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An extensive seismic swarm, as well as transient deformation, have continued since the end of November 2020 in the Noto Peninsula, central Japan, which is a non-volcanic/geothermal area far from the major plate boundaries. We present the transient deformation clarified from a combined analysis of multiple GNSS observation networks, seismicity, and their interpretation. We analyzed data at 30 continuous GNSS stations operated by SoftBank Corp., the Geospatial Information Authority of Japan (GSI), and universities. The total displacement pattern for two years shows horizontal inflation and uplift up to ~70 mm around the source of the earthquake swarm. In the first three months, the opening of the low-angle tensile crack is estimated with a volumetric increase of ~1.4 x 107 m3 at a depth of ~16 km. In the next 15 months, the observed deformation is well reproduced by shear-tensile sources, which suggests an aseismic reverse-type slip and expansion of a southeast-dipping fault zone at a depth of 14-16 km. The estimated shear-tensile sources locate at the downdip of the clusters of the earthquake swarm. We interpreted our deformation model and earthquake sequence as follows. Upwelling fluid sub-horizontally spread in a southeast-dipping fault zone. And they migrated up-dip along the fault zone and caused sub-meter aseismic slip below the seismogenic depth. The aseismic slip further triggered intensive earthquakes above the seismogenic depth.Acknowledgments: We are grateful to SoftBank Corp., ALES Corp., and GSI for providing us with GNSS observation data. This work was supported byJSPS KAKENHI Grant Number JP22K19949., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Currently, biological disease-modifying anti-rheumatic drugs (bDMARDs) with different modes of action [tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL-6Ri), or cytotoxic T-lymphocyte antigen 4–immunoglobulin (CTLA4-Ig)] are used in clinical practice to treat rheumatoid arthritis (RA). However, it is unclear which type of bDMARD is the most efficacious for a specific clinical situation. C-reactive protein (CRP) is an acute-phase reactant driven by IL-6 signalling. Here, we aimed to establish whether therapeutic efficacy differs between IL-6Ri and other bDMARDs with alternative modes of action in RA patients according to their CRP level. RA patients treated with bDMARDs were enrolled from an observational multicentre registry in Japan. Patients were classified into three groups according to baseline CRP tertiles. The overall 3 year retention rates of each bDMARD category were assessed. The Clinical Disease Activity Index (CDAI) was also assessed before and 3, 6, and 12 months after bDMARD initiation. A total of 1438 RA patients were included and classified into three groups according to tertiles of baseline CRP levels (CRP1, 0–0.3; CRP2, 0.3–1.8; CRP3, 1.8–18.4 mg/dL). In CRP3, the overall 3 year drug retention rates were significantly higher for IL-6Ri than for TNFi and CTLA4-Ig (77.5 vs 48.2 vs 67.3, respectively). No significant difference was evident in terms of CDAI 12 months after bDMARD initiation in CRP1–CRP3. IL-6Ri may be a favourable therapeutic option over TNFi and CTLA4-Ig in RA patients with high CRP levels.

Reports of early and catastrophic acute structural valve deterioration (SVD) in Trifecta valves (Abbott, St Paul, MN, USA) with multiple leaflet detachment are rare. We encountered two cases of early SVD in Trifecta valves with tears on two leaflets. Both cases presented with acute heart failure because of aortic insufficiency and underwent redo aortic valve replacement; one patient died due to multiple organ failure caused by cardiogenic shock. Durability issues with valves necessitate long-term vigilance in aortic valve replacement patients.

Background: Rheumatoid factor (RF) binds to the Fc portion of immunoglobulin and can bind to the Fc portion of anti-TNF monoclonal antibodies (TNFi), attenuating their clinical efficacy. We tried to determine whether the therapeutic efficacy is different between TNFi with or without the immunoglobulin Fc portion in rheumatoid arthritis (RA) patients depending upon the RF titres.Methods: RA patients treated with TNFi were enrolled from an observational multi-centre registry in Japan. TNFi treatments were divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, etanercept) and TNFi without Fc (certolizumab-pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) were compared by the Mann-Whitney U test between TNFi with and without the immunoglobulin Fc portion in each RF titre group.Results: A total of 705 RA patients were included and classified into four groups according to quartiles of baseline RF titres (RF1; RF 0-15.0 IU/mL, RF2; 15.0-55.0, RF3; 55.0-166, RF4; 166-7555). In RF4, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc (3.2 (2.3-4.2) vs. 2.7 (2.0-3.0)) (median, IQR) after 12 months of follow-up, while there were no significant differences in RF1, RF2, and RF3.Conclusion: TNFi without Fc (certolizumab-pegol) may be more efficacious than TNFi with Fc in RA patients with high RF titres.