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The dynamics of a magnetic domain wall (DW) under a transverse magnetic field Hy are investigated in two-dimensional (2D) Co/Ni microstrips, where an interfacial Dzyaloshinskii-Moriya interaction (DMI) exists with DMI vector D lying in +y direction. The DW velocity exhibits asymmetric behavior for ±Hy; that is, the DW velocity becomes faster when Hy is applied antiparallel to D. The key experimental results are reproduced in a 2D micromagnetic simulation, which reveals that the interfacial DMI suppresses the periodic change of the average DW angle φ even above the Walker breakdown and that Hy changes φ, resulting in a velocity asymmetry. This suggests that the 2D DW motion, despite its microscopic complexity, simply depends on the average angle of the DW and thus can be described using a one-dimensional soliton model. These findings provide insight into the magnetic DW dynamics in 2D systems, which are important for emerging spin-orbitronic applications.

The study investigates the propagation of a magnetic domain wall (DW) in a submicron magnetic wire consisting of a magnetic/nonmagnetic/magnetic trilayered structure with asymmetric notches by utilizing the giant magnetoresistance effect. The findings indicated that the depinning field of the DW from the notch depends on the propagation direction of the DW.

No Heading Superfluid properties of 4He adsorbed in uniform straight pore 1.8 nm in diameter were studied using a torsional oscillator. In the pore, the first one or two layers of adsorbed. 4He are solid, therefore the pore diameter is effectively reduced to about 1.1 or 0.4 nm. In order to investigate whether 4He becomes superfluid in such a narrow pore, we performed the oscillator experiments for two cases: 4He is adsorbed (1) on the bare substrate and (2) on the pore completely filled with N2 atoms. In the latter case, only superfluid film coating the surface of the substrate grain can be detected. Compared with this case, an additional superfluid signal originating from 4He in the pore is observed for the bare substrate. This strongly suggests that 4He in the pore is superfluid. [ABSTRACT FROM AUTHOR]

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus. Participants with eHHV-6B had higher risks of SLE and PAP; the former was validated in All of Us. eHHV-6B-positivity and high SLE disease activity index scores had strong correlations. Genome-wide association study and long-read sequencing mapped the integration of the HHV-6B genome to a locus on chromosome 22q. Epitope mapping and single-cell RNA sequencing revealed distinctive immune induction by eHHV-6B in patients with SLE. In addition, high anellovirus load correlated strongly with SLE, RA and COVID-19 status. Our analyses unveil relationships between the human virome and autoimmune and infectious diseases., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Major hepatectomy (MH) can increase the risk of adverse events (AEs) owing to impaired drug metabolism due to decreased liver volume and surgical injury. Thus, we performed this subgroup analysis using data from JCOG1113, a phase III trial comparing gemcitabine plus S-1 (GS) and gemcitabine plus cisplatin (GC) in patients with advanced and recurrent biliary tract cancer (BTC), to evaluate the effect of MH on the safety and efficacy of GC and GS regimens in patients with recurrent BTC., Methods: Of the 354 patients with advanced BTC enrolled in JCOG1113, 76 patients with postoperative recurrence (30 in the MH group and 46 in the non-MH group) were analyzed., Results: Grade ≥ 3 platelet count decreased in both arms was more frequent in the MH group than in non-MH group (GC, 0.0 vs. 17.6%; GS, 3.9 vs. 15.4%). However, in the MH group, the white blood cell decreased (GC, 55.0 vs. 38.5%; GS, 23.1 vs. 7.7%) and anemia (GC, 15.0 vs. 11.8%; GS, 23.1 vs. 7.7%) were less common than in the non-MH group. The MH and non-MH groups showed no significant difference in overall survival (OS) in both GC [median OS, 23.0 in MH vs. 16.9 months in non-MH (hazard ratio, 0.857; 95% CI 0.387-1.899)], and GS [median OS, 21.5 vs. 14.9 months (hazard ratio, 0.670; 95% CI 0.310-1.447)] arms., Conclusions: The safety and efficacy of gemcitabine-based chemotherapy were comparable between patients who underwent MH and those who underwent other surgeries., Competing Interests: Declarations. Conflict of interest: C.M. reports research Funding from Eisai, Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck biopharma, Daiichi Sankyo, Boehringer Ingelheim, and honoraria from Novartis, Yakult Honsha, Teijin Pahrma, Eisai, MSD, AstraZeneka, SERVIER, Boehringer Ingelheim, Taiho. J.M.reports Employment/Leadership position/Advisory role from Phizer and honoraria from Chugai Pharmaceutical, Taiho Pharmaceutical, AstraZeneca. S.K. reports research funding from Bayer, Boston Scientific, Chugai Pharmaceutical, Eisai, Eli Lilly Japan, Takeda, Taiho Pharmaceutical, Yakult Honsha. H.I reports fees for promotional materials from Medico’s Hirata, and honoraria from Boston Scientific, Kaneka Medix, Medico’s Hirata, SB KAWASUMI LABORATORIES, AstraZeneca. H.K. reports grants from BMS K.K., ONO Pharmaceutical, Eli Lilly Japan, MSD K.K., and Daiichi Sankyo, and honoraria from Bristol-Myers Squibb, Eli Lilly Japan, MSD K.K., Ono Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Merck Biopharma, Takeda Pharmaceutical, Yakult Pharmaceutical Industry, Teijin Pharma, Taiho Pharmaceutical, Otsuka Pharmaceutical, Nippon Kayaku, and GlaxoSmithKline. M.I. reports Research Funding from AstraZeneca, Boehringer Ingelheim GmbH, Eisai, J-pharma, Merk biopharma, Ono Pharmaceutical, Eli Lilly Japan, and honoraria from AstraZeneca, Guardant Health Japan, Incyte, Taiho Pharmaceutical. N.M. reports research funding from Novartis, MSD, Incyte, Ono Pharmaceutical, Seagen, Pfizer, Boehringer Ingelheim, AstraZeneca and honoraria from Yakult Honsha, AstraZeneca, Novartis, FUJIFILM Toyama Chemical, MSD, Taiho Pharmaceutical, Boehringer Ingelheim. F.J. reports Research funding from MSD, J-Pharma, Delta-fly-Phrama, Taiho Pharmaceutical, Eisai, Ono Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Yakult Honsha and honoraria from Ono Pharmaceutical, Chugai Pharmaceutical, Eisai, Incyte Biosiciences, Eli Lilly Japan, Fuji Film, AstraZeneca, Yakult Honsha. U.M. reports research funding from Taiho Pharmaceutical, AstraZeneca, MSD, Nihon Servier, Ono Pharmaceutical, Incyte Biosciences Japan GK, Chugai Pharmaceutical, Boehringer Ingelheim GmbH, J-pharma, Eisai, Novartis Pharma K.K, Astellas, J-pharma, Delta-fly-Phrama, Novocure GmbH, and Chiome Bioscience Inc. and honoraria from Taiho Pharmaceutical, AstraZeneca, K.K, Yakult Honsha, MSD K.K, Nihon Servier, Ono Pharmaceutical, Incyte Biosciences Japan GK, Chugai Pharmaceutical, Boehringer Ingelheim GmbH, J-pharma, Daiichi Sankyo, Eisai, Takeda Pharmaceutical, Novartis Pharma K.K., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Few studies have assessed vertical ground reaction force, contact time, contact area, and center of pressure during gait in the early phase post-total hip arthroplasty. This study aimed to investigate whether these parameters are more pronounced in participants post-total hip arthroplasty compared to healthy controls., Methods: We included 22 female participants who underwent total hip arthroplasty (age, 68.9 ± 7.2 years; body mass index, 22.9 ± 2.6 kg/m 2 ) and 11 healthy female controls (age, 50.3 ± 7.8 years; body mass index, 19.4 ± 1.7 kg/m 2 ) as controls. Vertical ground reaction force, contact time, contact area, and center of pressure during gait were measured using a force plate. Comparisons between the affected, unaffected, and control legs were conducted using one-way analysis of variance or the Kruskal-Wallis test, with additional comparisons using independent t-tests or the Mann-Whitney U test., Findings: The first peak force was lower, the time to the first peak force and heel contact time were longer, and the contact area at the second peak force was significantly larger in the affected leg than in the unaffected leg or the right leg of the controls. These parameters were significantly more asymmetrical in the total hip arthroplasty cohort compared to the controls, with significant differences in the starting position and center of pressure length., Interpretation: The loading timing, magnitude, and form of plantar contact during gait were more asymmetrical in the total hip arthroplasty cohort than in healthy females. Early-phase rehabilitation post-total hip arthroplasty should address these asymmetries., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disease that mainly affects the peripheral nerves and nerve roots and typically presents with distal dominant motor and sensory disturbances as clinical symptoms. Central nervous system (CNS) demyelination with inflammation occurs infrequently in patients with CIDP. Here, we present a unique autopsy report of CIDP causing severe demyelination along the entire spinal cord. A Japanese woman exhibited progressive muscle weakness, muscle atrophy, sensory disturbances, and tremors in her upper and lower extremities, which began in her 60s. A nerve conduction study revealed a marked prolongation of distal latencies and very low or no compound muscle action potential amplitudes, and cerebrospinal fluid protein levels were prominently elevated. Following the diagnosis of CIDP, a combination of methylprednisolone pulse therapy, high-dose intravenous immunoglobulin therapy, and plasma exchange mildly improved her symptoms. The patient died of septic shock at the age of 74 years. Neuropathological examination revealed demyelinating lesions with inflammation in the peripheral regions of the anterior, lateral, and posterior funiculi along the entire spinal cord (from the cervical to the sacral cord), and axons and neurons were well preserved in these lesions. The nerve roots in the cervical and lumbar plexuses, cauda equina, sciatic nerve, and sural nerve showed prominent swelling and edema with infiltration of inflammatory cells. Many onion bulbs were visible in the fascicles of the sciatic and sural nerves. Our results suggest that demyelination with inflammation can occur in the CNS and peripheral nervous system in CIDP, especially in patients with specific conditions, such as severe intrathecal inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Beck, Yamashita, Kawai, Yamamura, Okuno, Matsui, Toyooka, Morii, Mochizuki and Murayama.)

Background: The optimal medical treatment strategy after transcatheter aortic valve replacement (TAVR) has not been established, and might be affected by the extent of extravalvular cardiac damage. We aimed to investigate the prognostic association of renin-angiotensin system (RAS) inhibitors in TAVR patients stratified according to the extent of extravalvular cardiac damage., Methods: In a prospective TAVR registry, patients were retrospectively evaluated for baseline cardiac damage and classified into 5 stages of cardiac damage (0-4) according to established criteria. Clinical outcomes at 1 year were compared according to RAS inhibitor prescription at discharge., Results: Among 2247 eligible patients who underwent TAVR between August 2007 and June 2021, 1634 (72.7%) were prescribed RAS inhibitors at discharge. Eighty-three patients (3.7%) were classified as stage 0, 276 (12.3%) as stage 1, 889 (39.6%) as stage 2, 489 (21.8%) as stage 3, and 510 (22.7%) as stage 4. RAS inhibitor prescription after TAVR was associated with a reduced risk of 1-year mortality (adjusted hazard ratio [HR adjusted ], 0.59; 95% confidence interval [CI], 0.45-0.77). The protective association was accentuated among patients with cardiac stages 3 and 4 (HR adjusted , 0.54 [95% CI, 0.32-0.92]; and HR adjusted , 0.58 [95% CI, 0.36-0.92], respectively), but not statistically significant in for those with stage 2 (HR adjusted , 0.70; 95% CI, 0.43-1.14)., Conclusions: In patients who underwent TAVR, we found a strong association of RAS inhibitor prescription and improved clinical outcome in the overall population, and there were no signs of heterogeneity across stages of cardiac damage., Clinical Trial Registration: NCT01368250., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Incomplete Freund's adjuvant (IFA) has long been used to trigger autoimmune diseases in animal models, such as experimental autoimmune encephalitis and collagen-induced arthritis. However, the molecular mechanisms that control CD4 T cell effector functions and lead to the development of autoimmune diseases are not well understood. A self-antigen and heat-killed Mycobacterium tuberculosis emulsified in IFA augmented the activation of CD4 T cells, leading to the differentiation of pathogenic CD4 T cells in the draining lymph nodes. In contrast, IFA emulsification did not elicit Foxp3 + regulatory T cell expansion. We found that pathogenic Th1 cells expressed miR-147-3p, which targets multiple genes to affect T cell function. Finally, miR-147-3p expressed in CXCR6 + SLAMF6 - Th1 cells was required for the onset of neurological symptoms through the control of CXCR3 expression. Our findings demonstrate that miR-147-3p expressed in pathogenic CD4 T cells regulates the migratory potential in peripheral tissues and impacts the development of autoimmune diseases., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy over ROI-based methods. We evaluated its performance against 145 cortical retrograde tracer injections in male and female marmosets that were used as ground truth cellular connectivity on a voxel-by-voxel basis. The receiver operating characteristic (ROC) curve was calculated for each injection, and we achieved area under the ROC curve of 0.95 for undirected and 0.942 for directed SCA in the case of high cell count threshold. This indicates that SCA can reliably estimate the strong cellular connections between voxels in fMRI data. We then used our directed SCA method to analyze the human default mode network (DMN) and found that dlPFC (dorsolateral prefrontal cortex) and temporal lobe were separated from other DMN regions, forming part of the language-network that works together with the core DMN regions. We also found that the cerebellum (Crus I-II) was strongly targeted by the posterior parietal cortices and dlPFC, but reciprocal connections were not observed. Thus, the cerebellum may not be a part of, but instead a target of, the DMN and language-network. Summarily, our novel directed SCA method, visualized with a new functional flat mapping technique, opens a new paradigm for whole-brain functional analysis., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Objective: To integrate long-term daily continuous glucose monitoring (CGM) device data with electronic health records (EHR) for patients with type 1 and type 2 diabetes (T1D and T2D) in the national Veterans Affairs Healthcare System to assess real-world patterns of CGM use and the reliability of EHR-based CGM information. Research Design and Methods: This observational study used Dexcom CGM device data linked with EHR (from 2015 to 2020) for a large national cohort of patients with diabetes. We tracked the initiation and consistency of CGM use, assessed concordance of CGM use and measures of glucose control between CGM device data and EHR records, and examined results by age, ethnicity, and diabetes type. Results: The time from pharmacy release of CGM to patients to initiation of uploading CGM data to Dexcom servers averaged 3 weeks but demonstrated wide variation among individuals; importantly, this delay decreased markedly over the later years. The average daily wear time of CGM exceeded 22 h over nearly 3 years of follow-up. Patterns of CGM use were generally consistent across age, race/ethnicity groups, and diabetes type. There was strong concordance between EHR-based estimates of CGM use and Dexcom CGM wear time and between estimates of glucose control from both sources. Conclusions: The study demonstrates our ability to reliably integrate CGM devices and EHR data to provide valuable insights into CGM use patterns. The results indicate in the real-world environment that CGM is worn consistently over many years for both patients with T1D and T2D within the Veterans Affairs Healthcare System and is similar across major race/ethnic groups and age-groups.

While fatty acid oxidation (FAO) in mitochondria is a primary energy source for quiescent lymphocytes, the impact of promoting FAO in activated lymphocytes undergoing metabolic reprogramming remains unclear. Here, we demonstrate that pemafibrate, a selective PPARα modulator used clinically for the treatment of hypertriglyceridemia, transforms metabolic system of T-cells and alleviates several autoimmune diseases. Pemafibrate suppresses Th17 cells but not Th1 cells, through the inhibition of glutaminolysis and glycolysis initiated by enhanced FAO. In contrast, a conventional PPARα agonist fenofibrate significantly inhibits cell growth by restraining overall metabolisms even at a dose insufficient to induce fatty acid oxidation. Clinically, patients receiving pemafibrate showed a significant decrease of Th17/Treg ratio in peripheral blood. Our results suggest that augmented FAO by pemafibrate-mediated selective activation of PPARα restrains metabolic programs of Th17 cells and could be a viable option for the treatment of autoimmune diseases., Competing Interests: Declaration of competing interest All authors do not have any other financial support which could create a potential conflict of interest or the appearance of a conflict of interest concerning the work in the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The importance of transcatheter heart valve (THV) design on clinical outcome in patients with aortic stenosis (AS) and left ventricular (LV) systolic dysfunction remains unknown., Objectives: We aimed to compare 5-year outcomes of patients with severe AS and reduced LV ejection fraction (LVEF), undergoing transcatheter aortic valve implantation (TAVI) with balloon-expandable vs. self-expanding THVs., Methods: In a retrospective analysis from the Bern TAVI registry, patients with LVEF <50% who underwent TAVI with either balloon-expandable or self-expanding THVs were included. A 1:1 propensity-score matching was performed to account for baseline differences between groups., Results: A total of 759 patients were included between August 2007 and December 2022, and propensity-score matching resulted in 134 pairs. Technical success was achieved in over 85% of patients, and was similar in both groups. Self-expanding THVs were associated with a lower mean transvalvular gradient (7.1 ± 3.7 mmHg vs. 9.9 ± 4.3 mmHg; P < .001) and a higher incidence of ≥mild-to-moderate paravalvular regurgitation (36.3% vs. 11.3%; P < .001) compared to balloon-expandable THVs. At 5 years, patients treated with a self-expanding THV had higher all-cause mortality than those with a balloon-expandable THV (67.8% vs. 55.8%, HR adjusted : 1.44; 95% CI: 1.02-2.03; P = .037). There were no significant differences in other clinical outcomes up to 5 years between groups., Conclusions: In the setting of LV systolic dysfunction, patients treated with a self-expanding THV had higher risk of 5-year mortality compared to patients treated with a balloon-expandable THV., Clinical Trial Registration: https://www., Clinicaltrials: gov. NCT01368250., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In 2021, Japan approved transcatheter aortic valve replacement (TAVR) for end-stage renal disease patients on hemodialysis (ESRD-HD). Yet, clinical/anatomical differences and outcomes between patients with and without ESRD-HD remain underexplored. This single-center study enrolled consecutive patients who underwent TAVR with the SAPIEN 3 between 2021 and 2023. Baseline characteristics and outcomes up to 1 year were compared. Inverse probability treatment weighting (IPTW) approach and Cox regression were used. Among 287 eligible patients, 59 had ESRD-HD. Patients with ESRD-HD were predominantly male (59.2% vs. 40.7%; p = 0.01), younger (78.0 [73.5-83.5] vs. 84.0 [79.8-88.0]; < 0.001), with lower body mass index (21.4 [19.6-23.3] vs. 22.9 [20.3-25.3]; p = 0.02], higher surgical risk (Society of Thoracic Surgeons Predicted Risk of Mortality ≧8%: 28 [47.5%] vs. 34 [14.9%]; p < 0.001), and more peripheral artery disease (25.4% vs. 4.8%; p < 0.001). Patients with ESRD-HD had a significantly higher prevalence of severely calcified femoral arteries (12.5% vs. 2.6%; p < 0.001). However, there were no differences in the computed-tomographic (CT) anatomical characteristics of the aortic valve complex (AVC), including the aortic valve calcium score (1995 [1372-3374] vs. 2195 [1380-3172]; p = 0.65) or the presence of moderate or severe left ventricular outflow tract calcification (4.3% vs. 5.2%; p > 0.99). Major vascular complications were rare, and technical (98.3% vs. 98.7%; p > 0.99) and device success (75.9% vs. 82.4%; p = 0.26) rates were high in both. At 1 year, there were no significant differences in a composite endpoint of death, stroke, major bleeding, or myocardial infarction (32.4% vs. 33.2%; HR 1.12; 95% CI 0.45-2.80; p = 0.81), nor its components after baseline adjustment., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Aims: Predictors of true degenerative mitral stenosis (MS) in patients with aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) remain unknown. This study aimed to investigate the predictors and prognostic value of true degenerative MS in this population., Methods and Results: We retrospectively reviewed the records of 760 consecutive patients who underwent TAVI. The mitral valve area (MVA) was assessed using transthoracic echocardiography, and mitral valve calcification was assessed using multi-detector computed tomography. MS was defined as an MVA of ≤2.0 cm², and true MS was defined as moderate or severe MS following TAVI. In our TAVI cohort, we identified 72 (9.5%) patients with degenerative MS. Among these, true MS was observed in 38 (52.7%) patients. Echocardiographic data showed that the true MS group had a significantly lower MVA and higher trans-mitral gradient. The severity of mitral annular calcification was not significantly different between the two groups; however, the true MS group had significantly more posterior mitral leaflet and anterior mitral leaflet (AML) calcification. Multivariable logistic regression analysis showed that AML calcification was the independent predictor of true MS [adjusted odds ratio, 9.23; 95% confidence interval (CI) 2.84-29.9]. True MS was independently associated with poor prognosis (adjusted hazard ratio, 2.76; 95% CI 1.09-6.98)., Conclusion: Approximately half of the patients with concomitant degenerative MS who underwent TAVI had true MS, which was associated with a poor prognosis. Computed tomographic analysis of AML calcification was useful for predicting true MS., Competing Interests: Conflict of interest: M.I. is a consultant for Edwards Lifesciences and Abbott Medical Japan, and S.K. is a consultant for Abbott Medical Japan. The other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Evidence for risk stratification using exercise stress echocardiography (ESE) in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) is currently lacking. Cardiac power output (CPO) has demonstrated prognostic value in patients undergoing TAVI for severe AS. This study investigated prognoses in patients undergoing TAVI for severe AS and to explore the additional information that ESE can provide for risk stratification., Methods: In this retrospective observational study, we included 96 consecutive patients who underwent TAVI for severe AS and patients with preserved left ventricular (LV) ejection fraction (≥ 50%) who underwent ESE at 3-6 months after TAVI. CPO was calculated as 0.222 × cardiac output × mean blood pressure/LV mass, where 0.222 was the conversion constant to W/100 g of the LV myocardium. All patients were followed up for all-cause mortality and hospitalization for heart failure., Results: Of the 96 patients, 3 were excluded and 93 patients (82.0 years; 45.2% male) were included in this study. During a median follow-up period of 1446 (1271-1825) days, the composite end point was reached in 17 patients. Multivariable Cox regression analysis revealed that CPO at rest and the change in CPO from rest to exercise (ΔCPO) were independently associated with the composite end point (hazard ratio = 0.278, p = 0.023). The addition of ΔCPO resulted in an incremental value of the model containing clinical and resting echocardiography variables (p = 0.030)., Conclusions: This study suggests that resting CPO and exercise-induced changes in CPO are useful for risk stratification of patients undergoing TAVI for severe AS., (© 2024. Japanese Society of Echocardiography.)

Lung cancer is a type of cancer that can metastasize to the lungs, brain, bones, liver, adrenal glands, and other organs; however, the occurrence of brain metastases is the most common event. Symptoms of brain metastasis include motor dysfunction, mental dysfunction, seizures, headaches, nausea, and vomiting, and significantly reduce the quality of life of cancer patients. Brain metastases are a poor prognostic factor, and controlling them is extremely important for prolonging prognosis and improving the quality of life. Currently, local surgery and radiotherapy are recommended for their treatment. However, recently, cancer treatments using molecular-targeted drugs and immune checkpoint inhibitors have been introduced, which may also be effective against brain metastases. Therefore, it is necessary to determine whether local or systemic therapy is optimal for each case. In this review, we focus on recent findings regarding drug therapy in treating brain metastases from advanced non-small cell lung cancer., (© 2024. The Author(s).)

Background: The previous Japanese clinical practice guidelines for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) were published in 2017. Recently, for the first time in 6 years, the MS and NMOSD guideline development committee revised the Japanese guidelines for MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)., Methods: The committee utilized the Grading of Recommendations Assessment, Development, and Evaluation system based on the "Minds Handbook for Clinical Practice Guideline Development 2020 Ver. 3.0″ with a focus on clinical questions (CQs). The committee also discussed clinical issues other than CQs, categorizing them as a question-and-answer (Q&A) section, including "issues on which experts' opinions agree to a certain extent" and "issues that are important but not included in the CQ"., Results: The committee identified 3, 1, and 1 key CQs related to MS, NMOSD, and MOGAD, respectively, and presented recommendations. A Q&A session regarding disease-modifying therapies and relapse prevention therapies for MS, NMOSD, and MOGAD was conducted. The revised guidelines were published in September 2023., Conclusions: The Japanese guidelines for clinical practice on MS, NMOSD, and MOGAD were updated. Treatment strategies for MS, NMOSD, and MOGAD are changing, and these updated guidelines may assist with treatment decisions for these diseases in clinical practice., 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 study., (Copyright © 2024. Published by Elsevier B.V.)

Myasthenia gravis (MG) is etiologically associated with thymus abnormalities, but its pathology in the thymus remains unclear. In this study, we attempt to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We find that the majority of thymomas are constituted by the cortical region. However, the small medullary region is enlarged in seropositive thymomas and contains polygenic enrichment and MG-specific germinal center structures. Neuromuscular medullary thymic epithelial cells, previously identified as MG-specific autoantigen-producing cells, are enriched in the cortico-medullary junction. The medulla is characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells and effector regulatory T cells. Similar germinal center structures and immune microenvironments are also observed in the thymic hyperplasia medulla. This study shows that the medulla and junction areas are linked to MG pathology and provides insights into future MG research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Pembrolizumab is the standard therapy for urothelial carcinoma treatment; however, adverse events have been noted. Here, we report a rare case of vision loss as an immune-related adverse event of pembrolizumab therapy in a patient with metastatic renal pelvic cancer., Case Presentation: A 69-year-old man treated with pembrolizumab for lung and lymph node metastases of renal pelvic cancer experienced significant vision loss in both eyes after 11 treatment cycles. Without magnetic resonance imaging confirmation owing to an MRI-unsafe pacemaker, his clinical features suggested immune checkpoint inhibitor-associated optic neuritis. Pembrolizumab was discontinued, and the patient received steroid pulse and immunoglobulin therapy. His vision in the right eye improved, but that in the left eye remained unchanged. He maintained a partial response for 36 months despite pembrolizumab discontinuation., Conclusion: Despite its rarity, vision loss is a potential irAE in patients treated with ICIs, including pembrolizumab., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background: Obesity paradox in cardiovascular risk prediction has gained increasing attention in recent years. We aimed to investigate the impact of BMI on mortality following transcatheter aortic valve replacement (TAVR)., Methods: We performed a multi-center retrospective analysis of patients with severe aortic stenosis undergoing TAVR. Patients were categorized into: Underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (BMI ≥ 30). Multivariate cox-proportional hazard model was used to compare all-cause mortality., Results: Total of 6688 patients included (175 underweight, 2252 normal weight, 2368 overweight and 1893 with obesity). Mean age of patients was 81 ± 8 years with 55% males. Patients with obesity had higher prevalence of comorbidities but a lower overall STS score. Mortality at 30-days post-TAVR was lower in the obese population compared to underweight, normal weight, and overweight patients (1.6% vs. 6.9%, 3.6%, and 2.8%, respectively, p < 0.001). Similarly, 3-year mortality was lowest in patients with obesity (17.1% vs. 28.9%, 24.5% and 18.6%, respectively, p < 0.001). On multivariate analysis, long term all-cause mortality at 3-years remained significantly lower in patients with obesity compared to underweight (HR 1.74, 95% CI: 1.30-2.40, p < 0.001) and normal weight (HR: 1.41, 95% CI:1.21-1.63, p < 0.001) but not in overweight patients (HR: 1.10, 95% CI:0.94-1.28, p = 0.240)., Conclusion: In conclusion, patients with obesity have improved short and long term mortality following TAVR with an observed progressive increase in mortality with lower BMI ranges., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has highly heterogeneous clinical presentations, in which encephalitis is an important phenotype. Moreover, MOGAD has been reported to exhibit diverse imaging findings. However, there have been no previous reports of cases with perivascular radial gadolinium enhancement in periventricular regions, commonly reported in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. In this paper, we present two cases of MOGAD with this MRI feature, both of which underwent brain biopsy for the lesions. Brain biopsies revealed perivenous demyelination and inflammation consistent with acute disseminated encephalomyelitis (ADEM), with pronounced axonal damage in Case 1 and minimal axonal involvement in Case 2. Case 1 exhibited more severe cerebral atrophy than Case 2, correlating with the extent of axonal damage. Through these cases, we highlight the heterogeneity of radiological manifestations of MOGAD, expanding the spectrum beyond previously defined MRI patterns. Furthermore, histopathological analysis revealed distinct axonal involvement as a potential prognostic marker of brain atrophy. These observations emphasize the importance of considering MOGAD in the differential diagnosis, even in cases with atypical imaging findings, and highlight the significance of brain biopsy in guiding both diagnosis and prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shimizu, Beck, Murayama, Hoshi, Sumikura, Higashida, Fukasaka, Shimada, Nagashima, Fujioka, Hatayama, Okuno, Mochizuki and Sakaguchi.)

Several X-linked genes escape from X chromosome inactivation (XCI), while differences in escape across cell types and tissues are still poorly characterized. Here, we developed scLinaX for directly quantifying relative gene expression from the inactivated X chromosome with droplet-based single-cell RNA sequencing (scRNA-seq) data. The scLinaX and differentially expressed gene analyses with large-scale blood scRNA-seq datasets consistently identified the stronger escape in lymphocytes than in myeloid cells. An extension of scLinaX to a 10x multiome dataset (scLinaX-multi) suggested a stronger escape in lymphocytes than in myeloid cells at the chromatin-accessibility level. The scLinaX analysis of human multiple-organ scRNA-seq datasets also identified the relatively strong degree of escape from XCI in lymphoid tissues and lymphocytes. Finally, effect size comparisons of genome-wide association studies between sexes suggested the underlying impact of escape on the genotype-phenotype association. Overall, scLinaX and the quantified escape catalog identified the heterogeneity of escape across cell types and tissues., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The concept of non-mass abnormalities of the breast has been employed in Japan for approximately 20 years. Although B-mode findings are classified as non-mass abnormalities, the usefulness of adding color Doppler ultrasonography (US) and strain elastography to B-mode US is unclear. Therefore, we conducted a multicenter study (JABTS BC-07) to establish the diagnostic criteria for breast US, including color Doppler and elastography, for non-mass abnormalities of the breast and verify their diagnostic usefulness., Methods: We registered US images of non-mass abnormalities of the breast and their clinical and histopathological data from 13 institutions (202 malignant and 183 benign non-mass lesions). Furthermore, we evaluated the centralized image interpretation usefulness of the diagnostic criteria for B-mode and color Doppler US, as well as the sensitivity and specificity when color Doppler US and elastography were added to B-mode US., Results: Echogenic foci in the mammary gland (odds ratio 3.45, 95% confidence interval [CI] 1.92-6.19, p < 0.0001) and the configuration of internal solid components of the ducts (odds ratio 0.056, 95% CI 0.005-0.591, p < 0.0165) significantly differentiated benign and malignant non-mass abnormalities. The sensitivity of B-mode alone (83.7%) was significantly improved by adding color Doppler US (93.1%) (p = 0.0004); however, adding color Doppler US and elastography to B-mode US made no significant difference in either sensitivity or specificity., Conclusion: Although adding color Doppler US and elastography to B-mode US improved sensitivity, the diagnostic significance was limited. Therefore, a comprehensive diagnostic method comprising mammography and magnetic resonance imaging is warranted., (© 2024. The Author(s).)

A 71-year-old man with advanced lung adenocarcinoma was treated with carboplatin, pemetrexed, and pembrolizumab in June 2020. Pemetrexed and pembrolizumab maintenance therapy were continued until November 2022. A fever and severe fatigue occurred in December 2022; however, the cause of the infection was inconclusive based on the patient's symptoms, imaging findings, and culture tests. Although the patient was administered antibiotics, his general condition worsened. Considering the possible diagnosis of immune-related cytokine release syndrome (CRS), the patient was administered prednisolone (1 mg/kg/day) and showed improvement. In conclusion, CRS can occur even long after the initial administration of immune checkpoint inhibitor therapy.

Objectives: This study aimed to evaluate whether switching disease-modifying therapies (DMTs) from sphingosine-1 phosphate (S1P) receptor modulators to either natalizumab (NTZ) or dimethyl fumarate (DMF) could restore the effectiveness of SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis (MS)., Methods: This study included 9 controls and 33 patients with MS: 7 patients treated with DMF, 7 patients treated with NTZ, 9 patients treated with S1P receptor modulators, and 10 patients who had switched DMTs from S1P receptor modulators to DMF or NTZ by the second vaccine dose. The patients who had switched DMTs were classified into two groups, based on whether their lymphocyte counts were above or below 1000/μL at the time of vaccination. In addition, relapses within 6 months after switching DMTs were also evaluated in these patients. Six months after the second dose of the vaccination, anti-SARS-CoV-2 spike antibodies were evaluated in all participants, and spike specific CD4 + T cells were also assessed in patients who had switched DMTs from S1P receptor modulators., Results: Patients treated with S1P receptor modulators had lower levels of anti-SARS-CoV-2 spike antibodies than the controls and patients treated with DMF and NTZ. On the other hand, in patients who had switched DMTs from S1P receptor modulators, a recovery of lymphocyte counts above 1000/µL resulted in restored humoral and cellular immune responses to the vaccination. There were no neurological relapses in patients who had switched DMTs from S1P receptor modulators to NTZ., Conclusion: SARS-CoV-2 mRNA vaccination is expected to be effective in patients whose lymphocyte counts have recovered due to switching DMTs from S1P receptor modulators. Switching DMTs from S1P receptor modulators to NTZ before vaccination may be beneficial in achieving efficacy for SARS-CoV-2 mRNA vaccination, with a reduced risk of relapse., Competing Interests: Declaration of Competing Interest Tatsusada Okuno received research grants from Biogen and Mitsubishi Tanabe Pharma Corp. He has also received speaker fees from Biogen, Novartis and Mitsubishi Tanabe Pharma Corporation. Ichino Chinen is an employee of Biogen Japan and owns stocks of Biogen. Makoto Kinoshita has received speaker fees from Biogen and Novartis. Hisashi Murata has received payment for lectures from Alexion Pharmaceuticals Inc. and Mitsubishi Tanabe Pharma Corp. Hideki Mochizuki has received speaker fees from Biogen, Novartis and Mitsubishi Tanabe Pharma Corp., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine the outcomes for elderly patients with de novo metastatic germ cell tumors and the influence of patient age on adherence to standard chemotherapy., Methods: A total of 150 patients who were initially diagnosed with metastatic germ cell tumors and treated at our institution between 2007 and 2021 were included. Patients were classified according to three age groups: aged <40, 40-49, and ≥50 years. Clinicopathological features, adherence to standard first-line chemotherapy, overall survival, and disease-free survival were compared between these groups. We also analyzed the outcomes of patients who received low-intensity induction chemotherapy due to adverse events and/or comorbidities., Results: There was no significant difference in any of the survival outcomes and in the rate of adherence to standard first-line chemotherapy between the three age groups, although elderly patients with intermediate/poor prognosis group tended to receive less-intense chemotherapies. The rate of febrile neutropenia as a chemotherapy-related adverse event was significantly higher in patients aged ≥50 years. No statistical significance in survival outcomes was detected between the group of patients who received relatively low-intensity induction chemotherapy and those who received adequately intensive planned chemotherapy., Conclusions: The adherence rate of standard fist-line chemotherapy of elderly patients is almost comparable to that of younger patients, although some adverse events should be carefully managed. Even elderly patients with metastatic germ cell tumors can aim for equivalently good survival outcome like younger populations, with effort to adhere to standard chemotherapy., (© 2024 The Japanese Urological Association.)

The title compound, C 15 H 12 BN 3 , is a type of di-aza-borinane featuring substitution at 1, 2, and 3 positions in the nitro-gen-boron six-membered heterocycle. It is comprised of two almost planar units, the pyridyl ring and the Bdan (dan = 1,8-di-aminona-phtho) group, which subtend a dihedral angle of 24.57 (5)°. In the crystal, the mol-ecules are linked into R 4 4 (28) hydrogen-bonding networks around the fourfold inversion axis, giving cyclic tetra-mers. The mol-ecules form columnar stacks along the c axis., (© Yamamoto et al. 2024.)

Methotrexate (MTX)-related lymphoproliferative disease (LPD) is one of the most prominent late complications associated with MTX treatment. Although MTX-related LPD exhibits a relatively high incidence of extranodal disease, the incidence of disease in a urinary bladder is very low. The present study reports the case of a patient with MTX-related LPD involving a urinary bladder mass. A 75-year-old female patient, who had been receiving MTX for ~15 years, was referred to the hospital due to fever and hematuria. A computed tomography scan revealed the thickening of the urinary bladder wall, hydronephrosis and lymph node swelling. The histopathological findings of the urinary bladder mass resulted in a diagnosis of MTX-related LPD. Although MTX withdrawal did not have any effect, the subsequent chemotherapy resulted in complete remission. Although MTX-related LPD in the bladder is rare, it is pertinent to consider MTX-related LPD when hematuria is observed during MTX therapy., Competing Interests: All authors declare that they have no competing interests., (Copyright: © 2024 Manabe et al.)

Assessment of the immune response to influenza vaccines should include an assessment of both humoral and cell-mediated immunity. However, there is a lack of consensus regarding the timing of immunological assessment of humoral and cell-mediated immunity after vaccination. Therefore, we investigated the timing of immunological assessments after vaccination using markers of humoral and cell-mediated immunity. In the 2018/2019 influenza season, blood was collected from 29 healthy adults before and after vaccination with a quadrivalent inactivated influenza vaccine, and we performed serial measurements of humoral immunity (hemagglutination inhibition [HAI] and neutralizing antibody [NT]) and cell-mediated immunity (interferon-gamma [IFN-γ]). The HAI and NT titers before and after vaccination were strongly correlated, but no correlation was observed between the markers of cell-mediated and humoral immunity. The geometric mean titer and geometric mean concentration of humoral and cellular immune markers increased within 2 weeks after vaccination and had already declined by 8 weeks. This study suggests that the optimal time to assess the immune response is 2 weeks after vaccination. Appropriately timed immunological assessments can help ensure that vaccination is effective.

Aims: Cardiac power output (CPO) measures cardiac performance, and its prognostic significance in heart failure with preserved ejection fraction (EF) has been previously reported. However, the effectiveness of CPO in risk stratification of patients with valvular heart disease and post-operative valvular disease has not been reported. We aimed to determine the association between CPO and clinical outcomes in patients with preserved left ventricular (LV) EF after transcatheter aortic valve implantation (TAVI)., Methods and Results: This retrospective observational study included 1047 consecutive patients with severe aortic stenosis after TAVI. All patients were followed up for all-cause mortality and hospitalization for HF. CPO was calculated as 0.222 × cardiac output × mean blood pressure (BP)/LV mass, where 0.222 was the conversion constant to W/100 g of the LV myocardium. CPO was assessed using transthoracic echocardiography at discharge after TAVI. Of the 1047 patients, 253 were excluded following the exclusion criteria, including those with low LVEF, and 794 patients (84.0 [80.0-88.0] years; 35.8% male) were included in this study. During a median follow-up period of 684 (237-1114) days, the composite endpoint occurred in 196 patients. A dose-dependent association was observed between the CPO levels and all-cause mortality. Patients in the lowest CPO tertile had significantly lower event-free survival rates (log-rank test, P = 0.043). Multivariate Cox regression analysis showed that CPO was independently associated with adverse outcomes (hazard ratio = 0.561, P = 0.020). CPO provided an incremental prognostic effect in the model based on clinical and echocardiographic markers ( P = 0.034)., Conclusion: CPO is independently and incrementally associated with adverse outcomes in patients with preserved LVEF following TAVI., Competing Interests: Conflict of interest: M.I. is a consultant of Edwards Lifesciences and Abbott Medical Japan, and S.K. is a consultant of Abbott Medical Japan. All other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Use of volatile anesthetics is associated with worse outcome following tumor resection surgery compared with the use of intravenous anesthetics. However, the underlying mechanism has not been clearly delineated yet in vivo . The EO771 cell-based congenic breast cancer model was used in the present study. Isoflurane directly binds to and inhibits two adhesion molecules, leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1). Similarly, exposure to sevoflurane, another volatile anesthetic and LFA-1 inhibitor, is associated with an increase in breast cancer size compared with non-exposure. Thus, the present study first examined the role of LFA-1 and Mac-1 in the EO771 breast cancer model. Both LFA-1 deficiency and inhibition enhanced tumor growth, which was supported by cytokine and eicosanoid data profiles. By contrast, Mac-1 deficiency did not affect tumor growth. The exposure to isoflurane and sevoflurane was associated with an increase in breast cancer size compared with non-exposure. These data suggested that isoflurane enhanced tumor growth by interacting with LFA-1. Isoflurane exposure did not affect tumor growth in LFA-1-deficient mice. In summary, the present data showed that LFA-1 deficiency facilitated breast cancer growth, and isoflurane, an LFA-1 inhibitor, also increased breast cancer growth., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

The title compound, C 17 H 17 BN 3 I, is a type of di-aza-borinane featuring substitution at the 1, 2, and 3 positions of the nitro-gen-boron six-membered heterocycle. The organic mol-ecule has a planar structure, the dihedral angle between the pyridyl ring and the fused ring system being 3.46 (4)°. In the crystal, mol-ecules are stacked in a head-to-tail manner. The iodide ion makes close contacts with three organic mol-ecules and supports the alternating stack., (© Hashimoto and Okuno 2024.)

The cation of the title hydrated salt, C 17 H 17 BN 3 + ·I - ·H 2 O, is a di-aza-borinane featuring substitution at the 1, 2, and 3 positions in the nitro-gen-boron six-membered heterocycle. The cation is approximately planar with a dihedral angle between the pyridyl ring and the di-aza-borinane ring system of 5.40 (5)°. In the crystal, the cations stack along [100] in an alternating head-to-tail manner, while the iodide ion and water mol-ecule form one-dimensional hydrogen-bonded chains beside the cation stack. The cation stacks and I - -water chains are crosslinked by N-H⋯I and N-H⋯O hydrogen bonds., (© Hashimoto et al. 2024.)

Blue light emitted during arc welding is known to potentially cause photoretinopathy. To help prevent retinal injury, it is important to identify the hazards associated with various welding conditions. The present work conducted experiments involving gas metal arc welding of mild steel under various conditions, and measured the spectral radiance of the arcs. The effective radiance values, as used by the American Conference of Governmental Industrial Hygienists (ACGIH) to quantify exposure level of blue light, were subsequently calculated from the data. The resulting values were in the range of 5.0-118 W/cm 2 /sr, corresponding to hazardous levels according to ACGIH guidelines. The effective radiance was increased at higher welding currents and when pulsed currents were used rather than steady currents. The blue light hazard was also affected by the type of shielding gas employed. These data confirm that it is very hazardous to stare at arcs during gas metal arc welding of mild steel. As such, appropriate eye protection is necessary during arc welding, and directly staring at the arc should be avoided.

Background: The FUTURE trial (UMIN000029294) demonstrated the safety and efficacy of adding palbociclib after fulvestrant resistance in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced and metastatic breast cancer (ABC/MBC). In this planned sub-study, cancer panel sequencing of cell-free DNA (cfDNA) was utilized to explore prognostic and predictive biomarkers for further palbociclib treatment following fulvestrant resistance., Materials and Methods: Herein, 149 cfDNA samples from 65 patients with fulvestrant-resistant disease were analysed at the time of palbociclib addition after fulvestrant resistance (baseline), on day 15 of cycle 1, and at the end of treatment using the assay for identifying diverse mutations in 34 cancer-related genes., Results: During the course of treatment, mutations in ESR1, PIK3CA, FOXA1, RUNX1, TBX3, and TP53 were the most common genomic alterations observed. Analysis of genomic mutations revealed that before fulvestrant introduction, baseline PIK3CA mutations were marginally lower in metastatic aromatase inhibitor (AI)-treated patients compared to adjuvant AI-treated patients (P = 0.063). Baseline PIK3CA mutations were associated with poorer progression-free survival [hazard ratio: 1.62, P = 0.04]. Comparative analysis between baseline and early-changing gene mutations identified poor prognostic factors including early-changing MAP3K1 mutations (hazard ratio: 4.66, P = 0.04), baseline AR mutations (hazard ratio: 3.53, P = 0.04), and baseline PIK3CA mutations (hazard ratio: 3.41, P = 0.02). Notably, the relationship between ESR1 mutations and mutations in PIK3CA, MAP3K1, and TP53 weakened as treatment progressed. Instead, PIK3CA mutations became correlated with TP53 and FOXA1 mutations., Conclusions: Cancer panel testing for cfDNA identified prognostic and predictive biomarkers for palbociclib add-on therapy after acquiring fulvestrant resistance in patients with HR+/HER2- ABC/MBC., Competing Interests: Disclosure TI: research grant from Pfizer. NN: research grant from Chugai, Pfizer, Eisai, Mochida, Daiichi-Sankyo, and Novartis; and honoraria for lectures from Chugai, Eli Lilly, MSD, Daiichi-Sankyo, AstraZeneca, and Pfizer. KW: honoraria for lectures from Chugai, Eli Lilly, Nippon-Kayaku, Kyowa-Kirin, Novartis, Taiho, Eisai, Pfizer, Shionogi, Daiichi-Sankyo, and AstraZeneca. YK: honoraria for lectures from Eisai, Novartis, Astra Zeneca, Taiho, Pfizer, Daiichi-Sankyo, Eli Lilly, and Chugai. KK: honoraria for lectures from Pfizer, Taiho, Chugai, AstraZeneca, Eli Lilly, Eisai, and Novartis. HT: research grant from Daiichi-Sankyo, Eli Lilly, Kyowa-Kirin, Chugai, Novartis, and Taiho; and honoraria for lectures from Chugai, Pfizer, Eli Lilly, AstraZeneca, and Daiichi-Sankyo. UT: research grant from Chugai, Eisai, Taiho, and Nippon-Kayaku; and honoraria for lectures from Pfizer, Kyowa-Kirin, Eli Lilly, and Daiichi-Sankyo. YY: research grant from Chugai, Kyowa-Kirin, Eisai, Daiichi-Sankyo, Nippon-Kayaku, Taiho, Takeda, Lilly, Pfizer, and Novartis; honoraria for lectures from AstraZeneca, Chugai, Kyowa-Kirin, Novartis, Lilly, Pfizer, Daiichi-Sankyo, Nippon-Kayaku, Taiho, Eisai, Takeda, MSD, Sysmex, and Exact Science; advisory board: AstraZeneca, Chugai, Novartis, MSD, Lilly, Pfizer, and Daiichi-Sankyo; and Member of the Board of Directors at the Japanese Breast Cancer Society and Japan Breast Cancer Research Group. HI: research grant from Eisai, Daiichi-Sankyo, Takeda, and Chugai; and honoraria for lectures from Eisai, Pfizer, Daiichi-Sankyo, Chugai, and Kyowa-Kirin. NM: research grant from Chugai, Eli Lilly, AstraZeneca, Pfizer, Daiichi-Sankyo, MSD, Eisai, Novartis, Sanofi, Kyowa-Kirin, Nippon-Kayaku, and Ono-Pharma; honoraria for lectures from Chugai, Pfizer, AstraZeneca, Eli Lilly, Daiichi-Sankyo, and Eisai; and Board of Directors at the Japanese Breast Cancer Society. SS: research grant from Taiho, Eisai, Chugai, Takeda, MSD, AstraZeneca, and Daiichi-Sankyo; honoraria for lectures from Chugai, Kyowa-Kirin, MSD, Novartis, Eisai, Takeda, Daiichi-Sankyo, Eli Lilly, AstraZeneca, Pfizer, Taiho, Ono, and Nippon-Kayaku; participation on a data safety monitoring board or advisory board at Chugai/Roche, AstraZeneca, Eli Lilly, Pfizer, Kyowa-Kirin, Daiichi-Sankyo, and MSD; and executive board member at JBCRG, JBCS, JSMO, and BIG. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The MitraClip G4 system is a new iteration of the transcatheter edge-to-edge repair system. We assessed the impact of the G4 system on routine practice and outcomes in secondary mitral regurgitation (2°MR)., Methods and results: Consecutive patients with 2°MR treated with either the MitraClip G2 (n=89) or G4 (n=63) system between 2018 and 2021 were included. Baseline characteristics, procedures, and outcomes were compared. Inverse probability of treatment weighting and Cox regression were used to adjust for baseline differences. Baseline characteristics were similar, except for a lower surgical risk in the G4 group (Society of Thoracic Surgeons Predicted Risk of Mortality ≥8: 38.1% vs. 56.2%; P=0.03). In the G4 group, more patients had short (≤2 mm) coaptation length (83.7% vs. 54.0%; P<0.001) and fewer clips were used (17.5% vs. 36.0%; P=0.02). Acceptable MR reduction was observed in nearly all patients, with no difference between the G4 and G2 groups (100% vs. 97.8%, respectively; P=0.51). The G4 group had fewer patients with high transmitral gradients (>5mmHg; 3.3% vs. 13.6%; P=0.03). At 1 year, there was no significant difference between groups in the composite endpoint (death or heart failure rehospitalization) after baseline adjustment (10.5% vs. 20.2%; hazard ratio 0.39; 95% confidence interval 0.11-1.32; P=0.13)., Conclusions: The G4 system achieved comparable device outcomes to the early-generation G2, despite treating more challenging 2°MR with fewer clips.

Background: Renal congestion is a potential prognostic factor in patients with heart failure and recently, assessment has become possible with intrarenal Doppler ultrasonography (IRD). The association between renal congestion assessed by IRD and outcomes after mitral transcatheter edge-to-edge repair (TEER) is unknown, so we aimed to clarify renal congestion and its prognostic implications in patients with mitral regurgitation (MR) who underwent TEER using MitraClip system., Methods and results: Patients with secondary MR who underwent TEER and were assessed for intrarenal venous flow (IRVF) by IRD were classified according to their IRVF pattern as continuous or discontinuous. Of the 105 patients included, 78 patients (74%) formed the continuous group and 27 (26%) were the discontinuous group. Kaplan-Meier analysis revealed significant prognostic power of the IRVF pattern for predicting the composite outcome of all-cause death and heart failure rehospitalization (log-rank P=0.0257). On multivariate Cox regression analysis, the composite endpoint was independently associated with the discontinuous IRVF pattern (hazard ratio, 3.240; 95% confidence interval, 1.300-8.076; P=0.012) adjusted using inverse probability of treatment weighting., Conclusions: IRVF patterns strongly correlated with clinical outcomes without changes in renal function. Thus, they may be useful for risk stratification after mitral TEER for patients with secondary MR.

Aims: Current evidence on the prognostic value of exercise stress echocardiography (ESE) in asymptomatic patients with low-gradient severe aortic stenosis (AS) is limited. Therefore, this study aimed to elucidate its prognostic implications for patients with low-gradient severe AS and determine the added value of ESE in risk stratification for this population., Methods and Results: This retrospective observational study included 122 consecutive asymptomatic patients with either moderate [mean pressure gradient (MPG) < 40 mmHg and aortic valve area (AVA) 1.0-1.5 cm 2 ] or low-gradient severe (MPG < 40 mmHg and AVA < 1.0 cm 2 ) AS and preserved left ventricular ejection fraction (≥50%) who underwent ESE. All patients were followed up for AS-related events. Of 143 patients, 21 who met any exclusion criteria, including early interventions, were excluded, and 122 conservatively managed patients [76.5 (71.0-80.3) years; 48.3% male] were included in this study. During a median follow-up period of 989 (578-1571) days, 64 patients experienced AS-related events. Patients with low-gradient severe AS had significantly lower event-free survival rates than those with moderate AS (log-rank test, P < 0.001). Multivariable Cox regression analysis showed that the mitral E / e ' ratio during exercise was independently associated with AS-related events (hazard ratio = 1.075, P < 0.001) in patients with low-gradient severe AS., Conclusion: This study suggests that asymptomatic patients with low-gradient severe AS have worse prognoses than those with moderate AS. Additionally, the mitral E / e ' ratio during exercise is a useful parameter for risk stratification in patients with low-gradient severe AS., Competing Interests: Conflict of interest: M.I. is a consultant of Edwards Lifesciences and Abbott Medical Japan, and S.K. is a consultant of Abbott Medical Japan. All other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Video-assisted thoracoscopic surgery is a widely recommended treatment for empyema in advanced stages. However, only a few studies have evaluated prognostic factors among patients with empyema who underwent video-assisted thoracoscopic surgery. Furthermore, no studies have evaluated predictors of direct discharge home. Patients and Methods: This multicenter retrospective cohort study included 161 patients with empyema who underwent video-assisted thoracoscopic surgery in five acute-care hospitals. The primary outcome was the probability of direct discharge home. The secondary outcome was the length of hospital stay after surgery. We broadly assessed pre-operative factors and performed univariable logistic regression for the direct discharge home and univariable gamma regression for the length of hospital stay after surgery. Results: Of the 161 included patients, 74.5% were directly discharged home. Age (>70 years; -24.3%); altered mental status (-33.4%); blood urea nitrogen (>22.4 mg/dL; -19.4%); and pleural pH (<7.2; -17.6%) were associated with high probabilities of not being directly discharged home. Fever (15.2%) and albumin (> 2.7 g/dL; 20.2%) were associated with high probabilities of being directly discharged home. The median length of stay after surgery was 19 days. Age (>70 years; 6.2 days); altered mental status (5.6 days); purulence (2.7 days); pleural thickness (>2 cm; 5.1 days); bronchial fistula (14.6 days); albumin (>2.7 g/dL; 3.1 days); and C-reactive protein (>20 mg/dL; 3.6 days) were associated with a longer post-operation hospital stay. Conclusions: Physicians should consider using these prognostic factors to predict non-direct discharge to the home for patients with empyema.

Background: There is limited evidence on the association between the clinical course of patent ductus arteriosus (PDA) and prostaglandin (PG) metabolites. This study aimed to determine the influence of PDA treatment on urinary PG metabolite excretion in very-low-birth-weight (VLBW) infants., Methods: Urine samples were collected from 25 VLBW infants at 1, 3, and 7 days of age. Infants were separated into two groups: a PDA-treated group that received a cyclooxygenase-2 (COX) inhibitor (n = 12) and a control group that did not receive a COX inhibitor during the first 7 days after birth (n = 13). Urinary PG metabolite tetranor prostaglandin E 2 metabolite (t-PGEM) and tetranor prostaglandin D 2 metabolite (t-PGDM) levels were analyzed using liquid chromatography-tandem mass spectrometry., Results: Urinary t-PGEM excretion levels were not significantly different between the groups at 1, 3, and 7 days of age. Urinary t-PGDM excretion levels at 1 day of age were higher in PDA-treated infants than in control infants (median [interquartile range]: 5.5 [2.6, 12.2] versus 2.1 [1.0, 3.9] ng/mg creatinine; p = 0.017); however, among PDA-treated infants, the levels were significantly lower at 3 and 7 days than at 1 day of age (5.5 [2.6, 12.2] versus 3.4 [1.7, 4.5] and 4.0 [1.7, 5.3] ng/mg creatinine, respectively; p < 0.05). The urinary t-PGDM excretion level in the control group did not significantly differ among the time points., Conclusion: PDA and COX inhibitor administration affected PG metabolism in VLBW infants. Our results indicated that urinary t-PGDM excretion was significantly associated with PDA-treatment in preterm infants., Competing Interests: Conflicts of interest There is no Conflicts of Interests to be declared., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)