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There is a scarcity of data on clinical outcomes after intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with multivessel disease and chronic kidney disease (CKD). The Optimal Intravascular Ultrasound (OPTIVUS)-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1,015 patients who underwent multivessel IVUS-guided PCI including left anterior descending coronary artery target with an intention to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared the clinical outcomes between patients with and without CKD. The primary end point was a composite of death, myocardial infarction, stroke, or any coronary revascularization. There were 528 patients (52.0%) without CKD (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m 2 ), 391 patients (38.5%) with moderate CKD (60 >eGFR ≥30 ml/min/1.73 m 2 ), and 96 patients (9.5%) with severe CKD (eGFR <30 ml/min/1.73 m 2 or hemodialysis). The rate of meeting OPTIVUS criteria was not different across the 3 groups. The cumulative 1-year incidence of the primary end point was 9.1%, 9.0%, and 22.1% in patients without CKD, with moderate CKD, and with severe CKD, respectively (log-rank p <0.001). After adjusting confounders, the higher risk of severe CKD relative to no CKD remained significant for the primary end point (hazard ratio 2.42, 95% confidence interval 1.30 to 4.25, p = 0.01), whereas the risk of moderate CKD relative to no CKD was not significant for the primary end point (hazard ratio 0.97, 95% confidence interval 0.61 to 1.53, p = 0.88). In conclusion, in patients who underwent multivessel IVUS-guided PCI, and were managed with contemporary clinical practice, 1-year clinical outcomes were worse in patients with severe CKD, whereas 1-year clinical outcomes were not different between patients without CKD and with moderate CKD., Competing Interests: Declaration of competing interest Dr Yamamoto reports honoraria from Abbott Medical and Boston Scientific. Dr Morimoto reports lecturer's fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Pfizer (New York, NY), Tsumura and UCB; manuscript fee from Pfizer; advisory board for GlaxoSmithKline, Novartis, and Teijin. Dr Kimura reports research grant from Abbott Medical, and Boston Scientific; honoraria from Abbott Medical, Boston Scientific, Daiichi Sankyo, Sanofi, and Terumo; participation on advisory board from Abbott Medical, Boston Scientific, and Sanofi. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Short measurement scales are increasingly sought-after for reasons of efficiency and survey fatigue. A short four-item measure of an organization's climate for employee psychological health, the psychosocial safety climate (PSC-4), has gained international usage. However, the psychometric properties of its Japanese version (PSC-4J) are unknown. We examined the reliability and validity of the PSC-4J., Methods: An online survey containing the Japanese 12-item PSC scale (PSC-12J), from which the PSC-4J derived, and relevant variables (job demands, job resources, and outcomes) was administered to 2200 employees registered with a Japanese online survey provider. Two weeks later, the PSC-12J was measured again with a follow-up survey of 1400 respondents. Internal consistency and test-retest reliability were examined by Cronbach's α and intraclass correlation (ICC). Agreement between PSC-4J and PSC-12J was examined by Spearman's correlation. Structural validity was examined by confirmatory factor analysis (CFA) and item response theory (IRT) analysis. Convergent validity was examined by Spearman's correlations of PSC-4J with relevant variables, comparing these results with the PSC-12J., Results: Cronbach's α and ICC for PSC-4J were 0.91 and 0.68, respectively. Spearman's correlation between PSC-4J and PSC-12J was 0.97. The CFA assuming a one-factor structure showed good model fit. The IRT analysis indicated each PSC-4J item had very high discrimination and appropriate difficulty. Spearman's correlations of PSC-4J with relevant variables were slightly lower than for PSC-12J but in the theoretically expected direction., Conclusions: The PSC-4J, while slightly inferior to the PSC-12J in psychometric properties, provides comparable measurements with fewer items while maintaining adequate reliability and validity., (© 2025 Wiley Periodicals LLC.)

Background: Bioelectrical impedance analysis (BIA) is widely used as a convenient method of measuring body composition. The validity of the phase angle (PhA), impedance rate (IR), and resistance rate (RR) as indices of muscle quality using BIA has been suggested. This study aimed to investigate the relationship between these muscle quality indices and age, and to clarify their characteristics., Methods: The appendicular muscle mass (AMM), AMM corrected for body mass index (AMM/BMI), PhA, IR, and RR were determined using BIA in 1376 Japanese individuals (532 males and 844 females) aged 15-95 years. The PhA was determined from a 50-kHz current, and the IR and RR were determined from the impedance and resistance ratios between the 250- and 5-kHz currents., Results: AMM/BMI showed greater age-related changes than the other indices of muscle mass. Significant differences in PhA, IR, and RR were found for the whole body at age ≥ 50 years and for the lower limbs at age ≥ 30 years, compared to those in their 20 s. For the arms, age-related changes were small, and significant differences in PhA of females were only observed at aged ≥ 85 years, whereas significant differences in IR and RR were observed at aged ≥ 75 years, compared to those in their 20s., Conclusion: These results suggest that although PhA, IR, and RR in the whole body and lower limbs showed age-related changes, the change in PhA in the upper body was small, especially in females. However, IR and RR in the upper limbs of females reflected age-related changes more than PhA., Competing Interests: Declarations. Ethics approval and consent to participate: This study was reviewed and approved by the Research Ethics Committee of Kyushu Kyoritsu University (approval number: 2022–08) and Okayama Prefectural University (approval number: 20–72 and 23–62), and informed consent was obtained from all the participants prior to the examination. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: Long-term safety is fundamental for treatment decision-making. This integrated analysis of filgotinib clinical trials in rheumatoid arthritis (RA) and ulcerative colitis (UC) assessed adverse events of interest (AEI): major adverse cardiovascular events (MACE), venous thromboembolism (VTE) and malignancies., Methods: Data were integrated from all phase II and III trials that have investigated filgotinib 100 mg or 200 mg once daily in RA and UC to date., Results: Analyses represent >12 500 (RA) and >2800 (UC) patient-years of exposure (PYE) to filgotinib. Incidences of AEI in the integrated analysis population were low. Modest numerical increases in incidence rates occurred in patients aged ≥65 years, including MACE (patients with RA), and malignancies (excluding non-melanoma skin cancer (NMSC)) and NMSC (patients with RA or UC). VTE was rare; in patients with RA aged ≥65 years receiving filgotinib 200 mg, exposure-adjusted incidence rate (95% CI) for VTE was 0.3 (0.1, 0.8)/100 PYE; no VTE events occurred in patients with UC aged ≥65 years. In patients with RA aged ≥65 years, MACE incidence rates were identical between filgotinib 100 mg and 200 mg; rates of malignancies and NMSC were numerically higher with 200 mg compared with 100 mg., Conclusions: Data are consistent with previous overall safety analyses demonstrating low rates of AEI in the overall study population. Numerically increased rates of AEI occurred in patients aged ≥65 years; further data are needed to assess the effect of CV risk factors. Overall, in this analysis, there was no consistent filgotinib dose effect on AEI., Competing Interests: Competing interests: XM has received consultancy fees from BMS, Galapagos, GSK, Janssen, Novartis and Pfizer. SB has received consultancy fees from Galapagos; and is a founder of, and shareholder in, Liqomics. SA has received consultancy fees (paid to institution) from MSD; honoraria (paid to institution) from BMS, Ipsen, Roche; has participated on a data safety monitoring board or advisory board for Astellas; has a leadership role in BITOX network (www.BSMO.bbe/BITOX) and received grants or contracts (paid to BITOX) from AstraZeneca, BMS, Ipsen, MSD, Roche and Sanofi. ZS has received consultancy fees and honoraria from AbbVie, Eli Lilly, Gedeon Richter, Novartis, Pfizer and Sobi; and meeting attendance support from AbbVie, Pfizer and Sobi. CC-S has received consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Octapharma, Pfizer, Recludix and Sana Biotechnology; and grant/research support from AbbVie, Alexion, BMS, CSL Behring, Janssen, Octapharma, Pfizer and Priovant. SS has received honoraria and meeting attendance support from AbbVie, Amgen, Arena, Biogen, BMS, Celgene, Celltrion, Eli Lilly, Falk, Ferring, Fresenius Kabi, Galapagos, Gilead, Hikma, IMAB, Janssen, MSD, Pfizer, Protagonist, Proventin Bio and Sandoz/Hexal; and has participated in an advisory board for Takeda. EHSC has received speaker fees from AbbVie, Amgen, BMS, Chugai, Eli Lilly, Fresenius Kabi, Galapagos, Gilead, Novartis, Pfizer, Regeneron, Roche and Sanofi-Aventis; consultancy fees from AbbVie, Amgen, Biogen Therapeutics, Chugai, Eli Lilly, Fresenius Kabi, Galapagos, Gilead, GSK, Janssen, Novartis, R-Pharm, Roche, Sanofi-Genzyme, SynAct Pharma and UCB and grant/research support from Bio-Cancer, Biogen, Novartis, Pfizer, Roche and Sanofi. LP-B has received grants from Celltrion, Fresenius Kabi, Medac, MSD and Takeda; consultancy fees from AbbVie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Eli Lilly, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Vectivbio, Ventyx, Viatris and Ysopia; honoraria from AbbVie, Alfasigma S.p.A., Amgen, Arena, Biogen, Celltrion, Eli Lilly, Ferring, Galapagos, Genentech, Gilead, Janssen, Kern Pharma, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots and Viatris; meeting attendance support from AbbVie, Alfasigma S.p.A., Amgen, Celltrion, Connect Biopharm, Eli Lilly, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer and Tillots and participated in data safety monitoring or advisory boards for AbbVie, Alfasigma S.p.A., Amgen, Arena, Biogen, Celltrion, Eli Lilly, Ferring, Galapagos, Genentech, Gilead, Janssen, Kern Pharma, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots and Viatris. MS has received grants from Chugai and Novartis; honoraria from AbbVie, Alfasigma S.p.A., AstraZeneca, Boehringer Ingelheim, BMS, Chugai, EUSA-Pharma, Galapagos, Gilead, Janssen-Cilag, Mylan, Novartis, Onkowissen.de and Roche; meeting attendance support from Boehringer Ingelheim, Celgene, Chugai, Galapagos, Medac, Mylan, Roche and UCB and participated in data safety monitoring or advisory boards for AbbVie, Alfasigma S.p.A., Amgen, AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, EUSA-Pharma, Galapagos, Gilead, Hexal/Sandoz, Janssen-Cilag, Novartis, Onkowissen.de, Roche and UCB. YT has received honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer and Taisho and research grants from Chugai, Eisai, Mitsubishi Tanabe and Taisho. HtC received consultancy fees from Alveron, AstraZeneca, Galapagos, Novostia and Viatris and research funding from Bayer and Synapse. All revenues are deposited at the CARIM Institute for Research. He is a shareholder in Coagulation Profile. RW has received consultancy fees and honoraria from Celltrion and Galapagos. CJvdW has received research grants from Benelux, Falk, Ferring, Janssen and Pfizer; consultancy fees from Celltrion and Galapagos and speaker fees from AbbVie and UCB. EVEO received consultancy fees from Alfasigma S.p.A., Galapagos and Janssen; and is a shareholder in UCB. MF is an employee of, and holds stock options in, Galapagos. TM is a former employee of Galapagos. PVH has received consultancy fees from AOP Health, Aspen and Galapagos. CW is a former employee of Alfasigma S.p.A. and Galapagos and holds stock options in Galapagos. CR is a former employee of Galapagos and a current employee of Alfasigma S.p.A. AS has received consultancy fees from AbbVie, BMS and Johnson & Johnson; honoraria from AbbVie, BMS, Galapagos, Johnson & Johnson and Takeda and payments to institute from AbbVie, BMS, Galapagos and Takeda., (© 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.)

In light of the introduction of new Janus kinase inhibitors (JAKi), new indications for JAKi and recent safety considerations that have arisen since the preceding consensus statement on JAKi therapy, a multidisciplinary taskforce was assembled, encompassing patients, health care professionals, and clinicians with expertise in JAKi therapy across specialties. This taskforce, informed by two comprehensive systematic literature reviews, undertook the objective to update the previous expert consensus for using JAKi developed in 2019. The taskforce deliberated on overarching principles, indications, dosage and comedication strategies, warnings and contraindications, screening protocols, monitoring recommendations, and adverse effect profiles. The methodology was based on the European Alliance of Associations for Rheumatology standard operating procedures, with voting on these important elements. Furthermore, an updated research agenda was proposed. The task force did not address when a JAKi should be prescribed but rather considerations once this decision has been made. This update aimed to equip clinicians with the necessary knowledge and guidance for the efficient and safe administration of this expanding and significant class of drugs., Competing Interests: Competing interests PN received grants for research, clinical trials, and for advice and lectures from Pfizer, Novartis, Janssen, UCB, Lilly, AbbVie, Samsung, BMS, Servatus, and Amgen. AK reports speakers bureau and consultancy for AbbVie, Amgen, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, and UCB. DA reports consultancy fees, speakers’ bureau fees, and grant/research support from AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi. TD reports consulting fees from Roche, Novartis, GSK, and Astra Zeneca and participation in advisory boards of GNE, Roche, and Novartis. RF is a consultant for AbbVie, Pfizer, and BMS. IM reports honoraria/consultation fees and grants/research supports from AbbVie, Amgen, BMS, Causeway Therapeutics, Cabaletta, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi, UCB, Evelo, Compugen, AstraZeneca, and Moonlake. JP reports honoraria from BMS and Pfizer. NS consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. YT has received speaker fees and/or honoraria from Eli Lilly, AstraZeneca, AbbVie G.K., Gilead Sciences K.K., Chugai Pharmaceutical, Boehringer-Ingelheim, GlaxoSmithKline K.K, Eisai, Taisho Pharmaceutical, Bristol-Myers Squibb, and Pfizer and research grants from Mitsubishi Tanabe Pharma, Eisai, Chugai Pharmaceutical, and Taisho Pharmaceutical. MT is a speaker and/or consultant and/or advisory board member for Albireo, BiomX, Falk, Boehringer Ingelheim, Bristol-Myers Squibb, Falk, Genfit, Gilead, Intercept, Janssen, MSD, Madrigal, Novartis, Phenex, Pliant, Regulus, and Shire and reports grants/research support from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda, and UltraGenyx. KW reports consultant honoraria or research grants from Pfizer, AbbVie, Lilly, BMS, and Galapagos. MdW has received honoraria for consultancies and speaking through Stichting Tools from AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and Roche. JA reports Karolinska Institutet has entered into agreements with the following entities, with JA as PI, regarding the ARTIS national safety monitoring of rheumatology immunomodulators: Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, and Sanofi. XB reports grant/research support from AbbVie and Novartis; consulting fees from AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB Pharma; speakers’ bureau fees from AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB Pharma. W-HB reports honoraria as a speaker and/or advisor from AbbVie, BMS, Pfizer, and Sanofi. PE reports advisory roles for AbbVie, Activa, Astra-Zeneca, BMS, Boehringer Ingelheim, Galapagos,Gilead, Immunovant, Janssen, Lilly, and Novartis and participation in clinical trials for AbbVie, BMS, Lilly, Novartis, Pfizer, and Samsung. LG reports grants from AbbVie, Biogen, Lilly, Novartis, and UCB; personal fees from AbbVie, BMS, Celltrion, Janssen, Novartis, Pfizer, and UCB; honoraria for lectures from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada, and UCB; and nonfinancial support from AbbVie, Amgen, Biogen, Janssen, MSD, Pfizer, and UCB, outside the submitted work. JDI reports consultant in AbbVie, Anaptys Bio, Annexon Biosciences, AstraZeneca, BMS, Cyxone AB, Dragonfly, Eli Lilly, Galapagos NV, Gilead Sciences Ltd, GSK, Istesso, Janssen, Kenko International, Kira Biotech, Ono Pharma, Pfizer, Revelo Biotherapeutics, Roche, Sail, Sanofi, Sonoma Biotherapeutics, Topas, and UCB. MK reports advisory boards/consultancy for Novartis, BMS, and GSK. WM has acted as a paid consultant/participated in advisory boards for AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB; received research and/or educational grants from AbbVie, Novartis, Pfizer, and UCB; and received speaker fees from AbbVie, Janssen, Novartis, Pfizer and UCB. JP reports grants/research from BMS, Janssen, Mallinckrodt, and Pfizer (Seattle Genetics); is a consultant for AbbVie, Amgen, Astra Zeneca, Boehringer Ingelheim, Boxer Capital, Bristol Myers Squibb, Celltrion Healthcare, Eli Lilly, Frensenius Kabi, GSK, Janssen, Merck, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sandoz, Samsung, and Sanofi; is a speaker or in advisory board for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Certa, Eli Lilly, Frensenius Kabi, Janssen, Nordic Pharma, Novartis, Organon, Otsuka, Palleon, Pfizer, Sandoz, Sanofi, UCB, and Zura. MS-V received a grant for her PhD research from Roche and fees for lectures from Pfizer, outside the submitted work. KS reports speakers fees from UCB, Eli Lilly, and Rovi; research grants from Novo Nordic Foundation; and research support from the Danish Association for Rheumatism (Gigtforeningen). TS reports personal fees from AbbVie, Janssen, MSD, Novartis, and Roche, outside the submitted work. PCT reports research support from Galapagos (Alfasigma) and consultancy fees from Galapagos (Alfasigma), Gilead, Pfizer, AbbVie, and Lilly. TT reports speaking fee from AbbVie GK, Chugai, Eli Lilly Japan, Eisai, Gilead Sciences, Pfizer Japan, and Taisho Pharma and consultancy fees from AbbVie GK, Eli Lilly Japan, Gilead Sciences, Mitsubishi-Tanabe, and Taisho Pharma. FvdB reports speaker and/or consultancy fees from AbbVie, Amgen, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, Novartis, and UCB. RW acted as a PI and advisor for Celltrion and Galapagos. JSS reports research grants to his institution from AbbVie, AstraZeneca, Galapagos, and Lilly and honoraria for consultancies and/or speaking engagements from AbbVie, Ananda, AstraZeneca, Astro, BMS, Celgene, Celltrion, Chugai-Roche, Galapagos-Gilead, Immunovant, Janssen, Lilly, Novartis- Sandoz, Pfizer, R-Pharma, and Samsung. VK, EBL, LS-T, and MZ: none., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: In contrast to relapsing-remitting patterns, persistently active disease (PAD) is a disease activity pattern in patients with systemic lupus erythematosus (SLE) that is inadequately studied. We sought to identify the frequency and determinants of flare and PAD in SLE., Methods: Flare was defined using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI flare index), and PAD was defined as an SLEDAI-2K score of ≥4, excluding serology only, on two or more consecutive visits with a maximum six-month interval. Multivariable logistic regression was used to develop predictive models for flare and PAD, which were tested in an independent validation subset., Results: Among 3,811 patients over 2.8 (interquartile range 1.0-5.3) years of follow-up, 2,142 (56.2%) experienced flare and 1,786 (46.9%) had PAD, with 368 (9.7%) experiencing PAD but not flare. The most common flare features were nephritis and arthritis, whereas PAD was most commonly characterized by renal or mucocutaneous activity. After adjusting for prednisone dose and use of antimalarials and immunosuppressants, low gross domestic product in country of residence, smoking, arthritis, nephritis, and low complement levels were predictive for flare, whereas being in a low disease activity state for ≥50% of follow-up time (LLDAS50) was a protective factor. Renal activity and higher time-adjusted mean SLEDAI-2K were predictive of PAD, whereas LLDAS50 was protective. The models developed gave 72.1% and 83.8% correct classification of flare and PAD, respectively, in the validation cohort., Conclusion: Both flare and PAD are common disease activity patterns in SLE; both predict organ damage accrual but differ in disease features and predictive factors. Because 9.7% of patients experience PAD but not flare, flare measures alone do not adequately capture all patients in whom disease control is suboptimal., (© 2025 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: The dose level and duration needed for early rehabilitation of mechanically ventilated patients in the ICU need to be characterized. Therefore, this study aimed to assess the association between mobilization level, rehabilitation time, and dose (defined as the mean mobilization quantification score [MQS]) during ICU admission and the end point walking independence at hospital discharge in subjects needing ICU admission. Methods: This prospective, multi-center, cohort study included 9 ICUs. Consecutive subjects admitted to the ICU between September 2022-March 2023 receiving mechanical ventilation for >48 h were included in the study. The mean MQS score, highest ICU mobility score (IMS) during the ICU stay, time to the first mobilization day, ICU rehabilitation time (minutes of each rehabilitation physical activity from start to finish), frequency/d, baseline characteristics, and walking independence at hospital discharge were assessed. Results: Among the 116 subjects, 64 did and 51 did not walk independently at hospital discharge, respectively. Multiple logistic regression analysis revealed that the mean MQS and time to first mobilization were significantly associated with walking independence at hospital discharge. We observed that mean MQS was better than IMS, rehabilitation time, frequency, and time to first mobilization predicted walking independence based on receiver operating characteristic (ROC) curve comparison. Comparison of the mean MQS with that on the first mobilization day revealed superior predicting power of the mean MQS. The ROC curve cutoff value for the mean MQS was 4.0. Conclusions: This study shows that in subjects mechanically ventilated for >48 h the dose of rehabilitation calculated using the mean MQS during ICU was a better predictor of walking independence at hospital discharge than intensity, duration, or frequency of the mobilization therapy. Mean MQS during ICU stay may be used to measure and titrate optimal mobilization therapy.

Background: We previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented., Patients and Methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered., Results: In the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1-85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7-33.5) and 1.4 years [0.69-2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period., Conclusions: With longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC., Trial Registration Numbers: UMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036 . https://jrct.niph.go.jp/latest-detail/jRCTs071180036., Competing Interests: Declarations. Conflict of interest: Katsuyuki Hotta has personal fees from AZ, Chugai, Lilly, MSD, BMS, Ono, Boehringer-Ingelheim, NipponKayaku, Amgen, Taiho, Merck, and grants from MSD, AZ, Chugai, Lilly, BMS, Abbvie, Ono. Daijiro Harada has personal fees from Takeda Pharmaceutical Company Limited., Eli Lilly and Company, CHUGAI PHARMACEUTICAL CO., LTD., AstraZeneca K.K., TAIHO PHARMACEUTICAL CO., LTD., ONO PHARMACEUTICAL CO., LTD., Bristol-Myers Squibb Company, TOWA PHRMACEUTICAL CO., LTD., Nippon Boehringer Ingelheim Co., Ltd., and grants from MSD K.K., AstraZeneca K.K., Pfizer Japan Inc., ONO PHARMACEUTICAL CO., LTD., CHUGAI PHARMACEUTICAL CO., LTD., Eli Lilly and Company, Bristol-Myers Squibb Company, Takeda Pharmaceutical Company Limited. Akihiro Bessho has personal fees from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers Squibb, MSD, ONO Pharmaceutical, Eli Lilly, Daiichi Sankyo, Taiho Pharmaceutical, Boehringer Ingelheim, and grants from AstraZeneca, Chugai Pharmaceutical, MSD, Samsung Bioepis. Kentaro Tanaka has personal fees from AstraZeneca, Chugai, Johnson and Johnson, Nippon Boehringer Ingelheim. Koji Inoue has personal fees from AZ, Ono, Takeda, MSD, Daiichi Sankyo, Boehringer Ingelheim, Amgen, Lilly, Taiho. Kenichi Gemba has personal fees from Boehringer Ingelheim, BMS, AZ, MSD, Merck, Insmed, Lilly, Taiho, Chugai, NipponKayaku, Takeda. Toshio Kubo has personal fee from AstraZeneca. Eiki Ichihara has personal fees from AstraZeneca K.K., Novartis, Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Pfizer, Bristol-Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Boehringer Ingelheim, and receipt of equipment, materials or drugs from Janssen Pharmaceutical K.K., Astellas pharma, and grant from Janssen Pharmaceutical K.K. Hiromi Watanabe has personal fees from AZ, Chugai, Lilly. Kuniaki Katsui has personal fee from Accuray. Kenji Sugio has personal fees from AstraZeneca, Chugai, MSD, Eli Lilly Japan and grants from Chugai, MSD, Eli Lilly Japan, Daiichi Sankyo. Katsuyuki Kiura has personal fees from TAIHO Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Eli Lilly Japan K.K., Bristol-Myers Squibb K.K., Pfizer Japan Inc., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Company Limited, Nippon Kayaku Co., Ltd., NIPRO PHARMA CORPORATION, CHUGAI PHARMACEUTICAL CO., LTD., AstraZeneca K.K., Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD. and grants from TAIHO Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., ONO PHARMACEUTICAL CO., LTD., CHUGAI PHARMACEUTICAL CO., LTD., Nippon Kayaku Co., Ltd., TEIJIN PHARMA LIMITED., Shionogi Pharma Co., Ltd., Novartis Pharma K.K., Takeda Pharmaceutical Company Limited, KYORIN Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., MSD K.K., Pfizer Japan Inc. The other authors do not have any conflict of interest., (© 2025. The Author(s).)

In this study, we investigated the measurable residual leukemic stem cell (MR-LSC) population after allogeneic stem cell transplantation (allo-SCT) for high-risk acute myeloid leukemia (AML), utilizing T-cell immunoglobulin mucin-3 (TIM-3) expression as a functional marker of AML leukemic stem cells (LSCs). Analysis of the CD34 + CD38 - fraction of bone marrow cells immediately after achievement of engraftment revealed the presence of both TIM-3 + LSCs and TIM-3 - donor hematopoietic stem cells (HSCs) at varying ratios. Genetic analysis confirmed that TIM-3 + cells harbored patient-specific mutations identical to those found in AML clones, whereas TIM-3 - cells did not, indicating that TIM-3 + CD34 + CD38 - cells represent residual AML LSCs. In 92 allo-SCT occasions involving 83 AML patients, we enumerated the frequencies of TIM-3 + LSCs immediately after achieving hematologic complete remission with complete donor cell chimerism. Notably, only 22.2% of patients who achieved a TIM-3 + MR-LSC low status (<60%) experienced relapse, with a median event-free survival (EFS) of 1581 days (median follow-up duration was 2177 days among event-free survivors). Conversely, 87.5% of patients with TIM-3 + MR-LSC int/high (≥60%) relapsed, with a median EFS of 140.5 days. Furthermore, MR-LSC status emerged as a significant independent risk factor for relapse (hazard ratio, 8.56; p < 0.0001), surpassing the impact of patient disease status prior to allo-SCT, including failure to achieve complete remission (hazard ratio, 1.98; p = 0.048). These findings suggest that evaluating TIM-3 + MR-LSCs immediately after engraftment, which reflects the competitive reconstitution of residual TIM-3 + LSCs and donor HSCs, may be valuable for predicting outcomes in AML patients undergoing allo-SCT., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: FOLFOXIRI plus bevacizumab (BEV) is an option for first-line treatment of metastatic colorectal cancer (mCRC). However, there is no consensus on the optimal treatment strategy when disease progresses. The EFFORT open-label, multicenter, single-arm phase II study investigated whether FOLFIRI plus aflibercept retains activity after progression of FOLFOXIRI plus BEV treatment., Methods: The patients with unresectable mCRC who failed first-line FOLFOXIRI plus BEV received FOLFIRI plus aflibercept. The primary endpoint was progression-free survival (PFS) in the full analysis set (FAS). Angiogenic biomarkers were measured before treatment initiation., Results: From April 2019 to May 2021, 35 patients were enrolled and 34 were analysed in the FAS population (men, 18; median age, 63 years [range: 32-78]). The primary tumor was left-sided in most cases (23/34), 23 patients were RAS mutant, 3 patients had BRAF V600E mutation and 27 patients had liver metastases. The primary end-point was met with a median PFS of 4.3 months [80% confidence interval [CI] 3.7-5.1]. Median overall survival was 15.2 months [95% CI 8.9-22.7]. Per RECIST, there were 1 complete response, 4 partial responses, 21 stable diseases and 8 disease progressions. Overall response rate was 14.7% [95% CI 5.0-31.1], and disease control rate was 76.5% [95% CI 58.8-89.3]. Responses were more common in patients with high VEGF-C, low VEGF-D and low PlGF levels before treatment., Conclusion: FOLFIRI plus aflibercept, administered after failure of FOLFOXIRI plus BEV, is effective and has a manageable safety profile. This regimen may be a useful second-line treatment option for these patients., Competing Interests: Declarations. Conflict of interest: KA, MS, HY, YN, TK, KT, KB, HO, KH and SS declare no conflicts of interest. HSatake has received research funding from AsahiKASEI Co. Ltd., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. and Sanofi, honoraria from Bayer Co., Ltd., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Co., Ltd. and Yakult Honsha Co., Ltd. AM received honoraria from Eli Lilly, Japan K.K.; Taiho Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Bristol-Myers Squibb Co., Ltd.; and Daiichi Sankyo Co., Ltd. HS received research funding from Taiho Pharmaceutical Co. Ltd. and Chugai Pharmaceutical Co. Ltd.. AT received honoraria for lectures from ELI LILLY JAPAN K.K., TAIHO PHARMACEUTICAL CO., LTD., ONO PHARMACEUTICAL Co., Ltd., CHUGAI PHARMACEUTICAL Co., Ltd., Merck Biopharma Co., Ltd., NOVARTIS PHARMA K.K., TAKEDA PHARMACEUTICAL COMPANY LIMITED, DAIICHI SANKYO CO., LTD, MSD K.K., TSUMURA & Co., AstraZeneca K.K., Sun Pharmaceutical Industries Limited, ASAHI KASEI PHARMA CORPORATION. HB received scholarship grants from Eli Lilly Japan and K.K. EO received research funding from Guardant Health and honoraria for lectures from Ono, Takeda, Bayer, Chugai, Taiho, Eli Lilly, and Bristol Myers Squibb. Ethics statement: Approval of the research protocol by an Institutional Reviewer Board: Before the initiating the study, the principal investigator consulted a Certified Review Board (certification no. CRB718005), received approval from the study site manager, and submitted a trial plan to the Ministry of Health, Labour, and Welfare. Informed consent statement: This study was conducted in accordance with the Good Clinical Practice guidelines and guiding principles detailed in the Declaration of Helsinki and in keeping with the applicable local law(s) and regulations (s). Written informed consent for the study procedures was provided by all candidate patients before enrolment. Registry and the registration No. of the study/trial: This study was registered with the Japan Registry of Clinical Trials (registration number: jRCTs071190003). Animal studies: Not applicable., (© 2025. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Rationale: Accurate prognostic awareness (PA) and knowledge of the disease are critical for decision-making regarding treatment options, advance care planning, and end-of-life care. However, they have not been investigated in patients with interstitial lung disease (ILD). Objectives: To determine the prevalence of patients with ILD who have accurate PA and/or knowledge of acute exacerbation and whether accurate PA is associated with end-of-life medical interventions and quality of dying and death. Methods: Through a nationwide bereavement survey, we examined the prevalence of accurate PA and knowledge of acute exacerbation (AE) in patients with ILD who died in acute general hospitals between January 2018 and February 2020. Patients' PA and knowledge were assessed from the perspective of the bereaved. We also quantified the quality of dying and death from the perspective of the bereaved using three scales-the Good Death Inventory, the Quality of Dying and Death questionnaire, and the single-item Quality of Dying and Death overall score-and obtained information on end-of-life interventions from the electronic medical record. We examined the associations of accurate PA with end-of-life interventions and quality of dying and death. Results: A total of 296 patients whose caregivers completed questionnaires were analyzed. One hundred sixty-three patients (55.1%; 95% confidence interval [CI], 49.2-60.8%) who died of ILD had accurate PA, and 138 (46.9%; 95% CI, 41.1-52.8%) recognized that their disease could have AE. Multivariate regression analysis showed that accurate PA was associated with significantly fewer intensive care unit deaths (odds ratio, 0.28; 95% CI, 0.10-0.82; P  = 0.02). Patients with accurate PA had better quality of dying and death on all three scales. Conclusions: Approximately half of the patients who died of ILD did not recognize that their disease could lead to death or AE. The lower number of intensive care unit deaths and better quality of dying and death in patients with accurate PA suggest the potential benefits of obtaining accurate PA in patients with ILD.

Background: Immune editing, in which human leukocyte antigens (HLA) have critical roles, has been suggested to shape the landscape of human cancer. This study prospectively investigated whether HLA gene zygosity is associated with the prognosis of primary androgen deprivation therapy in advanced prostate cancer., Methods: KYUCOG-1401-A was conducted in conjunction with a prospective clinical trial (KYUCOG-1401). Among the patients enrolled in KYUCOG-1401 and treated with primary androgen deprivation therapy, only Japanese patients were included. HLA genotypes of HLA-A, B, C, DRB1, DQB1, and DPB1 were determined. The effect of divergence of HLA genotypes on time to progression, prostate cancer-specific survival, and overall survival was evaluated., Results: Among 127 patients, homozygosity for HLA-DRB1 (HR, 95% CI; 4.05, 1.54-10.7, P = 0.0047) and HLA-DQB1 (HR, 95% CI; 3.75, 1.47-9.58, P = 0.0058) was associated with an increased risk of prostate cancer-specific mortality. Patients with higher HLA evolutionary divergence scores at HLA-DQB1 (HR, 95% CI; 0.90, 0.82-0.97, P = 0.0093) had lower risks of prostate cancer-specific mortality. Androgen-responsive gene sets were upregulated in CD4low and CD8low tumors in the prostate cancer cohort, but not in the bladder and kidney cancer cohorts., Conclusions: This study suggested that the diversity of HLA-II loci including HLA-DRB1 and HLA-DQB1 plays an important role in advanced prostate cancer survival, contributing to improved risk stratification in advanced prostate cancer. Moreover, it was shown that CD4 + T cells play an important role in androgen deprivation therapy, suggesting that immunotherapy targeting CD4 + T cells is promising for prostate cancer., Competing Interests: Competing interests: MS received honoraria from Janssen Pharmaceutical, AstraZeneca, Astellas Pharma, Sanofi, and Bayer and research funding support from Daiichi Sankyo. TK received research funding support from Janssen Pharmaceutical, Astellas Pharma, Shin Nippon Biomedical Laboratories, Ono Pharmaceutical, Bayer, Sanofi, and Takeda Pharmaceutical. HM received honoraria from Janssen Pharmaceutical, AstraZeneca, Astellas Pharma, Bayer, Chugai Pharmaceutical, and Merck and research funding support from Janssen Pharmaceutical, Takeda Pharmaceutical, and Kyowa Kirin. HS received honoraria from Takeda Pharmaceutical and Astellas Pharma. TI received honoraria from Janssen Pharmaceutical and Astellas Pharma. TK received honoraria from Takeda Pharmaceutical, AstraZeneca and Merck. AY received honoraria from Janssen Pharmaceutical and Astellas Pharma. ME received honoraria from Takeda Pharmaceutical, Janssen Pharmaceutical, AstraZeneca, and Astellas Pharma and research funding support from Astellas Pharma, Sanofi, and Takeda Pharmaceutical. Ethics approval: The study protocol was approved by the institutional review board of each institute. Consent to participate: All participants provided written informed consent., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: This study investigated the association between leave use and improvement of work functioning impairment affecting presenteeism., Methods: A prospective, observational study was conducted among 5752 employees in a single corporate group in Japan to analyze the number of days of leave taken over a 1-year period and changes in work functioning impairment., Results: As the number of leave days increased, work functioning impairment improved significantly., Conclusions: These results suggest that allowing employees to take more leave significantly contributes to improving work functioning impairment. Companies need to promote appropriate leave use to improve employee health and overall work productivity., Competing Interests: Conflict of Interest: Dr. Fujino has the copyright to WFun with royalties paid from Sompo Health Support Inc., outside from this work. The other authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Introduction: Our previous work demonstrated that evaluating large ischemic cores using the apparent diffusion coefficient (ADC) could predict EVT outcomes, with the most frequent ADC (peak ADC) ≥520×10 -6 mm 2 /s associated with better clinical results. Since the degree of ADC reduction reflects the severity of ischemic stress, this study aimed to assess the utility of an ADC color map in visualizing this stress., Patients and Methods: This retrospective cohort study included consecutive patients with a low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) using diffusion-weighted imaging (DWI) who underwent successful EVT recanalization between April 2014 and March 2023. To create a visual representation of ischemic stress, we assigned different colors to diffusion-weighted image (DWI) lesions based on their ADC values: ≥520×10 -6 mm 2 /s, 520-440×10 -6 mm 2 /s, and <440×10 -6 mm 2 /s. We compared patients with peak ADC ≥520×10 -6 mm 2 /s to those with lower peak ADC to identify factors associated with the higher value., Results: A total of 78 patients were enrolled, with 34 having a peak ADC ≥520×10 -6 mm 2 /s. The optimal ratio for discriminating peak ADC ≥520×10 -6 mm 2 /s was found to be 60 % for the volume of the lesion with ADC ≥520×10 -6 mm 2 /s (ADC 520 ) relative to the total DWI lesion volume. This ratio demonstrated a sensitivity of 86 % and a specificity of 82 %., Discussion and Conclusion: The ADC color map effectively portrays the depth of ischemic stress. A large ischemic core with an ADC 520 /DWI ratio >60 % may be salvageable with EVT. This approach offers a visual means for assessing EVT suitability in acute large ischemic stroke., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

At autopsy, around half of the Alzheimer's disease (AD) brains exhibit Lewy body pathology, and the main component of Lewy body pathology is α-synuclein aggregates. This study investigated the prevalence of cerebrospinal fluid (CSF) α-synuclein aggregation and its association with demographic factors and cognitive decline among 1619 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with the test for α-synuclein aggregation by seed amplification assay (SAA). This cohort consisted of 595 cognitively normal (CN) individuals, 765 with mild cognitive impairment (MCI), and 259 with AD dementia. The results showed a higher prevalence of positive α-synuclein aggregation status in the AD dementia group (37.07 %) and the MCI group (22.75 %) compared to CN controls (16.13 %). Additionally, APOE ε4 carriers exhibited a higher prevalence of α-synuclein aggregation compared to non-carriers: 20.12 % for APOE ε4-/- (non-carriers), 24.82 % for APOE ε4 + /-, and 30.92 % for APOE ε4 + /+ . Longitudinally, positive CSF α-synuclein aggregation associated with accelerated cognitive decline, especially in the MCI and AD groups. Notably, positive aggregation status did not significantly affect cognitive trajectories in CN individuals. Moreover, APOE ε4 carriers with positive CSF α-synuclein aggregation experienced more pronounced cognitive decline. This study provides evidence that CSF α-synuclein aggregation is associated with cognitive function and the APOE ε4 allele. These findings suggest that CSF α-synuclein SAA, in combination with APOE ε4 status, could serve as biomarkers for predicting cognitive decline in AD., Competing Interests: Declaration of Competing Interest The authors report that there are no conflicts of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.)

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.)

Background: Although bleeding is a common procedure-related adverse event following endovascular therapy (EVT), limited data exist regarding the procedural and anatomical factors associated with its complications in patients with lower-extremity artery disease (LEAD) undergoing EVT. Methods: Data were extracted from a nationwide Japanese EVT registry of 73,990 patients who underwent EVT for symptomatic LEAD between January 2021 and December 2022. The primary outcome measure was in-hospital bleeding complications, including access site bleeding, nonaccess site bleeding, and hemorrhagic stroke. Results: The mean age of the patients was 75 ± 9 years, and 69% were men. In-hospital bleeding complications were observed in 613 (0.8%) patients. Logistic regression analysis demonstrated significant associations between bleeding complications and the following procedural, anatomical, and pharmacological variables: emergent revascularization (odds ratio [OR]: 1.90, 95% CI: 1.29-2.79), multiple approach sites (OR: 2.46, 95% CI: 2.00-3.01), bilateral arterial calcification (OR: 1.46, 95% CI: 1.19-1.79), chronic occlusion (OR: 1.53, 95% CI: 1.28-1.83), dual antiplatelet therapy (OR: 1.70, 95% CI: 1.27-2.28), and oral anticoagulant (OR: 1.63, 95% CI: 1.31-2.03). The adjusted incidence of in-hospital bleeding was 0.59% (95% CI: 0.51-0.68%) in patients with one of the identified procedural and anatomical risk factors, 0.96% (95% CI: 0.82-1.13%) in patients with two factors, and 2.40% (95% CI: 1.88-3.05%) in patients with three or four factors. Conclusions: Procedural and anatomical factors as well as antithrombotic strategies were significantly associated with an increased risk of in-hospital bleeding in patients with LEAD who underwent EVT., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions., Competing Interests: All committee members and working group members submitted disclosure forms of financial and academic conflict of interest (COI) prior to being requested to participate in individual activities. All COI were collected according to the guideline by the JSICM and the JAAM. Detailed information of COI and the roles in creating this clinical guideline are summarized in Data S4., (© 2025 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: Low-gradient (LG) aortic stenosis (AS) has not been fully characterized compared with high-gradient (HG) AS in terms of cardiac damage, frailty, aortic valve calcification, and clinical outcomes., Objectives: The aim of this study was to compare the clinical characteristics and outcomes between each hemodynamic type of LG AS and HG AS., Methods: The current study included 3,363 patients in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) Registry-2 after excluding patients without indexed stroke volume or left ventricular ejection fraction (LVEF) data. Patients were divided into 4 groups (LG AS with reduced LVEF: n = 285; paradoxical low flow, low gradient [LFLG]: n = 220; normal flow, low gradient [NFLG]: n = 872; HG: n = 1,986)., Results: Compared with HG AS, LG AS with reduced LVEF more often had cardiovascular comorbidities, advanced cardiac damage, and frailty with less severe valve calcification and paradoxical LFLG AS more often had atrial fibrillation, advanced cardiac damage, and frailty with less severe valve calcification, while NFLG AS had comparable cardiac damage and frailty with less severe valve calcification. Cumulative 3-year incidence of death or heart failure hospitalization was higher in LG AS with reduced LVEF and paradoxical LFLG than in HG AS. After adjusting for confounders, LG AS with reduced LVEF and paradoxical LFLG compared with HG AS were independently associated with higher risk for death or heart failure hospitalization (HR: 1.82; 95% CI: 1.49-2.23; P < 0.001; and HR: 1.43; 95% CI: 1.13-1.82; P = 0.003, respectively) but NFLG AS was not (HR: 1.03; 95% CI: 0.88-1.21; P = 0.68)., Conclusions: Clinical outcomes were significantly worse in LG AS with reduced LVEF and paradoxical LFLG AS and comparable in NFLG AS compared with HG AS., Competing Interests: Funding Support and Author Disclosures This work was supported by an educational grant from the Research Institute for Production Development (Kyoto, Japan). Dr Shirai has served as a clinical proctor for Edwards Lifesciences, Medtronic, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025. Published by Elsevier Inc.)

Objectives: To assess safety of baricitinib in Japanese patients with rheumatoid arthritis (RA) in real-world clinical practice., Methods: This all-case postmarketing surveillance study included patients initiating baricitinib for RA from September 2017 to April 2019. Treatment duration was recorded. Safety data were collected for up to 3 years from initiation (up to 4 weeks postdiscontinuation in discontinuing patients)., Results: Safety analyses included 4720 patients; 2580 (54.7%) were ≥65 years old. Baricitinib persistence rate was 45.4% (3-year Kaplan-Meier analysis); the most common discontinuation reason was insufficient effectiveness (n = 1005, 21.3%). Serious adverse events occurred in 600 patients [incidence rate (IR) 10.42/100 patient-years (PY); 95% confidence interval, 9.76-11.09]. There were 39 deaths [IR 0.43 (0.30-0.57)/100 PY]. Adverse events of special interest IRs per 100 PY were herpes zoster 4.68 (4.22-5.14), serious infection 3.05 (2.68-3.41), malignancy 1.09 (0.87-1.30), major adverse cardiovascular events 0.35 (0.23-0.48), and venous thromboembolism 0.25 (0.15-0.36). IRs did not increase with prolonged exposure., Conclusions: No new safety concerns were identified during this 3-year postmarketing surveillance study of baricitinib in Japanese patients with RA. Patients and clinicians should be cognizant of herpes zoster and other serious infection risks during baricitinib treatment, especially in the first 6 months., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by optic neuritis and transverse myelitis, with an unclear genetic background. A genome-wide meta-analysis of NMOSD in Japanese individuals (240 patients and 50,578 controls) identified significant associations with the major histocompatibility complex region and a common variant close to CCR6 (rs12193698; p = 1.8 × 10 -8 , odds ratio [OR] = 1.73). In single-cell RNA sequencing (scRNA-seq) analysis (25 patients and 101 controls), the CCR6 risk variant showed disease-specific expression quantitative trait loci effects in CD4 + T (CD4T) cell subsets. Furthermore, we detected somatic mosaic chromosomal alterations (mCAs) in various autoimmune diseases and found that mCAs increase the risk of NMOSD (OR = 3.37 for copy number alteration). In scRNA-seq data, CD4T cells with 21q loss, a recurrently observed somatic event in NMOSD, showed dysregulation of type I interferon-related genes. Our integrated study identified novel germline and somatic mutations associated with NMOSD pathogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Convenient and portable, sustained provision of safe drinking water is crucial for wilderness survival. In this study, a portable water collection bag utilising solar-driven interface evaporation technology has been developed. The water collection bag includes a plastic film, CB-PS microsphere evaporator, and a small vial. By placing on the water surface, the CB-PS microspheres float and absorb sunlight to quickly evaporate the surrounding water. The plastic film and vial make it easy and fast to collect clean and safe drinking water. The device boasts an impressive evaporation rate of 1.64 kg·m⁻²·h⁻¹ under 1 sun illumination. Moreover, the portable water collection bag can withstand harsh acidic and alkaline conditions, efficiently removing organic contaminants from wilderness water sources to meet drinking water standards. Importantly, it is designed for repeated use without any water evaporation rate decreasing. The portable water collection bag also exhibits strong resistance to salt, making it suitable for applications in desalinating seawater into freshwater.

Objective: Disease activity both between and within patients with SLE is highly variable, yet factors driving this variability remain unclear. This study aimed to identify predictors of variability in SLE disease activity over time., Methods: We analysed data from 2930 patients with SLE across 13 countries, collected over 38 754 clinic visits between 2013 and 2020. Clinic visit records were converted to panel data with 1-year intervals. The time-adjusted mean disease activity, termed AMS , was calculated. The yearly change in [Formula: see text], denoted as [Formula: see text], was regressed onto [Formula: see text] and other potential predictors using random-effects models. Some variables were split into a person-mean component to assess between-patient differences and a demeaned component to assess within-patient variability., Results: Overall, variability in SLE disease activity exhibited stabilisation over time. A significant inverse relationship emerged between a patient's disease activity in a given year and variability in disease activity in the subsequent year: a 1-point increase in person-mean disease activity was associated with a 0.27-point decrease (95% CI -0.29 to -0.26, p<0.001) in subsequent variability. Additionally, a 1-point increase in within-patient disease activity variability was associated with a 0.56-point decrease (95% CI -0.57 to -0.55, p<0.001) in the subsequent year. Furthermore, each 1-point increase in the annual average time-adjusted mean Physician Global Assessment was associated with a 0.08-point decrease (90% CI -0.13 to -0.03, p=0.002) in disease activity variability for the following year. Prednisolone dose and the duration of activity in specific organ systems exhibited negative and positive associations, respectively, with disease activity variability in the subsequent year. Patients from less affluent countries displayed greater disease activity variability compared with those from wealthier nations., Conclusion: Disease activity tends to be less variable among patients with higher or more variable disease activity in the previous year. Within-patient variability in disease activity has a stronger impact on subsequent fluctuations than differences between individual patients., Competing Interests: Competing interests: NL’s salary from Monash University was partly supported by a research grant from BMS. AH has received a research grant from AstraZeneca, consulting fees from EUSA Pharma (UK), GSK and UCB Australia and speaker fees/honoraria from AbbVie, Eli Lilly, Janssen, Limbic, Moose Republic and Novartis. SS has received consulting fees from Pfizer, AstraZeneca and ZP Therapeutics. MN has received an investigator grant from the National Health and Medical Research Council of Australia (NHMRC GNT1176538), research grants from Boehringer Ingelheim and Janssen, consulting fees from AstraZeneca and GSK, honoraria for presentations from AstraZeneca, Boehringer Ingelheim and GSK and support for conference attendance from Boehringer Ingelheim. SO has received speaker fees/honoraria from AstraZeneca and Limbic. ZL has received consulting fees from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis and UCB Pharma, and holds royalties with these companies. SN has received consulting and lecture/speaker fees from AstraZeneca, Biogen and Boehringer Ingelheim and is a non-paid member of Viatris (Idorsia) Advisory Board. YK has received payment/honoraria from GlaxoSmithKline KK, AstraZeneca KK, Sanofi KK, Pfizer Japan, Janssen Pharmaceutical KK, Chugai Pharmaceutical, Asahi Kasei Pharma, Astellas Pharma and Mitsubishi Tanabe Pharma. MH has received payment for postmarketing surveillance from GlaxoSmithKline KK, a research grant from Novartis Pharma, and honoraria for lectures from GlaxoSmithKline KK, AstraZeneca KK and Astellas Pharma. FG was a Director on the Board of the Australian Rheumatology Association at the time of the study. ZZ has received payment/honoraria from AbbVie, AstraZeneca KK, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Novartis, Pfizer, Roche, Sanofi, Janssen and UCB Pharma, and has participated in advisory boards for BeiGene. TT has received consultancy fees from AstraZeneca, Kowa and Mitsubishi Tanabe. KN has received speaker fees from Novartis. YT has received speaker fees and/or honoraria from AbbVie, Eisai, Chugai, Eli Lilly, Boehringer Ingelheim, GlaxoSmithKline, Taisho, AstraZeneca, Daiichi-Sankyo, Gilead, Pfizer, UCB, Asahi Kasei and Astellas, and received research grants from Boehringer Ingelheim, Taisho and Chugai. Y-HC has received advisory board fees and honoraria from Pfizer, Novartis, AbbVie, Johnson & Johnson, BMS, Roche, Lilly, GSK, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Eisai and CSL Behring, as well as research grants from the Taiwan Ministry of Science and Technology, Taiwan Department of Health, Taichung Veterans General Hospital, National Yang-Ming University, GSK, Pfizer, BMS, Roche and AstraZeneca, and Medigen Vaccine Biologics. JChoi is an employee of BMS. RK-R has received grants from GSK and Novartis. EM has received consulting fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Novartis, Takeda and UCB., (© 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.)

Objectives: Controlling intraoperative bleeding during endoscopic submucosal dissection (ESD) is essential to ensure the safety and reliability of the procedure. ESD in spray coagulation mode (SCM-ESD) is expected to ensure more effective bleeding control. This study aimed to investigate the superiority of SCM-ESD over conventional forced coagulation mode ESD (FCM-ESD) in terms of hemostatic ability for treating early gastric neoplasms (EGNs)., Methods: This multicenter randomized controlled trial (Spray-G Trial) was conducted at five Japanese institutions. Patients with intramucosal EGNs were enrolled and randomly assigned to either the SCM-ESD or FCM-ESD group. The primary outcome was ESD completion with an electrosurgical knife alone, that is, without the use of hemostatic forceps. The number and duration of hemostatic procedures using hemostatic forceps, procedure time, curability, and adverse events were also evaluated., Results: Each group included 65 patients. The rate of ESD completion without using hemostatic forceps was significantly higher for SCM-ESD than for FCM-ESD (83.1% vs. 13.8%, p<0.0001). SCM-ESD and FCM-ESD did not differ significantly in terms of procedure time (48.3 min vs. 56.0 min, p=0.1071), R0 resection (100% vs. 95.4%, p=0.2442), and rate of adverse events (3.1% vs. 6.2%, p=0.6801)., Conclusions: SCM-ESD significantly improved ESD completion rates for intramucosal EGNs without using hemostatic forceps. SCM-ESD is a promising technique that may streamline ESD by eliminating the need to exchange devices and reducing costs. (UMIN Clinical Trials Registry, Numbers: UMIN000047353)., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)