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Introduction: For patients with rheumatoid arthritis (RA) unresponsive to first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), the selection of second-line b/tsDMARDs is crucial to prevent progression to difficult-to-treat rheumatoid arthritis (D2TRA). However, indicators for selection are lacking. This study aimed to identify optimal second-line b/tsDMARDs among the phase III treatment strategies based on European League Against Rheumatism (EULAR) RA management recommendations., Methods: A total of 687 RA patients treated with second-line b/tsDMARDs (tumor necrosis factor inhibitor (n = 246), interleukin-6 receptor inhibitor [n = 195], cytotoxic T-lymphocyte-associated protein 4 immunoglobulin [n = 119], and Janus kinase inhibitor [n = 127]) were enrolled between October 2013 and April 2023. Rates of patients achieving Clinical Disease Activity Index (CDAI) remission and CDAI low disease activity (LDA), changes in CDAI, persistence rates, and adverse events within 24 weeks after treatment initiation were compared among the four groups. Propensity score-based inverse probability of treatment weighting (PS-IPTW) was used to minimize selection bias., Results: After PS-IPTW adjustment, the Janus kinase inhibitor (JAKi) group had the highest persistence rate among the four groups. At 24 weeks, the JAKi group showed the greatest improvement in CDAI and the highest CDAI remission rate. Among patients treated with JAKi as second-line b/tsDMARDs, upadacitinib (UPA) was most likely to achieve CDAI remission at 24 weeks. The comparison between the UPA group (n = 32) and the non-UPA JAKi group (tofacitinib and baricitinib [n = 95]) showed comparable persistence rates but significantly lower CDAI scores and higher CDAI remission rate at 24 weeks in the UPA group. No significant difference was noted in the overall incidence of adverse events among the four groups treated with b/tsDMARDs or between the groups treated with JAKi., Conclusions: Selecting JAKi, especially UPA, may effectively improve the disease activity for RA patients unresponsive to first-line b/tsDMARDs. Further large-scale studies are needed to clarify the efficacy and safety of UPA., Trial Registration: FIRST registry (approval number#04-23): October 2013, retrospectively registered., Competing Interests: Declarations. Conflict of Interest: Yusuke Miyazaki has received consulting fees, speaking fees, lecture fees, and/or honorariums from AstraZeneca, GlaxoSmithKline, Bristol-Myers, Astellas, Asahi-kasei, AbbVie, Chugai, Sanofi, Eisai, Eli Lilly, and Boehringer Ingelheim. Shingo Nakayamada has received consulting fees, speaking fees, lecture fees, and/or honorariums from AstraZeneca, GlaxoSmithKline, Pfizer, Bristol-Myers, Astellas, Asahi-kasei, AbbVie, Chugai, Sanofi, Eisai, Gilead Sciences, Mitsubishi-Tanabe, Janssen, Eli Lilly, Boehringer Ingelheim and Ayumi. Satoshi Kubo has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol-Myers, AbbVie, Eisai, Pfizer, AstraZeneca and also research grants from Daiichi-Sankyo, AbbVie, Boehringer Ingelheim, and Astellas. Masanobu Ueno has received speaking fees from GlaxoSmithKline. Yoshiya Tanaka has received speaking fees and/or honorariums from Gilead Sciences, AbbVie, Boehringer Ingelheim, Eli Lilly, Mitsubishi-Tanabe, Chugai, Amgen, YL Biologics, Eisai, Astellas, Bristol-Myers, and AstraZeneca; received research grants from Asahi-Kasei, AbbVie, Chugai, Mitsubishi-Tanabe, Eisai, Takeda, Corrona, Daiichi-Sankyo, Kowa, and Boehringer Ingelheim; and received consultant fees from Eli Lilly, Daiichi-Sankyo, Taisho, Ayumi, Sanofi, GlaxoSmithKline, and AbbVie. Ryuichiro Kanda, Shunsuke Fukuyo, Ippei Miyagawa, Ayako Yamaguchi, Yurie Satoh-Kanda, Naoaki Ohkubo, Yasuyuki Todoroki, Hiroaki Tanaka, Atsushi Nagayasu, Yuya Fujita, Takafumi Aritomi, Katsuhide Kusaka, Hidenori Sakai, Satsuki Matsunaga, and Hirotsugu Nohara have nothing to disclose. Yoshiya Tanaka is an Editorial Board member of Rheumatology and Therapy. Yoshiya Tanaka was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: This study was approved by the ethics review board of the University of Occupational and Environmental Health, Japan (approval number #04-23). The FIRST registry includes RA patients who initiated treatment with b/tsDMARDs. Informed consent was obtained from all patients who have consented to the FIRST registry., (© 2025. The Author(s).)

Background: Treatment of intrahepatic cholangiocarcinoma (ICC) remains challenging owing to the lack of clear guidelines on surgical resection. The 2021 ICC guidelines have not fully resolved the ongoing debate between surgical and nonsurgical treatment options. This study aimed to identify trends and issues in ICC treatment strategies in the clinical field by surveying the attitudes of hepatobiliary and pancreatic (HBP) surgeons., Methods: A survey was conducted among 235 board-certified HBP surgeons affiliated with the Japanese Society of Hepato-Biliary-Pancreatic Surgery. This survey explored the perspectives on tumor conditions that define resectable, borderline resectable, and unresectable diseases, focusing on tumor size, number, and vascular invasion., Results: Notable variability was observed in the criteria for oncological resectability. While 42.1% of the respondents considered a maximum tumor diameter of 5 cm as resectable, 37.5% indicated no size limit for resectability. Opinions regarding the resectability of tumors with lymph node involvement and vascular invasion vary widely, highlighting the need for standardized criteria., Conclusion: This survey revealed diverse approaches for defining resectability in ICC, emphasizing the necessity for more precise guidelines. Further research and expert consensus are required to establish standardized criteria that can guide clinical decision-making and improve patient outcomes., (© 2025 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC) with preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy. We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into three groups based on preprocedural thromboembolic or bleeding events under OAC therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy. In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3 year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32-15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45-58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522). Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with the conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC., Competing Interests: Declarations Conflict of interest The authors declare that there are no conflicts of interest., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Patients with nonvalvular atrial fibrillation (AF) not suitable for long-term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC) using the WATCHMAN device. The safety and efficacy of WATCHMAN-FLX (WM-FLX) compared with WATCHMAN-2.5 (WM-2.5), particularly in Asian populations, is unknown., Methods: We evaluated the background, procedure, and clinical outcomes of 199 patients who underwent LAAC between September 2019 and December 2022 and compared WM-2.5 (72 patients) with WM-FLX (127 patients)., Results: The mean age was 76 years, with 128 men, and 100 had nonparoxysmal AF (non-PAF). The mean CHA 2 DS 2 -VASc, and HAS-BLED were 5.1, and 3.2 points, respectively. WM-FLX group demonstrated a shorter procedure time than WM-2.5 group (50 vs. 42 min, p = 0.001). The WM-FLX group demonstrated no procedural-related acute cardiac tamponade, which was significantly low (5.6% vs. 0%, p = 0.02), and a significantly higher rate of complete seal at 45-day (63% vs. 80%, p = 0.04). WM-FLX group had a significantly higher cumulative 1-year incidence of device-related thrombosis (DRT) than WM-2.5 group (3.4% vs. 7.0%, Log-rank p = 0.01). Univariate analysis identified two DRT risk factors in the WM-FLX group: non-PAF (odds ratio [OR] 7.72; 95% confidence interval [CI] 1.20-48.7; p = 0.04), and 35-mm device (OR 5.13; 95% CI 1.31-19.8; p = 0.02)., Conclusions: WM-FLX significantly improved the procedural quality and safety of LAAC. However, DRT remains an important issue even in the novel LAAC device, being a hazard for patients with high DRT risk, such as having non-PAF and using 35-mm devices., (© 2024 Wiley Periodicals LLC.)

We investigated the characteristics of both integer and non-integer optical vortices (OVs) in the millimeter-wave regime generated by a spiral mirror. An OV, characterized by the phase term eiℓϕ, also known as a Laguerre–Gaussian (LG) beam, is a solution to the wave equation in cylindrical coordinates under the paraxial approximation in free space. This typically restricts the azimuthal mode number ℓ to integer values. However, the spiral mirror enables the generation of OVs with expected azimuthal mode numbers ℓ ̄ , which can take either integer or non-integer values in the reflected wave. We employed a field reconstruction method to analyze both integer and non-integer OVs with ℓ ̄ generated by the spiral mirror, decomposing them into their constituent integer ℓ components. Our results showed that when ℓ ̄ is specified as an integer, the generated OV primarily contains that single ℓ. In contrast, specifying a non-integer ℓ ̄ results in an OV composed of a superposition of multiple integer ℓ values. In other words, non-integer OVs are superpositions of LG beams with different integer azimuthal mode numbers. These OVs are generated by the spiral mirror with a focus function, allowing for the specification of arbitrary waist sizes and focal positions, as designed for this research. Furthermore, we revealed that this focus spiral mirror can also avoid the separation of singularities that were present in OVs generated by conventional flat spiral mirrors. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: S.K. has received speaking fees from Eli Lilly, GlaxoSmithKline, Abbvie, Bristol-Myers, Astra-Zeneca, Boehringer Ingelheim and Eisai, and research grants from Daiichi-Sankyo, Abbvie, Boehringer Ingelheim and Astellas. Y. T. has received speaking fees or honoraria from Abbvie, Eisai, Chugai, Eli-Lilly, Boehringer Ingelheim, GlaxoSmithKline, Taisho, AstraZeneca, Daiichi-Sankyo, Gilead, Pfizer, UCB, Asahi-kasei and Astellas, and research grants from Boehringer Ingelheim, Taisho and Chugai.

The MitraClip G4 device has controlled gripper actuation (CGA) system, which allows the anterior and posterior grippers operate separately in transcatheter edge-to-edge repair (TEER). We investigated the indications and outcomes of the use of CGA system during TEER for significant mitral regurgitation (MR). We reviewed 158 patients undergoing TEER with MitraClip G4 from September 2020 to July 2023. The CGA indications were: (1) for grasping and (2) for leaflet insertion confirmation. Leaflet grasping was completed with CGA in 18 patients (11 and 7 patients for grasping and leaflet insertion confirmation, respectively). Patients with flail leaflets or coaptation gap more frequently required CGA, indicating more complex mitral valve anatomy. The procedural success and adverse event rates (death, leaflet tear and single leaflet device attachment) were not different between the CGA and non-CGA groups. In patients requiring CGA, single leaflet device attachment was observed in 1 patient and leaflet tear in 1 patient during follow-up. In these two cases, CGA was required for grasping, and the clip was moved over a large distance (6.5 and 12.4 mm, respectively). In patients who had undergone CGA for confirmation, no device-related adverse event or MR recurrence was noted. In patients with complex mitral valve anatomy, CGA may be a safe and effective method for confirming leaflet insertion. It should be noted that when using CGA for leaflet grasping, especially when the clip is moved significantly, attention should be paid to leaflet adverse events., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear., Patients and Methods: This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies., Results: Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group., Conclusions: Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs., (© 2024. Society of Surgical Oncology.)

Background: Hemodialysis (HD) is associated with adverse cardiovascular events after percutaneous coronary intervention (PCI). Although the ultrathin strut biodegradable polymer sirolimus-eluting stent (ultrathin strut BP-SES) has had better results in patients undergoing PCI compared with other drug-eluting stents (DES), its usefulness in HD patients is unknown., Methods and Results: This study involved 286 lesions in 162 HD patients who underwent PCI with a DES between January 2018 and June 2022. The incidence of clinically driven target lesion revascularization (TLR), target vessel failure (TVF: cardiac death, target vessel MI and clinically driven target vessel revascularization [TVR]) was assessed. During a median 636 days, clinically driven TLR occurred in 32 lesions. Clinically driven TLR at 2 years was significantly lower in the ultrathin strut BP-SES group than in the other DES group (2.9% vs. 17.3%, log-rank P=0.028). TVF occurred in 43 patients. The cumulative incidence of TVF was not different between two groups; however, clinically driven TVR was significantly lower in patients treated with the ultrathin strut BP-SES than with other DES (4.5% vs. 25.7%, log-rank P=0.027). In the quantitative coronary angiography analysis, late lumen loss at follow-up was significantly smaller in the ultrathin strut BP-SES group (0.13±0.40 vs. 0.67±1.02 mm, P<0.001)., Conclusions: In patients on HD undergoing PCI, the incidence of clinically driven TLR was significantly lower in ultrathin strut BP-SES compared to other DES.

Anti-synthetase syndrome (ASyS) is a subset of idiopathic inflammatory myopathies characterized by a triad of myositis, interstitial lung disease, and arthritis. Patients with ASyS are generally treated with glucocorticoids, immunosuppressants, or both. We encountered a 53-year-old woman who developed anti-OJ autoantibodies-positive anti-synthetase syndrome following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Cov-2 messenger RNA (mRNA) vaccination. Her dyspnea and rash resolved within 4 weeks of the initial examination, achieving spontaneous remission without treatment 52 weeks after the diagnosis. This case suggests a potential association between SARS-CoV-2 infection, mRNA vaccination, and the transient development of anti-OJ antibodies-positive ASyS.

Helicobacter pylori (H. pylori) infection is one of the major risk factors of stomach cancer. Strains carrying the oncogenic cytotoxin CagA (cytotoxin-associated gene A) induce epithelial-mesenchymal transition (EMT) and contribute to tumor progression and metastasis. However, the mechanism in which CagA induces EMT has not been defined. In this study, using genetic methods in Drosophila, we identified Semaphorin 5A (SEMA5A) as a new target for CagA. We showed that infection with CagA-positive H. pylori downregulated the expression level of SEMA5A to induce expression of EMT-driving transcription factor Snail and mesenchymal marker N-cadherin, and promote invasive behavior in gastric epithelial cells. Furthermore, we demonstrated that transient over-expression of SEMA5A in H. pylori-infected cells inhibited CagA-mediated gain of mesenchymal phenotype. These results suggest that SEMA5A could be a key mediator of EMT and gastric carcinogenesis caused by CagA-positive H. pylori infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Sperm identification is crucial in sexual assault cases. While microscopic analysis is the gold standard for sperm detection, it is a laborious procedure even for trained personnel. Reverse transcription-quantitative real-time PCR (RT-qPCR) can enhance the screening by detecting sperm-specific mRNA markers, such as protamine 2 (PRM2). This study aimed to develop a one-step RT-qPCR assay targeting PRM2 mRNA. Our assay was capable of detecting as low as 0.01 μL of semen with high specificity and demonstrated successful detection of PRM2 mRNA in simulated-case samples. Owing to the simple workflow involved, our assay requires <30 min for RNA extraction and <60 min for RT-qPCR. Our assay enables high-throughput sperm screening and offers a promising strategy for enhancing the workflow of sexual assault cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the post-COVID-19 era, inbound medical care in Japan adapted to the growing demand for high-quality and precise healthcare. One form of this care is a complete medical examination, which has gained significant popularity among foreign residents of Japan and foreign visitors to Japan. From 2021 to 2024, 787 individuals from 27 countries underwent a complete medical examination at our facility. The annual growth rate in foreign residents undergoing a complete medical examination was 64% (2022 vs . 2021), 22% (2023 vs . 2022), and 10% (2024 vs . 2023); a notable proportion of those individuals were originally from China. These findings underscore the need for Japan's medical care to evolve in response to the diverse needs of an international clientele, highlighting the importance of tailored healthcare solutions in a globalized context., Competing Interests: The authors have no conflicts of interest to disclose., (2025, National Center for Global Health and Medicine.)

Objective: Various immune-cell subsets intricately mediate the pathogenesis of systemic lupus erythematosus (SLE). However, the role of CD8 + T cells in SLE remains unclear. We investigated the proportions and characteristics of peripheral CD8 + T cells and their association with clinical manifestations of SLE., Methods: We retrospectively enrolled 211 patients with SLE and 48 age- and sex-matched healthy controls (HCs). Peripheral CD8 + T cells were analysed using flow cytometry. The primary endpoint was the comparison of peripheral CD8 + T cell subset characteristics between patients and HCs., Results: Patients with SLE (mean age, 42.3 years; women, 89% and mean disease duration, 112.8 months) had significantly higher proportions of naïve CD8 + T cells (CCR7 + CD45RA + ), CD8 + terminally differentiated effector memory cells (CCR7 - CD45RA + ) and activated CD8 + T cells (CD38 + HLA-DR + ) in peripheral blood mononuclear cells than HCs (p<0.001). Activated CD8 + T cells produced granzyme B and interferon-γ, which correlated with serum double-stranded (ds) DNA antibodies (rs=0.3146, p<0.0001) and 50% haemolytic unit of complement (rs=-0.3215, p=0.0003), and were significantly increased in patients with active systemic, renal or haematological involvement (p<0.05). Cluster analysis-based subgroup classification based on CD8 cell differentiation and activation revealed a group with high numbers of activated CD8 + T cells, highly active SLE and organ damage, including active nephritis and persistently high cell counts after a 24-week treatment, indicating treatment resistance (high anti-dsDNA antibody titres and high glucocorticoid doses)., Conclusion: In SLE, greater proportions of highly cytotoxic and proinflammatory activated CD8 + T cells in peripheral blood-modulated disease activity, organ damage and residual treatment resistance, presenting a potential treatment target., Competing Interests: Competing interests: YM received consulting fees, speaker fees and honoraria from Eli Lilly and received research grants from GlaxoSmithKline. KS received a speaking fee from Chugai Pharmaceutical, Astellas Pharma, AbbVie, Taisho Pharmaceutical, Janssen Pharmaceuticals, Eli Lilly, Ayumi Pharmaceutical, Gilead Sciences, GlaxoSmithKline, Pfizer and UCB Japan; received consulting fees from Chugai Pharmaceutical and Astellas Pharma and received research funding from UCB Japan. SN received consulting fees, speaking fees, lecture fees and/or honoraria from AstraZeneca, GlaxoSmithKline, Pfizer, Bristol Myers Squibb, Astellas Pharma, Asahi Kasei Pharma, AbbVie, Chugai Pharmaceutical, Sanofi, Eisai, Gilead Sciences, Mitsubishi Tanabe Pharma, Janssen Pharmaceuticals, Eli Lilly, Boehringer Ingelheim and Ayumi Pharmaceutical. YT received speaker fees and/or honoraria from Eli Lilly, AstraZeneca, AbbVie, Gilead Sciences, Chugai Pharmaceutical, Boehringer Ingelheim, GlaxoSmithKline, Eisai, Taisho Pharmaceutical, Bristol Myers Squibb, Pfizer and Taiho Pharmaceutical, and research grants from Mitsubishi Tanabe Pharma, Eisai, Chugai Pharmaceutical and Taisho Pharmaceutical. The remaining authors declare that they have no conflict of interests., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Background: Transcatheter edge-to-edge repair (TEER) is used to treat patients with mitral regurgitation (MR). The Geriatric Nutritional Risk Index (GNRI) is a well-known nutritional marker that predicts mortality risk., Objectives: The objectives of this study were to elucidate the clinical association between the degree of GNRI and different etiologies of MR and to clarify the patient samples for whom GNRI is more relevant to clinical outcomes following TEER., Methods: Data from 3,554 patients with MR who underwent TEER were analyzed using a Japanese multicenter registry. The patients were classified into 4 groups: GNRI <82, GNRI 82 to 92, GNRI 92 to 98, and GNRI >98. Procedural and clinical outcomes were compared between GNRI groups. Short- and long-term all-cause mortality were explored using Cox regression analysis., Results: Among the 3,554 patients, the median GNRI was 92.3. The mean follow-up period was 586.8 ± 436.5 days; 806 patients died during the follow-up period. Thirty-day mortality occurred in 51 patients (1.4%), and the GNRI <82 group had the highest 30-day mortality rate. Kaplan-Meier curves showed significantly better prognoses for the entire cohort, functional MR, and degenerative MR across the 4 groups (P < 0.001). GNRI values, even after adjustment for multiple confounders, showed a stepwise increase in risk of death in the GNRI 92 to 98, GNRI 82 to 92, and GNRI <82 groups compared to GNRI >98 as the reference., Conclusions: Regardless of MR etiology, GNRI is a useful predictor of short- and long-term mortality in patients undergoing TEER. Although TEER is effective for MR patients in malnourished states, further studies focused on the value of identifying and addressing malnutrition in this population are needed., Competing Interests: Funding support and author disclosures The OCEAN-Mitral registry, which is part of the Optimized Catheter Valvular Intervention–Structural Heart Disease (OCEAN-SHD) registry, was supported by Edwards Lifesciences, Medtronic Japan, Boston Scientific, Abbott Medical Japan, and the Daiichi-Sankyo Company. Drs Yamamoto, Kubo, Saji, Izumo, Watanabe, Nakajima, Ohno, Enta, Shirai, Mizuno, Boda, Kodama, and Amaki are clinical proctors of transcatheter edge-to-edge repair for Abbott Medical and have received lecture/consultant fees from Abbott Medical. Dr Asami has received speaker fees from Abbott Medical. Dr Yamaguchi is a clinical proctor of transcatheter edge-to-edge repair for Abbott Medical and has received a lecture fee and a scholarship donation from Abbott Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Drs Kubo and Maruo are clinical proctors for Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: The biocompatibility of expanded polytetrafluoroethylene in the pulmonary position seems better than allogenic or xenogeneic reactivity. This study reviewed the application of pulmonary expanded polytetrafluoroethylene conduits having a hand-sewn tricuspid valve with diameters of 18-24 mm., Methods: All patients receiving this conduit between 2010 and 2022 were evaluated. A 0.1-mm-thick membrane and a standard-wall tube of expanded polytetrafluoroethylene were used for cusp and conduit material, respectively., Results: Eighty-four consecutive patients were included. The median operative age and weight were 12 (range, 1.2-40) years and 34 (range, 9.1-82) kg, respectively. Eighteen-, 20-, 22- and 24-mm conduits were used in 19, 5, 3 and 57 patients, respectively. The overall survival was 94% at 5 and 10 years with four non-valve-related deaths. There were five conduit replacements, all for 18-mm conduit stenosis. Freedom from conduit replacement was 98% and 83% at 5 and 10 years, respectively. Freedom from conduit stenosis ≥ moderate was 83% and 54% at 5 and 10 years, respectively. Freedom from pulmonary regurgitation ≥ moderate was 98% at 5 and 10 years. Linear mixed-effects models with echocardiographic data implied that 24-mm conduits functioned with a peak velocity <3.0 m/s and without moderate/severe regurgitation in patients with a body weight of up to 75 kg and a body surface area of up to 2.0 m2 for >12 years postoperatively., Conclusions: This conduit has shown favourable clinical outcomes and is a valid alternative, especially in young patients with increased risk for early failure of the existing products., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objective: Considering the diverse aetiologies and immunodysregulatory statuses observed in each patient with rheumatoid arthritis (RA), stratification based on peripheral blood immunophenotyping holds the potential to enhance therapeutic responses to molecular targeted therapies, biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs)., Methods: Immunophenotype analysis was conducted on a cohort of over 500 b/tsDMARDs-naïve patients using flow cytometry. Patients with RA were stratified based on their immunophenotypes, and the treatment response to each targeted therapy was evaluated. Validation was performed using an additional cohort of 183 b/tsDMARDs-naïve patients with RA., Results: Patients with RA were stratified into five clusters, two of which exhibited distinct RA phenotypes compared with controls, characterised by significant increases in CD4 + effector memory T cells re-expressing CD45RA. Notably, the effectiveness of different b/tsDMARDs varied across clusters. The group using promising b/tsDMARDs was labelled as 'expected' whereas the 'non-expected' group comprised those using others. The expected group outperformed the non-expected group with higher 26-week remission rates (39.9% vs 24.6%, p=0.0004) and low disease activity achievement (80.8% vs 60.2%, p<0.0001). Trajectory analysis showed the non-expected group's 26-week disease activity was influenced by Clinical Disease Activity Index at baseline unlike the expected group. Additionally, different molecular targeted therapies influenced the proportions of each immune cell subset variably. To validate, immunophenotyping was performed on a validation cohort. When 183 cases were grouped based on their b/tsDMARDs usage into expected/non-expected groups, the expected group had a higher remission rate (p=0.0021), further confirming the observed trend., Conclusion: Our findings offer valuable insights into the diversity of RA and potential therapeutic strategies grounded in the molecular underpinnings., (Copyright © 2024 European Alliance of Associations for Rheumatology (EULAR). Published by Elsevier B.V. All rights reserved.)

Background: Research on the impact of angiographically detected residual trabeculation after left atrial appendage closure (LAAC) is limited., Objectives: To investigate the incidence, characteristics, and clinical implications of angiographically detected residual trabeculation after LAAC using the WATCHMAN device., Methods: We analyzed 1350 consecutive patients with atrial fibrillation undergoing LAAC using the WATCHMAN device from the OCEAN-LAAC registry, which is a prospective ongoing, multicenter Japanese registry. The inclusion criteria comprised patients who successfully underwent LAAC and whose presence or absence of residual trabeculation can be confirmed using a contrast medium. The clinical outcomes were compared between patients with and without angiographically detected residual trabeculation., Results: Residual trabeculation was angiographically detected in 5.6% (75/1350 patients). At the procedure, the proportion of peri-device leak (PDL) was significantly higher in the residual trabeculation group than in the non-residual trabeculation group (20% vs. 5.1%, p < 0.001). However, the PDL and device-related thrombosis at 45 days and 1 year were comparable between the two groups (37% vs. 23%, p = 0.24; 28% vs. 31%, p = 0.84; 2.1% vs. 1.4%, p = 0.50; 6.9% vs. 6.0%, p = 0.69, respectively). The 3-year cumulative incidence of ischemic stroke, all cardiovascular death, and all-cause death were comparable between the two groups (5.7% vs. 5.5%, log-rank p = 0.96; 7.7% vs. 8.9%, log-rank p = 0.34, 31.4% vs. 22.3%, log-rank p = 0.71, respectively)., Conclusion: The angiographically detected residual trabeculation rate was 5.6%, and this population had a significantly higher prevalence of PDL at the procedure. However, the presence of residual trabeculation did not contribute to PDL or device-related thrombosis at follow-up or affect the clinical outcomes., (© 2024 Wiley Periodicals LLC.)

Background: Patients with atrial fibrillation and malignant left atrial appendage (LAA) may benefit from LAA closure (LAAC); however, evidence is limited., Objective: The purpose of this study was to determine management strategies and clinical outcomes in patients with atrial fibrillation and malignant LAA., Methods: Malignant LAA was defined as a history of ischemic stroke and/or evidence of LAA thrombus despite continuous oral anticoagulation (OAC) therapy (continuous for ≥3 weeks). We studied 80 patients with malignant LAA treated with LAAC. We compared these patients first against 44 patients with malignant LAA treated with OAC alone and second against 114 patients without malignant LAA who were treated with LAAC for conventional indications., Results: Among patients with malignant LAA (first comparison), those treated with LAAC had a higher 1-year cumulative incidence rate of ischemic stroke than did patients treated with OAC alone (6.3% vs 5.3%; log-rank, P = .09) whereas the difference in stroke risk while receiving OAC was comparable (2.7% vs 5.3%; log-rank, P = .84). Furthermore, all disabling stroke events in patients with malignant LAA treated with LAAC occurred only while not receiving OAC. Among patients treated with LAAC (second comparison), those with malignant LAA had a higher 1-year cumulative incidence rate of ischemic stroke (and ischemic stroke due to device-related thrombosis) than did those without malignant LAA (6.3% vs 2.2%; log-rank, P = .009 and 2.2% vs 0%; log-rank, P = .04, respectively). However, these differences in stroke risk were no longer significant while receiving OAC (2.7% vs 1.0%; log-rank, P = .11)., Conclusion: Combination performing LAAC and continuation of OAC may be options to prevent ischemic stroke in patients with high thromboembolic risk and malignant LAA., Competing Interests: Disclosures Drs Chatani and Kubo are clinical proctors for Boston Scientific and have received honoraria from Boston Scientific. All other authors declare no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: This study aims to investigate whether handgrip strength can predict all-cause mortality following transcatheter edge-to-edge repair (TEER), and whether it improves after TEER., Methods: The OCEAN-Mitral Registry includes 2077 patients who had handgrip strength test before TEER. Scores were divided into quartiles according to the handgrip strength. Additionally, 371 of them had follow-up handgrip strength test 1 year after TEER., Results: Quartile 4 (weakest) were more likely to be older, smaller, and more symptomatic due to heart failure than others as baseline characteristics. Multivariate analyses revealed that quartile 3 and 4 were independently associated with increased risk of all-cause mortality after TEER compared with quartile 1 as a referent (adjusted hazard ratio 1.58, 95 % confidence interval 1.06-2.35, p = 0.024 for quartile 3, and adjusted hazard ratio 2.40, 95 % confidence interval 1.62-3.55, P < 0.001 for quartile 4). In subanalysis, in primary MR, handgrip strength did not change in patients with successful MR reduction (MR ≤2+), whereas it significantly decreased in those without successful MR reduction (MR 3+/4+). Conversely, in secondary MR, it significantly increased in those with successful MR reduction, whereas it did not change in those without successful MR reduction., Conclusions: Weaker handgrip strength, one of the good indicators of frailty was associated with all-cause mortality following TEER. Reduction in MR was linked to improvements in frailty. This is the largest and the very first study showing that MR reduction ≤2+ after TEER would be important for improving frailty and keeping their resilience in this population., Condensed Abstract: The handgrip strength test is a quick and inexpensive way to assess the weakness as a part of frailty. The OCEAN-Mitral Registry includes 2077 patients who had handgrip strength test before transcatheter edge-to-edge repair. Weaker handgrip strength was independently associated with all-cause mortality following TEER. Itis useful for predicting mortality because of its ease. Additionally, we saw the change in frailty assessed by handgrip strength after TEER, and therefore MR reduction ≤2+ after TEER would be important for improving frailty or keeping their resilience in this population., Clinical Trials: OCEAN-Mitral registry (UMIN-ID: UMIN000023653)., Competing Interests: Declaration of competing interest Clinical proctor of TEER for Abbott Medical: Drs. Saji, Yamamoto, Asami, Enta, Shirai, Izumo, Mizuno, Watanabe, Amaki, Yamaguchi, Bota, Ohno, Ueno, Mizutani, Kubo, and Hayashida. Lecturer fees from Abbott Medical: Drs. Saji, Yamamoto, Asami, Enta, Shirai, Izumo, Mizuno, Watanabe, Amaki, Kodama, Yamaguchi, Bota, Ohno, and Kubo. Consultant fees from Abbott Medical: Drs. Saji, Yamamoto, Enta, Izumo, Shirai, Mizuno, Watanabe, Amaki, Bota, Ohno, Kubo, and Ohno. Scholarship donation from Abbott Medical: Drs. Isobe, and Yamaguchi. Advisor of Abbott Medical: Dr. Ohno. The other authors have no relationships relevant to the content of this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: Reversing heparin when managing coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) can provide hemostasis but may cause coronary thrombosis if a device is still present in a coronary artery., Aims: To assess the impact of heparin reversal while an intracoronary artery device is in place for CAP., Methods: This study analyzed CAP cases during PCI from January 2006 to October 2023. Patients were grouped according to implementing heparin reversal while an intracoronary artery device was in place. The safety outcome was coronary thrombosis after CAP. The efficacy outcomes were successful hemostasis and death from any cause., Results: CAP occurred in 368 of 22,368 cases (1.6%). Patients who had heparin reversal with a device in place comprised 211 (57%). Among these, coronary thrombosis occurred in 16 (7.6%). An activated clotting time (ACT) 〈150 seconds was significantly correlated with coronary thrombosis. Heparin reversal with a device in place was significantly associated with successful hemostasis (heparin reversal 91% vs. no heparin reversal 73%; adjusted odds ratio 2.78; 95% confidence interval 1.27-6.13; p = 0.011), but was not different for death from any cause (heparin reversal 4.3% vs. no heparin reversal 5.7%; adjusted odds ratio 0.97; 95% confidence interval 0.28-3.43; p = 0.964)., Conclusion: Heparin reversal with a device in place was associated with an increased risk of coronary thrombosis when ACT was less than 150 seconds. While it may not have a substantial association with a reduced risk of mortality, it offers an advantage in achieving successful hemostasis., (© 2024 Wiley Periodicals LLC.)

Aim/introduction: Although immune checkpoint inhibitor-related type 1 diabetes mellitus (ICI-T1DM) is a rare condition, it is of significant concern globally. We aimed to elucidate the precise incidence, risk factors, and impact of ICI-T1DM on survival outcomes., Materials and Methods: The study is a large retrospective cohort study, performed using the DeSC Japanese administrative claims database comprising 11 million patients. The database population is reportedly similar to the entire population of Japan. Patients administered ICI between 2014 and 2022 were enrolled in the study, including 21,121 patients. The risk factors for ICI-T1DM development and their characteristics were evaluated by logistic regression analysis. Development of a new irAE after the day following the first administration of ICI was set as the study outcome., Results: ICI-T1DM was observed in 102 (0.48%) of the 21,121 patients after ICI initiation. PD-(L)1 and CTLA-4 combination therapy was associated with an increased risk of ICI-T1DM compared with PD-1 monotherapy (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.21-4.58; P = 0.01). Patients with a prior diagnosis of diabetes mellitus (OR, 1.59; 95% CI, 1.03-2.46; P = 0.04) or hypothyroidism (OR, 2.48; 95% CI, 1.39-4.43; P < 0.01) also exhibited an increased risk of ICI-T1DM. The Kaplan-Meier analysis revealed that patients with ICI-T1DM showed higher survival rates than those without (log-lank test, P < 0.01). Multivariable Cox regression analysis demonstrated that ICI-T1DM development was associated with lower mortality (hazard ratio, 0.60; 95% CI, 0.37-0.99; P = 0.04)., Conclusions: Collectively, the results of this study demonstrate the precise incidence and risk factors of ICI-T1DM. The development of ICI-T1DM, like other irAEs, is associated with higher survival rates., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Renal impairment is associated with poor clinical outcomes in patients with cardiovascular diseases. Some studies have revealed the impact of renal impairment on the clinical outcomes of patients who underwent mitral valve transcatheter edge-to-edge repair (M-TEER). However, limited data are available regarding the impact of baseline renal impairment after M-TEER in Asian-Pacific patients with heart failure and severe mitral regurgitation., Objectives: This study sought to examine the effect of renal impairment on clinical outcomes after M-TEER using a large-scale nationwide registry in Japan., Methods: A total of 2,150 patients enrolled in the OCEAN-Mitral (Optimized Catheter Valvular Intervention) registry were divided into 3 groups according to the estimated glomerular filtration rate (eGFR) before M-TEER: normal eGFR (≥60 mL/min/1.73 m 2 ) (n = 291), renal impairment (<60 mL/min/1.73 m 2 ) (n = 1,746), and dialysis (n = 113). The impact of renal impairment and dialysis on major adverse cardiovascular events (MACE) (a composite of all-cause death and hospitalization for heart failure) was examined., Results: Kaplan-Meier analysis revealed that the renal impairment and dialysis groups had a significantly higher incidence of MACE (survival rates at 2 years: normal eGFR, 74.2% [95% CI: 66.9%-80.1%] vs renal impairment, 63.9% [95% CI: 61.0%-66.6%] vs dialysis, 50.9% [95% CI: 38.2%-62.2%]; P < 0.001). Multivariate Cox regression analysis identified dialysis as the strongest independent predictor of MACE (HR: 1.95; 95% CI: 1.33-2.85; P < 0.001)., Conclusions: Renal impairment was associated with an increased incidence of major adverse events, and dialysis was the strongest independent predictor of poor clinical outcomes after M-TEER in Asian-Pacific patients., Competing Interests: Funding Support and Author Disclosures The OCEAN-Mitral registry, which is part of the OCEAN-SHD registry, was supported by Edwards Lifesciences, Medtronic Japan, Boston Scientific, Abbott Medical Japan, and the Daiichi-Sankyo Company. The sponsors were not involved in the study, data collection, statistical analyses, or manuscript writing. Dr Yamaguchi is a clinical proctor of transcatheter edge-to-edge repair at Abbott Medical; and has received a lecture fee and a scholarship donation from Abbott Medical. Drs. Kubo, Saji, Izumo, Watanabe, Asami, Yamamoto, Nakajima, Amaki, Ohno Enta, Shirai, Mizuno, Naganuma, Bota, Ueno, Mizutani, and Hayashida are clinical proctors of transcatheter edge-to-edge repair at Abbott Medical. Drs. Kubo, Saji, Izumo, Watanabe, and Amaki have received consultant fees from Abbott Medical. Drs. Asami, Yamamoto, and Nakajima have received lecture fees from Abbott Medical. Dr Kodama has received speaker fees from Abbott Medical. Dr Ohno has received consultant, advisor, and speaker fees from Abbott Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Mitral transcatheter edge-to-edge repair (M-TEER) is a valid treatment option for severe mitral regurgitation (MR), necessitating accurate risk stratification of M-TEER candidates for effective patient selection, optimal periprocedural care and improved long-term outcomes. The body mass index (BMI) is a simple and practical prognostic index, and the obesity paradox has been widely reported., Methods and Results: Between April 2018 and June 2021, 2149 patients undergoing M-TEER were registered in the prospective multicentre registry and classified into three groups: underweight (BMI < 18.5 kg/m 2 ), normal weight (18.5 ≤ BMI < 25 kg/m 2 ) and overweight and obese (25 kg/m 2  ≦ BMI) [Correction added on 17 October 2024, after first online publication: In the preceding sentence, "18.5 ☆ BMI < 25 kg/m2" and "25 kg/m2 ☆ BMI" have been corrected to "18.5 ≤ BMI < 25 kg/m2" and "25 kg/m2  ≦  BMI" in this version.] The impact of underweight on the all-cause, cardiovascular and non-cardiovascular mortality following M-TEER was evaluated [follow-up duration: 436 (363-733) days]. The participants (median BMI: 21.1 kg/m 2 ) were categorized as underweight (n = 450, 20.9%), normal weight (n = 1409, 65.6%) and overweight and obese (n = 290, 13.5%). Compared with the other two groups, the underweight group exhibited several negative prognostic factors, including older age, frailty, no dyslipidaemia, hypoalbuminaemia, residual MR and non-home discharge. Underweight patients had the highest rate of all-cause, cardiovascular and non-cardiovascular mortality, whereas those in the other two groups were similar. As per the multivariate analysis, underweight itself was associated with all-cause mortality (hazard ratio: 1.52, 95% confidence interval: 1.17-1.97, P = 0.009) and cardiovascular mortality (hazard ratio: 1.45, 95% confidence interval: 1.04-2.01, P = 0.028)., Conclusions: Underweight patients had the highest mortality rate after M-TEER. Comorbidities, residual MR, discharge disposition and underweight status were correlated with postprocedural outcome., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: The association between periprocedural change in tricuspid regurgitation (TR) and outcomes in patients undergoing mitral transcatheter edge-to-edge repair (M-TEER) is unclear. This study aimed to examine the prognostic value of TR before and after M-TEER., Methods: Patients in the OCEAN-Mitral registry were divided into four groups according to baseline and post-procedure echocardiographic assessments: no TR/no TR (no TR), no TR/significant TR (new-onset TR), significant TR/no TR (normalized TR), and significant TR/significant TR (residual TR) (all represents before/after M-TEER). Tricuspid regurgitation ≥ moderate was defined as significant. The primary outcome was cardiovascular death or heart failure hospitalization. Tricuspid regurgitation pressure gradient was also evaluated., Results: The numbers of patients in each group were 2103 (no TR), 201 (new-onset TR), 504 (normalized TR), and 858 (residual TR). Baseline assessment for TR and TR pressure gradient was not associated with outcomes after M-TEER. In contrast, patients with new-onset TR had the highest adjusted risk for the primary outcome, followed by those with residual TR [compared with no TR as a reference, hazard ratio 1.83 (95% confidence interval: 1.39-2.40) for new-onset TR, 1.45 (1.23-1.72) for residual TR, and 0.82 (0.65-1.04) for normalized TR]. Similarly, from baseline to post-procedure, TR pressure gradient changes were associated with subsequent outcomes after M-TEER. New-onset and residual TR incidence was commonly associated with dilated tricuspid annulus diameter and atrial fibrillation., Conclusions: Post-procedural TR, but not baseline TR, was associated with outcomes after M-TEER. Careful TR assessment after the procedure would provide an optimal management for concomitant significant TR in patients undergoing M-TEER., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Atomically flat two-dimensional networks of boron are attracting attention as post-graphene materials. An introduction of cations between the boron atomic layers can exhibit unique electronic functions that are not achieved by neutral graphene or its derivatives. In the present study, we propose a synthesis strategy for ion-laminated boron layered materials in a solution phase, which enables the preparation of analogs by changing the alkali-metal species. The introduction of large cations extends the thermal range of the liquid-crystal phases because of weakened ionic interactions between borophene-like layers. An investigation of the capacitance of ion-laminated structures revealed a 10 5 -fold or better increase in capacitance when the borophene-like materials were introduced between electrodes. That is difficult for general materials since the dielectric constant of common materials is below several thousand., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Left atrial appendage closure (LAAC) has demonstrated favorable outcomes as an alternative to permanent anticoagulation in patients with nonvalvular atrial fibrillation (NVAF). In hemodialysis (HD) patients with NVAF, anticoagulation increases bleeding complications, with inconsistent benefits in stroke prevention., Objectives: This study aimed to clarify the benefit of LAAC for HD patients., Methods: Consecutive patients who underwent LAAC, as extracted from the Japanese multicenter registry, were eligible. When comparing HD and non-HD patients, perioperative events, including LAAC procedure success rates and the incidence of death, bleeding events, and ischemic stroke events, were analyzed., Results: Among 1,464 patients (mean age 77.1 ± 7.6 years, mean CHA 2 DS 2 -VASc score 4.9 ± 1.5, mean HAS-BLED score 3.1 ± 1.0), 172 were HD patients. The HD group had higher HAS-BLED scores, whereas more patients in the non-HD group had a history of Bleeding Academic Research Consortium type 3 bleeding. Device implantation success was 97.3% (95% CI: 96.3%-98.0%) (HD group; 97.1% [167 of 172], non-HD group; 97.3% [1,257 of 1,292]; P = 0.88). There were no in-hospital deaths, and perioperative complications were rare and did not differ between the 2 groups. The median follow-up period was 367 days (Q1-Q3: 242-422 days). The ischemic stroke rate following LAAC in the HD group was 1.1% (95% CI: 0.3%-1.9%) per 100 patient-years, comparable to the non-HD group., Conclusions: LAAC is feasible for HD patients and achieves results comparable to those in non-HD patients. Further research is necessary to determine the effectiveness of LAAC in preventing stroke in HD patients., Competing Interests: The OCEAN-LAAC registry, which is part of the OCEAN-SHD registry, is supported by Edwards Lifesciences, Medtronic, Boston Scientific, Abbott Medical, and Daiichi-Sankyo Company. Drs Nakashima, Yamamoto, Asami, Hachinohe, Ueno, and Kubo are clinical proctors for Boston Scientific. Dr Yamamoto has received lecture fees from Daiichi-Sankyo and Boston Scientific. Dr Saji has received lecture fees from Daiichi-Sankyo and Abbott Medical Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Objectives: This study aimed to identify characteristics of patients with rheumatoid arthritis (RA) with an inadequate response to Janus kinase inhibitors (JAKi-IR) and evaluate the efficacy and safety of subsequent treatments., Methods: This study included 434 patients with RA who started JAKi treatment. JAKi-IR patients were those who switched to another drug due to inadequate response or did not reach low disease activity within 26 weeks of beginning JAKi. The efficacy and safety of switched biological disease-modifying anti-rheumatic drugs (bDMARDs) or cycled targeted synthetic disease-modifying anti-rheumatic drugs were analysed 26 weeks after switching treatment in JAKi-IR patients., Results: Patients with JAKi-IR RA accounted for 31.8% (n=138/434). Multiple logistic regression identified factors contributing to JAKi-IR, such as the prior use of multiple ineffective bDMARDs and suboptimal JAKi dosing. There were no differences in patient background when comparing patients with RA with JAKi-IR who cycled to another JAKi (n=31) versus those who switched to bDMARDs (n=45). Among those cycling to another JAKi, the Clinical Disease Activity Index (CDAI) scores improved by week 26, with higher remission rates, while retention and adverse events remained similar. Trajectory analysis identified three CDAI response patterns, with the 'treatment response' group showing rapid and sustained improvement when cycling to another JAKi. Multiple logistic regression in this group identified another JAKi cycle as the critical factor for the treatment response., Conclusions: Cycling JAKis is more effective than switching to bDMARDs in JAKi-IR RA, with no differences in safety or retention. This study suggests that cycling to another JAKi may be appropriate for patients with RA with JAKi-IR., Competing Interests: Competing interests: YM has received consulting fees, speaking fees, and/or honoraria from Eli Lilly and has received research grants from GlaxoSmithKline. SN has received consulting fees, lecture fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, AbbVie, Astellas, Asahi-kasei, Sanofi, Chugai, Eisai, Gilead Sciences, Eli Lilly, Boehringer Ingelheim. SK has received speaking fees from Bristol-Myers. YT has received consulting fees, speaking fees, and/or honoraria from AbbVie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD and Santen, and received research grants from Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, AbbVie and Bristol-Myers. All other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Buerger's disease is characterised by peripheral ischaemia due to occlusion of small- and medium-sized arteries in the extremities. This report describes a case of Buerger's disease in a 51-year-old male who presented with findings resembling systemic sclerosis (SSc). The patient exhibited Raynaud's phenomenon in year 2015, which developed to skin hardening, nail avulsion, and ulceration of the right fingers in year 2018. Diagnostic testing showed positive microvasculopathy on nailfold videocapillaroscopy (NVC) and positive fibrosis on skin biopsy. Although the patient fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for SSc, several findings in this case were atypical for SSc, including left-right asymmetry in finger involvement, nail loss, and negative autoantibody tests. Contrast-enhanced computed tomography showed poor perfusion of the right ulnar artery, and a heavy smoking history was established in the patient case. Therefore, based on Shionoya's criteria, he was diagnosed with a case of Buerger's disease confined to the upper extremity. Smoking cessation and vasodilator therapy resulted in the prompt resolution of ischaemic symptoms, skin hardening, and ulcerations. Furthermore, NVC abnormalities improved, and ulnar artery occlusion showed reperfusion on repeat testing. The present case suggests that hypoxaemia-driven microvasculopathy may contribute to vascular occlusion and skin fibrosis observed in this atypical presentation., (© Japan College of Rheumatology 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic mediator. We show that 12-day fibroblast culture with TNF-α or IL-13 induces fibrogenesis, marked by progressively increasing type III and VI collagen formation, and that TGF-β1 co-stimulation amplifies these effects. Tofacitinib substantially reduced the formation of ECM proteins in response to IL-13, while fibrogenesis in response to TNF-α or TGF-β1 was marginally inhibited. The in vitro findings were supported by clinical observations in patients with active rheumatoid arthritis, which had elevated serum type III collagen formation, indicating ongoing fibrogenesis during inflammation. After 48-60 weeks of tofacitinib treatment, type III collagen degradation, aswell as formation, were significantly decreased compared to baseline, highlighting dual anti-inflammatory and anti-fibrogenic effects of tofacitinib. In contrast, other anti-inflammatory treatments including methotrexate, adalimumab and tocilizumab demonstrated anti-inflammatory effects only. Our results highlight fibro-inflammatory profiles associated with TNF-α or IL-13 stimulation, both alone and in combination with TGF-β1, and support the use of tofacitinib as an anti-fibrogenic treatment in chronic inflammatory conditions., Competing Interests: Declarations. Competing interests: Martin Pehrsson, Anne-Christine Bay-Jensen, Morten Karsdal, Peder Frederiksen and Joachim H. Mortensen are employees at Nordic Bioscience, Denmark. Nordic Bioscience is a biotechnology company doing contract research with the pharmaceutical industry. Anne-Christine Bay-Jensen and Morten Karsdal own stock in Nordic Bioscience. The biomarker assays PRO-C1, PRO-C3, PRO-C6, FBN-C and C3M are proprietary intellectual property of Nordic Bioscience. Frederik S. Gillesberg, Bent W. Deleuran, Tue W. Kragstrup, Satoshi Kubo and Yoshiya Tanaka have no competing interests in relation to this work., (© 2025. The Author(s).)

Background: Optimal medical therapy for patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) remains unclear. This study aimed to investigate the association between beta-blocker uptitration and clinical outcomes after M-TEER., Methods: Using data from the Japanese multicenter registry, we examined 1474 patients who underwent M-TEER for SMR between April 2018 and June 2021. Beta-blocker uptitration was defined as an increased dose of beta-blockers 1 month after M-TEER compared with that before M-TEER. The 2-year clinical outcomes were compared between patients with and without beta-blocker uptitration, utilizing multivariable Cox regression analyses and propensity score matching (PSM)., Results: Of the 1474 patients who underwent M-TEER, 272 (18.4 %) were receiving increasing doses of beta-blockers at the 1-month follow-up. These patients had lower left ventricular ejection fraction (LVEF) and higher B-type natriuretic peptide levels. Most patients in the beta-blocker uptitration group received less than the target dose of beta-blockers. Multivariable Cox regression analyses showed that beta-blocker uptitration was significantly associated with a lower risk of all-cause (adjusted hazard ratio [HR]: 0.55; 95 % confidence interval [CI]: 0.36-0.84; P = 0.006) and cardiovascular mortalities (adjusted HR: 0.45, 95 % CI: 0.26-0.79, P = 0.006). PSM analyses revealed consistent findings. Subgroup analyses revealed a significant interaction between beta-blocker uptitration and LVEF≤40 % (interaction P = 0.018)., Conclusions: In patients with SMR, beta-blocker uptitration after M-TEER was associated with better clinical outcomes, especially in the group with an LVEF≤40 %. Efforts to uptitrate guideline-directed medical therapy after M-TEER for SMR may be necessary, even if reaching the target dose proves challenging., Competing Interests: Declaration of competing interest Drs. Kubo, Saji, Izumo, Watanabe, and Amaki are clinical proctors of transcatheter edge-to-edge repair for Abbott Medical and have received consultant fees from Abbott Medical. Dr. Asami is clinical proctors of transcatheter edge-to-edge repair for Abbott Medical and received speaker fees from Abbott Medical. Dr. Kodama is a clinical proctor of transcatheter edge-to-edge repair for Abbott Medical and has received speaker fees from Abbott Medical. Dr. Yamamoto is a clinical proctor of transcatheter edge-to-edge repair for Abbott Medical and have received lecture fees from Abbott Medical. Dr. Yamaguchi is a clinical proctor of transcatheter edge-to-edge repair for Abbott Medical and has received a lecture fee and scholarship donation from Abbott Medical. Dr. Ohno is a clinical proctor of transcatheter edge-to-edge repair for Abbott Medical and has received consultant, advisor, and speaker fees from Abbott Medical. Drs. Enta, Shirai, Mizuno, Ueno, Bota, and Hayashida are clinical proctors of transcatheter edge-to-edge repair for Abbott Medical. The remaining authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to investigate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., loxoprofen) on pharyngitis-induced dysphagia in rats., Design: A pharyngitis rat model was generated by topical application of acetic acid to the laryngopharyngeal region. Changes in water swallowing were evaluated by endoscopic observation over time. A histological analysis of the laryngopharyngeal mucosa was performed. The effects of loxoprofen, antibacterial drugs, and transient receptor potential (TRP) channel inhibitors were investigated in model rats., Results: After acetic acid treatment, water-evoked swallowing was impaired on day 1 (prolonging the swallowing latency and interval and decreasing the number of swallows), and recovered until day 6. Administration of loxoprofen significantly alleviated impaired water swallowing. Histologically, loxoprofen significantly improved inflammation of the pharynx, including submucosal edema, but did not affect the loss of taste bud-like structures in the arytenoid. In contrast, the administration of antibacterial drugs or TRP channel inhibitors did not affect the impairment of water swallowing in the model group., Conclusion: These results demonstrate the efficacy of systemic administration of loxoprofen in improving swallowing impairment in a pharyngitis model rat. This study is the first to provide scientific evidence for the use of NSAIDs in the management of pharyngitis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chihiro Nakatomi reports financial support was provided by Daiichi Sankyo Healthcare Co Ltd. Sayaka Kubo reports a relationship with Daiichi Sankyo Healthcare Co Ltd that includes: employment. Tomoki Shimada reports a relationship with Daiichi Sankyo Healthcare Co Ltd that includes: employment. Keiko Tsuji reports a relationship with Daiichi Sankyo Healthcare Co Ltd that includes: employment. Sayaka Kubo, Tomoki Shimada, Keiko Tsuji has patent pending to Japan Patent Office. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)