

A wavelength tunable plastic laser with asymmetric distributed Bragg reflectors (DBRs) is proposed. This device consists of a pair of long-period waveguide gratings and a polymeric active waveguide doped with an organic dye. Due to the difference in grating periods between the two DBRs, the lasing wavelength can be tuned in accordance with a Vernier effect of the resonance between the reflection wavelengths. The plastic laser device operated with this principle has promise as a compact and widely tunable light source because a large wavelength shift in a wide emission band of an organic luminescent material can be expected with a small variation in the effective index. [ABSTRACT FROM PUBLISHER]

We demonstrated a wavelength-switchable lasing operation in a single-chip polymer waveguide device. This device has a single active layer codoped with two organic dyes, Stilbene 420 and Rhodamine B, and is equipped with a distributed-feedback resonator by a single-pitched grating. Since there is no significant spectral overlap between the emission band of Stilbene 420 and the absorption band of Rhodamine B, both of these dyes could be simultaneously activated as the optical gain media in the active layer. Under the optical pumping, bistable blue and red lasing emissions were obtained, which were attributed to the third-order distributed-feedback oscillation for the Stilbene 420 emission and the second-order distributed-feedback oscillation for the Rhodamine B emission, respectively. These lasing modes could be easily switched by changing the pumping wavelength. [ABSTRACT FROM PUBLISHER]

The authors have investigated the morphological evolution of Al whiskers grown by high temperature glancing angle deposition (HT-GLAD). The critical temperature of formation of the Al whisker at a deposition angle of 85° is found to be between 180 and 290 °C, and it is much lower than that reported for the Al whiskers grown on a hot tungsten wire by the conventional evaporation technique. The morphology of the whiskers grown at a substrate temperature of 290 °C reveals that a significant amount of Al is supplied to the whiskers through their base by surface diffusion and that the diffusion length of adatoms on the side surface of the whiskers reaches approximately 10 μm. It has also been confirmed that a significant number of Al atoms that have been incorporated into the whiskers move in such a manner that drastic changes can occur in the morphology of the whiskers. HT-GLAD is a potential process for providing nanosized metal whiskers. [ABSTRACT FROM AUTHOR]

The authors demonstrate the growth of unusual Al whiskers by glancing angle deposition on a high temperature (HT-GLAD) substrate, while the usual columnar structures completely disappear due to accelerated surface diffusion. HT-GLAD is essential for the nucleation of the whiskers and efficient supply of Al atoms on the side surface of the vertically growing whiskers. HT-GLAD will, for the first time, reveal the mechanisms for the vapor growth of metal whiskers. [ABSTRACT FROM AUTHOR]